Cleaved amphiregulin neo-epitope (AREG neo-epitope)

The cleaved amphiregulin neo-epitope is a specific antigenic site revealed on the residual transmembrane stalk of the amphiregulin (AREG) protein following its proteolytic cleavage by the metalloprotease TACE/ADAM17 [1, 2]. Amphiregulin is a member of the epidermal growth factor (EGF) family and serves as a ligand for the epidermal growth factor receptor (EGFR), playing a critical role in cell proliferation and survival, particularly in estrogen receptor-positive breast cancer [2, 5]. In many malignancies, AREG is overexpressed and actively shed from the cell surface to drive autocrine and paracrine signaling [1, 3]. The cleavage event releases the soluble signaling domain into the extracellular space but leaves behind a membrane-bound stalk containing a unique neo-epitope that is not accessible in the full-length, uncleaved protein [1, 2]. This neo-epitope has emerged as a highly selective therapeutic target for antibody-drug conjugates (ADCs) such as GMF-1A3-MMAE, which bind the stalk, undergo internalization, and deliver cytotoxic payloads directly to cancer cells [1, 6]. Targeting the cleaved form rather than the full protein or the receptor itself potentially enhances tumor specificity and reduces off-target effects associated with broader EGFR inhibition [2, 3].

Other names

Amphiregulin residual transmembrane stalkTACE-cleaved amphiregulinADAM17-cleaved amphiregulin stalkSoluble amphiregulin C-terminal neo-epitope