Oncolytic virotherapy with SOCS3 enhances viral replicative potency and oncolysis for gastric cancer

Shuichi Matsumura; Mikihito Nakamori; Toshiaki Tsuji; Tomoya Kato; Masaki Nakamura; Toshiyasu Ojima; Hiroshi Fukuhara; Yasushi Ino; Tomoki Todo; Hiroki Yamaue

doi:10.18632/oncotarget.27873

Oncolytic virotherapy with SOCS3 enhances viral replicative potency and oncolysis for gastric cancer

Oncotarget. 2021 Feb 16;12(4):344-354. doi: 10.18632/oncotarget.27873.

Authors

Affiliations

¹ Second Department of Surgery, Wakayama Medical University, Wakayama, Japan.
² Division of Digestive Surgery, Osaka Minami Medical Center, National Hospital Organization, Kawachinagano, Osaka, Japan.
³ Department of Urology, School of Medicine, Kyorin University, Tokyo, Japan.
⁴ Division of Innovative Cancer Therapy, The Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Abstract

Oncolytic virotherapy is an encouraging treatment using herpes simplex virus (HSV) for gastric cancer patients. To treat gastric cancer, we generated and evaluated the efficacy of an attractive type of oncolytic HSV expressing the suppressor of cytokine signaling 3 (SOCS3). We constructed a third-generation type of oncolytic HSV (T-SOCS3) arming with SOCS3 by a bacterial artificial chromosome (BAC) system. We examined the viral replicative intensification and oncolysis of T-SOCS3 for human gastric cancer cell lines ex vivo. T-SOCS3 enhanced its replication and potentiated its cell-killing effect for MKN1 human gastric cancer cell lines, which are resistant to a non-armed third-generation type of oncolytic HSV (T-01) ex vivo. T-SOCS3 also induced the destruction within human gastric cancer specimens. Armed oncolytic HSVs expressing SOCS3 may be an efficacious therapeutic agent for gastric cancer treatment.

Keywords: gastric cancer; herpes simplex virus; oncolytic virus.