Recombinant Bispecific Antibodies to the Human ErbB2 Receptor and Interferon-Beta

Abstract

The development of and research into new therapies that can selectively and effectively destroy tumor cells that overexpress the ErbB2 receptor is apressing task. Recently, research into the use of type I interferons in the treatment of cancer has intensified. Cytokine therapy is aimed at activating the cells of the immune system to fight tumors, but it has drawbacks that limit its use because of a number of side effectsthe severity of which varies depending on the dosage and type of used cytokine. At the moment, a number of studies are being conducted regarding the use of IFNin oncology. The studies areaimed at mitigating the systemic action of this cytokine. The immunocytokine complex made of a bispecific antibody against the ErbB2 receptor and recombinant IFNdeveloped in this study underlies themechanism meant to avoid the systemic action of this cytokine. Part of this study focuses on the development of full-length antibodies that bind to the ErbB2 receptor on the one hand, and bind and neutralize IFN, on the other hand, which allows us to consider the antibodies as a means of cytokine delivery to tumor cells.

Optimization of recombinant antibody production based on the vector design and the level of metabolites for generation of Ig- producing stable cell lines

“…Forward primers for PCR contained NdeI restriction endonuclease recognition site and reverse primers contained the sequences overlapping with the start of the constant domain of the human light kappa-chain and the CH1 constant domain of the human IgG1 heavy chain, respectively, at 5′-terminus (primers were used EuLA1Flid and 272RvL for VL, EuHPA272Flid and H-STApaI for VH). Constant domain coding sequence of LC was amplified using previously obtained plasmid vector pOpti-F10L-MluI [ 26 ] as a template and primers 272F CL and EMCVrev for CL. Further, coding sequence for the LC of the mAb was obtained by combining the variable domain with own leader peptide and constant domain of the LC of the human immunoglobulin.…”

Ten years in the making: application of CrossMab technology for the development of therapeutic bispecific antibodies and antibody fusion proteins

“…Most recently, Panina and colleagues described a novel bispecific heterodimeric HER2/IFNα-1 + 1 CrossMab CH 1 −CL with the ultimate goal to deliver IFNα into HER2 expressing tumors. 163 …”