Reovirus Oncolysis and the Next Frontiers for This Unique Oncoviral Immunotherapy Publisher



Sharifi N ; Darb Emamie A ; Rafiee N ; Pashangzadeh S ; Walia E ; Martin NT ; Hoang HD ; Xiang X ; Alain T
Source: Seminars in Immunology Published:2025

Abstract

Reovirus is one of the most clinically investigated oncolytic viruses, with over 50 clinical trials and more than 1700 patients treated to date. Although it has yet to achieve complete regulatory approval, reovirus remains a promising oncolytic virus candidate for cancer immunotherapy due to its preferential replication in malignant cells, minimal toxicity in normal tissues, availability to be delivered via multiple routes, and strong immunostimulatory properties. As a non-enveloped, double-stranded RNA virus of the Reoviridae family, reovirus is typically asymptomatic in healthy individuals unlike its pathogenic relative, rotavirus, thus making it especially attractive for clinical use. Recent research has significantly expanded its therapeutic potential beyond direct oncolysis, highlighting its ability to remodel the tumor microenvironment, activate both innate and adaptive immunity, and synergize with chemotherapy, radiotherapy, and immune checkpoint inhibitors. Moreover, advances in oral delivery, nanoparticle encapsulation, mesenchymal stem cell-mediated transport, and genetic engineering, have further enhanced its safety, targeting precision, and therapeutic efficacy. This review summarizes recent breakthroughs in reovirus-based virotherapy and explores emerging strategies that may unlock its full potential as a next-generation immunotherapeutic platform. © 2025 Elsevier B.V., All rights reserved.