Recent Advances in Oncolytic Virotherapy: Insights From Clinical Trials and Combination Treatment Strategies Publisher Pubmed



Salahi Ardekani O ; Zarezade M ; Meymandi B ; Azami N ; Mahdavi B ; Shahani T
Source: Virology Journal Published:2026

Abstract

Background and aim: Oncolytic virotherapy is a novel therapeutic paradigm in oncology that uses viruses to selectively replicate within cancer cells, causing targeted tumor cell destruction with minimal toxicity to healthy tissues. With the rapid growth of oncolytic virotherapy and the accumulation of clinical studies on this subject, the present review aims to provide a comprehensive evaluation of current achievements in cancer treatments involving oncolytic viruses (OVs). Main text: Numerous clinical trials have been conducted to assess the therapeutic efficacy and safety of OVs across a variety of cancer types. Several OVs have received approval worldwide, with the primary ones being T-VEC (Imlygic) in the treatment of melanoma (FDA/European approval), Oncorine (H101) for cancers of the head and neck (China), and Teserpaturev for gliomas (Japan). Furthermore, several other clinical trials are currently underway, demonstrating the growing interest in the clinical development of oncolytic virotherapy as a potentially effective anticancer strategy. These clinical trials have explored multiple strategies to enhance the safety and therapeutic efficacy of OVs. Approaches include genetic modifications to improve tumor specificity, promote effective cancer cell lysis, and stimulate robust antitumor immune responses. In addition, OVs have been combined with other treatment modalities, including radiotherapy, chemotherapy, cell-based therapies, immune checkpoint inhibitors, cancer vaccines, and targeted small-molecule agents. Innovative delivery systems, including cellular carriers, nanoparticles, hydrogels, and cell-based robotic platforms, have also been developed. Conclusion: Oncolytic virotherapy is a new and rapidly evolving treatment modality, which is promising in therapy against cancer. Clinical trials have proven that OVs can be a safe and effective way to treat cancer, making them an essential part of future therapies. © The Author(s) 2026.