NKT cells bridge the innate and acquired immune systems. A prime example of one such function is adjuvant activity: NKT cells augment anti-tumor responses by production of IFN-g, which acts on NK cells to eliminate MHC negative target tumor cells and also on CD8 cytotoxic T cells to kill MHC positive tumor cells. Thus, upon administration of dendritic cells (DCs) loaded with the NKT cell activating ligand a-GalCer, both MHC negative and positive tumor cells can be effectively eliminated. Based on these experimental findings, we have developed NKT cell-targeted adjuvant cell therapies with strong antitumor activity in humans.
A phase I/IIa clinical trial has been carried out in collaboration with Chiba University Hospital (Professors Nayayama/Motohashi) on 17 patients with advanced non-small lung cancer and 10 cases of head and neck tumors. Sixty percent of advanced lung cancer patients with high IFN-g production had a median survival time (MST) of around 30 months and remained as stable disease (SD) with only the primary a-GalCer/DC treatment. In the case of head and neck tumors, all 10 patients who completed the trial had SD or partial responses four weeks after a combination therapy using a-GalCer/DCs and activated NKT cells. We are currently collaborating with Prof. Okamoto, Chiba Univ. on head and neck tumor patients and also with the National Hospital Organization (Drs. Ito (Tokyo), Saka (Nagoya Medical Center) and Ichinose (Kyushu Cancer Center)) on a randomized Phase II clinical trial on Stage II-IIIA tumors after surgical resection to investigate 2-year relapse-free survival.