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用于癌症免疫疗法的 CAR T 细胞的可扩展制造。

Scalable Manufacturing of CAR T cells for Cancer Immunotherapy.

机构信息

Division of Medical Oncology, Department of Medicine, and Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.

Joint USC/CHLA Cell Therapy Program, University of Southern California, and Children's Hospital Los Angeles, Los Angeles, California.

出版信息

Blood Cancer Discov. 2021 Sep;2(5):408-422. doi: 10.1158/2643-3230.BCD-21-0084. Epub 2021 Aug 3.


DOI:10.1158/2643-3230.BCD-21-0084
PMID:34568831
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8462122/
Abstract

UNLABELLED: As of April 2021, there are five commercially available chimeric antigen receptor (CAR) T cell therapies for hematological malignancies. With the current transition of CAR T cell manufacturing from academia to industry, there is a shift toward Good Manufacturing Practice (GMP)-compliant closed and automated systems to ensure reproducibility and to meet the increased demand for cancer patients. In this review we describe current CAR T cells clinical manufacturing models and discuss emerging technological advances that embrace scaling and production optimization. We summarize measures being used to shorten CAR T-cell manufacturing times and highlight regulatory challenges to scaling production for clinical use. STATEMENT OF SIGNIFICANCE ∣: As the demand for CAR T cell cancer therapy increases, several closed and automated production platforms are being deployed, and others are in development.This review provides a critical appraisal of these technologies that can be leveraged to scale and optimize the production of next generation CAR T cells.

摘要

未加标签:截至 2021 年 4 月,已有五种用于血液系统恶性肿瘤的商业上可获得的嵌合抗原受体(CAR)T 细胞疗法。随着 CAR T 细胞制造从学术界向工业界的当前转变,正在向符合良好生产规范(GMP)的封闭和自动化系统转移,以确保重现性并满足癌症患者需求的增加。在这篇综述中,我们描述了当前的 CAR T 细胞临床制造模型,并讨论了采用规模化和生产优化的新兴技术进步。我们总结了用于缩短 CAR T 细胞制造时间的措施,并强调了规模化生产用于临床应用的监管挑战。

意义声明:随着对 CAR T 细胞癌症疗法的需求增加,正在部署几种封闭和自动化生产平台,还有其他平台正在开发中。本综述对这些可用于规模化和优化下一代 CAR T 细胞生产的技术进行了批判性评估。

相似文献

[1]
Scalable Manufacturing of CAR T cells for Cancer Immunotherapy.

Blood Cancer Discov. 2021-9

[2]
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[3]
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[4]
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[5]
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[6]
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[8]
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[9]
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[10]
[CAR T cells as drugs for novel therapies (advanced therapy medicinal products)].

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引用本文的文献

[1]
Clinical trials of nanoparticle-enhanced CAR-T and NK cell therapies in oncology: overcoming translational and clinical challenges - a mini review.

Front Med (Lausanne). 2025-8-6

[2]
Emerging Strategies for Targeting Angiogenesis and the Tumor Microenvironment in Gastrointestinal Malignancies: A Comprehensive Review.

Pharmaceuticals (Basel). 2025-8-5

[3]
Cryopreserved leukapheresis enables scalable and distributed CAR-T manufacturing: a multi-platform comparative study.

Sci Rep. 2025-8-14

[4]
Optimizing T cell transduction: a novel transduction device for efficient and scalable gene delivery.

J Transl Med. 2025-8-12

[5]
Emerging CAR immunotherapies: broadening therapeutic horizons beyond cancer.

Clin Exp Med. 2025-8-4

[6]
Advances in Gene Therapy with Oncolytic Viruses and CAR-T Cells and Therapy-Related Groups.

Curr Issues Mol Biol. 2025-4-10

[7]
An Optimized Method for Single Cell Cloning of Human CAR-T Cells Based on FBS-Coated Plates.

Adv Pharm Bull. 2024-12-26

[8]
CAR-T cell therapy in brain malignancies: obstacles in the face of cellular trafficking and persistence.

Front Immunol. 2025-6-19

[9]
The Design of a Multistage Monitoring Protocol for Dendritic Cell-Derived Exosome (DEX) Immunotherapy: A Conceptual Framework for Molecular Quality Control and Immune Profiling.

Int J Mol Sci. 2025-6-6

[10]
Optimising and adapting perfusion feeds in serum-free medium to intensify CAR-T cell expansion in stirred-tank bioreactors.

Front Bioeng Biotechnol. 2025-6-2

本文引用的文献

[1]
Development of CAR T-cell lymphoma in 2 of 10 patients effectively treated with piggyBac-modified CD19 CAR T cells.

Blood. 2021-10-21

[2]
Investigation of product-derived lymphoma following infusion of piggyBac-modified CD19 chimeric antigen receptor T cells.

Blood. 2021-10-21

[3]
Transient rest restores functionality in exhausted CAR-T cells through epigenetic remodeling.

Science. 2021-4-2

[4]
Standards efforts and landscape for rapid microbial testing methodologies in regenerative medicine.

Cytotherapy. 2021-5

[5]
Enriching leukapheresis improves T cell activation and transduction efficiency during CAR T processing.

Mol Ther Methods Clin Dev. 2021-2-6

[6]
Immunogenicity of CAR T cells in cancer therapy.

Nat Rev Clin Oncol. 2021-6

[7]
Comparative analysis of assays to measure CAR T-cell-mediated cytotoxicity.

Nat Protoc. 2021-3

[8]
Automated generation of gene-edited CAR T cells at clinical scale.

Mol Ther Methods Clin Dev. 2020-12-25

[9]
CD22-directed CAR T-cell therapy induces complete remissions in CD19-directed CAR-refractory large B-cell lymphoma.

Blood. 2021-4-29

[10]
The Challenge of Variability in Chimeric Antigen Receptor T cell Manufacturing.

Regen Eng Transl Med. 2020-9

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