Scientific Reports (Oct 2017)

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

DOI
https://doi.org/10.1038/s41598-017-14717-x
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 10

Abstract

Read online

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.