EGFR/CD3 Antibodies

Target Information

EGFR, epidermal growth factor receptor, is a receptor tyrosine kinases that signals in response to various growth factors. Overexpression has been linked to numerous types of cancer and EGFR is the target of both biological and small molecular therapeutics. EGFR is encoded by the EGFR gene located on chromosome 7 in humans. EGFR belongs to the HER/ERbB family of proteins that includes three other receptor tyrosine kinases, ERbB2, ERbB3, ERbB4. EGFR is a transmembrane receptor and binding of its cognate ligands such as EGF (Epidermal Growth Factor) and TGF alpha (Transforming Growth Factor alpha) to the extracellular domain leads to EGFR dimerization followed by autophosphorylation of the tyrosine residues in the cytoplasmic domain. Overexpression is observed in tumors of the head and neck, brain, bladder, stomach, breast, lung, endometrium, cervix, vulva, ovary, esophagus, stomach and in squamous cell carcinoma.

The CD3 complex, composed of gamma, delta, epsilon, and zeta subunits, is essential for the assembly, trafficking, and surface expression of the T cell receptor (TCR) complex. These subunits are structurally related members of the immunoglobulin superfamily and are encoded by closely linked genes on human chromosome 11. CD3 is expressed by thymocytes in a developmentally regulated manner and by all mature T cells, but not on B or NK cells. The CD3 subunits play a crucial role in transducing antigen-recognition signals into the cytoplasm of T cells. The cytoplasmic tails of CD3 subunits contain a double tyrosine-based motif that associates with cytoplasmic signal transduction molecules, mediating T cell activation through the TCR. Crosslinking of the TCR initiates intracellular biochemical pathways that result in cellular activation, proliferation, and potentially growth arrest and cell survival. CD3 is present on 68-82% of normal peripheral blood lymphocytes, 65-85% of thymocytes, and Purkinje cells in the cerebellum. Decreased percentages of T lymphocytes may be observed in some autoimmune diseases. Defects in the CD3 gene are associated with CD3 immunodeficiency, highlighting its importance in immune function and regulation.