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Induction of NKT cell-specific immune responses in cancer tissues after NKT cell-targeted adoptive immunotherapy |
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| Authors: | Yamasaki Kazuki Horiguchi Shigetoshi Kurosaki Motoyoshi Kunii Naoki Nagato Kaoru Hanaoka Hideki Shimizu Naomi Ueno Naoyuki Yamamoto Seiji Taniguchi Masaru Motohashi Shinichiro Nakayama Toshinori Okamoto Yoshitaka |
| Affiliation: | a Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan;b Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan;c Department of Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan;d Clinical Research Center, Chiba University Hospital, Chiba, Japan;e Division of Blood Transfusion, Chiba University Hospital, Chiba, Japan;f Department of Radiology, Graduate School of Medicine, Chiba University, Chiba, Japan;g Laboratory of Immune Regulation, RIKEN Research Center for Allergy and Immunology, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan |
| Abstract: | Vα24 natural killer T (NKT) cells have potent anti-tumor activity. We performed a phase II clinical study in patients with head and neck squamous cell carcinoma (HNSCC) using ex vivo expanded Vα24 NKT cells and α-galactosylceramide (αGalCer; KRN7000)-pulsed antigen-presenting cells (APCs) to investigate the efficacy and induction of NKT cell-specific immune responses. The subjects were 10 patients with locally recurrent and operable HNSCC. One course of nasal submucosal administration of αGalCer-pulsed APCs and intra-arterial infusion of activated NKT cells via tumor-feeding arteries was given before salvage surgery. Anti-tumor effects, NKT cell-specific immune responses in extirpated cancer tissue and peripheral blood, safety, and pathological effects were evaluated. Five cases achieved objective tumor regression. The number of NKT cells increased in cancer tissues in 7 cases and was associated with tumor regression. The combination therapy induced NKT cell-specific immune responses in cancer tissues that were associated with beneficial clinical effects. |
| Keywords: | Human NKT cell Tumor immunity |
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