Virotherapy

Virotherapy is a therapeutic approach in oncology that uses viruses to treat cancer. It encompasses oncolytic virotherapy, which uses replication-competent viruses that preferentially infect and lyse cancer cells, and viroimmunotherapy, which aims to stimulate an anti-tumor immune response through viral oncolysis or by delivering immunomodulatory genes. Virus platforms include herpes simplex virus, adenovirus, vaccinia, reovirus, parvovirus, and others that are engineered for safety and tumor selectivity.

Mechanisms include selective replication in cancer cells with defective antiviral responses, direct oncolysis, and the release of tumor antigens and danger signals that activate dendritic cells and T cells. Many vectors are engineered to express cytokines such as GM‑CSF to boost systemic immunity. Some approaches combine virotherapy with immune checkpoint inhibitors to enhance anti-tumor responses.

Regulatory status and examples: The first and best-known approval is talimogene laherparepvec (T-VEC), a modified herpes simplex virus, for advanced melanoma in 2015. Other oncolytic viruses have gained regulatory approval in different countries, such as G47∆-based therapies (Delytact) for glioblastoma in Japan, with ongoing trials globally. Numerous agents remain in clinical trials for a range of solid tumors.

Challenges include delivering virus to tumors, especially after intravenous administration, pre-existing immunity that neutralizes the virus, safety concerns about infection of normal tissues, and variable efficacy across tumor types. Ongoing research explores optimization of delivery methods, virus engineering, combination strategies, and biomarkers to identify responsive patients.