[Application of iPS Cell-Derived NKT Cells to Cancer Immunotherapy].

ABSTRACT

NKT cells are innate lymphocytes that express an invariant T cell receptor. Since activated NKT cells exert strong anti-tumor responses, NKT cells have been intensively studied for the purpose of their application to cancer immunotherapeutic approaches. Although human peripheral blood contained a very low fraction of NKT cells, and decreased number of NKT cells was also demonstrated in cancer-bearing patients, peripheral blood NKT cells can be activated by ligand-pulsed antigen presenting cells, and can produce a large amount of interferon-γ upon activation. The clinical trials of adoptive transfer of autologous NKT cells were already performed in patients with non-small cell lung cancer, and with head and neck cancer at Chiba University to show its effectiveness and limitation. Meanwhile, RIKEN reported NKT cell regeneration using iPS cell technology in mice, and subsequently established a protocol for regenerating NKT cells from human peripheral blood NKT cells using iPS cell technology. It was confirmed that the iPS cell-derived NKT cells (iPS-NKT) have sufficient expansion c apacity and potent direct and indirect cytotoxic activity in the humanized mice models, which suggests their therapeutic competence. We are currently planning an investigator-initiated clinical trial of allogeneic iPS-NKT cell therapy for head and neck cancer.