Novel Oncolytic Virus Armed with Cancer Suicide Gene and Normal Vasculogenic Gene for Improved Anti-Tumor Activity

Here, we developed a novel oncolytic vaccinia virus (NOV) with the dual advantages of cancer selectivity and normal vessel reconstructive activity by replacing the viral thymidine kinase (vTk) and vaccinia growth factor (VGF) genes with genes encoding TNF-related apoptosis-inducing ligand (TRAIL) an...

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Main Authors: Su-Nam Jeong, So Young Yoo
Format: Article
Language:English
Published: MDPI AG 2020-04-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/12/5/1070
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spelling doaj-64017451b44f4568a2dfdaa732a31c1c2020-11-25T03:14:01ZengMDPI AGCancers2072-66942020-04-01121070107010.3390/cancers12051070Novel Oncolytic Virus Armed with Cancer Suicide Gene and Normal Vasculogenic Gene for Improved Anti-Tumor ActivitySu-Nam Jeong0So Young Yoo1BIO-IT Foundry Technology Institute, Pusan National University, Busan 46241, KoreaBIO-IT Foundry Technology Institute, Pusan National University, Busan 46241, KoreaHere, we developed a novel oncolytic vaccinia virus (NOV) with the dual advantages of cancer selectivity and normal vessel reconstructive activity by replacing the viral thymidine kinase (vTk) and vaccinia growth factor (VGF) genes with genes encoding TNF-related apoptosis-inducing ligand (TRAIL) and angiopoietin 1 (Ang1), respectively. The pan-cancer-specific oncolytic potency of NOV was confirmed in various human and mouse cancer cell lines (colon, liver, pancreas, cholangiocarcinoma, cervical cancer, osteosarcoma, and melanoma). Vaccinia virus (VV) treatment directly induced early apoptosis in tumors within 24 h, and this effect was enhanced with further engineering; VGF and Tk deletion with Ang1 and TRAIL insertion. Meanwhile, treatment with the conventional anti-cancer drug cisplatin did not induce apoptosis. A virus-treated CT26 mouse colon cancer syngeneic model showed attenuated tumor growth, which was in accordance with the results of percent survival measurement, CD8 expression analysis, and TUNEL staining with advanced genetic engineering (vAng1 < vTRAIL < NOV). Taken together, our results indicate that NOV induces cancer tissue apoptosis and anti-tumor immunity and may constitute a highly advantageous therapeutic agent for next-generation solid tumor virotherapy with pan-cancer-specific oncolytic activity and high biosafety.https://www.mdpi.com/2072-6694/12/5/1070oncolytic virusangiopoietin 1TRAIL
collection DOAJ
language English
format Article
sources DOAJ
author Su-Nam Jeong
So Young Yoo
spellingShingle Su-Nam Jeong
So Young Yoo
Novel Oncolytic Virus Armed with Cancer Suicide Gene and Normal Vasculogenic Gene for Improved Anti-Tumor Activity
Cancers
oncolytic virus
angiopoietin 1
TRAIL
author_facet Su-Nam Jeong
So Young Yoo
author_sort Su-Nam Jeong
title Novel Oncolytic Virus Armed with Cancer Suicide Gene and Normal Vasculogenic Gene for Improved Anti-Tumor Activity
title_short Novel Oncolytic Virus Armed with Cancer Suicide Gene and Normal Vasculogenic Gene for Improved Anti-Tumor Activity
title_full Novel Oncolytic Virus Armed with Cancer Suicide Gene and Normal Vasculogenic Gene for Improved Anti-Tumor Activity
title_fullStr Novel Oncolytic Virus Armed with Cancer Suicide Gene and Normal Vasculogenic Gene for Improved Anti-Tumor Activity
title_full_unstemmed Novel Oncolytic Virus Armed with Cancer Suicide Gene and Normal Vasculogenic Gene for Improved Anti-Tumor Activity
title_sort novel oncolytic virus armed with cancer suicide gene and normal vasculogenic gene for improved anti-tumor activity
publisher MDPI AG
series Cancers
issn 2072-6694
publishDate 2020-04-01
description Here, we developed a novel oncolytic vaccinia virus (NOV) with the dual advantages of cancer selectivity and normal vessel reconstructive activity by replacing the viral thymidine kinase (vTk) and vaccinia growth factor (VGF) genes with genes encoding TNF-related apoptosis-inducing ligand (TRAIL) and angiopoietin 1 (Ang1), respectively. The pan-cancer-specific oncolytic potency of NOV was confirmed in various human and mouse cancer cell lines (colon, liver, pancreas, cholangiocarcinoma, cervical cancer, osteosarcoma, and melanoma). Vaccinia virus (VV) treatment directly induced early apoptosis in tumors within 24 h, and this effect was enhanced with further engineering; VGF and Tk deletion with Ang1 and TRAIL insertion. Meanwhile, treatment with the conventional anti-cancer drug cisplatin did not induce apoptosis. A virus-treated CT26 mouse colon cancer syngeneic model showed attenuated tumor growth, which was in accordance with the results of percent survival measurement, CD8 expression analysis, and TUNEL staining with advanced genetic engineering (vAng1 < vTRAIL < NOV). Taken together, our results indicate that NOV induces cancer tissue apoptosis and anti-tumor immunity and may constitute a highly advantageous therapeutic agent for next-generation solid tumor virotherapy with pan-cancer-specific oncolytic activity and high biosafety.
topic oncolytic virus
angiopoietin 1
TRAIL
url https://www.mdpi.com/2072-6694/12/5/1070
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AT soyoungyoo noveloncolyticvirusarmedwithcancersuicidegeneandnormalvasculogenicgeneforimprovedantitumoractivity
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