Antitumor efficacy of 34.5ENVE: a transcriptionally retargeted and "Vstat120"-expressing oncolytic virus

Mol Ther. 2012 Feb;20(2):287-97. doi: 10.1038/mt.2011.208. Epub 2011 Oct 25.


Here, we describe the construction and testing of a novel herpes simplex virus type 1 (HSV-1) derived oncolytic virus (OV): 34.5ENVE (viral ICP34.5 Expressed by Nestin promotor and Vstat120 Expressing), for the treatment of cancer. This virus showed significant glioma-specific killing and antiangiogenic effects in vitro and in vivo. Treatment of subcutaneous and intracranial glioma-bearing mice with 34.5ENVE showed a significant increase in median survival of mice in four different glioma models. Histology and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) revealed reduced microvessel density (MVD) and increased tumoral necrosis in 34.5ENVE-treated tumor tissue compared to control OV-treated tumor tissue. Collectively, these results describe the construction, efficacy, and impact on tumor microenvironment of a transcriptionally driven OV armed with Vstat120 gene expression. These preclinical results will facilitate future clinical testing of 34.5ENVE.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Movement
  • Cytopathogenic Effect, Viral
  • Endothelial Cells / metabolism
  • Endothelial Cells / virology
  • Female
  • Gene Expression
  • Gene Order
  • Genetic Therapy
  • Genetic Vectors / genetics*
  • Glioma / genetics
  • Glioma / therapy
  • Herpesvirus 1, Human / genetics*
  • Humans
  • Intermediate Filament Proteins / genetics
  • Mice
  • Mice, Nude
  • Necrosis / genetics
  • Neoplasms / genetics
  • Neoplasms / mortality
  • Neoplasms / therapy*
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Nerve Tissue Proteins / genetics
  • Nestin
  • Oncolytic Virotherapy*
  • Oncolytic Viruses / genetics*
  • Survival Analysis
  • Virus Replication


  • Intermediate Filament Proteins
  • NES protein, human
  • Nerve Tissue Proteins
  • Nes protein, mouse
  • Nestin