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PMID: 22031239 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Molecular therapy : the journal of the American Society of Gene Therapy ·Vol. 20 ·No. 2 ·2012-02-00 ·Pages 287-97

Yoo JY, Haseley A, Bratasz A, Chiocca EA, Zhang J, Powell K, Kaur B

Abstract

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.

MeSH Terms
Animals Cell Line Cell Movement Cytopathogenic Effect, Viral Endothelial Cells/metabolism,virology Female Gene Expression Gene Order Genetic Therapy Genetic Vectors/genetics Glioma/genetics,therapy Herpesvirus 1, Human/genetics Humans Intermediate Filament Proteins/genetics Mice Mice, Nude Necrosis/genetics Neoplasms/genetics,mortality,therapy Neovascularization, Pathologic/genetics,metabolism Nerve Tissue Proteins/genetics Nestin Oncolytic Virotherapy Oncolytic Viruses/genetics Survival Analysis Virus Replication
Chemicals
Intermediate Filament Proteins NES protein, human Nerve Tissue Proteins Nes protein, mouse Nestin
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Yoo Ji Young
Department of Neurological Surgery, Dardinger Laboratory for Neuro-oncology and Neurosciences, The Ohio State University Medical Center, Columbus, Ohio 43210, USA.
Haseley Amy
Bratasz Anna
Chiocca E Antonio
Zhang Jianying
Powell Kimerly
Kaur Balveen
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Article Info
Journal
Molecular therapy : the journal of the American Society of Gene Therapy
Abbr.
Mol Ther
ISSN
1525-0024
DOI
10.1038/mt.2011.208
Published
2012-02-00
Epub
2011-00-25
Pages
287-97
Language
English
Region
United States
NLM ID
100890581
PMCID
PMC3277242
Subset
IM
Grants
NCI NIH HHS · R01 CA150153 · United States
NINDS NIH HHS · R01 NS064607 · United States
NINDS NIH HHS · NS045758 · United States
NCI NIH HHS · 1R01CA150153 · United States
NINDS NIH HHS · 1R01NS064607 · United States
NINDS NIH HHS · P30 NS045758 · United States
NINDS NIH HHS · P30 NS045758-06A1 · United States
External Links
PubMed source DOI: 10.1038/mt.2011.208 PMC Full Text View journal details
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