Anti-HER2 Bispecific Antibody (Zanidatamab)

Zanidatamab, also known as ZW25, is a humanised, bispecific monoclonal antibody targeting two distinct HER2 (human epidermal growth factor receptor 2) epitopes (ECD2 and ECD4). Zanidatamab has anti-tumour activity. HER2 (human epidermal growth factor receptor 2), also known as erbB-2 or CD340, is a tyrosine kinase of the EFGR family of proteins. There is no known ligand, but it can form homodimers or heterodimers with other HER proteins. Once active, it activates the MAPK (mitogen-activated protein kinase) and PI3K (phosphatidylinositol-3 kinase) signaling pathways resulting in cell cycle progression and cell proliferation. HER2 over-expression is also known to occur in breast, ovarian, stomach, lung adenocarcinoma, aggressive forms of uterine cancer and gastric cancer. In 1990 the FDA approved the use of the monoclonal antibody trastuzumab in breast and stomach cancer. Other strategies to target HER2 that have been approved include ADCs (antibody-drug conjugate) and margetuximab (an HER2 antibody that can alter the Fc-receptor affinity to CD16 and induce cytotoxicity). Zanidatamab is a bispecific antibody that targets two non-overlapping domains of HER2. It is commercialized under the name Ziihera, for the treatment of HER2-positive biliary tract cancer.