Expression of tumor-rejection antigens in gynecologic cancers

We recently reported the four tumor-rejection antigens (SART1(259), SART2, SART3, and ART4) that possess tumor epitopes capable of inducing HLA-A2402- restricted cytotoxic T lymphocytes (CTLs) in cancer patients. This study in vestigated the expression of these tumor antigens in gynecologic cancers, i ncluding 33 ovarian cancers, 38 cervical cancers, and 40 endometrial cancer s. SART1(259) antigen was-detected in 56%, 35%, and 30% of ovarian, cervica l and endometrial cancers, while SART2 antigen was detected in 46%, 66%, an d 30% of these cancers, respectively. Both SART3 and ART4 antigens were det ectable in the majority of these gynecologic cancers tested. In contrast, n one of these antigens was detectable in any of the normal ovarian and uteri ne tissues tested. Peripheral blood mononuclear cells (PBMCs) of HLA-A24(+) patients with gynecologic cancers were found to produce significant levels of interferon-gamma in response to HLA-A24(+) SART3(+) gynecologic cancer cells after having been stimulated three times in vitro with either SART3(1 09-118) or SART3(315-323) peptide. These PBMCs lysed HLA-A24(+) SART3(+) gy necologic cancer cells, but not HLA-A24(-) SART3(+) gynecologic cancer cell s or HLA-A24(+) normal cells. Therefore, these four antigens and their pept ides, including SART3 peptides, would be appropriate molecules for use in s pecific immunotherapy of HLA-A24(+) gynecologic cancer patients.