Liposome-encapsulated plasmid DNA of telomerase-specific oncolytic adenovirus with stealth effect on the immune system

Abstract Oncolytic virotherapy has the disadvantage of being unsuitable for systemic delivery due to immune elimination. Liposomal encapsulation is well-recognized to reduce immune elimination and enhance the stability of drugs in the bloodstream. In the present study, the potential of liposome-enca...

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Autores principales: Katsuyuki Aoyama, Shinji Kuroda, Toshiaki Morihiro, Nobuhiko Kanaya, Tetsushi Kubota, Yoshihiko Kakiuchi, Satoru Kikuchi, Masahiko Nishizaki, Shunsuke Kagawa, Hiroshi Tazawa, Toshiyoshi Fujiwara
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/20760a868f17433c8d8ecd81b0ee0a17
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spelling oai:doaj.org-article:20760a868f17433c8d8ecd81b0ee0a172021-12-02T15:04:53ZLiposome-encapsulated plasmid DNA of telomerase-specific oncolytic adenovirus with stealth effect on the immune system10.1038/s41598-017-14717-x2045-2322https://doaj.org/article/20760a868f17433c8d8ecd81b0ee0a172017-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-14717-xhttps://doaj.org/toc/2045-2322Abstract Oncolytic virotherapy has the disadvantage of being unsuitable for systemic delivery due to immune elimination. Liposomal encapsulation is well-recognized to reduce immune elimination and enhance the stability of drugs in the bloodstream. In the present study, the potential of liposome-encapsulated plasmid DNA of telomerase-specific oncolytic adenovirus (TelomeScan) expressing GFP (Lipo-pTS) as an oncolytic adenoviral agent suitable for systemic delivery was investigated. Lipo-pTS, which has a diameter of 40–50 nm, showed potent antitumor effects on HCT116 colon carcinoma cells in vitro and in vivo. Tumor selectivity of Lipo-pTS was independent of coxsackie and adenovirus receptor (CAR). Importantly, Lipo-pTS reduced production of adenovirus-neutralizing antibodies (AdNAbs) after intravenous administration into immune-competent mice compared to TelomeScan, and even in the presence of AdNAbs, Lipo-pTS maintained strong cytotoxicity. In conclusion, Lipo-pTS has the potential to become an oncolytic adenoviral agent suitable for systemic delivery with the characteristics of CAR-independent antitumor activity and a stealth effect on the immune system.Katsuyuki AoyamaShinji KurodaToshiaki MorihiroNobuhiko KanayaTetsushi KubotaYoshihiko KakiuchiSatoru KikuchiMasahiko NishizakiShunsuke KagawaHiroshi TazawaToshiyoshi FujiwaraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Katsuyuki Aoyama
Shinji Kuroda
Toshiaki Morihiro
Nobuhiko Kanaya
Tetsushi Kubota
Yoshihiko Kakiuchi
Satoru Kikuchi
Masahiko Nishizaki
Shunsuke Kagawa
Hiroshi Tazawa
Toshiyoshi Fujiwara
Liposome-encapsulated plasmid DNA of telomerase-specific oncolytic adenovirus with stealth effect on the immune system
description Abstract Oncolytic virotherapy has the disadvantage of being unsuitable for systemic delivery due to immune elimination. Liposomal encapsulation is well-recognized to reduce immune elimination and enhance the stability of drugs in the bloodstream. In the present study, the potential of liposome-encapsulated plasmid DNA of telomerase-specific oncolytic adenovirus (TelomeScan) expressing GFP (Lipo-pTS) as an oncolytic adenoviral agent suitable for systemic delivery was investigated. Lipo-pTS, which has a diameter of 40–50 nm, showed potent antitumor effects on HCT116 colon carcinoma cells in vitro and in vivo. Tumor selectivity of Lipo-pTS was independent of coxsackie and adenovirus receptor (CAR). Importantly, Lipo-pTS reduced production of adenovirus-neutralizing antibodies (AdNAbs) after intravenous administration into immune-competent mice compared to TelomeScan, and even in the presence of AdNAbs, Lipo-pTS maintained strong cytotoxicity. In conclusion, Lipo-pTS has the potential to become an oncolytic adenoviral agent suitable for systemic delivery with the characteristics of CAR-independent antitumor activity and a stealth effect on the immune system.
format article
author Katsuyuki Aoyama
Shinji Kuroda
Toshiaki Morihiro
Nobuhiko Kanaya
Tetsushi Kubota
Yoshihiko Kakiuchi
Satoru Kikuchi
Masahiko Nishizaki
Shunsuke Kagawa
Hiroshi Tazawa
Toshiyoshi Fujiwara
author_facet Katsuyuki Aoyama
Shinji Kuroda
Toshiaki Morihiro
Nobuhiko Kanaya
Tetsushi Kubota
Yoshihiko Kakiuchi
Satoru Kikuchi
Masahiko Nishizaki
Shunsuke Kagawa
Hiroshi Tazawa
Toshiyoshi Fujiwara
author_sort Katsuyuki Aoyama
title Liposome-encapsulated plasmid DNA of telomerase-specific oncolytic adenovirus with stealth effect on the immune system
title_short Liposome-encapsulated plasmid DNA of telomerase-specific oncolytic adenovirus with stealth effect on the immune system
title_full Liposome-encapsulated plasmid DNA of telomerase-specific oncolytic adenovirus with stealth effect on the immune system
title_fullStr Liposome-encapsulated plasmid DNA of telomerase-specific oncolytic adenovirus with stealth effect on the immune system
title_full_unstemmed Liposome-encapsulated plasmid DNA of telomerase-specific oncolytic adenovirus with stealth effect on the immune system
title_sort liposome-encapsulated plasmid dna of telomerase-specific oncolytic adenovirus with stealth effect on the immune system
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/20760a868f17433c8d8ecd81b0ee0a17
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