[Challenges and prospects for CAR-T therapy]

The number of cases of chimeric antigen receptor T (CAR-T) cell therapy has been rapidly increasing in Japan since Tisagenlecleucel was approved in March 2019, and clinical experience with CAR-T therapy for CD19 has demonstrated that the therapy can be performed safely than initially expected. The current challenge for CAR-T therapy is insufficient response, as about 50% of patients who receive CD19 CAR-T therapy eventually relapse or become refractory. The causes can be generally classified as CAR-T cell exhaustion and lack of sufficient effector function, loss of the target antigen, and extremely rapid tumor growth, and countermeasures are being investigated and developed for each of these causes. Additionally, the development of novel CAR-T therapies is also desired. In this article, we discuss the current status and future prospects of these issues, including our own efforts.