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Implications of specific T-cell responses by different novel and known immunogenic tumor-associated antigens (TAA) in patients with metastatic lung cancer.

10619 Background: In the last years, new therapeutic strategies of lung cancer with encouraging results have been investigated including immunotherapeutic approaches, e.g. against MAGE-A3 and hTERT. Thus, tumor vaccination seems to be a promising strategy especially in situations of reduced tumor load, i.e. in maintenance therapy. Here we address the question, whether there are further interesting candidates besides the antigens MAGE-A3 and hTERT that induce intensive immune reactions in a high frequency in lung cancer and are therefore eligible for immunotherapeutic approaches.


METHODS
Immune reactions of CD8+ T-cells were measured in ELISPOT assays for IFN-gamma and granzyme B. Moreover, tetramer assays and chromium release assays were performed. Epitopes were tested derived from the lung-cancer associated antigens MAGE-A3 and hTERT, and from the antigens RHAMM, Survivin, WT-1, PRAME, HER2 and G250 known from other tumor entities as well as novel antigens, like Aurorakinases A and B. For these novel antigens more than 10 HLA-A2-binding peptides were predicted and tested in 20 healthy volunteers and 15 lung cancer patients.


RESULTS
Specific T-cell responses could be detected against at least one peptide in all patients. Most frequent responses were detected against PRAME (67%), hTERT (60%), G250 (60%) and RHAMM (40%). Lower frequency was measured for Survivin- (27%), WT-1- (27%), the two MAGE-A3- (27 and 20%) and Her2- (15%) derived peptides. Specific T-cell responses could be also detected against Aurorakinases A and B. The novel peptides AuraA01 and AuraB01 showed specific T-cell responses in 33% and 40% of patients respectively. Serological immune responses are under investigation.


CONCLUSIONS
Specific T-cell responses against several TAA could be detected for the antigens hTERT, PRAME, G250 and RHAMM in a high frequency of patients with lung cancer, but also in a lower frequency against several other antigen peptides. Moreover, novel immunogenic targets like Aurorakinases were identified. Therefore, further antigen structures are appropriate for immuno-targeted approaches in lung cancer.