CAR T cells for pediatric CNS tumors: Clinical experience and reverse translational opportunities

Central nervous system (CNS) tumors are one of the leading causes of cancer-related mortality in children and young adults. Despite decades of research, effective treatments for these tumors are still lacking and new therapeutic options are urgently needed. While chimeric antigen receptor (CAR) T cell therapies have revolutionized the treatment of hematologic malignancies, these cellular therapies are only beginning to show evidence of activity in CNS tumors. In this review, we will discuss current CAR T cell clinical trials with a focus on trials in the pediatric CNS tumor space. In addition, we will explore the power of reverse translation-defined by applying clinical research insights from bedside-to-bench to understand the mechanisms of CAR T cell success or failure in patients-for CNS tumor CAR T cells. Employing the full cycle of translational research, novel CAR T cell therapies are being tested in the clinic and reverse translational studies are being assessed at the bench. Combining these data, the CNS CAR T cell field is poised to iteratively improve CAR T cells for children and young adults with CNS tumors.