Umbilical cord blood natural killer cells improve anti-GD2 antibody efficacy in neuroblastoma: from mouse to human [human dataset]

Combined treatment with UCB NK cells and anti-GD2 led to synergistic effects in vitro and in mice and achieved complete and partial responses in two patients with relapsed/refractory NB, with no additive toxicity. Mechanistically, anti-GD2 antibody induced a “high activating-low inhibitory” phenotype of UCB NK cells, and donor UCB NK cells showed dynamically lower levels of immune checkpoints but higher levels of memory-like markers than those of recipient NK cells when combined with anti-GD2 therapy.

Collectively, this study is the first translational investigation of UCB NK cells combined with anti-GD2 therapy in NB, bridging preclinical mechanistic insights into an early clinical proof-of-concept. A phase I study of UCB NK cell infusion combined with anti-GD2 therapy in children with high-risk, relapsed/refractory NB is ongoing at our center (NCT06631391).