Targeting GD2 with CAR-T Cell Therapy in Neuroblastoma: Updates, Challenges, and Future Perspectives.

PURPOSE OF REVIEW: High-risk neuroblastoma remains a challenging pediatric cancer, with survival rates lagging despite advances in multimodal therapy. This review aims to critically synthesize recent advances in GD2-directed chimeric antigen receptor (CAR) T cell therapy for neuroblastoma and to highlight its potential to improve long-term outcomes.

RECENT FINDINGS: In early-phase trials of GD2-directed CAR-T cell therapy for relapsed or refractory neuroblastoma, no dose-limiting toxicities were observed. Objective responses ranged from 6% to 33%, with durable complete remissions reported beyond 10 years. Stable disease occurred in up to 55% of patients. Cytokine release syndrome was reported in 0-90% of cases, generally mild, and neurotoxicity was rare. CAR-T cell expansion and trafficking to tumor sites have been demonstrated in several studies, although they remain variable and often limited in solid tumor settings. GD2-directed CAR-T cell therapy demonstrates limited but measurable clinical activity, particularly in minimal residual disease settings, with an overall acceptable safety profile. Continued innovation in CAR design and integration into multimodal strategies may improve long-term outcomes for this aggressive pediatric cancer.