Ovarian cancer gene therapy using HPV-16 pseudovirion carrying the HSV-tk gene.

Ovarian cancer is the leading cause of death from all gynecological cancers and conventional therapies such as surgery, chemotherapy, and radiotherapy usually fail to control advanced stages of the disease. Thus, there is an urgent need for alternative and innovative therapeutic options. We reason t...

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Main Authors: Chien-Fu Hung, An Jen Chiang, Hsiao-Hsuan Tsai, Martin G Pomper, Tae Heung Kang, Richard R Roden, T-C Wu
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3398866?pdf=render
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spelling doaj-6290ab8911e7467c8c747308f2aac03e2020-11-25T01:48:14ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0177e4098310.1371/journal.pone.0040983Ovarian cancer gene therapy using HPV-16 pseudovirion carrying the HSV-tk gene.Chien-Fu HungAn Jen ChiangHsiao-Hsuan TsaiMartin G PomperTae Heung KangRichard R RodenT-C WuOvarian cancer is the leading cause of death from all gynecological cancers and conventional therapies such as surgery, chemotherapy, and radiotherapy usually fail to control advanced stages of the disease. Thus, there is an urgent need for alternative and innovative therapeutic options. We reason that cancer gene therapy using a vector capable of specifically delivering an enzyme-encoding gene to ovarian cancer cells will allow the cancer cell to metabolize a harmless prodrug into a potent cytotoxin, which will lead to therapeutic effects. In the current study, we explore the use of a human papillomavirus (HPV) pseudovirion to deliver a herpes simplex virus thymidine kinase (HSV-tk) gene to ovarian tumor cells. We found that the HPV-16 pseudovirion was able to preferentially infect murine and human ovarian tumor cells when administered intraperitoneally. Furthermore, intraperitoneal injection of HPV-16 pseudovirions carrying the HSV-tk gene followed by treatment with ganciclovir led to significant therapeutic anti-tumor effects in murine ovarian cancer-bearing mice. Our data suggest that HPV pseudovirion may serve as a potential delivery vehicle for ovarian cancer gene therapy.http://europepmc.org/articles/PMC3398866?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Chien-Fu Hung
An Jen Chiang
Hsiao-Hsuan Tsai
Martin G Pomper
Tae Heung Kang
Richard R Roden
T-C Wu
spellingShingle Chien-Fu Hung
An Jen Chiang
Hsiao-Hsuan Tsai
Martin G Pomper
Tae Heung Kang
Richard R Roden
T-C Wu
Ovarian cancer gene therapy using HPV-16 pseudovirion carrying the HSV-tk gene.
PLoS ONE
author_facet Chien-Fu Hung
An Jen Chiang
Hsiao-Hsuan Tsai
Martin G Pomper
Tae Heung Kang
Richard R Roden
T-C Wu
author_sort Chien-Fu Hung
title Ovarian cancer gene therapy using HPV-16 pseudovirion carrying the HSV-tk gene.
title_short Ovarian cancer gene therapy using HPV-16 pseudovirion carrying the HSV-tk gene.
title_full Ovarian cancer gene therapy using HPV-16 pseudovirion carrying the HSV-tk gene.
title_fullStr Ovarian cancer gene therapy using HPV-16 pseudovirion carrying the HSV-tk gene.
title_full_unstemmed Ovarian cancer gene therapy using HPV-16 pseudovirion carrying the HSV-tk gene.
title_sort ovarian cancer gene therapy using hpv-16 pseudovirion carrying the hsv-tk gene.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2012-01-01
description Ovarian cancer is the leading cause of death from all gynecological cancers and conventional therapies such as surgery, chemotherapy, and radiotherapy usually fail to control advanced stages of the disease. Thus, there is an urgent need for alternative and innovative therapeutic options. We reason that cancer gene therapy using a vector capable of specifically delivering an enzyme-encoding gene to ovarian cancer cells will allow the cancer cell to metabolize a harmless prodrug into a potent cytotoxin, which will lead to therapeutic effects. In the current study, we explore the use of a human papillomavirus (HPV) pseudovirion to deliver a herpes simplex virus thymidine kinase (HSV-tk) gene to ovarian tumor cells. We found that the HPV-16 pseudovirion was able to preferentially infect murine and human ovarian tumor cells when administered intraperitoneally. Furthermore, intraperitoneal injection of HPV-16 pseudovirions carrying the HSV-tk gene followed by treatment with ganciclovir led to significant therapeutic anti-tumor effects in murine ovarian cancer-bearing mice. Our data suggest that HPV pseudovirion may serve as a potential delivery vehicle for ovarian cancer gene therapy.
url http://europepmc.org/articles/PMC3398866?pdf=render
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