Current progress in chimeric antigen receptor T cell therapy for glioblastoma multiforme

Glioblastoma multiforme (GBM) is one of the deadliest brain tumors with a dismal prognosis and a median overall survival of approximately 20 months following diagnosis. The current standard point of care (SPOC) for GBM includes both chemo- and radiotherapeutic modalities which are not effective. CAR T immunotherapy has been proved to be effective for CD19-positive blood malignancies, and the application of CAR T cell therapy for solid tumors including GBM poses a great hope for GBM patients. CAR T technology depends on the use of patient-specific T cells that are genetically engineered to express the specific tumor-associated antigens. Interaction of CAR T cells with the tumor cells triggers the destruction/elimination of tumor cells by induction of cytotoxicity and release of a wide variety of cytokines. Despite the great promise of CAR T cell-based therapy for GBM, several challenges such as heterogeneity of GBM cancer cells, the antigen escape, and the hostile inhibitory GBM microenvironment still need to be tackled before its full approval at the clinical level. Here, we provided a focused review on the rationale of the use of different types of CAR T cells including Fc?Rs CAR T cells, different GBM-associated antigens, challenges still facing CAR T-based therapy for GBM, and strategies to overcome such challenges. Finally, we discussed the potential of ongoing clinical trials for GBM, and how such therapeutic modalities are expected to revolutionize the current SPOC for GBM.