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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...

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Autores principales: Matsugo, Hiromichi, Kitamura-Kobayashi, Tomoya, Kamiki, Haruhiko, Ishida, Hiroho, Sekine, Wataru, Takenaka-Uema, Akiko, Nakagawa, Takayuki, Murakami, Shin, Horimoto, Taisuke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
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.
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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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