Immunomic analysis of human sarcoma.
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.
Lee
Sang-Yull
SY
Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. .
Obata
Yuichi
Y
Yoshida
Masahiro
M
Stockert
Elisabeth
E
Williamson
Barbara
B
Jungbluth
Achim A
AA
Chen
Yao-Tseng
YT
Old
Lloyd J
LJ
Scanlan
Matthew J
MJ
D000951:Antigens, Neoplasm / Q000097:blood* / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology; D041321:Chromosomes, Human, X; D018076:DNA, Complementary / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005354:Fibrosarcoma / Q000097:blood; D015723:Gene Library; D006801:Humans; D058950:Melanoma-Specific Antigens; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000097:blood; D011506:Proteins / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012509:Sarcoma / Q000276:immunology*; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; C473332:CT7 antigen, human; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D018076:DNA, Complementary; C119317:MAGE-A10 antigen; C072013:MAGEA3 protein, human; C095204:MAGEA4 protein, human; C405429:MAGEC2 protein, human; D058950:Melanoma-Specific Antigens; D008565:Membrane Proteins; C473333:NY-SAR-35 antigen, human; D009363:Neoplasm Proteins; D011506:Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C093962:synovial sarcoma X breakpoint proteins