Oncolytic Virotherapy in Solid Tumors: A Current Review

Oncolytic viruses (OVs) are naturally occurring or genetically modified viruses that selectively target cancer cells for infection, replication, and lysis. Specifically, their tumor tropism and promising antitumoral efficacy through direct oncolysis and indirect immunogenic activation make OVs a novel immunotherapeutic class of high interest. OVs find particular relevance in solid tumors that are notoriously refractory to chemoradiation, are immunologically silent, express heterogeneous antigens, and are difficult to penetrate with existing agents. Distinct OVs have been identified; many have been extensively studied and have been approved or are pending approval in humans, including adenoviruses, herpes simplex viruses, reoviruses, vaccinia viruses, and measles viruses. While each virus type is unique in size, structure, targeting, replication, and behavior, they broadly share several antitumor mechanisms-direct oncolysis, immunogenic cell death, and modification of the tumor microenvironment. Modifications to OVs build on these features, ranging from genetic manipulation to insertion of cytokines or genes of interest, such as checkpoint inhibitors, altering virulence for tumor specificity or safety, to viral targeting enhancements. Moreover, the most recent iterations of OVs are often paired as combination therapies with chemotherapy, radiation, or other immunotherapeutic agents. This review aims to provide an up-to-date, in-depth discussion of major OVs, their precise mechanisms of action, modifications for improved therapeutic outcomes, and current combination therapy approaches against solid tumors in pre-clinical and clinical settings.