CAR assembly line: Taking CAR T-cell manufacturing to the next level

Abstract

The widespread adoption of chimeric antigen receptor (CAR) T-cell therapy has been limited by complex, resource-intensive manufacturing processes. This review discusses the latest innovations aiming to improve and streamline CAR T-cell production across key steps like T-cell activation, genetic modification, expansion, and scaling. Promising techniques highlighted include generating CAR T cells from non-activated lymphocytes to retain a stem-like phenotype and function, non-viral gene transfer leveraging platforms like transposon and CRISPR, all-in-one fully automated bioreactors like the CliniMACS Prodigy and the Lonza Cocoon, rapid CAR T-cell manufacturing via abbreviating or eliminating ex vivo T-cell culture, implementing decentralized point-of-care automated manufacturing platforms, and optimizing centralized bioreactor infrastructure integrating end-to-end automation. Adoption of these emerging technologies can reduce production costs and timelines while enhancing product quality and accessibility. However, significant knowledge gaps persist regarding the feasibility, superiority, and optimal protocols for effectively incorporating many emerging techniques into widespread clinical practice. Further validation through clinical studies is still needed for many of these novel approaches.