T-Cell Immunotherapy for Pediatric High-Grade Gliomas: New Insights to Overcoming Therapeutic Challenges
Dalia Haydar, Jorge Ibañez-Vega, Giedre Krenciute
Abstract
Despite decades of research, pediatric central nervous system (CNS) tumors remain the most debilitating, difficult to treat, and deadliest cancers. Current therapies, including radiation, chemotherapy, and/or surgery, are unable to cure these diseases and are associated with serious adverse effects and long-term impairments. Immunotherapy using chimeric antigen receptor (CAR) T cells has the potential to elucidate therapeutic antitumor immune responses that improve survival without the devastating adverse effects associated with other therapies. Yet, despite the outstanding performance of CAR T cells against hematologic malignancies, they have shown little success targeting brain tumors. This lack of efficacy is due to a scarcity of targetable antigens, interactions with the immune microenvironment, and physical and biological barriers limiting the homing and trafficking of CAR T cells to brain tumors. In this review, we summarize experiences with CAR T-cell therapy for pediatric CNS tumors in preclinical and clinical settings and focus on the current roadblocks and novel strategies to potentially overcome those therapeutic challenges.