Oncolytic poxviruses

Abstract

Modern data on selection and design of poxviruses, which are able to specifically lyse tumor cells of various origins and induce antitumor immunity and apoptosis of malignant cells, are presented in this review. Work is being carried out in several areas, including attenuation of viruses, insertion of immunomodulatory protein genes, and insertion of antitumor protein genes. Thymidine kinase and viral growth factor genes, inactivation of which results in an inability of the virus to replicate in nondividing cells and thus promotes an increase in selectivity for the tumor cells, make the greatest contribution in attenuation of the virus. Among the immunomodulatory proteins, interleukins 2 and 12 and granulocyte-macrophage colony-stimulating factor were the most promising in oncolytic viral therapy. An attempt to use the p53 protein gene, expressed by the Vaccinia virus, for targeted apoptosis of the tumor cells was described. Use of double and triple viral recombinants, which carry genes of differently directed effects, seems very promising. Encouraging results were obtained using the Vaccinia virus in cancer therapy by means of prodrugs and angiogenesis inhibitors. At present, two poxvirus strains are undergoing a third stage of clinical trials as antitumor drugs in the United States. © 2012 Allerton Press, Inc.