Eighteen-year survival after GD2-directed Chimeric Antigen Receptor-Modified Immune Effector Cell Treatment for Neuroblastoma

We report long-term outcomes up to 18 years of a clinical trial treating children with neuroblastoma with EBV-specific T lymphocytes and CD3-activated T cells – each expressing chimeric antigen receptors (CAR) targeting GD2 but without an embedded costimulatory sequence (1st generation CARs). These CARs incorporated barcoded sequences to track each infused population. Of 11 patients with active disease at infusion, three patients achieved a complete response that was sustained in 2, one for 8 years until lost to follow up and one for 18+ years. Of eight patients with no evidence of disease at time of CAR-T administration, five are disease-free at their last follow-up between 10-15 years post-infusion. Intermittent low levels of transgene were detected during the follow up period with significantly greater persistence in those who were long-term survivors. In conclusion, despite using first-generation vectors that are nowadays no longer employed because of the lack of costimulatory domains, patients with relapsed/refractory neuroblastoma achieved long-term disease control after receiving GD2 CAR-T cell therapy including one patient now in remission of relapsed disease for >18 years. Overall design: Single cell mRNA were extracted from three long-term survivors (#1144, 1290, and 1632)' both chimeric antigen receptor-activated T cells (CAR-ATCs) and EBV virus specific T cells (CAR-VSTs) products. Joint scRNA- and scTCR libraries were prepared using the 10x Genomics platform.