The biology of the 17–1A antigen (Ep-CAM)
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The glycoprotein recognized by the monoclonal antibody (mAb) 17–1A is present on most carcinomas, which makes it an attractive target for immunotherapy. Indeed, adjuvant treatment with mAb 17–1A did successfully reduce the 5 years mortality among colorectal cancer patients with minimal residual disease. Currently the antibody is approved for clinical use in Germany, and is on its way to approval in a number of other countries. New immunotherapeutic strategies targeting the 17–1A antigen are in development or even in early-phase clinical trials. Therefore, a better understanding of the biology of the 17–1A antigen may result in improved strategies for the treatment and diagnosis of human carcinomas. In this review the properties of the 17–1A antigen are discussed concerning tumor biology and the function of the molecule. This 40-kDa glycoprotein functions as an Epithelial Cell Adhesion Molecule, therefore the name Ep-CAM was suggested. Ep-CAM mediates Ca2+-independent homotypic cell–cell adhesions. Formation of Ep-CAM-mediated adhesions has a negative regulatory effect on adhesions mediated by classic cadherins, which may have strong effects on the differentiation and growth of epithelial cells. Indeed, in vivo expression of Ep-CAM is related to increased epithelial proliferation and negatively correlates with cell differentiation. A regulatory function of Ep-CAM in the morphogenesis of epithelial tissue has been demonstrated for a number of tissues, in particular pancreas and mammary gland. The function of Ep-CAM should be taken into consideration when developing new therapeutic approaches targeting this molecule.
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