Abstract
Treatment of high-risk paediatric neuroblastoma represents an unmet clinical need. Chimeric antigen receptor-modified T cell (CAR-T) therapy is a promising treatment option, but there exist some challenges regarding specificity and potency. The current study used ganglioside GD2 as a target for CAR-T construction because of its selective overexpression in neuroblastoma cells. We engineered a GD2-based CAR-T construct, including ICOS and 4-1BB co-stimulatory domains for better persistence. The cytotoxicity of the generated CAR-T cells (PG3-GD2-CAR-T) was verified using in vitro and in vivo assays. PG3-GD2-CAR-T cells exerted potent anti-tumour activity in vitro and in vivo, with minimal effects on peripheral blood cells. PG3-GD2-CAR-T cells exhibited encouraging specificity for and potency against neuroblastoma.
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