Expression of the SART1 tumor-rejection antigens in colorectal cancers

PURPOSE: Colorectal cancer is one of the major causes of cancer death in th e world, including in the United States and Japan. We recently identified t he tumor-rejection antigen gene SART1, which encodes both the SART1(259) an tigen expressed in the cytosol of epithelial cancers and the SART1(800) ant igen expressed in the nucleus of the majority of proliferating cells. This study investigated the expression of these tumor antigens to explore a pote ntial molecule for specific immunotherapy of colorectal cancer patients. ME THODS: SART1 antigens were investigated by Western blotting in six colorect al cancer cell lines and in 33 colorectal cancer tissues. The cancer cell l ines were tested for their ability to stimulate interferon-gamma production by the human-leukocte-antigen-A24-restricted and SART1-specific cytotoxic T lymphocytes and were also tested for their susceptibility to the lysis by the cytotoxic T lymphocytes. RESULTS: The SART1(259) antigen was detected in the cytosol of four of six cancer cell lines, 13 of 33 (39 percent) canc er tissues, and 0 of 20 nontumorous colorectal tissues. The SART1(800) anti gen was expressed in the nucleus of all the colorectal cancer cell lines, 1 8 of 33 (55 percent) cancer tissues, and 0 of 20 nontumorous tissues. The h uman-lymphocyte-antigen-A24-restricted and SART1-specific cytotoxic T lymph ocytes killed the human-lymphocyte-antigen-A24(+) SART1(259+) cancer cells. CONCLUSIONS: The SART1(259) antigen could be an appropriate target molecul e for specific immunotherapy of approximately 40 percent of the human-lymph ocyte-antigen-A24(+) patients with colorectal cancer.