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 | |
| 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
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
}
TY - JOUR
T1 - Recombinant targeted toxin based on HER2-specific DARPin possesses a strong selective cytotoxic effect in vitro and a potent antitumor activity in vivo
AU - Sokolova, Evgeniya
AU - Proshkina, Galina
AU - Kutova, Olga
AU - Shilova, Olga
AU - Ryabova, Anastasiya
AU - Schulga, Alexey
AU - Stremovskiy, Oleg
AU - Zdobnova, Tatiana
AU - Balalaeva, Irina
AU - Deyev, Sergey
PY - 2016/7/10
Y1 - 2016/7/10
N2 - 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.
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
KW - Pseudomonas aeruginosa exotoxin A
KW - Recombinant targeted toxin
KW - Targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=84968626578&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84968626578&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2016.05.020
DO - 10.1016/j.jconrel.2016.05.020
M3 - Article
VL - 233
SP - 48
EP - 56
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
ER -