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Rapid, Seamless Generation of Recombinant Poxviruses using Host Range and Visual Selection
Published on: May 24, 2020
Potent oncolytic activity of raccoonpox virus in the absence of natural pathogenicity
Laura Evgin1, Markus Vähä-Koskela, Julia Rintoul
1Department of Biochemistry, University of Ottawa, Centre for Cancer Therapeutics, Ottawa Health Research Institute, Ottawa, Ontario, Canada.
Abstract:
A number of oncolytic virus (OV) candidates currently in clinical trials are human viruses that have been engineered to be safer for patient administration by limiting normal cell targeting and replication. The newest OVs include viruses that cause no disease in humans, yet still have natural tumor tropism. Raccoonpox virus (RCNV) is a member of the Orthopoxvirus genus of Poxviridae and closely related to vaccinia virus, yet has no known pathogenicity in any mammalian species. A screen of cells from the NCI-60 cancer cell panel using growth curves demonstrated greater than a log increase in replication of RCNV in nearly 74% of the cell lines tested, similar to other tested OV poxviruses. In normal cell lines, pretreatment with interferon (IFN)-alpha/beta resulted in significant inhibition of RCNV replication. In both xenograft and syngeneic models of solid tumors, injection of RCNV resulted in significantly slower tumor progression and increased survival of mice. RCNV treatment also prolonged survival in treatment-resistant models of brain tumors and decreased tumor burden by systemic administration in models of lung metastasis.
Insights
Raccoonpox virus (RCNV) shows promise as an oncolytic virus (OV) therapy. This virus effectively replicates in most cancer cells and slows tumor growth in preclinical models, offering a new avenue for cancer treatment.
Area of Science:
- Virology
- Oncology
- Cancer Research
Background:
- Oncolytic viruses (OVs) are engineered or naturally occurring viruses used in cancer therapy.
- Raccoonpox virus (RCNV), an Orthopoxvirus, exhibits no known mammalian pathogenicity.
- Novel OVs with natural tumor tropism are being developed for enhanced safety and efficacy.
Purpose of the Study:
- To evaluate the oncolytic potential of Raccoonpox virus (RCNV).
- To assess RCNV replication in cancer cell lines and its efficacy in preclinical tumor models.
Main Methods:
- Cancer cell lines (NCI-60 panel) were screened for RCNV replication using growth curves.
- Interferon (IFN)-alpha/beta pretreatment was used to assess normal cell response.
- RCNV efficacy was evaluated in xenograft and syngeneic models of solid tumors, brain tumors, and lung metastasis.
Main Results:
- RCNV demonstrated over a log increase in replication in approximately 74% of tested cancer cell lines.
- Interferon pretreatment significantly inhibited RCNV replication in normal cell lines.
- RCNV injection significantly slowed tumor progression and increased survival in mice across multiple tumor models, including treatment-resistant and metastatic settings.
Conclusions:
- Raccoonpox virus (RCNV) exhibits significant oncolytic activity against a broad range of cancer cell lines.
- RCNV demonstrates therapeutic potential in slowing tumor progression and improving survival in preclinical cancer models.
- RCNV represents a promising candidate for oncolytic virus therapy, particularly due to its natural tumor tropism and lack of pathogenicity.
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