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

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.