Recombinant targeted toxin based on HER2-specific DARPin possesses a strong selective cytotoxic effect in vitro and a potent antitumor activity in vivo

Evgeniya Sokolova, Galina Proshkina, Olga Kutova, Olga Shilova, Anastasiya Ryabova, Alexey Schulga, Oleg Stremovskiy, Tatiana Zdobnova, Irina Balalaeva, Sergey Deyev

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

DARPins fused with other proteins are promising non-immunoglobulin scaffolds for specific binding to target cells. In this study HER2-specific DARPin (DARPin-9-29) was used as a tumor-targeting moiety for the delivery of a cytotoxic agent - the fragment of Pseudomonas aeruginosa exotoxin A. It was determined that DARPin-PE40 possesses a considerable cytotoxic activity and induces apoptosis in HER2-positive cells. Cytotoxic effect of DARPin-PE40 strongly correlates with the HER2 expression level. The effect of intravenous administration of DARPin-PE40 was tested in the xenograft model of breast cancer. It was shown that treatment of animals with DARPin-PE40 caused strong and prolonged suppression of xenograft tumor growth.

Original languageEnglish
Pages (from-to)48-56
Number of pages9
JournalJournal of Controlled Release
Volume233
DOIs
Publication statusPublished - 10 Jul 2016
Externally publishedYes

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Keywords

  • DARPin
  • HER2
  • PE40
  • Pseudomonas aeruginosa exotoxin A
  • Recombinant targeted toxin
  • Targeted therapy

ASJC Scopus subject areas

  • Pharmaceutical Science

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