A potential bat adenovirus-based oncolytic virus targeting canine cancers

Abstract 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) st...

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Autores principales:	Hiromichi Matsugo, Tomoya Kitamura-Kobayashi, Haruhiko Kamiki, Hiroho Ishida, Wataru Sekine, Akiko Takenaka-Uema, Takayuki Nakagawa, Shin Murakami, Taisuke Horimoto
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1f6668b97d5749b086f31d83f621b3f5
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spelling	oai:doaj.org-article:1f6668b97d5749b086f31d83f621b3f52021-12-02T18:51:53ZA potential bat adenovirus-based oncolytic virus targeting canine cancers10.1038/s41598-021-96101-42045-2322https://doaj.org/article/1f6668b97d5749b086f31d83f621b3f52021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96101-4https://doaj.org/toc/2045-2322Abstract 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.Hiromichi MatsugoTomoya Kitamura-KobayashiHaruhiko KamikiHiroho IshidaWataru SekineAkiko Takenaka-UemaTakayuki NakagawaShin MurakamiTaisuke HorimotoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hiromichi Matsugo Tomoya Kitamura-Kobayashi Haruhiko Kamiki Hiroho Ishida Wataru Sekine Akiko Takenaka-Uema Takayuki Nakagawa Shin Murakami Taisuke Horimoto A potential bat adenovirus-based oncolytic virus targeting canine cancers
description	Abstract 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	article
author	Hiromichi Matsugo Tomoya Kitamura-Kobayashi Haruhiko Kamiki Hiroho Ishida Wataru Sekine Akiko Takenaka-Uema Takayuki Nakagawa Shin Murakami Taisuke Horimoto
author_facet	Hiromichi Matsugo Tomoya Kitamura-Kobayashi Haruhiko Kamiki Hiroho Ishida Wataru Sekine Akiko Takenaka-Uema Takayuki Nakagawa Shin Murakami Taisuke Horimoto
author_sort	Hiromichi Matsugo
title	A potential bat adenovirus-based oncolytic virus targeting canine cancers
title_short	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_sort	potential bat adenovirus-based oncolytic virus targeting canine cancers
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1f6668b97d5749b086f31d83f621b3f5
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A potential bat adenovirus-based oncolytic virus targeting canine cancers

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