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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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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. |
format | Online Article Text |
id | pubmed-3913592 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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