Expression of the SART1 tumor rejection antigen in renal cell carcinoma

Abstract

We have previously described the SART1 gene, which encodes both the SART1₂₅₉ antigen expressed in the cytosol of the majority of squamous cell carcinomas and some adenocarcinomas and the SART1₈₀₀ antigen expressed in the nucleus of the majority of proliferating cells. The SART1₂₅₉ antigen is recognized by HLA-A24 and A26-restricted cytotoxic T lymphocytes (CTLs). The present study investigated the expression of these two antigens in renal cell carcinomas (RCCs) in order to identify an appropriate molecule for use in specific immunotherapy for RCC patients. These two antigens were detected in all RCC cell lines and cells of the primary cultures of the RCCs tested. Further, they were detectable in cells of the primary cultures of non-tumorous kidney tissues. In contrast to these cultured cells, SART1₂₅₉ was detectable in only a few uncultured RCC tissues (5/20, 25%) and was undetectable in non-tumorous kidney tissues. SART1₈₀₀ was also scarcely detectable in uncultured RCC tissues (3/20, 15%) and non-tumorous kidney tissues (4/20, 20%). HLA-A2402-restricted and tumor-specific CTL (KE4-CTL) used for the cloning of the SART1 gene showed significant levels of cytotoxicity to both the cells from the RCC cell line and the cells from the primary cultures of RCC tissues, but did not lyse any normal cells, including cells from the primary cultures of non-tumorous kidney tissues. The SART1-derived peptide at positions 690–698 induced HLA-A24 restricted CTLs cytotoxic to RCC cells from peripheral blood mononuclear cells (PBMCs) of RCC patients. Therefore, the SART1 peptide could be an appropriate molecule for use in peptide-based specific immunotherapy for RCC patients.