Research and development of combination therapy using iNKT cells and an anti-GD2 antibody toward neuroblastoma

2014 Fiscal Year Final Research Report

• Project/Area Number: 25861664
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatric surgery
• Research Institution: Chiba University
• Principal Investigator: MISE Naoko 千葉大学, 医学部附属病院, 医員 (40646402)
• Research Collaborator: MOTOHASHI Shinichiro 千葉大学, 大学院医学研究院, 教授 (60345022)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: NKT細胞 / 神経芽腫 / ADCC / NK細胞 / 抗GD2抗体

Outline of Final Research Achievements

Anti-ganglioside GD2 antibodies mainly work through antibody dependent cellular cytotoxicity (ADCC) and have demonstrated clinical benefit for children with neuroblastoma. In this report, we investigated the feasibility of combination therapy using iNKT cells and an anti-GD2 antibody.
As a result, iNKT cells were not directly associated with ADCC. However, when co-cultured with activated iNKT cells, the granzyme A (GrA), granzyme B (GrB) and interferon gamma (IFNγ) 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 contributed to the increase in NK cell cytotoxicity and further IFNγ 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.

Free Research Field

小児がん