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Sci Rep. 2019 Feb 12;9(1):1865. doi: 10.1038/s41598-018-38385-7.

Pre-surgical neoadjuvant oncolytic virotherapy confers protection against rechallenge in a murine model of breast cancer.

Author information

1
Ottawa Hospital Research Institute, Centre for Innovative Cancer Research, Ottawa, K1H 8L6, Canada.
2
University of Ottawa, Department of Biochemistry, Microbiology and Immunology, Ottawa, K1H 8M5, Canada.
3
McMaster University, Department of Pathology and Molecular Medicine, Hamilton, ON, Canada.
4
Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands.
5
CRCHUM - "Centre de recherche du Centre Hospitalier de l'Université de Montréal" and "Institut du cancer de Montréal", Montreal, H2X 0A9, Canada. marie-claude.bourgeois-daigneault.chum@ssss.gouv.qc.ca.
6
"Département de microbiologie, infectiologie et immunologie, Faculté de Médecine, Université de Montréal", Montreal, H3C3J7, Canada. marie-claude.bourgeois-daigneault.chum@ssss.gouv.qc.ca.

Abstract

The use of oncolytic viruses (OVs) for cancer treatment is emerging as a successful strategy that combines the direct, targeted killing of the cancer with the induction of a long-lasting anti-tumor immune response. Using multiple aggressive murine models of triple-negative breast cancer, we have recently demonstrated that the early administration of oncolytic Maraba virus (MRB) prior to surgical resection of the primary tumor is sufficient to minimize the metastatic burden, protect against tumor rechallenge, cure a fraction of the mice and sensitize refractory tumors to immune checkpoint blockade without the need for further treatment. Here, we apply our surgical model to other OVs: Vesicular stomatitis virus (VSV), Adenovirus (Ad), Reovirus (Reo) and Herpes simplex virus (HSV) and show that all of the tested OVs could positively change the outcome of the treated animals. The growth of the primary and secondary tumors was differently affected by the various OVs and most of the viruses conferred survival benefits in this neoadjuvant setting despite the absence of direct treatment following rechallenge. This study establishes that OV-therapy confers long-term protection when administered in the pre-operative window of opportunity.

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