Ten patients with head and neck squamous cell carcinoma were treated with allogeneic, iPSC-derived iNKT cells over 2-3 doses. One patient experienced a dose-limiting skin rash; otherwise, adverse events were low-grade without CRS or anti-HLA antibodies. iPSC-iNKT cells were mostly not detected in blood at 1 week after dosing. Five patients achieved stable disease, with minor tumor size reductions in 2 patients. Although endogenous T and NK cell counts did not change, enhanced activation (IFNγ, NF-κB, and TCR pathways) and clonal expansion (particularly in effector/memory CD8+ T cells) were observed in the 2 patients with tumor reduction.
Contributed by Alex Najibi
ABSTRACT: 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.
Author Info: (1) Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan. (2) Department of Otorhinolaryngology, Head and Neck Surg
Author Info: (1) Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan. (2) Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan. Clinical Research Center, Chiba University Hospital, Chiba, Japan. (3) Department of Medical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan. Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Science, Kanagawa, Japan. (4) Research Institute of Disaster Medicine, Chiba University, Chiba, Japan. Institute for Advanced Academic Research, Chiba University, Chiba, Japan. (5) Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Science, Kanagawa, Japan. (6) Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Science, Kanagawa, Japan. (7) Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Science, Kanagawa, Japan. (8) Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Science, Kanagawa, Japan. (9) Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Science, Kanagawa, Japan. (10) Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Science, Kanagawa, Japan. (11) Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Science, Kanagawa, Japan. (12) Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Science, Kanagawa, Japan. (13) Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Science, Kanagawa, Japan. (14) Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Science, Kanagawa, Japan. (15) Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Science, Kanagawa, Japan. (16) Department of Medical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan. (17) Center for Advanced Medicine, Chiba University Hospital, Chiba, Japan. (18) Diagnostic Radiology and Radiation Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan. (19) Clinical Research Center, Chiba University Hospital, Chiba, Japan. (20) Clinical Research Center, Chiba University Hospital, Chiba, Japan. (21) Chiba Rosai Hospital, Chiba, Japan. (22) Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan. (23) Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Science, Kanagawa, Japan. haruhiko.koseki@riken.jp. Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan. haruhiko.koseki@riken.jp. (24) Department of Medical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan. motohashi@faculty.chiba-u.jp.
