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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 3/2012

01-07-2012 | Translational Research and Biomarkers

A Novel Genetically Modified Oncolytic Vaccinia Virus in Experimental Models is Effective Against a Wide Range of Human Cancers

Authors: Dana Haddad, MD, Nanhai Chen, PhD, Qian Zhang, MD, PhD, Chun-Hao Chen, MD, Yong A. Yu, PhD, Lorena Gonzalez, MD, Jason Aguilar, MS, Pingdong Li, MD, Joyce Wong, MD, Aladar A. Szalay, PhD, Yuman Fong, MD

Published in: Annals of Surgical Oncology | Special Issue 3/2012

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Abstract

Background

Replication-competent oncolytic viruses have shown great promise as a potential cancer treatment. This study aimed to determine whether a novel vaccinia virus, GLV-1h151, with genetic modifications enhancing cancer specificity and enabling virus detection, is effective against a range of human cancers and is safe when administered in preclinical models.

Methods

GLV-1h151 was modified with deletion of thymidine kinase enhancing specificity and insertion of the green fluorescent protein (GFP) gene. The virus was tested in several human cancer cell lines for cytotoxicity including breast, lung, pancreatic, and colorectal. Virus replication was assessed via visualization of GFP expression and bioluminescence, and viral plaque assays. Finally, GLV-1h151 was administered systemically or intratumorally in mice with pancreatic cancer xenografts (PANC-1) to assess virus biodistribution, toxicity, and effect on tumor growth.

Results

GLV-1h151 effectively infected, replicated in, and killed several cancer cell types. Detection and visualization of virus replication was successful via fluorescence imaging of GFP expression, which was dose dependent. When administered intravenously or intratumorally in vivo, GLV-1h151 regressed tumor growth (P < 0.001) and displayed a good biosafety profile. GLV-1h151 infection and replication in tumors was successfully visualized via GFP and bioluminescence, with virus presence in tumors confirmed histologically.

Conclusions

GLV-1h151 is effective as an oncolytic agent against a wide range of cancers in cell culture and is effective against pancreatic human xenografts displaying a good biosafety profile and ability to be detected via optical imaging. GLV-1h151 thus adds another potential medium for the killing of cancer and detection of virus in infected tissue.
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Metadata
Title
A Novel Genetically Modified Oncolytic Vaccinia Virus in Experimental Models is Effective Against a Wide Range of Human Cancers
Authors
Dana Haddad, MD
Nanhai Chen, PhD
Qian Zhang, MD, PhD
Chun-Hao Chen, MD
Yong A. Yu, PhD
Lorena Gonzalez, MD
Jason Aguilar, MS
Pingdong Li, MD
Joyce Wong, MD
Aladar A. Szalay, PhD
Yuman Fong, MD
Publication date
01-07-2012
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue Special Issue 3/2012
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-011-2198-x

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