The screening of
cDNA expression libraries from human
tumors with serum antibody (SEREX) has proven to be a powerful method for identifying the repertoire of
tumor antigens recognized by the immune system of
cancer patients, referred to as the
cancer immunome. In this regard,
cancer/testis (CT)
antigens are of particular interest because of their immunogenicity and restricted expression patterns. Synoivial
sarcomas are striking with regard to CT
antigen expression, with >80% of specimens homogeneously expressing NY-ESO-1 and MAGE-A3. In the present study, 54
sarcoma patients were tested for serum
antibodies to NY-ESO-1, SSX2, MAGE-A1, MAGE-A3, MAGE-A4, MAGE-A10, CT7, and CT10. Two patients had detectable
antibodies to CT
antigens, and this seroreactivity was restricted to NY-ESO-1. Thus, although highly expressed in
sarcoma, CT
antigens do not induce frequent humoral immune responses in
sarcoma patients. Sera from these two patients were used to immunoscreen cDNA libraries from two
synovial sarcoma cell lines and normal testis, resulting in the identification of 113 distinct
antigens. Thirty-nine
antigens were previously identified by SEREX analysis of other
tumor types, and 2339
antigens (59%) had a serological profile that was not restricted to
cancer patients, indicating that only a proportion of SEREX-defined
antigens are
cancer-related. A novel CT
antigen, NY-SAR-35, mapping to chromosome Xq28 was identified among the
cancer-related
antigens, and encodes a putative extracellular
protein. In addition to testis-restricted expression, NY-SAR-35
mRNA was expressed in
sarcoma,
melanoma,
esophageal cancer,
lung cancer and
breast cancer. NY-SAR-35 is therefore a potential target for
cancer vaccines and
monoclonal antibody-based
immunotherapies.