CAR T Cell Therapy in Glioblastoma: Overcoming Challenges Related to Antigen Expression

SIMPLE SUMMARY: Glioblastoma is the most common brain cancer, and prognosis remains dismal. Continued efforts to find better treatments have shown the promise of immunotherapy, whereby the immune response against a tumor is augmented. One particular immunotherapy, CAR T therapy, involves engineering a patient’s own T cells to express a receptor that specifically targets antigens on tumor cells. This therapy has shown promise in preclinical experiments but has not shown benefit in clinical studies to date. This review explores the potential limitations of this therapy and possible ways of improving its effectiveness in treating glioblastoma. ABSTRACT: Glioblastoma (GBM) is the most common primary brain tumor, yet prognosis remains dismal with current treatment. Immunotherapeutic strategies have had limited effectiveness to date in GBM, but recent advances hold promise. One such immunotherapeutic advance is chimeric antigen receptor (CAR) T cell therapy, where autologous T cells are extracted and engineered to express a specific receptor against a GBM antigen and are then infused back into the patient. There have been numerous preclinical studies showing promising results, and several of these CAR T cell therapies are being tested in clinical trials for GBM and other brain cancers. While results in tumors such as lymphomas and diffuse intrinsic pontine gliomas have been encouraging, early results in GBM have not shown clinical benefit. Potential reasons for this are the limited number of specific antigens in GBM, their heterogenous expression, and their loss after initiating antigen-specific therapy due to immunoediting. Here, we review the current preclinical and clinical experiences with CAR T cell therapy in GBM and potential strategies to develop more effective CAR T cells for this indication.