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CAR T Cells and T-Cell Therapies for Cancer: A Translational Science Review.

作者信息

Brudno Jennifer N, Maus Marcela V, Hinrichs Christian S

机构信息

Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Department of Medicine, Massachusetts General Hospital Cancer Center, Boston.

出版信息

JAMA. 2024 Dec 10;332(22):1924-1935. doi: 10.1001/jama.2024.19462.


DOI:10.1001/jama.2024.19462
PMID:39495525
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11808657/
Abstract

IMPORTANCE: Chimeric antigen receptor (CAR) T cells are T lymphocytes that are genetically engineered to express a synthetic receptor that recognizes a tumor cell surface antigen and causes the T cell to kill the tumor cell. CAR T treatments improve overall survival for patients with large B-cell lymphoma and progression-free survival for patients with multiple myeloma. OBSERVATIONS: Six CAR T-cell products are approved by the US Food and Drug Administration (FDA) for 6 hematologic malignancies: B-cell acute lymphoblastic leukemia, large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia, and multiple myeloma. Compared with standard chemotherapy followed by stem cell transplant, CAR T cells improved 4-year overall survival in patients with large B-cell lymphoma (54.6% vs 46.0%). Patients with pediatric acute lymphoblastic leukemia achieved durable remission after CAR T-cell therapy. At 3-year follow-up, 48% of patients were alive and relapse free. In people with multiple myeloma treated previously with 1 to 4 types of non-CAR T-cell therapy, CAR T-cell therapy prolonged treatment-free remissions compared with standard treatments (in 1 trial, CAR T-cell therapy was associated with progression-free survival of 13.3 months compared with 4.4 months with standard therapy). CAR T-cell therapy is associated with reversible acute toxicities, such as cytokine release syndrome in approximately 40% to 95% of patients, and neurologic disorders in approximately 15% to 65%. New CAR T-cell therapies in development aim to increase efficacy, decrease adverse effects, and treat other types of cancer. No CAR T-cell therapies are FDA approved for solid tumors, but recently, 2 other T lymphocyte-based treatments gained approvals: 1 for melanoma and 1 for synovial cell sarcoma. Additional cellular therapies have attained responses for certain solid tumors, including pediatric neuroblastoma, synovial cell sarcoma, melanoma, and human papillomavirus-associated cancers. A common adverse effect occurring with these T lymphocyte-based therapies is capillary leak syndrome, which is characterized by fluid retention, pulmonary edema, and kidney dysfunction. CONCLUSIONS AND RELEVANCE: CAR T-cell therapy is an FDA-approved therapy that has improved progression-free survival for multiple myeloma, improved overall survival for large B-cell lymphoma, and attained high rates of cancer remission for other hematologic malignancies such as acute lymphoblastic leukemia, follicular lymphoma, and mantle cell lymphoma. Recently approved T lymphocyte-based therapies demonstrated the potential for improved outcomes in solid tumor malignancies.

摘要

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CAR T Cells and T-Cell Therapies for Cancer: A Translational Science Review.

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本文引用的文献

[1]
Siltuximab for chimeric antigen receptor T-cell therapy-related CRS and ICANS: a multicenter retrospective analysis.

Blood Adv. 2025-1-14

[2]
Secondary primary malignancies after CD-19 directed CAR-T-cell therapy in lymphomas: A report from the Italian CART-SIE study.

Br J Haematol. 2024-10

[3]
Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial final results.

Nat Med. 2024-8

[4]
Lisocabtagene maraleucel in follicular lymphoma: the phase 2 TRANSCEND FL study.

Nat Med. 2024-8

[5]
Phase 1 study of CAR-37 T cells in patients with relapsed or refractory CD37+ lymphoid malignancies.

Blood. 2024-9-12

[6]
Current understanding and management of CAR T cell-associated toxicities.

Nat Rev Clin Oncol. 2024-7

[7]
Long-term remission and survival in patients with relapsed or refractory multiple myeloma after treatment with LCAR-B38M CAR T cells: 5-year follow-up of the LEGEND-2 trial.

J Hematol Oncol. 2024-4-24

[8]
Afamitresgene autoleucel for advanced synovial sarcoma and myxoid round cell liposarcoma (SPEARHEAD-1): an international, open-label, phase 2 trial.

Lancet. 2024-4-13

[9]
Intraventricular CARv3-TEAM-E T Cells in Recurrent Glioblastoma.

N Engl J Med. 2024-4-11

[10]
Features and Factors Associated With Myeloid Neoplasms After Chimeric Antigen Receptor T-Cell Therapy.

JAMA Oncol. 2024-4-1

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