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Gene and Peptide Analyses of Newly Defined Lung Cancer Antigens Recognized by HLA-A2402-restricted Tumor-specific Cytotoxic T Lymphocytes¹

Cancer Vaccine Development Division, Kurume University Research Center for Innovative Cancer Therapy [A. Y., K. K., M. K., M. N., K. I.], Department of Immunology [A. Y., K. I.], and Department of Surgery [S. T.], Kurume University School of Medicine, Kurume 830-0011, Japan

We investigated tumor antigens recognized by HLA-A2402-restricted CTLs established from T cells infiltrating into lung adenocarcinoma. We report here 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. In normal tissues, clone 83 was expressed only in the colon, and hairpin-binding protein was not expressed at all, whereas BTBD2 was ubiquitously expressed. Clone 83, BTBD2, and hairpin-binding protein encoded two, one, and one epitope peptides that can be recognized by HLA-A2402-restricted CTLs, respectively. These epitope peptides possessed the ability to induce HLA-A24-restricted tumor-specific CTLs after in vitro stimulation in a culture of peripheral blood mononuclear cells from patients with lung cancer. These results suggest that these genes and peptides are potential candidates for cancer vaccines in HLA-A24⁺ patients with lung cancer.

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