Bispecific antibodies: design, therapy, perspectives

Sedykh, Sergey E; Prinz, Victor V; Buneva, Valentina N; Nevinsky, Georgy A

Immunoglobulins (antibodies [Abs]) are major protein components of the adaptive immune system, directed against foreign compounds and infectious agents. The IgG molecule consists of two light and two heavy chains connected by disulfide bonds; IgG is a monomer with a molecular weight of 146-160 kDa. Antigen-binding centers of Abs are formed by hypervariable regions of heavy and light chains. In the classical point of view, the Ab molecule contains two identical antigen-binding sites (two HL fragments) and is monospecific and bivalent. Immunoglobulins are expressed as receptors of the cell membrane of B lymphocytes, as well as in the form of soluble molecules secreted by plasma cells. Soluble Abs can bind virtually any natural and artificial molecules (antigens) with high affinity and specificity. The ability of Abs to recognize and bind a broad spectrum of antigens is ensured by their extraordinary diversity, reaching 10 8 -10 10 different variants of antigen-binding centers. Bispecific immunoglobulins contain two different antigen-binding sites. In the last 10 years, the number of articles devoted to bispecific Abs (BsAbs) has been steadily increasing. The particular interest in these molecules is due to their potential for therapeutic use. In 2014, the journal Nature Reviews Drug Discovery called BsAbs "next-generation antibodies."