Antitumor efficacy of 34.5ENVE: a transcriptionally retargeted and "Vstat120"-expressing oncolytic virus.
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.
Department of Neurological Surgery, Dardinger Laboratory for Neuro-oncology and Neurosciences, The Ohio State University Medical Center, Columbus, Ohio 43210, USA.
Ji Young
JY
Yoo
Amy
A
Haseley
Anna
A
Bratasz
E Antonio
EA
Chiocca
Jianying
J
Zhang
Kimerly
K
Powell
Balveen
B
Kaur
D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D003588:Cytopathogenic Effect, Viral; D042783:Endothelial Cells / Q000378:metabolism / Q000821:virology; D005260:Female; D015870:Gene Expression; D023061:Gene Order; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D005910:Glioma / Q000235:genetics / Q000628:therapy; D018259:Herpesvirus 1, Human / Q000235:genetics*; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D009336:Necrosis / Q000235:genetics; D009369:Neoplasms / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics; D064231:Nestin; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics*; D016019:Survival Analysis; D014779:Virus Replication
D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin