Current understanding of reovirus oncolysis mechanisms.

• Type of Material: Article
• Authors: Matthew B. Phillips, University of Arkansas; Johnasha D. Stuart, University of Arkansas; Roxana M. Rodríguez Stewart, Emory University; Jameson TL Berry, Emory University; Bernardo A. Mainou, Emory University; Karl W. Boehme, University of Arkansas
• Language: English
• Date: 2018
• Publisher: Dove Medical Press
• Publication Version: Final Published Version
• Copyright Statement: © 2018 Phillips et al. This work is published and licensed by Dove Medical Press Limited
• License: Creative Commons Attribution-Noncommercial 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.2147/OV.S143808
• Title of Journal or Parent Work: Oncolytic Virotherapy
• ISSN: 2253-1572
• Volume: 7
• Start Page: 53
• End Page: 63
• Grant/Funding Information: This research was supported by Public Health Award R01 AI118801 (K.W.B.), Children’s Healthcare of Atlanta, the Emory Children’s Pediatric Center, and Winship Cancer Institute IRG-14-188-01 from the American Cancer Society (B.A.M.).; Additional support was provided by the Center for Microbial Pathogenesis and Host Inflammatory Response (P20 GM103625).
• Keywords: immunotherapy; virotherapy; cancer; cell death; interferon
• Research Categories: Health Sciences, Immunology; Biology, Microbiology

Abstract

Mammalian orthoreovirus (reovirus) is under development as a cancer virotherapy. Clinical trials demonstrate that reovirus-based therapies are safe and tolerated in patients with a wide variety of cancers. Although reovirus monotherapy has proven largely ineffective, reovirus sensitizes cancer cells to existing chemotherapeutic agents and radiation. Clinical trials are underway to test the efficacy of reovirus in combination with chemotherapeutic and radiation regimens and to evaluate the effectiveness of reovirus in conjunction with immunotherapies. Central to the use of reovirus to treat cancer is its capacity to directly kill cancer cells and alter the cellular environment to augment other therapies. Apoptotic cell death is a prominent mechanism of reovirus cancer cell killing. However, reoviruses can also kill cancer cells through nonapoptotic mechanisms. Here, we describe mechanisms of reovirus cancer cell killing, highlight how reovirus is used in combination with existing cancer treatments, and discuss what is known as to how reovirus modulates cancer immunotherapy.