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Title:
Vinorelbine enhances the efficacy of GM-CSF-armed oncolytic vaccinia virus in a preclinical model of ovarian high grade serous carcinoma | bioRxiv
Description:
Vaccinia virus, known for its clinical safety has a tropism for primary and metastatic tumours 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 polymerisation 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 GM-CSF and expressing NeonGreen (ΔVFTK-NG-GM-CSF) is tumour 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 vinorelbine is a promising agent to combine with oncolytic vaccinia virus approaches for the management of ovarian cancer. ### Competing Interest Statement The authors have declared no competing interest. Cancer Research UK, C422/A29942, CC2096 Wellcome Trust, CC2096 Medical Research Council, CC2096 Ovarian Cancer Action, PSN418
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Keywords {🔍}
cancer, biology, vaccinia, ovarian, view, orcid, profile, virus, vinorelbine, clinical, preprint, oncolytic, medrxiv, subject, reviews, combination, research, biorxiv, university, trials, epidemiology, search, results, model, high, grade, serous, carcinoma, michael, peer, pdf, approaches, recombinant, agents, identify, treatment, enhance, lacking, δvf, death, trp, cell, mouse, δvftknggmcsf, agent, competing, interest, authors, declared, information,
Topics {✒️}
epidemiology subject categories δvftk-ng-gm-csf virus clinical trials δvftk-ng-gm-csf biorxiv subject category ovarian cancer treatment genetics microbiology author/funder ovarian cancer reviews epidemiology papers health-related information recombinant vaccinia viruses oncolytic vaccinia monotherapies δvf virus lacking peer review [ keyword advanced search cc2096 wellcome trust syngeneic mouse model clinical safety study suggests vinorelbine viral thymidine kinase generous financial support chan zuckerberg initiative imperial college london vrije universiteit amsterdam articles animal behavior gm-csf competing interest statement context preprint vinorelbine enhances oncolytic approaches identify combination agents ovarian tissue induce death competing interest preclinical model attractive agents identify drugs vaccinia results follow antonio postigo metastatic tumours potential promise expressing neongreen tumour specific c422/a29942 psn418 copyright copyright holder
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