Oncolytic viruses in cancer therapy: Mechanisms, challenges, and emerging clinical applications

Oncolytic virus therapy is a promising and evolving strategy in cancer treatment that uses viruses to selectively destroy tumour cells and stimulate systemic antitumour immune responses. The purpose of this review is to provide a comprehensive overview of the mechanisms of action, recent therapeutic advances, and clinical potential of Oncolytic Viruses (OVs). A comprehensive literature review was conducted using major biomedical databases, including PubMed, Scopus, ScienceDirect, Web of Science, Directory of Open Access Journals, and Google Scholar. Relevant peer-reviewed articles, clinical trials, and regulatory data, mostly from the past 4 to 6 years, were screened, focusing on virus platforms, mechanisms of action, clinical outcomes, and emerging strategies. Several OVs, such as herpes simplex virus 1 (HSV-1), human adenovirus type 5 (HAdV-C5), mammalian orthoreovirus type 3 Dearing strain (T3D; pelareorep), and Vaccinia virus-derived platforms (e.g., JX-594/Pexa-Vec), have shown significant therapeutic efficacy. Among them, Talimogene laherparepvec (T-VEC) (a genetically engineered HSV-1) has been approved by the Food and Drug Administration for melanoma treatment. These viruses mediate their effects through direct oncolysis, induction of immunogenic cell death, and immune activation within the tumour microenvironment. Combination strategies involving immune checkpoint inhibitors (ICIs) and chemotherapy have shown synergistic effects. Despite encouraging clinical outcomes, challenges such as immune clearance, limited systemic delivery, and variable patient responses persist. Innovations, including synthetic viral engineering, nanoparticle-assisted delivery, and immune-enhancing combinations, are being explored to address these limitations. OVT offers a dual-action therapeutic approach and holds significant promise in the field of precision oncology. Continued innovation and clinical validation are essential for its widespread adoption in cancer care.