Fig.1: Zanidatamab is a biparatopic anti-HER2 Ab that binds HER2-expressing tumor cells with greater Ab saturation than trastuzumab or pertuzumab 
a Zanidatamab is a humanized, biparatopic, immunoglobulin 1 (IgG1)-like Ab with an scFv (light blue) that binds the juxtamembrane ECD4 of HER2 and a Fab (dark blue) that binds the ECD2 dimerization domain of HER2, the same domains targeted by trastuzumab and pertuzumab, respectively. b Representative class-averaged TEM image, derived from 216 images, showing the 3-lobed structure of zanidatamab with putative assignments of the scFv, Fab, and Fc region from a single experiment. c Zanidatamab binds with greater Ab saturation to tumor cell lines compared to trastuzumab or pertuzumab. Flow cytometry was used to quantify the binding of zanidatamab, trastuzumab, pertuzumab, and tras + pert (1:1) to SK-BR-3 tumor cells. In c, data are mean ± SEM from n = 3 independent experiments.
Fig.2: Zenocutuzumab (MCLA-128) works by blocking the action of the growth factor NRG1 and prohibiting it from binding to HER3 .
HER3 is a protein that sits on the surface of cancer cells, which when it combines with a second surface protein HER2, it sends signals to drive tumor growth and survival. NRG1 induces the combination of HER2 and HER3.
Zenocutuzumab (MCLA-128) is a bispecific antibody recognizing HER2 and HER3. Zenocutuzumab (MCLA-128) is designed to have a ‘dock and block’ mechanism:
First, zenocutuzumab (MCLA-128) docks onto HER2.
Then, it is able to block HER3’s ability to bind NRG1.
Fig 3: Construction and characterization ofanti-HER2 bsAb KN026 . (A) Schematic drawing of the bsAb KN026. (B) Thermal stability ofKN026 was examined by differential scanning calorimetry (DSC). (C) Binding affinity of KN026, trastuzumab (Tmab) and pertuzumab (Pmab) against dual antigens was determined by sandwich ELISA. (D) The binding affinity assessment of KN026, trastuzumab (Tmab) and pertuzumab (Pmab) to HER2 on human cancer cells (BT474, NCI-N87, Calu-3).
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