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

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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5 Citations (Scopus)

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.

Original languageEnglish
Article number14177
JournalScientific reports
Volume7
Issue number1
DOIs
Publication statusPublished - Dec 1 2017

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