A New Combinatorial Bispecific Protein that Selectively Binds HER2 and HER3 Receptors

Abstract

Cancer is one of the most socially significant diseases of the 21st century. Since the advent of Paul Ehrlich’s “magic bullet” concept, the idea of targeted cancer therapy has captivated researchers around the world. The most successful drugs in this niche are antibody-drug conjugates, however, they also have a number of limitations in their use. Peptide-cytotoxic agent conjugates have become a new class of drugs. They have a number of advantages, including small size, ease of production, and distribution in tumor tissues. This paper describes the process of cloning, expression, purification, and characterization of a bispecific protein targeting HER2 and HER3 receptors, which are key targets in breast cancer therapy. As a result of the work carried out, a recombinant protein with a high interaction constant with the HER2 receptor, as well as serum albumin, was obtained. The presence of specificity to albumin provides additional properties to a potential drug based on it, namely, an increased level of circulation in the bloodstream. Based on the results of cellular studies, it was shown that the drug effectively binds and internalizes into breast cancer cell lines with high surface coexpression of HER2 and HER3 receptors, which makes it potentially promising for therapy.