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嵌合抗原受体免疫细胞疗法的研究进展。

Advances in manufacturing chimeric antigen receptor immune cell therapies.

机构信息

Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, USA.

Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA.

出版信息

Semin Immunopathol. 2024 Aug 16;46(5):12. doi: 10.1007/s00281-024-01019-4.


DOI:10.1007/s00281-024-01019-4
PMID:39150566
Abstract

Biomedical research has witnessed significant strides in manufacturing chimeric antigen receptor T cell (CAR-T) therapies, marking a transformative era in cellular immunotherapy. Nevertheless, existing manufacturing methods for autologous cell therapies still pose several challenges related to cost, immune cell source, safety risks, and scalability. These challenges have motivated recent efforts to optimize process development and manufacturing for cell therapies using automated closed-system bioreactors and models created using artificial intelligence. Simultaneously, non-viral gene transfer methods like mRNA, CRISPR genome editing, and transposons are being applied to engineer T cells and other immune cells like macrophages and natural killer cells. Alternative sources of primary immune cells and stem cells are being developed to generate universal, allogeneic therapies, signaling a shift away from the current autologous paradigm. These multifaceted innovations in manufacturing underscore a collective effort to propel this therapeutic approach toward broader clinical adoption and improved patient outcomes in the evolving landscape of cancer treatment. Here, we review current CAR immune cell manufacturing strategies and highlight recent advancements in cell therapy scale-up, automation, process development, and engineering.

摘要

生物医药研究在制造嵌合抗原受体 T 细胞(CAR-T)疗法方面取得了重大进展,标志着细胞免疫治疗进入了一个变革的时代。然而,现有的自体细胞疗法制造方法仍然存在成本、免疫细胞来源、安全风险和可扩展性等方面的挑战。这些挑战促使人们最近努力优化使用自动化封闭系统生物反应器和人工智能创建的模型进行细胞疗法的工艺开发和制造。同时,正在应用非病毒基因转移方法,如 mRNA、CRISPR 基因组编辑和转座子,来工程化 T 细胞和其他免疫细胞,如巨噬细胞和自然杀伤细胞。正在开发替代的原代免疫细胞和干细胞来源,以产生通用的同种异体疗法,这标志着从当前的自体范式转变。这些多方面的制造创新突显了人们共同努力,推动这一治疗方法在癌症治疗的不断发展的格局中更广泛地临床应用和改善患者的治疗效果。在这里,我们回顾了当前的 CAR 免疫细胞制造策略,并强调了细胞疗法放大、自动化、工艺开发和工程方面的最新进展。

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Advances in manufacturing chimeric antigen receptor immune cell therapies.

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引用本文的文献

[1]
The Evolving Treatment Landscape for the Elderly Multiple Myeloma Patient: From Quad Regimens to T-Cell Engagers and CAR-T.

Cancers (Basel). 2025-8-5

[2]
Engineered immune cell therapies for solid tumors: pharmacological advances, clinical outcomes, and future directions.

Front Pharmacol. 2025-6-12

[3]
Trogocytosis in CAR immune cell therapy: a key mechanism of tumor immune escape.

Cell Commun Signal. 2024-10-28

本文引用的文献

[1]
CAR-T cell manufacturing: Major process parameters and next-generation strategies.

J Exp Med. 2024-2-5

[2]
Unanswered questions following reports of secondary malignancies after CAR-T cell therapy.

Nat Med. 2024-2

[3]
Early predictive factors of failure in autologous CAR T-cell manufacturing and/or efficacy in hematologic malignancies.

Blood Adv. 2024-1-23

[4]
Lipid nanoparticles outperform electroporation in mRNA-based CAR T cell engineering.

Mol Ther Methods Clin Dev. 2023-10-18

[5]
Expanding access to CAR T cell therapies through local manufacturing.

Nat Biotechnol. 2023-12

[6]
Automated production of gene-modified chimeric antigen receptor T cells using the Cocoon Platform.

Cytotherapy. 2023-12

[7]
Current approaches to develop "off-the-shelf" chimeric antigen receptor (CAR)-T cells for cancer treatment: a systematic review.

Exp Hematol Oncol. 2023-8-21

[8]
Prediction of lymphoma response to CAR T cells by deep learning-based image analysis.

PLoS One. 2023

[9]
Harnessing the potential of CAR-T cell therapy: progress, challenges, and future directions in hematological and solid tumor treatments.

J Transl Med. 2023-7-7

[10]
The role of automation in meeting the growing demand for CAR T-cell therapies.

Am J Manag Care. 2023-6

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