An oncolytic virus as a promising candidate for the treatment of radioresistant oral squamous cell carcinoma

Shunsuke Gohara; Kosuke Shinohara; Ryoji Yoshida; Ryusho Kariya; Hiroshi Tazawa; Masashi Hashimoto; Junki Inoue; Ryuta Kubo; Hikaru Nakashima; Hidetaka Arita; Sho Kawaguchi; Keisuke Yamana; Yuka Nagao; Asuka Iwamoto; Junki Sakata; Yuichiro Matsuoka; Hisashi Takeshita; Masatoshi Hirayama; Kenta Kawahara; Masashi Nagata; Akiyuki Hirosue; Yoshikazu Kuwahara; Manabu Fukumoto; Seiji Okada; Yasuo Urata; Toshiyoshi Fujiwara; Hideki Nakayama

doi:10.1016/j.omto.2022.10.001

An oncolytic virus as a promising candidate for the treatment of radioresistant oral squamous cell carcinoma

Mol Ther Oncolytics. 2022 Oct 8:27:141-156. doi: 10.1016/j.omto.2022.10.001. eCollection 2022 Dec 15.

Authors

Shunsuke Gohara¹, Kosuke Shinohara¹, Ryoji Yoshida¹, Ryusho Kariya², Hiroshi Tazawa³, Masashi Hashimoto³, Junki Inoue¹, Ryuta Kubo¹, Hikaru Nakashima¹, Hidetaka Arita¹, Sho Kawaguchi¹, Keisuke Yamana¹, Yuka Nagao¹, Asuka Iwamoto¹, Junki Sakata¹, Yuichiro Matsuoka¹, Hisashi Takeshita¹, Masatoshi Hirayama¹, Kenta Kawahara¹, Masashi Nagata¹, Akiyuki Hirosue¹, Yoshikazu Kuwahara⁴, Manabu Fukumoto⁵, Seiji Okada⁶, Yasuo Urata⁶, Toshiyoshi Fujiwara³, Hideki Nakayama¹

Affiliations

¹ Department of Oral and Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
² Oncolys Biopharma, Inc., Tokyo, Japan.
³ Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
⁴ Radiation Biology and Medicine, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
⁵ Pathology Informatics Team, RIKEN Center for Advanced Intelligence Project, Chuo-ku, Tokyo, Japan.
⁶ Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection and Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

Abstract

We evaluated the usefulness of an oncolytic virus (Suratadenoturev; OBP-301) against radioresistant oral squamous cell carcinoma. We confirmed the expression of human telomerase reverse transcriptase and the coxsackievirus and adenovirus receptor in cell lines. Also, we examined the potential presence in a patient who has received existing therapy that is amenable to treatment with OBP-301. We evaluated: (1) the antitumor effects of OBP-301 alone and in combination with radiotherapy on radioresistant cell lines, (2) the molecular mechanism underlying the radiosensitizing effect and cell death increased by the combination therapy, and (3) the antitumor effect of the combination therapy in vivo using xenograft models (a radioresistant cell line-derived xenograft in mouse and a patient-derived xenograft). Human telomerase reverse transcriptase and the coxsackievirus and adenovirus receptor were expressed in all cell lines. OBP-301 decreased the proliferative activity of these cell lines in a concentration-dependent manner, and significantly enhanced the antitumor effect of irradiation. Phosphorylated STAT3 and its downstream molecules, which correlated with apoptosis and autophagy, showed significant changes in expression after treatment with OBP-301. The combination therapy exerted a significant antitumor effect versus radiotherapy alone in both xenograft models. Combination of OBP-301 with radiotherapy exerts a synergistic effect and may represent a promising treatment for radioresistant oral squamous cell carcinoma.

Keywords: OBP-301; STAT3; apoptosis; autophagy; oncolytic virus; oral squamous cell carcinoma; patient-derived xenograft model; radioresistance.