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

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• 作者：Evgeniya Sokolova^a ; ^b ; Galina Proshkina^a ; Olga Kutova^b ; Olga Shilova^a ; Anastasiya Ryabova^c ; ^d ; Alexey Schulga^a ; Oleg Stremovskiy^a ; Tatiana Zdobnova^a ; ^b ; Irina Balalaeva^b ; Sergey Deyev^a ; ^b ; ^{deyev@ibch.ru" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Recombinant targeted toxin ; Targeted therapy ; HER2 ; DARPin ; PE40 ; Pseudomonas aeruginosa exotoxin A
• 刊名：Journal of Controlled Release
• 出版年：2016
• 出版时间：10 July 2016
• 年：2016
• 卷：233
• 期：Complete
• 页码：48-56
• 全文大小：1331 K

文摘

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.