Advancements in oncolytic virus therapy: a new horizon for ovarian cancer

Ovarian cancer remains the most lethal gynecological malignancy, and the limited durability of standard treatments has motivated the development of new therapeutic strategies. Oncolytic viruses selectively replicate within and lyse tumor cells, releasing tumor antigens and inflammatory signals that can convert an immunosuppressive tumor microenvironment into an immune-inflamed state. This review evaluates the principal platforms used in ovarian cancer, including adenovirus, reovirus, measles virus, vaccinia virus, herpes simplex virus, and vesicular stomatitis virus. We compare engineering approaches that enhance tumor-selective replication, cellular entry, transgene delivery, and local immune activation, and discuss strategies to overcome neutralizing antibodies, restricted intratumoral spread, off-target toxicity, and tumor heterogeneity. Particular emphasis is placed on cytokine- or bispecific T-cell engager-armed viruses and their combination with chemotherapy, immune checkpoint blockade, and cellular immunotherapy. Early-phase studies support the feasibility of intraperitoneal delivery, whereas a single-arm phase 2 study of Olvi-Vec followed by platinum-based chemotherapy reported encouraging results, and a randomized phase 3 trial is ongoing. No oncolytic viruses have been approved for ovarian cancer; however, current evidence supports biomarker-guided and rationally sequenced clinical development.