Article

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.

0 Bookmarks
 · 
130 Views
  • [Show abstract] [Hide abstract]
    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.
    Angewandte Chemie International Edition 04/2014; · 11.34 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Personalized medicine is a modern healthcare approach where information on each person's unique clinical constitution is exploited to realize early disease intervention based on more informed medical decisions. The application of diagnostic tools in combination with measurement evaluation that can be performed in a reliable and automated fashion plays a key role in this context. As the progression of various cancer diseases and the effectiveness of their treatments are related to a varying number of tumor cells that circulate in blood, the determination of their extremely low numbers by liquid biopsy is a decisive prognostic marker. To detect and enumerate circulating tumor cells (CTCs) in a reliable and automated fashion, we apply methods from machine learning using a naive Bayesian classifier (NBC) based on a probabilistic generative mixture model. Cells are collected with a functionalized medical wire and are stained for fluorescence microscopy so that their color signature can be used for classification through the construction of Red-Green-Blue (RGB) color histograms. Exploiting the information on the fluorescence signature of CTCs by the NBC does not only allow going beyond previous approaches but also provides a method of unsupervised learning that is required for unlabeled training data. A quantitative comparison with a state-of-the-art support vector machine, which requires labeled data, demonstrates the competitiveness of the NBC method. © 2014 International Society for Advancement of Cytometry.
    Cytometry Part A 04/2014; · 3.71 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Stimulation of CD40 can augment anti-cancer T cell immune responses by triggering effective activation and maturation of antigen-presenting cells (APCs). Although CD40 agonists have clinical activity in humans, the associated systemic activation of the immune system triggers dose-limiting side-effects. To increase the tumor selectivity of CD40 agonist-based therapies, we developed an approach in which soluble trimeric CD40L (sCD40L) is genetically fused to tumor targeting antibody fragments, yielding scFv:CD40L fusion proteins. We hypothesized that scFv:CD40L fusion proteins would have reduced CD40 agonist activity similar to sCD40L but will be converted to a highly agonistic membrane CD40L-like form of CD40L upon anchoring to cell surface exposed antigen via the scFv domain. Targeted delivery of CD40L to the carcinoma marker EpCAM on carcinoma cells induced dose-dependent paracrine maturation of DCs ~20-fold more effective than a non-targeted control scFv:CD40L fusion protein. Similarly, targeted delivery of CD40L to the B cell leukemia marker CD20 induced effective paracrine maturation of DCs. Of note, the CD20-selective delivery of CD40L also triggered loss of cell viability in certain B cell leukemic cell lines as a result of CD20-induced apoptosis. Targeted delivery of CD40L to cancer cells is a promising strategy that may help to trigger cancer-localized activation of CD40 and can be modified to exert additional anti-cancer activity via the targeting domain.
    Molecular Cancer 04/2014; 13(1):85. · 5.13 Impact Factor