Anti-ganglioside GD2 antibodies mainly work through antibody dependent cellular cytotoxicity (ADCC) and have demonstrated clinical benefit for children with neuroblastoma. However, high-risk neuroblastoma still has a high recurrence rate. To further improvement in the outcomes, ways to maximize the cytotoxic effects of anti­GD2 therapies with the least toxicities are inquired. Activated invariant Natural Killer T (iNKT) cells enhance both innate and type I acquired anti-tumor immunity by producing several kinds of cytokines. In this report, we investigated the feasibility of combination therapy using iNKT cells and an anti-GD2 antibody. Although some of the expanded iNKT cells expressed Natural Killer (NK) cell markers, including FcgR, iNKT cells were not directly associated with ADCC. When co-cultured with activated iNKT cells, the granzyme A (GrA), granzyme B (GrB) and interferon gamma (IFNg) production from NK cells were upregulated, and the cytotoxicity of the NK cells treated with anti-GD2 antibodies was increased. Not only cytokines produced by activated iNKT cells, but also NK-NKT cell contact or NK cell-dendritic cell contact contributed to the increase in NK cell cytotoxicity and further IFNg production by iNKT cells and NK cells. In conclusion, iNKT cell-based immunotherapy could be an appropriate candidate for anti-GD2 antibody therapy for neuroblastoma.