Identification of a CTL-directed epitope encoded by an intron of the putative tumor suppressor gene Testin of the common fragile site 7G region: a peptide vaccine candidate for HLA-B52+ and HLA-62+ cancer patients.

Abstract

Although cytotoxic T lymphocyte (CTL)-directed epitopes binding to human histocompatibility leukocyte antigen (HLA)-A molecules have been well characterized, those binding to HLA-B molecules have not, largely due to their large diversity. In this study we report a unique cancer antigen gene, tentatively named Testin-related gene (TRG), which encodes CTL-directed epitopes on the HLA-B52 molecules most frequently expressed in Asians. TRG is located in an intron of the putative tumor suppressor gene Testin in the common fragile site 7G region at 7q31.2. TRG mRNA was expressed in the majority of cancer cells and cancer tissue tested, whereas it was scarcely expressed in the majority of normal tissues, and only low-level expression of TRG was detected in the heart, liver, and pancreas. One TRG peptide had the ability to induce HLA-B52-restricted CTL cytotoxic to TRG+ tumor cells in peripheral blood mononuclear cells (PBMC) of epithelial cancer patients. This peptide also induced HLA-B62-restricted and tumor-reactive CTL in PBMC of cancer patients. Therefore, this TRG-derived peptide might be appropriate for use in peptide-based immunotherapy for relatively large numbers of cancer patients throughout the world, given that 34% of Japanese, 27% of Chinese, and 13% of Caucasians express either HLA-B52 or HLA-B62 molecules