NCIt definition : An engineered immunoglobulin G1 (IgG1) bi-specific monoclonal antibody that targets
two different non-overlapping epitopes of the human tumor-associated antigen (TAA)
epidermal growth factor receptor 2 (HER2), ECD2 and ECD4, with potential immunomodulating
and antineoplastic activities. Upon administration, zanidatamab targets and binds
to the two distinct HER2 domains on the tumor cell surface. This results in dual HER2
signal blockade, HER2 clustering, receptor internalization and downregulation. This
also induces a cytotoxic T-lymphocyte (CTL) response and antibody-dependent cell-mediated
cytotoxicity (ADCC) against tumor cells that overexpress HER2. Antibody-dependent
cellular phagocytosis (ADCP) is also induced and further stimulates the immune system
to kill HER2-overexpressing tumor cells. The HER2 receptor internalization also further
inhibits HER2 activation, HER2-mediated signaling and HER2-mediated tumor cell growth.
HER2, a tyrosine kinase receptor, is overexpressed by many cancer cell types.;