Her-2/PD-1 Antibodies

Target Information

HER2, also known as ErbB2, is a member of the epidermal growth factor receptor (EGFR/ErbB) family of receptor tyrosine kinases. Unlike other family members, HER2 has no known direct ligand and functions primarily through heterodimerization with other ErbB receptors, leading to activation of downstream signaling pathways such as PI3K/AKT and MAPK that regulate cell proliferation, survival, and differentiation. HER2 is overexpressed or amplified in several cancers, most notably breast and gastric cancers, where it is associated with aggressive disease and poor prognosis. Due to its role in tumor growth and its cell surface accessibility, HER2 is an important target for monoclonal antibodies, antibody-drug conjugates, and other targeted therapies.

Cell-mediated immune responses are initiated by T lymphocytes that are themselves stimulated by cognate peptides bound to MHC molecules on antig en-presenting cells (APC). T-cell activation is generally self-limited as activated T cells express receptors such as PD-1 (also known as PDCD-1) that mediate inhibitory signals from the APC. PD-1 can bind two different but related ligands, PDL-1 and PDL-2. Upon binding to either of these ligands, signals generated by PD-1 inhibit the activation of the immune response in the absence of "danger signals" such as LPS or other molecules associated with bacteria or other pathogens. Evidence for this is seen in PD1-null mice who exhibit hyperactivated immune systems and autoimmune diseases. Despite its predicted molecular weight, PD-1 often migrates at higher molecular weight in SDS-PAGE.