title: Recombinant Immunotoxin 4D5scFv-PE40 for Targeted Therapy of HER2-Positive Tumors.
abstract: Recombinant immunotoxins are extremely promising agents for the targeted therapy of tumors with a certain molecular profile. In this work, we studied the properties of a new recombinant HER2-specific immunotoxin composed of the scFv antibody and a fragment of Pseudomonas exotoxin A (4D5scFv-PE40). High affinity of the immunotoxin for the HER2 tumor marker, its selective cytotoxicity against HER2-overexpressing cells, and its storage stability were demonstrated. The 50% inhibitory concentration (IC50) of the 4D5scFv-PE40 immunotoxin for HER2-overexpressing cancer cells was 2.5-3 orders of magnitude lower compared to that for CHO cells not expressing this tumor marker and was 2.5-3 orders of magnitude lower than IC50 of free PE40 for HER2-overexpressing cancer cells. These findings provide a basis for expecting in the long run high therapeutic index values of the 4D5scFv-PE40 immunotoxin for its use in vivo.
authors.affiliation: Lobachevsky State University of Nizhny Novgorod, pr. Gagarina 23, 603950, Nizhny Novgorod, Russia ; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117997, Moscow, Russia.
authors.forename: E A
authors.initials: EA
authors.lastname: Sokolova
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117997, Moscow, Russia.
authors.forename: O A
authors.initials: OA
authors.lastname: Stremovskiy
authors.affiliation: Lobachevsky State University of Nizhny Novgorod, pr. Gagarina 23, 603950, Nizhny Novgorod, Russia.
authors.forename: T A
authors.initials: TA
authors.lastname: Zdobnova
authors.affiliation: Lobachevsky State University of Nizhny Novgorod, pr. Gagarina 23, 603950, Nizhny Novgorod, Russia.
authors.forename: I V
authors.initials: IV
authors.lastname: Balalaeva
authors.affiliation: Lobachevsky State University of Nizhny Novgorod, pr. Gagarina 23, 603950, Nizhny Novgorod, Russia ; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117997, Moscow, Russia.
authors.forename: S M
authors.initials: SM
authors.lastname: Deyev
keywords: 4D5scFv; HER2 tumor marker; Pseudomonas exotoxin A; recombinant immunotoxin; targeted therapy