CAR-T in relapsed refractory high-grade glioma and glioblastoma – who, what, when and how?

Recurrent high-grade gliomas have a dismal prognosis. This review article aimed to explore and help answer the questions about which group of patients would benefit from chimeric antigen receptor therapy (CAR-T) cell therapy in this setting, the timing of intervention and the therapeutic efficacy. CAR-T cell therapy involves the extraction of T-cells from patients, genetic modification of these cells to express chimeric antigen receptors on their cell surface, which are selectively targeted towards tumour-expressed antigens and a procedure of immune-depletion followed by re-introducing these engineered CAR-T cells into the host via infusion. Gliomas, particularly glioblastoma, present unique challenges due to their immune-evasive nature, location within the central nervous system and antigenic heterogeneity. Thus, several potential antigenic targets are being explored for CAR-T cell therapy, including B7 homolog 3, Disiloganglioside, Eph-A2, Eph-A3, IL-13Ra2, HER2, EGFRvIII and Matrix metalloproteinase-2.