Nachweis spezifischer T-Zell-vermittelter Immunantworten gegen Tumor assoziierte Antigene bei Lungenkrebs
Auch gedruckt in der BibliothekW: W-H 14.473
Steinhauser, Maximilian Felix
Ressourcen- / MedientypDissertation, Text
Datum der Freischaltung2015-11-25
Recently, new approaches like kinase inhibitors and monoclonal antibodies and immunotherapy showed promising results in lung cancer therapy. Vaccination with TAAs, such as MAGE-A3 and hTERT are beeing tested in phase III studies. Therefore it is important to identify new immunogenic targets for immunotherapy. In this study, t-cell mediated specific immune response against 11 peptide epitopes have been tested in patients with advanced NSCLC (n=12) and SCLC (n=2), who haven been selected for HLA-A2 expression from 35 Patients. Therefore mixed lymphocyte/peptide culture and ELISpot assays for interferon gamma and granzyme B were performed. Peptides derived from TAAs RHAMM, PRAME, WT-1, hTERT, Survivin, MAGE A3, G250, HER2 and aurora kinases A and B were tested. 13 of 14 patients showed cellular immune response against at least 1 peptide. Every peptide was able to induce positive reactions in at least 3 patients in one ELISpot assay. G250 G2 and PRAME P3 seem to be interesting targets for immunotherapies, as they induced t-cellular mediated immune response 67 % and 64 % of patients. Both TAAs are expressed by lung cancer in high frequency. This work showed, that patients with advanced lung cancer are able to generate specific t-cell mediated immune responses against varoius peptides epitopes derived from tumor associated antigens. Therefore these peptides are potential targets for immunotherapies against lung cancer.