A guide to CAR T cell therapies: development, current status and future prospects

Since the first clinical approval in 2017, chimeric antigen receptor (CAR) T cell therapy has emerged as one of the most powerful modalities for redirecting the immune response against cancer. Building on decades of foundational discoveries in T cell biology and synthetic immunoengineering, CAR T cell therapy has transformed the treatment of B cell malignancies, resulting in durable remissions in patients with B cell leukaemias, lymphomas and multiple myeloma. Next-generation CAR designs are now expanding the reach of this approach into autoimmune disease and solid tumours. Innovations in gene editing, allogeneic manufacturing and in vivo delivery are improving the scalability, safety and accessibility of CAR T cell therapies, although challenges persist in overcoming antigen heterogeneity and tumour microenvironmental barriers and in promoting the long-term persistence of CAR T cells. In this Review, we summarize the key discoveries that laid the foundations for CAR T cell therapies and provide a broad overview of the current principles of CAR design, their clinical development and emerging strategies aimed at enhancing efficacy, broadening indications and achieving durable immune control across disease types.