Preclinical Testing Oncolytic Vaccinia Virus Strain GLV-5b451 Expressing an Anti-VEGF Single-Chain Antibody for Canine Cancer Therapy

Viruses. 2015 Jul 20;7(7):4075-92. doi: 10.3390/v7072811.

Abstract

Virotherapy on the basis of oncolytic vaccinia virus (VACV) strains is a novel approach for canine cancer therapy. Here we describe, for the first time, the characterization and the use of VACV strain GLV-5b451 expressing the anti-vascular endothelial growth factor (VEGF) single-chain antibody (scAb) GLAF-2 as therapeutic agent against different canine cancers. Cell culture data demonstrated that GLV-5b451 efficiently infected and destroyed all four tested canine cancer cell lines including: mammary carcinoma (MTH52c), mammary adenoma (ZMTH3), prostate carcinoma (CT1258), and soft tissue sarcoma (STSA-1). The GLV-5b451 virus-mediated production of GLAF-2 antibody was observed in all four cancer cell lines. In addition, this antibody specifically recognized canine VEGF. Finally, in canine soft tissue sarcoma (CSTS) xenografted mice, a single systemic administration of GLV-5b451 was found to be safe and led to anti-tumor effects resulting in the significant reduction and substantial long-term inhibition of tumor growth. A CD31-based immuno-staining showed significantly decreased neo-angiogenesis in GLV-5b451-treated tumors compared to the controls. In summary, these findings indicate that GLV-5b451 has potential for use as a therapeutic agent in the treatment of CSTS.

Keywords: angiogenesis; antibody production; cancer; canine cancer cell lines; canine cancer therapy; canine soft tissue sarcoma (CSTS); oncolytic virus.

MeSH terms

  • Animals
  • Dog Diseases / genetics
  • Dog Diseases / metabolism
  • Dog Diseases / therapy*
  • Dogs
  • Female
  • Mice
  • Mice, Nude
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / therapy
  • Neoplasms / veterinary*
  • Oncolytic Virotherapy*
  • Oncolytic Viruses / genetics*
  • Oncolytic Viruses / metabolism
  • Single-Chain Antibodies / genetics
  • Single-Chain Antibodies / immunology*
  • Single-Chain Antibodies / therapeutic use
  • Vaccinia virus / genetics*
  • Vaccinia virus / metabolism
  • Vascular Endothelial Growth Factor A / immunology*

Substances

  • Single-Chain Antibodies
  • Vascular Endothelial Growth Factor A