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Species D Human Adenovirus Type 9 Exhibits Better Virus-Spread Ability for Antitumor Efficacy among Alternative Serotypes

Species C human adenovirus serotype 5 (HAdV-C5) is widely used as a vector for cancer gene therapy, because it efficiently transduces target cells. A variety of HAdV-C5 vectors have been developed and tested in vitro and in vivo for cancer gene therapy. While clinical trials with HAdV-C5 vectors res...

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Autores principales: Uchino, Junji, Curiel, David T., Ugai, Hideyo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3913592/
https://www.ncbi.nlm.nih.gov/pubmed/24503714
http://dx.doi.org/10.1371/journal.pone.0087342
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author Uchino, Junji
Curiel, David T.
Ugai, Hideyo
author_facet Uchino, Junji
Curiel, David T.
Ugai, Hideyo
author_sort Uchino, Junji
collection PubMed
description Species C human adenovirus serotype 5 (HAdV-C5) is widely used as a vector for cancer gene therapy, because it efficiently transduces target cells. A variety of HAdV-C5 vectors have been developed and tested in vitro and in vivo for cancer gene therapy. While clinical trials with HAdV-C5 vectors resulted in effective responses in many cancer patients, administration of HAdV-C5 vectors to solid tumors showed responses in a limited area. A biological barrier in tumor mass is considered to hinder viral spread of HAdV-C5 vectors from infected cells. Therefore, efficient virus-spread from an infected tumor cell to surrounding tumor cells is required for successful cancer gene therapy. In this study, we compared HAdV-C5 to sixteen other HAdV serotypes selected from species A to G for virus-spread ability in vitro. HAdV-D9 showed better virus-spread ability than other serotypes, and its viral progeny were efficiently released from infected cells during viral replication. Although the HAdV-D9 fiber protein contains a binding site for coxsackie B virus and adenovirus receptor (CAR), HAdV-D9 showed expanded tropism for infection due to human CAR (hCAR)-independent attachment to target cells. HAdV-D9 infection effectively killed hCAR-negative cancer cells as well as hCAR-positive cancer cells. These results suggest that HADV-D9, with its better virus-spread ability, could have improved therapeutic efficacy in solid tumors compared to HAdV-C5.
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spelling pubmed-39135922014-02-06 Species D Human Adenovirus Type 9 Exhibits Better Virus-Spread Ability for Antitumor Efficacy among Alternative Serotypes Uchino, Junji Curiel, David T. Ugai, Hideyo PLoS One Research Article Species C human adenovirus serotype 5 (HAdV-C5) is widely used as a vector for cancer gene therapy, because it efficiently transduces target cells. A variety of HAdV-C5 vectors have been developed and tested in vitro and in vivo for cancer gene therapy. While clinical trials with HAdV-C5 vectors resulted in effective responses in many cancer patients, administration of HAdV-C5 vectors to solid tumors showed responses in a limited area. A biological barrier in tumor mass is considered to hinder viral spread of HAdV-C5 vectors from infected cells. Therefore, efficient virus-spread from an infected tumor cell to surrounding tumor cells is required for successful cancer gene therapy. In this study, we compared HAdV-C5 to sixteen other HAdV serotypes selected from species A to G for virus-spread ability in vitro. HAdV-D9 showed better virus-spread ability than other serotypes, and its viral progeny were efficiently released from infected cells during viral replication. Although the HAdV-D9 fiber protein contains a binding site for coxsackie B virus and adenovirus receptor (CAR), HAdV-D9 showed expanded tropism for infection due to human CAR (hCAR)-independent attachment to target cells. HAdV-D9 infection effectively killed hCAR-negative cancer cells as well as hCAR-positive cancer cells. These results suggest that HADV-D9, with its better virus-spread ability, could have improved therapeutic efficacy in solid tumors compared to HAdV-C5. Public Library of Science 2014-02-04 /pmc/articles/PMC3913592/ /pubmed/24503714 http://dx.doi.org/10.1371/journal.pone.0087342 Text en © 2014 Uchino et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Uchino, Junji
Curiel, David T.
Ugai, Hideyo
Species D Human Adenovirus Type 9 Exhibits Better Virus-Spread Ability for Antitumor Efficacy among Alternative Serotypes
title Species D Human Adenovirus Type 9 Exhibits Better Virus-Spread Ability for Antitumor Efficacy among Alternative Serotypes
title_full Species D Human Adenovirus Type 9 Exhibits Better Virus-Spread Ability for Antitumor Efficacy among Alternative Serotypes
title_fullStr Species D Human Adenovirus Type 9 Exhibits Better Virus-Spread Ability for Antitumor Efficacy among Alternative Serotypes
title_full_unstemmed Species D Human Adenovirus Type 9 Exhibits Better Virus-Spread Ability for Antitumor Efficacy among Alternative Serotypes
title_short Species D Human Adenovirus Type 9 Exhibits Better Virus-Spread Ability for Antitumor Efficacy among Alternative Serotypes
title_sort species d human adenovirus type 9 exhibits better virus-spread ability for antitumor efficacy among alternative serotypes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3913592/
https://www.ncbi.nlm.nih.gov/pubmed/24503714
http://dx.doi.org/10.1371/journal.pone.0087342
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