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Chimeric Antigen Receptor Therapeutic Strategies: The Future of Glioblastoma Management

Atsushi Natsume and Courtney Pendleton

The field of adoptive cellular therapy, using autologous T-cells modified ex vivo to specifically target tumor cells prior to being reintroduced to the patient, has become a new focus of research endeavors searching for a novel and efficacious treatment for oncologic disease, including glioblastoma. Chimeric Antigen Receptor (CAR)-T-cells consist of a single chain variable fragment of a monoclonal antibody coupled with extant T-cell intracellular signaling cascade systems using a viral vector ex vivo. This provides the advantage of targeting tumor specific surface markers, while minimizing off-target effects and potential toxicity. Additionally, the CAR T-cells bypass the need for MHC-restricted presentation, a system which is frequently down-regulated in tumor cells. Among the surface antigens described as targets for CAR T-cell therapy for GBMs, Epidermal growth factor variant III (EGFRvIII), HER2 (HER2/neu, ERBB2), interleukin-13 receptor α2 subunit (IL-13Rα2), and erythropoietin-producing hepatocellular carcinoma A2 (EphA2) are the leading options for tumor specific surface antigens to target with CAR-T cells. This article reviews history and advantages of CAR-T cell therapies, and discuss future directions.