Expression of the SART1 tumor rejection antigen in renal cell carcinoma

We have previously described the SART1 gene, which encodes both the SART1(2 59) antigen expressed in the cytosol of the majority of squamous cell carci nomas and some adenocarcinomas and the SART1(800) antigen expressed in the nucleus of the majority of proliferating cells. The SART1(259) antigen is r ecognized by HLA-A24 and A26-restricted cytotoxic T lymphocytes (CTLs). The present study investigated the expression of these two antigens in renal c ell carcinomas (RCCs) in order to identify an appropriate molecule for use in specific immunotherapy for RCC patients. These two antigens were detecte d in all RCC cell lines and cells of the primary cultures of the RCCs teste d. Further, they were detectable in cells of the primary cultures of non-tu morous kidney tissues. In contrast to these cultured cells. SART1(259) was detectable in only a few uncultured RCC tissues (5/20, 25%) and was undetec table in non-tumorous kidney tissues. SART1(800), was also scarcely detecta ble 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 cultur es of RCC tissues, but did not lyse any normal cells, including cells from the primary cultures of non-tumorous kidney tissues. The SART1-derived pept ide at positions 690-698 induced HLA-A24 restricted CTLs cytotoxic to RCC c ells from peripheral blood mononuclear cells (PBMCs) of RCC patients, There fore, the SART1 peptide could be an appl appropriate molecule for use in pe ptide-based specific immunotherapy for RCC patients.