We have enrolled 6 metastatic melanoma patients into the Phase 1 CARPETS clinical trial of autologous third-generation CAR-T cell therapy targeted toward GD2. No significant adverse events were attributable to the CAR-T cell therapy. In vivo persistence of the adoptively transferred CAR-T cells was not observed beyond two months post-infusion except in the one patient who received prior lymphodepleting chemotherapy using cyclophosphamide and fludarabine. We have in vitro evidence to suggest that the lack of in vivo persistence may have resulted from activation-induced cell death (AICD). We are now modifying our ex vivo culture conditions both to favour transduction of T cells with a memory phenotype rather than an effector phenotype and reduce the likelihood of AICD. Our clinical protocol modification will also include broadening the eligibility to enrol patients with other types of GD2-expressing malignancy