Bispecific antibodies (BsAbs) are bioengineered antibodies that contain two different binding sites within a single molecule, which can specifically bind two different types of antigen. The most widely used application of bi-specific antibody is in cancer immunotherapy, which create a therapeutic treatment approach for diseases with specific medical needs.
Compared with traditional antibodies, bispecific antibodies have many advantages. The two arms can bring an antigen-expressing cell in close proximity to a killing cell and thus destroy the tumor cell; the two binding sites can significantly increase affinity or internalization rates of particular antigens on a cell's surface by binding to two different epitopes on an antigen; they usually have a higher cytotoxic potential to bind to antigens with low expression level. Binding tumor cells using a bi-specific antibody-drug conjugate (ADC) also holds great promise for the future development of therapeutics for a variety of diseases.
With the development of antibody engineering, many types of bispecific antibodies have been designed to enable short half-life, immunogenicity and side-effects caused by cytokine liberation. They include tri-functional antibodies, chemically linked Fabs, and various types of bivalent and trivalent single-chain variable fragments (scFvs), fusion proteins mimicking the variable domains of two antibodies. The furthest developed of these newer formats are the bi-specific T-cell engagers (BiTEs) and mAb2's, antibodies engineered to contain an Fcab antigen-binding fragment instead of the Fc constant region.