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. 2020 May 30;3(2):126–145. doi: 10.1093/abt/tbaa011

Figure 1.

Figure 1

The bsAbs developed by Chinese biopharmaceutical companies in different formats. The structure diagrams of YBODY®, CRIB™, ITab™, FIT-Ig™, WuXiBody™, and SMAB™ are illustrated. (A) YBODY® composites three segments including a Fab, scFv, and Fc region, wherein the Fab targets tumor-associated antigen (TAA), scFv to IAA, and heterodimeric Fc is stabilized by KiHs and a salt bridge. (B) and (C) In CRIB™ platform, the charge network among various Fc bonds is manipulated to increase the formation of heterodimers. (D) In ITab™, a Fab domain binds to CD3 and two scFv domains bind to tumor surface antigen to form an immune synapse to recruit and activate T cells at the tumor site. (E) In tetravalent FIT-Ig™ technology, two parental antibodies are combined into one single molecule, where the Fab A is structurally fused to Fab B in tandem at its N-terminus. (F, G, and H) In WuXiBody™, TCR Cα/Cβ pair, (where TCR Cα and TCR Cβ represent the α and β chains of human TCR constant region, respectively), is used to substitute the first constant domain of the heavy chain (CH1) and the constant domain of the κ or λ light chain (CL) of one of the two Fabs, while maintaining the variable regions of heavy chain (VH) and light chain(VL) pair (VH/VL) of this Fab and the whole structure of the other Fab to be their native forms. WuXiBody can be assembled by 1 or 2 of the different Fabs connected with each Fc of a heterodimer or a homodimer to provide 1 + 1 asymmetric bivalent (F), 2 + 1 asymmetric trivalent (G) and 2 + 2 symmetric tetravalent (H) bispecific antibodies (bsAbs), respectively. (I–L) In SMAB™, a VHH is fused to the C-terminal end of each light chain (I), or to the N-terminal end of each HC (J), or to the N-terminal end of each light chain (K), or to the C-terminal end of each HC (L) to provide 2 + 2 symmetric tetravalent bsAbs. (M) 17 of 20 bsAbs, which are currently under clinical trials in China have disclosed their structural formats, among which include seven asymmetric IgG-like bsAbs (7 of 17, 41.2%), six symmetric IgG-like bsAb (6 of 17, 35.3%), one bispecific fragment (1 of 17, 5.9%), and three antibody-receptor fusion proteins (3 of 17, 17.6%). Asymmetric IgG-like structure can be sub-classified as scFv-Fab IgG (A), hetero-H+ common LC IgG (B), hetero-VHH (C), and Fab-arm exchange (N). Symmetric IgG-like structure can be sub-classified as (Fab)2-IGG (E), VHH-Fc-VHH (O), tandem VHHs-Fc (P), (Fab)2-(scFv)2-Fc (Q) where the two identical scFvs target antigen A and two Fabs target antigen B, and IgG-(scFv)2 (R); bispecific fragments structure involved scFv(s) and Fab(s) (D), and an antibody-receptor fusion protein (S) consisting a whole monoclonal antibody connected on its two C-terminal of HCs with the ex-cellular domain of the receptor.