The Road to CAR T-Cell Therapies for Pediatric CNS Tumors: Obstacles and New Avenues

Abstract

Pediatric central nervous system (CNS) tumors are the most common solid tumors diagnosed in children and are the leading cause of pediatric cancer-related death. Those who do survive are faced with the long-term adverse effects of the current standard of care treatments of chemotherapy, radiation, and surgery. There is a pressing need for novel therapeutic strategies to treat pediatric CNS tumors more effectively while reducing toxicity – one of these novel modalities is chimeric antigen receptor (CAR) T-cell therapy. Currently approved for use in several hematological malignancies, there are promising pre-clinical and early clinical data that suggest CAR-T cells could transform the treatment of pediatric CNS tumors. There are, however, several challenges that must be overcome to develop safe and effective CAR T-cell therapies for CNS tumors. Herein, we detail these challenges, focusing on those unique to pediatric patients including antigen selection, tumor immunogenicity and toxicity. We also discuss our perspective on future avenues for CAR T-cell therapies and potential combinatorial treatment approaches.

CAR-T-Cell-Based Cancer Immunotherapies: Potentials, Limitations, and Future Prospects

“…Investigating BTIC-specific antigens, using suitable preclinical controls, and creating novel strategies for multivalent CARs are some potential solutions. With continuing innovation and creative implementation of novel therapies, CAR-T cell therapy has the potential to improve treatment and reduce toxicity in children with CNS malignancies [ 141 ].…”