The FDA's approval of Gilead Sciences and Kite Pharmaceutical's axicabtagene ciloleucel for relapsed or refractory large B cell lymphoma in October marked the second green light for the emerging chimeric antigen receptor (CAR) T cell modality. In August, the agency approved Novartis's tisagenlecleucel for acute lymphoblastic leukaemia.

CAR Ts are ex vivo gene therapies, in which T cells are removed from cancer patients, genetically modified to express cancer-seeking receptors, and then re-infused back into patients. Both axicabtagene ciloleucel and tisagenlecleucel are modified so that the engineered immune cells can target the B cell antigen CD19, leading to the depletion of normal and malignant B cells for the treatment of various blood cancers.

The approval of axicabtagene ciloleucel was based on a 101-patient pivotal trial, which showed third-line use of the therapy resulted in an objective response rate of 72% and a complete remission rate of 51% in patients with large B cell lymphoma. The treatment carries a black box warning noting the risk of cytokine release syndrome and neurological toxicities. Novartis's tisagenlecleucel, which the company recently submitted for regulatory approval in the large B cell lymphoma setting, also carries these warnings on its label.

The field is working to mitigate toxicity risks for next-generation CAR Ts, and to figure out how to use the modality in solid tumours (Nat. Rev. Drug Discov. 16, 301–304; 2017).

Gilead acquired Kite in August for US$12 billion. Analysts forecast that the newly approved CAR T could achieve sales of more than $3 billion by 2023, according to Clarivate Analytics' Cortellis database. The company has two other engineered T cell therapies in its clinical pipeline: a phase I CAR T that targets BCMA, for multiple myeloma, and a phase I engineered T cell receptor product that targets MAGEA3 and MAGEA6, for solid tumours.