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

## TL;DR

Vinorelbine improves the effectiveness of oncolytic vaccinia virus in treating ovarian cancer in preclinical models.

## Contribution

The study identifies vinorelbine as a combination agent that enhances oncolytic vaccinia virus efficacy in ovarian cancer.

## Key findings

- Vinorelbine and vaccinia virus combination induces apoptosis in murine ovarian cancer cells.
- Combining ΔVFTK-NG-GM-CSF virus with vinorelbine prolongs survival in a mouse model of ovarian cancer.
- Vinorelbine is a tubulin polymerization inhibitor that synergizes with oncolytic vaccinia virus.

## Abstract

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 Trp53−/− murine ovarian cancer cells. We identified a class of tubulin polymerization inhibitors including vinorelbine. The combination of vinorelbine and vaccinia induces ID8 Trp53−/− 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.

Way and colleagues explore strategies to enhance the efficacy of a recombinant oncolytic vaccinia virus designed for greater tumor specificity in ovarian cancer therapy. Their findings reveal that combining this virus with vinorelbine significantly improves survival in a syngeneic model of high-grade serous ovarian carcinoma.