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 journal › Article

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 language	English
Pages (from-to)	48-56
Number of pages	9
Journal	Journal of Controlled Release
Volume	233
DOIs	https://doi.org/10.1016/j.jconrel.2016.05.020
Publication status	Published - 10 Jul 2016
Externally published	Yes

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Keywords

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

ASJC Scopus subject areas

Pharmaceutical Science

Cite this

Sokolova, E., Proshkina, G., Kutova, O., Shilova, O., Ryabova, A., Schulga, A., Stremovskiy, O., Zdobnova, T., Balalaeva, I., & Deyev, S. (2016). Recombinant targeted toxin based on HER2-specific DARPin possesses a strong selective cytotoxic effect in vitro and a potent antitumor activity in vivo. Journal of Controlled Release, 233, 48-56. https://doi.org/10.1016/j.jconrel.2016.05.020

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 journal › Article

Sokolova, E, Proshkina, G, Kutova, O, Shilova, O, Ryabova, A, Schulga, A, Stremovskiy, O, Zdobnova, T, Balalaeva, I & Deyev, S 2016, 'Recombinant targeted toxin based on HER2-specific DARPin possesses a strong selective cytotoxic effect in vitro and a potent antitumor activity in vivo', Journal of Controlled Release, vol. 233, pp. 48-56. https://doi.org/10.1016/j.jconrel.2016.05.020

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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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.",

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AU - Shilova, Olga

AU - Ryabova, Anastasiya

AU - Schulga, Alexey

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Access to Document

10.1016/j.jconrel.2016.05.020