Chimeric Antigen Receptor Therapy of Brain Tumors

Malignant gliomas such as glioblastoma (GBM) account for more deaths annually than cancer of the kidney or melanoma. Current therapy for GBM consists of surgical resection followed by radiation and chemotherapy, which is limited by toxicity to systemic tissues and surrounding eloquent brain. Despite aggressive therapy, these tumors remain universally fatal; therefore, it is important to develop alternate therapies for this deadly disease. T lymphocytes can be genetically modified to express chimeric antigen receptors (CAR) comprised of antibody-T cell receptor hybrids that redirect them to target and destroy cancer cells. Although CAR T cell immunotherapy has shown efficacy in treating hematogenous malignancies, therapies for solid tumors face increased challenges, including suppressive tumor microenvironments, trafficking issues, and identification of safe targets. In this chapter, we discuss the historical development of CAR tumor immunotherapy, preclinical treatments for brain tumors, clinical successes and failures, and current state-of the art ongoing trials for patients with GBM.