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Novel Recombinant Anti-HER2/neu Immunotoxin: Design and Antitumor Efficiency

E. A. Sokolova1,2*, T. A. Zdobnova1,2, O. A. Stremovskiy2, I. V. Balalaeva1, and S. M. Deyev1,2

1Lobachevsky State University of Nizhny Novgorod, pr. Gagarina 23, 603950 Nizhny Novgorod, Russia; fax: +7 (831) 462-3085; E-mail: unn@unn.ru; malehanova@mail.ru

2Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117997 Moscow, Russia; fax: +7 (495) 335-0812; E-mail: office@ibch.ru

* To whom correspondence should be addressed.

Received July 7, 2014
The novel HER2/neu-specific recombinant immunotoxin 4D5scFv-PE40 consisting of 4D5scFv antibody (targeting module) and Pseudomonas exotoxin A fragment (effector module) combined in a single polypeptide chain via a flexible linker has been expressed and purified. This immunotoxin conserves specificity and affinity that are characteristics of the parental antibody 4D5scFv and exhibits selective and strong cytotoxic effect against cancer cells overexpressing HER2/neu receptor. The results of the experiments both in vitro (in cell cultures) and in vivo (in tumor-bearing animals) demonstrate high potential of 4D5scFv-PE40 for targeted therapy of tumors overexpressing HER2/neu.
KEY WORDS: recombinant immunotoxin, 4D5scFv, Pseudomonas exotoxin A, receptor HER2/neu, targeted therapy

DOI: 10.1134/S0006297914120128