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CAR 装配线:将 CAR-T 细胞生产提升至新水平

英文原题:CAR assembly line: Taking CAR T-cell manufacturing to the next level.

查看英文原题

CAR assembly line: Taking CAR T-cell manufacturing to the next level.

PubMed 2024/12/06(内容时间) Best Pract Res Clin Haematol Q2 · IF 3.4(JCR 2025)

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中文摘要

嵌合抗原受体(CAR)T细胞疗法的广泛采用受到复杂、资源密集型生产流程的限制。本综述讨论了旨在改进和简化CAR-T 细胞生产的最新创新,涵盖T细胞激活、基因修饰、扩增和规模化等关键步骤。重点介绍的有前景的技术包括:从未激活的淋巴细胞生成CAR-T 细胞以保留干细胞样表型和功能,利用转座子和CRISPR等平台进行非病毒基因转移,像CliniMACS Prodigy和Lonza Cocoon这样的一体化全自动生物反应器,通过缩短或消除体外T细胞培养实现CAR-T 细胞快速生产,实施去中心化的即时检测自动化生产平台,以及优化整合端到端自动化的集中式生物反应器基础设施。采用这些新兴技术可以降低生产成本和缩短时间线,同时提高产品质量和可及性。然而,关于将许多新兴技术有效纳入广泛临床实践的可行性、优越性和最佳方案,仍存在显著的知识空白。其中许多新方法仍需通过临床研究进一步验证。

展开英文摘要原文

The widespread adoption of chimeric antigen receptor (CAR) T-cell therapy has been limited by complex, resource-intensive manufacturing processes. This review discusses the latest innovations aiming to improve and streamline CAR T-cell production across key steps like T-cell activation, genetic modification, expansion, and scaling.

Promising techniques highlighted include generating CAR T cells from non-activated lymphocytes to retain a stem-like phenotype and function, non-viral gene transfer leveraging platforms like transposon and CRISPR, all-in-one fully automated bioreactors like the CliniMACS Prodigy and the Lonza Cocoon, rapid CAR T-cell manufacturing via abbreviating or eliminating ex vivo T-cell culture, implementing decentralized point-of-care automated manufacturing platforms, and optimizing centralized bioreactor infrastructure integrating end-to-end automation.

Adoption of these emerging technologies can reduce production costs and timelines while enhancing product quality and accessibility.

However, significant knowledge gaps persist regarding the feasibility, superiority, and optimal protocols for effectively incorporating many emerging techniques into widespread clinical practice.

Further validation through clinical studies is still needed for many of these novel approaches.

论文信息

作者
Wang J、Caimi PF
单位
Department of Hematology/Oncology, University Hospitals Seidman Cancer Center, Cleveland, OH, USA. Electronic address: jxw1170@case.edu.United States
文献类型
综述
期刊
Best practice & research. Clinical haematology2024 Dec
原文标识
PubMed 40074509 · DOI 10.1016/j.beha.2024.101595