Chimeric antigen receptor adoptive immunotherapy in central nervous system tumors: state of the art on clinical trials, challenges, and emerging strategies to addressing them

PURPOSE OF REVIEW: Central nervous system (CNS) tumors represent a significant unmet medical need due to their enduring burden of high mortality and morbidity. Chimeric antigen receptor (CAR) T-cell therapy emerges as a groundbreaking approach, offering hope for improved treatment outcomes. However, despite its successes in hematological malignancies, its efficacy in solid tumors, including CNS tumors, remains limited. Challenges such as the intricate tumor microenvironment (TME), antigenic heterogeneity, and CAR T-cell exhaustion hinder its effectiveness. This review aims to explore the current landscape of CAR T-cell therapy for CNS tumors, highlighting recent advancements and addressing challenges in achieving therapeutic efficacy. RECENT FINDINGS: Innovative strategies aim to overcome the barriers posed by the TME and antigen diversity, prevent CAR T-cell exhaustion through engineering approaches and combination therapies with immune checkpoint inhibitors to improving treatment outcomes. SUMMARY: Researchers have been actively working to address these challenges. Moreover, addressing the unique challenges associated with neurotoxicity in CNS tumors requires specialized management strategies. These may include the development of grading systems, monitoring devices, alternative cell platforms and incorporation of suicide genes. Continued research efforts and clinical advancements are paramount to overcoming the existing challenges and realizing the full potential of CAR T-cell therapy in treating CNS tumors.