학술논문
An oncolytic virus as a promising candidate for the treatment of radioresistant oral squamous cell carcinoma
Document Type
article
Author
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
Source
Molecular Therapy: Oncolytics, Vol 27, Iss , Pp 141-156 (2022)
Subject
Language
English
ISSN
2372-7705
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.