Oncolytic Virus Therapy

Oncolytic viruses exploit defects in cancer cell antiviral defense and proliferation pathways to replicate selectively in tumors and induce direct lysis. Native oncolytic viruses include reovirus and Newcastle disease virus while engineered platforms use herpes simplex, vaccinia, adenovirus, and vesicular stomatitis virus modified to enhance tumor selectivity, attenuate normal tissue infection, and express therapeutic transgenes.

Talimogene laherparepvec is a genetically modified herpes simplex virus type one expressing granulocyte macrophage colony stimulating factor approved for intralesional injection in unresectable cutaneous, subcutaneous, and nodal melanoma with response rates of approximately twenty six percent and durable responses including in distant uninjected lesions through immune mediated bystander effect.

Combination strategies pair oncolytic virus with checkpoint inhibitors anti PD1 or anti CTLA4 to amplify immune activation, with chemotherapy to enhance tumor cell killing, or with adoptive cell therapy. Adverse effects include injection site reactions, fever, fatigue, and rare herpetic infection in immunocompromised contacts. Ongoing trials evaluate intravenous oncolytic viruses for systemic disease and combinations in glioblastoma, pancreatic cancer, and other refractory tumors.