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

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...

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Autores principales: Aoyama, Katsuyuki, Kuroda, Shinji, Morihiro, Toshiaki, Kanaya, Nobuhiko, Kubota, Tetsushi, Kakiuchi, Yoshihiko, Kikuchi, Satoru, Nishizaki, Masahiko, Kagawa, Shunsuke, Tazawa, Hiroshi, Fujiwara, Toshiyoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5658411/
https://www.ncbi.nlm.nih.gov/pubmed/29074882
http://dx.doi.org/10.1038/s41598-017-14717-x
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author Aoyama, Katsuyuki
Kuroda, Shinji
Morihiro, Toshiaki
Kanaya, Nobuhiko
Kubota, Tetsushi
Kakiuchi, Yoshihiko
Kikuchi, Satoru
Nishizaki, Masahiko
Kagawa, Shunsuke
Tazawa, Hiroshi
Fujiwara, Toshiyoshi
author_facet Aoyama, Katsuyuki
Kuroda, Shinji
Morihiro, Toshiaki
Kanaya, Nobuhiko
Kubota, Tetsushi
Kakiuchi, Yoshihiko
Kikuchi, Satoru
Nishizaki, Masahiko
Kagawa, Shunsuke
Tazawa, Hiroshi
Fujiwara, Toshiyoshi
author_sort Aoyama, Katsuyuki
collection PubMed
description 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.
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spelling pubmed-56584112017-10-31 Liposome-encapsulated plasmid DNA of telomerase-specific oncolytic adenovirus with stealth effect on the immune system Aoyama, Katsuyuki Kuroda, Shinji Morihiro, Toshiaki Kanaya, Nobuhiko Kubota, Tetsushi Kakiuchi, Yoshihiko Kikuchi, Satoru Nishizaki, Masahiko Kagawa, Shunsuke Tazawa, Hiroshi Fujiwara, Toshiyoshi Sci Rep Article 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. Nature Publishing Group UK 2017-10-26 /pmc/articles/PMC5658411/ /pubmed/29074882 http://dx.doi.org/10.1038/s41598-017-14717-x Text en © The Author(s) 2017 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Aoyama, Katsuyuki
Kuroda, Shinji
Morihiro, Toshiaki
Kanaya, Nobuhiko
Kubota, Tetsushi
Kakiuchi, Yoshihiko
Kikuchi, Satoru
Nishizaki, Masahiko
Kagawa, Shunsuke
Tazawa, Hiroshi
Fujiwara, Toshiyoshi
Liposome-encapsulated plasmid DNA of telomerase-specific oncolytic adenovirus with stealth effect on the immune system
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5658411/
https://www.ncbi.nlm.nih.gov/pubmed/29074882
http://dx.doi.org/10.1038/s41598-017-14717-x
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