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Single-cell analysis of the multiple myeloma microenvironment after γ-secretase inhibition and CAR T-cell therapy.
|
Chimeric antigen receptor (CAR) T cells and bispecific antibodies targeting B-cell maturation antigen (BCMA) have significantly advanced the treatment of relapsed and refractory multiple myeloma. Resistance to BCMA-targeting therapies, nonetheless, remains a significant challenge. BCMA shedding by γ-secretase is a known resistance mechanism, and preclinical studies suggest that inhibition may improve anti-BCMA therapy. Leveraging a phase 1 clinical trial of the γ-secretase inhibitor (GSI), crenigacestat, with anti-BCMA CAR T cells (FCARH143), we used single-nuclei RNA sequencing and assay for transposase-accessible chromatin sequencing to characterize the effects of GSI on the tumor microenvironment. The most significant impacts of GSI involved effects on monocytes, which are known to promote tumor growth. In addition to observing a reduction in the frequency of nonclassical monocytes, we also detected significant changes in gene expression, chromatin accessibility, and inferred cell-cell interactions after exposure to GSI. Although many genes with altered expression are associated with γ-secretase-dependent signaling, such as Notch, other pathways were affected, indicating GSI has far-reaching effects. Finally, we detected monoallelic deletion of the BCMA locus in some patients with prior exposure to anti-BCMA therapy, which significantly correlated with reduced progression-free survival (PFS; median PFS, 57 vs 861 days). GSIs are being explored in combination with the full spectrum of BCMA-targeting agents, and our results reveal widespread effects of GSI on both tumor and immune cell populations, providing insight into mechanisms for enhancing BCMA-directed therapies.
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] | 2024-10-07 | 39 |
39374522
|
[
"anti-BCMA CAR T cells",
"anti-BCMA therapy",
"T cells",
"anti-BCMA",
"GSI",
"widespread effects",
"γ-secretase",
"BCMA",
"gene expression",
"effects",
"inferred cell-cell interactions",
"nonclassical monocytes",
"significant changes",
"altered expression",
"chromatin accessibility",
"tumor growth",
"Chimeric antigen receptor",
"median PFS",
"BCMA-targeting therapies",
"prior exposure",
"B-cell maturation antigen",
"many genes",
"other pathways",
"monocytes",
"mechanisms",
"preclinical studies",
"CAR",
"BCMA-directed therapies",
"PFS",
"bispecific antibodies"
] |
[] | 0 |
10.1182/blood.2024025231
|
[
"Coffey",
"Ataca Atilla",
"Atilla",
"Landgren",
"Cowan",
"Simon",
"Pont",
"Comstock",
"Hill",
"Riddell",
"Green"
] |
[
"Myeloma Division, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL.",
"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA.",
"Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, WA.",
"Myeloma Division, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL.",
"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA.\nImmunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, WA.",
"Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, WA.\nTranslational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA.",
"Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, WA.\nTranslational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA.\nGalapagos B.V., Oegstgeest, The Netherlands.",
"Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA.",
"Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, WA.\nTranslational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA.",
"Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, WA.\nTranslational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA.",
"Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, WA.\nTranslational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA.\nDivision of Transplantation and Cellular Therapy, Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL."
] |
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[] | 5.114026 | 5.920232 |
39373395
| 401 |
Siglec-G Suppresses CD8
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] | 2024-10-07 | 79 |
39373395
|
[
"CD8"
] |
[
"CD8+ T cells",
"Siglec‐G",
"metabolic rewiring",
"tumor immunotherapy"
] | 0 |
10.1002/advs.202403438
|
[
"Yin",
"Li",
"Shen",
"Yu",
"Cui",
"Wu",
"He",
"Yu",
"Chen",
"Lu",
"Qiu",
"Song",
"Qian",
"Zou",
"Yu",
"Xu"
] |
[
"National Key Laboratory of Immunity & Inflammation, Naval Medical University/Second Military Medical University, Shanghai, 200433, China.",
"National Key Laboratory of Immunity & Inflammation, Naval Medical University/Second Military Medical University, Shanghai, 200433, China.",
"National Key Laboratory of Immunity & Inflammation, Naval Medical University/Second Military Medical University, Shanghai, 200433, China.",
"Department of Colorectal Surgery, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.",
"National Key Laboratory of Immunity & Inflammation, Naval Medical University/Second Military Medical University, Shanghai, 200433, China.",
"National Key Laboratory of Immunity & Inflammation, Naval Medical University/Second Military Medical University, Shanghai, 200433, China.",
"National Key Laboratory of Immunity & Inflammation, Naval Medical University/Second Military Medical University, Shanghai, 200433, China.",
"National Key Laboratory of Immunity & Inflammation, Naval Medical University/Second Military Medical University, Shanghai, 200433, China.",
"National Key Laboratory of Immunity & Inflammation, Naval Medical University/Second Military Medical University, Shanghai, 200433, China.",
"National Key Laboratory of Immunity & Inflammation, Naval Medical University/Second Military Medical University, Shanghai, 200433, China.",
"National Key Laboratory of Immunity & Inflammation, Naval Medical University/Second Military Medical University, Shanghai, 200433, China.",
"National Key Laboratory of Immunity & Inflammation, Naval Medical University/Second Military Medical University, Shanghai, 200433, China.",
"National Key Laboratory of Immunity & Inflammation, Naval Medical University/Second Military Medical University, Shanghai, 200433, China.",
"School of Anesthesiology, Naval Medical University, Shanghai, 200433, China.\nFaculty of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.",
"National Key Laboratory of Immunity & Inflammation, Naval Medical University/Second Military Medical University, Shanghai, 200433, China.",
"National Key Laboratory of Immunity & Inflammation, Naval Medical University/Second Military Medical University, Shanghai, 200433, China."
] |
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[] | 33.516708 | 7.054447 |
39373147
| 402 |
Targeted therapy of multiple myeloma by IL21-NKG2D CAR-T cells.
|
NKG2D chimeric antigen receptor (CAR)-modified T cells (NKG2D CAR-T cells) have been reported to be preclinically efficient in several tumors, but little is known whether NKG2D CAR-T cells co-expressing IL21 (IL21-NKG2D CAR-T cells) display greater antitumor activity in multiple myeloma (MM). In this study, the lentivirus has been produced for expression of the IL21 sequence linked to the extracellular NKG2D sequence with the signal peptide linked through the CD8α hinge-transmembrane domain to the 4-1BB molecule fused with the CD3-ζ chain signaling domain, and the engineered IL21-NKG2D CAR-T cells and NKG2D CAR-T cells were constructed. The CAR expression on CAR-T cells was assessed by flow cytometry, and the killing effects of CAR-T cells on MM were assessed by the cytotoxicity assay and ELISA assay. Moreover, xenograft models were also established to evaluate the ability of IL21-NKG2D-CAR-T cells to eliminate MM in vivo. Our results indicated that NKG2D CAR-T cells had dramatic cytotoxicity on MM cells in vitro, and co-expression of IL-21 significantly increased the cytotoxicity of NKG2D CAR-T cells on MM cells. Remarkably, we found that dexamethasone enhanced the cytotoxicity of IL21-NKG2D CAR-T cells on MM cells. Furthermore, IL21-NKG2D CAR-T cells also displayed significant anti-myeloma activity in vivo. In conclusion, IL21-NKG2D CAR-T cells had dramatic cytotoxicity on MM cells in vitro and in vivo, and a system to apply IL21-NKG2D CAR-T cells and low dosage of dexamethasone for the future study of the targeted therapy for MM has been established.
|
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] | 2024-10-07 | 1 |
39373147
|
[
"MM cells",
"CAR)-modified T cells",
"NKG2D CAR-T cells",
"IL21-NKG2D CAR-T cells",
"CAR-T cells",
"dramatic cytotoxicity",
"MM",
"expressing IL21 (IL21-NKG2D CAR-T cells",
"the engineered IL21-NKG2D CAR-T cells",
"significant anti-myeloma activity",
"IL21-NKG2D-CAR-T cells",
"NKG2D chimeric antigen receptor",
"greater antitumor activity",
"expression",
"domain",
"CAR",
"the IL21 sequence",
"several tumors",
"low dosage",
"flow cytometry",
"vivo",
"dexamethasone",
"multiple myeloma",
"xenograft models",
"The CAR expression",
"the extracellular NKG2D sequence",
"IL-21",
"-",
"the CD8α hinge-transmembrane domain",
"ELISA"
] |
[
"CAR-T cells",
"IL21",
"Multiple myeloma",
"NKG2D",
"dexamethasone"
] | 0 |
10.1177/10815589241291846
|
[
"Han",
"Wang",
"Chen",
"Liu",
"Mei",
"Yang",
"Xu"
] |
[
"China Regional Research Center, International Center for Genetic Engineering and Biotechnology, Taizhou, Jiangsu, P. R. China.\nCenter for Self-Propelled Nanotechnologies, College of Biotechnology, Suzhou Industrial Park Institute of Services Outsourcing, Suzhou, Jiangsu, P. R. China.",
"China Regional Research Center, International Center for Genetic Engineering and Biotechnology, Taizhou, Jiangsu, P. R. China.",
"School of Basic Medical Sciences, Wannan Medical College, Wuhu, Anhui, P. R. China.",
"China Regional Research Center, International Center for Genetic Engineering and Biotechnology, Taizhou, Jiangsu, P. R. China.",
"Center for Self-Propelled Nanotechnologies, College of Biotechnology, Suzhou Industrial Park Institute of Services Outsourcing, Suzhou, Jiangsu, P. R. China.",
"China Regional Research Center, International Center for Genetic Engineering and Biotechnology, Taizhou, Jiangsu, P. R. China.\nCenter for Self-Propelled Nanotechnologies, College of Biotechnology, Suzhou Industrial Park Institute of Services Outsourcing, Suzhou, Jiangsu, P. R. China.\nTranslational Cancer Research Laboratory, Suzhou Acumen Medical Technology, Suzhou, Jiangsu, P. R. China.",
"China Regional Research Center, International Center for Genetic Engineering and Biotechnology, Taizhou, Jiangsu, P. R. China.\nCenter for Self-Propelled Nanotechnologies, College of Biotechnology, Suzhou Industrial Park Institute of Services Outsourcing, Suzhou, Jiangsu, P. R. China.\nTranslational Cancer Research Laboratory, Suzhou Acumen Medical Technology, Suzhou, Jiangsu, P. R. China."
] |
[
"39373147"
] |
[] | 11.059297 | 6.06376 |
39372944
| 403 |
Scalable intracellular delivery via microfluidic vortex shedding enhances the function of chimeric antigen receptor T-cells.
|
Adoptive chimeric antigen receptor T-cell (CAR-T) therapy is transformative and approved for hematologic malignancies. It is also being developed for the treatment of solid tumors, autoimmune disorders, heart disease, and aging. Despite unprecedented clinical outcomes, CAR-T and other engineered cell therapies face a variety of manufacturing and safety challenges. Traditional methods, such as lentivirus transduction and electroporation, result in random integration or cause significant cellular damage, which can limit the safety and efficacy of engineered cell therapies. We present hydroporation as a gentle and effective alternative for intracellular delivery. Hydroporation resulted in 1.7- to 2-fold higher CAR-T yields compared to electroporation with superior cell viability and recovery. Hydroporated cells exhibited rapid proliferation, robust target cell lysis, and increased pro-inflammatory and regulatory cytokine secretion in addition to improved CAR-T yield by day 5 post-transfection. We demonstrate that scaled-up hydroporation can process 5 × 10
|
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] | 2024-10-07 | 63 |
39372944
|
[
"engineered cell therapies",
"other engineered cell therapies",
"superior cell viability",
"Hydroporated cells",
"autoimmune disorders",
"significant cellular damage",
"solid tumors",
"improved CAR-T yield",
"lentivirus transduction",
"electroporation",
"hydroporation",
"heart disease",
"random integration",
"rapid proliferation",
"unprecedented clinical outcomes",
"intracellular delivery",
"-inflammatory and regulatory cytokine secretion",
"Adoptive chimeric antigen receptor T-cell (CAR-T) therapy",
"Traditional methods",
"CAR-T",
"hematologic malignancies",
"day",
"addition",
"efficacy",
"to 2-fold higher CAR-T yields",
"-",
"manufacturing and safety challenges",
"aging",
"2-fold",
"transfection"
] |
[
"AAV",
"CAR-T",
"CRISPR",
"Cell Therapy",
"Cytokine",
"Gene editing",
"Intracellular delivery",
"Microfluidics",
"Serial killing",
"Vortex shedding"
] | 0 |
10.21203/rs.3.rs-4870379/v1
10.1158/2159-8290.CD-24-0102
10.1101/2021.10.26.465897
10.1038/s43018-024-00768-3
10.1101/2023.04.17.535914
|
[
"Sytsma",
"Allain",
"Bourke",
"Faizee",
"Fathi",
"Berdeaux",
"Ferreira",
"Brewer",
"Li",
"Pan",
"Rothrock",
"Nyberg",
"Li",
"Wilson",
"Eyquem",
"Pawell"
] |
[
"Indee Labs, Berkeley, CA, USA.",
"Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.\nDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.\nUniversité Paris Cité, INSERM UMR976, Hôpital Saint-Louis, Paris, France.",
"Indee Labs, Berkeley, CA, USA.",
"Indee Labs, Berkeley, CA, USA.",
"CellChorus, Houston, TX, United States.",
"CellChorus, Houston, TX, United States.",
"Indee Labs, Berkeley, CA, USA.\nDepartment of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.\nDepartment of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, USA.\nHollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.",
"Indee Labs, Berkeley, CA, USA.",
"Indee Labs, Berkeley, CA, USA.",
"Indee Labs, Berkeley, CA, USA.",
"Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.\nDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.",
"Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.\nDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.",
"Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.\nDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.",
"Indee Labs, Berkeley, CA, USA.",
"Indee Labs, Berkeley, CA, USA.\nGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.\nDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.\nUCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.\nInstitute for Human Genetics (IHG), University of California, San Francisco, San Francisco, CA, USA.\nParker Institute for Cancer Immunotherapy, San Francisco, CA, USA.\nDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.",
"Indee Labs, Berkeley, CA, USA."
] |
[
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] |
[] | 8.882622 | 3.022911 |
39372412
| 404 |
Generating advanced CAR-based therapy for hematological malignancies in clinical practice: targets to cell sources to combinational strategies.
|
Chimeric antigen receptor T (CAR-T) cell therapy has been a milestone breakthrough in the treatment of hematological malignancies, offering an effective therapeutic option for multi-line therapy-refractory patients. So far, abundant CAR-T products have been approved by the United States Food and Drug Administration or China National Medical Products Administration to treat relapsed or refractory hematological malignancies and exhibited unprecedented clinical efficiency. However, there were still several significant unmet needs to be progressed, such as the life-threatening toxicities, the high cost, the labor-intensive manufacturing process and the poor long-term therapeutic efficacy. According to the demands, many researches, relating to notable technical progress and the replenishment of alternative targets or cells, have been performed with promising results. In this review, we will summarize the current research progress in CAR-T eras from the "targets" to "alternative cells", to "combinational drugs" in preclinical studies and clinical trials.
|
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] | 2024-10-07 | 124 |
39372412
|
[
"alternative cells",
"hematological malignancies",
"China National Medical Products Administration",
"alternative targets",
"notable technical progress",
"several significant unmet needs",
"cells",
"unprecedented clinical efficiency",
"clinical trials",
"preclinical studies",
"multi-line therapy-refractory patients",
"relapsed or refractory hematological malignancies",
"abundant CAR-T products",
"the current research progress",
"promising results",
"CAR-T",
"an effective therapeutic option",
"CAR-T eras",
"the United States Food and Drug Administration",
"the poor long-term therapeutic efficacy",
"the labor-intensive manufacturing process",
"the high cost",
"\"combinational drugs",
"the life-threatening toxicities",
"a milestone breakthrough",
"the replenishment",
"the treatment",
"the \"targets",
"the demands",
"this review"
] |
[
"allogeneic",
"chimeric antigen receptor T cell",
"combinatorial therapy",
"hematological malignancies",
"targets"
] | 0 |
10.3389/fimmu.2024.1435635
10.1073/pnas.86.24.10024
10.1016/j.eclinm.2024.102516
10.3390/ijms20061283
10.1111/imr.12131
10.1073/pnas.90.2.720
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|
[
"Zhou",
"Yang",
"Jing",
"Zhu"
] |
[
"Department of Hematology, Zhongnan Hospital, Wuhan University, Wuhan, China.",
"The First Clinical Medical College, Wuhan University, Wuhan, China.",
"The Second Clinical Medical College, Wuhan University, Wuhan, China.",
"National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.\nInstitute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China."
] |
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[] | 7.908573 | 3.942144 |
39371522
| 405 |
A rapid method to assess the
|
The clinical efficacy of chimeric antigen and T cell receptor (TCR) T cell immunotherapies is attributed to their ability to proliferate and persist
We sought to achieve this by adapting a recently developed Severe acute respiratory syndrome
We demonstrated that a simple pulsing of whole blood with a peptide corresponding to the epitope recognized by the specific HBV-TCR elicited Th1 cytokine secretion in both patients only after HBV-TCR T cell treatment and not before. The amount of cytokines secreted also showed an infusion-dose-dependent association.
These findings support the utility of the whole blood cytokine release assay in monitoring the
|
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] | 2024-10-07 | 15 |
39371522
|
[
"whole blood",
"T cell receptor",
"cytokines",
"TCR",
"HBV-TCR T cell treatment",
"the whole blood cytokine release",
"chimeric antigen",
"TCR) T cell immunotherapies",
"HBV-TCR",
"the specific HBV-TCR elicited Th1 cytokine secretion",
"a recently developed Severe acute respiratory syndrome",
"assay",
"an infusion-dose-dependent association",
"The clinical efficacy",
"that a simple pulsing",
"their ability",
"the epitope",
"both patients",
"the utility",
"The amount",
"These findings",
"We",
"this"
] |
[
"T cell therapy",
"adoptive cell transfer",
"hepatitis B",
"hepatocellular carcinoma"
] | 0 |
10.1093/immadv/ltae007
10.1182/bloodadvances.2023010364
10.1136/jitc-2022-006596
10.1016/j.ebiom.2022.103941
10.1053/j.gastro.2018.03.029
10.1016/j.ymthe.2019.01.018
10.1038/leu.2015.52
10.1007/s00262-014-1572-5
10.1007/s12072-021-10250-2
10.1053/j.gastro.2019.01.251
10.1093/immadv/ltab026
10.1093/immadv/ltad015
10.1002/hep4.1857
10.1182/bloodadvances.2022007246
|
[
"Tan",
"Hang",
"Tan",
"Krishnamoorthy",
"Chow",
"Wong",
"Wai",
"Bertoletti"
] |
[
"Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore.",
"Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore.",
"Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore.",
"Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore, Singapore.",
"Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore, Singapore.",
"Lion TCR Pte Ltd., Singapore, Singapore.",
"Lion TCR Pte Ltd., Singapore, Singapore.",
"Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore."
] |
[
"39371522",
"37748131",
"37217245",
"35301179",
"29567081",
"30819612",
"25721896",
"24938475",
"34850325",
"30711630",
"35919490",
"37636242",
"34623327",
"34935312",
"35938863"
] |
[] | 8.353856 | 5.041142 |
39370422
| 406 |
GLUT1 overexpression in CAR-T cells induces metabolic reprogramming and enhances potency.
|
The intensive nutrient requirements needed to sustain T cell activation and proliferation, combined with competition for nutrients within the tumor microenvironment, raise the prospect that glucose availability may limit CAR-T cell function. Here, we seek to test the hypothesis that stable overexpression (OE) of the glucose transporter GLUT1 in primary human CAR-T cells would improve their function and antitumor potency. We observe that GLUT1OE in CAR-T cells increases glucose consumption, glycolysis, glycolytic reserve, and oxidative phosphorylation, and these effects are associated with decreased T cell exhaustion and increased Th
|
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] | 2024-10-07 | 72 |
39370422
|
[
"T cell activation",
"decreased T cell exhaustion",
"glucose availability",
"glucose consumption",
"primary human CAR-T cells",
"CAR-T cell function",
"stable overexpression",
"CAR-T cells",
"oxidative phosphorylation",
"glycolytic reserve",
"OE",
"nutrients",
"competition",
"GLUT1",
"glycolysis",
"proliferation",
"the glucose transporter",
"antitumor",
"GLUT1OE",
"The intensive nutrient requirements",
"potency",
"the tumor microenvironment",
"their function",
"the hypothesis",
"these effects",
"the prospect",
"We",
"we"
] |
[] | 0 |
10.1038/s41467-024-52666-y
|
[
"Guerrero",
"Klysz",
"Chen",
"Malipatlolla",
"Lone",
"Fowler",
"Stuani",
"May",
"Bashti",
"Xu",
"Huang",
"Michael",
"Contrepois",
"Dhingra",
"Fisher",
"Svensson",
"Davis",
"Kasowski",
"Feldman",
"Sotillo",
"Mackall"
] |
[
"Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, tanford, CA, USA.",
"Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, tanford, CA, USA.",
"Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, tanford, CA, USA.",
"Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, tanford, CA, USA.",
"Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.",
"Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, tanford, CA, USA.",
"Division of Pediatric Hematology/Oncology/Stem Cell Transplant and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.",
"Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, tanford, CA, USA.",
"Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, tanford, CA, USA.",
"Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, tanford, CA, USA.",
"Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, tanford, CA, USA.",
"Metabolic Health Center, Stanford University School of Medicine, Stanford, CA, USA.",
"Metabolic Health Center, Stanford University School of Medicine, Stanford, CA, USA.",
"Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, tanford, CA, USA.",
"Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, tanford, CA, USA.",
"Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.\nStanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA, USA.\nStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.",
"Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, tanford, CA, USA.\nDivision of Pediatric Hematology/Oncology/Stem Cell Transplant and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.",
"Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.\nDepartment of Genetics, Stanford University, Stanford, CA, USA.\nSean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford University, Stanford, CA, USA.\nDivision of Bone Marrow Transplant-Cell Therapy, Dept of Medicine, Stanford University School of Medicine, Stanford, CA, USA.",
"Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, tanford, CA, USA.",
"Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, tanford, CA, USA. esotillo@stanford.edu.",
"Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, tanford, CA, USA. cmackall@stanford.edu.\nDivision of Pediatric Hematology/Oncology/Stem Cell Transplant and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA. cmackall@stanford.edu.\nDivision of Bone Marrow Transplant-Cell Therapy, Dept of Medicine, Stanford University School of Medicine, Stanford, CA, USA. cmackall@stanford.edu.\nParker Institute for Cancer Immunotherapy, San Francisco, CA, USA. cmackall@stanford.edu."
] |
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[] | 10.167542 | 4.899618 |
39370355
| 407 |
The Road More or Less Traveled- Examining the Role of Consolidative Allogeneic Hematopoietic Stem Cell Transplantation After Chimeric Antigen Receptor T Cell Therapy in B-cell ALL.
|
Treatment with CD19-targeted chimeric antigen receptor T cell therapy (CD19-CART) has improved salvage rates in children and adults with relapsed and/or refractory B-cell acute lymphoblastic leukemia (ALL). However, not all patients treated with CD19-CAR T cells achieve long-term remission. The role of allogeneic hematopoietic stem cell transplantation as consolidative therapy remains undefined. We aim to review the current literature published to date regarding prognostic markers indicating durable ALL response to CD19-CART and risk factors for relapse after CD19-CART to identify patient cohorts who may benefit from consolidative hematopoietic stem cell transplantation.
|
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] | 2024-10-07 | 1 |
39370355
|
[
"consolidative hematopoietic stem cell transplantation",
"allogeneic hematopoietic stem cell transplantation",
"CD19-targeted chimeric antigen receptor T cell therapy",
"consolidative therapy",
"CD19-CAR T cells",
"prognostic markers",
"salvage rates",
"patient cohorts",
"relapsed and/or refractory B-cell acute lymphoblastic leukemia",
"CD19-CART",
"risk factors",
"date",
"adults",
"children",
"relapse",
"ALL",
"long-term remission",
"Treatment",
"the current literature",
"durable ALL response",
"The role",
"not all patients",
"We",
"who"
] |
[
"Acute lymphoblastic leukemia",
"Allogeneic hematopoietic stem cell transplant",
"CD19",
"Chimeric antigen receptor T cells",
"Consolidation",
"Relapse-free survival"
] | 0 |
10.1053/j.seminhematol.2024.08.004
|
[
"Choe",
"Summers"
] |
[
"Clinical Research Division, Fred Hutch Cancer Center, Seattle, Washington, USA; Department of Pediatrics, University of Washington, Seattle, Washington, USA.",
"Department of Pediatrics, University of Washington, Seattle, Washington, USA; Seattle Children's Therapeutics, Seattle Children's Research Institute, Seattle, Washington, USA. Electronic address: corinne.summers@seattlechildrens.org."
] |
[
"39370355"
] |
[] | 6.60949 | 5.620846 |
39368372
| 408 |
Cabozantinib enhances CAIX specific CAR-T cells against renal cancer by improving effector functions and augmenting tumor immune microenvironment.
|
Despite demonstrating promising outcomes in treating hematologic malignancies, the efficacy of chimeric antigen receptor-modified T (CAR-T) cell therapy remains limited when applied to solid tumors due to tumor immune microenvironment (TIME). Strategies to augment CAR-T cell efficacy against solid tumors have been investigated by ameliorating TIME to a certain extent. In this study, Cabozantinib was utilized in combination with CAR-T cells targeting carbonic anhydrase IX (CAIX) for the treatment of renal cancer. Our findings indicate that combination therapy with CAIX-CAR-T and Cabozantinib demonstrated synergistic efficacy against an orthotopic xenograft tumor model and a subcutaneous tumor model of renal cell carcinoma in mice. Mechanistically, it was observed that CAR-T cells combined with Cabozantinib led to an increase in the infiltration of tumor-infiltrating T cells, while reducing tumor-associated macrophages and M2 polarization. Additionally, Cabozantinib blocked the programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis by decreasing the expression of PD-L1 in tumor cells and PD-1 in T cells. Furthermore, Cabozantinib promoted CAR-T cell effector function and reduced T cell exhaustion. This combination therapy represents a novel approach to enhancing CAR-T cell efficacy against solid tumors and holds significant promise for advancing CAR-T cell therapy in clinical settings.
|
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] | 2024-10-06 | 1 |
39368372
|
[
"tumor cells",
"T cells",
"reduced T cell exhaustion",
"solid tumors",
"renal cell carcinoma",
"tumor-infiltrating T cells",
"CAR-T cell efficacy",
"CAR-T cell therapy",
"CAR-T cell effector function",
"CAR-T cells",
"synergistic efficacy",
"Cabozantinib",
"an orthotopic xenograft tumor model",
"tumor-associated macrophages",
"a subcutaneous tumor model",
"renal cancer",
"combination",
"hematologic malignancies",
"the programmed cell",
"carbonic anhydrase",
"significant promise",
"CAR-T",
"TIME",
"M2 polarization",
"This combination therapy",
"that combination therapy",
"CAIX",
"clinical settings",
"IX",
"outcomes"
] |
[
"CAR-T",
"Cabozantinib",
"Combination therapy",
"Tumor microenvironment"
] | 0 |
10.1016/j.bbrc.2024.150781
|
[
"Li",
"Yang",
"Li",
"Zhao",
"Xue",
"Lu",
"Tang",
"Gao",
"Zheng",
"Zhang",
"Sun"
] |
[
"Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, PR China; Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, PR China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, PR China.",
"General Surgery Department, Xuzhou Mine Hospital, Xuzhou, Jiangsu, PR China.",
"Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, PR China; Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, PR China.",
"Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, PR China; Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, PR China.",
"Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, PR China; Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, PR China.",
"Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, PR China.",
"Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, PR China; Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, PR China.",
"Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, PR China; Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, PR China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, PR China.",
"Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, PR China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, PR China.",
"Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, PR China; Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, PR China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, PR China. Electronic address: qingzhang@xzhmu.edu.cn.",
"Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, PR China; Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, PR China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, PR China. Electronic address: sssun@xzhmu.edu.cn."
] |
[
"39368372"
] |
[] | 9.779484 | 4.925597 |
39368275
| 409 |
Enhancing CAR-T cell therapy against solid tumor by drug-free triboelectric immunotherapy.
|
Chimeric antigen receptor (CAR) T cell therapy is a highly effective immunotherapy for hematological tumors, but its efficacy against most solid tumors remains challenging. Herein, a novel synergistic combination therapy of drug-free triboelectric immunotherapy and CAR-T cell therapy against solid tumor was proposed. A triboelectric nanogenerator (TENG) that can generate pulsed direct-current by coupling triboelectrification effect and electrostatic breakdown effect was fabricated. The TENG can generate up to 30 pulse direct-current peaks with peak current output ≈35 μA in a single sliding to power the triboelectric immunotherapy. The pulsed direct-current stimulation induced immunogenic cell death of tumor cells (survival rate of 35.9 %), which promoted dendritic cells maturation, accelerated the process of antigen presentation to CAR-T cells and enhanced the systemic adaptive immune response. Furthermore, triboelectric immunotherapy promoted M1-like macrophage polarization, reduced regulatory T cells differentiation and reprogrammed the tumor immunosuppressive microenvironment, which ultimately enhanced the efficacy of CAR-T cells to eradicate nearly 60 % of NALM6 solid tumor mass. Notably, considering that triboelectric immunotherapy is a safe and effective drug-free antitumor strategy, the combined therapy did not increase the burden of double-medication on patients.
|
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] | 2024-10-06 | 1 |
39368275
|
[
"T cell therapy",
"tumor cells",
"regulatory T cells differentiation",
"dendritic cells maturation",
"immunogenic cell death",
"triboelectric immunotherapy",
"solid tumor",
"most solid tumors",
"NALM6 solid tumor mass",
"CAR-T cell therapy",
"hematological tumors",
"CAR-T cells",
"electrostatic breakdown effect",
"CAR",
"triboelectrification effect",
"drug-free triboelectric immunotherapy",
"Chimeric antigen receptor",
"antigen presentation",
"survival rate",
"a novel synergistic combination therapy",
"peak current output ≈35 μA",
"the triboelectric immunotherapy",
"the tumor immunosuppressive microenvironment",
"pulsed direct-current",
"TENG",
"the combined therapy",
"The pulsed direct-current stimulation",
"M1-like macrophage polarization",
"NALM6",
"M1"
] |
[
"CAR-T cell",
"Immunosuppressive microenvironment",
"Solid tumor treatment",
"Triboelectric immunotherapy",
"Triboelectric nanogenerator"
] | 0 |
10.1016/j.biomaterials.2024.122871
|
[
"Li",
"Wang",
"Hu",
"He",
"Huang",
"Liu",
"Wang",
"Jiang"
] |
[
"Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China; Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE), Wuhan University, Wuhan 430072, China.",
"Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China; Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE), Wuhan University, Wuhan 430072, China.",
"Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China; Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE), Wuhan University, Wuhan 430072, China.",
"Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China; Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE), Wuhan University, Wuhan 430072, China.",
"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300020, China; Tianjin Institutes of Health Science, Tianjin 301600, China.",
"School of Chemistry and Materials Sciences & School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan 430074, China; Hubei Key Laboratory of Radiation Chemistry and Functional Materials, School of Nuclear Technology and Chemistry and Biology, Hubei University of Science and Technology, Xianning 437100, China.",
"Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing 100083, China.",
"Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China; Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE), Wuhan University, Wuhan 430072, China. Electronic address: jiangpeng@whu.edu.cn."
] |
[
"39368275"
] |
[] | 9.909678 | 4.373467 |
39367952
| 410 |
Antitumor effects of intracranial injection of B7-H3-targeted Car-T and Car-Nk cells in a patient-derived glioblastoma xenograft model.
|
Glioblastoma multiforme (GBM) is the most lethal primary brain tumor for which novel therapies are needed. Recently, chimeric antigen receptor (CAR) T cell therapy has been shown to be effective against GBM, but it is a personalized medicine and requires high cost and long time for the cell production. CAR-transduced natural killer (NK) cells can be used for "off-the-shelf" cellular immunotherapy because they do not induce graft-versus-host disease. Therefore, we aimed to analyze the anti-GBM effect of CAR-T or NK cells targeting B7-H3, which is known to be highly expressed in GBM.
CAR-T cells targeting B7-H3 were generated using previously reported anti-B7-H3 scFv sequences. Cord blood (CB)-derived NK cells transduced with the B7-H3 CAR were also generated. Their anti-GBM effect was analyzed in vitro. The antitumor effect of intracranial injection of the B7-H3 CAR-T or NK cells was investigated in an in vivo xenograft model with patient-derived GBM cells.
Both B7-H3 CAR-T cells and CAR-NK cells exhibited marked cytotoxicity against patient-derived GBM cells in vitro. Furthermore, intracranial injection of CAR-T cells and CAR-NK cells targeting B7-H3 resulted in a significant antitumor effect against patient-derived GBM xenografts.
Not only CAR-T cells but also CB-derived CAR-NK cells targeting B7-H3 may have the potential to eliminate GBM cells.
|
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] | 2024-10-06 | 48 |
39367952
|
[
"GBM cells",
"GBM",
"patient-derived GBM cells",
"CAR-NK cells",
"CAR-T cells",
"anti-B7-H3",
"CAR",
"B7-H3 CAR",
"(CB)-derived NK cells",
"patient-derived GBM xenografts",
"Both B7-H3 CAR-T cells",
"B7-H3",
"CAR-T or NK cells",
"previously reported anti-B7-H3",
"intracranial injection",
"the cell production",
"high cost",
"the B7-H3 CAR-T or NK cells",
"Their anti-GBM effect",
"the anti-GBM effect",
"long time",
"B7-H3 CAR-",
"the B7-H3 CAR",
"also CB-derived CAR-NK cells",
"marked cytotoxicity",
"CAR-transduced natural killer (NK) cells",
"Not only CAR-T cells",
"Cord blood",
"a significant antitumor effect",
"scFv sequences"
] |
[
"Antitumor effect",
"B7-H3",
"CAR-NK cell therapy",
"Glioblastoma (GBM)"
] | 0 |
10.1007/s00262-024-03808-0
|
[
"Tachi",
"Kijima",
"Kuroda",
"Ikeda",
"Murakami",
"Nakagawa",
"Yaga",
"Nakagawa",
"Utsugi",
"Hirayama",
"Okita",
"Kagawa",
"Kishima",
"Imai",
"Hosen"
] |
[
"Department of Neurosurgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 5650871, Japan.",
"Department of Neurosurgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 5650871, Japan. n-kijima@nsurg.med.osaka-u.ac.jp.",
"Department of Neurosurgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 5650871, Japan.",
"World Premier International Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.",
"Department of Neurosurgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 5650871, Japan.",
"Department of Neurosurgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 5650871, Japan.",
"Department of Respiratory Medicine, Osaka General Hospital, Osaka, Japan.",
"Department of Neurosurgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 5650871, Japan.",
"Department of Neurosurgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 5650871, Japan.",
"Department of Neurosurgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 5650871, Japan.",
"Department of Neurosurgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 5650871, Japan.",
"Department of Neurosurgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 5650871, Japan.",
"Department of Neurosurgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 5650871, Japan.",
"Department of Pediatrics, Faculty of Medicine, University of Toyama, Toyama, Japan.",
"World Premier International Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan. hnaoki@bldon.med.osaka-u.ac.jp.\nDepartment of Hematology and Oncology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 5650871, Japan. hnaoki@bldon.med.osaka-u.ac.jp."
] |
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] |
[] | 10.104031 | 7.18975 |
39366753
| 411 |
Antigen-independent activation is critical for the durable antitumor effect of GUCY2C-targeted CAR-T cells.
|
Chimeric antigen receptor (CAR)-T cells face many obstacles in solid tumor therapy, including heterogeneous antigen expression and inefficient T cell persistence. Guanylyl cyclase C (GUCY2C) has been identified as a suitable tumor antigen for targeted therapy due to its intestinal-restricted expression pattern in normal tissues and steady overexpression in gastrointestinal tumors, especially colorectal cancer. An antigen-sensitive and long-lasting CAR-T cell targeting GUCY2C was investigated in this study.
Using constructed tumor cell lines with various GUCY2C expression densities, we screened out an antigen-sensitive single chain variable fragment (scFv) that enabled CAR-T cells to efficiently eradicate the GUCY2C lowly expressed tumor cells. CAR-T cells with different compositions of the hinge, transmembrane and costimulatory domains were also constructed for selection of the long-lasting CAR-T format with durable antitumor efficacy in vitro and in tumor-bearing mice. The underlying mechanism was further investigated based on mutation of the hinge and transmembrane domains.
We found that the composition of the antigen-sensitive scFv, CD8α hinge, CD8α transmembrane, and CD28 costimulatory domains boosted CAR-T cells to rapidly kill tumors, maintain high expansion capacity, and long-term efficacy in various colorectal cancer models. The durable antitumor function was attributed to the optimal CAR tonic signaling that conferred CAR-T cells with autonomous activation, proliferation, survival and cytokine release in the absence of antigen stimulation. The tonic signaling was associated with the length and the cysteine residues in the CD8α hinge and transmembrane domains.
This study demonstrated a potent GUCY2C-targeted CAR-T cell for gastrointestinal tumor therapy and highlights the importance of adequate tonic signaling for effective CAR-T cell therapy against solid tumors.
|
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] | 2024-10-06 | 43 |
39366753
|
[
"tumor cells",
"constructed tumor cell lines",
"gastrointestinal tumor therapy",
"solid tumor therapy",
"CAR)-T cells",
"gastrointestinal tumors",
"inefficient T cell persistence",
"solid tumors",
"tumors",
"heterogeneous antigen expression",
"various GUCY2C expression densities",
"effective CAR-T cell therapy",
"Chimeric antigen receptor",
"targeted therapy",
"antigen stimulation",
"CAR-T cells",
"durable antitumor efficacy",
"CAR",
"GUCY2C",
"various colorectal cancer models",
"CD28 costimulatory domains",
"a suitable tumor antigen",
"adequate tonic",
"high expansion capacity",
"that conferred CAR-T cells",
"a potent GUCY2C-targeted CAR-T cell",
"different compositions",
"Guanylyl cyclase C",
"normal tissues",
"tumor-bearing mice"
] |
[
"Adoptive cell therapy - ACT",
"Chimeric antigen receptor - CAR",
"Colorectal Cancer"
] | 0 |
10.1136/jitc-2024-009960
10.3322/caac.21660
10.3322/caac.21601
10.1615/CritRevOncog.2020035067
10.1126/science.aan6733
10.1080/14737140.2024.2334784
10.1080/17512433.2017.1292124
10.1172/JCI57925
10.1073/pnas.93.25.14827
10.1016/j.humpath.2004.12.002
10.1111/j.1600-0854.2006.00398.x
10.1111/j.1749-6632.2000.tb05246.x
10.1158/1078-0432.CCR-19-3275
10.1080/2162402X.2016.1227897
10.1158/2326-6066.CIR-16-0362
10.15252/embj.2018100928
10.1097/01.cji.0000161397.96582.59
10.3390/cells9051182
10.1038/s41467-023-37616-4
10.1038/nm.3838
10.3390/ijms23074056
10.3389/fimmu.2018.02486
10.1038/nbt.2725
10.1038/s41571-022-00704-3
10.1016/j.tem.2013.01.001
10.1371/journal.pone.0189953
10.1038/s41571-024-00874-2
10.1038/s41591-022-01800-8
10.1186/s13045-023-01491-9
10.3389/fimmu.2023.1321596
10.1016/j.ccell.2021.12.005
10.1038/nrd4597
10.1038/s41586-023-05707-3
10.1158/2326-6066.CIR-14-0127
10.1038/mt.2014.208
10.1016/j.ymthe.2017.07.013
10.1038/s41591-019-0421-7
10.1038/s41590-020-0781-7
10.1073/pnas.2104758118
10.1038/s41586-019-1805-z
10.1038/s41591-021-01326-5
10.1038/s41422-023-00789-0
10.1038/s41422-024-00936-1
|
[
"Qi",
"Liu",
"Liu",
"Wei",
"Ma",
"Lu",
"Tao",
"Zhang",
"Wang",
"He",
"Li",
"Dai",
"Ding",
"Shen"
] |
[
"State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Early Drug Development Centre, Peking University Cancer Hospital, Beijing, China shenlin@bjmu.edu.cn dingyanping@imunopharm.com changsongqi@bjmu.edu.cn.",
"Beijing Imunopharm Technology Co Ltd, Beijing, China.",
"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Early Drug Development Centre, Peking University Cancer Hospital, Beijing, China.",
"Beijing Imunopharm Technology Co Ltd, Beijing, China.",
"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital, Beijing, China.",
"Beijing Imunopharm Technology Co Ltd, Beijing, China.",
"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital, Beijing, China.",
"State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital, Beijing, China.",
"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital, Beijing, China.",
"Beijing Imunopharm Technology Co Ltd, Beijing, China.",
"State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital, Beijing, China.",
"Beijing Imunopharm Technology Co Ltd, Beijing, China.",
"Beijing Imunopharm Technology Co Ltd, Beijing, China shenlin@bjmu.edu.cn dingyanping@imunopharm.com changsongqi@bjmu.edu.cn.",
"State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital, Beijing, China shenlin@bjmu.edu.cn dingyanping@imunopharm.com changsongqi@bjmu.edu.cn."
] |
[
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] |
[] | 8.959483 | 5.765018 |
39364400
| 412 |
High specificity of engineered T cells with third generation CAR (CD28-4-1BB-CD3-ζ) based on biotin-bound monomeric streptavidin for potential tumor immunotherapy.
|
Immunotherapy has revolutionized cancer treatment, and Chimeric Antigen Receptor T cell therapy (CAR-T) is a groundbreaking approach. Traditional second-generation CAR-T therapies have achieved remarkable success in hematological malignancies, but there is still room for improvement, particularly in developing new targeting strategies. To address this limitation, engineering T cells with multi-target universal CARs (UniCARs) based on monomeric streptavidin has emerged as a versatile approach in the field of anti-tumor immunotherapy. However, no studies have been conducted on the importance of the intracellular signaling domains of such CARs and their impact on efficiency and specificity.
Here, we developed second-generation and third-generation UniCARs based on an extracellular domain comprising an affinity-enhanced monomeric streptavidin, in addition to CD28 and 4-1BB co-stimulatory intracellular domains. These UniCAR structures rely on a biotinylated intermediary, such as an antibody, for recognizing target antigens. In co-culture assays, we performed a functional comparison between the third-generation UniCAR construct and two second-generation UniCAR variants, each incorporating either the CD28 or 4-1BB as co-stimulatory domain.
We observed that components in culture media could inhibit the binding of biotinylated antibodies to monomeric streptavidin-CARs, potentially compromising their efficacy. Furthermore, third-generation UniCAR-T cells showed robust cytolytic activity against cancer cell lines upon exposure to specific biotinylated antibodies like anti-CD19 and anti-CD20, underscoring their capability for multi-targeting. Importantly, when assessing engineered UniCAR-T cell activation upon encountering their target cells, third-generation UniCAR-T cells exhibited significantly enhanced specificity compared to second-generation CAR-T cells.
First, optimizing culture conditions would be essential before deploying UniCAR-T cells clinically. Moreover, we propose that third-generation UniCAR-T cells are excellent candidates for preclinical research due to their high specificity and multi-target anti-tumor cytotoxicity.
|
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39364400
|
[
"engineering T cells",
"multi-target anti-tumor cytotoxicity",
"multi-target universal CARs",
"co-stimulatory domain",
"anti-tumor immunotherapy",
"cancer cell lines",
"such CARs",
"engineered UniCAR-T cell activation",
"UniCAR-T cells",
"specific biotinylated antibodies",
"UniCAR",
"anti-CD19 and anti-CD20",
"biotinylated antibodies",
"co-culture assays",
"third-generation UniCAR-T cells",
"second-generation CAR-T cells",
"culture media",
"third",
"culture conditions",
"Traditional second-generation CAR-T therapies",
"cancer treatment",
"monomeric streptavidin",
"robust cytolytic activity",
"specificity",
"hematological malignancies",
"new targeting strategies",
"remarkable success",
"second",
"Chimeric Antigen",
"the third-generation UniCAR construct"
] |
[
"Chimeric Antigen Receptor",
"Treg",
"engineered cells",
"immunosuppression",
"streptavidin-based CAR"
] | 0 |
10.3389/fimmu.2024.1448752
10.1186/s13287-022-03163-w
10.3389/fimmu.2022.886546
10.1038/bcj.2017.53
10.1002/ajh.25442
10.1097/PPO.0000000000000514
10.1016/j.addr.2012.09.039
10.3390/ijms21239163
10.1016/0006-291X(87)90502-X
10.1038/nm.3838
10.1002/cti2.1049
10.1056/NEJMra0904569
10.1056/NEJMoa1215134
10.1038/gt.2010.91
10.1073/pnas.1524193113
10.1186/s13045-018-0677-2
10.1038/bcj.2016.61
10.1080/2162402X.2017.1368604
10.1002/bit.24605
10.1016/j.ymthe.2020.09.027
10.1002/ajh.26519
10.1038/s41409-021-01463-y
10.1080/00365513.2020.1858493
10.1126/sciimmunol.abd4344
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10.1016/j.ccell.2019.12.014
10.3389/fimmu.2021.639818
10.1038/s41467-023-40303-z
10.3390/cancers15123081
10.1038/s41422-023-00789-0
10.1186/s40425-017-0246-1
10.1038/mt.2009.210
10.1089/hum.2007.028
10.1089/hum.2013.209
10.1038/mt.2013.192
10.1182/blood-2011-10-387969
10.1080/2162402X.2021.1945804
|
[
"Gallego-Valle",
"Pérez-Fernández",
"Rosales-Magallares",
"Gil-Manso",
"Castellá",
"Gonzalez-Navarro",
"Correa-Rocha",
"Juan",
"Pion"
] |
[
"Group of Advanced Immuno-Regulation (GIRA), Gregorio Marañon Health Research Institute Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Hospital General Gregorio Marañon, Madrid, Spain.",
"Group of Advanced Immuno-Regulation (GIRA), Gregorio Marañon Health Research Institute Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Hospital General Gregorio Marañon, Madrid, Spain.",
"Group of Advanced Immuno-Regulation (GIRA), Gregorio Marañon Health Research Institute Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Hospital General Gregorio Marañon, Madrid, Spain.",
"Group of Advanced Immuno-Regulation (GIRA), Gregorio Marañon Health Research Institute Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Hospital General Gregorio Marañon, Madrid, Spain.\nImmune-Regulation Laboratory (LIR), Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Hospital General Gregorio Marañon, Madrid, Spain.",
"Immunology Service, Centre for Biomedical Diagnosis (CDB), Hospital Clínic de Barcelona (HCB), Joint Platform for Immunotherapy of Hospital Sant Joan de Deu, Barcelona, Spain.",
"Immunology Service, Centre for Biomedical Diagnosis (CDB), Hospital Clínic de Barcelona (HCB), Joint Platform for Immunotherapy of Hospital Sant Joan de Deu, Barcelona, Spain.",
"Immune-Regulation Laboratory (LIR), Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Hospital General Gregorio Marañon, Madrid, Spain.",
"Immunology Service, Centre for Biomedical Diagnosis (CDB), Hospital Clínic de Barcelona (HCB), Joint Platform for Immunotherapy of Hospital Sant Joan de Deu, Barcelona, Spain.",
"Group of Advanced Immuno-Regulation (GIRA), Gregorio Marañon Health Research Institute Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Hospital General Gregorio Marañon, Madrid, Spain."
] |
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[] | 8.666682 | 4.750244 |
39364321
| 413 |
EGFRVIII and EGFR targeted chimeric antigen receptor T cell therapy in glioblastoma.
|
Glioblastoma is the most common primary brain tumor. Although there have been significant advances in surgical techniques, chemo and immunotherapies, and radiation therapy, outcomes continue to be devastating for these patients with minimal improvements in survival. Chimeric antigen receptor T cell therapy is a revolutionary approach that is a new pillar in the treatment of cancer. CAR T cell therapy has produced remarkable results in hematological malignancies; however, multiple limitations currently prevent it from being a first-line therapy, especially for solid tumors. Epidermal growth factor receptor is classically amplified in glioblastoma, and a variant, EGFR variant III, is expressed on glioblastoma, making it an exciting potential target for CAR T cell therapy. Although preclinical has exciting potential, clinical data has been heterogeneous. In this review, we assess the state of field of EGFR-targeted CAR T cells.
|
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] | 2024-10-04 | 56 |
39364321
|
[
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"radiation therapy",
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"exciting potential",
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"surgical techniques",
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"III",
"a first-line therapy",
"Glioblastoma",
"survival",
"cancer",
"the most common primary brain tumor",
"a new pillar",
"a revolutionary approach"
] |
[
"CAR T cell",
"EGFR",
"EGFRvIII",
"chimeric antigen receptor T cell",
"epidermal growth factor receptor",
"epidermal growth factor receptor variant III",
"glioblastoma",
"solid tumor"
] | 0 |
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10.1186/s12943-019-1092-1
10.1186/s13045-020-00856-8
10.1093/noajnl/vdac185
10.1126/scitranslmed.abe7378
10.1038/s41587-019-0192-1
10.1056/NEJMoa2314390
10.18632/oncotarget.27389
10.1038/s41591-024-02893-z
10.1007/s10875-012-9689-9
10.1186/s40425-017-0222-9
10.1172/JCI83416
|
[
"Sterner",
"Sterner"
] |
[
"Department of Neurosurgery, Inova Fairfax Medical Campus, Fairfax, VA, United States.",
"Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States."
] |
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[] | 10.050704 | 7.324924 |
39364307
| 414 |
Next-Generation Therapies for Multiple Myeloma.
|
Recent therapeutic advances have significantly improved the outcome for patients with multiple myeloma (MM). The backbone of successful standard therapy is the combination of Ikaros degraders, glucocorticoids, and proteasome inhibitors that interfere with the integrity of myeloma-specific superenhancers by directly or indirectly targeting enhancer-bound transcription factors and coactivators that control expression of MM dependency genes. T cell engagers and chimeric antigen receptor T cells redirect patients' own T cells onto defined tumor antigens to kill MM cells. They have induced complete remissions even in end-stage patients. Unfortunately, responses to both conventional therapy and immunotherapy are not durable, and tumor heterogeneity, antigen loss, and lack of T cell fitness lead to therapy resistance and relapse. Novel approaches are under development to target myeloma-specific vulnerabilities, as is the design of multimodality immunological approaches, including and beyond T cells, that simultaneously recognize multiple epitopes to prevent antigen escape and tumor relapse.
|
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] | 2024-10-04 | 92 |
39364307
|
[
"T cells",
"T cell engagers",
"T cell fitness lead",
"defined tumor antigens",
"MM cells",
"multiple myeloma",
"successful standard therapy",
"therapy resistance",
"chimeric antigen receptor",
"tumor heterogeneity",
"multimodality immunological approaches",
"patients own T cells",
"multiple epitopes",
"MM dependency genes",
"patients",
"Ikaros degraders",
"Recent therapeutic advances",
"proteasome inhibitors",
"Novel approaches",
"complete remissions",
"antigen loss",
"antigen escape and tumor relapse",
"MM",
"myeloma-specific superenhancers",
"myeloma-specific vulnerabilities",
"expression",
"enhancer-bound transcription factors",
"coactivators",
"Ikaros",
"glucocorticoids"
] |
[
"CAR T cell",
"EP300",
"T cell engagers",
"bispecific antibody",
"chimeric antigen receptor",
"multiple myeloma",
"superenhancers"
] | 0 |
10.1146/annurev-cancerbio-061421-014236
|
[
"Meermeier",
"Bergsagel",
"Chesi"
] |
[
"Department of Immunology, Mayo Clinic, Scottsdale, Arizona, USA.",
"Department of Medicine, Mayo Clinic, Scottsdale, Arizona, USA.",
"Department of Medicine, Mayo Clinic, Scottsdale, Arizona, USA."
] |
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[] | 4.845499 | 6.370408 |
39358720
| 415 |
Efficacy and safety of CAR-T therapy targeting CLL1 in patients with extramedullary diseases of acute myeloid leukemia.
|
The incidence of extramedullary diseases (EMDs) in patients diagnosed with acute myeloid leukemia (AML) is approximately 10-20%. These patients exhibit a significantly distinct etiology, therapeutic response, and prognosis compared to patients without EMDs. CLL1 CAR-T therapy has been demonstrated satisfactory efficacy and safety in the treatment of refractory and relapsed AML patients. However, concerns have been raised regarding the potential impact of extramedullary niduses on the effectiveness of CLL1 CAR-T therapy.
A total of 47 patients were enrolled in this study, including 27 patients with isolated AML tumor bone marrow infiltration and 20 patients with both extramedullary and bone marrow infiltration of AML. CLL1 CAR-T cells were manufactured and subjected to rigorous quality control in the hematology laboratory of Tianjin First Central Hospital. The efficacy and adverse reactions were assessed following CAR-T cell infusion, while expansion of CAR-T cells, levels of cytokines releasing, and other indicators were closely monitored.
Among the 20 patients with EMDs and the 27 individuals without EMDs, complete remission in bone marrow was achieved by 65.00% and 81.48% of patients, respectively. Meanwhile, among the patients with EMDs, 55.00% achieved complete remission while 10.00% achieved partial remission when assessing the efficacy of CLL1 CAR-T cells against extramedullary niduses. Although the overall survival, progression-free survival, and duration of remission period appeared to be shorter for patients with EMDs compared to those without EMDs, this difference did not reach statistical significance. The incidence rates of complications were comparable between both groups. Meanwhile, there were no significant differences observed in the levels of CAR-T cell expansion and accompanying cytokines release between patients with and without EMDs.
Our study findings have demonstrated the efficacy of CLL1 CAR-T therapy in the treatment of AML patients with EMDs, while also indicating manageable occurrence rates of complications within a tolerable range. The CLL1 CAR-T therapy, serving as an ideal strategy for AML patients irrespective of the presence of EMDs, effectively ameliorates the conditions of AML patients and provides them with an opportunity to undergo curative hematopoietic stem cell transplantation while significantly enhancing their prognosis.
|
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] | 2024-10-03 | 34 |
39358720
|
[
"AML patients",
"patients",
"EMDs",
"isolated AML tumor bone marrow infiltration",
"curative hematopoietic stem cell transplantation",
"CLL1 CAR-T cells",
"CLL1 CAR-T therapy",
"complete remission",
"CAR-T cell expansion",
"AML",
"remission period",
"CAR-T cells",
"extramedullary niduses",
"bone marrow",
"partial remission",
"manageable occurrence rates",
"satisfactory efficacy",
"Tianjin First Central Hospital",
"extramedullary diseases",
"rigorous quality control",
"CAR-T cell infusion",
"accompanying cytokines",
"The CLL1 CAR-T therapy",
"acute myeloid leukemia",
"therapeutic response",
"complications",
"other indicators",
"20 patients",
"27 patients",
"47 patients"
] |
[
"CAR-T",
"CLL1, acute myeloid leukemia",
"Extramedullary diseases"
] | 0 |
10.1186/s12967-024-05705-7
|
[
"Zhao",
"Bai",
"Guo",
"Zhang",
"Liu",
"Zhao",
"Xie",
"Meng",
"Zhang",
"He",
"Zhao"
] |
[
"The First Central Clinical College of Tianjin Medical University, Tianjin, 300380, China.",
"The First Central Clinical College of Tianjin Medical University, Tianjin, 300380, China.",
"The First Central Clinical College of Tianjin Medical University, Tianjin, 300380, China.",
"Nankai University School of Medicine, Tianjin, 300380, China.",
"The First Central Clinical College of Tianjin Medical University, Tianjin, 300380, China.",
"The First Central Clinical College of Tianjin Medical University, Tianjin, 300380, China.",
"Nankai University School of Medicine, Tianjin, 300380, China.",
"Nankai University School of Medicine, Tianjin, 300380, China.",
"Department of Hematology, Tianjin First Central Hospital, No.2 Baoshanxi Rd, Xiqing District, Tianjin, 300380, China.",
"Department of Hematology, Tianjin First Central Hospital, No.2 Baoshanxi Rd, Xiqing District, Tianjin, 300380, China.",
"Department of Hematology, Tianjin First Central Hospital, No.2 Baoshanxi Rd, Xiqing District, Tianjin, 300380, China. mingfengzhao@sina.com."
] |
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[] | 6.622343 | 6.946392 |
39358663
| 416 |
PD-1 blockade does not improve efficacy of EpCAM-directed CAR T-cell in lung cancer brain metastasis.
|
Lung cancer brain metastasis has a devastating prognosis, necessitating innovative treatment strategies. While chimeric antigen receptor (CAR) T-cell show promise in hematologic malignancies, their efficacy in solid tumors, including brain metastasis, is limited by the immunosuppressive tumor environment. The PD-L1/PD-1 pathway inhibits CAR T-cell activity in the tumor microenvironment, presenting a potential target to enhance therapeutic efficacy. This study aims to evaluate the impact of anti-PD-1 antibodies on CAR T-cell in treating lung cancer brain metastasis.
We utilized a murine immunocompetent, syngeneic orthotopic cerebral metastasis model for repetitive intracerebral two-photon laser scanning microscopy, enabling in vivo characterization of red fluorescent tumor cells and CAR T-cell at a single-cell level over time. Red fluorescent EpCAM-transduced Lewis lung carcinoma cells (
Compared to controls receiving T-cell lacking a CAR, mice receiving EpCAM-directed CAR T-cell showed higher intratumoral CAR T-cell densities in the beginning after intraparenchymal injection. This finding was accompanied with reduced tumor growth and translated into a survival benefit. Additional anti-PD-1 treatment, however, did not affect intratumoral CAR T-cell persistence nor tumor growth and thereby did not provide an additional therapeutic effect.
CAR T-cell therapy for brain malignancies appears promising. However, additional anti-PD-1 treatment did not enhance intratumoral CAR T-cell persistence or effector function, highlighting the need for novel strategies to improve CAR T-cell therapy in solid tumors.
|
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] | 2024-10-03 | 67 |
39358663
|
[
"red fluorescent tumor cells",
"Lung cancer brain metastasis",
"lung cancer brain metastasis",
"Additional anti-PD-1 treatment",
"additional anti-PD-1 treatment",
"EpCAM-directed CAR T-cell",
"intratumoral CAR T-cell persistence",
"tumor growth",
"higher intratumoral CAR T-cell densities",
"reduced tumor growth",
"brain metastasis",
"CAR T-cell therapy",
"solid tumors",
"CAR T-cell activity",
"CAR T-cell",
"brain malignancies",
"intratumoral CAR T-cell persistence or effector function",
"Red fluorescent EpCAM-transduced Lewis lung carcinoma cells",
"innovative treatment strategies",
"therapeutic efficacy",
"hematologic malignancies",
"(CAR) T-cell show promise",
"novel strategies",
", syngeneic orthotopic cerebral metastasis model",
"vivo characterization",
"chimeric antigen receptor",
"the immunosuppressive tumor environment",
"the tumor microenvironment",
"intraparenchymal injection",
"a single-cell level"
] |
[
"Brain metastasis",
"CAR T cell",
"Lung cancer",
"PD-1-blockade"
] | 0 |
10.1007/s00262-024-03837-9
|
[
"Blobner",
"Dengler",
"Eberle",
"Herold",
"Xu",
"Beck",
"Mühlbauer",
"Müller",
"Teske",
"Karschnia",
"van den Heuvel",
"Schallerer",
"Ishikawa-Ankerhold",
"Thon",
"Tonn",
"Subklewe",
"Kobold",
"Harter",
"Buchholz",
"von Baumgarten"
] |
[
"Department of Neurosurgery, LMU University Hospital, Ludwig Maximilians University (LMU), 81377, Munich, Germany.\nGerman Cancer Consortium (DKTK), Partner Site Munich, A Partnership Between the DKFZ Heidelberg and the University Hospital of the LMU, Munich, Germany.\nDivision of Neuro-Oncology, Department of Neurosurgery, Ludwig Maximilians University School of Medicine, Marchioninistrasse 15, 81377, Munich, Germany.",
"German Cancer Consortium (DKTK), Partner Site Munich, A Partnership Between the DKFZ Heidelberg and the University Hospital of the LMU, Munich, Germany.",
"German Cancer Consortium (DKTK), Partner Site Munich, A Partnership Between the DKFZ Heidelberg and the University Hospital of the LMU, Munich, Germany.",
"German Cancer Consortium (DKTK), Partner Site Munich, A Partnership Between the DKFZ Heidelberg and the University Hospital of the LMU, Munich, Germany.",
"German Cancer Consortium (DKTK), Partner Site Munich, A Partnership Between the DKFZ Heidelberg and the University Hospital of the LMU, Munich, Germany.\nDepartment of Neurology, LMU University Hospital, Ludwig Maximilians University (LMU), 81377, Munich, Germany.",
"German Cancer Consortium (DKTK), Partner Site Munich, A Partnership Between the DKFZ Heidelberg and the University Hospital of the LMU, Munich, Germany.\nCenter for Neuropathology and Prion Research, Faculty of Medicine LMU Munich, Ludwig-Maximilians-University (LMU), Munich, Germany.",
"Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, 81675, Munich, Germany.",
"German Cancer Consortium (DKTK), Partner Site Munich, A Partnership Between the DKFZ Heidelberg and the University Hospital of the LMU, Munich, Germany.\nDepartment of Neurology, LMU University Hospital, Ludwig Maximilians University (LMU), 81377, Munich, Germany.",
"Department of Neurosurgery, LMU University Hospital, Ludwig Maximilians University (LMU), 81377, Munich, Germany.\nGerman Cancer Consortium (DKTK), Partner Site Munich, A Partnership Between the DKFZ Heidelberg and the University Hospital of the LMU, Munich, Germany.",
"Department of Neurosurgery, LMU University Hospital, Ludwig Maximilians University (LMU), 81377, Munich, Germany.\nGerman Cancer Consortium (DKTK), Partner Site Munich, A Partnership Between the DKFZ Heidelberg and the University Hospital of the LMU, Munich, Germany.",
"Department of Medicine I, Ludwig-Maximilians-University School of Medicine, Munich, Germany.",
"German Cancer Consortium (DKTK), Partner Site Munich, A Partnership Between the DKFZ Heidelberg and the University Hospital of the LMU, Munich, Germany.",
"Department of Medicine I, Ludwig-Maximilians-University School of Medicine, Munich, Germany.",
"Department of Neurosurgery, LMU University Hospital, Ludwig Maximilians University (LMU), 81377, Munich, Germany.\nGerman Cancer Consortium (DKTK), Partner Site Munich, A Partnership Between the DKFZ Heidelberg and the University Hospital of the LMU, Munich, Germany.\nDivision of Neuro-Oncology, Department of Neurosurgery, Ludwig Maximilians University School of Medicine, Marchioninistrasse 15, 81377, Munich, Germany.",
"Department of Neurosurgery, LMU University Hospital, Ludwig Maximilians University (LMU), 81377, Munich, Germany.\nGerman Cancer Consortium (DKTK), Partner Site Munich, A Partnership Between the DKFZ Heidelberg and the University Hospital of the LMU, Munich, Germany.",
"German Cancer Consortium (DKTK), Partner Site Munich, A Partnership Between the DKFZ Heidelberg and the University Hospital of the LMU, Munich, Germany.\nDepartment of Medicine III, Ludwig-Maximilians-University School of Medicine, Munich, Germany.\nBavarian Cancer Research Center (BZKF), 91054, Erlangen, Germany.",
"German Cancer Consortium (DKTK), Partner Site Munich, A Partnership Between the DKFZ Heidelberg and the University Hospital of the LMU, Munich, Germany.\nDepartment of Medicine IV, Division of Clinical Pharmacology, LMU University Hospital Munich, Munich, Germany.",
"German Cancer Consortium (DKTK), Partner Site Munich, A Partnership Between the DKFZ Heidelberg and the University Hospital of the LMU, Munich, Germany.\nCenter for Neuropathology and Prion Research, Faculty of Medicine LMU Munich, Ludwig-Maximilians-University (LMU), Munich, Germany.\nBavarian Cancer Research Center (BZKF), 91054, Erlangen, Germany.",
"Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, 81675, Munich, Germany.",
"Department of Neurosurgery, LMU University Hospital, Ludwig Maximilians University (LMU), 81377, Munich, Germany. Louisa.vonBaumgarten@med.uni-muenchen.de.\nGerman Cancer Consortium (DKTK), Partner Site Munich, A Partnership Between the DKFZ Heidelberg and the University Hospital of the LMU, Munich, Germany. Louisa.vonBaumgarten@med.uni-muenchen.de.\nDepartment of Neurology, LMU University Hospital, Ludwig Maximilians University (LMU), 81377, Munich, Germany. Louisa.vonBaumgarten@med.uni-muenchen.de.\nBavarian Cancer Research Center (BZKF), 91054, Erlangen, Germany. Louisa.vonBaumgarten@med.uni-muenchen.de.\nDivision of Neuro-Oncology, Department of Neurosurgery, Ludwig Maximilians University School of Medicine, Marchioninistrasse 15, 81377, Munich, Germany. Louisa.vonBaumgarten@med.uni-muenchen.de."
] |
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[] | 9.70583 | 6.210761 |
39358273
| 417 |
[Practical guidance for CAR T-cell therapy in adults].
|
Chimeric antigen receptor (CAR) T-cell therapy is an innovative treatment for B-cell malignancies and multiple myeloma. CAR T-cell therapy is now approved in Japan and has become one of the essential therapeutic options for chemotherapy-resistant disease. It has many unique features that distinguish it from conventional chemotherapies, including the limitations imposed by the production of CAR-T cells from autologous T cells, and the limited availability and mandatory waiting period for treatment. Importantly, each patient has only one opportunity to receive CAR T-cell therapy. To achieve the maximum therapeutic benefit from CAR T-cell therapy, it is necessary to understand all aspects of CAR T-cell therapy, including factors that influence its efficacy. The design of the entire treatment sequence, including before and after CAR T-cell therapy, is also important to optimize clinical outcomes. In addition, since this treatment is only available at a limited number of facilities, effective coordination between local hospitals and treatment centers is also important. This educational session will focus on the practical aspects of CAR T-cell therapy in adults and will provide indispensable knowledge for providing CAR T-cell therapy to patients with B-cell lymphoma and multiple myeloma.
|
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39358273
|
[
"autologous T cells",
"CAR T-cell therapy",
"treatment centers",
"treatment",
"CAR) T-cell therapy",
"CAR-T cells",
"conventional chemotherapies",
"many unique features",
"B-cell malignancies",
"B-cell lymphoma",
"mandatory waiting period",
"effective coordination",
"local hospitals",
"multiple myeloma",
"Chimeric antigen receptor",
"indispensable knowledge",
"the entire treatment sequence",
"clinical outcomes",
"patients",
"facilities",
"the essential therapeutic options",
"an innovative treatment",
"Japan",
"the maximum therapeutic benefit",
"adults",
"chemotherapy-resistant disease",
"factors",
"a limited number",
"the limited availability",
"this treatment"
] |
[
"Adults",
"B-cell lymphoma",
"CAR T-cell therapy",
"Multiple myeloma"
] | 0 |
10.11406/rinketsu.65.1155
|
[
"Kitawaki"
] |
[
"Department of Hematology, Kyoto University Hospital."
] |
[
"39358273"
] |
[] | 7.219411 | 4.712764 |
39353594
| 418 |
Immunoediting Dynamics in Glioblastoma: Implications for Immunotherapy Approaches.
|
Glioblastoma is an aggressive primary brain tumor that poses many therapeutic difficulties because of the high rate of proliferation, genetic variability, and its immunosuppressive microenvironment. The theory of cancer immunoediting, which includes the phases of elimination, equilibrium, and escape, offers a paradigm for comprehending interactions between the immune system and glioblastoma. Immunoediting indicates the process by which immune cells initially suppress tumor development, but thereafter select for immune-resistant versions leading to tumor escape and progression. The tumor microenvironment (TME) in glioblastoma is particularly immunosuppressive, with regulatory T cells and myeloid-derived suppressor cells being involved in immune escape. To achieve an efficient immunotherapy for glioblastoma, it is crucial to understand these mechanisms within the TME. Existing immunotherapeutic modalities such as chimeric antigen receptor T cells and immune checkpoint inhibitors have been met with some level of resistance because of the heterogeneous nature of the immune response to glioblastoma. Solving these issues is critical to develop novel strategies capable of modulating the TME and re-establishing normal immune monitoring. Further studies should be conducted to identify the molecular and cellular events that underlie the immunosuppressive tumor microenvironment in glioblastoma. Comprehending and modifying the stages of immunoediting in glioblastoma could facilitate the development of more potent and long-lasting therapies.
|
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] | 2024-10-03 | 165 |
39353594
|
[
"tumor development",
"immune escape",
"immune checkpoint inhibitors",
"chimeric antigen receptor T cells",
"normal immune monitoring",
"tumor escape",
"regulatory T cells",
"glioblastoma",
"many therapeutic difficulties",
"TME",
"novel strategies",
"cancer immunoediting",
"Existing immunotherapeutic modalities",
"comprehending interactions",
"the immunosuppressive tumor microenvironment",
"which immune cells",
"an aggressive primary brain tumor",
"genetic variability",
"Immunoediting",
"myeloid-derived suppressor cells",
"Further studies",
"The tumor microenvironment",
"the immune system",
"the immune response",
"elimination",
"equilibrium",
"proliferation",
"resistance",
"myeloid",
"its immunosuppressive microenvironment"
] |
[
"chimeric antigen receptor-T",
"glioblastoma",
"immunoediting",
"immunotherapy",
"tumor microenvironment"
] | 0 |
10.1177/10732748241290067
|
[
"Amin",
"Hossain",
"Jerin",
"Mahmud",
"Rahman",
"Rafiqul Islam",
"Islam"
] |
[
"Department of Biochemistry & Microbiology, North South University, Dhaka, Bangladesh.",
"Department of Biochemistry & Microbiology, North South University, Dhaka, Bangladesh.",
"Department of Biochemistry & Microbiology, North South University, Dhaka, Bangladesh.",
"Department of Public Health, North South University, Dhaka, Bangladesh.",
"Department of Physiology and Biophysics, Howard University, College of Medicine, Washington, DC, USA.",
"Surgery Branch, National Cancer Institute, National Institute of Health, Bethesda, USA.",
"Department of Biochemistry & Microbiology, North South University, Dhaka, Bangladesh."
] |
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] |
[] | 10.185403 | 7.386109 |
39352918
| 419 |
PD1CD28 chimeric molecule enhances EGFRvⅢ specific CAR-T cells in xenograft experiments in mouse models.
|
Over the years, CAR-T cell therapy has achieved remarkable success in treating hematological malignancies. However, this efficacy has not been replicated in the context of glioblastoma (GBM). In this study, a PD1CD28 chimeric molecule was introduced into EGFRvⅢ-directed CAR-T cells, generating EGFRvⅢ-P2A-PD1CD28 CAR-T cells. Notably, this modification significantly increased IL-2 secretion and enhanced antigen-dependent activation of CAR-T cells, especially when programmed cell death ligand 1 (PD-L1) was present in vitro. In addition, the in vivo xenograft experiments revealed that the PD1CD28 chimeric molecule played a pivotal role in reducing recurrence rates, effectively controlling recurrent tumor volume, and ultimately prolonging the survival of mice. Collectively, these findings suggest that EGFRvⅢ-directed CAR-T cells co-expressing the PD1CD28 chimeric molecule have the potential to significantly enhance the treatment efficacy against GBM.
|
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] | 2024-10-03 | 40 |
39352918
|
[
"cell death ligand",
"recurrent tumor volume",
"EGFRvⅢ-directed CAR-T cells",
"CAR-T cell therapy",
"CAR-T cells",
"vivo xenograft experiments",
"a PD1CD28 chimeric molecule",
"the PD1CD28 chimeric molecule",
"remarkable success",
"recurrence rates",
"EGFRvⅢ-P2A-PD1CD28 CAR-T cells",
"hematological malignancies",
"GBM",
"enhanced antigen-dependent activation",
"glioblastoma",
"mice",
"addition",
"the treatment efficacy",
"a pivotal role",
"this efficacy",
"(PD-L1",
"the potential",
"the survival",
"the context",
"this modification",
"these findings",
"the years",
"this study"
] |
[] | 0 |
10.1371/journal.pone.0310430
10.1056/NEJMoa1308345
10.1016/j.ijrobp.2021.12.152
10.1056/NEJMoa043330
10.1093/neuonc/nou087
10.1038/s41590-019-0433-y
10.1038/nrc.2016.97
10.1038/s41591-019-0421-7
10.1158/1078-0432.CCR-20-3863
10.1172/JCI85309
10.1126/scitranslmed.aaa4963
10.1097/CJI.0000000000000260
10.1002/cti2.1283
10.1186/s40425-019-0806-7
10.1126/scitranslmed.aaa0984
10.1038/bjc.1996.260
10.1111/j.1349-7006.2000.tb00882.x
10.1158/0008-5472.CAN-15-2524
10.1126/scitranslmed.3010162
10.3389/fonc.2015.00005
10.1074/jbc.272.5.2927
10.18632/oncotarget.8201
10.1038/onc.2014.448
10.1158/1078-0432.CCR-18-1625
10.1126/scitranslmed.aad7118
10.1172/JCI83092
10.1182/blood-2016-09-738245
10.1038/nbt.4195
10.1016/j.omto.2018.08.002
10.1186/s40425-018-0340-z
10.1016/j.jcyt.2020.05.007
10.1080/2162402X.2019.1684127
10.1038/s41408-021-00499-z
10.1093/neuonc/nov172
10.1215/15228517-2008-104
10.1007/s13402-022-00747-9
10.1007/s11899-023-00687-7
10.1038/s41571-022-00704-3
10.1371/journal.pone.0094281
|
[
"Chen",
"Xian",
"Zhao",
"Zhang",
"Xu"
] |
[
"School of Pharmacy, Quanzhou Medical College, Quanzhou, Fujian, China.",
"Institute of Immunotherapy, Fujian Medical University, Fuzhou, Fujian, China.\nTcelltech Biological Science and Technology Inc., Fuzhou, Fujian, China.",
"Laboratory Animal Center, Fujian Medical University, Fuzhou, Fujian, China.",
"School of Pharmacy, Fujian Medical University, Fuzhou, Fujian, China.",
"Laboratory of Snake Venom, The Center of Translational Hematology, Fujian Medical University, Fuzhou, Fujian, China."
] |
[
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"24722266"
] |
[] | 9.99767 | 7.284836 |
39355240
| 420 |
Case report: Successful combination of CLL1 CAR-T therapy and hematopoietic stem cell transplantation in a 73-year-old patient diagnosed with refractory acute myeloid leukemia.
|
The incidence of Acute myeloid leukemia (AML) increases with advancing age, and the prognosis for elderly patients is significantly poorer compared to younger patients. Although the combination therapy of venetoclax and hypomethylating agents has demonstrated improved prognosis in patients unable to tolerate intensive chemotherapy, there remains a therapeutic blank for those who fail to achieve remission with current treatment regimens. Here, we report the successful clinical utilization of autogenous CLL1 CAR-T therapy combined with hematopoietic stem cell transplantation in a 73-year-old patient diagnosed with refractory AML. The patient achieved morphological complete remission (CR) with incomplete marrow recovery and a slight presence of minimal residual disease (MRD) after receiving CLL1 CAR-T therapy. To further enhance the treatment and promote the recovery of hemopoiesis, we performed bridged allogenic hematopoietic stem cell transplantation (allo-HSCT) 20 days after the infusion of CLL1 CAR-T cells. The patient achieved MRD-negative CR following HSCT treatment. His primary disease maintained a complete remission status during the 11-month follow-up period. The patient encountered grade 2 cytokine release syndrome and grade 4 granulocytopenia subsequent to the infusion of CAR-T cells, while several rounds of infection and graft-versus-host disease were observed following allo-HSCT. Nevertheless, all these concerns were successfully addressed through comprehensive provision of supportive treatments. We have successfully demonstrated a highly effective and safe combination strategy involving CLL1 CAR-T therapy and allo-HSCT, which has exhibited remarkable tolerability and holds great promise even for elderly patients with AML.
|
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] | 2024-10-02 | 20 |
39355240
|
[
"elderly patients",
"younger patients",
"patients",
"HSCT treatment",
"bridged allogenic hematopoietic stem cell transplantation",
"hematopoietic stem cell transplantation",
"morphological complete remission",
"autogenous CLL1 CAR-T therapy",
"CLL1 CAR-T cells",
"minimal residual disease",
"CLL1 CAR-T therapy",
"incomplete marrow recovery",
"supportive treatments",
"current treatment regimens",
"remission",
"improved prognosis",
"HSCT",
"refractory AML",
"CAR-T cells",
"Acute myeloid leukemia",
"comprehensive provision",
"AML",
"intensive chemotherapy",
"advancing age",
"great promise",
"allogenic hematopoietic",
"hypomethylating agents",
"CR",
"remarkable tolerability",
"Acute myeloid"
] |
[
"CLL1",
"acute myeloid leukemia",
"chimeric antigen receptor T cell",
"hematopoietic stem cell transplantation",
"older"
] | 0 |
10.3389/fimmu.2024.1454614
10.1097/HS9.0000000000000914
10.1182/blood-2011-12-379008
10.2217/fon-2022-0565
10.1007/s00277-020-04375-x
10.1002/ajh.26039
10.1182/blood-2018-08-868752
10.1038/s41375-022-01703-0
10.1186/s13045-022-01308-1
10.1038/s41408-021-00425-3
10.1182/blood-2005-09-3724
10.1200/JCO.2009.22.2547
10.1158/1078-0432.CCR-19-1900
10.1016/S1470-2045(18)30010-X
10.1056/NEJMoa1817226
10.1056/NEJMoa1215134
10.1038/s41591-021-01436-0
10.1016/j.jtct.2023.03.012
10.1002/hem3.v8.3
10.3389/fimmu.2024.1389227
|
[
"Zhao",
"Wang",
"Zhang",
"Zhang",
"Zhang",
"Zhao",
"Liu",
"Guo",
"Zhao"
] |
[
"The First Central Clinical College of Tianjin Medical University, Tianjin, China.",
"The First Central Clinical College of Tianjin Medical University, Tianjin, China.\nDepartment of Intensive Care Medicine, Tianjin Hospital, Tianjin, China.",
"Department of Hematology, Tianjin First Central Hospital, Tianjin, China.",
"The First Central Clinical College of Tianjin Medical University, Tianjin, China.",
"Nankai University School of Medicine, Tianjin, China.",
"The First Central Clinical College of Tianjin Medical University, Tianjin, China.",
"The First Central Clinical College of Tianjin Medical University, Tianjin, China.",
"The First Central Clinical College of Tianjin Medical University, Tianjin, China.",
"The First Central Clinical College of Tianjin Medical University, Tianjin, China.\nDepartment of Hematology, Tianjin First Central Hospital, Tianjin, China."
] |
[
"39355240",
"37304938",
"22383796",
"36912693",
"33796898",
"33119898",
"30361262",
"36151140",
"35799191",
"33619261",
"16455952",
"19858393",
"32054729",
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] |
[] | 6.628761 | 6.753066 |
39354225
| 421 |
CAR-redirected natural killer T cells demonstrate superior antitumor activity to CAR-T cells through multimodal CD1d-dependent mechanisms.
|
Human natural killer T (NKT) cells have been proposed as a promising cell platform for chimeric antigen receptor (CAR) therapy in solid tumors. Here we generated murine CAR-NKT cells and compared them with CAR-T cells in immune-competent mice. Both CAR-NKT cells and CAR-T cells showed similar antitumor effects in vitro, but CAR-NKT cells showed superior antitumor activity in vivo via CD1d-dependent immune responses in the tumor microenvironment. Specifically, we show that CAR-NKT cells eliminate CD1d-expressing M2-like macrophages. In addition, CAR-NKT cells promote epitope spreading and activation of endogenous T cell responses against tumor-associated neoantigens. Finally, we observed that CAR-NKT cells can co-express PD1 and TIM3 and show an exhaustion phenotype in a model of high tumor burden. PD1 blockade as well as vaccination augmented the antitumor activity of CAR-NKT cells. In summary, our results demonstrate the multimodal function of CAR-NKT cells in solid tumors, further supporting the rationale for developing CAR-NKT therapies in the clinic.
|
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] | 2024-10-02 | 54 |
39354225
|
[
"endogenous T cell responses",
"NKT",
"murine CAR-NKT cells",
"CAR-NKT cells",
"solid tumors",
"high tumor burden",
"CAR-NKT therapies",
"CAR-T cells",
"Both CAR-NKT cells",
"Human natural killer T (NKT) cells",
"superior antitumor activity",
"similar antitumor effects",
"a promising cell platform",
"-express PD1",
"CAR",
"chimeric antigen receptor",
"CD1d-dependent immune responses",
"tumor-associated neoantigens",
"M2",
"TIM3",
"vivo",
"activation",
"epitope",
"vaccination",
"the tumor microenvironment",
"the antitumor activity",
"CAR) therapy",
"CD1d-expressing M2-like macrophages",
"summary",
"PD1"
] |
[] | 0 |
10.1038/s43018-024-00830-0
10.1007/s00428-021-03238-8
10.1158/1078-0432.CCR-19-1835
10.1038/s41571-022-00704-3
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10.3389/fimmu.2015.00255
10.1038/nri1309
10.1084/jem.188.8.1521
10.4049/jimmunol.167.6.3114
10.1038/ni.2096
10.1200/JCO.2011.38.8819
10.1084/jem.20031462
10.1158/1078-0432.CCR-05-0877
10.1172/JCI37869
10.1182/blood-2016-11-751065
10.1016/j.celrep.2018.02.058
10.1038/s41591-020-1074-2
10.1182/blood-2013-11-541235
10.1016/j.ccell.2018.08.017
10.1158/1078-0432.CCR-21-1329
10.1126/sciimmunol.abn6563
10.1038/s41586-019-0985-x
10.1007/s00262-022-03287-1
10.1038/s41418-022-01059-z
10.1158/2326-6066.CIR-17-0341
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10.1016/j.isci.2020.101238
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10.1172/JCI138560
10.1146/annurev-med-012017-043208
10.1084/jem.20042592
10.1016/j.immuni.2014.06.010
10.3389/fimmu.2020.583084
10.2217/imt-2018-0012
10.1016/j.jbc.2021.101341
10.15252/emmm.201910698
10.1038/nri724
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10.1016/j.celrep.2019.03.028
10.1038/s41587-019-0398-2
10.1016/j.immuni.2019.03.009
|
[
"Zhou",
"Wang",
"Dou",
"Delfanti",
"Tsahouridis",
"Pellegry",
"Zingarelli",
"Atassi",
"Woodcock",
"Casorati",
"Dellabona",
"Kim",
"Guo",
"Savoldo",
"Tsagaratou",
"Milner",
"Metelitsa",
"Dotti"
] |
[
"Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.\nDepartment of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA.",
"Center for Advanced Innate Cell Therapy, Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.",
"Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.",
"Experimental Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.",
"Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.",
"Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.",
"Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.",
"Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.",
"Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.\nDivision of Oncology, Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, USA.",
"Experimental Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.",
"Experimental Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.",
"Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.\nDivision of Oncology, Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, USA.",
"Center for Advanced Innate Cell Therapy, Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.",
"Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.\nDepartment of Pediatrics, University of North Carolina, Chapel Hill, NC, USA.",
"Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.\nDepartment of Genetics, University of North Carolina, Chapel Hill, NC, USA.",
"Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.\nDepartment of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA.",
"Center for Advanced Innate Cell Therapy, Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.",
"Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA. gdotti@med.unc.edu.\nDepartment of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA. gdotti@med.unc.edu."
] |
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[] | 11.132955 | 5.963625 |
39354195
| 422 |
Allogeneic CD5-specific CAR-T therapy for relapsed/refractory T-ALL: a phase 1 trial.
|
Refractory or relapsed T cell acute lymphoblastic leukemia (r/r T-ALL) patients have poor prognoses, due to the lack of effective salvage therapies. Recently, CD7-targeting chimeric antigen receptor (CAR)-T therapies show efficacy in patients with r/r T-ALL, but relapse with CD7 loss is common. This study evaluates a CD5-gene-edited CAR-T cell therapy targeting CD5 in 19 r/r T-ALL patients, most of whom had previously failed CD7 CAR-T interventions. CAR-T products were derived from previous transplant donors (Cohort A) or newly matched donors (Cohort B). Primary endpoints were dose-limiting toxicity at 21 days and adverse events within 30 days. Secondary endpoints were responses, pharmacokinetics and severe adverse events after 30 days. A total of 16 received infusions, 10 at target dose of 1 × 10
|
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] | 2024-10-02 | 34 |
39354195
|
[
"severe adverse events",
"previous transplant donors",
"effective salvage therapies",
"CAR)-T therapies",
"adverse events",
"target dose",
"CD7 loss",
"Secondary endpoints",
"Primary endpoints",
"Cohort A",
"patients",
"r/r T-ALL",
"CD7 CAR-T interventions",
"Cohort B",
"poor prognoses",
"CD5",
"CD7-targeting chimeric antigen receptor",
"CAR-T products",
"pharmacokinetics",
"responses",
"CAR)-T",
"relapse",
"efficacy",
"dose-limiting toxicity",
"a CD5-gene-edited CAR-T cell therapy",
"16 received infusions",
"newly matched donors",
"/r T-ALL",
"the lack",
"A total"
] |
[] | 0 |
10.1038/s41591-024-03282-2
|
[
"Pan",
"Tan",
"Shan",
"Seery",
"Deng",
"Ling",
"Xu",
"Duan",
"Wang",
"Wang",
"Yu",
"Zheng",
"Xu",
"Hu",
"Tan",
"Yuan",
"Tian",
"Yan",
"Han",
"Zhang",
"Feng"
] |
[
"State Key Laboratory of Experimental Hematology, Boren Clinical Translational Center, Department of Hematology, Beijing Gobroad Boren Hospital, Beijing, China. panj@gobroadhealthcare.com.",
"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.\nTianjin Institutes of Health Science, Tianjin, China.",
"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.\nTianjin Institutes of Health Science, Tianjin, China.",
"School of Pharmacy, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.",
"Cytology Laboratory, Beijing Gobroad Boren Hospital, Beijing, China.",
"State Key Laboratory of Experimental Hematology, Boren Clinical Translational Center, Department of Hematology, Beijing Gobroad Boren Hospital, Beijing, China.",
"State Key Laboratory of Experimental Hematology, Boren Clinical Translational Center, Department of Hematology, Beijing Gobroad Boren Hospital, Beijing, China.",
"State Key Laboratory of Experimental Hematology, Boren Clinical Translational Center, Department of Hematology, Beijing Gobroad Boren Hospital, Beijing, China.",
"State Key Laboratory of Experimental Hematology, Boren Clinical Translational Center, Department of Hematology, Beijing Gobroad Boren Hospital, Beijing, China.",
"State Key Laboratory of Experimental Hematology, Boren Clinical Translational Center, Department of Hematology, Beijing Gobroad Boren Hospital, Beijing, China.",
"Medical Laboratory, Beijing Gobroad Boren Hospital, Beijing, China.",
"Medical Laboratory, Beijing Gobroad Boren Hospital, Beijing, China.",
"Medical Laboratory, Beijing Gobroad Boren Hospital, Beijing, China.",
"Nanjing IASO Biotherapeutics, Nanjing, China.",
"Nanjing IASO Biotherapeutics, Nanjing, China.",
"Department of Biostatistics, University of Texas MD Anderson Cancer Center, Austin, TX, USA.",
"Gobroad Research Center, Gobroad Medical Group, Beijing, China.",
"Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, Nanjing, China.",
"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.\nTianjin Institutes of Health Science, Tianjin, China.",
"Department of Hospital Management, Gobroad Medical Group, Beijing, China.",
"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China. fengxiaoming@ihcams.ac.cn.\nTianjin Institutes of Health Science, Tianjin, China. fengxiaoming@ihcams.ac.cn.\nCentral Laboratory, Fujian Medical University Union Hospital, Fuzhou, China. fengxiaoming@ihcams.ac.cn."
] |
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] |
[] | 6.444951 | 5.771719 |
39351902
| 423 |
C-CAR066, a novel fully human anti-CD20 CAR-T therapy for relapsed or refractory large B-cell lymphoma after failure of anti-CD19 CAR-T therapy: A phase I clinical study.
|
Managing large B-cell lymphoma (LBCL) that is refractory to or relapsed after chimeric antigen receptor (CAR)-T therapy remains a significant challenge. Here we aimed to investigate the safety and efficacy of C-CAR066, an autologous fully human anti-CD20 specific CAR-T, for relapsed/refractory LBCL after failure of anti-CD19 CAR-T therapy. This first-in-human, single-arm, phase 1 study was conducted at two sites in China. Eligible patients had to be histologically confirmed with CD20-positive LBCL and must have received prior anti-CD19 CAR-T therapy. Patients received a single intravenous infusion of C-CAR066 at a target dose of 2.0 × 10
|
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] | 2024-10-01 | 1 |
39351902
|
[
"prior anti-CD19 CAR-T therapy",
"anti-CD19 CAR-T therapy",
"CAR)-T therapy",
"LBCL",
"chimeric antigen receptor",
"Eligible patients",
"relapsed/refractory LBCL",
"Patients",
"an autologous fully human anti-CD20 specific CAR-T",
"CD20-positive LBCL",
"efficacy",
"CAR)-T",
"large B-cell lymphoma",
"a single intravenous infusion",
"C-CAR066",
"failure",
"China",
"first",
", single-arm",
"a significant challenge",
"a target dose",
"the safety",
"two sites",
"1",
"10",
"2.0 ×",
"2.0 × ",
"that",
"two",
"we"
] |
[] | 0 |
10.1002/ajh.27488
|
[
"Li",
"Liu",
"Zhou",
"Ye",
"Zhu",
"Huang",
"Li",
"Zheng",
"Zhu",
"Yao",
"Zhu",
"Yao",
"Qiu",
"Liang",
"Zou"
] |
[
"Tongji Hospital of Tongji University, Shanghai, China.",
"State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.\nTianjin Institutes of Health Science, Tianjin, China.",
"Tongji Hospital of Tongji University, Shanghai, China.",
"Tongji Hospital of Tongji University, Shanghai, China.",
"Shanghai AbelZeta Ltd., Shanghai, China.",
"Shanghai AbelZeta Ltd., Shanghai, China.",
"Shanghai AbelZeta Ltd., Shanghai, China.",
"Shanghai AbelZeta Ltd., Shanghai, China.",
"Shanghai AbelZeta Ltd., Shanghai, China.",
"Shanghai AbelZeta Ltd., Shanghai, China.",
"University of Maryland School of Medicine, Baltimore, Maryland, USA.",
"Shanghai AbelZeta Ltd., Shanghai, China.",
"State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.\nTianjin Institutes of Health Science, Tianjin, China.",
"Tongji Hospital of Tongji University, Shanghai, China.",
"State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.\nTianjin Institutes of Health Science, Tianjin, China."
] |
[
"39351902"
] |
[] | 6.377262 | 5.39333 |
39350256
| 424 |
Therapeutic targets of armored chimeric antigen receptor T cells navigating the tumor microenvironment.
|
Chimeric antigen receptor (CAR) T cell therapy, which targets tumors with high specificity through the recognition of particular antigens, has emerged as one of the most rapidly advancing modalities in immunotherapy, demonstrating substantial success against hematological malignancies. However, previous generations of CAR-T cell therapy encountered numerous challenges in treating solid tumors, such as the lack of suitable targets, high immunosuppression, suboptimal persistence, and insufficient infiltration owing to the complexities of the tumor microenvironment, all of which limited their efficacy. In this review, we focus on the current therapeutic targets of fourth-generation CAR-T cells, also known as armored CAR-T cells, and explore the mechanisms by which these engineered cells navigate the tumor microenvironment by targeting its various components. Enhancing CAR-T cells with these therapeutic targets holds promise for improving their effectiveness against solid tumors, thus achieving substantial clinical value and advancing the field of CAR-T cell therapy. Additionally, we discuss potential strategies to overcome existing challenges and highlight novel targets that could further enhance the efficacy of CAR-T cell therapy in treating solid tumors.
|
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] | 2024-10-01 | 173 |
39350256
|
[
"T cell therapy",
"solid tumors",
"tumors",
"novel targets",
"suitable targets",
"CAR-T cell therapy",
"armored CAR-T cells",
"substantial clinical value",
"CAR-T cells",
"substantial success",
"existing challenges",
"high immunosuppression",
"high specificity",
"numerous challenges",
"particular antigens",
"Chimeric antigen receptor",
"CAR",
"fourth-generation CAR-T cells",
"insufficient infiltration",
"suboptimal persistence",
"potential strategies",
"previous generations",
"the current therapeutic targets",
"the tumor microenvironment",
"hematological malignancies",
"these engineered cells",
"these therapeutic targets",
"immunotherapy",
"promise",
"fourth"
] |
[
"Cancer immunotherapy",
"Chimeric antigen receptor (CAR) T cell",
"Solid tumor",
"T cell engineering",
"Tumor microenvironment"
] | 0 |
10.1186/s40164-024-00564-w
|
[
"Li",
"Chen",
"Li",
"Zhang",
"Li",
"Zhang",
"Luo",
"Zheng"
] |
[
"Harbin Medical University Cancer Hospital, Harbin, 150081, China.\nDepartment of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, China.\nHeilongjiang Province Key Laboratory of Molecular Oncology, Harbin,150081, China.",
"Harbin Medical University Cancer Hospital, Harbin, 150081, China.\nHeilongjiang Province Key Laboratory of Molecular Oncology, Harbin,150081, China.",
"Harbin Medical University Cancer Hospital, Harbin, 150081, China.\nDepartment of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, China.\nHeilongjiang Province Key Laboratory of Molecular Oncology, Harbin,150081, China.",
"Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, China.",
"Harbin Medical University Cancer Hospital, Harbin, 150081, China.\nDepartment of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, China.\nHeilongjiang Province Key Laboratory of Molecular Oncology, Harbin,150081, China.",
"Harbin Medical University Cancer Hospital, Harbin, 150081, China.\nDepartment of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, China.\nHeilongjiang Province Key Laboratory of Molecular Oncology, Harbin,150081, China.",
"Harbin Medical University Cancer Hospital, Harbin, 150081, China.\nDepartment of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, China.\nHeilongjiang Province Key Laboratory of Molecular Oncology, Harbin,150081, China.",
"Harbin Medical University Cancer Hospital, Harbin, 150081, China. zhengtongsen@hrbmu.edu.cn.\nDepartment of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, China. zhengtongsen@hrbmu.edu.cn.\nDepartment of Phase 1 Trials Center, Harbin Medical University Cancer Hospital, Harbin, 150081, China. zhengtongsen@hrbmu.edu.cn.\nHeilongjiang Province Key Laboratory of Molecular Oncology, Harbin,150081, China. zhengtongsen@hrbmu.edu.cn."
] |
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] |
[] | 9.589241 | 4.667443 |
39349829
| 425 |
Revisiting T-cell adhesion molecules as potential targets for cancer immunotherapy: CD226 and CD2.
|
Cancer immunotherapy aims to initiate or amplify immune responses that eliminate cancer cells and create immune memory to prevent relapse. Immune checkpoint inhibitors (ICIs), which target coinhibitory receptors on immune effector cells, such as CTLA-4 and PD-(L)1, have made significant strides in cancer treatment. However, they still face challenges in achieving widespread and durable responses. The effectiveness of anticancer immunity, which is determined by the interplay of coinhibitory and costimulatory signals in tumor-infiltrating immune cells, highlights the potential of costimulatory receptors as key targets for immunotherapy. This review explores our current understanding of the functions of CD2 and CD226, placing a special emphasis on their potential as novel agonist targets for cancer immunotherapy. CD2 and CD226, which are present mainly on T and NK cells, serve important functions in cell adhesion and recognition. These molecules are now recognized for their costimulatory benefits, particularly in the context of overcoming T-cell exhaustion and boosting antitumor responses. The importance of CD226, especially in anti-TIGIT therapy, along with the CD2‒CD58 axis in overcoming resistance to ICI or chimeric antigen receptor (CAR) T-cell therapies provides valuable insights into advancing beyond the current barriers of cancer immunotherapy, underscoring their promise as targets for novel agonist therapy.
|
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] | 2024-10-01 | 174 |
39349829
|
[
"cancer cells",
"immune effector cells",
"cell adhesion",
"immune responses",
"costimulatory receptors",
"Cancer immunotherapy",
"cancer immunotherapy",
"immune memory",
"novel agonist therapy",
"cancer treatment",
"anti-TIGIT therapy",
"coinhibitory receptors",
"novel agonist targets",
"tumor-infiltrating immune cells",
"antitumor responses",
"important functions",
"CD226",
"T and NK cells",
"key targets",
"immunotherapy",
"Immune checkpoint inhibitors",
"T-cell exhaustion",
"significant strides",
"valuable insights",
"anticancer immunity",
"chimeric antigen receptor (CAR) T-cell therapies",
"targets",
"CD2",
"coinhibitory and costimulatory signals",
"ICIs"
] |
[] | 0 |
10.1038/s12276-024-01317-9
|
[
"Jo",
"Sim",
"Yun",
"Park",
"Jin"
] |
[
"Chemical and Biological Integrative Research Center, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, South Korea.",
"Chemical and Biological Integrative Research Center, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, South Korea.",
"Department of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.",
"Chemical and Biological Integrative Research Center, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, South Korea. ypark@kist.re.kr.",
"Department of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. hsjin@amc.seoul.kr."
] |
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] |
[] | 10.642791 | 4.385923 |
39349459
| 426 |
CRISPR/Cas9 editing of NKG2A improves the efficacy of primary CD33-directed chimeric antigen receptor natural killer cells.
|
Chimeric antigen receptor (CAR)-modified natural killer (NK) cells show antileukemic activity against acute myeloid leukemia (AML) in vivo. However, NK cell-mediated tumor killing is often impaired by the interaction between human leukocyte antigen (HLA)-E and the inhibitory receptor, NKG2A. Here, we describe a strategy that overcomes CAR-NK cell inhibition mediated by the HLA-E-NKG2A immune checkpoint. We generate CD33-specific, AML-targeted CAR-NK cells (CAR33) combined with CRISPR/Cas9-based gene disruption of the NKG2A-encoding KLRC1 gene. Using single-cell multi-omics analyses, we identified transcriptional features of activation and maturation in CAR33-KLRC1
|
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] | 2024-10-01 | 66 |
39349459
|
[
"Chimeric antigen receptor",
"human leukocyte antigen",
"NK cell-mediated tumor killing",
"acute myeloid leukemia",
"CAR-NK cell inhibition",
"single-cell multi-omics analyses",
"transcriptional features",
"antileukemic activity",
"AML",
"CAR33",
"KLRC1",
"myeloid",
"activation",
"NK",
"HLA)-E",
"CD33-specific, AML-targeted CAR-NK cells",
"NKG2A.",
"maturation",
"the HLA-E-NKG2A immune checkpoint",
"CRISPR/Cas9-based gene disruption",
"CAR33-KLRC1",
"the inhibitory receptor",
"AML-targeted",
"vivo",
"the NKG2A-encoding KLRC1 gene",
"CRISPR/Cas9",
"the interaction",
"a strategy",
"We",
"that"
] |
[] | 0 |
10.1038/s41467-024-52388-1
|
[
"Bexte",
"Albinger",
"Al Ajami",
"Wendel",
"Buchinger",
"Gessner",
"Alzubi",
"Särchen",
"Vogler",
"Rasheed",
"Jung",
"Wolf",
"Bhayadia",
"Oellerich",
"Klusmann",
"Penack",
"Möker",
"Cathomen",
"Rieger",
"Imkeller",
"Ullrich"
] |
[
"Goethe University Frankfurt, Department of Pediatrics, Experimental Immunology and Cell Therapy, Frankfurt am Main, Germany.\nGoethe University Frankfurt, Department of Pediatrics, Frankfurt am Main, Germany.\nGoethe University Frankfurt, Frankfurt Cancer Institute, Frankfurt am Main, Germany.\nGerman Red Cross Blood Service Baden-Württemberg - Hessen, Institute for Transfusion Medicine and Immunohematology, Frankfurt am Main, Germany.",
"Goethe University Frankfurt, Department of Pediatrics, Experimental Immunology and Cell Therapy, Frankfurt am Main, Germany.\nGoethe University Frankfurt, Department of Pediatrics, Frankfurt am Main, Germany.\nGoethe University Frankfurt, Frankfurt Cancer Institute, Frankfurt am Main, Germany.",
"Goethe University Frankfurt, Frankfurt Cancer Institute, Frankfurt am Main, Germany.\nUniversity Cancer Center (UCT), Frankfurt am Main, Germany.\nGoethe University Frankfurt, University Hospital, Neurological Institute / Edinger Institute, Frankfurt am Main, Germany.",
"Goethe University Frankfurt, Department of Pediatrics, Experimental Immunology and Cell Therapy, Frankfurt am Main, Germany.\nGoethe University Frankfurt, Department of Pediatrics, Frankfurt am Main, Germany.\nGoethe University Frankfurt, Frankfurt Cancer Institute, Frankfurt am Main, Germany.\nInstitute for Organic Chemistry and Biochemistry, Technical University of Darmstadt, Darmstadt, Germany.\nGerman Cancer Consortium (DKTK) partner site Frankfurt/Mainz, Frankfurt am Main, Germany.\nGerman Cancer Research Center (DKFZ), Heidelberg, Germany.",
"Goethe University Frankfurt, Department of Pediatrics, Experimental Immunology and Cell Therapy, Frankfurt am Main, Germany.\nGoethe University Frankfurt, Department of Pediatrics, Frankfurt am Main, Germany.\nGoethe University Frankfurt, Frankfurt Cancer Institute, Frankfurt am Main, Germany.",
"Goethe University Frankfurt, Frankfurt Cancer Institute, Frankfurt am Main, Germany.\nGoethe University Frankfurt, University Hospital, Department of Medicine II - Hematology and Oncology, Frankfurt am Main, Germany.",
"Institute for Transfusion Medicine and Gene Therapy, Medical Center - University of Freiburg, Freiburg, Germany.\nCenter for Chronic Immunodeficiency, Faculty of Medicine, University of Freiburg, Freiburg, Germany.",
"Goethe University Frankfurt, Institute for Experimental Pediatric Hematology and Oncology, Frankfurt am Main, Germany.",
"Goethe University Frankfurt, Institute for Experimental Pediatric Hematology and Oncology, Frankfurt am Main, Germany.",
"Charité, University Berlin and Humboldt-University Berlin, Department of Hematology, Oncology and Tumor Immunology, Berlin, Germany.\nClinical Pathology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt.",
"Charité, University Berlin and Humboldt-University Berlin, Department of Hematology, Oncology and Tumor Immunology, Berlin, Germany.",
"Goethe University Frankfurt, Frankfurt Cancer Institute, Frankfurt am Main, Germany.\nGerman Cancer Consortium (DKTK) partner site Frankfurt/Mainz, Frankfurt am Main, Germany.\nGoethe University Frankfurt, University Hospital, Department of Medicine II - Hematology and Oncology, Frankfurt am Main, Germany.",
"Goethe University Frankfurt, Department of Pediatrics, Frankfurt am Main, Germany.\nGoethe University Frankfurt, Frankfurt Cancer Institute, Frankfurt am Main, Germany.",
"Goethe University Frankfurt, Frankfurt Cancer Institute, Frankfurt am Main, Germany.\nGerman Cancer Consortium (DKTK) partner site Frankfurt/Mainz, Frankfurt am Main, Germany.\nGoethe University Frankfurt, University Hospital, Department of Medicine II - Hematology and Oncology, Frankfurt am Main, Germany.",
"Goethe University Frankfurt, Department of Pediatrics, Frankfurt am Main, Germany.\nGoethe University Frankfurt, Frankfurt Cancer Institute, Frankfurt am Main, Germany.",
"Charité, University Berlin and Humboldt-University Berlin, Department of Hematology, Oncology and Tumor Immunology, Berlin, Germany.\nGerman Cancer Consortium (DKTK) partner site Berlin, Berlin, Germany.",
"Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany.",
"Institute for Transfusion Medicine and Gene Therapy, Medical Center - University of Freiburg, Freiburg, Germany.\nCenter for Chronic Immunodeficiency, Faculty of Medicine, University of Freiburg, Freiburg, Germany.\nGerman Cancer Consortium (DKTK) partner site Freiburg, Freiburg, Germany.",
"Goethe University Frankfurt, Frankfurt Cancer Institute, Frankfurt am Main, Germany.\nGoethe University Frankfurt, University Hospital, Department of Medicine II - Hematology and Oncology, Frankfurt am Main, Germany.\nCardio-Pulmonary-Institute, Frankfurt am Main, Germany.",
"Goethe University Frankfurt, Frankfurt Cancer Institute, Frankfurt am Main, Germany.\nUniversity Cancer Center (UCT), Frankfurt am Main, Germany.\nGoethe University Frankfurt, University Hospital, Neurological Institute / Edinger Institute, Frankfurt am Main, Germany.",
"Goethe University Frankfurt, Department of Pediatrics, Experimental Immunology and Cell Therapy, Frankfurt am Main, Germany. evelyn@ullrichlab.de.\nGoethe University Frankfurt, Department of Pediatrics, Frankfurt am Main, Germany. evelyn@ullrichlab.de.\nGoethe University Frankfurt, Frankfurt Cancer Institute, Frankfurt am Main, Germany. evelyn@ullrichlab.de.\nGerman Cancer Consortium (DKTK) partner site Frankfurt/Mainz, Frankfurt am Main, Germany. evelyn@ullrichlab.de."
] |
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[] | 11.265341 | 5.993004 |
39349228
| 427 |
Nanoparticle-mediated universal CAR-T therapy.
|
In recent years, chimeric antigen receptor (CAR)-T cell therapy has been highly successful in treating hematological malignancies, leading to significant advancements in the cancer immunotherapy field. However, the typical CAR-T therapy necessitates the enrichment of patients' own leukocytes for ex vivo production of CAR-T cells, this customized pattern requires a complicated and time-consuming manufacturing procedure, making it costly and less accessible. The off-the-shelf universal CAR-T strategy could reduce manufacturing costs and realize timely drug administration, presenting as an ideal substitute for typical CAR-T therapy. Utilizing nanocarriers for targeted gene delivery is one of the approaches for the realization of universal CAR-T therapy, as biocompatible and versatile nanoparticles could deliver CAR genes to generate CAR-T cells in vivo. Nanoparticle-mediated in situ generation of CAR-T cells possesses multiple advantages, including lowered cost, simplified manufacturing procedure, and shortened administration time, this strategy is anticipated to provide a potentially cost-effective alternative to current autologous CAR-T cell manufacturing, thus facilitating the prevalence and improvement of CAR-T therapy.
|
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] | 2024-10-01 | 1 |
39349228
|
[
"CAR)-T cell therapy",
"CAR genes",
"manufacturing costs",
"simplified manufacturing procedure",
"CAR",
"current autologous CAR-T cell manufacturing",
"typical CAR-T therapy",
"CAR-T cells",
"universal CAR-T therapy",
"CAR-T therapy",
"lowered cost",
"targeted gene delivery",
"timely drug administration",
"chimeric antigen receptor",
"significant advancements",
"ex vivo production",
"hematological malignancies",
"the typical CAR-T therapy",
"multiple advantages",
"situ generation",
"recent years",
"CAR)-T",
"improvement",
"a complicated and time-consuming manufacturing procedure",
"biocompatible and versatile nanoparticles",
"nanocarriers",
"patients own leukocytes",
"the cancer immunotherapy field",
"vivo",
"this customized pattern"
] |
[
"Gene delivery",
"Lipid nanoparticles",
"Nanoparticle",
"Universal CAR-T therapy"
] | 0 |
10.1016/j.ijpharm.2024.124779
|
[
"Fan",
"Zheng",
"Huang",
"Lu",
"Shang",
"Du"
] |
[
"School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China.",
"School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China.",
"School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China.",
"State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Biomaterials and Tissue Engineering Research Center, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, China. Electronic address: lmx2306@126.com.",
"Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: shangzhi90@gamil.com.",
"Department of Dermatology, Shanghai Key Laboratory of Medical Mycology, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China. Electronic address: Dumingwei7939@126.com."
] |
[
"39349228"
] |
[] | 8.778243 | 3.196746 |
39348664
| 428 |
Immune reconstitution and evolution of B-cell-stimulating cytokines after R-CHOP therapy for HIV-associated DLBCL.
|
HIV infection is associated with an increased risk of diffuse large B-cell lymphoma (DLBCL). In this prospective study, we analyzed the evolution of B-cell activating cytokines (interleukin-6 [IL-6], IL-10, and B-cell activating factor [BAFF]) and main functional subsets of circulating B and T cells in 51 patients with HIV-associated DLBCL treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, Oncovin [vincristine], and prednisone). R-CHOP therapy was associated with a decrease of IL-10, whereas IL-6 levels fluctuated, and BAFF levels increased during the first 3 months and decreased thereafter. We observed a rapid rise in CD19+ B cells composed mostly of naïve B cells whereas marginal zone-like B cells and memory B cells recovered gradually. With a median follow-up of 41 months, progression-free survival and overall survival at 5 years were 61.8% (95% confidence interval [CI], 47.6-80.4) and 67.4% (95% CI, 53.4-85.0), respectively. Progression (17.5%) and sepsis (12.5%) were the main causes of death. Baseline risk factors for death and progression were poor revised International Prognostic Index (P = .049), natural killer cell lymphopenia (P = .001), lower proportion of naïve B cells (P = .017), and higher IL-6 serum levels (P = .001). Our data suggest that patients treated with R-CHOP for HIV-associated DLBCL have a disturbed peripheral B-cell compartment and that the low pool size of circulating naïve B cells negatively affects their clinical outcome. In an era of development of B-cell-depleting therapies including B-cell-targeting chimeric antigen receptor T cells, assessment of perturbations within nontumoral B-cell counterparts are warranted for risk profiling in HIV-associated DLBCL. This trial was registered at www.ClinicalTrials.gov as #NCT01164436.
|
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] | 2024-09-30 | 50 |
39348664
|
[
"naïve B cells",
"memory B cells",
"circulating naïve B cells",
"CD19+ B cells",
"T cells",
"natural killer cell lymphopenia",
"circulating B",
"B-cell activating cytokines",
"B-cell-targeting chimeric antigen receptor T cells",
"marginal zone-like B cells",
"large B-cell lymphoma",
"nontumoral B-cell counterparts",
"Baseline risk factors",
"BAFF levels",
"IL-6 levels",
"HIV infection",
"risk profiling",
"P",
"main functional subsets",
"a disturbed peripheral B-cell compartment",
"serum levels",
"Progression",
"progression",
"B-cell-depleting therapies",
"overall survival",
"lower proportion",
"International Prognostic Index",
"higher IL-6",
"HIV-associated DLBCL",
"patients"
] |
[] | 0 |
10.1182/bloodadvances.2024014116
|
[
"Liévin",
"Maillard",
"Hendel-Chavez",
"Krzysiek",
"Lancar",
"Algarte-Genin",
"Costagliola",
"Assoumou",
"Taoufik",
"Besson"
] |
[
"Department of Hematology and Oncology, Hospital of Versailles, Le Chesnay, France.\nLaboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, Imagine Institute, University of Paris, INSERM U1163, Paris, France.",
"Médecine Intensive et Réanimation, Hôpital Saint-Louis, AP-HP, Université Paris Cité, Paris, France.",
"Department of Immunology, Assistance Publique Hôpitaux de Paris, Hôpital Bicêtre, Kremlin-Bicêtre, France.\nINSERM U1186, Institut Gustave Roussy, Villejuif, France.",
"Department of Immunology, Assistance Publique Hôpitaux de Paris, Hôpital Bicêtre, Kremlin-Bicêtre, France.\nINSERM UMR 996, Inflammation Microbiome and Immunosurveillance, Paris-Saclay University, Orsay, France.",
"INSERM UMR 996, Inflammation Microbiome and Immunosurveillance, Paris-Saclay University, Orsay, France.",
"Institut Pierre Louis d'Epidémiologie et de Santé Publique, IPLESP, Sorbonne Université, INSERM UMR-S 1136, Paris, France.",
"Institut Pierre Louis d'Epidémiologie et de Santé Publique, IPLESP, Sorbonne Université, INSERM UMR-S 1136, Paris, France.",
"Institut Pierre Louis d'Epidémiologie et de Santé Publique, IPLESP, Sorbonne Université, INSERM UMR-S 1136, Paris, France.",
"Department of Immunology, Assistance Publique Hôpitaux de Paris, Hôpital Bicêtre, Kremlin-Bicêtre, France.\nINSERM U1186, Institut Gustave Roussy, Villejuif, France.",
"Department of Hematology and Oncology, Hospital of Versailles, Le Chesnay, France.\nUniversité Versailles Saint Quentin en Yvelines, Université Paris-Saclay, Montigny le Bretonneux, France.\nINSERM U1018, Centre for Research in Epidemiology and Population Health, Villejuif, France."
] |
[
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] |
[] | 6.269019 | 6.128504 |
39346763
| 429 |
Muc16CD is a novel CAR T cell target antigen for the treatment of pancreatic cancer.
|
Pancreatic cancer is an aggressive malignancy with a 5-year survival rate of 13% that remains refractory to current immunotherapies, such as chimeric antigen receptor (CAR) T cells. These engineered cells can produce robust anti-tumor responses but require a reliable tumor-associated antigen (TAA) target. Here, we describe the retained ectodomain of Muc16, Muc16CD, as a novel TAA for targeting by CAR T cell therapy in pancreatic cancer. We establish clinically relevant, endogenous Muc16 and Muc16CD expression in pancreatic tumor tissues for CAR T cell targeting. Muc16CD-directed CAR T cells can both recognize and activate in a polyfunctional manner in response to patient-derived pancreatic tumor cells. Last, we demonstrate that Muc16CD-directed CAR T cells can elicit an anti-tumor response
|
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39346763
|
[
"robust anti-tumor responses",
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"a novel TAA",
"an aggressive malignancy",
"a polyfunctional manner",
"the retained ectodomain",
"a 5-year survival rate",
"13%",
"5-year",
"We",
"that",
"we"
] |
[
"CAR T cells",
"MT: Regular Issue",
"Muc16",
"adoptive cellular therapy",
"cellular immunotherapy",
"pancreatic cancer",
"tumor-associated antigens"
] | 0 |
10.1016/j.omton.2024.200868
10.1186/s13287-020-02128-1
10.1038/ncomms15095
10.1016/j.canlet.2021.01.031
10.1007/s10637-017-0525-1
10.1016/j.omto.2022.01.010
10.1056/NEJMoa2119662
10.1080/14728222.2018.1498845
10.1371/journal.pone.0126633
10.1038/onc.2011.297
10.1158/1078-0432.Ccr-16-2530
10.1371/journal.pone.0026839
10.1186/s13048-024-01373-9
10.1097/PAI.0b013e3181dbfcd2
10.1038/nbt.4195
10.1038/s41598-017-10940-8
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10.1186/s12967-015-0460-x
10.1016/j.ygyno.2020.06.089
10.1007/s13304-023-01587-4
10.1126/science.aan2507
10.3390/cancers12123730
10.1158/2159-8290.Cd-19-0094
10.1158/1078-0432.CCR-10-0192
10.1200/JCO.2024.42.16_suppl.3514
10.1016/j.ymthe.2020.12.029
10.1158/1078-0432.Ccr-18-0290
10.1158/2159-8290.Cd-22-0876
10.1038/s41571-020-0363-5
10.1038/s41571-019-0297-y
10.1097/ppo.0000000000000510
10.3390/ijms24108707
10.1136/jitc-2020-001100
10.1136/jitc-2023-008086
10.1158/1078-0432.Ccr-23-3841
10.1186/s12967-023-04080-z
10.1038/srep01870
10.3390/ijms21114067
10.3390/cancers15051357
10.1158/2159-8290.CD-15-0583
10.1158/0008-5472.Can-23-1542
10.1053/j.gastro.2018.03.029
10.1158/1535-7163.Mct-22-0073
10.1038/s41419-019-1711-1
10.1038/s41698-023-00423-7
10.1002/cjp2.260
10.1038/s41467-022-34242-4
10.1136/jitc-2022-SITC2022.0310
10.1182/blood-2023-182952
10.1016/j.xinn.2024.100625
10.1111/bph.16257
10.1038/leu.2016.373
|
[
"Lin",
"Blake",
"Liu",
"Freeman",
"Lesinski",
"Yang",
"Rafiq"
] |
[
"Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA.",
"Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA.",
"Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA.",
"Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA.",
"Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA.\nWinship Cancer Institute, Atlanta, GA, USA.",
"Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA.\nWinship Cancer Institute, Atlanta, GA, USA.",
"Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA.\nWinship Cancer Institute, Atlanta, GA, USA."
] |
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[] | 9.673902 | 5.495922 |
39342286
| 430 |
Targeting GPRC5D for multiple myeloma therapy.
|
Given its nearly ubiquitous expression on plasma cells and limited expression on essential normal tissue, the G protein-coupled receptor class C group 5 member D (GPRC5D) presents a promising opportunity for utilization as an immunotherapy target in multiple myeloma (MM). The therapeutic strategies targeting GPRC5D, such as bispecific antibodies (BsAbs), chimeric antigen receptor (CAR) T cells, and antibody-drug conjugates (ADCs), have been prominently emphasized in relapsed/refractory MM (R/R MM) in recent years. Further clinical trials are necessary to confirm the long-term efficacy of GPRC5D-targeting immunotherapies alone, explore their potentials co-targeting with other specific antigens, or investigate their combinations with existing treatments to overcome MM resistance. This review provides an overview of current research progress in GPRC5D, encompassing its biological characteristics and translational journey from laboratory to clinical application.
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] | 2024-09-29 | 70 |
39342286
|
[
"GPRC5D",
"chimeric antigen receptor",
"MM resistance",
"current research progress",
"bispecific antibodies",
"T cells",
"MM",
"plasma cells",
"essential normal tissue",
"Further clinical trials",
"other specific antigens",
"limited expression",
"GPRC5D-targeting immunotherapies",
"translational journey",
"existing treatments",
"clinical application",
"multiple myeloma",
"recent years",
"the G protein-coupled receptor class C group 5 member D",
"relapsed/refractory MM (R/R MM",
"utilization",
"ADCs",
"co",
"antibody-drug conjugates",
"CAR",
"laboratory",
"an immunotherapy target",
"its biological characteristics",
"a promising opportunity",
"the long-term efficacy"
] |
[
"Bispecific antibodies",
"Chimeric antigen receptor T cell",
"G protein-coupled receptor class C group 5 member D",
"Immunotherapy",
"Multiple myeloma"
] | 0 |
10.1186/s13045-024-01611-z
|
[
"Zhou",
"Wang",
"Chen",
"Li",
"Xu",
"Zhao"
] |
[
"Department of Hematology, Affiliated Hospital of Xuzhou Medical University, #99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China.\nBlood Diseases Institute, Xuzhou Medical University, #84 West Huaihai Road, Xuzhou, 221002, Jiangsu, China.",
"Department of Hematology, Affiliated Hospital of Xuzhou Medical University, #99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China.\nBlood Diseases Institute, Xuzhou Medical University, #84 West Huaihai Road, Xuzhou, 221002, Jiangsu, China.",
"Department of Hematology, Affiliated Hospital of Xuzhou Medical University, #99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China.\nBlood Diseases Institute, Xuzhou Medical University, #84 West Huaihai Road, Xuzhou, 221002, Jiangsu, China.",
"Department of Hematology, Affiliated Hospital of Xuzhou Medical University, #99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China. lizhenyumd@163.com.\nBlood Diseases Institute, Xuzhou Medical University, #84 West Huaihai Road, Xuzhou, 221002, Jiangsu, China. lizhenyumd@163.com.",
"Department of Hematology, Affiliated Hospital of Xuzhou Medical University, #99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China. lihmd@163.com.\nBlood Diseases Institute, Xuzhou Medical University, #84 West Huaihai Road, Xuzhou, 221002, Jiangsu, China. lihmd@163.com.",
"Department of Hematology, Affiliated Hospital of Xuzhou Medical University, #99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China. Kainyzhao@163.com.\nBlood Diseases Institute, Xuzhou Medical University, #84 West Huaihai Road, Xuzhou, 221002, Jiangsu, China. Kainyzhao@163.com."
] |
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[] | 4.863545 | 6.205312 |
39341801
| 431 |
Mathematical modeling insights into improving CAR T cell therapy for solid tumors with bystander effects.
|
As an adoptive cellular therapy, Chimeric Antigen Receptor T cell (CAR T cell) therapy has shown remarkable success in hematological malignancies but only limited efficacy against solid tumors. Compared with blood cancers, solid tumors present a series of challenges that ultimately combine to neutralize the function of CAR T cells. These challenges include, but are not limited to, antigen heterogeneity - variability in the expression of the antigen on tumor cells, as well as trafficking and infiltration into the solid tumor tissue. A critical question for solving the heterogeneity problem is whether CAR T therapy induces bystander effects, such as antigen spreading. Antigen spreading occurs when CAR T cells activate other endogenous antitumor CD8 T cells against antigens that were not originally targeted. In this work, we develop a mathematical model of CAR T cell therapy for solid tumors that considers both antigen heterogeneity and bystander effects. Our model is based on in vivo treatment data that includes a mixture of target antigen-positive and target antigen-negative tumor cells. We use our model to simulate large cohorts of virtual patients to better understand the relationship involving bystander killing. We also investigate several strategies for enhancing bystander effects, thus increasing CAR T cell therapy's overall efficacy for solid tumors.
|
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] | 2024-09-29 | 31 |
39341801
|
[
"CAR T cell therapy",
"CAR T cells",
"CAR T therapy",
"tumor cells",
"solid tumors",
"other endogenous antitumor CD8 T cells",
"bystander effects",
"CAR T cell therapys overall efficacy",
"Chimeric Antigen Receptor T cell (CAR T cell) therapy",
"bystander killing",
"antigen",
"antigens",
"vivo treatment data",
"virtual patients",
"large cohorts",
"the solid tumor tissue",
"target antigen-positive and target antigen-negative tumor cells",
"hematological malignancies",
"remarkable success",
"several strategies",
"blood cancers",
"challenges",
"both antigen heterogeneity and bystander effects",
"an adoptive cellular therapy",
"antigen heterogeneity - variability",
"Antigen",
"the heterogeneity problem",
"infiltration",
"a mathematical model",
"trafficking"
] |
[] | 0 |
10.1038/s41540-024-00435-4
|
[
"Kara",
"Jackson",
"Jones",
"Sison",
"McGee Ii"
] |
[
"Department of Mathematics, Spelman College, Atlanta, GA, USA.",
"Department of Mathematics, University of Michigan, Ann Arbor, MI, USA.",
"Department of Mathematics, University of Missouri, Columbia, MO, USA.",
"Department of Mathematics, Spelman College, Atlanta, GA, USA. erdikara@spelman.edu.",
"Department of Mathematics and Computer Science, College of the Holy Cross, Worcester, MA, USA."
] |
[
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] |
[] | 9.61738 | 4.915134 |
39339264
| 432 |
Nanotechnology in Advancing Chimeric Antigen Receptor T Cell Therapy for Cancer Treatment.
|
Chimeric antigen receptor (CAR) T cell therapy has emerged as a groundbreaking treatment for hematological cancers, yet it faces significant hurdles, particularly regarding its efficacy in solid tumors and concerning associated adverse effects. This review provides a comprehensive analysis of the advancements and ongoing challenges in CAR-T therapy. We highlight the transformative potential of nanotechnology in enhancing CAR-T therapy by improving targeting precision, modulating the immune-suppressive tumor microenvironment, and overcoming physical barriers. Nanotechnology facilitates efficient CAR gene delivery into T cells, boosting transfection efficiency and potentially reducing therapy costs. Moreover, nanotechnology offers innovative solutions to mitigate cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Cutting-edge nanotechnology platforms for real-time monitoring of CAR-T cell activity and cytokine release are also discussed. By integrating these advancements, we aim to provide valuable insights and pave the way for the next generation of CAR-T cell therapies to overcome current limitations and enhance therapeutic outcomes.
|
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] | 2024-09-28 | 187 |
39339264
|
[
"T cell therapy",
"T cells",
"efficient CAR gene delivery",
"CAR-T cell therapies",
"CAR",
"cytokine release syndrome",
"therapy costs",
"CAR-T therapy",
"solid tumors",
"cytokine release",
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"Nanotechnology",
"nanotechnology",
"immune effector cell-associated neurotoxicity syndrome",
"significant hurdles",
"associated adverse effects",
"valuable insights",
"hematological cancers",
"current limitations",
"targeting precision",
"ongoing challenges",
"transfection efficiency",
"innovative solutions",
"Chimeric antigen receptor",
"Cutting-edge nanotechnology platforms",
"physical barriers",
"therapeutic outcomes",
"real-time monitoring",
"the immune-suppressive tumor microenvironment",
"ICANS"
] |
[
"CAR-T therapy",
"barriers",
"central nervous system (CNS) tumors",
"nanotechnology"
] | 0 |
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|
[
"Kang",
"Mita",
"Zhou",
"Wu",
"Yue",
"Babu",
"Chen"
] |
[
"Materials Research and Education Center, Materials Engineering, Department of Mechanical Engineering, Auburn University, Auburn, AL 36849, USA.\nDepartment of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, Auburn, AL 36849, USA.",
"Department of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, Auburn, AL 36849, USA.\nFaculty of Pharmacy, Mulawarman University, Samarinda 75119, Kalimantan Timur, Indonesia.",
"Materials Research and Education Center, Materials Engineering, Department of Mechanical Engineering, Auburn University, Auburn, AL 36849, USA.",
"Materials Research and Education Center, Materials Engineering, Department of Mechanical Engineering, Auburn University, Auburn, AL 36849, USA.",
"Department of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, Auburn, AL 36849, USA.",
"Department of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, Auburn, AL 36849, USA.",
"Materials Research and Education Center, Materials Engineering, Department of Mechanical Engineering, Auburn University, Auburn, AL 36849, USA."
] |
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[] | 9.851225 | 3.558452 |
39335203
| 433 |
Advancing Cholangiocarcinoma Care: Insights and Innovations in T Cell Therapy.
|
Cholangiocarcinoma (CCA) is a rare and aggressive malignancy originating from the bile ducts, with poor prognosis and limited treatment options. Traditional therapies, such as surgery, chemotherapy, and radiation, have shown limited efficacy, especially in advanced cases. Recent advancements in immunotherapy, particularly T cell-based therapies like chimeric antigen receptor T (CAR T) cells, tumor-infiltrating lymphocytes (TILs), and T cell receptor (TCR)-based therapies, have opened new avenues for improving outcomes in CCA. This review provides a comprehensive overview of the current state of T cell therapies for CCA, focusing on CAR T cell therapy. It highlights key challenges, including the complex tumor microenvironment and immune evasion mechanisms, and the progress made in preclinical and clinical trials. The review also discusses ongoing clinical trials targeting specific CCA antigens, such as MUC1, EGFR, and CD133, and the evolving role of precision immunotherapy in enhancing treatment outcomes. Despite significant progress, further research is needed to optimize these therapies for solid tumors like CCA. By summarizing the most recent clinical results and future directions, this review underscores the promising potential of T cell therapies in revolutionizing CCA treatment.
|
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39335203
|
[
"T cell therapies",
"CAR T cell therapy",
"T cell receptor",
"CCA treatment",
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"chimeric antigen receptor T",
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"preclinical and clinical trials",
"the complex tumor microenvironment",
"outcomes",
"radiation",
"tumor-infiltrating lymphocytes"
] |
[
"CAR T cell therapy",
"CCA",
"immunotherapy",
"precision medicine",
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] | 0 |
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|
[
"Dadgar",
"Arunachalam",
"Hong",
"Phoon",
"Arpi-Palacios",
"Uysal",
"Wehrle",
"Aucejo",
"Ma",
"Melenhorst"
] |
[
"Cleveland Clinic Foundation, Enterprise Cancer Institute, Translational Hematology & Oncology Research, Cleveland, OH 44114, USA.",
"Cleveland Clinic Foundation, Lerner Research Institute, Center for Immunotherapy and Precision Immuno-Oncology, Cleveland, OH 44195, USA.",
"Cleveland Clinic Foundation, Lerner Research Institute, Center for Immunotherapy and Precision Immuno-Oncology, Cleveland, OH 44195, USA.",
"Cleveland Clinic Foundation, Lerner Research Institute, Center for Immunotherapy and Precision Immuno-Oncology, Cleveland, OH 44195, USA.",
"Cleveland Clinic Foundation, Lerner Research Institute, Center for Immunotherapy and Precision Immuno-Oncology, Cleveland, OH 44195, USA.",
"Cleveland Clinic Foundation, Lerner Research Institute, Center for Immunotherapy and Precision Immuno-Oncology, Cleveland, OH 44195, USA.",
"Cleveland Clinic Foundation, Digestive Diseases & Surgery Institute, Cleveland, OH 44195, USA.",
"Cleveland Clinic Foundation, Digestive Diseases & Surgery Institute, Cleveland, OH 44195, USA.",
"Cleveland Clinic Foundation, Taussig Cancer Institute, Cleveland, OH 44106, USA.",
"Cleveland Clinic Foundation, Lerner Research Institute, Center for Immunotherapy and Precision Immuno-Oncology, Cleveland, OH 44195, USA."
] |
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[] | 11.071493 | 4.185277 |
39335157
| 434 |
Syngeneic Mouse Models for Pre-Clinical Evaluation of CAR T Cells.
|
Chimeric antigen receptor (CAR) T cells have revolutionized the treatment of hematological malignancies. Unfortunately, this improvement has yet to be translated into the solid tumor field. Current immunodeficient models used in pre-clinical testing often overestimate the efficacy of CAR T cell therapy as they fail to recapitulate the immunosuppressive tumor microenvironment characteristic of solid tumors. As CAR T cell monotherapy is unlikely to be curative for many solid tumors, combination therapies must be investigated, for example, stromal remodeling agents and immunomodulators. The evaluation of these combination therapies requires a fully immunocompetent mouse model in order to recapitulate the interaction between the host's immune system and the CAR T cells. This review will discuss the need for improved immunocompetent murine models for the pre-clinical evaluation of CAR T cells, the current use of such models and future directions.
|
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39335157
|
[
"CAR T cell therapy",
"CAR T cells",
"CAR T cell monotherapy",
"improved immunocompetent murine models",
"many solid tumors",
"Current immunodeficient models",
"solid tumors",
"pre-clinical testing",
"such models",
"combination therapies",
"stromal remodeling agents",
"the CAR T cells",
"CAR",
"the pre-clinical evaluation",
"the solid tumor field",
"the immunosuppressive tumor microenvironment characteristic",
"hematological malignancies",
"future directions",
"example",
"these combination therapies",
"order",
"a fully immunocompetent mouse model",
"immunomodulators",
"the current use",
"the hosts immune system",
"The evaluation",
"the interaction",
"the need",
"the treatment",
"the efficacy"
] |
[
"CAR T cells",
"adoptive cellular therapy",
"combination therapy",
"immunotherapy",
"solid tumors",
"syngeneic models"
] | 0 |
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|
[
"Ahmed",
"Cutmore",
"Marshall"
] |
[
"Centre for Tumour Biology, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK.\nCollege of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia.",
"Centre for Tumour Biology, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK.",
"Centre for Tumour Biology, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK."
] |
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[] | 9.729282 | 4.985786 |
39335104
| 435 |
MCMC Methods for Parameter Estimation in ODE Systems for CAR-T Cell Cancer Therapy.
|
Chimeric antigen receptor (CAR)-T cell therapy represents a breakthrough in treating resistant hematologic cancers. It is based on genetically modifying T cells transferred from the patient or a donor. Although its implementation has increased over the last few years, CAR-T has many challenges to be addressed, for instance, the associated severe toxicities, such as cytokine release syndrome. To model CAR-T cell dynamics, focusing on their proliferation and cytotoxic activity, we developed a mathematical framework using ordinary differential equations (ODEs) with Bayesian parameter estimation. Bayesian statistics were used to estimate model parameters through Monte Carlo integration, Bayesian inference, and Markov chain Monte Carlo (MCMC) methods. This paper explores MCMC methods, including the Metropolis-Hastings algorithm and DEMetropolis and DEMetropolisZ algorithms, which integrate differential evolution to enhance convergence rates. The theoretical findings and algorithms were validated using Python and Jupyter Notebooks. A real medical dataset of CAR-T cell therapy was analyzed, employing optimization algorithms to fit the mathematical model to the data, with the PyMC library facilitating Bayesian analysis. The results demonstrated that our model accurately captured the key dynamics of CAR-T cell therapy. This conclusion underscores the potential of parameter estimation to improve the understanding and effectiveness of CAR-T cell therapy in clinical settings.
|
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] | 2024-09-28 | 23 |
39335104
|
[
"CAR)-T cell therapy",
"Bayesian parameter estimation",
"model parameters",
"CAR-T cell therapy",
"parameter estimation",
"DEMetropolisZ algorithms",
"CAR-T cell dynamics",
"Monte Carlo integration",
"optimization algorithms",
"Bayesian inference",
"Monte Carlo",
"Bayesian statistics",
"ordinary differential equations",
"Bayesian analysis",
"differential evolution",
"algorithms",
"Bayesian",
"MCMC methods",
"genetically modifying T cells",
"cytokine release syndrome",
"many challenges",
"resistant hematologic cancers",
"Chimeric antigen receptor",
"cytotoxic activity",
"convergence rates",
"Jupyter Notebooks",
"Markov chain Monte Carlo (MCMC) methods",
"instance",
"clinical settings",
"the mathematical model"
] |
[
"Bayesian",
"CAR-T cell therapy",
"MCMC",
"Markov chain",
"Metropolis–Hastings",
"Monte Carlo",
"ODEs",
"Python",
"differential evolution",
"immunotherapy",
"oncology",
"parameter estimation"
] | 0 |
10.3390/cancers16183132
10.1016/0006-291X(87)90502-X
10.4049/jimmunol.0900447
10.1038/s41571-023-00754-1
10.1016/j.ebiom.2022.103941
10.3389/fcell.2022.1034257
10.3389/fimmu.2020.00487
10.1016/j.humimm.2020.12.002
10.1016/j.omto.2021.03.014
10.1136/jitc-2020-001688
10.1038/s41586-019-1805-z
10.1038/s41375-023-01905-0
10.1002/jcph.1691
10.1080/19420862.2019.1688616
10.3390/cancers13122941
10.1002/cpt.2040
10.3389/fimmu.2023.1115536
10.3390/cancers14225576
10.1371/journal.pcbi.1010651
10.1111/2041-210X.13727
10.1016/j.vaccine.2019.03.075
10.1145/3580305.3599792
10.1007/s11222-008-9104-9
10.3389/fams.2019.00055
10.7717/peerj-cs.1516
10.1007/s11538-021-00869-5
10.2307/2348942
10.1006/jmva.1994.1028
10.2307/3318737
10.1239/jap/1183667414
10.1198/jcgs.2009.06134
10.1038/s41592-019-0686-2
10.21105/joss.01143
10.1007/978-1-4757-4145-2
10.1080/00031305.1995.10476177
10.3390/app10010272
10.1023/A:1022602019183
10.1023/A:1008202821328
|
[
"Antonini",
"Mu",
"Sansaloni-Pastor",
"Varma",
"Kabak"
] |
[
"Cilag GmbH International, 6300 Zug, Switzerland.",
"Cilag GmbH International, 6300 Zug, Switzerland.",
"Actelion Pharmaceuticals Ltd., 4123 Allschwil, Switzerland.",
"Johnson & Johnson World Headqtrs US, Bridgewater, NJ 08807, USA.",
"Johnson & Johnson World Headqtrs US, Bridgewater, NJ 08807, USA."
] |
[
"39335104",
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] |
[] | 8.048907 | 4.250957 |
39334383
| 436 |
Survival advantage of native and engineered T cells is acquired by mitochondrial transfer from mesenchymal stem cells.
|
Apoptosis, a form of programmed cell death, is critical for the development and homeostasis of the immune system. Chimeric antigen receptor T (CAR-T) cell therapy, approved for hematologic cancers, retains several limitations and challenges associated with ex vivo manipulation, including CAR T-cell susceptibility to apoptosis. Therefore, strategies to improve T-cell survival and persistence are required. Mesenchymal stem/stromal cells (MSCs) exhibit immunoregulatory and tissue-restoring potential. We have previously shown that the transfer of umbilical cord MSC (UC-MSC)-derived mitochondrial (MitoT) prompts the genetic reprogramming of CD3
We used a cell-free approach using artificial MitoT (Mitoception) of UC-MSC derived MT to peripheral blood mononuclear cells (PBMCs) followed by RNA-seq analysis of CD3
Gene expression related to apoptosis, cell death and/or responses to different stimuli was modified in CD3
Artificial MitoT prevents STS-induced apoptosis of human CD3
|
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] | 2024-09-28 | 60 |
39334383
|
[
"cell death",
"programmed cell death",
"peripheral blood mononuclear cells",
"artificial MitoT",
"human CD3",
"CAR T-cell susceptibility",
"CD3",
"RNA-seq analysis",
"MitoT",
"ex vivo manipulation",
"Mesenchymal stem/stromal cells",
"Apoptosis",
"apoptosis",
"T-cell survival",
"several limitations",
"hematologic cancers",
"umbilical cord",
"MSC",
"different stimuli",
"CD3\nArtificial MitoT",
"UC",
"CD3\nGene expression",
"a cell-free approach",
"MSCs",
"STS-induced apoptosis",
"challenges",
"CAR-T",
"MT",
"PBMCs",
"RNA"
] |
[
"Chimeric antigen receptor T (CAR-T) cells",
"Induced-apoptosis",
"Mesenchymal stromal/stem cells",
"Mitochondria transfer"
] | 0 |
10.1186/s12967-024-05627-4
|
[
"Court",
"Parra-Crisóstomo",
"Castro-Córdova",
"Abdo",
"Aragão",
"Lorca",
"Figueroa",
"Bonamino",
"Khoury"
] |
[
"IMPACT, Center of Interventional Medicine for Precision and Advanced Cellular Therapy, Santiago, Chile.\nCell for Cells, Santiago, Chile.\nLaboratory of Nano-Regenerative Medicine, Centro de Investigación e Innovación Biomédica (CiiB), Faculty of Medicine, Universidad de los Andes, Av. La Plaza 2501, Las Condes, Santiago, Chile.",
"Cell for Cells, Santiago, Chile.\nLaboratory of Nano-Regenerative Medicine, Centro de Investigación e Innovación Biomédica (CiiB), Faculty of Medicine, Universidad de los Andes, Av. La Plaza 2501, Las Condes, Santiago, Chile.",
"IMPACT, Center of Interventional Medicine for Precision and Advanced Cellular Therapy, Santiago, Chile.\nLaboratory of Nano-Regenerative Medicine, Centro de Investigación e Innovación Biomédica (CiiB), Faculty of Medicine, Universidad de los Andes, Av. La Plaza 2501, Las Condes, Santiago, Chile.",
"Cell and Gene Therapy Program, National Cancer Institute (INCA), Rio de Janeiro, Brazil.",
"Cell and Gene Therapy Program, National Cancer Institute (INCA), Rio de Janeiro, Brazil.",
"IMPACT, Center of Interventional Medicine for Precision and Advanced Cellular Therapy, Santiago, Chile.\nLaboratory of Nano-Regenerative Medicine, Centro de Investigación e Innovación Biomédica (CiiB), Faculty of Medicine, Universidad de los Andes, Av. La Plaza 2501, Las Condes, Santiago, Chile.",
"IMPACT, Center of Interventional Medicine for Precision and Advanced Cellular Therapy, Santiago, Chile.\nLaboratory of Nano-Regenerative Medicine, Centro de Investigación e Innovación Biomédica (CiiB), Faculty of Medicine, Universidad de los Andes, Av. La Plaza 2501, Las Condes, Santiago, Chile.\nConsorcio Regenero and R-MATIS, Chilean Consortium for Regenerative Medicine, and Manufacture of Advanced Therapies for Innovative Science, Santiago, Chile.",
"Cell and Gene Therapy Program, National Cancer Institute (INCA), Rio de Janeiro, Brazil.\nVice-Presidency of Research and Biological Collections (VPPCB), Oswaldo Cruz Foundation, (FIOCRUZ), Rio de Janeiro, Brazil.",
"IMPACT, Center of Interventional Medicine for Precision and Advanced Cellular Therapy, Santiago, Chile. mkhoury@uandes.cl.\nCell for Cells, Santiago, Chile. mkhoury@uandes.cl.\nLaboratory of Nano-Regenerative Medicine, Centro de Investigación e Innovación Biomédica (CiiB), Faculty of Medicine, Universidad de los Andes, Av. La Plaza 2501, Las Condes, Santiago, Chile. mkhoury@uandes.cl.\nConsorcio Regenero and R-MATIS, Chilean Consortium for Regenerative Medicine, and Manufacture of Advanced Therapies for Innovative Science, Santiago, Chile. mkhoury@uandes.cl."
] |
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[] | 8.973327 | 4.34808 |
39334276
| 437 |
Mesenchymal stem cell infusion for enhancing hematopoietic recovery and addressing cytopenias in CAR-T cell therapy.
|
Chimeric antigen receptor (CAR)-T therapy has emerged as a promising treatment for hematologic malignancies. However, cytopenia remains one of the most frequent and challenging adverse effects of this therapy.
We conducted a retrospective analysis of 26 patients with relapsed/refractory aggressive B-cell lymphoma who received CAR-T therapy at our center. Subsequently, to investigate measures to address cytopenias following CAR-T therapy, we isolated and generated murine CAR-T cells and bone marrow-derived mesenchymal stem cells (MSCs), establishing a murine syngeneic CAR-T therapy model. We assessed the impact of MSC infusion on hematopoietic recovery post-CAR-T therapy by evaluating complete blood count, bone marrow hematopoietic stem cells and their subpopulations, bone marrow histomorphology, and hematopoiesis-related genes.
All patients experienced cytopenias to varying degrees, with complete lineage involvement in half of the patients. Grade ≥ 3 cytopenias were observed in 88.46% of the patients. CAR-T therapy was associated with a higher incidence of biphasic, late-onset, or prolonged cytopenias. Survival analysis indicated that neutropenia and lymphopenia tended to be associated with better prognosis, whereas thrombocytopenia tended to be related to poorer outcomes. Through animal experiments, we discovered that MSCs infusion boosted HSCs and their long-term subpopulations, enhancing hematopoietic recovery, particularly in the megakaryocyte lineage, and mitigating bone marrow damage. Importantly, both in vitro and in vivo experiments demonstrated that MSCs did not compromise the activity or antitumor efficacy of CAR-T cells.
Our findings propose MSCs infusion as a promising strategy to address cytopenias, particularly thrombocytopenia, after CAR-T therapy. This approach could help overcome certain limitations of cellular immunotherapy by enhancing hematopoietic recovery without compromising the efficacy of CAR-T cells.
1 Cytopenia is a frequently observed adverse effect following CAR-T therapy, and it is often characterized by biphasic and prolonged patterns. 2 MSCs play a critical role in promoting hematopoietic recovery and mitigating bone marrow damage in a murine model of CAR-T therapy 3 The activity and antitumor efficacy of CAR-T cells were not impaired by MSCs.
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] | 2024-09-28 | 40 |
39334276
|
[
"bone marrow hematopoietic stem cells",
"CAR)-T therapy",
"mitigating bone marrow damage",
"bone marrow damage",
"bone marrow histomorphology",
"hematopoietic recovery",
"MSCs infusion",
"hematopoietic recovery post-CAR-T therapy",
"CAR-T therapy",
"cytopenia",
"cytopenias",
"murine CAR-T cells",
"CAR-T cells",
"bone marrow-derived mesenchymal stem cells",
"MSCs",
"complete lineage involvement",
"MSC infusion",
"antitumor efficacy",
"a murine syngeneic CAR-T therapy model",
"complete blood count",
"certain limitations",
"Survival analysis",
"cellular immunotherapy",
"Chimeric antigen receptor",
"varying degrees",
"better prognosis",
"animal experiments",
"vivo experiments",
"murine",
"poorer outcomes"
] |
[
"Cellular immunotherapy",
"Chimeric antigen receptor T-cell therapy",
"Cytopenia",
"Mesenchymal stem cells",
"Thrombocytopenia"
] | 0 |
10.1186/s13287-024-03941-8
|
[
"Xia",
"Wang",
"Shen",
"Xu",
"Xu",
"Li",
"Fan",
"Chen"
] |
[
"Department of Hematology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.\nDepartment of Hematology, Taizhou School of Clinical Medicine, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Nanjing Medical University, Taizhou, 225300, Jiangsu, China.",
"Department of Hematology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.",
"Department of Hematology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.",
"Department of Hematology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.",
"Department of Hematology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.",
"Department of Hematology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.",
"Department of Hematology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. fanlei3014@126.com.",
"Department of Hematology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. chenljb@126.com."
] |
[
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] |
[] | 5.617054 | 4.705984 |
39333315
| 438 |
Cytokine-mediated CAR T therapy resistance in AML.
|
Acute myeloid leukemia (AML) is a rapidly progressive malignancy without effective therapies for refractory disease. So far, chimeric antigen receptor (CAR) T cell therapy in AML has not recapitulated the efficacy seen in B cell malignancies. Here we report a pilot study of autologous anti-CD123 CAR T cells in 12 adults with relapsed or refractory AML. CAR T cells targeting CD123
|
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39333315
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"Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.\nCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.",
"Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.\nImmunology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.",
"Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.",
"Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.",
"Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.",
"Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.",
"Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.",
"Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.",
"Hematologics Inc., Seattle, WA, USA.",
"Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.",
"Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.",
"Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.",
"Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.\nCenter for Cell Therapy and Transplant, University of Pennsylvania, Philadelphia, PA, USA.",
"Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.\nCenter for Cell Therapy and Transplant, University of Pennsylvania, Philadelphia, PA, USA.",
"Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.",
"Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.\nCenter for Cell Therapy and Transplant, University of Pennsylvania, Philadelphia, PA, USA.",
"Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.\nCenter for Cell Therapy and Transplant, University of Pennsylvania, Philadelphia, PA, USA.",
"Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.\nCenter for Cell Therapy and Transplant, University of Pennsylvania, Philadelphia, PA, USA.",
"Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.\nCenter for Cell Therapy and Transplant, University of Pennsylvania, Philadelphia, PA, USA.",
"Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.\nCenter for Cell Therapy and Transplant, University of Pennsylvania, Philadelphia, PA, USA.",
"Novartis Biomedical Research, Cambridge, MA, USA.",
"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.",
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"Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.",
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"Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.\nCenter for Cell Therapy and Transplant, University of Pennsylvania, Philadelphia, PA, USA.",
"Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.\nDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.",
"Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. saar.gill2@pennmedicine.upenn.edu.\nDivision of Hematology-Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA. saar.gill2@pennmedicine.upenn.edu.\nCenter for Cell Therapy and Transplant, University of Pennsylvania, Philadelphia, PA, USA. saar.gill2@pennmedicine.upenn.edu."
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[] | 6.842594 | 7.206715 |
39333103
| 439 |
Histone marks identify novel transcription factors that parse CAR-T subset-of-origin, clinical potential and expansion.
|
Chimeric antigen receptor-modified T cell (CAR-T) immunotherapy has revolutionised blood cancer treatment. Parsing the genetic underpinnings of T cell quality and CAR-T efficacy is challenging. Transcriptomics inform CAR-T state, but the nature of dynamic transcription during activation hinders identification of transiently or minimally expressed genes, such as transcription factors, and over-emphasises effector and metabolism genes. Here we explore whether analyses of transcriptionally repressive and permissive histone methylation marks describe CAR-T cell functional states and therapeutic potential beyond transcriptomic analyses. Histone mark analyses improve identification of differences between naïve, central memory, and effector memory CD8 + T cell subsets of human origin, and CAR-T derived from these subsets. We find important differences between CAR-T manufactured from central memory cells of healthy donors and of patients. By examining CAR-T products from a clinical trial in lymphoma (NCT01865617), we find a novel association between the activity of the transcription factor KLF7 with in vivo CAR-T accumulation in patients and demonstrate that over-expression of KLF7 increases in vitro CAR-T proliferation and IL-2 production. In conclusion, histone marks provide a rich dataset for identification of functionally relevant genes not apparent by transcriptomics.
|
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] | 2024-09-28 | 64 |
39333103
|
[
"T cell quality",
"central memory cells",
"Histone mark analyses",
"transcription factors",
"histone marks",
"CAR-T cell functional states",
"central memory",
"effector memory",
"dynamic transcription",
"Chimeric antigen receptor-modified T cell",
"CAR-T state",
"CAR-T products",
"identification",
"CAR-T efficacy",
"vivo CAR-T accumulation",
"CAR-T",
"transcriptomic analyses",
"important differences",
"blood cancer treatment",
"CD8 + T cell subsets",
"analyses",
"KLF7",
"therapeutic potential",
"human origin",
"differences",
"patients",
"healthy donors",
"vitro CAR-T proliferation and IL-2 production",
"CAR-T) immunotherapy",
"the transcription factor"
] |
[] | 0 |
10.1038/s41467-024-52503-2
|
[
"Fiorenza",
"Zheng",
"Purushe",
"Bock",
"Sarthy",
"Janssens",
"Sheih",
"Kimble",
"Kirchmeier",
"Phi",
"Gauthier",
"Hirayama",
"Riddell",
"Wu",
"Gottardo",
"Maloney",
"Yang",
"Henikoff",
"Turtle"
] |
[
"Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia. salvatore.fiorenza@sydney.edu.au.",
"Basic Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.\nBioinformatics and Computational Biology Department, University of Texas, MD Anderson Cancer Center, Houston, TX, USA.",
"Clinical Research Division, Fred Hutchinson Cancer Cente, Seattle, WA, USA.",
"Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.",
"Clinical Research Division, Fred Hutchinson Cancer Cente, Seattle, WA, USA.",
"Basic Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.\nDepartment of Epigenetics, Van Andel Institute, Grand Rapids, MI, USA.",
"Clinical Research Division, Fred Hutchinson Cancer Cente, Seattle, WA, USA.",
"Clinical Research Division, Fred Hutchinson Cancer Cente, Seattle, WA, USA.",
"Clinical Research Division, Fred Hutchinson Cancer Cente, Seattle, WA, USA.",
"Clinical Research Division, Fred Hutchinson Cancer Cente, Seattle, WA, USA.",
"Clinical Research Division, Fred Hutchinson Cancer Cente, Seattle, WA, USA.",
"Clinical Research Division, Fred Hutchinson Cancer Cente, Seattle, WA, USA.",
"Clinical Research Division, Fred Hutchinson Cancer Cente, Seattle, WA, USA.",
"Clinical Research Division, Fred Hutchinson Cancer Cente, Seattle, WA, USA.",
"Biomedical Data Sciences, Lausanne University Hospital, Lausanne, Switzerland.",
"Clinical Research Division, Fred Hutchinson Cancer Cente, Seattle, WA, USA.",
"Sydney Precision Data Science Centre, The University of Sydney, Sydney, NSW, Australia.",
"Basic Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.",
"Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.\nRoyal North Shore Hospital, St. Leonards, NSW, Australia."
] |
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[] | 8.298454 | 4.423576 |
39332423
| 440 |
Challenges and solutions for cellular therapy development in autoimmune diseases.
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39332423
|
[] |
[] | 0 |
10.1016/S2665-9913(24)00274-1
|
[
"Volkmann",
"Varga",
"Blazar",
"Pavletic"
] |
[
"Department of Medicine, Division of Rheumatology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA. Electronic address: evolkmann@mednet.ucla.edu.",
"Department of Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA.",
"Department of Pediatrics, Division of Blood and Marrow Transplant & Cellular Therapy, University of Minnesota, Minneapolis, MN, USA.",
"Immune Deficiency and Cellular Therapy Program, Center for Cancer Research, National Cancer Institute, US National Institutes of Health, Bethesda, MD, USA."
] |
[
"39332423"
] |
[] | 33.005775 | 7.484975 |
39329777
| 441 |
Overcoming Antigen Escape and T-Cell Exhaustion in CAR-T Therapy for Leukemia.
|
Leukemia is a prevalent pediatric cancer with significant challenges, particularly in relapsed or refractory cases. Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a personalized cancer treatment, modifying patients' T cells to target and destroy resistant cancer cells. This study reviews the current therapeutic options of CAR-T therapy for leukemia, addressing the primary obstacles such as antigen escape and T-cell exhaustion. We explore dual-targeting strategies and their potential to improve treatment outcomes by preventing the loss of target antigens. Additionally, we examine the mechanisms of T-cell exhaustion and strategies to enhance CAR-T persistence and effectiveness. Despite remarkable clinical successes, CAR-T therapy poses risks such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Our findings highlight the need for ongoing research to optimize CAR-T applications, reduce toxicities, and extend this innovative therapy to a broader range of hematologic malignancies. This comprehensive review aims to provide valuable insights for improving leukemia treatment and advancing the field of cancer immunotherapy.
|
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39329777
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"target antigens",
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"a prevalent pediatric cancer",
"this innovative therapy",
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"immune effector cell-associated neurotoxicity syndrome",
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[
"Bartoszewska",
"Tota",
"Kisielewska",
"Skowron",
"Sebastianka",
"Stefaniak",
"Molik",
"Rubin",
"Kraska",
"Choromańska"
] |
[
"Faculty of Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 5, 50-345 Wroclaw, Poland.\nStudent Research Group No K148, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland.",
"Faculty of Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 5, 50-345 Wroclaw, Poland.\nStudent Research Group No K148, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland.",
"Faculty of Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 5, 50-345 Wroclaw, Poland.\nStudent Research Group No K148, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland.",
"Faculty of Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 5, 50-345 Wroclaw, Poland.\nStudent Research Group No K148, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland.",
"Faculty of Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 5, 50-345 Wroclaw, Poland.\nStudent Research Group No K148, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland.",
"Faculty of Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 5, 50-345 Wroclaw, Poland.\nStudent Research Group No K148, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland.",
"Faculty of Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 5, 50-345 Wroclaw, Poland.\nStudent Research Group No K148, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland.",
"Faculty of Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 5, 50-345 Wroclaw, Poland.\nStudent Research Group No K148, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland.",
"Faculty of Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 5, 50-345 Wroclaw, Poland.\nStudent Research Group No K148, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland.",
"Department of Molecular and Cellular Biology, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland."
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[] | 6.960016 | 6.758739 |
39329700
| 442 |
Revolutionizing Cancer Treatments through Stem Cell-Derived CAR T Cells for Immunotherapy: Opening New Horizons for the Future of Oncology.
|
Recent advances in cellular therapies have paved the way for innovative treatments of various cancers and autoimmune disorders. Induced pluripotent stem cells (iPSCs) represent a remarkable breakthrough, offering the potential to generate patient-specific cell types for personalized as well as allogeneic therapies. This review explores the application of iPSC-derived chimeric antigen receptor (CAR) T cells, a cutting-edge approach in allogeneic cancer immunotherapies. CAR T cells are genetically engineered immune cells designed to target specific tumor antigens, and their integration with iPSC technology holds immense promise for enhancing the efficacy, safety, and scalability of cellular therapies. This review begins by elucidating the principles behind iPSC generation and differentiation into T cells, highlighting the advantage of iPSCs in providing a uniform, inexhaustible source of CAR T cells. Additionally, we discuss the genetic modification of iPSC-derived T cells to express various CARs, emphasizing the precision and flexibility this affords in designing customized therapies for a diverse range of malignancies. Notably, iPSC-derived CAR T cells demonstrate a superior proliferative capacity, persistence, and anti-tumor activity compared to their conventionally derived counterparts, offering a potential solution to challenges associated with conventional CAR T cell therapies. In conclusion, iPSC-derived CAR T cells represent a groundbreaking advancement in cellular therapies, demonstrating unparalleled potential in revolutionizing the landscape of immunotherapies. As this technology continues to evolve, it holds the promise of providing safer, more effective, and widely accessible treatment options for patients battling cancer and other immune-related disorders. This review aims to shed light on the transformative potential of iPSC-derived CAR T cells and inspire further research and development in this dynamic field.
|
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39329700
|
[
"CAR T cells",
"conventional CAR T cell therapies",
"T cells",
"Induced pluripotent stem cells",
"various CARs",
"cellular therapies",
"allogeneic therapies",
"CAR) T cells",
"CAR",
"customized therapies",
"various cancers",
"allogeneic cancer immunotherapies",
"iPSC-derived CAR T cells",
"specific tumor antigens",
"unparalleled potential",
"patient-specific cell types",
"iPSC technology",
"anti-tumor activity",
"immense promise",
"iPSC-derived T cells",
"innovative treatments",
"iPSC generation",
"cancer",
"genetically engineered immune cells",
"further research",
"iPSC",
"patients",
"iPSCs",
"autoimmune disorders",
"Recent advances"
] |
[
"chimeric antigen receptor (CAR)",
"differentiation",
"immunotherapy",
"induced pluripotent stem cells (iPSCs)"
] | 0 |
10.3390/cells13181516
10.1038/s41392-024-01809-0
10.1038/nbt.2678
10.1016/j.stem.2020.02.011
10.1158/2643-3230.BCD-21-0084
10.1007/s40290-022-00428-w
10.3389/fimmu.2022.903562
10.1093/stmcls/sxac040
10.1038/s41551-022-00969-0
10.36401/JIPO-22-7
10.1016/j.transci.2023.103828
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10.1016/j.stem.2022.06.014
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10.1016/j.soc.2019.02.005
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10.1182/blood.2022016205
10.1016/j.stem.2022.02.009
10.1089/cell.2023.0041
10.1111/cpr.13661
10.1158/1078-0432.CCR-18-2035
10.1016/S0140-6736(20)32334-5
10.1016/S2352-3026(22)00245-9
10.1016/S1470-2045(23)00436-9
10.1038/s41375-024-02220-y
10.1158/1078-0432.CCR-20-3863
10.1186/s13287-021-02510-7
10.1158/0008-5472.CAN-14-3321
10.1002/eji.202049107
10.3389/fmolb.2021.675179
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10.1016/j.ccell.2024.01.002
10.1038/s41467-020-20658-3
10.1016/j.ymthe.2021.05.016
10.1111/exd.14686
10.1016/j.ymthe.2021.10.006
|
[
"Mishra",
"Kalyuzhny"
] |
[
"Cellinfinitybio, San Francisco, CA 94107, USA.",
"Biotechne 2, Minneapolis, MN 55413, USA."
] |
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[] | 8.919354 | 3.487668 |
39328551
| 443 |
Immune checkpoint blockade and CAR T-cell therapy in T-cell/histiocyte-rich large B-cell lymphoma: Challenges and opportunities.
|
T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a highly aggressive large B-cell lymphoma defined by a paucity of malignant B cells amidst a dense infiltrate of reactive T cells and histiocytes. The unique tumor microenvironment (TME) of THRLBCL, marked by extensive immune infiltration and high PD-L1 expression, poses significant challenges for immunotherapies. This review explores the therapeutic potential and resistance mechanisms of immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T-cell therapy in THRLBCL. While ICIs show promise due to the immune-suppressive nature of the TME, CAR T-cell therapy has demonstrated limited efficacy, often hindered by primary resistance and early relapse. Combining CAR T-cell therapy with ICIs and Bruton tyrosine kinase (BTK) inhibitors and developing novel CAR constructs targeting multiple antigens are potential strategies to enhance treatment outcomes. Further prospective studies are essential to corroborate these strategies and improve the prognosis for this challenging lymphoma subtype.
|
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] | 2024-09-27 | 20 |
39328551
|
[
"malignant B cells",
"reactive T cells",
"immune checkpoint inhibitors",
"extensive immune infiltration",
"novel CAR",
"CAR T-cell therapy",
"potential strategies",
"CAR",
"primary resistance",
"multiple antigens",
"antigen receptor",
"Bruton tyrosine kinase",
"Further prospective studies",
"THRLBCL",
"TME",
"significant challenges",
"limited efficacy",
"inhibitors",
"CAR) T-cell therapy",
"ICIs",
"T-cell/histiocyte-rich large B-cell lymphoma",
"treatment outcomes",
"early relapse",
"high PD-L1 expression",
"a highly aggressive large B-cell lymphoma",
"BTK",
"this challenging lymphoma subtype",
"promise",
"Bruton",
"the therapeutic potential and resistance mechanisms"
] |
[
"CAR T-cell",
"Immune checkpoint inhibitors",
"T-cell/histiocyte-rich large B-Cell lymphoma",
"Tumor microenvironment"
] | 0 |
10.1016/j.heliyon.2024.e38023
10.1080/10428194.2019.1639166
10.1200/jco.2003.06.046
10.1182/blood-2020-136489
10.3390/cancers11070915
10.1016/j.pathol.2019.08.013
10.1182/bloodadvances.2022007046
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10.1158/1078-0432.Ccr-20-1457
10.1182/blood.2021012634
|
[
"Sahin",
"Akin"
] |
[
"Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkey.",
"Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkey."
] |
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[] | 6.778215 | 6.005676 |
39328262
| 444 |
Exploring the potential of the convergence between extracellular vesicles and CAR technology as a novel immunotherapy approach.
|
Cancer therapy is a dynamically evolving field, witnessing the emergence of innovative approaches that offer a promising outlook for patients grappling with persistent disease. Within the realm of therapeutic exploration, chimeric antigen receptor (CAR) T cells as well as CAR NK cells, have surfaced as novel approaches, each possessing unique attributes and transformative potential. Immune cells engineered to express CARs recognizing tumour-specific antigens, have shown remarkable promise in treating terminal cancers by combining the precision of antibody specificity with the potent cytotoxic function of T cells. However, their application in solid tumours is still in its nascent stages, presenting unique major challenges. On the same note, CAR NK cells offer a distinct immunotherapeutic approach, utilizing CARs on NK cells, providing advantages in safety, manufacturing simplicity, and a broader scope for cancer treatment. Extracellular vesicles (EVs) have emerged as promising therapeutic agents due to their ability to carry crucial biomarkers and biologically active molecules, serving as vital messengers in the intercellular communication network. In the context of cancer, the therapeutic potential of EVs lies in delivering tumour-suppressing proteins, nucleic acid components, or targeting drugs with precision, thereby redefining the paradigm of precision medicine. The fusion of CAR technology with the capabilities of EVs has given rise to a new therapeutic frontier. CAR T EVs and CAR NK EVs, leveraging the power of EVs, have the potential to alleviate challenges associated with live-cell therapies. EVs are suggested to reduce the side effects linked to CAR T cell therapy and hold the potential to revolutionize the penetrance in solid tumours. EVs act as carriers of pro-apoptotic molecules and RNA components, enhancing immune responses and thereby expanding their therapeutic potential. In this review article, we navigate dynamic landscapes, with our objective being to evaluate comparative efficacy, safety profiles, manufacturing complexities, and clinical applicability.
|
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39328262
|
[
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"cancer",
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"dynamic landscapes",
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[
"NK cells",
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"The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences Ben-Gurion University Beer-Sheva Israel.",
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"The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences Ben-Gurion University Beer-Sheva Israel."
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] |
[] | 9.753142 | 3.482319 |
39325974
| 445 |
EASIX and m-EASIX predict CRS and ICANS in pediatric and AYA patients after CD19-CAR T-cell therapy.
|
Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are complications of CD19-directed chimeric antigen receptor (CD19-CAR) T-cell therapy. The Endothelial Activation and Stress Index (EASIX) and modified EASIX (m-EASIX) scores have been retrospectively proven to be predictive of CRS and ICANS in adult CAR T-cell recipients. However, these scores have not been evaluated in pediatric cohorts. We retrospectively report on 76 pediatric and adolescent and young adult (AYA) patients with relapsed/refractory B-cell acute lymphoblastic leukemia treated with CD19-CAR T cells at St. Jude Children's Research Hospital or Johns Hopkins Hospital. Data included patient, disease, and treatment characteristics. EASIX and m-EASIX scores were calculated at days -5 before, 0, and +3 after CAR T-cell infusion. CRS and ICANS occurred in 47 and 17 patients, respectively. At all evaluated time points, the median EASIX scores were higher for patients who developed severe CRS and any grade ICANS, and the median m-EASIX scores were higher in patients who developed severe CRS and severe ICANS than those with no/mild CRS/ICANS. Receiver operating characteristic curve analysis showed that both scores were strong predictors of CRS, especially severe CRS, at all time points. Any grade and severe ICANS were best predicted by both scores at day +3. m-EASIX uniformly outperformed EASIX, except for predicting any grade ICANS. Our results validate the potential utility of EASIX and m-EASIX scores for predicting CAR T-cell-related complications for pediatric and AYA patients.
|
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] | 2024-09-26 | 1 |
39325974
|
[
"m-EASIX",
"EASIX",
"severe CRS",
"severe ICANS",
"CRS",
"patient",
"patients",
"m-EASIX scores",
"adult CAR T-cell recipients",
"the median EASIX scores",
"CAR T-cell infusion",
"EASIX and m-EASIX scores",
"Receiver operating characteristic curve analysis",
"immune effector cell-associated neurotoxicity syndrome",
"ICANS",
"CD19-CAR T cells",
"Johns Hopkins Hospital",
"Cytokine release syndrome",
"the median m-EASIX scores",
"pediatric cohorts",
"CAR T-cell-related complications",
"pediatric and AYA patients",
"complications",
"especially severe CRS",
"strong predictors",
"relapsed/refractory B-cell acute lymphoblastic leukemia",
"St. Jude Childrens Research Hospital",
"CD19-directed chimeric antigen receptor",
"AYA",
"treatment characteristics"
] |
[] | 0 |
10.1182/bloodadvances.2024014027
|
[
"Zandaki",
"Selukar",
"Bi",
"Li",
"Zinsky",
"Bonifant",
"Epperly",
"Keerthi",
"Triplett",
"Gottschalk",
"Naik",
"Talleur"
] |
[
"Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN.",
"Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN.",
"Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN.",
"Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN.",
"Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.\nDepartment of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD.",
"Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.\nDepartment of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD.",
"Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN.",
"Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN.",
"Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN.",
"Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN.",
"Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN.",
"Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN."
] |
[
"39325974"
] |
[] | 5.847211 | 4.453657 |
39322664
| 446 |
Single-cell CAR T atlas reveals type 2 function in 8-year leukaemia remission.
|
Despite a high response rate in chimeric antigen receptor (CAR) T cell therapy for acute lymphocytic leukaemia (ALL)
|
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] | 2024-09-26 | 46 |
39322664
|
[
"chimeric antigen receptor",
"acute lymphocytic leukaemia",
"CAR",
"ALL",
"a high response rate"
] |
[] | 0 |
10.1038/s41586-024-07762-w
|
[
"Bai",
"Feng",
"McClory",
"de Oliveira",
"Diorio",
"Gregoire",
"Tao",
"Yang",
"Zhao",
"Peng",
"Sferruzza",
"Zhou",
"Zhou",
"Kerr",
"Baysoy",
"Su",
"Yang",
"Camara",
"Chen",
"Tang",
"June",
"Melenhorst",
"Grupp",
"Fan"
] |
[
"Department of Biomedical Engineering, Yale University, New Haven, CT, USA.",
"Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.\nInstitute of Materials Science & Engineering, EPFL, Lausanne, Switzerland.",
"Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.\nDepartment of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.",
"Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.",
"Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.\nDepartment of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.",
"Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.",
"Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.",
"Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.",
"Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.",
"Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.",
"Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.",
"Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.",
"Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.\nInstitute of Materials Science & Engineering, EPFL, Lausanne, Switzerland.",
"Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.",
"Department of Biomedical Engineering, Yale University, New Haven, CT, USA.",
"Department of Biomedical Engineering, Yale University, New Haven, CT, USA.",
"Department of Biomedical Engineering, Yale University, New Haven, CT, USA.",
"Department of Genetics and Institute for Biomedical Informatics, University of Pennsylvania, Philadelphia, PA, USA.",
"Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.",
"Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland. li.tang@epfl.ch.\nInstitute of Materials Science & Engineering, EPFL, Lausanne, Switzerland. li.tang@epfl.ch.",
"Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. cjune@upenn.edu.\nCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. cjune@upenn.edu.\nParker Institute for Cancer Immunotherapy at University of Pennsylvania, Philadelphia, PA, USA. cjune@upenn.edu.",
"Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. melenhj@ccf.org.",
"Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA. grupp@chop.edu.\nDepartment of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA. grupp@chop.edu.",
"Department of Biomedical Engineering, Yale University, New Haven, CT, USA. rong.fan@yale.edu.\nDepartment of Pathology, Yale University School of Medicine, New Haven, CT, USA. rong.fan@yale.edu.\nYale Stem Cell Center, Yale University School of Medicine, New Haven, CT, USA. rong.fan@yale.edu.\nHuman and Translational Immunology, Yale University School of Medicine, New Haven, CT, USA. rong.fan@yale.edu.\nYale Cancer Center, Yale University School of Medicine, New Haven, CT, USA. rong.fan@yale.edu."
] |
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[] | 6.697814 | 5.93149 |
39322661
| 447 |
Transferrin receptor targeting chimeras for membrane protein degradation.
|
Cancer cells require high levels of iron for rapid proliferation, leading to significant upregulation of cell-surface transferrin receptor 1 (TfR1), which mediates iron uptake by binding to the iron-carrying protein transferrin
|
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] | 2024-09-26 | 62 |
39322661
|
[
"iron uptake",
"iron",
"Cancer cells",
"high levels",
"rapid proliferation",
"significant upregulation",
"transferrin",
"cell-surface transferrin receptor",
"the iron-carrying protein",
"which"
] |
[] | 0 |
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|
[
"Zhang",
"Duque-Jimenez",
"Facchinetti",
"Brixi",
"Rhee",
"Feng",
"Jänne",
"Zhou"
] |
[
"Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.\nDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.",
"Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.",
"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.\nDepartment of Medicine, Harvard Medical School, Boston, MA, USA.\nLowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.",
"Harvard University, Boston, MA, USA.",
"Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.\nDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.",
"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.\nDepartment of Medicine, Harvard Medical School, Boston, MA, USA.\nLowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.",
"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.\nDepartment of Medicine, Harvard Medical School, Boston, MA, USA.\nLowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.\nBelfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA, USA.",
"Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA. xin_zhou1@dfci.harvard.edu.\nDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA. xin_zhou1@dfci.harvard.edu."
] |
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[] | 33.185524 | 7.502739 |
39321344
| 448 |
Impact of soluble BCMA and non-T-cell factors on refractoriness to BCMA-targeting T-cell engagers in multiple myeloma.
|
Adoptive T-cell therapy is a promising therapy for multiple myeloma (MM), but its efficacy hinges on understanding the relevant biologic and predictive markers of response. B-cell maturation antigen (BCMA) is a key target antigen in MM with active development of multiple anti-BCMA T-cell engagers (TCEs) and chimeric antigen receptor T-cell therapies. The regulation of surface BCMA expression by MM cells, which leads to shedding of soluble BCMA (sBCMA), has triggered debate about the significance of sBCMA as a predictive marker and its potential impact on treatment outcomes. To address this, we leveraged whole-genome sequencing and in vitro assays to demonstrate that sBCMA may independently predict primary refractoriness to anti-BCMA therapies. In addition to sBCMA, tumor burden and surface BCMA antigen density collectively influenced the anti-BCMA TCE cytotoxic efficacy. Correlative analyses of 163 patients treated with the anti-BCMA TCE teclistamab validated and further underscored the association between elevated baseline sBCMA (>400 ng/mL) and refractoriness. Importantly, increasing the TCE dose, using TCE against alternative targets (eg, GPRC5D), and gamma secretase inhibitors were able to overcome the high sBCMA levels. These findings highlight the importance of taking into account the baseline sBCMA levels, disease burden, and TCE dose intensity when administering anti-BCMA TCEs, thereby offering critical insights for optimizing therapeutic strategies to overcome specific high-risk features and primary anti-BCMA TCE refractoriness.
|
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] | 2024-09-25 | 30 |
39321344
|
[
"primary anti-BCMA TCE refractoriness",
"anti-BCMA",
"anti-BCMA therapies",
"anti-BCMA TCEs",
"elevated baseline sBCMA",
"MM cells",
"sBCMA",
"the anti-BCMA TCE cytotoxic efficacy",
"multiple anti-BCMA T-cell engagers",
"the anti-BCMA TCE teclistamab",
"TCE",
"surface BCMA expression",
"soluble BCMA",
"BCMA",
"primary refractoriness",
"chimeric antigen receptor T-cell therapies",
"disease burden",
"alternative targets",
"MM",
"gamma secretase inhibitors",
"tumor burden",
"multiple myeloma",
"the baseline sBCMA levels",
"B-cell maturation antigen",
"therapeutic strategies",
"Adoptive T-cell therapy",
"critical insights",
"active development",
"refractoriness",
"treatment outcomes"
] |
[] | 0 |
10.1182/blood.2024026212
|
[
"Lee",
"Durante",
"Skerget",
"Vishwamitra",
"Benaoudia",
"Ahn",
"Poorebrahim",
"Barakat",
"Jung",
"Leblay",
"Ziccheddu",
"Diamond",
"Papadimitriou",
"Cohen",
"Landgren",
"Neri",
"Maura",
"Bahlis"
] |
[
"Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada.",
"Sylvester Comprehensive Cancer Center, Myeloma Research Institute, University of Miami, Miami, FL.",
"Janssen Research & Development, Spring House, PA.",
"Janssen Research & Development, Spring House, PA.",
"Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada.",
"Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada.",
"Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada.",
"Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada.",
"Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada.",
"Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada.",
"Sylvester Comprehensive Cancer Center, Myeloma Research Institute, University of Miami, Miami, FL.",
"Sylvester Comprehensive Cancer Center, Myeloma Research Institute, University of Miami, Miami, FL.",
"Sylvester Comprehensive Cancer Center, Myeloma Research Institute, University of Miami, Miami, FL.",
"Department of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA.",
"Sylvester Comprehensive Cancer Center, Myeloma Research Institute, University of Miami, Miami, FL.",
"Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada.",
"Sylvester Comprehensive Cancer Center, Myeloma Research Institute, University of Miami, Miami, FL.",
"Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada."
] |
[
"39321344",
"35661166",
"37783970",
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[] | 4.81164 | 6.19461 |
39321207
| 449 |
Preclinical Evaluation of AZD6422, an Armored Chimeric Antigen Receptor T Cell Targeting CLDN18.2 in Gastric, Pancreatic, and Esophageal Cancers.
|
Claudin 18.2 (CLDN18.2) is a surface membrane protein that is crucial for maintaining tight junctions in gastric mucosal cells and is highly expressed in gastric, esophageal, and pancreatic cancers. Thus, CLDN18.2 is suited for exploration as a clinical target for chimeric antigen receptor T-cell (CAR-T) therapy in these indications. Although CAR-T therapies show promise, a challenge faced in their development for solid tumors is the immunosuppressive tumor microenvironment, which is often characterized by the presence of immune and stromal cells secreting high levels of TGFβ. The addition of TGFβ armoring can potentially expand CAR-T activity in solid tumors. We report on the preclinical development of a CLDN18.2-targeting CAR-T therapy showing effectiveness in patient models with CLDN18.2-positive gastric, esophageal, and pancreatic tumors.
The lead lentivirus product contains a unique single-chain variable fragment; CD28 and CD3z costimulatory and signaling domains; and dominant-negative TGF-β receptor armoring, enhancing targeting and safety and counteracting suppression. We developed a shortened cell manufacturing process to enhance the potency of the final product AZD6422.
AZD6422 exhibited significant antitumor activity and tolerability in multiple patient-derived tumor xenograft models with various CLDN18.2 and TGF-β levels, as determined by IHC. The efficacy of armored CAR-T cells in tumor models with elevated TGFβ was increased in vitro and in vivo. In vitro restimulation assays established greater persistence and cytolytic function of AZD6422 compared with a traditionally manufactured CAR-T.
AZD6422 was safe and efficacious in patient-derived, CLDN18.2-positive murine models of gastrointestinal cancers. Our data support further clinical development of AZD6422 for patients with these cancers.
|
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] | 2024-09-25 | 67 |
39321207
|
[
"tumor models",
"gastric mucosal cells",
"solid tumors",
"pancreatic tumors",
"further clinical development",
"patient models",
"multiple patient-derived tumor xenograft models",
"CLDN18.2",
"significant antitumor activity",
"armored CAR-T cells",
"patients",
"high levels",
"greater persistence",
"elevated TGFβ",
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"cytolytic function",
"tight junctions",
"gastrointestinal cancers",
"a shortened cell manufacturing process",
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"TGFβ",
"CLDN18.2-positive gastric",
"patient-derived, CLDN18.2-positive murine models",
"chimeric antigen receptor T-cell (CAR-T) therapy",
"a CLDN18.2-targeting CAR-T therapy",
"CD28",
"CD3z"
] |
[] | 0 |
10.1158/1078-0432.CCR-24-1853
|
[
"Barrett",
"Britton",
"Carrasco",
"Breen",
"Broggi",
"Hatke",
"Clark",
"Yang",
"Phipps",
"Ortiz",
"Janocha",
"Zanvit",
"Giraldo",
"Martin",
"Lapointe",
"Harder",
"Cornish",
"Attili",
"Mazor",
"Damschroder",
"Cobbold",
"Moody",
"Bosco"
] |
[
"Early Oncology Research, Gaithersburg, Maryland.",
"Biologics Engineering, Gaithersburg, Maryland.",
"Early Oncology Research, Gaithersburg, Maryland.",
"Early Oncology Research, Gaithersburg, Maryland.",
"Oncology Translational Medicine, Gaithersburg, Maryland.",
"Biologics Engineering, Gaithersburg, Maryland.",
"Biologics Engineering, Gaithersburg, Maryland.",
"Biologics Engineering, Gaithersburg, Maryland.",
"Biologics Engineering, Gaithersburg, Maryland.",
"Early Oncology Research, Gaithersburg, Maryland.",
"Early Oncology Research, Gaithersburg, Maryland.",
"Early Oncology Research, Gaithersburg, Maryland.",
"Translational Pathology, Oncology R&D, AstraZeneca, Gaithersburg, Maryland.",
"Oncology Translational Medicine, Gaithersburg, Maryland.",
"Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom.",
"Computational Pathology, AstraZeneca, Munich, Germany.",
"Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom.",
"Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom.",
"Biologics Engineering, Gaithersburg, Maryland.",
"Biologics Engineering, Gaithersburg, Maryland.",
"Early Oncology Research, Gaithersburg, Maryland.",
"Early Oncology Research, Gaithersburg, Maryland.",
"Early Oncology Research, Gaithersburg, Maryland."
] |
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[] | 8.621586 | 6.212189 |
39317919
| 450 |
CAR T-cells for pediatric solid tumors: where to go from here?
|
Despite the great success that chimeric antigen receptor (CAR) T-cells have had in patients with B-cell malignancies and multiple myeloma, they continue to have limited efficacy against most solid tumors. Especially in the pediatric population, pre- and post-treatment biopsies are rarely performed due to ethical reasons, and thus, our understanding is still very limited regarding the mechanisms in the tumor microenvironment by which tumor cells exclude effectors and attract immune-suppressive cells. Nevertheless, based on the principles that are known, current T-cell engineering has leveraged some of these processes and created more potent CAR T-cells. The recent discovery of new oncofetal antigens and progress made in CAR design have expanded the potential pool of candidate antigens for therapeutic development. The most promising approaches to enhance CAR T-cells are novel CAR gating strategies, creative ways of cytokine delivery to the TME without enhancing systemic toxicity, and hijacking the chemokine axis of tumors for migratory purposes. With these new modifications, the next step in the era of CAR T-cell development will be the clinical validation of these promising preclinical findings.
|
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] | 2024-09-25 | 176 |
39317919
|
[
"tumor cells",
"new oncofetal antigens",
"CAR T-cell development",
"chimeric antigen receptor",
"candidate antigens",
"most solid tumors",
"CAR T-cells",
"novel CAR gating strategies",
"current T-cell engineering",
"tumors",
"limited efficacy",
"CAR design",
"ethical reasons",
"therapeutic development",
"B-cell malignancies",
"systemic toxicity",
"cytokine delivery",
"creative ways",
"CAR",
"immune-suppressive cells",
"multiple myeloma",
"CAR) T-cells",
"more potent CAR T-cells",
"pre- and post-treatment biopsies",
"migratory purposes",
"progress",
"effectors",
"the tumor microenvironment",
"patients",
"these promising preclinical findings"
] |
[
"Adoptive T-cell therapy",
"CAR",
"Pediatric oncology",
"Solid tumors"
] | 0 |
10.1007/s10555-024-10214-6
|
[
"Trautmann",
"Yakobian",
"Nguyen"
] |
[
"Pediatric Oncology Branch, NCI, NIH, NCI, 10 Center Drive, 1W-5832, Bethesda, MD, 20892, USA.",
"Pediatric Oncology Branch, NCI, NIH, NCI, 10 Center Drive, 1W-5832, Bethesda, MD, 20892, USA.",
"Pediatric Oncology Branch, NCI, NIH, NCI, 10 Center Drive, 1W-5832, Bethesda, MD, 20892, USA. hongharosa.nguyen@nih.gov."
] |
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[] | 9.195315 | 4.845809 |
39317455
| 451 |
Neurofilament light chain levels as an early predictive biomarker of neurotoxicity after CAR T-cell therapy.
|
Immune effector cell-associated neurotoxicity syndrome (ICANS) remains a significant cause of morbidity associated with CD19-targeted chimeric antigen receptor (CAR) T-cell therapy. Early prediction of patients who will develop ICANS would be crucial to better guide individualized management of high-risk patients, but specific predictive markers are still missing. Serum neurofilament light chain (NfL) levels are a sensitive indicator of neuroaxonal injury in neurological diseases. Elevated NfL levels at the time of CAR T-cell infusion have been associated with the severity of ICANS, but their utility for earlier identification of patients with subclinical neurological damage has not been evaluated.We studied all consecutive adult patients who received commercial CAR T cells for relapsed/refractory B-cell lymphomas at Saint-Louis Hospital between January 2019 and February 2023. Patients with pre-existing or current neurological disease were excluded. NfL levels were quantified in frozen serum collected at the time of the decision to treat (ie, the day of leukapheresis) and at the time of treatment (ie, the day of infusion).Of the 150 study patients, 28% developed ICANS of any grade, including 15.3% of grade 2-4. Receiving a CAR construct with a CD28 domain (58% of patients) was the strongest predictor of grade 2-4 ICANS. Serum NfL levels were significantly higher in patients with grade 2-4 ICANS than in those with grade 0-1 ICANS, both at the time of leukapheresis and infusion. In multivariate models, NfL above the cut-off value was independently associated with grade 2-4 ICANS at leukapheresis (NfL>75 pg/mL, OR 4.2, 95% CI 1.2 to 14.2, p=0.022) and infusion (NfL>58 pg/mL, OR 4.3, 95% CI 1.3 to 13.7, p=0.015).In conclusion, high NfL levels at the time of the decision to proceed with CAR T-cell manufacturing may represent an early surrogate of underlying loss of neuroaxonal integrity that increases the risk of subsequent neurotoxicity. Incorporating NfL levels into the decision-making process based on each patient's risk profile could help determine the appropriate CAR product when possible, and guide the prophylactic or therapeutic management of ICANS.
|
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] | 2024-09-25 | 26 |
39317455
|
[
"Patients",
"patients",
"high NfL levels",
"Serum NfL levels",
"commercial CAR T cells",
"Elevated NfL levels",
"NfL levels",
"Incorporating NfL levels",
"neurological diseases",
"Serum NfL",
"subclinical neurological damage",
"ICANS",
"grade",
"high-risk patients",
"earlier identification",
"CAR T-cell infusion",
"Immune effector cell-associated neurotoxicity syndrome",
"neuroaxonal integrity",
"NfL",
"CAR T-cell manufacturing",
"Early prediction",
"neuroaxonal injury",
"CAR",
"all consecutive adult patients",
"specific predictive markers",
"individualized management",
"NfL>58 pg",
"subsequent neurotoxicity",
"pre-existing or current neurological disease",
"underlying loss"
] |
[
"Chimeric antigen receptor - CAR",
"Immune effector cell-associated neurotoxicity syndrome - ICANS",
"Lymphoma"
] | 0 |
10.1136/jitc-2024-009525
10.1002/ajh.26301
10.1038/s41577-021-00547-6
10.1200/JCO.19.02104
10.1038/s41598-020-76055-9
10.1038/s41591-022-01969-y
10.1186/s12885-023-11753-x
10.1016/j.bbmt.2018.12.758
10.1038/nrclinonc.2017.148
10.1136/jitc-2020-001511
10.1182/blood.2022017414
10.1158/2159-8290.CD-17-0698
10.1158/2159-8290.CD-17-1319
10.1016/j.jtct.2022.03.006
10.1182/blood-2017-06-793141
10.1182/bloodadvances.2020003885
10.1182/bloodadvances.2021004575
10.1136/jitc-2022-005459
10.1158/2643-3230.BCD-23-0056
10.1038/s41582-018-0058-z
10.1182/bloodadvances.2021006144
10.1001/jamaoncol.2022.3738
10.1038/s41591-018-0036-4
10.1038/s41591-023-02404-6
10.1038/s41591-018-0041-7
10.1182/bloodadvances.2023010653
|
[
"Larue",
"Bouvier",
"Maillard",
"Cuffel",
"Allain",
"Ursu",
"Carpentier",
"Azoulay",
"Thieblemont",
"Di Blasi",
"Caillat-Zucman"
] |
[
"Laboratoire d'Immunologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Cité, Paris, France.",
"Laboratoire d'Immunologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Cité, Paris, France.",
"Médecine intensive et réanimation, Hôpital Saint-Louis, AP-HP, Université Paris Cité, Paris, France.",
"Laboratoire d'Immunologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Cité, Paris, France.\nINSERM UMR976, Institut de Recherche St-Louis, Université Paris Cité, Paris, France.",
"Laboratoire d'Immunologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Cité, Paris, France.\nINSERM UMR976, Institut de Recherche St-Louis, Université Paris Cité, Paris, France.",
"Service de Neurologie, Hôpital Saint-Louis, AP-HP, Université Paris Cité, Paris, France.",
"Service de Neurologie, Hôpital Saint-Louis, AP-HP, Université Paris Cité, Paris, France.",
"Médecine intensive et réanimation, Hôpital Saint-Louis, AP-HP, Université Paris Cité, Paris, France.",
"Service d'Hémato-Oncologie, Hôpital Saint-Louis, AP-HP, Université Paris Cité, Paris, France.",
"Service d'Hémato-Oncologie, Hôpital Saint-Louis, AP-HP, Université Paris Cité, Paris, France.",
"Laboratoire d'Immunologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Cité, Paris, France sophie.caillat-zucman@aphp.fr.\nINSERM UMR976, Institut de Recherche St-Louis, Université Paris Cité, Paris, France."
] |
[
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[] | 5.869861 | 4.434309 |
39316265
| 452 |
CAR T cells in solid tumors and metastasis: paving the way forward.
|
CAR T cell therapy, hailed as a breakthrough in cancer treatment due to its remarkable outcomes in hematological malignancies, encounters significant hurdles when applied to solid tumors. While notable responses to CAR T cells remain sporadic in these patients, challenges persist due to issues such as on-target off-tumor toxicity, difficulties in their trafficking and infiltration into the tumor, and the presence of a hostile and immunosuppressive microenvironment. This review aims to explore recent endeavors aimed at overcoming these obstacles in CAR T cell therapy for solid tumors. Specifically, we will delve into promising strategies for enhancing tumor specificity through antigen targeting, addressing tumor heterogeneity, overcoming physical barriers, and counteracting the immune-suppressive microenvironment.
|
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] | 2024-09-24 | 115 |
39316265
|
[
"CAR T cell therapy",
"CAR T cells",
"solid tumors",
"tumor specificity",
"tumor heterogeneity",
"tumor",
"physical barriers",
"hematological malignancies",
"significant hurdles",
"cancer treatment",
"recent endeavors",
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"target",
"issues",
"challenges",
"difficulties",
"the tumor",
"its remarkable outcomes",
"the immune-suppressive microenvironment",
"a hostile and immunosuppressive microenvironment",
"the presence",
"these patients",
"a breakthrough",
"these obstacles",
"their trafficking",
"This review",
"we"
] |
[
"Adoptive cell therapies",
"CAR T cells",
"Metastasis",
"Solid tumors"
] | 0 |
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|
[
"Sirini",
"De Rossi",
"Moresco",
"Casucci"
] |
[
"Innovative Immunotherapies Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy.\nVita-Salute San Raffaele University, Milan, Italy.",
"Innovative Immunotherapies Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy.\nVita-Salute San Raffaele University, Milan, Italy.",
"Innovative Immunotherapies Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy.\nVita-Salute San Raffaele University, Milan, Italy.",
"Innovative Immunotherapies Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy. casucci.monica@hsr.it."
] |
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[] | 9.713539 | 4.656773 |
39316087
| 453 |
Recent advancements in improving the efficacy and safety of chimeric antigen receptor (CAR)-T cell therapy for hepatocellular carcinoma.
|
The liver is one of the most frequent sites of primary malignancies in humans. Hepatocellular carcinoma (HCC) is one of the most prevalent solid tumors with poor prognosis. Current treatments showed limited efficacy in some patients, and, therefore, alternative strategies, such as immunotherapy, cancer vaccines, adoptive cell therapy (ACT), and recently chimeric antigen receptors (CAR)-T cells, are developed to offer better efficacy and safety profile in patients with HCC. Unlike other ACTs like tumor-infiltrating lymphocytes (TILs), CAR-T cells are equipped with engineered CAR receptors that effectively identify tumor antigens and eliminate cancer cells without major histocompatibility complex (MHC) restriction. This process induces intracellular signaling, leading to T lymphocyte recruitment and subsequent activation of other effector cells in the tumor microenvironment (TME). Until today, novel approaches have been used to develop more potent CAR-T cells with robust persistence, specificity, trafficking, and safety. However, the clinical application of CAR-T cells in solid tumors is still challenging. Therefore, this study aims to review the advancement, prospects, and possible avenues of CAR-T cell application in HCC following an outline of the CAR structure and function.
|
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] | 2024-09-24 | 133 |
39316087
|
[
"cancer cells",
"other effector cells",
"CAR)-T cells",
"adoptive cell therapy",
"solid tumors",
"tumor antigens",
"T lymphocyte recruitment",
"engineered CAR receptors",
"CAR-T cell application",
"CAR",
"CAR-T cells",
"antigen receptors",
"limited efficacy",
"better efficacy",
"cancer vaccines",
"primary malignancies",
"more potent CAR-T cells",
"safety profile",
"HCC",
"possible avenues",
"intracellular signaling",
"other ACTs",
"alternative strategies",
"robust persistence",
"subsequent activation",
"tumor-infiltrating lymphocytes",
"patients",
"novel approaches",
"safety",
"Current treatments"
] |
[
"Adoptive cell therapy",
"CAR-T cell",
"Hepatocellular carcinoma",
"Immunotherapy"
] | 0 |
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|
[
"Ren",
"Huang"
] |
[
"Department of Interventional Radiology, The First Affiliated Hospital, Sun Yat-Sen University, No.58 Zhongsahn 2nd Road, Guangzhou, Guangdong, 510080, China.",
"Department of Interventional Radiology, The First Affiliated Hospital, Sun Yat-Sen University, No.58 Zhongsahn 2nd Road, Guangzhou, Guangdong, 510080, China. rent5@mail2.sysu.edu.cn."
] |
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[] | 10.987785 | 4.066543 |
39315411
| 454 |
CD8α Structural Domains Enhance GUCY2C CAR-T Cell Efficacy.
|
Despite success in treating some hematological malignancies, CAR-T cells have not yet produced similar outcomes in solid tumors due, in part, to the tumor microenvironment, poor persistence, and a paucity of suitable target antigens. Importantly, the impact of the CAR components on these challenges remains focused on the intracellular signaling and antigen-binding domains. In contrast, the flexible hinge and transmembrane domains have been commoditized and are the least studied components of the CAR. Here, we compared the hinge and transmembrane domains derived from either the CD8ɑ or CD28 molecule in identical GUCY2C-targeted third-generation designs for colorectal cancer. While these structural domains do not contribute to differences in antigen-independent contexts, such as CAR expression and differentiation and exhaustion phenotypes, the CD8ɑ structural domain CAR has a greater affinity for GUCY2C. This results in increased production of inflammatory cytokines and granzyme B, improved cytolytic effector function with low antigen-expressing tumor cells, and robust anti-tumor efficacy
|
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] | 2024-09-24 | 50 |
39315411
|
[
"CAR expression",
"solid tumors",
"suitable target antigens",
"CAR",
"improved cytolytic effector function",
"robust anti-tumor efficacy",
"low antigen-expressing tumor cells",
"inflammatory cytokines",
"granzyme B",
"the CD8ɑ structural domain CAR",
"CD28 molecule",
"poor persistence",
"similar outcomes",
"exhaustion phenotypes",
"increased production",
"CAR-T cells",
"colorectal cancer",
"these structural domains",
"third",
"the flexible hinge and transmembrane domains",
"identical GUCY2C-targeted third-generation designs",
"CD8ɑ",
"the CAR components",
"differentiation",
"differences",
"the hinge and transmembrane domains",
"the intracellular signaling and antigen-binding domains",
"part",
"the tumor microenvironment",
"antigen-independent contexts"
] |
[
"CAR-T cell therapy",
"Chimeric antigen receptor",
"GUCY2C",
"colorectal cancer"
] | 0 |
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|
[
"Baybutt",
"Entezari",
"Caspi",
"Staudt",
"Carlson",
"Waldman",
"Snook"
] |
[
"Department of Pharmacology, Physiology, and Cancer Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.",
"Department of Pharmacology, Physiology, and Cancer Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.",
"Department of Pharmacology, Physiology, and Cancer Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.",
"Department of Pharmacology, Physiology, and Cancer Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.",
"Department of Pharmacology, Physiology, and Cancer Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.",
"Department of Pharmacology, Physiology, and Cancer Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.\nSidney Kimmel Comprehensive Cancer Center, Jefferson Health, Philadelphia, PA, USA.",
"Department of Pharmacology, Physiology, and Cancer Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.\nSidney Kimmel Comprehensive Cancer Center, Jefferson Health, Philadelphia, PA, USA.\nDepartment of Microbiology & Immunology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA."
] |
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[] | 8.616257 | 5.273539 |
39314323
| 455 |
NRF2 translation block by inhibition of cap-dependent initiation sensitizes lymphoma cells to ferroptosis and CAR-T immunotherapy.
|
Cancers coopt stress-response pathways to drive oncogenesis, dodge immune surveillance, and resist cytotoxic therapies. Several of these provide protection from ferroptosis, iron-mediated oxidative cell death. Here, we found dramatic sensitization to ferroptosis upon disruption of cap-dependent translation in diffuse large B-cell lymphoma (DLBCL). Specifically, rocaglate inhibitors of the eIF4A1 RNA helicase synergized with pharmacologic ferroptosis inducers, driven by a collapse of glutathione production that protects polyunsaturated fatty acids from ferroptotic oxidation. These effects occur despite initial up-regulation of specific protective factors. We find lost translation of NRF2, oncogenic master regulator of antioxidant gene-expression, is a key consequence of eIF4A1 inhibition. In vivo, combination of the clinical rocaglate zotatifin with a pharmacologically optimized ferroptosis inducer eradicated DLBCL patient derived xenografts. Moreover, we found zotatifin pre-exposure sensitized DLBCL to CD19-directed chimeric antigen receptor (CAR-19) T cells. Translational disruption therefore provides new opportunities to leverage therapeutic impacts of ferroptosis inducers including cytotoxic immunotherapies.
|
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] | 2024-09-24 | 1 |
39314323
|
[
"ferroptosis inducers",
"pharmacologic ferroptosis inducers",
"ferroptosis",
"oncogenic master regulator",
"dodge immune surveillance",
"lost translation",
"DLBCL patient derived xenografts",
"specific protective factors",
"Translational disruption",
"fatty acids",
"glutathione production",
"new opportunities",
"cytotoxic therapies",
"therapeutic impacts",
"cytotoxic immunotherapies",
"disruption",
"diffuse large B-cell lymphoma",
"dramatic sensitization",
"iron-mediated oxidative cell death",
"eIF4A1 inhibition",
"ferroptotic oxidation",
"RNA",
"oncogenesis",
"a pharmacologically optimized ferroptosis inducer",
"NRF2",
"initial up-regulation",
"cap-dependent translation",
"CD19-directed chimeric antigen receptor (CAR-19) T cells",
"antioxidant gene-expression",
"protection"
] |
[] | 0 |
10.1101/2024.09.09.612133
|
[
"Manara",
"Newsam",
"Saralamma",
"Russo",
"Martinez",
"Fattakhov",
"Cunningham",
"Alaoui",
"Chahar",
"Carbone",
"Lightfuss",
"Barroso",
"Hoffman",
"Maura",
"Bilbao",
"Schatz"
] |
[
null,
null,
null,
null,
null,
null,
null,
null,
null,
null,
null,
null,
null,
null,
null,
null
] |
[
"39314323"
] |
[] | 7.856158 | 5.999997 |
39314273
| 456 |
Microbial metabolite-guided CAR T cell engineering enhances anti-tumor immunity via epigenetic-metabolic crosstalk.
|
Emerging data have highlighted a correlation between microbiome composition and cancer immunotherapy outcome. While commensal bacteria and their metabolites are known to modulate the host environment, contradictory effects and a lack of mechanistic understanding impede the translation of microbiome-based therapies into the clinic. In this study, we demonstrate that abundance of the commensal metabolite pentanoate is predictive for survival of chimeric antigen receptor (CAR) T cell patients in two independent cohorts. Its implementation in the CAR T cell manufacturing workflow overcomes solid tumor microenvironments in immunocompetent cancer models by hijacking the epigenetic-metabolic crosstalk, reducing exhaustion and promoting naive-like differentiation. While synergy of clinically relevant drugs mimicked the phenotype of pentanoate-engineered CAR T cells
|
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] | 2024-09-24 | 47 |
39314273
|
[
"T cell patients",
"immunocompetent cancer models",
"cancer immunotherapy outcome",
"solid tumor microenvironments",
"chimeric antigen receptor",
"microbiome composition",
"commensal bacteria",
"mechanistic understanding",
"pentanoate-engineered CAR T cells",
"contradictory effects",
"the CAR T cell",
"CAR",
"Emerging data",
"exhaustion",
"the commensal metabolite pentanoate",
"survival",
"workflow",
"abundance",
"microbiome-based therapies",
"naive-like differentiation",
"synergy",
"the host environment",
"the epigenetic-metabolic crosstalk",
"clinically relevant drugs",
"their metabolites",
"two independent cohorts",
"a correlation",
"the translation",
"the phenotype",
"a lack"
] |
[] | 0 |
10.1101/2024.08.19.608538
10.1038/s41591-022-01726-1
10.1182/blood.2018885863
10.3389/fimmu.2017.01036
10.1126/science.1241165
10.1126/science.aad1329
10.1126/science.aac4255
10.1126/science.aan3706
10.1038/s41586-019-0878-z
10.1038/s41591-023-02234-6
10.1038/s41591-022-01702-9
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10.1038/nature12726
10.1073/pnas.1322269111
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10.1126/science.1241165
10.1038/s41591-022-01959-0
10.1126/scitranslmed.3000677
10.1016/j.immuni.2016.01.021
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10.1038/s41591-023-02453-x
10.1182/blood-2022-157423
10.1159/000538303
10.1038/nm.3444
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10.1126/scitranslmed.abh0272
10.1136/jitc-2022-006522
10.1016/j.ymthe.2024.05.006
10.1182/bloodadvances.2022008272
10.1038/s41586-024-07242-1
10.1016/j.cmet.2022.03.013
10.1038/s41586-023-06546-y
10.1016/j.ccell.2015.09.004
10.1126/science.1164097
10.1016/j.tim.2021.04.007
10.1038/s43018-023-00669-x
10.1172/jci.insight.133393
10.1038/s41586-024-07487-w
10.1093/nar/gkae300
10.1093/nar/gkr366
10.1021/acs.jcim.6b00174
10.1002/pro.4792
10.3389/fmolb.2021.729513
10.1093/bioinformatics/bty816
10.1021/ac802689c
|
[
"Staudt",
"Nikolka",
"Perl",
"Franz",
"Leblay",
"Yuan",
"Warmuth",
"Fantes",
"Skorupskaitė",
"Fei",
"Bromberg",
"Martin-Uriz",
"Rodriguez-Madoz",
"Ziegler-Martin",
"Gholam",
"Benz",
"Tran",
"Freitag",
"Riester",
"Stein-Thoeringer",
"Schmitt",
"Kleigrewe",
"Weber",
"Mangold",
"Einsele",
"Prosper",
"Ellmeier",
"Busch",
"Visekruna",
"Slingerland",
"Shouval",
"Hiller",
"van den Brink",
"Pausch",
"Neri",
"Hudecek",
"Poeck",
"Luu"
] |
[
"Lehrstuhl für Zelluläre Immuntherapie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.",
"Department of Bioinformatics and Biochemistry, Braunschweig Integrated Centre of Systems Biology (BRICS), Technische Universität Braunschweig, Braunschweig, Germany.",
"University Hospital Regensburg, Department of Internal Medicine III, Hematology & Internal Oncology, Regensburg, Germany.",
"Lehrstuhl für Zelluläre Immuntherapie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.",
"Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, Alberta, Canada.",
"Precision Oncology Hub, Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, Alberta, Canada.",
"Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany.",
"University Hospital Regensburg, Department of Internal Medicine III, Hematology & Internal Oncology, Regensburg, Germany.",
"Life Sciences Center - European Molecular Biology Laboratory (LSC-EMBL) Partnership for Genome Editing Technologies, Vilnius University - Life Sciences Center, Vilnius University, Vilnius, Lithuania.",
"Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.",
"Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.",
"Hemato-Oncology Program, Cima Universidad de Navarra, Centro de Investigacion Biomedica en Red de Cancer (CIBERONC), Cancer Center Clinica Universidad de Navarra (CCUN), IdiSNA, Pamplona, Spain.",
"Hemato-Oncology Program, Cima Universidad de Navarra, Centro de Investigacion Biomedica en Red de Cancer (CIBERONC), Cancer Center Clinica Universidad de Navarra (CCUN), IdiSNA, Pamplona, Spain.",
"Lehrstuhl für Zelluläre Immuntherapie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.",
"Lehrstuhl für Zelluläre Immuntherapie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.",
"Lehrstuhl für Zelluläre Immuntherapie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.",
"Medical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Vienna, Austria.",
"Lehrstuhl für Zelluläre Immuntherapie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.",
"Lehrstuhl für Zelluläre Immuntherapie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.\nMildred Scheel Early Career Center, University Hospital of Würzburg, Würzburg, Germany.",
"Innere Medizin I, Universitätsklinikum Tübingen & M3 Research Center, Universitätsklinikum Tübingen.",
"Department of Hematology, Oncology and Rheumatology, University Clinic Heidelberg, Heidelberg, Germany.",
"Bavarian Center for Biomolecular Mass Spectrometry (BayBioMS), Technical University of Munich, Freising, Germany.",
"Lehrstuhl für Zelluläre Immuntherapie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.",
"Lehrstuhl für Zelluläre Immuntherapie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.\nInstitute for Medical Microbiology and Hygiene, Philipps-University Marburg, Marburg, Germany.",
"Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.",
"Hematology and Cell Therapy Department, Clinica Universidad de Navarra (CUN), Hemato-Oncology Program, Cima Universidad de Navarra. Centro de Investigacion Biomedica en Red de Cancer (CIBERONC), Cancer Center Clinica Universidad de Navarra (CCUN), IdiSNA, Pamplona, Spain.",
"Medical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Vienna, Austria.",
"Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany.",
"Institute for Medical Microbiology and Hygiene, Philipps-University Marburg, Marburg, Germany.",
"City of Hope Comprehensive Cancer Center, Duarte, CA.",
"Adult Bone Marrow Transplantation Service and Cellular Therapy Service, Memorial Sloan Kettering Cancer Center, New York, New York.\nWeill Cornell Medical College, New York, New York.",
"Department of Bioinformatics and Biochemistry, Braunschweig Integrated Centre of Systems Biology (BRICS), Technische Universität Braunschweig, Braunschweig, Germany.",
"City of Hope Comprehensive Cancer Center, Duarte, CA.",
"Life Sciences Center - European Molecular Biology Laboratory (LSC-EMBL) Partnership for Genome Editing Technologies, Vilnius University - Life Sciences Center, Vilnius University, Vilnius, Lithuania.",
"Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, Alberta, Canada.",
"Lehrstuhl für Zelluläre Immuntherapie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.\nBavarian Cancer Research Center (BZKF), Regensburg & Würzburg, Germany.",
"University Hospital Regensburg, Department of Internal Medicine III, Hematology & Internal Oncology, Regensburg, Germany.\nBavarian Cancer Research Center (BZKF), Regensburg & Würzburg, Germany.\nLeibniz Institute for Immunotherapy (LIT), Regensburg, Germany.",
"Lehrstuhl für Zelluläre Immuntherapie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.\nLeibniz Institute for Immunotherapy (LIT), Regensburg, Germany."
] |
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] |
[] | 10.178726 | 5.000697 |
39314237
| 457 |
Validation of a PD-1/CD28 chimeric switch receptor to augment CAR-T function in dogs with spontaneous B cell lymphoma.
|
Chimeric antigen receptor (CAR) T cell therapy has achieved unprecedented clinical outcomes in patients with relapsed/refractory B cell leukemias; however, response rates in patients with large B cell lymphoma (LBCL) are less impressive. Expression of PD-1 on activated T cells and PD-L1 on malignant, stromal, and immune cells within the tumor microenvironment (TME) contribute to CAR-T exhaustion, hypofunction, and treatment failures. Here, a comparative approach is taken to develop a chimeric switch receptor (CSR) with potential to augment CAR-T persistence, function, and clinical efficacy in immune competent, pet dogs with spontaneous B cell lymphoma (BCL). We show that similar to human CAR-T cells, expression of a PD-1/CD28 CSR in canine CAR-T cells results in enhanced function against PD-L1
|
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] | 2024-09-24 | 59 |
39314237
|
[
"spontaneous B cell lymphoma",
"large B cell lymphoma",
"canine CAR-T cells",
"human CAR-T cells",
"Chimeric antigen receptor",
"unprecedented clinical outcomes",
"relapsed/refractory B cell leukemias",
"clinical efficacy",
"activated T cells",
"enhanced function",
"patients",
"CAR) T cell therapy",
"CSR",
"pet dogs",
"response rates",
"function",
"CAR-T exhaustion",
"CAR-T persistence",
"treatment failures",
"a chimeric switch receptor",
"Expression",
"potential",
"malignant, stromal, and immune cells",
"TME",
"hypofunction",
"PD-1",
"LBCL",
"PD-L1",
"BCL",
"a PD-1/CD28 CSR"
] |
[
"Cancer",
"Therapeutics",
"Veterinary medicine"
] | 0 |
10.1016/j.isci.2024.110863
10.1056/NEJMoa1709866
10.1056/NEJMoa2024850
10.1056/NEJMoa1707447
10.1016/S0140-6736(21)01222-8
10.1080/10428194.2023.2258244
10.1126/science.aaa6204
10.1146/annurev-med-062315-120245
10.1038/s41591-020-1061-7
10.1158/2159-8290.CD-21-1586
10.1158/1078-0432.CCR-13-2627
10.1016/j.ccell.2022.12.005
10.1038/nri.2017.108
10.1084/jem.192.7.1027
10.1126/science.aaf1292
10.1158/1078-0432.CCR-13-0458
10.1016/j.omto.2016.11.005
10.1158/2159-8290.CD-21-0407
10.1182/blood.2021012634
10.1182/blood-2016-09-738245
10.1158/1078-0432.CCR-17-0867
10.1038/nbt.4195
10.1186/s40425-019-0806-7
10.1080/2162402X.2021.1901434
10.1186/s13045-021-01044-y
10.1158/0008-5472.CAN-15-2524
10.1080/19420862.2021.2004638
10.1097/CJI.0000000000000052
10.1111/vco.12602
10.1158/1535-7163.MCT-21-0726
10.1016/j.xpro.2021.100905
10.1080/2162402X.2019.1676615
10.1038/s41571-019-0184-6
10.3389/fvets.2022.824982
10.1080/19420862.2023.2287250
10.1371/journal.pone.0235518
10.1038/s41591-018-0010-1
10.4049/jimmunol.1003870
10.1172/JCI83092
10.3892/or.2019.7263
10.1016/j.leukres.2010.01.021
10.1126/science.aao3290
10.1038/s41591-022-01698-2
10.1126/science.aan3706
10.1007/s10577-007-1212-4
10.1158/0008-5472.CAN-12-3546
10.1038/mt.2016.146
10.1182/blood-2015-02-629600
10.1056/NEJMoa1804980
10.1056/NEJMoa1708566
10.3390/vetsci8070120
10.1093/jnci/djv146
10.1158/1078-0432.CCR-20-1457
10.1038/s41392-020-00277-6
10.4049/jimmunol.179.10.6494
10.1016/j.ymthe.2018.09.009
10.1016/j.dci.2018.05.022
10.3389/fimmu.2023.1162700
10.1158/0008-5472.CAN-16-1922
|
[
"Yoshimoto",
"Kudo",
"Rotolo",
"Foos",
"Olenick",
"Takagi",
"Mason"
] |
[
"Laboratory of Small Animal Surgery, Department of Veterinary Medicine, School of Veterinary Medicine, Azabu University, Sagamihara, Kanagawa, Japan.",
"Laboratory of Small Animal Surgery, Department of Veterinary Medicine, School of Veterinary Medicine, Azabu University, Sagamihara, Kanagawa, Japan.",
"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.\nCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.",
"Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.\nCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.",
"Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.",
"Laboratory of Small Animal Surgery, Department of Veterinary Medicine, School of Veterinary Medicine, Azabu University, Sagamihara, Kanagawa, Japan.",
"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.\nCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA."
] |
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] |
[] | 7.213763 | 5.905509 |
39313679
| 458 |
Biomimetic cell stimulation with a graphene oxide antigen-presenting platform for developing T cell-based therapies.
|
Chimeric antigen receptor (CAR)-engineered T cells represent a front-line therapy for cancers. However, the current CAR T cell manufacturing protocols do not adequately reproduce immunological synapse formation. Here, in response to this limitation, we have developed a flexible graphene oxide antigen-presenting platform (GO-APP) that anchors antibodies onto graphene oxide. By decorating anti-CD3 (αCD3) and anti-CD28 (αCD28) on graphene oxide (GO-APP
|
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39313679
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|
[
"Zhu",
"Yu",
"Li",
"Ma",
"Wang",
"Liu",
"Li",
"Kim",
"Zhu",
"Hahn",
"Zhou",
"Brown",
"Zhang",
"Pelegrini",
"Hsiai",
"Yang",
"Huang"
] |
[
"Department of Materials Science and Engineering, University of California, Los Angeles, Los Angeles, CA, USA.\nDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.\nDepartment of Bioengineering, University of California, Los Angeles, Los Angeles, CA, USA.\nDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.",
"Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.",
"Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.",
"Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.",
"Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.",
"Department of Materials Science and Engineering, University of California, Los Angeles, Los Angeles, CA, USA.",
"Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.",
"Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.",
"Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.",
"Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.",
"Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.",
"Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.",
"Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.",
"Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.",
"Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, USA.\nDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.",
"Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA. liliyang@ucla.edu.\nEli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA. liliyang@ucla.edu.\nJonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. liliyang@ucla.edu.\nMolecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA. liliyang@ucla.edu.",
"Department of Materials Science and Engineering, University of California, Los Angeles, Los Angeles, CA, USA. yhuang@seas.ucla.edu.\nJonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. yhuang@seas.ucla.edu.\nCalifornia Nanosystems Institute, University of California, Los Angeles, Los Angeles, CA, USA. yhuang@seas.ucla.edu."
] |
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[] | 8.63632 | 4.228988 |
39313307
| 459 |
BCMA-BBZ-OX40 CAR-T Therapy Using an Instant Manufacturing Platform in Multiple Myeloma.
|
Chimeric antigen receptor (CAR)-T cell has revolutionary efficacy against relapsed/refractory multiple myeloma (R/R MM). However, current CAR-T cell therapy has several limitations including long vein-to-vein time and limited viability.
A 4-1BB-costimulated B-cell maturation antigen (BCMA) CAR-T integrating an independently-expressed OX40 (BCMA-BBZ-OX40) was designed and generated by a traditional manufacturing process (TraditionCART) or instant manufacturing platform (named InstanCART). The tumor-killing efficiency, differentiation, exhaustion, and expansion level were investigated in vitro and in tumor-bearing mice. An investigator-initiated clinical trial was performed in patients with R/R MM to evaluate the outcomes of both TraditionCART and InstanCART. The primary objective was safety within 1 month after CAR-T cell infusion. The secondary objective was the best overall response rate.
Preclinical studies revealed that integrated OX40 conferred BCMA CAR-T cells with superior cytotoxicity and reduced exhaustion levels. InstanCART process further enhanced the proliferation and T-cell stemness of BCMA-BBZ-OX40 CAR-T cells. BCMA-BBZ-OX40 CAR-T cells were successfully administered in 22 patients with R/R MM, including 15 patients with TraditionCART and 7 patients with InstanCART. Up to 50% (11/22) patients had a high-risk cytogenetic profile and 36% (8/22) had extramedullary disease. CAR-T therapy caused grade 1-2 cytokine release syndrome in 19/22 (80%) patients, grade 1 neurotoxicity in 2/22 (9%) patients and led to ≥grade 3 adverse events including neutropenia (20/22, 91%), thrombocytopenia (15/22, 68%), anemia (12/22, 55%), creatinine increased (1/22, 5%), hepatic enzymes increased (5/22, 23%), and sepsis (1/22, 5%). The best overall response rate was 100%, and 64% (14/22) of the patients had a complete response or better. The median manufacturing time was shorter for InstanCART therapy (3 days) than for TraditionCART therapy (10 days). Expansion and duration were dramatically higher for InstanCART cells than for TraditionCART cells.
BCMA-BBZ-OX40 CAR-T cells were well tolerated and exhibited potent responses in patients with R/R MM. InstanCART shortened the manufacturing period compared to TraditionCART, and improved the cellular kinetics. Our results demonstrated the potency and feasibility of OX40-modified BCMA CAR-T cells using InstanCART technology for R/R MM therapy.
This trial was registered at www.
gov as #NCT04537442.
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] | 2024-09-24 | 36 |
39313307
|
[
"CAR)-T cell",
"TraditionCART cells",
"CAR-T cell infusion",
"current CAR-T cell therapy",
"patients",
"R/R MM therapy",
"OX40",
"OX40-modified BCMA CAR-T cells",
"R/R MM",
"instant manufacturing platform",
"T-cell stemness",
"BCMA",
"TraditionCART therapy",
"reduced exhaustion levels",
"potent responses",
"expansion level",
"BCMA-BBZ-OX40 CAR-T cells",
"CAR-T therapy",
"Chimeric antigen receptor",
"(R/R MM",
"revolutionary efficacy",
". InstanCART",
"exhaustion",
"several limitations",
"superior cytotoxicity",
"The best overall response rate",
"the best overall response rate",
"InstanCART cells",
"Expansion",
"hepatic enzymes"
] |
[
"Chimeric Antigen Receptor - CAR",
"Hematologic Malignancies",
"Immunotherapy",
"Multiple Myeloma",
"T cell"
] | 0 |
10.1136/jitc-2024-009476
10.1038/s41571-020-0427-6
10.1038/nri3405
10.1016/j.immuni.2016.04.017
10.1016/s1074-7613(01)00191-1
10.1084/jem.20021937
10.1073/pnas.0600205103
10.1016/j.immuni.2005.03.012
10.1128/MCB.18.1.558
10.1074/jbc.273.10.5808
10.4049/jimmunol.1003156
10.3389/fimmu.2013.00139
10.3390/biom12091303
10.1186/s13045-022-01244-0
10.1126/scitranslmed.aba7308
10.1002/ajh.26586
10.1158/2326-6066.CIR-17-0405
10.1016/S1470-2045(16)30206-6
10.1016/j.bbmt.2018.12.758
10.1038/s41408-022-00643-3
10.1016/j.cell.2021.11.016
10.1038/nature22395
10.1016/j.omtm.2016.12.006
10.3322/caac.21771
10.1016/S0140-6736(21)00933-8
10.3390/cancers13112639
10.1158/2159-8290.CD-22-1276
10.1038/s41408-022-00694-6
10.1038/s41408-022-00688-4
10.1056/NEJMoa2024850
10.1002/ajh.27023
10.1002/hon.2958
10.1016/j.tranon.2022.101465
10.1038/s41571-023-00754-1
10.1016/j.blre.2018.11.002
10.1136/jitc-2022-005957
|
[
"Wang",
"Yang",
"Ma",
"Feng",
"Li",
"Zhang",
"Bai",
"Ding",
"Liu",
"Wu",
"Lu",
"Feng",
"Li",
"He",
"Li",
"Liu"
] |
[
"Department of Hematology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing (100730), China.\nChinese Academy of Medical Sciences & Peking Union Medical College, Beijing (100730), China.",
"Department of Hematology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing (100730), China.",
"Department of Pulmonary and Critical Care Medicine, The Sixth Medical Center of PLA General Hospital, Beijing, China.\nBeijing Imunopharm Technology Co., Ltd, Beijing, China.",
"Department of Hematology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing (100730), China.",
"Department of Hematology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing (100730), China.",
"Department of Hematology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing (100730), China.",
"Department of Hematology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing (100730), China.",
"Beijing Imunopharm Technology Co., Ltd, Beijing, China.",
"Beijing Imunopharm Technology Co., Ltd, Beijing, China.",
"Beijing Imunopharm Technology Co., Ltd, Beijing, China.",
"Beijing Imunopharm Technology Co., Ltd, Beijing, China.",
"Beijing Imunopharm Technology Co., Ltd, Beijing, China.",
"Department of Hematology, China-Japan Friendship Hospital, Beijing, China.",
"Beijing Imunopharm Technology Co., Ltd, Beijing, China liuhui8140@126.com lijian@pumch.cn heting@imunopharm.com.",
"Department of Hematology, Peking Union Medical College Hospital, Beijing, China liuhui8140@126.com lijian@pumch.cn heting@imunopharm.com.\nChinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.",
"Department of Hematology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing (100730), China liuhui8140@126.com lijian@pumch.cn heting@imunopharm.com."
] |
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[] | 5.086227 | 5.829724 |
39312667
| 460 |
Engineered CD4 T cells for in vivo delivery of therapeutic proteins.
|
The CD4 T cell, when engineered with a chimeric antigen receptor (CAR) containing specific intracellular domains, has been transformed into a zero-order drug-delivery platform. This introduces the capability of prolonged, disease-specific engineered protein biologics production, at the disease site. Experimental findings demonstrate that CD4 T cells offer a solution when modified with a CAR that includes 4-1BB but excludes CD28 intracellular domain. In this configuration, they achieve ~3X transduction efficiency of CD8 T cells, ~2X expansion rates, generating ~5X more biologic, and exhibit minimal cytolytic activity. Cumulatively, this addresses two main hurdles in the translation of cell-based drug delivery: scaling the production of engineered T cell ex vivo and generating sufficient biologics in vivo. When programmed to induce IFNβ upon engaging the target antigen, the CD4 T cells outperforms CD8 T cells, effectively suppressing cancer cell growth in vitro and in vivo. In summary, this platform enables precise targeting of disease sites with engineered protein-based therapeutics while minimizing healthy tissue exposure. Leveraging CD4 T cells' persistence could enhance disease management by reducing drug administration frequency, addressing critical challenges in cell-based therapy.
|
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] | 2024-09-23 | 81 |
39312667
|
[
"CD4 T cells",
"CD8 T cells",
"engineered T cell ex vivo",
"cancer cell growth",
"disease sites",
"specific intracellular domains",
"disease management",
"CD4 T cells persistence",
"drug administration frequency",
"cell-based drug delivery",
"The CD4 T cell",
"CD28 intracellular domain",
"the CD4 T cells",
"~3X transduction efficiency",
"cell-based therapy",
"~2X expansion rates",
"minimal cytolytic activity",
"engineered protein-based therapeutics",
"prolonged, disease-specific engineered protein biologics production",
"healthy tissue exposure",
"sufficient biologics",
"precise targeting",
"CAR",
"critical challenges",
"vivo",
"Experimental findings",
"~5X",
"the disease site",
"IFNβ",
"a chimeric antigen receptor"
] |
[
"CD4 CAR T cells",
"Cell-based drug delivery",
"T cell engineering",
"T cell manufacturing",
"nuclear factor of the activated T cell response element"
] | 0 |
10.1073/pnas.2318687121
10.1002/btm2.10605
10.1101/2022.06.26.497669
10.1038/s41587-022-01245-x
10.3390/ijms21218412
|
[
"Radhakrishnan",
"Newmyer",
"Javitz",
"Bhatnagar"
] |
[
"Biosciences Division, SRI International, Menlo Park, CA 94025.",
"Biosciences Division, SRI International, Menlo Park, CA 94025.",
"Education Division, SRI International, Menlo Park, CA 94025.",
"Biosciences Division, SRI International, Menlo Park, CA 94025."
] |
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[] | 8.850332 | 3.975867 |
39312080
| 461 |
Beyond Conventional Treatments: Exploring CAR-T Cell Therapy for Cancer Stem Cell Eradication.
|
For decades cancer remained the center of attention in the scientific community as its survival rates are low. Researchers from all around the world wanted to know the core of the problem as to what initiates cancer in a patient and helps with its progression. Many postulations came to light, but Cancer Stem Cells (CSC) was the most appealing and convincing.
In this review, we shed light on a potential solution to the problem by reviewing CAR-T cells (Chimeric antigen receptor T cells). These specialized T cells are designed to detect specific antigens on cancer cells. We analyse the steps of their formation from the collection of T cells from the patient's bloodstream and modifying it to exhibit specific CAR structures on their surfaces, to reinjecting them back and evaluating their efficacy. We thoroughly investigate the structure of the CAR design with improvements across different generations. The focus extends to the unique properties of CSCs as in how targeting specific markers on them can enhance the precision of cancer therapy.
Despite the successes, the review discusses the existing limitations and toxicities associated with CAR-derived therapies, highlighting the ongoing need for research and refinement. Looking ahead, we explore proposed strategies aimed at optimizing CAR-T cell therapy to mitigate adverse effects for improved cancer treatments.
|
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] | 2024-09-23 | 74 |
39312080
|
[
"cancer cells",
"T cells",
"Chimeric antigen receptor T cells",
"specific CAR structures",
"cancer therapy",
"improved cancer treatments",
"specific antigens",
"cancer",
"specific markers",
"CAR-T cell therapy",
"Cancer Stem Cells",
"CAR-T cells",
"light",
"proposed strategies",
"CAR",
"adverse effects",
"CAR-derived therapies",
"Many postulations",
"different generations",
"These specialized T cells",
"attention",
"CSCs",
"CSC",
"toxicities",
"improvements",
"research",
"the CAR design",
"Researchers",
"refinement",
"decades"
] |
[
"CSC antigens",
"Cancer stem cells",
"Chimeric antigen receptor T cells",
"Immunotherapy"
] | 0 |
10.1007/s12015-024-10786-4
|
[
"Rabie",
"Mohran",
"Gaber",
"Ali",
"Abd El Naby",
"Ghoniem",
"Abd Elmaksod",
"Abdallah"
] |
[
"Faculty of Pharmacy, Fayoum University, Fayoum, Egypt.",
"Zoology Department, Faculty of Science, Alexandria University, Alexandria, Egypt. sci.ahmedatef77896@alexu.edu.eg.",
"Molecular Biology and Chemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt.",
"Chemistry Department, Faculty of Science, KFS University, Kafr El-Sheikh, Egypt.",
"Zoology-Chemistry Department, Faculty of Science, Beni Suef University, Beni Suef, Egypt.",
"Biotechnology and Chemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt.",
"Zoology-Chemistry Department, Faculty of Science, Mansoura University, Mansoura, Egypt.",
"Hormones Department, Medical Research and Clinical Studies Institute, National research Centre, Cairo, Egypt."
] |
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[] | 9.602975 | 3.807336 |
39310556
| 462 |
On Route to Chimeric Antigen Receptor T-cell (CAR T) Therapy, Less Is More: Adaptive Bridging Radiotherapy in Large B-cell Lymphoma.
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CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has appreciably advanced treatment for relapsed or refractory large B-cell lymphoma (LBCL). During the critical interim of four to six weeks, until CAR T-cells are ready, radiation therapy (RT) can be used to control the disease. We present the case of a 64-year-old female with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who received adaptive RT for bilateral adrenal masses as a bridging strategy before undergoing CAR T-cell therapy and enrolled in an adaptive RT clinical trial. A plan was developed to deliver up to five once-weekly fractions (5 Gy per fraction) of CT-based online adaptive RT (Varian Ethos with HyperSight imaging, Varian Medical Systems, Palo Alto, CA). The patient experienced rapid symptomatic relief, with no RT-related toxicities. The patient received RT at only half of the sessions (two out of four sessions) due to excellent tumor shrinkage on cone-beam CT (CBCT). As such, the patient was treated at a lower total dose (10 Gy) than she otherwise would have received with standard RT. Post-RT PET/CT showed significant disease regression, compatible with partial response, prior to CAR T-cell infusion. This case shows the successful application of adaptive RT as bridging therapy prior to CAR T-cell therapy, and we expect the results of this adaptive RT trial to guide the future of adaptive RT in relapsed/refractory B-cell lymphomas.
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] | 2024-09-23 | 8 |
39310556
|
[
"adaptive RT",
"RT",
"standard RT",
"CT-based online adaptive RT",
"CAR T-cell therapy",
"an adaptive RT clinical trial",
"this adaptive RT trial",
"Post-RT PET/CT",
"CAR T-cell infusion",
"Varian Medical Systems",
"CAR T-cells",
"RT (Varian Ethos",
"significant disease regression",
"large B-cell lymphoma",
"CT",
"rapid symptomatic relief",
"excellent tumor shrinkage",
"therapy",
"relapsed/refractory diffuse large B-cell lymphoma",
"RT for bilateral",
"bilateral adrenal masses",
"CAR) T-cell therapy",
"Palo Alto",
"HyperSight imaging",
"relapsed/refractory B-cell lymphomas",
"fraction",
"partial response",
"no RT-related toxicities",
"CD19-targeted chimeric antigen receptor",
"weekly"
] |
[
"adaptive radiation therapy",
"bridging therapy",
"car t-cell therapy",
"ethos",
"large b-cell lymphoma"
] | 0 |
10.7759/cureus.67572
|
[
"Ababneh",
"Bobić",
"Pursley",
"Patel"
] |
[
"Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, USA.",
"Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, USA.",
"Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, USA.",
"Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, USA."
] |
[
"39310556",
"36821768",
"35952976",
"38860643",
"33350894",
"33470210",
"31027635",
"37660057"
] |
[] | 6.351922 | 5.543318 |
39310093
| 463 |
Empowering brain tumor management: chimeric antigen receptor macrophage therapy.
|
Brain tumors pose formidable challenges in oncology due to the intricate biology and the scarcity of effective treatment modalities. The emergence of immunotherapy has opened new avenues for innovative therapeutic strategies. Chimeric antigen receptor, originally investigated in T cell-based therapy, has now expanded to encompass macrophages, presenting a compelling avenue for augmenting anti-tumor immune surveillance. This emerging frontier holds promise for advancing the repertoire of therapeutic options against brain tumors, offering potential breakthroughs in combating the formidable malignancies of the central nervous system. Tumor-associated macrophages constitute a substantial portion, ranging from 30% to 50%, of the tumor tissue and exhibit tumor-promoting phenotypes within the immune-compromised microenvironment. Constructing CAR-macrophages can effectively repolarize M2-type macrophages towards an M1-type phenotype, thereby eliciting potent anti-tumor effects. CAR-macrophages can recruit T cells to the brain tumor site, thereby orchestrating a remodeling of the immune niche to effectively inhibit tumor growth. In this review, we explore the potential limitations as well as strategies for optimizing CAR-M therapy, offering insights into the future direction of this innovative therapeutic approach.
|
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] | 2024-09-23 | 170 |
39310093
|
[
"Brain tumors",
"brain tumors",
"tumor growth",
"innovative therapeutic strategies",
"anti-tumor immune surveillance",
"potent anti-tumor effects",
"macrophages",
"therapeutic options",
"formidable challenges",
"new avenues",
"T cells",
"potential breakthroughs",
"Tumor-associated macrophages",
"effective treatment modalities",
"the brain tumor site",
"tumor-promoting phenotypes",
"Chimeric antigen receptor",
"T cell-based therapy",
"M2-type macrophages",
"strategies",
"the tumor tissue",
"promise",
"this innovative therapeutic approach",
"CAR-macrophages",
"oncology",
"CAR-M therapy",
"insights",
"M2",
"M1",
"immunotherapy"
] |
[
"Brain tumor",
"Chimeric antigen receptor",
"Immunotherapy",
"Macrophage"
] | 0 |
10.7150/thno.98290
|
[
"Feng",
"Shen",
"Qi",
"Zhang",
"Ni"
] |
[
"Department of Neurosurgery, Qilu Hospital and Institute of Brain and Brain-Inspired Science, Cheeloo College of Medicine, Shandong University, 107 Wenhua Xi Road, Jinan, 250012, Shandong, China.",
"Department of Neurosurgery, Qilu Hospital and Institute of Brain and Brain-Inspired Science, Cheeloo College of Medicine, Shandong University, 107 Wenhua Xi Road, Jinan, 250012, Shandong, China.",
"Department of Neurosurgery, Qilu Hospital and Institute of Brain and Brain-Inspired Science, Cheeloo College of Medicine, Shandong University, 107 Wenhua Xi Road, Jinan, 250012, Shandong, China.",
"Department of Neurosurgery, Qilu Hospital and Institute of Brain and Brain-Inspired Science, Cheeloo College of Medicine, Shandong University, 107 Wenhua Xi Road, Jinan, 250012, Shandong, China.",
"Department of Neurosurgery, Qilu Hospital and Institute of Brain and Brain-Inspired Science, Cheeloo College of Medicine, Shandong University, 107 Wenhua Xi Road, Jinan, 250012, Shandong, China."
] |
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[] | 10.353474 | 5.431636 |
39308793
| 464 |
TYRP1 directed CAR T cells control tumor progression in preclinical melanoma models.
|
Despite therapeutic efficacy observed with immune checkpoint blockade in advanced melanoma, many tumors do not respond to treatment, representing a need for new therapies. Here, we have generated chimeric antigen receptor (CAR) T cells targeting TYRP1, a melanoma differentiation antigen expressed on the surface of melanomas, including rare acral and uveal melanomas. TYRP1-targeted CAR T cells demonstrate antigen-specific activation and cytotoxic activity
|
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39308793
|
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[
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10.1016/j.omton.2024.200862
10.1056/NEJMoa1709684
10.1200/JCO.21.00612
10.1200/Jco.2016.66.7220
10.1056/NEJMra2034861
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10.1056/NEJMoa1604958
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10.1084/jem.171.4.1375
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10.1073/pnas.93.25.14809
10.1158/1078-0432.CCR-16-1241
10.1126/science.aav8692
10.1016/j.cell.2023.06.002
10.1158/2326-6066.CIR-21-0536
10.1038/s41587-023-02060-8
10.1038/s41467-024-45221-2
10.1182/blood-2007-11-120998
10.1038/ng.2764
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10.1158/1078-0432.CCR-10-0192
10.1126/scitranslmed.3005930
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10.1080/17425255.2016.1223047
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10.1007/s00262-017-2034-7
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10.1111/imr.12772
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10.1126/scitranslmed.abb5191
10.1093/bioinformatics/btp692
10.1073/pnas.92.15.6733
10.1038/nbt.4195
10.1038/nature01593
10.1097/PAI.0b013e3181dbfcd2
|
[
"Hackett",
"Hirschhorn",
"Tang",
"Purdon",
"Marouf",
"Piersigilli",
"Agaram",
"Liu",
"Schad",
"de Stanchina",
"Rafiq",
"Monette",
"Wolchok",
"Merghoub",
"Brentjens"
] |
[
"Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA.\nSwim Across America and Ludwig Collaborative Laboratory, Department of Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA.\nParker Institute for Cancer Immunotherapy and Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, NY 10065, USA.",
"Swim Across America and Ludwig Collaborative Laboratory, Department of Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA.\nParker Institute for Cancer Immunotherapy and Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, NY 10065, USA.",
"Swim Across America and Ludwig Collaborative Laboratory, Department of Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA.\nParker Institute for Cancer Immunotherapy and Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, NY 10065, USA.",
"Roswell Park Cancer Center, Buffalo, NY 14203, USA.",
"Swim Across America and Ludwig Collaborative Laboratory, Department of Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA.\nParker Institute for Cancer Immunotherapy and Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, NY 10065, USA.",
"Laboratory of Comparative Pathology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, The Rockefeller University, New York, NY 10065, USA.",
"Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.",
"Swim Across America and Ludwig Collaborative Laboratory, Department of Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA.\nParker Institute for Cancer Immunotherapy and Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, NY 10065, USA.",
"Swim Across America and Ludwig Collaborative Laboratory, Department of Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA.\nParker Institute for Cancer Immunotherapy and Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, NY 10065, USA.",
"Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.",
"Department of Hematology and Medical Oncology, Emory University School of Medicine, and Winship Cancer Institute, Atlanta, GA 30322, USA.",
"Laboratory of Comparative Pathology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, The Rockefeller University, New York, NY 10065, USA.",
"Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA.\nSwim Across America and Ludwig Collaborative Laboratory, Department of Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA.\nParker Institute for Cancer Immunotherapy and Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, NY 10065, USA.",
"Swim Across America and Ludwig Collaborative Laboratory, Department of Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA.\nParker Institute for Cancer Immunotherapy and Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, NY 10065, USA.",
"Roswell Park Cancer Center, Buffalo, NY 14203, USA."
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[] | 8.950677 | 4.92091 |
39308670
| 465 |
Comparison of the Efficacy and Safety of Axi-Cel and Tisa-Cel Based on Meta-Analysis.
|
This study aimed to analyze the efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy for B-cell lymphoma using published literature data. Literature on CAR-T therapy for B-cell lymphoma was collected by searching common databases. The literature was screened, quality assessed, and data extracted according to the inclusion and exclusion criteria. We performed a quantitative meta-analysis of the efficacy and safety of combined literature data. If the data could not be combined, descriptive analysis was performed. The meta-analysis results indicated that compared with tisagenlecleucel (tisa-cel), axicabtagene ciloleucel (axi-cel) had higher objective response rate (ORR) and complete response rate, with odds ratio (OR) of 0.63 for both sides (95% confidence interval [CI], 0.50-0.79) and statistically significant differences. Partial response rate was lower with axi-cel than with tisa-cel, with an OR of 1.02 for tisa-cel versus axi-cel (95% CI, 0.75-1.40) and no statistically significant difference. Compared with tisa-cel, axi-cel had longer progression-free survival and overall survival, with risk ratios of 0.70 (95% CI, 0.62-0.80) and 0.71 (95% CI, 0.61-0.84) for axi-cel and tisa-cel, respectively. Compared with tisa-cel, axi-cel had higher incidence rates of cytokine release syndrome (CRS) and immune effector cell-related neurotoxicity syndrome (ICANS), with ORs of 3.84 (95% CI, 2.10-7.03) and 4.4 (95% CI, 2.81-6.91), respectively. CAR T-cell therapy is an effective treatment option for relapsed/refractory B-cell lymphoma. Axi-cel has better ORR and survival advantages compared with tisa-cel; however, axi-cel has higher incidence rates of CRS and ICANS compared with tisa-cel.
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] | 2024-09-23 | 35 |
39308670
|
[
"higher incidence rates",
"higher objective response rate",
"combined literature data",
"published literature data",
"Partial response rate",
"descriptive analysis",
"data",
"cytokine release syndrome",
"overall survival",
"Literature",
"immune effector cell-related neurotoxicity syndrome",
"CAR T-cell therapy",
"odds ratio",
"B-cell lymphoma",
"risk ratios",
"safety",
"CI",
"tisa-cel",
"CRS",
"axi-cel",
"ICANS",
"axicabtagene ciloleucel",
"relapsed/refractory B-cell lymphoma",
"common databases",
"tisa-cel, axi-cel",
"CAR-T therapy",
"chimeric antigen receptor T-cell (CAR-T) therapy",
"longer progression-free survival",
"95% confidence interval",
"better ORR and survival advantages"
] |
[
"Axi-cel",
"B-Cell Lymphoma",
"CAR-T Therapy",
"Chimeric Antigen Receptor T Cells (CAR-T)",
"Efficacy",
"Meta-analysis",
"Safety",
"Tisa-cel"
] | 0 |
10.7150/jca.99427
|
[
"Liao",
"Zeng",
"Lu",
"Zheng",
"Guo",
"Ke",
"Wang",
"Sun",
"Rong",
"He",
"Zhong",
"Huang",
"Tan",
"Cen"
] |
[
"Department of Hematology/Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, China.\nState Key Laboratory of Targeting Oncology, Guangxi Medical University, Nanning, Guangxi, 530021, China.",
"Department of Hematology/Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, China.\nDepartment of Thyroid and Breast Surgery, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Guangxi, Nanning, 530022, China.",
"Department of Pharmacy Foresea Life Insurance Guangxi Hospital, Nanning, Guangxi, 530200, China.",
"Department of Hematology/Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, China.",
"Department of Hematology/Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, China.",
"Department of Hematology/Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, China.",
"Department of Hematology/Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, China.",
"Department of Hematology/Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, China.",
"Department of Hematology/Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, China.",
"Department of Hematology/Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, China.",
"Department of Hematology/Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, China.",
"College of Oncology, Guangxi Medical University,Nanning, Guangxi, 530021, China.",
"Department of Hematology/Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, China.",
"Department of Hematology/Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, China."
] |
[
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[] | 5.836479 | 4.985871 |
39308543
| 466 |
Advancements in adoptive CAR immune cell immunotherapy synergistically combined with multimodal approaches for tumor treatment.
|
Adoptive immunotherapy, notably involving chimeric antigen receptor (CAR)-T cells, has obtained Food and Drug Administration (FDA) approval as a treatment for various hematological malignancies, demonstrating promising preclinical efficacy against cancers. However, the intricate and resource-intensive autologous cell processing, encompassing collection, expansion, engineering, isolation, and administration, hamper the efficacy of this therapeutic modality. Furthermore, conventional CAR T therapy is presently confined to addressing solid tumors due to impediments posed by physical barriers, the potential for cytokine release syndrome, and cellular exhaustion induced by the immunosuppressive and heterogeneous tumor microenvironment. Consequently, a strategic integration of adoptive immunotherapy with synergistic multimodal treatments, such as chemotherapy, radiotherapy, and vaccine therapy etc., emerges as a pivotal approach to surmount these inherent challenges. This collaborative strategy holds the key to addressing the limitations delineated above, thereby facilitating the realization of more precise personalized therapies characterized by heightened therapeutic efficacy. Such synergistic strategy not only serves to mitigate the constraints associated with adoptive immunotherapy but also fosters enhanced clinical applicability, thereby advancing the frontiers of therapeutic precision and effectiveness.
|
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39308543
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|
[
"Chang",
"Chang",
"Bao",
"Dong"
] |
[
"Department of Biomedical Engineering, The Hong Kong Polytechnic University, 999077, Hong Kong, China.\nThe Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, 518000, China.",
"Department of Biomedical Engineering, The Hong Kong Polytechnic University, 999077, Hong Kong, China.",
"Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN, 47907, USA.\nPurdue University Institute for Cancer Research, West Lafayette, IN, 47907, USA.",
"Department of Biomedical Engineering, The Hong Kong Polytechnic University, 999077, Hong Kong, China.\nThe Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, 518000, China."
] |
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[] | 9.744507 | 4.174986 |
39307298
| 467 |
From promise to progress: the dynamic landscape of glioblastoma immunotherapy.
|
Glioblastoma multiforme (GBM) is the most common CNS cancer, it has dismal survival rates despite several effective mediators: intensified cytotoxic therapy, chimeric antigen receptor (CAR)-T cell therapy, viral therapy, adoptive cell therapy, immune checkpoint blockade therapy, radiation therapy and vaccine therapy. This review examines the basic concepts underlying immune targeting and examines products such as checkpoint blockade drugs, CAR-T cells, oncolytic viruses, combinatory multimodal immunotherapy and cancer vaccines. New approaches to overcoming current constraints and challenges in GBM therapy are discussed, based on recent studies into these tactics, findings from ongoing clinical trials, as well as previous trial results.
|
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] | 2024-09-23 | 1 |
39307298
|
[
"immune checkpoint blockade therapy",
"CAR)-T cell therapy",
"GBM therapy",
"adoptive cell therapy",
"cytotoxic therapy",
"vaccine therapy",
"radiation therapy",
"viral therapy",
"checkpoint blockade drugs",
"ongoing clinical trials",
"dismal survival rates",
"several effective mediators",
"previous trial results",
"chimeric antigen receptor",
"current constraints",
"recent studies",
"GBM",
"oncolytic viruses",
"combinatory multimodal immunotherapy and cancer vaccines",
"New approaches",
"findings",
"CNS",
"challenges",
"CAR-T cells",
"CAR)-T",
"products",
"Glioblastoma",
"the most common CNS cancer",
"the basic concepts",
"these tactics"
] |
[
"CAR immunotherapies",
"Glioblastoma",
"immune checkpoint blockade therapy",
"immunotherapy",
"vaccine"
] | 0 |
10.1016/j.drudis.2024.104188
|
[
"Ijaz",
"Ullah",
"Aslam",
"Khurshid",
"Chen",
"Guo"
] |
[
"School of Science, Shenzhen Key Laboratory of Flexible Printed Electronics Technology, Shenzhen Key Laboratory of Advanced Functional Carbon Materials Research and Comprehensive Application, Harbin Institute of Technology, Shenzhen 518055, China; Institute of Microbiology, Government College University Faisalabad, Pakistan.",
"School of Science, Shenzhen Key Laboratory of Flexible Printed Electronics Technology, Shenzhen Key Laboratory of Advanced Functional Carbon Materials Research and Comprehensive Application, Harbin Institute of Technology, Shenzhen 518055, China.",
"Institute of Microbiology, Government College University Faisalabad, Pakistan.",
"Institute of Microbiology, Government College University Faisalabad, Pakistan.",
"Department of Traumatic Orthopedics, Shenzhen Longhua District Central Hospital, Shenzhen, China. Electronic address: pfchen@sibs.ac.cn.",
"School of Science, Shenzhen Key Laboratory of Flexible Printed Electronics Technology, Shenzhen Key Laboratory of Advanced Functional Carbon Materials Research and Comprehensive Application, Harbin Institute of Technology, Shenzhen 518055, China. Electronic address: guobing2020@hit.edu.cn."
] |
[
"39307298"
] |
[] | 10.169341 | 7.414433 |
39306853
| 468 |
Protocol for preparing metabolically reprogrammed human CAR T cells and evaluating their in vitro effects.
|
Chimeric antigen receptor (CAR) T cell therapy represents a cutting-edge cancer treatment, making the development and testing of CAR T cells crucial for advancing this therapeutic strategy. We present a protocol for creating and characterizing human epidermal growth factor receptor 2 (HER2)- and glypican-3 (GPC3)-metabolic reprogramming (MR)-CAR T cells by overexpressing adenosine deaminase 1 (ADA1) and CD26 (also known as dipeptidylpeptidase-4 or DPP4). This approach effectively converts immunosuppressive adenosine into inosine, which supports T cell survival in glucose-deficient tumor microenvironments. The protocol includes producing retroviral vectors, generating CAR T cells, and conducting ecto-ADA1 activity, cytotoxicity, cell migration, and RNA sequencing assays. For complete details on the use and execution of this protocol, please refer to Hu et al.
|
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] | 2024-09-22 | 5 |
39306853
|
[
"cell migration",
"human epidermal growth factor receptor",
"CAR T cells",
"adenosine deaminase",
"immunosuppressive adenosine",
"T cell survival",
"Chimeric antigen receptor",
"retroviral vectors",
"CAR) T cell therapy",
"complete details",
"execution",
"CD26",
"Hu",
"cytotoxicity",
"inosine",
"testing",
"RNA",
"glucose-deficient tumor microenvironments",
"dipeptidylpeptidase-4",
"ecto-ADA1 activity",
"Hu et al",
"DPP4",
"assays",
"a cutting-edge cancer treatment",
"The protocol",
"a protocol",
"this protocol",
"(HER2)- and glypican-3 (GPC3)-metabolic reprogramming (MR)-CAR T cells",
"et al",
"this therapeutic strategy"
] |
[
"biotechnology and bioengineering",
"cancer",
"clinical protocol",
"immunology",
"metabolism",
"molecular biology",
"tissue engineering"
] | 0 |
10.1016/j.xpro.2024.103333
10.21203/rs.3.rs-4103623/v1
|
[
"Hu",
"Sarkar",
"Song"
] |
[
"Department of Translational Medical Sciences, School of Medicine, Texas A&M University, Houston, TX 77030, USA; Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M University, Houston, TX 77030, USA.",
"Department of Translational Medical Sciences, School of Medicine, Texas A&M University, Houston, TX 77030, USA; Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M University, Houston, TX 77030, USA.",
"Department of Translational Medical Sciences, School of Medicine, Texas A&M University, Houston, TX 77030, USA; Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M University, Houston, TX 77030, USA. Electronic address: xsong@tamu.edu."
] |
[
"39306853",
"38688275",
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"4840442"
] |
[] | 8.665166 | 4.445843 |
39306365
| 469 |
Recent advances and progress in immunotherapy of solid cancers.
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Adoptive cell therapy using chimeric antigen receptor (CAR) technology has become mainstream by employing advanced engineering platforms to promote cancer immunotherapy. CAR T cells have shown remarkable efficacy in the treatment of hematological malignancies; however, the value of this therapy remains inconclusive in the context of solid tumors. Immunotherapy of solid tumors is restrained by several obstacles including the presence of an immunosuppressive tumor microenvironment (TME), limited tumor trafficking, inhibited immune cell infiltration, absence of tumor-specific antigens, and off-target toxicity and adverse events associated with these therapies. Despite recent advances in CAR T cell construction, including the integration of co-stimulatory domains and the creation of armed CAR T cells, with promising outcomes in the treatment of some solid tumors, there are still many unresolved obstacles that need to be overcome. To surmount these impediments to effective CAR T cell therapies, other immune cells, such as natural killer cells and macrophages, have been engineered to serve as appealing alternatives for successful cancer immunotherapy of solid tumors. CAR NK cells demonstrate significant clinical advantages due to their ready availability and minimal toxicity. CAR macrophage (M) cells provide considerable therapeutic potential due to their ability to penetrate the TME of solid tumors. In this review, we comprehensively examine the latest developments and prospects of engineered immune cell-based cancer immunotherapies specifically designed for treating solid tumors. In addition, we provide a concise overview of current clinical trials that are examining the safety and effectiveness of modified immune cells, such as CAR T, CAR NK, and CAR M, in their ability to specifically target solid tumors and promote improved therapeutic outcomes in patients with diverse solid cancers.
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] | 2024-09-22 | 1 |
39306365
|
[
"CAR T cells",
"armed CAR T cells",
"CAR T cell construction",
"effective CAR T cell therapies",
"solid tumors",
"CAR NK cells",
"modified immune cells",
"other immune cells",
"Adoptive cell therapy",
"inhibited immune cell infiltration",
"natural killer cells",
"diverse solid cancers",
"limited tumor trafficking",
"CAR M",
"engineered immune cell-based cancer immunotherapies",
"successful cancer immunotherapy",
"cancer immunotherapy",
"CAR T",
"CAR NK",
"CAR",
"improved therapeutic outcomes",
"current clinical trials",
"significant clinical advantages",
"many unresolved obstacles",
"co-stimulatory domains",
"considerable therapeutic potential",
"some solid tumors",
"several obstacles",
"advanced engineering platforms",
"tumor-specific antigens"
] |
[
"CAR NK cells",
"CAR T cells",
"CAR macrophages",
"Immunotherapy",
"Solid cancers"
] | 0 |
10.1016/bs.acr.2024.05.004
|
[
"Kumar",
"Emdad",
"Das",
"Fisher"
] |
[
"Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States; VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States. Electronic address: amit.kumar@vcuhealth.org.",
"Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States; VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States; VCU Massey Comprehensive Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States.",
"Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States; VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States; VCU Massey Comprehensive Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States.",
"Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States; VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States; VCU Massey Comprehensive Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States. Electronic address: paul.fisher@vcuhealth.org."
] |
[
"39306365"
] |
[] | 9.833407 | 4.982627 |
39305562
| 470 |
Point of care CD19 chimeric antigen receptor (CAR) T-cells for relapsed/refractory acute myeloid leukemia (AML) with aberrant CD19 antigen expression.
|
Relapsed/refractory (r/r) acute myeloid leukemia (AML) is associated with poor prognosis. CD19 is a B-cell marker, is aberrantly expressed in AML, mostly with t(8; 21)(q22; q22.1). Here we report the results of a phase 2 study giving point of care produced CD19 CAR T- cells for r/r AML with aberrant expression of CD19 (NCT04257175). Lymphodepletion included fludarabine and cyclophosphamide The response was evaluated by bone marrow (BM) aspiration on day 28. Six patients (5 adults and 1 child) were included. Median number of previous chemotherapy lines was 4 (range, 3-8) and four patients received CAR T-cells 8-18 months post allogeneic hematopoietic stem cell transplantation (allo-HSCT). Cytokine release syndrome (CRS) of any grade occurred in all patients, and 1 patient had grade 3 CRS. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 2 patients at low grades. Tocilizumab was administered to 2 patients and corticosteroids to 3 patients. Four patients achieved a complete remission (CR), while 2/6 progressed (PD). Three patients (2 with CR and 1 with PD) underwent allo-HSCT (it was the second transplant in 2) 2-5 months post CAR T-cells infusion. The median duration of response in patients achieving CR was 8.5 (range; 3-14) months. However, all patients eventually died within 5 (1-18) months. In conclusion, CD19 CAR T- cell treatment for AML is feasible and safe. However, the response is short and should be followed by allo-HSCT. Hopefully, future long term results will be improved by combining the CAR T- cell therapy with the emerging novel effective anti-leukemic compounds.
|
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] | 2024-09-22 | 1 |
39305562
|
[
"CD19 CAR T- cells",
"CD19 CAR T- cell treatment",
"T- cell therapy",
"patients",
"AML",
"Immune effector cell-associated neurotoxicity syndrome",
"future long term results",
"CAR T-cells",
"CAR T-cells infusion",
"CD19",
"r/r AML",
"response",
"months",
"Cytokine release syndrome",
"previous chemotherapy lines",
"bone marrow",
"low grades",
"the emerging novel effective anti-leukemic compounds",
"Median number",
"aberrant expression",
"CR",
"8-18 months post allogeneic hematopoietic stem cell transplantation",
"PD",
"1 patient",
"2 patients",
"3 patients",
"Four patients",
"Six patients",
"Three patients",
"all patients"
] |
[
"Acute myeloid leukemia",
"CD19 aberrant expression",
"Chimeric antigen receptor",
"T-cells",
"Translocation 8:21"
] | 0 |
10.1016/j.retram.2024.103471
|
[
"Danylesko",
"Shem-Tov",
"Yerushalmi",
"Jacoby",
"Toren",
"Shouval",
"Itzhaki",
"Avigdor",
"Shimoni",
"Nagler"
] |
[
"Division of Hematology and Bone Marrow Transplantation, Sheba Medical Center, Ramat Gan, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: alexivetta@gmail.com.",
"Division of Hematology and Bone Marrow Transplantation, Sheba Medical Center, Ramat Gan, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.",
"Division of Hematology and Bone Marrow Transplantation, Sheba Medical Center, Ramat Gan, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.",
"Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Division of Pediatric Hematology and Oncology, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel.",
"Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Division of Pediatric Hematology and Oncology, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel.",
"Division of Hematology and Bone Marrow Transplantation, Sheba Medical Center, Ramat Gan, Israel; Department of Medicine, Weill Cornell Medical College, New York, New York, USA; Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA.",
"Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Ella Lemelbaum Institute of Immuno-Oncology, Sheba Medical Center, Ramat Gan, Israel.",
"Division of Hematology and Bone Marrow Transplantation, Sheba Medical Center, Ramat Gan, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.",
"Division of Hematology and Bone Marrow Transplantation, Sheba Medical Center, Ramat Gan, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.",
"Division of Hematology and Bone Marrow Transplantation, Sheba Medical Center, Ramat Gan, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel."
] |
[
"39305562"
] |
[] | 6.617 | 5.918034 |
39298141
| 471 |
Chimeric Antigen Receptor T Cells Targeting CD19 and GCC in Metastatic Colorectal Cancer: A Nonrandomized Clinical Trial.
|
Chimeric antigen receptor (CAR) T-cell therapy (CART) has transformed the treatment landscape of hematologic cancer, but has negligible effects for adult solid cancers. In this trial, an autologous CAR T-cell product demonstrated antitumor activity in heavily pretreated patients with metastatic colorectal cancer (mCRC).
To evaluate the safety and efficacy of guanylate cyclase-C (GCC19) CART in participants with metastatic colorectal cancer (mCRC).
This single-arm, nonrandomized, phase 1 trial was conducted at the First Hospital of Jilin University from December 3, 2020, to April 13, 2022. Data analysis was conducted from May 2022 to April 2024. Adults with relapsed and refractory mCRC expressing GCC were treated with GCC19CART, a mixture of autologous CAR T cells transduced with lentiviral vectors expressing genes that encode either CD-19 CAR or GCC CAR.
Safety and tolerability of CAR T-cell therapy targeting GCC in patients with mCRC without therapeutic options is capable of conferring a reasonable likeliness of clinical benefit. Other outcomes included objective response rate, progression-free survival, overall survival, and immune activation.
Of 15 patients 9 (60%) were women, and the median (range) age was 44 (33-61) years. Treatment with GCC19CART was associated with the development of cytokine release syndrome and diarrhea in most patients, all of which were self-limited and manageable. The objective response rate was 40%, with a partial response in 2 of 8 and 4 of 7 patients treated with either 1 × 106 cells/kg or 2 × 106 cells/kg. Median overall survival was 22.8 months (95% CI, 13.4-26.1) at data cutoff; the median progress-free survival was 6.0 months in the high dose level group (95% CI, 3.0 to not available).
The results of this nonrandomized clinical trial suggest that GCC19CART was safe and tolerable in heavily pretreated patients with mCRC and is the first CAR T-cell therapy known to produce objective clinical activity in refractory cancer. Given the paucity of effective therapeutics developed for colorectal cancer in recent decades, the observation that CD-19 CART target engagement can robustly induce GCC19CART target engagement sufficient to produce objective activity may serve as a foundation to develop effective cellular therapy in mCRC and other solid cancers.
Chinese Clinical Trial Registry: ChiCTR2000040645.
|
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] | 2024-09-22 | 14 |
39298141
|
[
"metastatic colorectal cancer",
"autologous CAR T cells",
"objective clinical activity",
"colorectal cancer",
"Median overall survival",
"most patients",
"objective activity",
"adult solid cancers",
"other solid cancers",
"patients",
"objective response rate",
"refractory cancer",
"effective cellular therapy",
"hematologic cancer",
"GCC19CART target engagement",
"overall survival",
"CAR T-cell therapy",
"GCC CAR",
"mCRC",
"Chinese Clinical Trial Registry",
"GCC19CART",
"antitumor activity",
"clinical benefit",
"cytokine release syndrome",
"CD-19 CAR",
"the first CAR T-cell therapy",
"effective therapeutics",
"data cutoff",
"CAR) T-cell therapy",
"Data analysis"
] |
[] | 0 |
10.1001/jamaoncol.2024.3891
10.6004/jnccn.2021.0012
10.6004/jnccn.2022.0051
10.1016/j.annonc.2022.10.003
10.1038/s41571-019-0297-y
10.1371/journal.pone.0189953
10.1080/2162402X.2016.1227897
10.1007/s12026-011-8253-7
10.1038/s41591-018-0010-1
10.1158/1078-0432.CCR-11-3050
10.1158/2159-8290.CD-20-1661
10.1053/j.gastro.2020.01.006
10.1016/S2468-1253(20)30014-5
10.6004/jnccn.2020.0012
|
[
"Chen",
"Pu",
"Zhao",
"Li",
"Wang",
"Zhu",
"Liang",
"Niu",
"Huang",
"Tang",
"Wang",
"Yang",
"Jia",
"Jiang",
"Han",
"Wang",
"Chen",
"Wang",
"Rowinsky",
"Kennedy",
"Lu",
"Cui",
"Wu",
"Xiao",
"Cui"
] |
[
"Cancer Center, the First Hospital of Jilin University, Changchun, China.",
"Innovative Cellular Therapeutics Co, Ltd, Shanghai, China.",
"Cancer Center, the First Hospital of Jilin University, Changchun, China.",
"Cancer Center, the First Hospital of Jilin University, Changchun, China.",
"Cancer Center, the First Hospital of Jilin University, Changchun, China.",
"Innovative Cellular Therapeutics Co, Ltd, Shanghai, China.",
"Cancer Center, the First Hospital of Jilin University, Changchun, China.",
"Cancer Center, the First Hospital of Jilin University, Changchun, China.",
"Innovative Cellular Therapeutics Co, Ltd, Shanghai, China.",
"Innovative Cellular Therapeutics Co, Ltd, Shanghai, China.",
"Cancer Center, the First Hospital of Jilin University, Changchun, China.",
"Innovative Cellular Therapeutics Co, Ltd, Shanghai, China.",
"Innovative Cellular Therapeutics Co, Ltd, Shanghai, China.",
"Innovative Cellular Therapeutics Co, Ltd, Shanghai, China.",
"Innovative Cellular Therapeutics Co, Ltd, Shanghai, China.",
"Innovative Cellular Therapeutics Co, Ltd, Shanghai, China.",
"Innovative Cellular Therapeutics Co, Ltd, Shanghai, China.",
"Innovative Cellular Therapeutics Co, Ltd, Shanghai, China.",
"Innovative Cellular Therapeutics Inc, Rockville, Maryland.",
"80 Horseshoe Pt, Phoenixville, Pennsylvania.",
"Innovative Cellular Therapeutics Inc, Rockville, Maryland.",
"Cancer Center, the First Hospital of Jilin University, Changchun, China.",
"Innovative Cellular Therapeutics Co, Ltd, Shanghai, China.",
"Innovative Cellular Therapeutics Inc, Rockville, Maryland.",
"Cancer Center, the First Hospital of Jilin University, Changchun, China."
] |
[
"39298141",
"33724754",
"36240850",
"36307056",
"31848460",
"29261789",
"27853651",
"22038530",
"29713085",
"22291136",
"33837065",
"31945371",
"32553146",
"32135517"
] |
[] | 8.980217 | 6.5317 |
39304585
| 472 |
CAR-T cells for the treatment of pediatric chronic myeloid leukemia in repeatedly relapsed lymphoid blast phase.
|
Chronic myeloid leukemia presenting de novo in the blast phase (CML-BP) is a rare diagnosis among pediatric malignancies. We report on a 16-year-old male who presented with CML-BP lymphoid at diagnosis. He was treated with shortened acute lymphoblastic leukemia induction plus the tyrosine kinase inhibitor (TKI) imatinib followed by dasatinib. After achieving molecular remission (MR), hematopoietic stem cell transplantation (HSCT) was performed early after diagnosis. Despite prophylactic dasatinib, he relapsed 3 months later with the kinase domain mutation T315I. Multiple therapeutic approaches including ponatinib, blinatumomab, a 2nd HSCT from a different donor, donor lymphocyte infusions, and high-dose asciminib all resulted in subsequent relapse. Another molecular response was achieved by combining ponatinib plus asciminib with chemotherapy. In this situation, CD19-directed CAR-T cells (Kymriah
|
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] | 2024-09-21 | 15 |
39304585
|
[
"shortened acute lymphoblastic leukemia induction",
"hematopoietic stem cell transplantation",
"donor lymphocyte infusions",
"Multiple therapeutic approaches",
"T315I. Multiple",
"ponatinib",
"diagnosis",
"molecular remission",
"asciminib",
"prophylactic dasatinib",
"subsequent relapse",
"dasatinib",
"Chronic myeloid",
"pediatric malignancies",
"CML-BP lymphoid",
"MR",
"TKI",
"the kinase domain mutation",
"blinatumomab",
"high-dose asciminib",
"HSCT",
"CML-BP",
"myeloid",
"a rare diagnosis",
"a different donor",
"Kymriah",
"chemotherapy",
"a 2nd HSCT",
"the blast phase",
"Another molecular response"
] |
[
"Blast phase",
"CD19 CAR-T cells",
"Chronic myeloid leukemia",
"Refractory leukemia"
] | 0 |
10.1007/s00277-024-06011-4
|
[
"Kramp",
"Heydrich-Karsten",
"Sembill",
"Karow",
"Lion",
"Chitadze",
"Suttorp",
"Cario",
"Metzler"
] |
[
"Pediatric Oncology and Hematology, Department of Pediatrics and Adolescent Medicine, University Medical Center Schleswig-Holstein Kiel, Kiel, Germany.",
"Pediatric Oncology and Hematology, Department of Pediatrics and Adolescent Medicine, University Medical Center Schleswig-Holstein Kiel, Kiel, Germany.",
"Pediatric Oncology and Hematology, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, 91054, Erlangen, Germany.\nComprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Erlangen, Germany.",
"Pediatric Oncology and Hematology, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, 91054, Erlangen, Germany.\nComprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Erlangen, Germany.",
"St. Anna Children's Cancer Research Institute (CCRI), Vienna, Austria.",
"Clinical Research Unit CATCH-ALL (KFO, German Research Foundation), Christian- Albrechts-University of Kiel, Kiel, Germany.\nMedical Department II, Hematology and Oncology, Christian-Albrechts University of Kiel, University Hospital Schleswig-Holstein, Kiel, Germany.",
"Pediatric Hemato-Oncology, Medical Faculty, Technical University Dresden, Dresden, Germany.",
"Pediatric Oncology and Hematology, Department of Pediatrics and Adolescent Medicine, University Medical Center Schleswig-Holstein Kiel, Kiel, Germany.\nClinical Research Unit CATCH-ALL (KFO, German Research Foundation), Christian- Albrechts-University of Kiel, Kiel, Germany.",
"Pediatric Oncology and Hematology, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, 91054, Erlangen, Germany. Markus.Metzler@uk-erlangen.de.\nComprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Erlangen, Germany. Markus.Metzler@uk-erlangen.de."
] |
[
"39304585",
"28522462",
"30917954",
"36309558",
"36707619",
"38755421",
"38803040",
"33651091",
"33332189",
"35447373",
"32062061",
"38085116",
"34405773",
"31988993",
"38448401"
] |
[] | 6.538946 | 6.330602 |
39301632
| 473 |
Claudin 1, 4, 6 and 18 isoform 2 as targets for the treatment of cancer (Review).
|
The 24 claudin (
|
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] | 2024-09-21 | 88 |
39301632
|
[
"The 24 claudin",
"24"
] |
[
"TGF‑β",
"WNT",
"epithelial‑mesenchymal transition",
"fibroblast growth factor receptor",
"immunosuppressive tumor microenvironment",
"intratumor heterogeneity",
"non‑small cell lung cancer",
"ovarian cancer",
"pancreatic cancer",
"splicing variant"
] | 0 |
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|
[
"Katoh",
"Katoh"
] |
[
"Department of Global Network, M & M Precision Medicine, Tokyo 113‑0033, Japan.",
"Department of Global Network, M & M Precision Medicine, Tokyo 113‑0033, Japan."
] |
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[] | 32.942616 | 7.490846 |
39301248
| 474 |
Strategies to Overcome Hurdles in Cancer Immunotherapy.
|
Despite marked advancements in cancer immunotherapy over the past few decades, there remains an urgent need to develop more effective treatments in humans. This review explores strategies to overcome hurdles in cancer immunotherapy, leveraging innovative technologies including multi-specific antibodies, chimeric antigen receptor (CAR) T cells, myeloid cells, cancer-associated fibroblasts, artificial intelligence (AI)-predicted neoantigens, autologous vaccines, and mRNA vaccines. These approaches aim to address the diverse facets and interactions of tumors' immune evasion mechanisms. Specifically, multi-specific antibodies and CAR T cells enhance interactions with tumor cells, bolstering immune responses to facilitate tumor infiltration and destruction. Modulation of myeloid cells and cancer-associated fibroblasts targets the tumor's immunosuppressive microenvironment, enhancing immunotherapy efficacy. AI-predicted neoantigens swiftly and accurately identify antigen targets, which can facilitate the development of personalized anticancer vaccines. Additionally, autologous and mRNA vaccines activate individuals' immune systems, fostering sustained immune responses against cancer neoantigens as therapeutic vaccines. Collectively, these strategies are expected to enhance efficacy of cancer immunotherapy, opening new horizons in anticancer treatment.
|
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] | 2024-09-21 | 131 |
39301248
|
[
"cancer immunotherapy",
"cancer neoantigens",
"tumor cells",
"CAR T cells",
"T cells",
"sustained immune responses",
"immune responses",
"immunotherapy efficacy",
"multi-specific antibodies",
"personalized anticancer vaccines",
"myeloid cells",
"autologous vaccines",
"tumor infiltration",
"mRNA vaccines",
"therapeutic vaccines",
"chimeric antigen receptor",
"antigen targets",
"anticancer treatment",
"cancer-associated fibroblasts",
"tumors immune evasion mechanisms",
"new horizons",
"innovative technologies",
"interactions",
"artificial intelligence",
"CAR",
"strategies",
"autologous and mRNA vaccines",
"efficacy",
"marked advancements",
"individuals immune systems"
] |
[] | 0 |
10.34133/bmr.0080
|
[
"Kim",
"Lee",
"Moon",
"Lee",
"Lee",
"Kim",
"Jung",
"Seo",
"Chung"
] |
[
"Research Institute for Pharmaceutical Sciences, College of Pharmacy, College of Pharmacy,Seoul National University, Seoul 08826, Republic of Korea.",
"Interdisciplinary Program for Bioengineering, Seoul National University, Seoul 08826, Republic of Korea.",
"Research Institute for Pharmaceutical Sciences, College of Pharmacy, College of Pharmacy,Seoul National University, Seoul 08826, Republic of Korea.",
"Department of Anatomy and Cell Biology, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.",
"Research Institute for Pharmaceutical Sciences, College of Pharmacy, College of Pharmacy,Seoul National University, Seoul 08826, Republic of Korea.\nMolecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea.\nArontier Co., Seoul 06735, Republic of Korea.",
"Interdisciplinary Program for Bioengineering, Seoul National University, Seoul 08826, Republic of Korea.\nSchool of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Republic of Korea.\nInstitute of Chemical Processes, Institute of Engineering Research, and BioMAX, Seoul National University, Seoul 08826, Republic of Korea.",
"Department of Anatomy and Cell Biology, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.",
"Research Institute for Pharmaceutical Sciences, College of Pharmacy, College of Pharmacy,Seoul National University, Seoul 08826, Republic of Korea.",
"Research Institute for Pharmaceutical Sciences, College of Pharmacy, College of Pharmacy,Seoul National University, Seoul 08826, Republic of Korea."
] |
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] |
[] | 10.736259 | 4.193228 |
39301026
| 475 |
ReCARving the future: bridging CAR T-cell therapy gaps with synthetic biology, engineering, and economic insights.
|
Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of hematologic malignancies, offering remarkable remission rates in otherwise refractory conditions. However, its expansion into broader oncological applications faces significant hurdles, including limited efficacy in solid tumors, safety concerns related to toxicity, and logistical challenges in manufacturing and scalability. This review critically examines the latest advancements aimed at overcoming these obstacles, highlighting innovations in CAR T-cell engineering, novel antigen targeting strategies, and improvements in delivery and persistence within the tumor microenvironment. We also discuss the development of allogeneic CAR T cells as off-the-shelf therapies, strategies to mitigate adverse effects, and the integration of CAR T cells with other therapeutic modalities. This comprehensive analysis underscores the synergistic potential of these strategies to enhance the safety, efficacy, and accessibility of CAR T-cell therapies, providing a forward-looking perspective on their evolutionary trajectory in cancer treatment.
|
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39301026
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|
[
"Ali",
"DiPersio"
] |
[
"Stem Cell Transplant and Cellular Immunotherapy Program, Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, United States.",
"Center for Gene and Cellular Immunotherapy, Washington University in Saint Louis, Saint Louis, MO, United States."
] |
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] | 2024-09-20 | 14 |
39300321
|
[] |
[] | 0 |
10.1038/s43018-024-00826-w
10.1056/NEJMoa2024850
10.1200/JCO.22.00842
10.1038/s41573-023-00807-1
10.1038/s43018-024-00763-8
10.1182/blood.2020007445
10.1158/1078-0432.CCR-20-1434
10.1158/2643-3230.BCD-22-0018
10.1182/blood-2022-168903
10.1016/j.ccell.2023.02.008
10.1182/blood.2023022499
10.1158/2643-3230.BCD-22-0126
10.1172/JCI126397
10.3389/fimmu.2022.832645
10.1038/s43018-023-00637-5
|
[
"Hassan",
"Davila"
] |
[
"Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.",
"Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA. Marco.Davila@roswellpark.org."
] |
[
"39300321",
"33626253",
"35658469",
"37907724",
"38641734",
"33512407",
"32669372",
"36026513",
"36898378",
"38194680",
"36026510",
"30896447",
"35222421",
"37993694"
] |
[] | 32.965523 | 7.53306 |
39299100
| 477 |
Optimizing CAR-T cell Culture: Differential effects of IL-2, IL-12, and IL-21 on CAR-T cells.
|
Chimeric antigen receptor (CAR)-T therapy has demonstrated sustained clinical remission in numerous hematologic malignancies and has expanded to encompass solid tumors and autoimmune diseases. While progress is being made in establishing optimal culture conditions for CAR-T cells, the identification of the most effective cytokine for promoting their persistence in vitro remains elusive.
Here, we employed scRNA-seq (single-cell RNA sequencing) analysis to investigate the potential alterations in biological processes within CAR-T cells following exposure to cytokines (IL-2, IL-12, and IL-21) and antigens. Transcriptomic changes in diverse CAR-T groups were compared following various treatments, with a focus on epigenetic modifications, metabolic shifts, cellular senescence, and exhaustion.
Our study reveals that CAR-T cells treated with antigen, IL-2, and IL-12 exhibit signs of exhaustion and senescence, whereas those treated with IL-21 do not display these characteristics. The activities of glycolysis and epigenetic changes were significantly increased by treatments with antigens, IL-2, and IL-12, while IL-21 treatment maintained the oxidative phosphorylation (OXPHOS) of CAR-T cells.
Our findings suggest that IL-21 may play a role in preventing senescence and could be utilized in combination with other strategies, such as IL-2 and IL-12, for CAR-T culture.
|
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0.0064756120555102825
] | 2024-09-20 | 1 |
39299100
|
[
"IL-12",
"cellular senescence",
"numerous hematologic malignancies",
"various treatments",
"sustained clinical remission",
"Chimeric antigen receptor",
"optimal culture conditions",
"senescence",
"CAR-T cells",
"epigenetic modifications",
"solid tumors",
"treatments",
"CAR)-T therapy",
"Transcriptomic changes",
"cytokines",
"metabolic shifts",
"other strategies",
"antigens",
"biological processes",
"autoimmune diseases",
"diverse CAR-T groups",
"CAR-T culture",
"exhaustion",
"CAR)-T",
"RNA",
"combination",
"glycolysis and epigenetic changes",
"analysis",
"OXPHOS",
"antigen"
] |
[
"CAR-T",
"Cellular senescence",
"Epigenetic changes",
"Exhausted T cells",
"Metabolic reprogramming",
"scRNA-seq"
] | 0 |
10.1016/j.cyto.2024.156758
|
[
"Zhang",
"Kong",
"Yin",
"Shi",
"Li",
"Qiu",
"Yue",
"Wang",
"Sun",
"Lin",
"Fu",
"Wang",
"Sun",
"Gao",
"Jiang",
"Guo"
] |
[
"Translational Medical Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.",
"Translational Medical Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.",
"Translational Medical Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.",
"Precision Medicine Center, Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China.",
"Translational Medical Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.",
"Precision Medicine Center, Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China.",
"Department of Laboratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.",
"Department of Blood Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.",
"Translational Medical Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.",
"Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, China.",
"Department of Laboratory Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, China.",
"Department of Laboratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.",
"Basic Medical Research Center, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China. Electronic address: sunxianlei@zzu.edu.cn.",
"Department of Emergency Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. Electronic address: gaoyanxiazzu@163.com.",
"Henan Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine and Department of Emergency Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. Electronic address: jiang48231@163.com.",
"Translational Medical Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. Electronic address: guorq2007@163.com."
] |
[
"39299100"
] |
[] | 8.194063 | 4.734343 |
39295145
| 478 |
Synergistic integration of mRNA-LNP with CAR-engineered immune cells: Pioneering progress in immunotherapy.
|
Chimeric antigen receptor T cell (CAR-T) therapy has emerged as a revolutionary approach in the treatment of malignancies. Despite its remarkable successes, this field continues to grapple with challenges such as scalability, safety concerns, limited therapeutic effect, in vivo persistence, and the need for precise control over CAR expression. In the post-pandemic era of COVID-19 vaccine immunization, the application of messenger RNA (mRNA) encapsulated within lipid nanoparticles (LNPs) has recently garnered significant attention as a potential solution to address these challenges. This review delves into the dynamic landscape of mRNA-LNP technology and its potential implications for CAR-engineered immune cell-based immunotherapy.
|
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] | 2024-09-19 | 180 |
39295145
|
[
"COVID-19 vaccine immunization",
"limited therapeutic effect",
"CAR expression",
"mRNA",
"vivo persistence",
"safety concerns",
"messenger RNA",
"significant attention",
"lipid nanoparticles",
"CAR",
"challenges",
"COVID-19",
"scalability",
"CAR-engineered immune cell-based immunotherapy",
"mRNA-LNP technology",
"LNPs",
"the post-pandemic era",
"Chimeric antigen receptor T cell (CAR-T) therapy",
"its potential implications",
"a potential solution",
"malignancies",
"a revolutionary approach",
"the dynamic landscape",
"precise control",
"its remarkable successes",
"these challenges",
"the application",
"the need",
"this field",
"the treatment"
] |
[
"CAR-engineered immune cells",
"chimeric antigen receptor",
"immunotherapy",
"mRNA-LNP"
] | 0 |
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|
[
"Chen",
"Shu",
"Hu",
"Mei"
] |
[
"Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, Hubei, China; Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease, Wuhan 430022, China.",
"Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, Hubei, China; Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease, Wuhan 430022, China.",
"Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, Hubei, China; Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease, Wuhan 430022, China.",
"Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, Hubei, China; Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease, Wuhan 430022, China. Electronic address: hmei@hust.edu.cn."
] |
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[] | 9.949536 | 3.351338 |
39294514
| 479 |
Emerging immunologic approaches as cancer anti-angiogenic therapies.
|
Targeting tumor angiogenesis, the formation of new blood vessels supporting cancer growth and spread, has been an intense focus for therapy development. However, benefits from anti-angiogenic drugs like bevacizumab have been limited by resistance stemming from activation of compensatory pathways. Recent immunotherapy advances have sparked interest in novel immunologic approaches that can induce more durable vascular pruning and overcome limitations of existing angiogenesis inhibitors. This review comprehensively examines these emerging strategies, including modulating tumor-associated macrophages, therapeutic cancer vaccines, engineered nanobodies and T cells, anti-angiogenic cytokines/chemokines, and immunomodulatory drugs like thalidomide analogs. For each approach, the molecular mechanisms, preclinical/clinical data, and potential advantages over conventional drugs are discussed. Innovative therapeutic platforms like nanoparticle delivery systems are explored. Moreover, the importance of combining agents with distinct mechanisms to prevent resistance is evaluated. As tumors hijack angiogenesis for growth, harnessing the immune system's specificity to disrupt this process represents a promising anti-cancer strategy covered by this review.
|
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] | 2024-09-19 | 109 |
39294514
|
[
"anti-angiogenic drugs",
"anti-angiogenic cytokines",
"tumor angiogenesis",
"therapeutic cancer vaccines",
"cancer growth",
"immunomodulatory drugs",
"conventional drugs",
"novel immunologic approaches",
"existing angiogenesis inhibitors",
"distinct mechanisms",
"nanoparticle delivery systems",
"Innovative therapeutic platforms",
"new blood vessels",
"angiogenesis",
"a promising anti-cancer strategy",
"tumors",
"Recent immunotherapy advances",
"potential advantages",
"growth",
"resistance",
"engineered nanobodies",
"T cells",
"compensatory pathways",
"therapy development",
"thalidomide analogs",
"interest",
"limitations",
"tumor-associated macrophages",
"agents",
"bevacizumab"
] |
[
"Antiangiogenic vaccines",
"Chimeric antigen receptor T cells (CART)",
"Immune checkpoint inhibitors",
"Immunotherapy",
"Nanoparticles"
] | 0 |
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|
[
"Azimi",
"Manavi",
"Afshinpour",
"Khorram",
"Vafadar",
"Rezaei-Tazangi",
"Arabzadeh",
"Arabzadeh",
"Ebrahimi",
"Aref"
] |
[
"Department of Biochemistry, Medical Faculty, Saveh Branch, Islamic Azad University, Saveh, Iran.",
"Otolaryngology Department, Tehran University of Medical Science, Tehran, Iran.",
"Department of Chemistry and Biochemistry, South Dakota State University (SDSU), Brookings, SD, USA.",
"Bone and Joint Diseases Research Center, Department of Orthopedic Surgery, Shiraz University of Medical Sciences, Shiraz, Iran.",
"Department of Orthopeadic Surgery, Kerman University of Medical Sciences, Kerman, Iran.",
"Department of Anatomy, School of Medicine, Fasa University of Medical Sciences, Fasa, Iran.",
"Xi'an Jaiotong University Medical Campus, Xi'an Jaiotong University, Xi'an, Shaanxi Province, China.",
"Xi'an Jaiotong University Medical Campus, Xi'an Jaiotong University, Xi'an, Shaanxi Province, China.",
"Genetics Division, Department of Cell and Molecular Biology and Microbiology, Faculty of Science and Technology, University of Isfahan, Isfahan, Iran. Nasimeb69@gmail.com.",
"Mass General Cancer Center, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. aaref@mgh.harvard.edu.\nBroad Institute of MIT and Harvard, Cambridge, MA, USA. aaref@mgh.harvard.edu."
] |
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[] | 10.7324 | 4.179516 |
39294295
| 480 |
Efficient combinatorial adaptor-mediated targeting of acute myeloid leukemia with CAR T-cells.
|
CAR T-cell products targeting lineage-specific cell-of-origin antigens, thereby eliminating both tumor and healthy counterpart cells, are currently clinically approved therapeutics in B- and plasma-cell malignancies. While they represent a major clinical improvement, they are still limited in terms of efficacy by e.g. single, sometimes low-expressed antigen targeting, and in terms of safety by e.g., lack of on-off activity. Successful cell-of-origin non-discriminative targeting of heterogeneous hematopoietic stem and progenitor cell malignancies, such as acute myeloid leukemia (AML), will require antigen-versatile targeting and off-switching of effectors in order to then allow rescue by hematopoietic stem cell transplantation (HSCT), preventing permanent myeloablation. To address this, we developed adaptor-CAR (AdFITC-CAR) T-cells targeting fluoresceinated AML antigen-binding diabody adaptors. This platform enables the use of adaptors matching the AML-antigen-expression profile and conditional activity modulation. Combining adaptors significantly improved lysis of AML cells in vitro. In therapeutic xenogeneic mouse models, AdFITC-CAR T-cells co-administered with single diabody adaptors were as efficient as direct CAR T-cells, and combinatorial use of adaptors further enhanced therapeutic efficacy against both, cell lines and primary AML. Collectively, this study provides proof-of-concept that AdFITC-CAR T-cells and combinations of adaptors can efficiently enhance immune-targeting of AML.
|
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] | 2024-09-19 | 63 |
39294295
|
[
"AML cells",
"hematopoietic stem cell transplantation",
"cell lines",
"healthy counterpart cells",
"single diabody adaptors",
"adaptors",
"primary AML",
"heterogeneous hematopoietic stem and progenitor cell malignancies",
"AML antigen-binding diabody adaptors",
"AML",
"CAR T-cell products",
"direct CAR T-cells",
"therapeutic efficacy",
"plasma-cell malignancies",
"therapeutic xenogeneic mouse models",
"AdFITC-CAR T-cells",
"combinatorial use",
"acute myeloid leukemia",
"conditional activity modulation",
"efficacy",
"terms",
"origin",
"permanent myeloablation",
"AdFITC-CAR",
"HSCT",
"concept",
"effectors",
"order",
"myeloid",
"rescue"
] |
[] | 0 |
10.1038/s41375-024-02409-1
|
[
"Volta",
"Myburgh",
"Pellegrino",
"Koch",
"Maurer",
"Manfredi",
"Hofstetter",
"Kaiser",
"Schneiter",
"Müller",
"Buehler",
"De Luca",
"Favalli",
"Magnani",
"Schroeder",
"Neri",
"Manz"
] |
[
"Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.\nDepartment of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.",
"Department of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.",
"Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.\nDepartment of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.",
"Department of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.\nDepartment of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.",
"Department of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.",
"Department of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.",
"Department of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.",
"Department of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.",
"Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.",
"Department of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.",
"Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.",
"Philochem AG, Otelfingen, Switzerland.",
"Philochem AG, Otelfingen, Switzerland.",
"Department of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.\nComprehensive Cancer Center Zurich (CCCZ), Zurich, Switzerland.",
"Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.",
"Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.\nPhilochem AG, Otelfingen, Switzerland.",
"Department of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Zurich, Switzerland. markus.manz@usz.ch.\nComprehensive Cancer Center Zurich (CCCZ), Zurich, Switzerland. markus.manz@usz.ch."
] |
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[] | 7.08539 | 7.053379 |
39292778
| 481 |
Development of an antigen-based approach to noninvasively image CAR T cells in real time and as a predictive tool.
|
CAR T cell therapy has revolutionized the treatment of a spectrum of blood-related malignancies. However, treatment responses vary among cancer types and patients. Accurate monitoring of CAR T cell dynamics is crucial for understanding and evaluating treatment efficacy. Positron emission tomography (PET) offers a comprehensive view of CAR T cell homing, especially in critical organs such as lymphoid structures and bone marrow. This information will help assess treatment response and predict relapse risk. Current PET imaging methods for CAR T require genetic modifications, limiting clinical use. To overcome this, we developed an antigen-based imaging approach enabling whole-body CAR T cell imaging. The probe detects CAR T cells in vivo without affecting their function. In an immunocompetent B cell leukemia model, CAR-PET signal in the spleen predicted early mortality risk. The antigen-based CAR-PET approach allows assessment of CAR T therapy responses without altering established clinical protocols. It seamlessly integrates with FDA-approved and future CAR T cell generations, facilitating broader clinical application.
|
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] | 2024-09-18 | 90 |
39292778
|
[
"CAR T cells",
"CAR T cell therapy",
"CAR T cell dynamics",
"CAR T",
"CAR T therapy responses",
"whole-body CAR T cell imaging",
"treatment response",
"treatment responses",
"Current PET imaging methods",
"treatment efficacy",
"FDA-approved and future CAR T cell generations",
"established clinical protocols",
"broader clinical application",
"PET",
"clinical use",
"an immunocompetent B cell leukemia model",
"early mortality risk",
"lymphoid structures",
"critical organs",
"genetic modifications",
"Positron emission tomography",
"cancer types",
"relapse risk",
"bone marrow",
"Accurate monitoring",
"understanding",
"CAR-PET signal",
"assessment",
"an antigen-based imaging approach",
"vivo"
] |
[] | 0 |
10.1126/sciadv.adn3816
|
[
"Fröse",
"Rowley",
"Farid",
"Rakhshandehroo",
"Leclerc",
"Mak",
"Allen",
"Moravej",
"Munaretto",
"Millan-Barea",
"Codet",
"Glockner",
"Jacobson",
"Hemann",
"Rashidian"
] |
[
"David H. Koch Institute for Integrative Cancer Research, Cambridge, MA 02142, USA.\nDepartment of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.",
"Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.\nHarvard Medical School, Boston, MA 02215, USA.",
"Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.",
"Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.",
"David H. Koch Institute for Integrative Cancer Research, Cambridge, MA 02142, USA.",
"David H. Koch Institute for Integrative Cancer Research, Cambridge, MA 02142, USA.",
"Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.",
"Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.",
"Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.",
"David H. Koch Institute for Integrative Cancer Research, Cambridge, MA 02142, USA.",
"Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.",
"Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.",
"Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.",
"David H. Koch Institute for Integrative Cancer Research, Cambridge, MA 02142, USA.\nDepartment of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.",
"Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.\nHarvard Medical School, Boston, MA 02215, USA.\nDepartment of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.\nParker Institute for Cancer Immunotherapy, San Francisco, CA 94129, USA."
] |
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[] | 7.721539 | 4.718761 |
39290703
| 482 |
Case report: Bridging radiation therapy before chimeric antigen receptor T-cell therapy induces sustained remission in patients with relapsed/refractory double-expressor diffuse large B-cell lymphoma with localized compressive symptoms.
|
High-risk double-expressor diffuse large B-cell lymphoma has an inferior prognosis following standard first-line therapy. After failure of second-line therapy, treatment options are limited if accompanied by localized compressive symptoms. Chimeric Antigen Receptor T cell (CAR-T) therapy preceded by bridging radiotherapy may be an effective emerging therapy.
We report a 66-year-old female patient diagnosed with stage IV double-expressor diffuse large B-cell lymphoma. The patient achieved progressive disease after two cycles of rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, and prednisone and continued to develop cervical lymph node recurrence after second-line therapy. The patient was infused with CAR-T cells after receiving focal bridging radiotherapy and remained in complete response more than 9 months after treatment. In addition, the patients did not experience serious adverse reactions related to radiotherapy as well as CAR-T cell therapy.
In this article, we describe a patient with double-expressor diffuse large B-cell lymphoma with localized compression symptoms after second-line treatment failure who benefited from CAR-T combined with focal bridging radiotherapy.
|
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] | 2024-09-18 | 28 |
39290703
|
[
"Chimeric Antigen Receptor T cell",
"focal bridging radiotherapy",
"bridging radiotherapy",
"radiotherapy",
"localized compression symptoms",
"treatment options",
"cervical lymph node recurrence",
"stage IV double-expressor diffuse large B-cell lymphoma",
"localized compressive symptoms",
"CAR-T cell therapy",
"double-expressor diffuse large B-cell lymphoma",
"serious adverse reactions",
"liposomal doxorubicin",
"treatment",
"second-line treatment failure",
"progressive disease",
"second-line therapy",
"second",
"standard first-line therapy",
"High-risk double-expressor diffuse large B-cell lymphoma",
"complete response",
"CAR-T cells",
"rituximab",
"cyclophosphamide",
"an effective emerging therapy",
"vincristine",
"prednisone",
"failure",
"IV",
"CAR-T"
] |
[
"bridging therapy",
"chimeric antigen receptor T-cell immunotherapy",
"double-expressor diffuse large B-cell lymphoma",
"lymphoma",
"radiotherapy"
] | 0 |
10.3389/fimmu.2024.1441404
10.1002/ajh.26151
10.1038/s41408-023-00970-z
10.1053/j.seminhematol.2023.12.001
10.1016/j.jtct.2023.06.012
10.1182/blood.2022018730
10.1093/annonc/mdy203
10.1002/ajh.27075
10.1016/S0140-6736(20)31366-0
10.1056/NEJMoa1804980
10.1056/NEJMoa1707447
10.1186/s12943-023-01775-1
10.1016/S1470-2045(18)30864-7
10.1056/NEJMoa2116133
10.1038/s41591-022-01731-4
10.1182/bloodadvances.2022009019
10.1111/bjh.17738
10.1136/jitc-2022-004567
10.1016/j.ijrobp.2020.05.014
10.1016/j.radonc.2021.11.031
10.3390/cancers15061747
10.1016/j.ijrobp.2019.02.046
10.3389/fimmu.2022.1033512
10.1038/s42255-022-00537-5
10.1016/j.ijrobp.2018.06.306
10.1016/j.ijrobp.2019.05.065
10.1002/hon.68_2630
10.3324/haematol.2023.282804
10.1038/s41419-023-05829-6
10.1038/s41392-022-01102-y
10.1002/ajh.27409
|
[
"Yang",
"Wu",
"Yang",
"Sun",
"Xing",
"Liu",
"Xing",
"Yu"
] |
[
"Shandong University Cancer Center, Shandong University, Jinan, Shandong, China.\nDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, and Shandong Academy of Medical Sciences, Jinan, Shandong, China.",
"Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, and Shandong Academy of Medical Sciences, Jinan, Shandong, China.\nDepartment of Graduate, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.",
"Department of Graduate, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.\nDepartment of Nuclear Medicine, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.",
"Department of Nuclear Medicine, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.",
"Department of Hematology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.",
"Department of Hematology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.",
"Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, and Shandong Academy of Medical Sciences, Jinan, Shandong, China.",
"Shandong University Cancer Center, Shandong University, Jinan, Shandong, China.\nDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, and Shandong Academy of Medical Sciences, Jinan, Shandong, China."
] |
[
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[] | 6.315331 | 5.508888 |
39289138
| 483 |
CAR T-cell-associated neurotoxicity: A comprehensive review.
|
Chimeric antigen receptor T-cell (CAR T-cell) therapies have emerged as a promising treatment modality for several malignancies, particularly haematological malignancies, by inducing robust antitumour responses. However, CAR T-cell therapies are associated with a spectrum of adverse events, including neurological complications. We here provide a review of neurological adverse events observed in patients undergoing CAR T-cell therapy, focusing on their incidence, clinical manifestations, underlying mechanisms and potential management strategies.
|
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] | 2024-09-18 | 1 |
39289138
|
[
"neurological adverse events",
"adverse events",
"several malignancies",
"CAR T-cell therapies",
"CAR T-cell therapy",
"underlying mechanisms",
"potential management strategies",
"robust antitumour responses",
"neurological complications",
"CAR T-cell",
"patients",
"a promising treatment modality",
"particularly haematological malignancies",
"their incidence, clinical manifestations",
"a spectrum",
"a review",
"We"
] |
[
"Brain",
"CAR T-cell therapy",
"Haematological malignancies",
"Immune effector cell-associated neurotoxicity syndrome (ICANS)",
"Neurotoxicity",
"Toxicity"
] | 0 |
10.1016/j.neurol.2024.07.005
|
[
"Ursu",
"Belin",
"Cuzzubbo",
"Carpentier"
] |
[
"Service de neurologie, hôpital Saint-Louis, AP-HP, 1, avenue Claude-Vellefaux, 75010 Paris, France.",
"Service de neurologie, hôpital Saint-Louis, AP-HP, 1, avenue Claude-Vellefaux, 75010 Paris, France.",
"Service de neurologie, hôpital Saint-Louis, AP-HP, 1, avenue Claude-Vellefaux, 75010 Paris, France; Paris-Diderot, université de Paris, 75010 Paris, France.",
"Service de neurologie, hôpital Saint-Louis, AP-HP, 1, avenue Claude-Vellefaux, 75010 Paris, France; Paris-Diderot, université de Paris, 75010 Paris, France. Electronic address: antoine.carpentier@aphp.fr."
] |
[
"39289138"
] |
[] | 6.275187 | 4.099858 |
39289094
| 484 |
Advancing CAR T-cell therapies: Preclinical insights and clinical translation for hematological malignancies.
|
Chimeric antigen receptor (CAR) T-cell therapy has achieved significant success in achieving durable and potentially curative responses in patients with hematological malignancies. CARs are tailored fusion proteins that direct T cells to a specific antigen on tumor cells thereby eliciting a targeted immune response. The approval of several CD19-targeted CAR T-cell therapies has resulted in a notable surge in clinical trials involving CAR T cell therapies for hematological malignancies. Despite advancements in understanding response mechanisms, resistance patterns, and adverse events associated with CAR T-cell therapy, the translation of these insights into robust clinical efficacy has shown modest outcomes in both clinical trials and real-world scenarios. Therefore, the assessment of CAR T-cell functionality through rigorous preclinical studies plays a pivotal role in refining therapeutic strategies for clinical applications. This review provides an overview of the various in vitro and animal models used to assess the functionality of CAR T-cells. We discuss the findings from preclinical research involving approved CAR T-cell products, along with the implications derived from recent preclinical studies aiming to optimize the functionality of CAR T-cells. The review underscores the importance of robust preclinical evaluations and the need for models that accurately replicate human disease to bridge the gap between preclinical success and clinical efficacy.
|
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] | 2024-09-18 | 1 |
39289094
|
[
"CAR T cell therapies",
"direct T cells",
"tumor cells",
"robust preclinical evaluations",
"robust clinical efficacy",
"recent preclinical studies",
"rigorous preclinical studies",
"preclinical success",
"clinical trials",
"preclinical research",
"CAR T-cell therapy",
"clinical efficacy",
"CAR T-cell functionality",
"approved CAR T-cell products",
"clinical applications",
"CAR T-cells",
"several CD19-targeted CAR T-cell therapies",
"response mechanisms",
"CAR) T-cell therapy",
"significant success",
"Chimeric antigen receptor",
"resistance patterns",
"hematological malignancies",
"models",
"human disease",
"therapeutic strategies",
"adverse events",
"modest outcomes",
"both clinical trials",
"CARs"
] |
[
"CAR T-cells",
"Hematological malignancies",
"Long-term remissions",
"Preclinical studies",
"Predictors of response",
"Translational immunology"
] | 0 |
10.1016/j.blre.2024.101241
|
[
"Arunachalam",
"Grégoire",
"Coutinho de Oliveira",
"Melenhorst"
] |
[
"Cell Therapy & Immuno-Engineering Program, Center for Immunotherapy and Precision Immuno-Oncology, Lerner College of Medicine, Cleveland Clinic, Cleveland, OH 44195, United States of America.",
"Cell Therapy & Immuno-Engineering Program, Center for Immunotherapy and Precision Immuno-Oncology, Lerner College of Medicine, Cleveland Clinic, Cleveland, OH 44195, United States of America.",
"Cell Therapy & Immuno-Engineering Program, Center for Immunotherapy and Precision Immuno-Oncology, Lerner College of Medicine, Cleveland Clinic, Cleveland, OH 44195, United States of America.",
"Cell Therapy & Immuno-Engineering Program, Center for Immunotherapy and Precision Immuno-Oncology, Lerner College of Medicine, Cleveland Clinic, Cleveland, OH 44195, United States of America. Electronic address: melenhj@ccf.org."
] |
[
"39289094"
] |
[] | 7.916535 | 4.445917 |
39286335
| 485 |
Linker-specific monoclonal antibodies present a simple and reliable detection method for scFv-based CAR NK cells.
|
Chimeric antigen receptor (CAR) T cell therapies have demonstrated significant successes in treating cancer. Currently, there are six approved CAR T cell products available on the market that target different malignancies of the B cell lineage. However, to overcome the limitations of CAR T cell therapies, other immune cells are being investigated for CAR-based cell therapies. CAR natural killer (NK) cells can be applied as allogeneic cell therapy, providing an economical, safe, and efficient alternative to autologous CAR T cells. To improve CAR research and future in-patient monitoring of cell therapeutics, a simple, reliable, and versatile CAR detection reagent is crucial. As most existing CARs contain a single-chain variable fragment (scFv) with either a Whitlow or a G4S linker site, linker-specific monoclonal antibodies (mAbs) can detect a broad range of CARs. This study demonstrates that these linker-specific mAbs can detect different CAR NK cells
|
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] | 2024-09-17 | 37 |
39286335
|
[
"different CAR NK cells",
"allogeneic cell therapy",
"cell therapeutics",
"other immune cells",
"CAR research",
"most existing CARs",
"CAR T cell therapies",
"CAR",
"CARs",
"CAR-based cell therapies",
"autologous CAR T cells",
"different malignancies",
"CAR) T cell therapies",
"six approved CAR T cell products",
"the B cell lineage",
"CAR natural killer (NK) cells",
"significant successes",
"mAbs",
"Chimeric antigen receptor",
"linker-specific monoclonal",
"a G4S linker site",
"scFv",
"Whitlow",
"patient",
"these linker-specific mAbs",
"a simple, reliable, and versatile CAR detection reagent",
"cancer",
"a single-chain variable fragment",
"a broad range",
"an economical, safe, and efficient alternative"
] |
[
"CAR NK cells",
"CAR detection methods",
"cell therapy",
"chimeric antigen receptor",
"diagnostics",
"flow cytometry",
"gene therapy",
"scFv",
"single-chain variable fragment"
] | 0 |
10.1016/j.omtm.2024.101328
10.1016/j.pathol.2021.02.002
10.1186/s13046-021-02214-z
10.1634/theoncologist.2019-0233
10.1056/NEJMoa2024850
10.1016/j.ebiom.2020.102975
10.1056/NEJMoa1910607
10.1038/s41568-022-00491-0
10.1038/s41591-023-02785-8
10.1073/pnas.2112006119
10.1182/blood-2017-05-781351
10.1136/jitc-2023-006699
10.1038/s41408-021-00537-w
10.3389/fimmu.2020.01770
10.1371/journal.pone.0057838
10.3389/fimmu.2021.658314
10.1182/bloodadvances.2023009714
10.1016/j.ebiom.2020.102931
10.1093/protein/6.8.989
10.1158/1538-7445.AM2019-1204
10.1038/leu.2017.226
10.1038/s41571-023-00832-4
10.1016/S0140-6736(23)01126-1
10.1038/s41423-020-0488-6
10.3390/cells10113208
10.1093/protein/12.4.357
10.1101/cshperspect.a041251
10.3390/ijms23020903
10.1016/j.slasd.2023.01.008
10.1126/science.1103478
10.1002/cyto.a.20918
10.1007/s40265-016-0540-0
10.3389/fmolb.2022.823174
10.1038/s41408-021-00465-9
10.1016/j.omtm.2020.06.024
10.3389/fimmu.2023.1290488
10.1038/sj.gt.3301253
|
[
"Schindler",
"Ruppel",
"Müller",
"Koehl",
"Fricke",
"Schmiedel"
] |
[
"Department for Cell and Gene Therapy Development, Fraunhofer Institute for Cell Therapy and Immunology (IZI), 04103 Leipzig, Germany.",
"Department for Cell and Gene Therapy Development, Fraunhofer Institute for Cell Therapy and Immunology (IZI), 04103 Leipzig, Germany.",
"Department of Preclinical Development and Validation, Fraunhofer Institute for Cell Therapy and Immunology (IZI), 04103 Leipzig, Germany.\nFraunhofer Cluster of Excellence Immune-Mediated Diseases, 60596 Frankfurt, Germany.",
"Department for Cell and Gene Therapy Development, Fraunhofer Institute for Cell Therapy and Immunology (IZI), 04103 Leipzig, Germany.\nInstitute for Clinical Immunology, University of Leipzig, 04103 Leipzig, Germany.\nFraunhofer Cluster of Excellence Immune-Mediated Diseases, 60596 Frankfurt, Germany.",
"Department for Cell and Gene Therapy Development, Fraunhofer Institute for Cell Therapy and Immunology (IZI), 04103 Leipzig, Germany.\nFraunhofer Cluster of Excellence Immune-Mediated Diseases, 60596 Frankfurt, Germany.\nMedicine Campus MEDiC of the Technical University of Dresden at Klinikum Chemnitz gGmbH, 09116 Chemnitz, Germany.",
"Department for Cell and Gene Therapy Development, Fraunhofer Institute for Cell Therapy and Immunology (IZI), 04103 Leipzig, Germany.\nInstitute for Clinical Immunology, University of Leipzig, 04103 Leipzig, Germany."
] |
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] |
[] | 11.254626 | 5.927213 |
39285441
| 486 |
Proteasome inhibition enhances the anti-leukemic efficacy of chimeric antigen receptor (CAR) expressing NK cells against acute myeloid leukemia.
|
Relapsed and refractory acute myeloid leukemia (AML) carries a dismal prognosis. CAR T cells have shown limited efficacy in AML, partially due to dysfunctional autologous T cells and the extended time for generation of patient specific CAR T cells. Allogeneic NK cell therapy is a promising alternative, but strategies to enhance efficacy and persistence may be necessary. Proteasome inhibitors (PI) induce changes in the surface proteome which may render malignant cells more vulnerable to NK mediated cytotoxicity. Here, we investigated the potential benefit of combining PIs with CAR-expressing allogeneic NK cells against AML.
We established the IC50 concentrations for Bortezomib and Carfilzomib against several AML cell lines. Surface expression of class-I HLA molecules and stress-associated proteins upon treatment with proteasome inhibitors was determined by multiparameter flow cytometry. Using functional in vitro assays, we explored the therapeutic synergy between pre-treatment with PIs and the anti-leukemic efficacy of NK cells with or without expression of AML-specific CAR constructs against AML cell lines and primary patient samples. Also, we investigated the tolerability and efficacy of a single PI application strategy followed by (CAR-) NK cell infusion in two different murine xenograft models of AML.
AML cell lines and primary AML patient samples were susceptible to Bortezomib and Carfilzomib mediated cytotoxicity. Conditioned resistance to Azacitidine/Venetoclax did not confer primary resistance to PIs. Treating AML cells with PIs reduced the surface expression of class-I HLA molecules on AML cells in a time-and-dose dependent manner. Stress-associated proteins were upregulated on the transcriptional level and on the cell surface. NK cell mediated killing of AML cells was enhanced in a synergistic manner. PI pre-treatment increased effector-target cell conjugate formation and Interferon-γ secretion, resulting in enhanced NK cell activity against AML cell lines and primary samples in vitro. Expression of CD33- and CD70-specific CARs further improved the antileukemic efficacy. In vivo, Bortezomib pre-treatment followed by CAR-NK cell infusion reduced AML growth, leading to prolonged overall survival.
PIs enhance the anti-leukemic efficacy of CAR-expressing allogeneic NK cells against AML in vitro and in vivo, warranting further exploration of this combinatorial treatment within early phase clinical trials.
|
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] | 2024-09-17 | 72 |
39285441
|
[
"AML cells",
"AML cell lines",
"NK cell",
"NK cells",
"several AML cell lines",
"NK cell infusion",
"CAR T cells",
"enhanced NK cell activity",
"Allogeneic NK cell therapy",
"patient specific CAR T cells",
"malignant cells",
"dysfunctional autologous T cells",
"primary AML patient samples",
"AML growth",
"AML",
"CAR-expressing allogeneic NK cells",
"Allogeneic NK",
"CAR-NK cell infusion",
"NK mediated cytotoxicity",
"PI pre-treatment increased effector-target cell conjugate formation",
"CAR",
"Surface expression",
"limited efficacy",
"Bortezomib pre",
"AML-specific CAR constructs",
"primary patient samples",
"efficacy",
"primary samples",
"treatment",
"the cell surface"
] |
[] | 0 |
10.1186/s13045-024-01604-y
|
[
"Sedloev",
"Chen",
"Unglaub",
"Schanda",
"Hao",
"Besiridou",
"Neuber",
"Schmitt",
"Raffel",
"Liu",
"Janssen",
"Müller-Tidow",
"Schmitt",
"Sauer"
] |
[
"Department of Medicine V, Hematology, Oncology and Rheumatology, University Hospital Heidelberg, 69120, Heidelberg, Germany.",
"Department of Medicine V, Hematology, Oncology and Rheumatology, University Hospital Heidelberg, 69120, Heidelberg, Germany.",
"Department of Medicine V, Hematology, Oncology and Rheumatology, University Hospital Heidelberg, 69120, Heidelberg, Germany.",
"Department of Medicine V, Hematology, Oncology and Rheumatology, University Hospital Heidelberg, 69120, Heidelberg, Germany.",
"Department of Medicine V, Hematology, Oncology and Rheumatology, University Hospital Heidelberg, 69120, Heidelberg, Germany.",
"Department of Medicine V, Hematology, Oncology and Rheumatology, University Hospital Heidelberg, 69120, Heidelberg, Germany.",
"Department of Medicine V, Hematology, Oncology and Rheumatology, University Hospital Heidelberg, 69120, Heidelberg, Germany.",
"Department of Medicine V, Hematology, Oncology and Rheumatology, University Hospital Heidelberg, 69120, Heidelberg, Germany.",
"Department of Medicine V, Hematology, Oncology and Rheumatology, University Hospital Heidelberg, 69120, Heidelberg, Germany.",
"Department of Medicine V, Hematology, Oncology and Rheumatology, University Hospital Heidelberg, 69120, Heidelberg, Germany.",
"Department of Medicine V, Hematology, Oncology and Rheumatology, University Hospital Heidelberg, 69120, Heidelberg, Germany.",
"Department of Medicine V, Hematology, Oncology and Rheumatology, University Hospital Heidelberg, 69120, Heidelberg, Germany.",
"Department of Medicine V, Hematology, Oncology and Rheumatology, University Hospital Heidelberg, 69120, Heidelberg, Germany.",
"Department of Medicine V, Hematology, Oncology and Rheumatology, University Hospital Heidelberg, 69120, Heidelberg, Germany. tim.sauer@med.uni-heidelberg.de."
] |
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[] | 6.810004 | 7.236089 |
39283669
| 487 |
Peripheral Blood-Derived PD-1/CD28-CD19 CAR-Modified PD-1+ T-Cell Therapy in Patients with Solid Tumors.
|
T cells expressing programmed cell death 1 (PD-1) in the peripheral blood (PB) of patients with tumors possess therapeutic potential; however, the immunosuppressive, PD-1-triggered signaling pathway and limited proliferative capacity of PD-1+ T cells present challenges to their therapeutic application. Here, we observed no discernible distinction between PD-1+ and PD-1- T cells in terms of clonal overlap. However, CD8+PD-1+ T cells from PB and tumor tissues exhibited tighter clustering based on clone size. Single-cell RNA sequencing analysis showed that PD-1+ T cells from PB highly expressed cytotoxicity-related genes and were enriched for T-cell activation-related pathways compared with PD-1- T cells from PB or tumor tissues. Consistent with this, PB-derived PD-1+ T cells exhibited strong cytotoxicity toward autologous tumor cells and tumor cell lines. To augment PD-1+ T-cell activity against solid tumors in vivo, we introduced a PD-1/CD28 fusion receptor combined with a CD19 chimeric antigen receptor into PD-1+ T cells, which were then expanded in vitro. The modified PD-1+ T cells exhibited superior proliferation and antitumor abilities in vitro. In addition, four patients with cancer were infused with autologous PD-1/CD28-CD19 chimeric antigen receptor PD-1+ T cells. None of these patients experienced severe side effects, and one patient with melanoma achieved a complete response that was maintained for 6.7 months. The three other patients had stable disease. Collectively, these results suggested that cell therapy with modified PB-derived PD-1+ T cells is both safe and effective, and it may constitute a promising treatment strategy for patients with cancer.
|
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] | 2024-09-17 | 1 |
39283669
|
[
"PD-1+ T cells",
"T cells",
"autologous tumor cells",
"PD-1- T cells",
"tumor cell lines",
"cell therapy",
"CD8+PD-1+ T cells",
"programmed cell death",
"PB-derived PD-1+ T cells",
"modified PB-derived PD-1+ T cells",
"The modified PD-1+ T cells",
"PD-1+ T-cell activity",
"PD-1",
"patients",
"solid tumors",
"PB",
"tumors",
"Single-cell RNA",
"T-cell activation-related pathways",
"severe side effects",
"therapeutic potential",
"PB and tumor tissues",
"PB or tumor tissues",
"limited proliferative capacity",
"tighter clustering",
"strong cytotoxicity",
"superior proliferation",
"stable disease",
"a PD-1/CD28 fusion receptor",
"clone size"
] |
[] | 0 |
10.1158/2326-6066.CIR-24-0037
|
[
"Zhang",
"Zhao",
"Zhao",
"Chen",
"Li",
"Liu",
"Shen",
"Song",
"Miao",
"Guo",
"Mou",
"Zhao",
"Gu",
"Zhang"
] |
[
"Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.",
"Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.",
"Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.",
"Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.",
"Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.",
"Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.",
"Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.",
"Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.",
"Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.",
"Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.",
"Chineo Medical Technology Co., Ltd., Beijing, China.",
"Chineo Medical Technology Co., Ltd., Beijing, China.",
"Chineo Medical Technology Co., Ltd., Beijing, China.",
"Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.\nState Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, China.\nSchool of Life Sciences, Zhengzhou University, Zhengzhou, China."
] |
[
"39283669"
] |
[] | 9.623018 | 5.83187 |
39283287
| 488 |
Comprehensive characterization of cytopenia after chimeric antigen receptor-T cell infusion in patients with relapsed or refractory multiple myeloma.
|
Many studies have demonstrated the effectiveness of chimeric antigen receptor-T (CAR-T) cell therapy for relapsed or refractory multiple myeloma (RRMM), but the hematologic toxicity has not been well characterized.
A total of 111 adults with RRMM who received BCMA CAR-T cells, BCMA + CD19 CAR-T cells or tandem BCMA/CD19 dual-target (BC19) CAR-T cells infusion were enrolled. We characterized cytopenia and hematologic recovery at different time points after CAR-T-cell therapy, analyzed the effect of cytopenia on prognosis and identified the risk factors.
Patients had a high probability of cytopenia, with anemia, neutropenia and thrombocytopenia occurring in 92%, 95% and 73%, respectively. There were 60 (54%) patients had prolonged hematologic toxicity (PHT) after D28. The median hemoglobin and platelet count were significantly lower at D28 post-CAR-T cell therapy than at baseline. Hemoglobin increased to above baseline at D90. The median absolute neutrophil count was lower than baseline at D0 and D28, and it recovered to baseline at D180. The baseline level of lactate dehydrogenase was associated with thrombocytopenia. Extramedullary involvement was associated with hemoglobin recovery, while the baseline level of albumin and types of CAR-T were related to platelet recovery. Patients with anemia at baseline and at D0, D180 and D360 had shorter progression-free survival (PFS), while anemia at D0, D60, D180 and D360 was associated with shorter overall survival (OS). Neutropenia at D0 was associated with shorter PFS and patients with neutropenia at D90 or D180 had shorter OS. Patients with thrombocytopenia at any time had shorter PFS and OS. Compared to patients without PHT, patients with PHT had shorter PFS and OS.
The majority of RRMM patients treated with CAR-T cells experienced cytopenia. Cytopenia occurred at specific time points was associated with a poorer prognosis.
|
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] | 2024-09-17 | 1 |
39283287
|
[
"RRMM patients",
"shorter PFS",
"shorter overall survival",
"shorter OS",
"different time points",
"specific time points",
"Patients",
"patients",
"D28 post-CAR-T cell therapy",
"hemoglobin recovery",
"BCMA CAR-T cells",
"CD19 CAR-T cells",
"cytopenia",
"D180",
"platelet recovery",
"CAR-T cells",
"D0",
"platelet count",
"baseline",
"RRMM",
"anemia",
"D28",
"hematologic toxicity",
"CAR-T-cell therapy",
"shorter progression-free survival",
"BCMA",
"lactate dehydrogenase",
"cytopenia and hematologic recovery",
"neutropenia",
"Many studies"
] |
[
"chimeric antigen receptor-T cells",
"cytopenia",
"hematologic recovery",
"multiple myeloma"
] | 0 |
10.1016/j.jcyt.2024.08.007
|
[
"Cheng",
"Shao",
"Wang",
"Chen",
"Sun",
"Chen",
"Liu",
"Wang",
"Chen",
"Sang",
"Qi",
"Li",
"Sun",
"Shi",
"Qiao",
"Wu",
"Zeng",
"Zheng",
"Li",
"Xu",
"Cao"
] |
[
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.",
"Cancer Institute, Xuzhou Medical University, Xuzhou, China.",
"Jiangsu Bone Marrow Stem Cell Institute, Xuzhou, China.",
"Jiangsu Bone Marrow Stem Cell Institute, Xuzhou, China.",
"Jiangsu Bone Marrow Stem Cell Institute, Xuzhou, China.",
"Cancer Institute, Xuzhou Medical University, Xuzhou, China.",
"Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China. Electronic address: lily9711214@126.com.",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China. Electronic address: lihmd@163.com.",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China. Electronic address: zimu05067@163.com."
] |
[
"39283287"
] |
[] | 5.265028 | 5.44065 |
39281717
| 489 |
CAR-T in cancer therapeutics and updates.
|
Chimeric antigen receptor (CAR) T-cell therapy has emerged as a groundbreaking approach in cancer treatment, utilizing the immune system's capabilities to combat malignancies. This innovative therapy involves extracting T-cells from a patient's blood, genetically modifying them to target specific cancer cells, and reinfusing them back into the patient's body. The genetically modified T-cells then seek out and eliminate cancer cells, offering a promising therapeutic strategy. Since its initial approval in 2017, CAR-T therapy has witnessed remarkable advancements and updates. Notably, CAR-T therapy, which was initially developed for hematological malignancies, has expanded its scope to target solid tumors. Currently, clinical trials are underway to explore the efficacy of CAR-T therapy in treating various solid tumors, such as lung cancer, breast cancer, and ovarian cancer. These trials hold great potential to revolutionize cancer treatment and provide new hope to patients with challenging-to-treat solid tumors. In this mini-review, we present an overview of CAR-T therapy's mechanisms, emphasizing its role in targeting cancer cells and the potential therapeutic benefits. Additionally, we discuss the recent progress and updates in CAR-T therapy, particularly its application in treating solid tumors, and highlight the ongoing clinical trials aimed at broadening its therapeutic horizon. The evolving landscape of CAR-T therapy signifies a promising direction in cancer therapeutics, with the potential to revolutionize the treatment of both hematological and solid tumor malignancies.
|
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39281717
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10.1182/blood-2010-04-281931
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10.1038/s41408-022-00629-1
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10.1200/JCO.2021.39.15_suppl.2507
10.1038/s41375-021-01253-x
10.1038/bcj.2014.39
10.1172/JCI116534
10.2147/OTT.S205678
10.1182/blood-2022-169928
10.1182/blood.V130.Suppl_1.811.811
10.1182/blood-2022-170201
10.1146/annurev-immunol-032712-095951
10.1038/s41586-019-1410-1
10.3389/fimmu.2018.02940
10.1182/blood-2019-129998
10.1038/s41571-022-00643-z
10.3389/fonc.2020.01000
10.1038/s41586-022-04489-4
10.1056/NEJMoa2210859
10.1182/blood-2006-08-039347
10.1016/j.ccell.2023.03.003
10.3390/cancers12061660
10.1158/0008-5472.CAN-15-0159
10.1016/j.tibtech.2021.12.009
10.1038/s41598-019-46938-7
10.1200/JCO.2023.41.16_suppl.6095
10.1038/nbt.2459
10.1038/s41591-018-0290-5
10.1038/s41586-023-05778-2
10.1007/s11427-016-5024-7
10.1093/nsr/nwab172
10.1038/s41571-019-0297-y
10.1016/S0140-6736(20)32334-5
10.1038/s41591-022-02182-7
10.1038/s41422-022-00721-y
|
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[] | 9.456782 | 4.137388 |
39274330
| 490 |
Use of Eltrombopag to Improve Thrombocytopenia and Tranfusion Requirement in Anti-CD19 CAR-T Cell-Treated Patients.
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39274330
|
[] |
[
"CAR-T",
"adverse events",
"eltrombopag",
"neutropenia",
"pan-cytopenia",
"platelet transfusion",
"red blood cell transfusion",
"thrombocytopenia",
"thrombopoietin receptor agonist"
] | 0 |
10.3390/jcm13175117
10.1056/NEJMp1711886
10.1007/s11912-021-01161-4
10.1016/j.blre.2022.100929
10.3389/fimmu.2023.1285406
10.1136/ard-2024-225638
10.1016/j.bbmt.2018.12.758
10.1182/blood.2023020578
10.1182/blood.2020010543
10.1182/bloodadvances.2020002509
10.1182/bloodadvances.2022008320
10.3324/haematol.2019.238634
10.1186/s12885-021-09102-x
10.1182/blood.2022017415
10.3389/fimmu.2023.1141779
10.3390/jcm12206422
10.1007/s40265-019-01159-0
10.1056/NEJMoa1613878
10.1177/2040620721998126
10.1016/j.bbmt.2019.05.023
10.1182/bloodadvances.2022008066
10.1111/ejh.14141
10.7326/M14-1589
10.1056/NEJMoa1707447
10.1056/NEJMoa1709866
10.1016/j.omtm.2018.11.010
10.1200/JCO.1999.17.4.1244
10.6004/jnccn.2017.0147
10.1016/j.blre.2023.101139
10.1055/a-2250-9369
10.1345/aph.1P042
10.1097/01.HS9.0000847688.01787.13
10.1182/bloodadvances.2021004716
10.1007/s00277-022-04889-6
10.1136/jitc-2021-002721
10.1016/j.jtct.2024.01.074
10.1038/s41591-022-01969-y
10.1016/j.jaci.2020.07.025
10.1038/s41409-019-0487-3
10.1182/blood.2023021305
10.1111/tid.14157
10.1056/NEJMoa2109965
10.1016/j.exphem.2017.09.006
10.1182/blood-2018-11-884486
10.1016/j.thromres.2016.05.008
10.1182/blood-2008-08-175745
10.3390/ijms24098349
10.1182/blood-2012-04-425512
10.1111/ejh.12181
|
[
"Mingot-Castellano",
"Reguera-Ortega",
"Zafra Torres",
"Hernani",
"Lopez-Godino",
"Guerreiro",
"Herrero",
"López-Corral",
"Luna",
"Gonzalez-Pinedo",
"Chinea-Rodriguez",
"Africa-Martín",
"Bailen",
"Martinez-Cibrian",
"Balsalobre",
"Filaferro",
"Alonso-Saladrigues",
"Barba",
"Perez-Martinez",
"Calbacho",
"Perez-Simón",
"Sánchez-Pina",
"On Behalf Of The Spanish Group Of Hematopoietic Transplant And Cell Therapy Geth-Tc"
] |
[
"Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla, IBiS/CSIC, Universidad de Sevilla, 41004 Sevilla, Spain.",
"Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla, IBiS/CSIC, Universidad de Sevilla, 41004 Sevilla, Spain.",
"Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.",
"INCLIVA Health Research Institute, Hospital Clínico Universitario, 46010 Valencia, Spain.",
"Hematology Department, Centro Regional de Hemodonación, IMIB-Pascual Parrilla, Hospital Universitario Morales-Meseguer, 30008 Murcia, Spain.",
"Servicio de Hematología, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain.",
"Hospital Infantil Universitario del Niño Jesús, 28009 Madrid, Spain.",
"IBSAL, CIBERONC, Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), Hospital Universitario de Salamanca (Spain), 37007 Salamanca, Spain.",
"Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain.",
"Hospital Universitario de Gran Canaria Dr. Negrín, 35010 Las Palmas de Gran Canaria, Spain.",
"Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain.",
"IBSAL, CIBERONC, Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), Hospital Universitario de Salamanca (Spain), 37007 Salamanca, Spain.",
"Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, 28009 Madrid, Spain.",
"Hospital Clinic Barcelona, Institut de Recerca Sant Joan de Déu, Barcelona Hospital Sant Joan de Déu, 08950 Barcelona, Spain.",
"University Hospital Vall d'Hebron, 08035 Barcelona, Spain.",
"University Hospital Vall d'Hebron, 08035 Barcelona, Spain.",
"Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, 08950 Barcelona, Spain.",
"Grupo Español de Trasplante Hematopoyético y Terapia Celular, 28040 Madrid, Spain.",
"Pediatric Hematology-Oncology Department, La Paz University Hospital, 28034 Madrid, Spain.\nPediatric Department, Autonomous University of Madrid, 28034 Madrid, Spain.\nCIBERER-ISCIII, IdiPAZ-CNIO Pediatric OncoHematology Clinical Research Unit, 28034 Madrid, Spain.",
"Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.",
"Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla, IBiS/CSIC, Universidad de Sevilla, 41004 Sevilla, Spain.",
"Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.",
null
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[] | 32.980507 | 7.53251 |
|
39273462
| 491 |
The Current Landscape of Secondary Malignancies after CAR T-Cell Therapies: How Could Malignancies Be Prevented?
|
Chimeric antigen receptor (CAR) T-cell therapies have revolutionised the field of haematological malignancies by achieving impressive remission rates in patients with highly refractory haematological malignancies, improving overall survival. To date, six commercial anti-CD19 and anti-BCMA CAR T-cell products have been approved by the Food and Drug Administration (FDA) for the treatment of relapsed/refractory B-cell haematological malignancies and multiple myeloma. The indications for CAR T-cell therapies are gradually expanding, with these therapies being investigated in a variety of diseases, including non-malignant ones. Despite the great success, there are several challenges surrounding CAR T-cell therapies, such as non-durable responses and high-grade toxicities. In addition, a new safety concern was added by the FDA on 28 November 2023 following reports of T-cell malignancies in patients previously treated with either anti-CD19 or anti-BCMA autologous CAR T-cell therapies both in clinical trials and in the real-world setting. Since then, several reports have been published presenting the incidence and analysing the risks of other secondary malignancies after CAR T-cell therapies. In this opinion article, the current landscape of secondary malignancies after CAR T-cell therapies is presented, along with a proposed strategy for future research aiming at potentially diminishing or abrogating the risk of developing secondary malignancies after CAR T-cell therapies.
|
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] | 2024-09-14 | 79 |
39273462
|
[
"haematological malignancies",
"secondary malignancies",
"other secondary malignancies",
"CAR T-cell therapies",
"non-durable responses",
"CD19 or anti-BCMA autologous CAR T-cell therapies",
"non-malignant ones",
"T-cell malignancies",
"six commercial anti-CD19 and anti-BCMA CAR T-cell products",
"several reports",
"relapsed/refractory B-cell haematological malignancies",
"Chimeric antigen receptor (CAR) T-cell therapies",
"highly refractory haematological malignancies",
"several challenges",
"impressive remission rates",
"FDA",
"future research",
"clinical trials",
"patients",
"reports",
"overall survival",
"multiple myeloma",
"these therapies",
"diseases",
"a new safety concern",
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|
[
"Bouziana",
"Bouzianas"
] |
[
"Department of Hematology, King's College Hospital, London SE59RS, UK.",
"BReMeL, Biopharmaceutical and Regenerative Medicine Laboratories, 55534 Thessaloniki, Greece."
] |
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[] | 6.61101 | 4.666247 |
39273050
| 492 |
Pre-Clinical Models for CAR T-Cell Therapy for Glioma.
|
Immunotherapy represents a transformative shift in cancer treatment. Among myriad immune-based approaches, chimeric antigen receptor (CAR) T-cell therapy has shown promising results in treating hematological malignancies. Despite aggressive treatment options, the prognosis for patients with malignant brain tumors remains poor. Research leveraging CAR T-cell therapy for brain tumors has surged in recent years. Pre-clinical models are crucial in evaluating the safety and efficacy of these therapies before they advance to clinical trials. However, current models recapitulate the human tumor environment to varying degrees. Novel in vitro and in vivo techniques offer the opportunity to validate CAR T-cell therapies but also have limitations. By evaluating the strengths and weaknesses of various pre-clinical glioma models, this review aims to provide a roadmap for the development and pre-clinical testing of CAR T-cell therapies for brain tumors.
|
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39273050
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] |
[
"Brain Tumor Immunotherapy Lab, Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.\nFaculty of Medicine, KU Leuven, 3000 Leuven, Belgium.",
"Brain Tumor Immunotherapy Lab, Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.",
"Brain Tumor Immunotherapy Lab, Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.",
"Brain Tumor Immunotherapy Lab, Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.",
"Brain Tumor Immunotherapy Lab, Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.",
"Brain Tumor Immunotherapy Lab, Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.",
"Brain Tumor Immunotherapy Lab, Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.",
"Brain Tumor Immunotherapy Lab, Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.",
"Brain Tumor Immunotherapy Lab, Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.",
"Brain Tumor Immunotherapy Lab, Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.",
"Brain Tumor Immunotherapy Lab, Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA."
] |
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[] | 9.740224 | 7.167469 |
39272927
| 493 |
Mutation in p53 is the most frequent event in cancer development and a leading cause of cancer therapy resistance due to evasion of the apoptosis cascade. Beyond chemotherapies and radiation therapies, growing evidence indicates that p53-mutant tumors are resistant to a broad range of immune-based therapies, such as immune checkpoint inhibitors, chimeric antigen receptor (CAR) T, and hematopoietic stem cell transplantation (HSCT). This highlights the role of p53 mutations in driving immune evasion of tumor cells. In this review, we first summarize recent studies revealing mechanisms by which p53-mutant tumors evade immune surveillance from T cells, natural killer (NK) cells, and macrophages. We then review how these mutant tumor cells reshape the tumor microenvironment (TME), modulating bystander cells such as macrophages, neutrophils, and regulatory T (Treg) cells to foster immunosuppression. Additionally, we review clinical observations indicative of immune evasion associated with p53 loss or mutations. Finally, we discuss therapeutic strategies to enhance immune response in p53 wild-type (WT) or mutant tumors.
|
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] | 2024-09-14 | 97 |
39272927
|
[
"tumor cells",
"immune evasion",
"T cells",
"mutant tumors",
"p53 mutations",
"bystander cells",
"hematopoietic stem cell transplantation",
"immune checkpoint inhibitors",
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"immune response",
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"chimeric antigen receptor",
"evasion",
"cancer development",
"recent studies",
"growing evidence",
"Mutation",
"mutations",
"therapeutic strategies",
"clinical observations",
"macrophages",
"regulatory T (Treg) cells",
"foster immunosuppression",
"immune-based therapies",
"the tumor microenvironment"
] |
[
"immune evasion",
"immunotherapy",
"mouse double minute 2",
"p53",
"p53 mutation"
] | 0 |
10.3390/cancers16173069
10.1002/cac2.12374
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10.1126/science.abc8697
10.3390/ijms17111942
|
[
"Wang",
"Tan",
"Chitkara",
"Bhatt"
] |
[
"Department of Pharmacy & Pharmaceutical Sciences, National University of Singapore, Singapore 117559, Singapore.",
"Department of Pharmacy & Pharmaceutical Sciences, National University of Singapore, Singapore 117559, Singapore.",
"Duke-NUS Medical School, Singapore 169857, Singapore.",
"Department of Pharmacy & Pharmaceutical Sciences, National University of Singapore, Singapore 117559, Singapore."
] |
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[] | 10.837131 | 4.751407 |
|
39272178
| 494 |
In vivo CAR T cell therapy against angioimmunoblastic T cell lymphoma.
|
For angioimmunoblastic T cell lymphoma (AITL), a rare cancer, no specific treatments are available and survival outcome is poor. We previously developed a murine model for AITL that mimics closely human disease and allows to evaluate new treatments. As in human AITL, the murine CD4
To prevent fratricide among CAR T cells when delivering an CD4-specific CAR, we used a lentiviral vector (LV) encoding an anti-CD4 CAR, allowing exclusive entry into CD8 T cells.
These anti-CD4CAR CD8-targeted LVs achieved in murine AITL biopsies high CAR-expression levels in CD8 T cells. Malignant CD4 Tfh cells were eliminated from the mAITL lymphoma, while the CAR + CD8 T cells expanded upon encounter with the CD4 receptor and were shaped into functional cytotoxic cells. Finally, in vivo injection of the CAR + CD8-LVs into our preclinical AITL mouse model carrying lymphomas, significantly prolonged mice survival. Moreover, the in vivo generated functional CAR + CD8 T cells efficiently reduced neoplastic T cell numbers in the mAITL tumors.
This is the first description of in vivo generated CAR T cells for therapy of a T cell lymphoma. The strategy described offers a new therapeutic concept for patients suffering from CD4-driven T cell lymphomas.
|
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] | 2024-09-14 | 65 |
39272178
|
[
"CAR T cells",
"CD8 T cells",
"generated CAR T cells",
"angioimmunoblastic T cell lymphoma",
"Malignant CD4 Tfh cells",
"neoplastic T cell numbers",
"functional cytotoxic cells",
"CAR",
"human AITL",
"AITL",
"CD4-driven T cell lymphomas",
"new treatments",
"a T cell lymphoma",
"murine AITL biopsies high CAR-expression levels",
"an anti-CD4 CAR",
"survival outcome",
"our preclinical AITL mouse model",
"These anti-CD4CAR CD8-targeted LVs",
"exclusive entry",
"mAITL",
"an CD4-specific CAR",
"the CAR + CD8 T cells",
"vivo",
"vivo injection",
"the CD4 receptor",
"a new therapeutic concept",
"patients",
"+ CD8-LVs",
"LV",
"significantly prolonged mice survival"
] |
[
"AITL",
"CAR T",
"CD8-targeted virus envelope",
"Cancer therapy",
"In vivo gene therapy",
"Lentiviral vector",
"Preclinical model",
"Pseudotyping",
"T cell lymphoma"
] | 0 |
10.1186/s13046-024-03179-5
10.1097/MD.0b013e3181573059
10.3324/haematol.2015.126300
10.1182/blood-2007-08-105759
10.1016/0002-9343(75)90466-0
10.1200/JCO.2008.16.4558
10.1200/JCO.2016.71.2083
10.1097/DAD.0000000000000144
10.1182/blood-2016-09-692541
10.1038/s41388-023-02699-2
10.1016/j.ccell.2018.01.001
10.1182/blood-2017-11-818617
10.1016/j.ccell.2023.01.003
10.1038/s41389-020-00259-x
10.1016/j.ccell.2019.07.008
10.1182/blood-2006-10-055145
10.1186/s13046-024-02952-w
10.1038/s41591-022-01765-8
10.1038/s41586-023-06243-w
10.1097/PPO.0000000000000636
10.1007/s11060-019-03311-y
10.1038/s41591-018-0201-9
10.1182/blood-2014-02-558163
10.1371/journal.ppat.1005641
10.1016/j.ymthe.2022.05.018
10.1038/gt.2013.23
10.1038/mt.2008.128
10.1038/s41596-021-00510-8
10.1371/journal.pone.0079047
10.1182/bloodadvances.2020002229
10.1038/nmeth.1514
10.1182/blood-2012-02-412973
10.4049/jimmunol.1500956
10.1038/mt.2010.298
10.1016/j.omtm.2021.09.014
10.1016/j.ymthe.2020.05.005
10.1016/j.omtm.2019.03.003
10.3390/cancers14102392
10.1016/j.jtct.2023.10.013
10.1038/leu.2015.311
10.3389/fimmu.2022.997482
10.1182/blood.V99.7.2342
10.1172/JCI92026
10.1016/j.immuni.2015.01.017
10.1084/jem.20141432
10.1182/blood-2005-07-2955
10.1016/j.immuni.2018.06.012
10.1038/ni.1877
10.3892/ol.2014.2356
10.1038/nature24649
10.1182/blood.2019002038
10.1016/j.clml.2019.03.022
10.1200/JCO.2015.65.9789
10.3324/haematol.2013.084913
10.3389/fimmu.2020.626820
10.1111/j.1365-2141.2009.07606.x
10.4049/jimmunol.164.12.6213
10.3389/fphar.2015.00095
10.7150/jca.28952
10.3390/cancers12071915
10.1016/j.bcp.2019.113711
10.1016/j.omtm.2022.06.004
|
[
"Krug",
"Saidane",
"Martinello",
"Fusil",
"Michels",
"Buchholz",
"Ricci",
"Verhoeyen"
] |
[
"Université Côte d'Azur, INSERM, C3M, 06204, Nice, France.\nEquipe Labellisée Ligue Contre Le Cancer, 06204, Nice, France.",
"Université Côte d'Azur, INSERM, C3M, 06204, Nice, France.\nEquipe Labellisée Ligue Contre Le Cancer, 06204, Nice, France.",
"Université Côte d'Azur, INSERM, C3M, 06204, Nice, France.",
"CIRI - International Center for Infectiology Research, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Lyon, F-69007, Lyon, France.",
"Molecular Biotechnology and Gene Therapy, Paul-Ehrlich-Institut, 63225, Langen, Germany.",
"Molecular Biotechnology and Gene Therapy, Paul-Ehrlich-Institut, 63225, Langen, Germany.\nFrankfurt-Cancer-Institute (FCI), Goethe-University, Frankfurt, Germany.",
"Université Côte d'Azur, INSERM, C3M, 06204, Nice, France.\nEquipe Labellisée Ligue Contre Le Cancer, 06204, Nice, France.",
"Université Côte d'Azur, INSERM, C3M, 06204, Nice, France. els.verhoeyen@unice.fr.\nEquipe Labellisée Ligue Contre Le Cancer, 06204, Nice, France. els.verhoeyen@unice.fr.\nCIRI - International Center for Infectiology Research, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Lyon, F-69007, Lyon, France. els.verhoeyen@unice.fr."
] |
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[] | 6.981794 | 7.080266 |
39272132
| 495 |
18F-FDG PET/CT metrics-based stratification of large B-cell lymphoma receiving CAR-T cell therapy: immunosuppressive tumor microenvironment as a negative prognostic indicator in patients with high tumor burden.
|
Chimeric antigen receptor T (CAR-T) cell therapy has greatly improved the prognosis of relapsed and refractory patients with large B-cell lymphoma (LBCL). Early identification and intervention of patients who may respond poorly to CAR-T cell therapy will help to improve the efficacy. Ninety patients from a Chinese cohort who received CAR-T cell therapy and underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scans at the screening stage (median time to infusion 53.5 days, range 27-176 days), 1 month and 3 months after CAR-T cell infusion were analyzed, with RNA-sequencing conducted on 47 patients at the screening stage. Patients with maximum diameter of the largest lesion (Dmax) < 6 cm (N = 60) at screening stage showed significantly higher 3-month complete response rate (85.0% vs. 33.3%, P < 0.001), progression-free survival (HR 0.17; 95% CI 0.08-0.35, P < 0.001) and overall survival (HR 0.18; 95% CI 0.08-0.40, P < 0.001) than those with Dmax ≥ 6 cm (N = 30). Besides, at the screening stage, Dmax combined with extranodal involvement was more efficient in distinguishing patient outcomes. The best cut-off values for total metabolic tumor volume (tMTV) and total lesion glycolysis (tTLG) at the screening stage were 50cm
|
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] | 2024-09-14 | 11 |
39272132
|
[
"patient outcomes",
"Patients",
"patients",
"screening stage",
"total lesion glycolysis",
"total metabolic tumor volume",
"CAR-T cell therapy",
"Dmax",
"CAR-T cell infusion",
"large B-cell lymphoma",
"overall survival",
"extranodal involvement",
"median time",
"P",
"relapsed and refractory patients",
"HR",
"the screening stage",
"CI",
"maximum diameter",
"N",
"Early identification",
"18F-fluorodeoxyglucose positron emission tomography/computed tomography",
"tMTV",
"18F",
"CAR-T",
"RNA",
"tTLG",
"intervention",
"the largest lesion",
"47 patients"
] |
[
"18F-FDG PET/CT",
"CAR-T cell therapy",
"Large B-cell lymphoma",
"Microenvironment"
] | 0 |
10.1186/s40364-024-00650-5
10.1186/s13045-024-01540-x
10.1097/RLU.0000000000003756
10.1186/s13045-022-01256-w
10.1038/s41408-023-00895-7
10.1002/hon.3231
10.1016/j.bbmt.2019.02.008
10.1182/blood.2023021002
10.1007/s11684-022-0972-8
|
[
"Sheng",
"Shen",
"Yan",
"Wang",
"Zheng",
"Zhang",
"Yang",
"Wu",
"Xu",
"Cheng",
"Bachy",
"Sesques",
"Jacquet-Francillon",
"Jiang",
"Zhao",
"Wang"
] |
[
"Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.",
"Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.",
"Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.",
"Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.",
"Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.",
"Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.",
"Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.",
"Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.",
"Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.",
"Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.",
"Department of Haematology, Hospices Civils de Lyon, Lyon, France.",
"Department of Haematology, Hospices Civils de Lyon, Lyon, France.",
"Department of Nuclear Medicine, Hospices Civils de Lyon, Lyon, France.",
"Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.",
"Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. zhao.weili@yahoo.com.",
"Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. wl11194@rjh.com.cn."
] |
[
"39272132",
"36821768",
"38649972",
"38467921",
"34115706",
"35346315",
"37591834",
"37795759",
"30769193",
"38211334",
"37060525"
] |
[] | 6.175362 | 5.336115 |
39269445
| 496 |
PTPRZ1-Targeting RNA CAR T Cells Exert Antigen-Specific and Bystander Antitumor Activity in Glioblastoma.
|
The great success of chimeric antigen receptor (CAR) T-cell therapy in the treatment of patients with B-cell malignancies has prompted its translation to solid tumors. In the case of glioblastoma (GBM), clinical trials have shown modest efficacy, but efforts to develop more effective anti-GBM CAR T cells are ongoing. In this study, we selected protein tyrosine phosphatase receptor type Z (PTPRZ1) as a target for GBM treatment. We isolated six anti-human PTPRZ1 single-chain variable fragments from a human phage display library and produced second-generation CAR T cells in an RNA format. Patient-derived GBM PTPRZ1-knockin cell lines were used to select the CAR construct that showed high cytotoxicity while consistently displaying high CAR expression (471_28z). CAR T cells incorporating 471_28z were able to release IFNγ, IL2, TNFα, granzyme B, IL17A, IL6, and soluble FasL and displayed low tonic signaling. Additionally, they maintained an effector memory phenotype after in vitro killing. In addition, 471_28z CAR T cells displayed strong bystander killing against PTPRZ1-negative cell lines after preactivation by PTPRZ1-positive tumor cells but did not kill antigen-negative nontumor cells. In an orthotopic xenograft tumor model using NOD/SCIDγ mice, a single dose of anti-PTPRZ1 CAR T cells significantly delayed tumor growth. Taken together, these results validate PTPRZ1 as a GBM target and prompt the clinical translation of anti-PTPRZ1 CAR T cells.
|
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] | 2024-09-13 | 1 |
39269445
|
[
"CAR T cells",
"anti-PTPRZ1 CAR T cells",
"more effective anti-GBM CAR T cells",
"anti-PTPRZ1",
"high CAR expression",
"CAR",
"second-generation CAR T cells",
"471_28z CAR T cells",
"PTPRZ1",
"PTPRZ1-positive tumor cells",
"PTPRZ1-negative cell lines",
"chimeric antigen receptor",
"protein tyrosine phosphatase receptor type Z",
"GBM treatment",
"solid tumors",
"antigen-negative nontumor cells",
"tumor growth",
"Patient-derived GBM PTPRZ1-knockin cell lines",
"GBM",
"clinical trials",
"six anti-human PTPRZ1 single-chain variable fragments",
"B-cell malignancies",
"granzyme B",
"soluble FasL",
"modest efficacy",
"high cytotoxicity",
"low tonic",
"CAR) T-cell therapy",
"the CAR construct",
"PTPRZ1-negative"
] |
[] | 0 |
10.1158/2326-6066.CIR-23-1094
|
[
"Martinez Bedoya",
"Marinari",
"Davanture",
"Castillo Cantero",
"Erraiss",
"Dockerill",
"Barluenga",
"Winssinger",
"Schaller",
"Bijlenga",
"Momjian",
"Voize",
"Tissot",
"Kandalaft",
"Hammel",
"Cosson",
"Walker",
"Dutoit",
"Migliorini"
] |
[
"Brain Tumor and Immune Cell Engineering Laboratory, Agora Cancer Research Center, Lausanne, Switzerland.\nSwiss Cancer Center Léman (SCCL), Lausanne, Switzerland.\nCenter for Translational Research in Onco-Hematology, University of Geneva, Geneva, Switzerland.",
"Brain Tumor and Immune Cell Engineering Laboratory, Agora Cancer Research Center, Lausanne, Switzerland.\nSwiss Cancer Center Léman (SCCL), Lausanne, Switzerland.\nCenter for Translational Research in Onco-Hematology, University of Geneva, Geneva, Switzerland.",
"Brain Tumor and Immune Cell Engineering Laboratory, Agora Cancer Research Center, Lausanne, Switzerland.\nSwiss Cancer Center Léman (SCCL), Lausanne, Switzerland.\nCenter for Translational Research in Onco-Hematology, University of Geneva, Geneva, Switzerland.",
"Brain Tumor and Immune Cell Engineering Laboratory, Agora Cancer Research Center, Lausanne, Switzerland.\nSwiss Cancer Center Léman (SCCL), Lausanne, Switzerland.\nCenter for Translational Research in Onco-Hematology, University of Geneva, Geneva, Switzerland.",
"Brain Tumor and Immune Cell Engineering Laboratory, Agora Cancer Research Center, Lausanne, Switzerland.\nSwiss Cancer Center Léman (SCCL), Lausanne, Switzerland.\nCenter for Translational Research in Onco-Hematology, University of Geneva, Geneva, Switzerland.",
"Department of Organic Chemistry, NCCR Chemical Biology, Faculty of Science, University of Geneva, Geneva, Switzerland.",
"Department of Organic Chemistry, NCCR Chemical Biology, Faculty of Science, University of Geneva, Geneva, Switzerland.",
"Department of Organic Chemistry, NCCR Chemical Biology, Faculty of Science, University of Geneva, Geneva, Switzerland.",
"Division of Neurosurgery, Department of Clinical Neurosciences, Geneva University Hospital, Geneva, Switzerland.",
"Division of Neurosurgery, Department of Clinical Neurosciences, Geneva University Hospital, Geneva, Switzerland.",
"Division of Neurosurgery, Department of Clinical Neurosciences, Geneva University Hospital, Geneva, Switzerland.",
"Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.\nCenter of Experimental Therapeutics, Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.\nLudwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland.",
"Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.\nCenter of Experimental Therapeutics, Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.\nLudwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland.",
"Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.\nCenter of Experimental Therapeutics, Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.\nLudwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland.",
"Geneva Antibody Facility, Faculty of Medicine, University of Geneva, Geneva, Switzerland.",
"Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland.",
"Brain Tumor and Immune Cell Engineering Laboratory, Agora Cancer Research Center, Lausanne, Switzerland.\nSwiss Cancer Center Léman (SCCL), Lausanne, Switzerland.\nCenter for Translational Research in Onco-Hematology, University of Geneva, Geneva, Switzerland.",
"Brain Tumor and Immune Cell Engineering Laboratory, Agora Cancer Research Center, Lausanne, Switzerland.\nSwiss Cancer Center Léman (SCCL), Lausanne, Switzerland.\nCenter for Translational Research in Onco-Hematology, University of Geneva, Geneva, Switzerland.",
"Brain Tumor and Immune Cell Engineering Laboratory, Agora Cancer Research Center, Lausanne, Switzerland.\nSwiss Cancer Center Léman (SCCL), Lausanne, Switzerland.\nCenter for Translational Research in Onco-Hematology, University of Geneva, Geneva, Switzerland.\nDepartment of Oncology, Geneva University Hospital, Geneva, Switzerland."
] |
[
"39269445"
] |
[] | 10.014798 | 7.267088 |
39269432
| 497 |
Efficient Capture and Traceless Release of Functional CD8
|
The chimeric antigen receptor (CAR) T cells targeting CD4 expressed cells in acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML) could reduce the risk of off target effects in normal tissues. However, the efficacy of adoptive cell therapy is predominantly attributed to CD8
|
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] | 2024-09-13 | 1 |
39269432
|
[
"adoptive cell therapy",
"acute lymphoblastic leukemia",
"acute myeloid leukemia",
"cells",
"off target effects",
"normal tissues",
"CAR) T cells",
"CAR",
"AML",
"myeloid",
"CD4",
"CD8",
"The chimeric antigen receptor",
"T-ALL",
"the risk",
"(AML",
"the efficacy"
] |
[] | 0 |
10.1021/acs.analchem.4c03135
|
[
"Abdulla",
"Abudureheman",
"Chen",
"Ghalandari",
"Yan",
"Zhou",
"Su",
"Zhang",
"Duan",
"Ding"
] |
[
"Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200092, China.\nState Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.",
"Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.",
"Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.",
"State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.",
"Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200092, China.",
"Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.",
"Department of Neurosurgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092, China.",
"Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200092, China.",
"Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.",
"Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200092, China.\nState Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China."
] |
[
"39269432"
] |
[] | 6.948949 | 6.60338 |
39268892
| 498 |
Logistical challenges of CAR T-cell therapy in non-Hodgkin lymphoma: a survey of healthcare professionals.
|
Chimeric antigen receptor T-cell (CAR T) therapy is a new treatment for patients with non-Hodgkin lymphoma that have not responded to other types of treatment. CAR T therapy uses a person's own immune cells (T cells), which are modified in a laboratory to attack cancer cells. While CAR T therapy has the potential to be effective, there are challenges associated with the treatment process. In this study, we surveyed 133 healthcare professionals (HCPs) in the United States and United Kingdom to understand their experiences with logistical challenges involved in navigating the CAR T process. More than 60% of participants identified two or more logistical challenges at every stage of the CAR T treatment process. The most commonly reported challenges included long waiting periods, limited room at hospitals, availability of caregivers to support patients and issues related to out-of-pocket costs, travel and lodging for patients who are treated at specialized centers. In the United States, challenges related to insurance coverage and out-of-pocket costs for patients were highlighted. More than half of HCPs reported that patients' cancer getting worse while waiting to receive CAR T was a reason why patients may not proceed to treatment. While operational improvements might address some challenges in the CAR T treatment process, these findings highlight the need for more convenient, readily available and easily administered therapies for patients with non-Hodgkin lymphoma.
|
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] | 2024-09-13 | 21 |
39268892
|
[
"CAR T therapy",
"T cells",
"logistical challenges",
"CAR T",
"patients",
"challenges",
"non-Hodgkin lymphoma",
"cancer cells",
"non-Hodgkin",
"treatment",
"the CAR T treatment process",
"therapies",
"CAR",
"United Kingdom",
"long waiting periods",
"the CAR T process",
"limited room",
"insurance coverage",
"patients cancer",
"pocket",
"Chimeric antigen receptor T-cell (CAR T) therapy",
"other types",
"the treatment process",
"specialized centers",
"operational improvements",
"HCPs",
"hospitals",
"availability",
"two or more logistical challenges",
"caregivers"
] |
[
"CAR T cell therapy",
"access to care",
"clinical decision-making",
"logistical challenges",
"non-Hodgkin lymphoma"
] | 0 |
10.1080/14796694.2024.2393566
10.1056/NEJMoa1804980
10.1038/s41591-021-01622-0
10.1056/NEJMoa1707447
10.1016/S1470-2045(21)00591-X
10.1016/S0140-6736(20)31366-0
10.1056/NEJMoa1914347
10.3892/mco.2020.2103
10.1200/EDBK_397912
10.37765/ajmc.2021.88737
10.21037/atm-20-5546
10.1007/s12325-021-01839-y
10.12927/hcpol.2021.26430
10.1016/j.jval.2022.04.989
10.2217/imt-2020-0118
10.1191/1478088706qp063oa
10.2217/fon-2021-0160
10.1002/pon.5674
10.1001/jamanetworkopen.2020.2072
10.1200/OP.22.00315
10.1002/ajh.27155
10.1182/bloodadvances.2022009019
|
[
"Sureda",
"Adam",
"Yang",
"Griffin",
"Baker",
"Johnston",
"Navarro",
"Alhasani",
"Chhibber",
"Wang",
"Mutebi"
] |
[
"Institut Català d'Oncologia, Hospital Duran i Reynals, IDIBELL, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.",
"Broadstreet HEOR, Vancouver, BC, Canada.",
"Genmab US, Inc., Plainsboro, NJ, USA.",
"Broadstreet HEOR, Vancouver, BC, Canada.",
"Broadstreet HEOR, Vancouver, BC, Canada.",
"Broadstreet HEOR, Vancouver, BC, Canada.",
"Genmab US, Inc., Plainsboro, NJ, USA.",
"Genmab US, Inc., Plainsboro, NJ, USA.",
"Genmab US, Inc., Plainsboro, NJ, USA.",
"Abbvie Inc., North Chicago, IL, USA.",
"Genmab US, Inc., Plainsboro, NJ, USA."
] |
[
"39268892",
"35579590",
"30501490",
"34921238",
"29226797",
"34895487",
"32888407",
"32242358",
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"37433102",
"34407361",
"34277836",
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] |
[] | 7.197243 | 4.363303 |
39266530
| 499 |
Bispecific antibodies in the treatment of multiple myeloma.
|
The treatment paradigm in myeloma is constantly changing. Upfront use of monoclonal antibodies like daratumumab along with proteasome inhibitors (PI)s, and immune modulators (IMiD)s have significantly improved survival and outcomes, but also cause unique challenges at the time of relapse. Engaging immune T cells for tumour cell kill with chimeric antigenic T-cell (CAR T-cell) therapy and bispecific antibodies have become important therapeutic options in relapsed multiple myeloma. Bispecific antibodies are dual antigen targeting constructs that engage the T cells to plasma cells through various target antigens like B-cell membrane antigen (BCMA), G-protein-coupled receptor family C group 5 member D (GPRC5D), and Fc receptor-homolog 5 (FcRH5). These agents have proven to induce deep and durable responses in heavily pre-treated myeloma patients with a predictable safety profile and the ease of off-the-shelf availability. Significant research is ongoing to overcome resistance mechanisms like T cell exhaustion, target antigen mutation or loss and high disease burden. Various trials are also studying these agents as first line options in the newly diagnosed setting. These agents play an important role in the relapsed setting, and efforts are underway to optimize their sequencing in the myeloma treatment algorithm.
|
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39266530
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[
"Engaging immune T cells",
"T cell exhaustion",
"plasma cells",
"tumour cell kill",
"target antigen mutation",
"various target antigens",
"important therapeutic options",
"dual antigen",
"relapsed multiple myeloma",
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"unique challenges",
"the T cells",
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"resistance mechanisms",
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"Upfront use",
"the myeloma treatment algorithm",
"outcomes",
"Fc",
"GPRC5D",
"daratumumab",
"G-protein-coupled receptor family C group 5 member D",
"IMiD)s"
] |
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|
[
"Devasia",
"Chari",
"Lancman"
] |
[
"Princess Margaret Cancer Centre, Toronto, ON, Canada.",
"University of California, San Francisco, San Francisco, CA, USA.",
"Princess Margaret Cancer Centre, Toronto, ON, Canada. Guido.lancman@uhn.ca."
] |
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] |
[] | 4.927389 | 6.345455 |
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