[Cancer Immunotherapy Using Allogeneic NKT Cells].

ABSTRACT

We have developed autologous NKT cell-targeted immunotherapy for lung cancer and head and neck cancer at Chiba University. We induce α-galactosylceramide(αGalCer)-pulsed antigen-presenting cells(APCs)from patients' peripheral blood mononuclear cells(PBMCs)in vitro and give them back to the patients. We transferred them intravenously to patients with lung cancer and demonstrated the potential to improve survival time. For patients with head and neck cancer, we transferred them via the nasal submucosa with ex vivo expanded autologous NKT cells. We demonstrated an increased response rate compared with αGalCer-pulsed APCs alone. This suggested that combination therapy of αGalCer-pulsed APCs and NKT cells can increase the response rate. However, NKT cells circulate at less than 0.1% in human PBMCs. Producing enough autologous NKT cells for adoptive immunotherapy is tough. Furthermore, the immunologic function of patient-derived NKT cells can vary among patients. Because stable cell production in number and nature is essential to show effective treatment results, the development of NKT cell-targeted immunotherapy is moving forward using allogeneic NKT cells worldwide. In this circumstance, we, RIKEN and Chiba University, have been developing allogeneic induced pluripotent stem cell(iPS cell)- derived NKT cell therapy. The phase Ⅰ clinical trial of iPS cell-derived NKT cell therapy for head and neck cancer is ongoing.