Cleaved amphiregulin neo-epitope on the residual transmembrane stalk (AREG-stalk)

The cleaved amphiregulin neo-epitope on the residual transmembrane stalk is a highly specific tumor-associated antigen generated through the proteolytic processing of pro-amphiregulin. Amphiregulin (AREG) is initially synthesized as a membrane-bound precursor that undergoes ectodomain shedding by the metalloproteinase ADAM17 to release the mature, soluble growth factor which activates the EGFR pathway. This cleavage event leaves behind a truncated transmembrane stalk on the cell surface that exposes a unique neo-epitope not present in the full-length precursor. Because AREG shedding is significantly upregulated in various epithelial malignancies to drive autocrine signaling, this residual stalk serves as a selective marker for cancer cells with high growth factor turnover. Therapeutic strategies, such as the antibody-drug conjugate KHK2866, exploit this specificity by targeting the neo-epitope to deliver cytotoxic agents directly to the tumor microenvironment while sparing healthy tissues where AREG processing is minimal.

Other names

Amphiregulin residual transmembrane stalkC-terminal fragment of pro-amphiregulinCleaved pro-AREGAREG neo-epitopePro-amphiregulin stalk

Antibody-drug conjugate (ADC) targeting the neo-epitope created after ADAM17-mediated shedding of amphiregulin to deliver a cytotoxic payload specifically to tumor cells.