Modulation von tumor-assoziierten Antigenen durch Cholesterylhemisuccinat bei Ovarialkarzinom-Zellen
There is strong evidence that malignant cells bear tumor-associated antigens (TAA). The antigenicity of tumor cells, however, is too weak to elicit an effective immune reaction against tumor growth. In order to induce an increase of the immunogenicity, ovarian carcinoma cells growing in cell culture were treated with cholesteryl hemisuccinate (CHS). This agent is well known as a modulator of the fluidity of the cell membrane causing an altered expression of a variety of membrane proteins, possibly by vertical displacement. Antibodies detecting these cells were found by immunocytochemistry in autologous and allogenic ascites. Using flow cytometry analysis, an increase in fluorescence intensity was observed on trypsinized cells stained with purified autologous and allogenic IgG after CHS incubation for 2 to 3 h. Avoiding possible trypsin induced shedding of antigens, a cell ELISA was developed to analyse the exposition of antigens on viable adherent cells in 96-well plates. Using this approach, the kinetic of the autologous and allogenic antibody bindings could be studied. These experiments confirmed the results obtained by flow cytometry in respect to the autologous antibody binding. The binding of allogenic IgG was in this case far less enhanced by CHS. The results suggest a potent role of CHS as an enhancer of antigen exposition. Therefore, CHS could be a possible candidate for an immunomodulating agent for using in an active specific vaccination and immunotherapy of cancer.
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