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在封闭生物反应器中进行NK和CAR-NK扩增的可扩展工艺开发。

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

作者信息

Wang Xuening, Byrne Maeve Elizabeth, Liu Chang, Ma Minh Tuyet, Liu Dongfang

机构信息

Department of Pathology, Immunology and Laboratory Medicine, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, NJ, United States.

Center for Immunity and Inflammation, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, NJ, United States.

出版信息

Front Immunol. 2024 Jul 24;15:1412378. doi: 10.3389/fimmu.2024.1412378. eCollection 2024.

DOI:10.3389/fimmu.2024.1412378
PMID:39114666
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11303211/
Abstract

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.

摘要

大量生产功能性自然杀伤细胞（NK细胞）和嵌合抗原受体自然杀伤细胞（CAR-NK细胞）是基于NK细胞的免疫疗法的瓶颈之一。在本研究中，我们利用G-Rex 100M生物反应器开发了一种大规模、可靠且可行的NK细胞和CAR-NK细胞生产方法，该生物反应器依赖于透气膜技术。该系统可容纳大量培养基，并增强了氧气供应，为大规模扩增用于癌症治疗的外周血NK细胞（PBNK细胞）和CAR-NK细胞创造了有利条件。在这些生物反应器中扩增的外周血NK细胞（PBNK细胞）和CAR-NK细胞均保留了相似的免疫表型，并且对肝癌（HCC）细胞表现出与在G-Rex 6孔生物反应器中扩增的NK细胞和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，从而建立了一个强大的平台用于扩大NK细胞和CAR-NK细胞的生产规模。这种方法对于开发“现货”NK细胞很有前景，为NK细胞免疫疗法的未来临床应用提供了支持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a48/11303211/2c1028d2e30b/fimmu-15-1412378-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a48/11303211/b756652fcdd8/fimmu-15-1412378-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a48/11303211/d35139a28180/fimmu-15-1412378-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a48/11303211/12637bd15fd5/fimmu-15-1412378-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a48/11303211/3e86783cf4e4/fimmu-15-1412378-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a48/11303211/89d811cb23c3/fimmu-15-1412378-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a48/11303211/ac9c56f65911/fimmu-15-1412378-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a48/11303211/650c8cdd3c3f/fimmu-15-1412378-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a48/11303211/2c1028d2e30b/fimmu-15-1412378-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a48/11303211/b756652fcdd8/fimmu-15-1412378-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a48/11303211/d35139a28180/fimmu-15-1412378-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a48/11303211/12637bd15fd5/fimmu-15-1412378-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a48/11303211/3e86783cf4e4/fimmu-15-1412378-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a48/11303211/89d811cb23c3/fimmu-15-1412378-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a48/11303211/ac9c56f65911/fimmu-15-1412378-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a48/11303211/650c8cdd3c3f/fimmu-15-1412378-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a48/11303211/2c1028d2e30b/fimmu-15-1412378-g008.jpg

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