Manufacturing of CAR-T Cells: The Assembly Line

The recent approval of five chimeric antigen receptor (CAR)-T cell products by the US food and drug administration (FDA) in the context of hematological malignancies has generated the impetus to broaden CAR-T cell therapy applications, resulting in growing production demand. Successful CAR-T cell manufacturing is not only the foundation of these promising therapies, but the choice of manufacturing platform and technology also contributes to defining the CAR-T cell product phenotype, therapeutic efficacy, potential toxicities, and affects the cost of goods. Although multiple methodologies and cell manufacturing platforms have become available, the core components of autologous CAR-T cell manufacturing such as source material collection, T cell isolation, activation, genetic modification, expansion, end of process formulation and cryopreservation remain constant. Current methodologies and cell manufacturing platforms are highlighted in the context of recent clinical trials. Quality requirement and quality control assays enabling the release of clinical CAR-T cell products for infusion are also underscored. The broadening of the scope of CAR-T cell applications beyond cancer therapies is also touched upon as this novel therapeutic paradigm is still evolving.