采用质量源于设计方法建立搅拌罐生物反应器中 CAR-T 细胞生产的可规模化灌流策略

Chimeric antigen receptor T cell (CAR-T) therapies show high remission rates for relapsed and refractory leukemia and lymphoma.

However, manufacturing challenges hinder their commercial viability and patient accessibility.

This study applied quality-by-design principles to identify perfusion critical process parameters for CAR-T expansion in stirred tank bioreactors to maximize yields. A design of experiments in the Ambr 250 High Throughput Perfusion small-scale bioreactor revealed that earlier perfusion starts (48 h vs. 96 h post-inoculation) and higher perfusion rates (1.

0 VVD vs. 0. 25 VVD) significantly increased cytotoxic CAR-T cell yields without compromising critical quality attributes. Optimizing perfusion improved growth kinetics and yields across donor samples, achieving densities >21 10 6 cells/mL in 7 days, outperforming traditional fed-batch and static flask cultures.

This study underscores the importance of optimizing perfusion parameters to maximize CAR-T yields and quality and highlights the utility of scale-down models in reducing time, costs and risks associated with process development.