AUTHOR=Kaminskiy Yaroslav , Degtyarev Vitaly , Stepanov Alexey , Maschan Michael 

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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1600403

DOI=10.3389/fimmu.2025.1600403

ISSN=1664-3224

ABSTRACT=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.