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

Figure 2.

Figure 2

MOAs of 18 bsAbs in Chinese clinical trials. (A) Among the 18 bsAbs, five of which are by T-cell redirection (5 of 18, 27.8%), six by dual-checkpoints blockade (6 of 18, 33.3%), two by dual signaling inhibitions (2 of 18, 11.1%), one by co-localized blocking (1 of 18, 5.6%), two by biparatopic bsAbs (2 of 18, 11.1%), and two by tumor-targeted immunomodulators (2 of 18, 11.1%). (B) T-cell redirection refers to bridge T cells and tumor cells by binding to both a TAA and IAA and redirecting the cytotoxic activity of effector T cells to attack specifically to the tumor cells. Represent projects in using the MOA include M802 (HER2 × CD3, by YZYBio), M701 (EPCAM×CD3, by YZYBio), A-319 (CD19 × CD3, by Generon), K193 (CD19 × CD3, by Lvzhu), and ES101 (PD-L1 × CD137, by Elpiscience). (C) Dual checkpoints blockade is by two-checkpoint blockers integrated into one antibody to inhibit two immune checkpoints simultaneously. AK104 (PD-1 × CTLA-4, by Akeso), KN046 (PD-L1 × CTLA-4, by Alphamab), IBI318 (PD-1 × PD-L1, by Innovent), HX009 (PD-1 × CD47, by HanxBio), IBI322 (PD-L1 × CD47, by Innovent), and MGD013 (PD-1 × LAG-3) are six of these examples. (D) Dual signaling inhibitions are to target two different receptors for preventing the receptors from phosphorylation and/or from the activation of both receptor-mediated signaling pathways to inhibit tumor proliferation. EMB-01 (EGFR × c-MET, by Epimab) and SI-B001 (HER3 × EGFR, by Biokin) are two of these typical bsAbs. (E) Co-localized blocking is by inhibiting two or more tumor cell intrinsic and extrinsic pathways to raise the possibility of superior antitumor activity compared with the monotherapy. SHR-1701 (PD-L1 × TGF-β, by Hengrui) is one of such bsAbs. (F) Biparatopic bsAbs are by binding to two different epitopes of the same antigen or same receptor to enhance the antigen–antibody affinity and to improve the drug efficacy. Both KN026 (HER2 × HER2, by Alphamab) and MBS301 (HER2 × HER2, by Mabworks) bind to the D2 and D4 subdomains of HER2. (G) Tumor-targeted immunomodulators are designed for binding to both one TAA (e.g. HER2, CD20) to inhibit TAA signaling pathway and one immunomodulating receptor (e.g. PD-1, CD47) to regulate the immune system to attack the tumors. IBI315 (HER2 × PD-1, by Innovent) and IMM0306 (CD20 × CD47, by ImmuneOnco) utilize such MOAs.