CAR T cell therapy for central nervous system solid tumors: current progress and future directions

Central nervous system (CNS) tumors are the second most common type of cancer in children and remain the leading cause of mortality in pediatric oncology. For patients with high-risk CNS tumors, standard treatments often prove ineffective, with survival rates being less than 10%. Hence, there is an urgent need to develop alternative treatment strategies for this patient population. Globally, numerous clinical trials are actively investigating a range of novel therapeutic approaches, from pharmacological and immunological therapies to physical modalities targeting the tumor. Among these emerging therapies, CAR T cell therapy has shown great promise, with the first objective clinical responses already reported. This review aims to evaluate the current landscape of CAR T cell therapy for pediatric CNS tumors, focusing on clinical efficacy, toxicity profiles of systemic and locoregional delivery, antigen heterogeneity, and key challenges in clinical implementation. We provide a comprehensive analysis of reported clinical trials, including not only CAR T cell studies but also investigations involving tumor-infiltrating lymphocytes (TILs), NK and lymphokine-activated killer (LAK) cells, offering a broader perspective on immunotherapeutic approaches for CNS malignancies.