2022 Volume 31 Issue 2 Pages 1-6
The recent progress in cancer immunotherapy has been remarkable, and the immune checkpoint inhibitors have brought about a paradigm shift in cancer treatment. Chimeric antigen receptor (CAR)-T-cell therapy has shown excellent anti-tumor effects in hematological malignancies, and CAR-T cell therapy (tisagenlecleucel) has already been approved in Japan for the treatment of relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) and relapsed or refractory diffuse large B-cell lymphoma (DLBCL). On the other hand, several CAR-T cell therapies have not been successful in clinical trials for solid tumors. The reason may be the ability of CAR-T cells to reach solid tumors, and the physical and immunological barriers surrounding solid tumors. The development of CAR-T cell therapy for brain tumors, which are solid tumors, faces the same problem, but in addition, there are concerns about diffi culties due to problems specifi c to the central nervous system. In this review, we discuss the major challenges facing CAR-T cell therapy in malignant brain tumors. These include neuroanatomical considerations, obstacles to effector T cell traffi cking, immunosuppression in the tumor microenvironment, antigen heterogeneity, and off-tumor toxicity. This will be followed by an update on the current clinical status of CAR T-cell therapy for malignant brain tumors.
