The biology of the 17-1A antigen (Ep-CAM).

Department of Pathology, Leiden University Medical Center, The Netherlands.
Journal of Molecular Medicine (Impact Factor: 4.77). 11/1999; 77(10):699-712. DOI:10.1007/s001099900038
Source: PubMed

ABSTRACT 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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    ABSTRACT: The ability to engineer and re-program the surfaces of cells would provide an enabling synthetic biological method for the design of cell- and tissue-based therapies. A new cell surface-engineering strategy is described that uses lipid-chemically self-assembled nanorings (lipid-CSANs) that can be used for the stable and reversible modification of any cell surface with a molecular reporter or targeting ligand. In the presence of a non-toxic FDA-approved drug, the nanorings were quickly disassembled and the cell-cell interactions reversed. Similar to T-cells genetically engineered to express chimeric antigen receptors (CARS), when activated peripheral blood mononuclear cells (PBMCs) were functionalized with the anti-EpCAM-lipid-CSANs, they were shown to selectively kill antigen-positive cancer cells. Taken together, these results demonstrate that lipid-CSANs have the potential to be a rapid, stable, and general method for the reversible engineering of cell surfaces and cell-cell interactions.
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M Balzar