title: 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.
authors.affiliation: M.M. Shemyakin and Y.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 16/10 Miklukho-Maklaya St., Moscow 117997, Russia; Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., Nizhny Novgorod 603950, Russia.
authors.forename: Evgeniya
authors.initials: E
authors.lastname: Sokolova
authors.affiliation: M.M. Shemyakin and Y.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 16/10 Miklukho-Maklaya St., Moscow 117997, Russia.
authors.forename: Galina
authors.initials: G
authors.lastname: Proshkina
authors.affiliation: Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., Nizhny Novgorod 603950, Russia.
authors.forename: Olga
authors.initials: O
authors.lastname: Kutova
authors.affiliation: M.M. Shemyakin and Y.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 16/10 Miklukho-Maklaya St., Moscow 117997, Russia.
authors.forename: Olga
authors.initials: O
authors.lastname: Shilova
authors.affiliation: Prokhorov General Physics Institute, Russian Academy of Sciences, 38 Vavilova St, Moscow 119991, Russia; National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), 31 Kashirskoe highway, Moscow 115409, Russia.
authors.forename: Anastasiya
authors.initials: A
authors.lastname: Ryabova
authors.affiliation: M.M. Shemyakin and Y.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 16/10 Miklukho-Maklaya St., Moscow 117997, Russia.
authors.forename: Alexey
authors.initials: A
authors.lastname: Schulga
authors.affiliation: M.M. Shemyakin and Y.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 16/10 Miklukho-Maklaya St., Moscow 117997, Russia.
authors.forename: Oleg
authors.initials: O
authors.lastname: Stremovskiy
authors.affiliation: M.M. Shemyakin and Y.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 16/10 Miklukho-Maklaya St., Moscow 117997, Russia; Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., Nizhny Novgorod 603950, Russia.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Zdobnova
authors.affiliation: Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., Nizhny Novgorod 603950, Russia.
authors.forename: Irina
authors.initials: I
authors.lastname: Balalaeva
authors.affiliation: M.M. Shemyakin and Y.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 16/10 Miklukho-Maklaya St., Moscow 117997, Russia; Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., Nizhny Novgorod 603950, Russia. Electronic address: deyev@ibch.ru.
authors.forename: Sergey
authors.initials: S
authors.lastname: Deyev
mesh_terms: D036002:ADP Ribose Transferases / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001427:Bacterial Toxins / Q000008:administration & dosage* / Q000627:therapeutic use; D016466:CHO Cells; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003412:Cricetulus; D005098:Exotoxins / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage* / Q000627:therapeutic use; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008819:Mice, Nude; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000627:therapeutic use; D047368:Tumor Burden / Q000187:drug effects; D037521:Virulence Factors / Q000008:administration & dosage* / Q000627:therapeutic use; D000097668:Pseudomonas aeruginosa Exotoxin A
chemical_list: D036002:ADP Ribose Transferases; D000970:Antineoplastic Agents; D001427:Bacterial Toxins; D005098:Exotoxins; D000922:Immunotoxins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C508053:ERBB2 protein, human
keywords: DARPin; HER2; PE40; Pseudomonas aeruginosa exotoxin A; Recombinant targeted toxin; Targeted therapy