Abstract
The main aim of our work was to create a full-length bispecific antibody (BsAb) as a vehicle for the targeted delivery of interferon-beta (IFN-β) to ErbB2+ tumor cells in the form of non-covalent complex of BsAb and IFN-β. Such a construct is a CrossMab-type BsAb, consisting of an ErbB2-recognizing trastuzumab moiety, a part of chimeric antibody to IFN-β, and human IgG1 Fc domain carrying knob-into-hole amino acid substitutions necessary for the proper assembly of bispecific molecules. The IFN-β- recognizing arm of BsAb not only forms a complex with the cytokine but neutralizes its activity, thus providing a mechanism to avoid the side effects of the systemic action of IFN-β by blocking IFN-β Interaction with cell receptors in the process of cytokine delivery to tumor sites. Enzyme sandwich immunoassay confirmed the ability of BsAb to bind to human IFN-β comparable to that of the parental chimeric mAb. The BsAb binds to the recombinant ErbB2 receptor, as well as to lysates of ErbB2+ tumor cell lines. The inhibition of the antiproliferative effect of IFN-β by BsAb (IC50 = 49,3 µg/mL) was demonstrated on the HT29 cell line. It can be proposed that the BsAb obtained can serve as a component of the immunocytokine complex for the delivery of IFN-β to ErbB2-associated tumor cells.
Highlights
The development and research of new therapies for tumors with the overexpression of the ErbB2 receptor are urgent tasks
We describe the construction of a molecular complex of IFN-β and bispecific antibody (BsAb) anti-ErbB2 and anti-IFN-β for the targeted therapy of ErbB2+ solid tumors
A panel of hybridomas producing murine monoclonal antibodies against recombinant human IFN-β expressed in E. coli cells was prepared according to conventional techniques
Summary
The development and research of new therapies for tumors with the overexpression of the ErbB2 receptor are urgent tasks. Research on the use of type I interferons in the treatment of oncological diseases has intensified. Cytokine therapy is aimed at activating the cells of the immune system to fight against tumors, but it has drawbacks that limit its use, which manifest themselves in a number of side effects. A number of studies are being carried out on the use of IFN-β in oncology aimed at reducing the systemic effect of this cytokine. Breast cancer is the most common, accounting for 13.1% of the total incidence. As a cause of death, it ranks in5th place, taking
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
