CAR-T cell manufacturing landscape—Lessons from the past decade and considerations for early clinical development

Abstract

CAR-T cell therapies have consolidated their position over the last decade as an effective alternative to conventional chemotherapies for the treatment of a number of haematological malignancies. With an exponential increase in the number of commercial therapies and hundreds of Phase 1 trials exploring CAR-T cell efficacy in different settings (including autoimmunity and solid tumours), demand for manufacturing capabilities in recent years has considerably increased. In this review, we explore the current landscape of CAR-T cell manufacturing and discuss some of the challenges limiting production capacity worldwide. We describe the latest technical developments in GMP production platform design to facilitate the delivery of a range of increasing complex CAR-T cell products, and the challenges associated with translation of new scientific developments into clinical products for patients. We explore all aspects of the manufacture process, namely early development, manufacturing technology, quality control and the requirements for industrial scaling. Finally, we discuss the challenges faced as a small academic team, responsible for the delivery of a high number of innovative products to patients. We describe our experience in the set-up of an effective bench-to-clinic pipeline, with a streamlined workflow, for implementation of a diverse portfolio of Phase 1 trials.