Identification of a cluster of tumor antigens recognized by CTh of colon cancer patients

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Background : Colon cancer is one of major malignant tumors to which development of new treatment modality is needed. To provide scientific basis of specific immunotherapy of colon cancer, this study focused on identification of a cluster of tumor antigens and their epitopes recognized by HLA-A2-restricted and tumor-reactive cytotoxic T lymphocytes (CTLs) generated from tumor-infiltrating lymphocytes (TIL) of a colon cancer patient.Methods : The HLA-A2-restricted and tumor-reactive OK-Cm line was established from TILs of a patient with colon cancer. A gene-expression cloning method was used to identify genes coding for tumor antigens recognized by the OK-CTLd subline. To identify CTL-directed epitopes, the CTLs were incubated for 18 hr with T2 cells pre-pulsed with each peptide at different doses for 2 hr followed by harvesting of supernatant to measure IFN-γ by ELISA.Results : We identified 27 genes, including 9 unique genes. Thirteen (56.5%) of the 23 genes with known or presumed functions encoded proliferation-related proteins. The others mainly consisted of genes encoding transporters. Among 393 peptides with HLA-A2 binding motifs encoded by the 27 genes, 68 peptides were recognized by the parental CTLs, and 26 peptides among them were also recognized by CTLs in the circulation of colon cancer patients. Further, 16 of these 26 peptides possessed the ability to induce HLA-A2 restricted and peptide-specific CTLs cytotoxic to colon tumor cells in peripheral blood mononuclear cells of colon cancer patients. In the other hands, 5 and 7 peptides encoded by 2 and 4 genes, respectively, were identified with recognized by HLA-B46 and -A31 restricted CTL.Conclusion : These antigens and peptides could be appropriate in use for specific immunotherapy of HLA-A2^+ colon cancer patients.