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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Methodol. Mar 26, 2016; 6(1): 25-42
Published online Mar 26, 2016. doi: 10.5662/wjm.v6.i1.25
Clinical development of reovirus for cancer therapy: An oncolytic virus with immune-mediated antitumor activity
Jun Gong, Esha Sachdev, Alain C Mita, Monica M Mita
Jun Gong, Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA 91010, United States
Esha Sachdev, Alain C Mita, Monica M Mita, Division of Experimental Therapeutics Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
Author contributions: All authors equally contributed to this paper with literature review, drafting, critical revision, editing, and final approval of the final version.
Conflict-of-interest statement: All authors declare no potential conflicts of interests and no financial support.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Monica M Mita, MD, Co-director, Division of Experimental Therapeutics Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd, SCCT Mezzanine MS 35, Los Angeles, CA 90048, United States. monica.mita@cshs.org
Telephone: +1-310-2486729 Fax: +1-310-2486740
Received: December 17, 2015
Peer-review started: December 23, 2015
First decision: January 18, 2016
Revised: January 28, 2016
Accepted: February 16, 2016
Article in press: February 17, 2016
Published online: March 26, 2016
Processing time: 91 Days and 19.8 Hours
Abstract

Reovirus is a double-stranded RNA virus with demonstrated oncolysis or preferential replication in cancer cells. The oncolytic properties of reovirus appear to be dependent, in part, on activated Ras signaling. In addition, Ras-transformation promotes reovirus oncolysis by affecting several steps of the viral life cycle. Reovirus-mediated immune responses can present barriers to tumor targeting, serve protective functions against reovirus systemic toxicity, and contribute to therapeutic efficacy through antitumor immune-mediated effects via innate and adaptive responses. Preclinical studies have demonstrated the broad anticancer activity of wild-type, unmodified type 3 Dearing strain reovirus (Reolysin®) across a spectrum of malignancies. The development of reovirus as an anticancer agent and available clinical data reported from 22 clinical trials will be reviewed.

Keywords: Reovirus; Type 3 Dearing; Oncolytic virus; Ras; Epidermal growth factor receptor; Clinical trial; Preclinical; Immune modulation

Core tip: Reovirus has demonstrated oncolysis or preferential replication in cancer cells. The anticancer activity of reovirus has been demonstrated across a spectrum of malignancies in the preclinical setting. The relatively tolerable toxicity profile of reovirus renders it an attractive agent as part of combination therapy in cancer treatment. Reovirus-mediated immune modulation contributes to its antitumor activity via innate and adaptive immune responses and renders it an attractive component of immunotherapy. Here we compile the most extensive list of clinical trials investigating the anticancer efficacy of reovirus to date.