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

Am J Vet Res. 2012 Aug;73(8):1252-61. doi: 10.2460/ajvr.73.8.1252.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis
  • Blotting, Western
  • Cell Death
  • Cell Line, Tumor
  • Dog Diseases / therapy*
  • Dogs
  • Gene Deletion
  • Humans
  • Microscopy, Electron, Transmission
  • Myxoma virus / genetics
  • Myxoma virus / metabolism
  • Myxoma virus / physiology*
  • Neoplasms / therapy
  • Neoplasms / veterinary*
  • Oncolytic Virotherapy*
  • Oncolytic Viruses / genetics
  • Oncolytic Viruses / metabolism
  • Oncolytic Viruses / physiology
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rabbits
  • Viral Proteins / genetics
  • Viral Proteins / metabolism*

Substances

  • Serp2 protein, myxoma virus
  • Viral Proteins
  • Proto-Oncogene Proteins c-akt