Molecular Therapy: Oncology (Dec 2024)
Local treatment of HVJ-E with T cell costimulatory molecule stimulation elicits systemic anti-tumor effects
- Airi Ishibashi,
- Yue Li,
- Yuuta Hisatomi,
- Noriko Ohta,
- Yuko Uegaki,
- Atsushi Tanemura,
- Riuko Ohashi,
- Koji Kitamura,
- Kotaro Saga,
- Yasuhide Yoshimura,
- Satoko Inubushi,
- Kyoso Ishida,
- Sadahiro Iwabuchi,
- Shinichi Hashimoto,
- Eiji Kiyohara,
- Hideo Yagita,
- Yasufumi Kaneda,
- Keisuke Nimura
Affiliations
- Airi Ishibashi
- Division of Gene Therapy Science, Department of Genome Biology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
- Yue Li
- Division of Gene Therapy Science, Department of Genome Biology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan; Division of Gene Therapy Science, Gunma University Initiative for Advanced Research, Gunma University, Maebashi, Gunma 371-8511, Japan
- Yuuta Hisatomi
- Division of Gene Therapy Science, Department of Genome Biology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
- Noriko Ohta
- Division of Gene Therapy Science, Department of Genome Biology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan; Division of Gene Therapy Science, Gunma University Initiative for Advanced Research, Gunma University, Maebashi, Gunma 371-8511, Japan
- Yuko Uegaki
- Division of Gene Therapy Science, Department of Genome Biology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
- Atsushi Tanemura
- Department of Dermatology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
- Riuko Ohashi
- Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; Histopathology Core Facility, Center for Research Promotion, Niigata University School of Medicine, Niigata 951-8510, Japan
- Koji Kitamura
- Division of Gene Therapy Science, Department of Genome Biology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan; Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
- Kotaro Saga
- Division of Gene Therapy Science, Department of Genome Biology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
- Yasuhide Yoshimura
- Division of Gene Therapy Science, Department of Genome Biology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
- Satoko Inubushi
- Division of Gene Therapy Science, Department of Genome Biology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
- Kyoso Ishida
- Division of Gene Therapy Science, Department of Genome Biology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan; Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
- Sadahiro Iwabuchi
- Department of Molecular Pathophysiology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama 641-8509, Japan
- Shinichi Hashimoto
- Department of Molecular Pathophysiology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama 641-8509, Japan
- Eiji Kiyohara
- Department of Dermatology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
- Hideo Yagita
- Department of Immunology, Juntendo University School of Medicine, Bunkyo-Ku, Tokyo 113-8421, Japan
- Yasufumi Kaneda
- Division of Gene Therapy Science, Department of Genome Biology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
- Keisuke Nimura
- Division of Gene Therapy Science, Department of Genome Biology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan; Division of Gene Therapy Science, Gunma University Initiative for Advanced Research, Gunma University, Maebashi, Gunma 371-8511, Japan; Corresponding author: Keisuke Nimura, Division of Gene Therapy Science, Gunma University Initiative for Advanced Research, Gunma University, Maebashi, Gunma 371-8511, Japan.
- Journal volume & issue
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Vol. 32,
no. 4
p. 200893
Abstract
The tumor-infiltrating lymphocyte (TIL) is a crucial factor in controlling tumor growth. A therapeutic method activating TIL is desired for treating patients with metastatic tumors. Here, we show that treating a local tumor with a combination therapy of UV-irradiated hemagglutinating virus of Japan envelope (HVJ-E) plus agonist antibodies, including OX40, against T cell costimulatory molecules induces systemic anti-tumor effects in a T cell-dependent manner in multiple cancer cell lines. Transcriptome and T cell receptor repertoire analyses revealed that HVJ-E + anti-OX40 antibody treatment activates CD4 and CD8 T cells and promotes T cell trafficking between tumors. These systemic anti-tumor effects required an association between Nkg2d and Nkg2d ligands. Our findings provide insights into how systemic anti-tumor effects are induced and may help the development of therapeutic strategies for eliciting such effects.
