Expression of the SART3 tumor rejection antigen in renal cell carcinoma

Purpose: We recently reported that SART3 tumor rejection antigen is recogni zed by HLA class I restricted cytotoxic T lymphocytes from patients with es ophageal cancer. We now investigate the expression of SART3 antigen in rena l cell carcinoma to identify an appropriate molecule that may be used in sp ecific immunotherapy of renal cell carcinoma. Materials and Methods: Renal cell carcinoma and nontumorous kidney tissues were obtained at surgery. A section of each sample was minced with scissors and stored at -80C until use. SART3 antigen expression was examined in unc ultured renal cell carcinoma and nontumorous kidney tissues. We also evalua ted the ability of derived peptides to include cytotoxic T lymphocytes in p eripheral blood mononuclear cells from patients with renal cell carcinoma. Results: The SART3 antigen was detected in all renal cell carcinoma cell li nes, primary cultures of renal cell carcinoma and nontumorous kidney tissue s, and in the cytosol of 57% and 15% of renal cell carcinoma and nontumorou s kidney tissues, respectively. HLA-A2402 restricted and tumor specific cyt otoxic T lymphocytes (KE4) used in cloning of the SART3 gene were significa ntly cytotoxic to cells from renal cell carcinoma cell lines and primary cu ltures of renal cell carcinoma tissue but they did not lyse normal cells, i ncluding those from primary cultures of nontumorous kidney tissue. The SART 3 peptides derived from positions 109-118 and 315-323 induced HLA-A24 restr icted cytotoxic T lymphocytes to renal cell carcinoma cells from peripheral blood mononuclear cells of patients with renal cell carcinoma. Conclusions: The SART3 antigen and derived peptides may be applied to the s pecific immunotherapy of HLA-A24(+) renal cell carcinoma.