Enriching central memory T cells using novel bioreactor design for T cell manufacturing

IF 3.7 3区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Cytotherapy Pub Date : 2025-01-01 DOI:10.1016/j.jcyt.2024.10.001

Sixun Chen, Akshaya V. Prabhu, Ahmad Amirul Bin Abdul Rahim, Kang-Zheng Lee, Dan Liu

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引用次数: 0

Abstract

Background

The manufacturing of T cell therapies aims to achieve high yields of product with potent phenotypes. We have developed a novel bioreactor, bioreactor with expandable culture area—dual chamber (BECA-D), which has previously demonstrated functionality for scaled T cell manufacturing.

Methods and Results

Methods and Results: In this study, incorporation of a stirring mechanism into the double-chamber bioreactor design was tested to homogenize the media components between the two chambers. In addition to the improved media homogenization, the stirring culture was observed to have higher yield and enrichment of central memory T cells, a T cell subpopulation that has been associated with improved therapeutic efficacy compared with a static control. BECA-D with a stirring mechanism was evaluated for its performance in culturing T cells in comparison with a static control, BECA-D, and an industry benchmark, G-Rex10 (Wilson Wolf Manufacturing). BECA-D with a stirring mechanism was able to preferentially promote the enrichment of central memory T cells compared with the static cultures, indicative of the effect of the stirring mechanism.

Conclusion

By achieving high T cell yields with a favorable subpopulation profile, the mechanical method of incorporating stirring into a double-chamber bioreactor such as BECA-D carries great potential as a useful research and manufacturing tool to support advanced T-cell therapy manufacturing.

查看原文本刊更多论文

利用新型生物反应器设计制造 T 细胞，丰富中枢记忆 T 细胞。

背景：制造 T 细胞疗法的目的是获得具有强效表型的高产量产品。我们开发了一种新型生物反应器--带可扩展培养区-双室（BECA-D）的生物反应器，该生物反应器先前已证明具有规模化制造 T 细胞的功能：方法与结果：方法与结果：在这项研究中，对双室生物反应器设计中的搅拌机制进行了测试，以均匀两个室之间的培养基成分。与静态对照组相比，除了提高培养基均质化效果外，还观察到搅拌培养具有更高的中心记忆 T 细胞产量和富集度，而中心记忆 T 细胞是一种与提高疗效相关的 T 细胞亚群。与静态对照 BECA-D 和行业基准 G-Rex10（Wilson Wolf Manufacturing 公司）相比，我们对带有搅拌机制的 BECA-D 培养 T 细胞的性能进行了评估。与静态培养相比，带有搅拌机制的 BECA-D 能够优先促进中枢记忆 T 细胞的富集，这表明了搅拌机制的作用：通过实现具有良好亚群特征的高 T 细胞产量，在双室生物反应器（如 BECA-D）中加入搅拌的机械方法极有可能成为支持先进 T 细胞疗法制造的有用研究和制造工具。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cytotherapy 医学-生物工程与应用微生物

CiteScore

6.30

自引率

4.40%

发文量

683

审稿时长

49 days

期刊介绍： The journal brings readers the latest developments in the fast moving field of cellular therapy in man. This includes cell therapy for cancer, immune disorders, inherited diseases, tissue repair and regenerative medicine. The journal covers the science, translational development and treatment with variety of cell types including hematopoietic stem cells, immune cells (dendritic cells, NK, cells, T cells, antigen presenting cells) mesenchymal stromal cells, adipose cells, nerve, muscle, vascular and endothelial cells, and induced pluripotential stem cells. We also welcome manuscripts on subcellular derivatives such as exosomes. A specific focus is on translational research that brings cell therapy to the clinic. Cytotherapy publishes original papers, reviews, position papers editorials, commentaries and letters to the editor. We welcome "Protocols in Cytotherapy" bringing standard operating procedure for production specific cell types for clinical use within the reach of the readership.