Epidermal growth factor receptor–Fc gamma receptor IIIa interface (EGFR–CD16A)

The Epidermal growth factor receptor (EGFR)–Fc gamma receptor IIIa (CD16A) cell–cell interface is a therapeutic target created by bispecific molecules designed to bridge EGFR-expressing tumor cells with CD16A-expressing innate immune cells, such as natural killer (NK) cells and macrophages. EGFR is a transmembrane glycoprotein and member of the ErbB family of receptor tyrosine kinases, frequently overexpressed or mutated in various solid tumors where it drives uncontrolled cell proliferation and survival (UniProt P00533). CD16A is a low-affinity IgG receptor found on innate effector cells that triggers antibody-dependent cellular cytotoxicity (ADCC) upon activation (UniProt P08637). By physically linking these two proteins, therapeutic agents like the bispecific innate cell engager AFM24 facilitate the formation of a synthetic immunological synapse, leading to the targeted destruction of cancer cells (Affimed, 2024). This approach is designed to be independent of EGFR signaling mutations, such as KRAS or BRAF, which often confer resistance to traditional EGFR-targeted tyrosine kinase inhibitors or monoclonal antibodies (NCT04059913). Consequently, the EGFR–CD16A interface serves as a strategic focal point for redirecting the innate immune system to combat refractory or metastatic EGFR-positive malignancies.

Other names

EGFR-CD16AEGFR-FcγRIIIaEGFR-CD16EGFR-Fc gamma receptor IIIa interfaceEGFR-Innate Cell Engager target

Recruitment and activation of CD16A-positive innate immune cells, such as natural killer (NK) cells and macrophages, to EGFR-expressing tumor cells to induce targeted lysis via antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).