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

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

Keywords

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

ASJC Scopus subject areas

Pharmaceutical Science

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10.1016/j.jconrel.2016.05.020

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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 › peer-review

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

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AU - Sokolova, Evgeniya

AU - Proshkina, Galina

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AU - Shilova, Olga

AU - Ryabova, Anastasiya

AU - Schulga, Alexey

AU - Stremovskiy, Oleg

AU - Zdobnova, Tatiana

AU - Balalaeva, Irina

AU - Deyev, Sergey

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AB - 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.

KW - DARPin

KW - HER2

KW - PE40

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KW - Recombinant targeted toxin

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