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封闭生物反应器中 NK 与 CAR-NK 扩增的可规模化工艺开发

英文原题:Scalable process development of NK and CAR-NK expansion in a closed bioreactor.

查看英文原题

Scalable process development of NK and CAR-NK expansion in a closed bioreactor.

PubMed 2024/07/24(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

生产大量功能性NK和CAR-NK细胞是NK免疫治疗的瓶颈之一。在本研究中,我们利用依赖透气膜技术的G-Rex 100M生物反应器,开发了一种大规模、可靠且可行的NK和CAR-NK生产方法。该系统可容纳大量培养基并增强氧气输送,为癌症治疗所需的大规模PBNK和CAR-NK扩增创造了有利条件。在这些生物反应器中扩增的外周血NK细胞(PBNKs)和CAR-NK细胞保留了相似的免疫表型,并对肝细胞癌(HCC)细胞表现出与在G-Rex 6孔生物反应器中扩增的NK和CAR-NK细胞相当的细胞毒性。重要的是,冷冻保存对使用G-Rex 100M生物反应器扩增的NK细胞的细胞毒性影响极小,建立了一个稳健的NK和CAR-NK细胞规模化生产平台。该方法有望推动“现货型”NK细胞的开发,支持NK细胞免疫治疗未来的临床实施。

展开英文摘要原文

Production of large amounts of functional NK and CAR-NK cells represents one of the bottlenecks for NK-based immunotherapy. In this study, we developed a large-scale, reliable, and practicable NK and CAR-NK production using G-Rex 100M bioreactors, which depend on a gas-permeable membrane technology.

This system holds large volumes of medium with enhanced oxygen delivery, creating conditions conducive to large-scale PBNK and CAR-NK expansions for cancer therapy. Both peripheral blood NK cells (PBNKs) and CAR-NKs expanded in these bioreactors retained similar immunophenotypes and exhibited comparable cytotoxicity towards hepatocellular carcinoma (HCC) cells akin to that of NK and CAR-NK cells expanded in G-Rex 6 well bioreactors.

Importantly, cryopreservation minimally affected the cytotoxicity of NK cells expanded using the G-Rex 100M bioreactors, establishing a robust platform for scaled-up NK and CAR-NK cell production. This method is promising for the development of "off-the-shelf" NK cells, supporting the future clinical implementation of NK cell immunotherapy.

论文信息

作者
Wang X、Byrne ME、Liu C、Ma MT、Liu D
单位
Department of Pathology, Immunology and Laboratory Medicine, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, NJ, United States.United States
文献类型
美国 NIH 资助研究 · 非美国政府资助研究
期刊
Frontiers in immunology2024
原文标识
PubMed 39114666 · DOI 10.3389/fimmu.2024.1412378