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

Abstract

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Shuichi Matsumura1, Mikihito Nakamori1^,4, Toshiaki Tsuji1, Tomoya Kato1, Masaki Nakamura1, Toshiyasu Ojima1, Hiroshi Fukuhara2, Yasushi Ino3, Tomoki Todo3 and Hiroki Yamaue1 1 Second Department of Surgery, Wakayama Medical University, Wakayama, Japan 2 Department of Urology, School of Medicine, Kyorin University, Tokyo, Japan 3 Division of Innovative Cancer Therapy, The Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan 4 Division of Digestive Surgery, Osaka Minami Medical Center, National Hospital Organization, Kawachinagano, Osaka, Japan Correspondence to: Mikihito Nakamori, email: chamcham@wakayama-med.ac.jp Keywords: oncolytic virus; herpes simplex virus; gastric cancer Received: October 15, 2020 Accepted: January 19, 2021 Published: February 16, 2021 Copyright: © 2021 Matsumura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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.