Fig. 1
From: Bi-specific and tri-specific antibodies- the next big thing in solid tumor therapeutics
a: Some formats of IgG –like bispecific antibodies and a trispecific antibody. (A) Quadroma created by combining the light and heavy chains of two different monoclonal antibodies resulting in two antigen binding sites aimed at different tumor antigens eg. Catumaxomab (B) Two antibody chains with engineered CH3 domain to create a “knob” in one heavy chain and a “hole” in the other to promote heterodimerization. This allows only specific pairing of heavy chains to reduce mispairing. (C) Variable domains of two mABs fused to create a dual- specific antibody (D) CrossMab exchanging of the CH1 domain of one heavy chain with the constant domain of the corresponding light chain for better light chain pairing (E) Bispecific antibody with two unique antigen-binding sites and a chemotherapy payload attached to the constant domain (F) Trispecific antibody engineered to bind to three different ligands on tumor cell. b: Some formats of bispecific antibody fragments and fusion proteins. (A) scFvs – Combination of the variable region of one light chain with the variable region of one heavy chain fragment is the basic element for antigen binding. (B) bi-Nanobody- Combination of two different single variable heavy chain domains which are able to bind different tumor antigens. (C) BiTE- Tandem single chain variable fragments from different antibodies joined by a flexible peptide chain. (D) Diabody – Bivalent molecules composed of two chains each comprising a variable light chain and variable heavy chain domain, either from the same or different antibodies. (E) TandAbs - Two pairs of variable light chain and variable heavy chain domains are connected in a single polypeptide chain to form a tetravalent tandAb. (F) DNL-Fab3 – Trivalent bispecific antibody composed of three Fab fragments joined by the utilization of the specific interaction between the regulatory subunits of cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) and the anchoring domains of A kinase anchoring proteins (AKAP). (G) DART – Two polypeptide chains derived from the variable heavy chain from one molecule linked to a variable light chain of another molecule. (H) DART-Fc - DARTs with a Fc fragment designed to prolong serum retention time. (I) scFv-HAS-scFV- Association of two single chain variable fragments through modified dimerization domains