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GMF-1A3 is a rabbit monoclonal antibody that selectively targets the cell-associated residual transmembrane stalk of cleaved amphiregulin (AREG), a neo-epitope revealed following TACE/ADAM17-mediated proteolytic cleavage. Unlike conventional anti-AREG antibodies, GMF-1A3 does not interact with uncleaved amphiregulin, allowing it to specifically target cells with high rates of amphiregulin shedding. Developed by the Gundersen Medical Foundation and the Kabara Cancer Research Institute, GMF-1A3 has been formulated into an antibody-drug conjugate (ADC), GMF-1A3-MMAE, by conjugation with the cytotoxic payload monomethyl auristatin E (MMAE). Upon binding to cleaved AREG, the ADC is internalized and releases MMAE, which inhibits tubulin polymerization and induces cell death. GMF-1A3 is also being evaluated as an immunohistochemistry-based companion diagnostic to identify patients with high levels of cleaved amphiregulin across various solid tumors, including breast, prostate, liver, lung, and colorectal cancers.
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