Vinorelbine enhances the efficacy of oncolytic vaccinia virus in a preclinical model of ovarian high grade serous carcinoma
File(s)
Accepted version
Author(s)
McNeish, Iain
Way, Michael
Drymiotou, Stephanie
Type
Journal Article
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<sup>−/−</sup> murine ovarian cancer cells. We identified a class of tubulin polymerization inhibitors including vinorelbine. The combination of vinorelbine and vaccinia induces ID8 Trp53<sup>−/−</sup> 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.
Date Issued
2026-03
Date Acceptance
2025-11-21
Citation
Molecular Therapy: Oncolytics
ISSN
2372-7705
Publisher
Elsevier
Start Page
201105
End Page
201105
Journal / Book Title
Molecular Therapy: Oncolytics
Volume
34
Issue
1
Publication Status
Accepted
Article Number
201105