Triple Combination Therapy using Hyperthermia, Radiation, and Immune  Checkpoint Inhibitor Enhances Local and Abscopal Effects in Murine Pancreatic                    Cancer Model

Ayaka OKUUCHI; Shohei KATSUKI; Kazumasa MINAMI; Wataru TAKENAKA; Shotaro TATEKAWA; Keisuke TAMARI; Yoriko IBUKI; Yoshinosuke HAMADA; Masahiko KOIZUMI; Kazuhiko OGAWA; Yutaka TAKAHASHI

doi:10.11344/nano.17.1

ORIGINAL ARTICLES

Triple Combination Therapy using Hyperthermia, Radiation, and Immune Checkpoint Inhibitor Enhances Local and Abscopal Effects in Murine Pancreatic Cancer Model

Ayaka OKUUCHI, Shohei KATSUKI, Kazumasa MINAMI, Wataru TAKENAKA, Shotaro TATEKAWA, Keisuke TAMARI, Yoriko IBUKI, Yoshinosuke HAMADA, Masahiko KOIZUMI, Kazuhiko OGAWA, Yutaka TAKAHASHI

Author information

Ayaka OKUUCHI
Department of Medical Physics and Engineering, The University of Osaka, Graduate School of Medicine, Osaka, Japan
Shohei KATSUKI
Department of Medical Physics and Engineering, The University of Osaka, Graduate School of Medicine, Osaka, Japan
Kazumasa MINAMI
Department of Medical Physics and Engineering, The University of Osaka, Graduate School of Medicine, Osaka, Japan
Wataru TAKENAKA
Department of Medical Physics and Engineering, The University of Osaka, Graduate School of Medicine, Osaka, Japan
Shotaro TATEKAWA
Department of Radiation Oncology, The University of Osaka, Graduate School of Medicine, Osaka, Japan
Keisuke TAMARI
Department of Radiation Oncology, The University of Osaka, Graduate School of Medicine, Osaka, Japan
Yoriko IBUKI
Department of Radiation Oncology, The University of Osaka, Graduate School of Medicine, Osaka, Japan
Yoshinosuke HAMADA
Department of Health Economics and Management, The University of Osaka, Graduate School of Medicine, Osaka, Japan
Masahiko KOIZUMI
Department of Medical Physics and Engineering, The University of Osaka, Graduate School of Medicine, Osaka, Japan
Department of Radiology, Nozaki Tokushukai Hospital, Osaka, Japan
Kazuhiko OGAWA
Department of Radiation Oncology, The University of Osaka, Graduate School of Medicine, Osaka, Japan
Yutaka TAKAHASHI
Department of Medical Physics and Engineering, The University of Osaka, Graduate School of Medicine, Osaka, Japan

Keywords: radiation therapy, hyperthermia, immune checkpoint inhibitor, abscopal effect, pancreatic cancer

JOURNAL OPEN ACCESS

2025 Volume 17 Issue 1 Pages 1-8

DOI https://doi.org/10.11344/nano.17.1

Details

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a significant cause of cancer-related deaths. A previous study showed that combination therapy with high-dose radiotherapy and an anti-CTLA-4 antibody (C4) enhanced distant anti-tumor effects, referred to as the abscopal effect. Hyperthermia (HT) enhances the anti-tumor effects in combination with radiotherapy (RT) or chemotherapy. However, the local and abscopal effects of RT with HT combined with C4 therapy for PDAC remain unclear. Here, we investigated whether combination therapy with HT, RT, and C4 is an effective therapeutic strategy for PDAC. Murine PDAC cells were inoculated into both legs of C57BL/6 mice, and the mice were treated only one leg with HT and/or RT. C4 was administered intraperitoneally every 3 days for a total of three doses. According to in vitro experiments, the radiosensitizing effect of HT was approximately 23%. In vivo experiments, no radiosensitizing or abscopal effect of HT to 10 Gy of RT was obtained, and the same results were observed when C4 was used in combination. However, the dose escalation to 14 Gy with HT and C4 induced the abscopal effect. These results suggest that the radiosensitizing effect of HT plays a role not only at local sites, but also at abscopal sites via C4. Further studies using more focal and high-temperature HT (eg; magnetic nanomaterial-based HT) may unveil enhanced therapeutic efficacy and safety.

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