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Oncolysis of canine tumor cells by myxoma virus lacking the serp2 gene

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  • 1 Department of Pathobiology, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.
  • | 2 Department of Pathobiology, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.
  • | 3 Department of Pathobiology, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.
  • | 4 Department of Pathobiology, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.
  • | 5 Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL 32611.
  • | 6 Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL 32611.
  • | 7 Department of Pathobiology, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.

Abstract

Objective—To determine the oncolytic efficacy of an attenuated form of myxoma virus lacking the serp2 gene in canine tumor cells.

Sample—Primary cells were isolated from tumors that were surgically removed from dogs and from connective tissue obtained from the cadaver of a dog. Cells of various established cell lines from tumors and nontumorous tissues were obtained.

Procedures—Experiments were performed with cells in monolayer culture. Cell cultures were inoculated with wild-type myxoma viruses or myxoma viruses lacking the serp2 gene, and measures of cytopathic effects, viral growth kinetics, and cell death and apoptosis were determined.

Results—Myxoma viruses replicated in cells of many of the primary and established canine tumor cell lines. Canine tumor cells in which expression of activated protein kinase B was upregulated were more permissive to myxoma virus infection than were cells in which expression of activated protein kinase B was not upregulated. Myxoma viruses lacking the serp2 gene caused more cytopathic effects in canine tumor cells because of apoptosis than did wild-type myxoma viruses.

Conclusions and Clinical Relevance—Results of the present study indicated myxoma viruses lacking the serp2 gene may be useful for treatment of cancer in dogs.

Impact for Human Medicine—Results of the present study may be useful for development of novel oncolytic treatments for tumors in humans.

Abstract

Objective—To determine the oncolytic efficacy of an attenuated form of myxoma virus lacking the serp2 gene in canine tumor cells.

Sample—Primary cells were isolated from tumors that were surgically removed from dogs and from connective tissue obtained from the cadaver of a dog. Cells of various established cell lines from tumors and nontumorous tissues were obtained.

Procedures—Experiments were performed with cells in monolayer culture. Cell cultures were inoculated with wild-type myxoma viruses or myxoma viruses lacking the serp2 gene, and measures of cytopathic effects, viral growth kinetics, and cell death and apoptosis were determined.

Results—Myxoma viruses replicated in cells of many of the primary and established canine tumor cell lines. Canine tumor cells in which expression of activated protein kinase B was upregulated were more permissive to myxoma virus infection than were cells in which expression of activated protein kinase B was not upregulated. Myxoma viruses lacking the serp2 gene caused more cytopathic effects in canine tumor cells because of apoptosis than did wild-type myxoma viruses.

Conclusions and Clinical Relevance—Results of the present study indicated myxoma viruses lacking the serp2 gene may be useful for treatment of cancer in dogs.

Impact for Human Medicine—Results of the present study may be useful for development of novel oncolytic treatments for tumors in humans.

Contributor Notes

Supported by University of Illinois College of Veterinary Medicine Department of Pathology, the University of Illinois College of Veterinary Medicine Companion Animal Grants Memorial Fund, the Wayne D. and Josephine Spangler Fund, and the National Center for Research Resources (National Institutes of Health, T35 RR020292).

Presented as an oral presentation at the American College of Veterinary Pathologists–American Society for Veterinary Clinical Pathology Annual Meeting, Monterey, Calif, June 2010.

The authors thank Drs. Gail Scherba and Joanna Shisler for assistance with reporting of data and Karen Kelly for performance of transmission electron microscopy.

Address correspondence to Dr. MacNeill (almac@illinois.edu).