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A potential bat adenovirus-based oncolytic virus targeting canine cancers
Although a canine adenovirus (CAdV)-based oncolytic virus (OV) candidate targeting canine tumors has been reported, its oncolytic effect could be attenuated by CAdV vaccine-induced neutralizing antibodies in dog patients. To circumvent this issue, we focused on the bat adenovirus (BtAdV) strain, whi...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373906/ https://www.ncbi.nlm.nih.gov/pubmed/34408176 http://dx.doi.org/10.1038/s41598-021-96101-4 |
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author | Matsugo, Hiromichi Kitamura-Kobayashi, Tomoya Kamiki, Haruhiko Ishida, Hiroho Sekine, Wataru Takenaka-Uema, Akiko Nakagawa, Takayuki Murakami, Shin Horimoto, Taisuke |
author_facet | Matsugo, Hiromichi Kitamura-Kobayashi, Tomoya Kamiki, Haruhiko Ishida, Hiroho Sekine, Wataru Takenaka-Uema, Akiko Nakagawa, Takayuki Murakami, Shin Horimoto, Taisuke |
author_sort | Matsugo, Hiromichi |
collection | PubMed |
description | Although a canine adenovirus (CAdV)-based oncolytic virus (OV) candidate targeting canine tumors has been reported, its oncolytic effect could be attenuated by CAdV vaccine-induced neutralizing antibodies in dog patients. To circumvent this issue, we focused on the bat adenovirus (BtAdV) strain, which was previously isolated from healthy microbats. We previously showed that this virus replicated efficiently in canine cell lines and did not serologically cross-react with CAdVs, suggesting that it may offer the possibility of an OV candidate for canine tumors. Here, we tested the growth properties and cytotoxicity of the BtAdV Mm32 strain in a panel of canine tumor cells and found that its characteristics were equivalent to those of CAdVs. To produce an Mm32 construct with enhanced tumor specificity, we established a novel reverse genetics system for BtAdV based on bacterial artificial chromosomes, and generated a recombinant virus, Mm32-E1Ap + cTERTp, by inserting a tumor-specific canine telomerase reverse transcriptase promoter into its E1A regulatory region. The growth and cytotoxicity of this recombinant were superior to those of wild-type Mm32 in canine tumor cells, unlike in normal canine cells. These data suggest that Mm32-E1Ap + cTERTp could be a promising OV for alternative canine cancer therapies. |
format | Online Article Text |
id | pubmed-8373906 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-83739062021-08-20 A potential bat adenovirus-based oncolytic virus targeting canine cancers Matsugo, Hiromichi Kitamura-Kobayashi, Tomoya Kamiki, Haruhiko Ishida, Hiroho Sekine, Wataru Takenaka-Uema, Akiko Nakagawa, Takayuki Murakami, Shin Horimoto, Taisuke Sci Rep Article Although a canine adenovirus (CAdV)-based oncolytic virus (OV) candidate targeting canine tumors has been reported, its oncolytic effect could be attenuated by CAdV vaccine-induced neutralizing antibodies in dog patients. To circumvent this issue, we focused on the bat adenovirus (BtAdV) strain, which was previously isolated from healthy microbats. We previously showed that this virus replicated efficiently in canine cell lines and did not serologically cross-react with CAdVs, suggesting that it may offer the possibility of an OV candidate for canine tumors. Here, we tested the growth properties and cytotoxicity of the BtAdV Mm32 strain in a panel of canine tumor cells and found that its characteristics were equivalent to those of CAdVs. To produce an Mm32 construct with enhanced tumor specificity, we established a novel reverse genetics system for BtAdV based on bacterial artificial chromosomes, and generated a recombinant virus, Mm32-E1Ap + cTERTp, by inserting a tumor-specific canine telomerase reverse transcriptase promoter into its E1A regulatory region. The growth and cytotoxicity of this recombinant were superior to those of wild-type Mm32 in canine tumor cells, unlike in normal canine cells. These data suggest that Mm32-E1Ap + cTERTp could be a promising OV for alternative canine cancer therapies. Nature Publishing Group UK 2021-08-18 /pmc/articles/PMC8373906/ /pubmed/34408176 http://dx.doi.org/10.1038/s41598-021-96101-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Matsugo, Hiromichi Kitamura-Kobayashi, Tomoya Kamiki, Haruhiko Ishida, Hiroho Sekine, Wataru Takenaka-Uema, Akiko Nakagawa, Takayuki Murakami, Shin Horimoto, Taisuke A potential bat adenovirus-based oncolytic virus targeting canine cancers |
title | A potential bat adenovirus-based oncolytic virus targeting canine cancers |
title_full | A potential bat adenovirus-based oncolytic virus targeting canine cancers |
title_fullStr | A potential bat adenovirus-based oncolytic virus targeting canine cancers |
title_full_unstemmed | A potential bat adenovirus-based oncolytic virus targeting canine cancers |
title_short | A potential bat adenovirus-based oncolytic virus targeting canine cancers |
title_sort | potential bat adenovirus-based oncolytic virus targeting canine cancers |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373906/ https://www.ncbi.nlm.nih.gov/pubmed/34408176 http://dx.doi.org/10.1038/s41598-021-96101-4 |
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