Allogeneic GD2-CART01 for Treatment of patients with Relapsed/Refractory High-Risk Neuroblastoma

Allogeneic chimeric antigen receptor (CAR) T-cells targeting disialoganglioside-GD2 (ALLO_GD2-CART01) combined with allogeneic hematopoietic stem cells transplantation (HSCT) represents a feasible and safe option for relapsed/refractory high-risk neuroblastoma (r/r HR-NB) patients, who had failed autologous GD2-CART01 or with profound lymphopenia. We present data from 5 children refractory to >3 lines of therapy, with a high heterogeneity of their treatment journey, but all receiving ALLO_GD2-CART01 allogenic transplantation. All children experienced grade 2/3 cytokine release syndrome; one patient developed neurotoxicity. Moderate acute graft-versus-host-disease occurred in all patients. ALLO_GD2-CART01 persisted for more than 6 weeks. Three patients achieved complete response, one partial response and one stable disease. Transcriptomic profile of the allogeneic products, in comparison to CAR T cells expanding in vivo after infusion, shows an increased expression of genes associated with cytotoxic activity, immune regulation, inflammation, stress response, metabolic dynamics, cell trafficking and adhesion. After infusion, the transcriptomic signaling of ALLO_GD2-CART01 was associated to cell polarization, trafficking, cytotoxicity/activation. These data suggest that the use of ALLO_GD2-CART01 is feasible and safe for r/r HR-NB.