Immunomic analysis of human sarcoma Journal Article

Authors: Lee, S. Y.; Obata, Y.; Yoshida, M.; Stockert, E.; Williamson, B.; Jungbluth, A. A.; Chen, Y. T.; Old, L. J.; Scanlan, M. J.
Article Title: Immunomic analysis of human sarcoma
Abstract: 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 23/39 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.
Keywords: immunohistochemistry; unclassified drug; human cell; proteins; reverse transcription polymerase chain reaction; gene expression; neoplasm proteins; membrane proteins; cancer cell culture; tumor cells, cultured; gene library; tumor antigen; sarcoma; molecular sequence data; fibrosarcoma; antigens, neoplasm; tissue distribution; cancer vaccines; messenger rna; reverse transcriptase polymerase chain reaction; rna, messenger; cancer testis antigen; melanoma antigen 3; ny eso 1 antigen; expressed sequence tag; nucleotide sequence; antigen recognition; recombinant protein; chromosomes, human, x; enzyme-linked immunosorbent assay; synovial sarcoma; repressor proteins; serology; immunoglobulin g antibody; complementary dna; chromosome map; dna, complementary; chromosome xp; polyadenylated rna; humans; human; priority journal; article; ny sar 35 antigen
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 100
Issue: 5
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2003-03-04
Start Page: 2651
End Page: 2656
Language: English
DOI: 10.1073/pnas.0437972100
PUBMED: 12601173
PROVIDER: scopus
PMCID: PMC151395
Notes: Export Date: 12 September 2014 -- Source: Scopus
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MSK Authors
  1. Matthew J Scanlan
    48 Scanlan
  2. Sang Yull Lee
    16 Lee
  3. Achim Jungbluth
    340 Jungbluth
  4. Lloyd J Old
    385 Old