Institut für Ernährungsmedizin

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Bedeutung von Tumorantigenen bei Hauttumorpatienten
(2008) Wiedemann, Nicole; Eichmüller, Stefan
Essential prerequisites for the development of specific immunotherapies and procedures for diagnosis and prognosis of tumor diseases are the knowledge and characterization of tumor antigens. Potential antigens for immunotherapeutic strategies and diagnosis tools should be tumor-specific. Moreover, indications for immune responses in patients e.g. antibody or T cell responses should be available. In this thesis, antibody responses of patients of cutaneous T cell lymphoma (CTCL), melanoma (MM) and controls were investigated using two different methods. In addition, the tumor antigen GAGE-7b was characterized using a rabbit polyclonal antibody. In order to test antibody frequencies of various tumor antigens in parallel, a serum antibody detection array (SADA) was established. Testing 42 tumor antigens, antibodies against 14 antigens were only detectable in patients but not in controls. Serum antibody frequencies of antigens GBP-5ta, GBP-5a, HD-MM48 and HD-MM-19 were significantly higher in MM patients compared to controls. The same was true for antigens HD-MM-48 and HD-CL-02 comparing CTCL patients and controls. In summary, antibody frequencies were relatively low ranging most frequently from 0% to 10% which limits the use of the respective antigens as diagnostic targets. An additional method to measure immunoreactivities of 13 cancer testis and tumor-associated antigens in different groups named multiplex serology was used. Antibodies against LAGE-1a were detected significantly more frequently in MM patients in comparison to controls. In addition, this higher antibody frequency in MM patients was stage dependent. For antigens MAGE-A3, GAGE-7b and se57-1 a higher antibody frequency in MM patients was measured likewise. Antibody titers of MM and CTCL patients rarely changed over time, thus seroconversions were seen only sporadically. Significantly higher reactivities could be identified for MAGE-A1 and A9 in CTCL patients of different stages compared to controls. In future, analyzing patients immunized with interferon-g, tumor or dendritic cells or immunotherapy targeting specific tumor antigens would be of high interest. For the first time, a comprehensively characterized rabbit polyclonal antibody against GAGE-7b was generated and used in Western Blot and immunohistology. In Western Blot analysis, 59% of all MM cell lines tested expressed GAGE-7b, whereas no protein was detected in both CTCL cell lines and control tissues except testis. This expression pattern was confirmed by immunocytology. Immunohistological tests confirmed that 53% of MM tissues are positive for GAGE-7b protein expression. Moreover, antibodies against GAGE-7b could be identified in 6% of MM and CTCL patients whereas controls had no detectable antibody responses. On the basis of the achieved results, the GAGE-7b antibody recognizes probably all GAGE family members. Future analysis using this antibody may permit the elucidation of functional aspects of GAGE expression in tumor diseases.

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