安非雷古林
癌症研究
皮调节素
单克隆抗体
表皮生长因子受体
癌症
表皮生长因子
抗体
化学
结合
表位
生物
免疫学
医学
受体
内科学
生物化学
数学分析
数学
作者
Kristopher A. Lofgren,Nicolette C. Reker,Sreeja Sreekumar,Paraic A. Kenny
摘要
Amphiregulin is a transmembrane protein which, when cleaved by the TACE/ADAM17 protease, releases a soluble epidermal growth factor receptor ligand domain that promotes proliferation of normal and malignant cells. We previously described a rabbit monoclonal antibody, GMF-1A3, that selectively recognizes the cell-associated cleaved amphiregulin epitope. Antibody-drug conjugates had anti-tumor activity against human breast cancer xenografts. Several tumor types express amphiregulin, but evidence for a functional requirement for amphiregulin in these malignancies is limited. By directly evaluating amphiregulin cleavage with immunohistochemistry, GMF-1A3 provides a more direct measure of amphiregulin activity. Using 370 specimens from 10 tumor types (as well as normal controls), we demonstrate that cleaved amphiregulin is widely expressed in solid tumors and is especially common (> 50% of cases) in breast, prostate, liver and lung cancer. As a potential companion diagnostic for this antibody-drug conjugate, this assay allows identification of tumors with high levels of the cleaved amphiregulin target.
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