Vinorelbine enhances the efficacy of oncolytic vaccinia virus in a preclinical model of ovarian high-grade serous carcinoma

Vaccinia virus, known for its clinical safety, has a tropism for primary and metastatic tumors as well as ovarian tissue. Consequently, oncolytic approaches with recombinant vaccinia viruses have emerged as attractive agents against ovarian cancer. Unfortunately, oncolytic vaccinia monotherapies are yet to live up to their potential promise. Given this, there is a need to identify combination agents that improve the effectiveness of vaccinia in ovarian cancer treatment. We screened 9,000 compounds to identify drugs that enhance the ability of a recombinant vaccinia virus lacking VGF and F1 (ΔVF) to induce death of ID8 <i>Trp53</i> ^-/- murine ovarian cancer cells. We identified a class of tubulin polymerization inhibitors including vinorelbine. The combination of vinorelbine and vaccinia induces ID8 <i>Trp53</i> ^-/- cell death via apoptosis. In a syngeneic mouse model of high-grade serous ovarian carcinoma, ΔVF virus lacking the viral thymidine kinase (TK), armed with granulocyte-macrophage colony-stimulating factor (GM-CSF), and expressing NeonGreen (ΔVFTK-NG-GM-CSF) is tumor-specific. A combination of the ΔVFTK-NG-GM-CSF virus with vinorelbine prolongs mouse survival compared to the treatment of mice with either agent alone. Our study suggests that vinorelbine is a promising agent to combine with oncolytic vaccinia virus for the management of ovarian cancer.