Tomohisa Iinuma, Tomoya Kurokawa, Takahiro Aoki, Atsushi Onodera, Tominaga Fukazawa, Daisuke Yamada, Genta Kitahara, Momoko Okoshi, M Yamaguchi, Hiroko Okura, Satoko Sasaki, Yoshie Sasako, Sachiko Kira, Jafar Sharif, Yukio Tsuchiyama, Midori Kobayashi, Norihiko Kobayashi, Takuro Horikoshi, Yosuke Inaba, Hideki Hanaoka, Yoshitaka Okamoto, Toyoyuki Hanazawa, Haruhiko Koseki, Shinichiro Motohashi
Invariant Natural killer T (iNKT) cells exhibit cytotoxic activity and immunomodulatory functions and have gained interest in cancer immunotherapy. We conducted a phase 1, first-in human clinical trial to evaluate the safety and efficacy of clinical-grade allogeneic iNKT cells generated from induced pluripotent stem cells (iPSC-iNKT cells) in patients with recurrent head and neck cancer (jRCT2033200116). The primary endpoint was the incidence of dose-limiting toxicity (DLT). The secondary endpoints were to assess safety and efficacy, as well as to evaluate immunological dynamics. iPSC-iNKT cells were administered intra-arterially to 10 patients. One subject developed grade 3 skin rash at the second dose, identified as DLT. No other severe adverse events were observed in any patients. Tumor progression was suppressed in two patients, in whom clonal expansion of memory- and effector-phenotype CD8+ T cells was observed, along with activation of the IFN-γ signaling pathway. Here, we show that iPSC-iNKT cells are safe and possess therapeutic potential as an immunotherapy for solid tumors. A first-in-human clinical trial of iPS cell-derived invariant natural killer T cells in patients with recurrent head and neck cancer demonstrated safety and early signs of efficacy, showing tumor growth suppression and activation of immune pathways.