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

IF 6.1 2区 医学 Q1 ENGINEERING, BIOMEDICAL
Tiffany Hood, Pierre Springuel, Fern Slingsby, Viktor Sandner, Winfried Geis, Timo Schmidberger, Nicola Bevan, Quentin Vicard, Julia Hengst, Noushin Dianat, Qasim A. Rafiq
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引用次数: 0

Abstract

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 × 106 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.
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来源期刊
Bioengineering & Translational Medicine
Bioengineering & Translational Medicine Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
8.40
自引率
4.10%
发文量
150
审稿时长
12 weeks
期刊介绍: Bioengineering & Translational Medicine, an official, peer-reviewed online open-access journal of the American Institute of Chemical Engineers (AIChE) and the Society for Biological Engineering (SBE), focuses on how chemical and biological engineering approaches drive innovative technologies and solutions that impact clinical practice and commercial healthcare products.
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