Establishing a scalable perfusion strategy for the manufacture of CAR-T cells in stirred-tank bioreactors using a quality-by-design approach.

• Tác giả: Nicola Bevan, Noushin Dianat, Winfried Geis, Julia Hengst, Tiffany Hood, Qasim A Rafiq, Viktor Sandner, Timo Schmidberger, Fern Slingsby, Pierre Springuel, Quentin Vicard
• Ngôn ngữ: eng
• Ký hiệu phân loại: 657.8333 Accounting for enterprises engaged in specific kinds of activities
• Thông tin xuất bản: United States : Bioengineering & translational medicine , 2025
• Bộ sưu tập: NCBI
• ID: 748493

Tóm tắt

 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