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

22 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

Fingerprint

Immunotoxins
Heterografts
Cytotoxins
Intravenous Administration
Neoplasms
Apoptosis
Breast Neoplasms
Growth
Proteins
In Vitro Techniques
Therapeutics
Pseudomonas aeruginosa toxA protein

Keywords

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

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Recombinant targeted toxin based on HER2-specific DARPin possesses a strong selective cytotoxic effect in vitro and a potent antitumor activity in vivo. / Sokolova, Evgeniya; Proshkina, Galina; Kutova, Olga; Shilova, Olga; Ryabova, Anastasiya; Schulga, Alexey; Stremovskiy, Oleg; Zdobnova, Tatiana; Balalaeva, Irina; Deyev, Sergey.

In: Journal of Controlled Release, Vol. 233, 10.07.2016, p. 48-56.

Research output: Contribution to journalArticle

Sokolova, Evgeniya ; Proshkina, Galina ; Kutova, Olga ; Shilova, Olga ; Ryabova, Anastasiya ; Schulga, Alexey ; Stremovskiy, Oleg ; Zdobnova, Tatiana ; Balalaeva, Irina ; Deyev, Sergey. / Recombinant targeted toxin based on HER2-specific DARPin possesses a strong selective cytotoxic effect in vitro and a potent antitumor activity in vivo. In: Journal of Controlled Release. 2016 ; Vol. 233. pp. 48-56.
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AU - Shilova, Olga

AU - Ryabova, Anastasiya

AU - Schulga, Alexey

AU - Stremovskiy, Oleg

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AU - Balalaeva, Irina

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