Identification of Genes Encoding Lung Cancer Antigens Recognized by Cytotoxic T-lymphocytes and Development of Cancer Vaccines

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Lung cancer is among the most commonly occurring malignancies in the world and is one of the few that continuous to show an increasing incidence. Prognosis of patients with unrespectable progressive stages of non-small cell lung cancer is very poor, since chemotherapy is the only modality for these patients and response rate to anti-cancer drugs in patients with non-small cell lung cancer is low. Therefore, development of new therapeutic modalities for lung cancer is necessary. Specific immunotherapy is one of the most prominent and hopeful modalities in lung cancer treatment. We have investigated tumor rejection antigens recognized by HLA-A2402-restricted cytotoxic T lymphocytes (CTLs) established from T cells infiltrating into lung cancer, and we show that a multidrug resistance-associated protein 3 (MRP3) is a tumor rejection antigen recognized by HLA.-A2402-restricted cytotoxic T-lymphocytes (CTLs) established from T cells infiltrating into lung adenocarcinoma. MRP3 is expressed in … More differing quantities in tumor cells of various tissue types and origins. Four dominant MRP3-derived antigenic peptides which are recognized by the CTLs have been identified, each possessing in vitro immunogenicity. We also reported three newly identified tumor antigen genes, including one unreported gene, temporarily referred to as clone 83, and two known genes, BTB domain containing-2 (BTBD2) and hairpin-binding protein. These genes were preferentially expressed in most of the cell lines of lung cancer, and also of ovarian cancer and renal cell carcinoma at the mRNA level. The expression of these genes was confirmed in lung and other cancer tissue specimens. Clone 83, BTBD2, and hairpin-binding protein encoded 2, 1, and 1 epitope peptides that can be recognized by HLA-A2402-restricted CTLs, respectively, and each peptides possessing in vitro immimogenicity. These results suggest that these genes and peptides are potential candidates for cancer vaccines in HLA-A24^+ patients with lung cancer. Less