Effect of tumor-associated antigens on specific T-cell responses in patients with metastatic lung cancer and potential use as immunogenic targets for a (polyvalent) vaccination strategy.

Abstract

e13064 Background: In spite of many attempts to improve overall survival and to prolong the relapse-free survival in advanced and metastatic lung cancer, therapeutic approaches including chemotherapy and radiation have reached a plateau of efficacy. Therefore, new strategies of tumor therapy have been investigated like immunotherapeutic approaches. Tumor cells can be efficiently killed by specific T-cells of the immune system. Methods: We investigated the frequency of specific T-cell responses of CD8-positive T cells against several known but also newly characterized HLA-A2-restricted epitopes derived from the tumor-associated antigens MAGE-A3, RHAMM, hTERT, Survivin, WT-1, PRAME, HER2/neu, and G250 in patients with metastatic lung cancer. For new epitopes HLA-A2-binding motifs were predicted using computer analysis based on known binding affinities. More than 10 peptides with most favorable characteristics were evaluated in ELISPOT assays for interferon gamma and granzyme B secretion by CD8 positive T cells in patients with metastatic lung cancer. Results: Specific T-cell responses could be detected against at least one peptide in all patients with non-small cell lung cancer before treatment with chemotherapy. Most frequent responses could be detected (50% or more of patients) against a peptide derived from hTERT and PRAME. Lower frequency of specific T-cell responses was found for Survivin- (40%), G250- (33%), and MageA3-derived peptides (20%), no responses against RHAMM-, HER2neu-, and WT1-derived peptides. Conclusions: Taken together, specific T- cell responses against several TAAs could be detected for the antigens hTERT and PRAME in 50% or more of patients with lung cancer, but also in a lower frequency against MAGEA3, G250 and Survivin peptides. Therefore, immunotherapeutic approaches targeting these antigen structures is a new therapeutic option for these patients in advanced lung cancer. No significant financial relationships to disclose.