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临床试验中的嵌合抗原受体 T 细胞:用于临床应用的修饰 T 细胞生产方面的最新成果和挑战。

CAR T Cells in Trials: Recent Achievements and Challenges that Remain in the Production of Modified T Cells for Clinical Applications.

机构信息

1 Institute of Cellular Therapeutics , Hannover Medical School, Hannover, Germany.

2 Institute of Clinical Immunology, University Hospital Leipzig , Leipzig, Germany.

出版信息

Hum Gene Ther. 2018 May;29(5):559-568. doi: 10.1089/hum.2017.254. Epub 2018 Apr 5.


DOI:10.1089/hum.2017.254
PMID:29620951
Abstract

The adoptive transfer of chimeric antigen receptor (CAR)-modified T cells is attracting growing interest for the treatment of malignant diseases. Early trials with anti-CD19 CAR T cells have achieved spectacular remissions in B-cell leukemia and lymphoma, so far refractory, very recently resulting in the Food and Drug Administration approval of CD19 CAR T cells for therapy. With further applications and increasing numbers of patients, the reproducible manufacture of high-quality clinical-grade CAR T cells is becoming an ever greater challenge. New processing techniques, quality-control mechanisms, and logistic developments are required to meet both medical needs and regulatory restrictions. This paper summarizes the state-of-the-art in manufacturing CAR T cells and the current challenges that need to be overcome to implement this type of cell therapy in the treatment of a variety of malignant diseases and in a greater number of patients.

摘要

嵌合抗原受体 (CAR)-修饰 T 细胞的过继转移在恶性疾病的治疗方面引起了越来越多的关注。早期使用抗 CD19 CAR T 细胞的试验在 B 细胞白血病和淋巴瘤方面取得了显著的缓解效果,这些疾病以前是无法治愈的,最近甚至导致食品和药物管理局批准 CD19 CAR T 细胞用于治疗。随着进一步的应用和越来越多的患者,可重复生产高质量临床级 CAR T 细胞正成为一个越来越大的挑战。需要新的加工技术、质量控制机制和物流发展,以满足医疗需求和监管限制。本文总结了制造 CAR T 细胞的最新技术进展,以及在将这种细胞疗法应用于治疗多种恶性疾病和更多患者方面需要克服的当前挑战。

相似文献

[1]
CAR T Cells in Trials: Recent Achievements and Challenges that Remain in the Production of Modified T Cells for Clinical Applications.

Hum Gene Ther. 2018-4-5

[2]
Current State of CAR T-Cell Therapy in Chronic Lymphocytic Leukemia.

Int J Mol Sci. 2021-5-24

[3]
Anti-CD19 CAR T-Cell Therapy for B-Cell Non-Hodgkin Lymphoma.

Transfus Med Rev. 2020-1

[4]
CAR T Cell Therapy in Acute Lymphoblastic Leukemia and Potential for Chronic Lymphocytic Leukemia.

Curr Treat Options Oncol. 2016-6

[5]
A Syngeneic Mouse B-Cell Lymphoma Model for Pre-Clinical Evaluation of CD19 CAR T Cells.

J Vis Exp. 2018-10-16

[6]
Chimeric antigen receptor T-cell therapy for the treatment of aggressive B-cell non-Hodgkin lymphomas: efficacy, toxicity, and comparative chimeric antigen receptor products.

Expert Opin Biol Ther. 2019-7-25

[7]
The severe cytokine release syndrome in phase I trials of CD19-CAR-T cell therapy: a systematic review.

Ann Hematol. 2018-5-15

[8]
Efficiency of CD19 chimeric antigen receptor-modified T cells for treatment of B cell malignancies in phase I clinical trials: a meta-analysis.

Oncotarget. 2015-10-20

[9]
Chimeric antigen receptor T cells for acute lymphoblastic leukemia.

Am J Hematol. 2019-3-22

[10]
Chimeric Antigen Receptor (CAR) T Cells: Lessons Learned from Targeting of CD19 in B-Cell Malignancies.

Drugs. 2017-3

引用本文的文献

[1]
Surveying local CAR T-cell manufacturing processes to facilitate standardization and expand accessibility.

J Transl Med. 2025-5-6

[2]
Turning "trashed" genomic loci into treasurable sites for integrating chimeric antigen receptors in T and NK cells.

Mol Ther. 2025-4-2

[3]
A self-activated and protective module enhances the preclinical performance of allogeneic anti-CD70 CAR-T cells.

Front Immunol. 2025-1-17

[4]
CAR-T cell therapy: developments, challenges and expanded applications from cancer to autoimmunity.

Front Immunol. 2025-1-9

[5]
The advent of chimeric antigen receptor T Cell therapy in recalibrating immune balance for rheumatic autoimmune disease treatment.

Front Pharmacol. 2024-12-12

[6]
A preclinical study of allogeneic CD19 chimeric antigen receptor double-negative T cells as an off-the-shelf immunotherapy drug against B-cell malignancies.

Clin Transl Immunology. 2024-12-24

[7]
CAR-engineered NK cells versus CAR T cells in treatment of glioblastoma; strength and flaws.

J Neurooncol. 2025-2

[8]
Allogeneic CAR-T cells for cancer immunotherapy.

Immunotherapy. 2024

[9]
Recent updates on allogeneic CAR-T cells in hematological malignancies.

Cancer Cell Int. 2024-9-3

[10]
Advances in manufacturing chimeric antigen receptor immune cell therapies.

Semin Immunopathol. 2024-8-16

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