A guide to manufacturing CAR T cell therapies

• Published in: Current opinion in biotechnology Vol. 53; pp. 164 - 181
• Main Authors: Vormittag, Philipp, Gunn, Rebecca, Ghorashian, Sara, Veraitch, Farlan S
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2018
• Subjects: antigens; chimerism; clinical trials; Clinical Trials as Topic; Genetic Therapy; Guidelines as Topic; Humans; Immunotherapy, Adoptive; manufacturing; patients; processing technology; Quality Control; Receptors, Chimeric Antigen - metabolism; T-lymphocytes; therapeutics
• ISSN: 0958-1669; 1879-0429; 1879-0429
• DOI: 10.1016/j.copbio.2018.01.025

[Display omitted] •CAR T cell clinical trial manufacturing data is investigated.•Three dominant process routes are uncovered.•The trend in CAR T cell manufacturing is towards automation.•Tailored off-the-shelf equipment for CAR T cell manufacturing is required. In recent years, chimeric antigen receptor (CAR) modified T cells have been used as a treatment for haematological malignancies in several phase I and II trials and with Kymriah of Novartis and Yescarta of KITE Pharma, the first CAR T cell therapy products have been approved. Promising clinical outcomes have yet been tempered by the fact that many therapies may be prohibitively expensive to manufacture. The process is not yet defined, far from being standardised and often requires extensive manual handling steps. For academia, big pharma and contract manufacturers it is difficult to obtain an overview over the process strategies and their respective advantages and disadvantages. This review details current production processes being used for CAR T cells with a particular focus on efficacy, reproducibility, manufacturing costs and release testing. By undertaking a systematic analysis of the manufacture of CAR T cells from reported clinical trial data to date, we have been able to quantify recent trends and track the uptake of new process technology. Delivering new processing options will be key to the success of the CAR-T cells ensuring that excessive manufacturing costs do not disrupt the delivery of exciting new therapies to the wide possible patient cohort.