CAR T-cells for the treatment of CNS malignancies

Chimeric antigen receptor (CAR) T-cell therapy has undergone great advances since the development of the first-generation CAR in the early 1990s. Currently there are seven FDA approved CAR T-cell therapies for the treatment of hematological malignancies, with marked clinical success. However, the application of CAR T-cell therapies to solid tumors, particularly CNS malignancies, provide unique challenges. This review provides historical perspective on CAR T-cell therapy, describes CAR structures and current generations, and details challenges with the application of CAR T-cells to CNS malignancies. In addition, an extensive summary of all clinical trials, as of March 2026, utilizing CAR T-cell therapy for primary and secondary CNS malignancies are provided. Specific attention is given to detailing CAR structure, route of administration, and dosing. Furthermore, outcomes and adverse events for each trial are described for completed studies and studies reporting interim results. As the application of CAR T-cell therapy continues to expand in CNS malignancies, it is imperative that clinical studies provide adequate details on CAR structures, try to more quickly adopt/act on preclinical successes, and seek novel application strategies to advance growth in the field.