Potent oncolytic activity of raccoonpox virus in the absence of natural pathogenicity.
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.
Evgin
Laura
L
Department of Biochemistry, University of Ottawa, Centre for Cancer Therapeutics, Ottawa Health Research Institute, Ottawa, Ontario, Canada.
Vähä-Koskela
Markus
M
Rintoul
Julia
J
Falls
Theresa
T
Le Boeuf
Fabrice
F
Barrett
John W
JW
Bell
John C
JC
Stanford
Marianne M
MM
D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000235:genetics / Q000502:physiology*; D011212:Poxviridae / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D016898:Interferon-alpha