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

• Published in: Cytotherapy (Oxford, England)
• Main Authors: Chen, Sixun, Prabhu, Akshaya V., Bin Abdul Rahim, Ahmad Amirul, Lee, Kang-Zheng, Liu, Dan
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 05.10.2024
• Subjects: biomanufacturing; bioreactor; cell therapy; central memory T cells; immunotherapy; memory T cells; biomanufacturing; central memory T cells; bioreactor; cell therapy; memory T cells; immunotherapy
• ISSN: 1465-3249; 1477-2566; 1477-2566
• DOI: 10.1016/j.jcyt.2024.10.001

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: 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. 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. [Display omitted]