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

被引：52

作者：

Sokolova, Evgeniya ^{[1
,2
]}

Proshkina, Galina ^{[1
]}

Kutova, Olga ^{[2
]}

Shilova, Olga ^{[1
]}

Ryabova, Anastasiya ^{[3
,4
]}

Schulga, Alexey ^{[1
]}

Stremovskiy, Oleg ^{[1
]}

Zdobnova, Tatiana ^{[1
,2
]}

Balalaeva, Irina ^{[2
]}

Deyev, Sergey ^{[1
,2
]}

机构：

[1] Russian Acad Sci, MM Shemyakin & YA Ovchinnikov Inst Bioorgan Chem, 16-10 Miklukho Maklaya St, Moscow 117997, Russia

[2] Lobachevsky State Univ Nizhny Novgorod, 23 Gagarin Ave, Nizhnii Novgorod 603950, Russia

[3] Russian Acad Sci, Prokhorov Gen Phys Inst, 38 Vavilova St, Moscow 119991, Russia

[4] Natl Res Nucl Univ MEPhI, Moscow Engn Phys Inst, 31 Kashirskoe Highway, Moscow 115409, Russia

来源：

JOURNAL OF CONTROLLED RELEASE | 2016年 / 233卷

基金：

俄罗斯科学基金会;

关键词：

Recombinant targeted toxin; Targeted therapy; HER2; DARPin; PE40; Pseudomonas aeruginosa exotoxin A; ANKYRIN REPEAT PROTEINS; PSEUDOMONAS EXOTOXIN; BREAST-CANCER; ENDOPLASMIC-RETICULUM; BINDING-PROTEINS; FUSION TOXIN; CELLS; RECEPTOR; ONCOGENE; HER2;

D O I：

10.1016/j.jconrel.2016.05.020

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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. (C) 2016 Elsevier B.V. All rights reserved.

引用

页码：48 / 56

页数：9

共 15 条

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