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Frequent T cell responses against immunogenic targets in lung cancer patients for targeted immunotherapy.

To date, lung cancer is one of the leading causes of cancer mortality with short overall survival despite adequate therapy. New immunotherapeutic strategies using peptides derived from tumor-associated antigens (TAAs) can induce a specific cytotoxic T cell (CTL) response leading to a targeted tumor cell death. In the present study, we addressed whether there are further significant immunogenic candidate targets that may induce strong immune reactions with a high frequency in lung cancer patients eligible for cellular immunotherapeutic approaches, such as in a polyvalent vaccination approach. In this study, we investigated specific CTL responses of 14 HLA-A*0201-positive patients (of 33 screened patients) with non-small cell lung cancer (NSCLC; n=12) or small cell lung cancer (SCLC; n=2) against several known and novel TAA-derived peptides from lung cancer and/or other tumor entities, by measuring granzyme B (GrB) and/or interferon γ (IFNγ) secretion using enzyme-linked immunospot (ELISpot) analysis. Specific T cell responses could be detected for hTERT (4/13), two MAGE-A3-derived peptides (4/13 and 3/13, respectively), RHAMM (4/14), PRAME (8/14), G250 (7/12), survivin (3/13), HER2 (5/10) and WT1 (2/14), but also novel epitopes derived from Aurora kinase A (4/13) and B (5/13). Additionally, simultaneous CTL responses against the different peptides were examined and specific T cell responses against at least one of these TAAs could be detected in 13/14 (93%) patients. It could be shown that all patients with immune reactions against RHAMM and hTERT showed also immune responses against PRAME. Furthermore, patients with CTL responses against the Aurora kinase A peptide (Aura A1) also demonstrated a response against the Aurora kinase B peptide (Aura B1). Taken together, we showed that these TAA-derived peptides induce frequent specific T cell responses in patients with metastatic lung cancer and are, therefore, novel candidates for targeted immunotherapies and polyvalent approaches.