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Cancer
Immunity, Vol. 1, p. 4 (30 March 2001) Submitted:
16 February 2001. Accepted: 19 February 2001.
Contributed by: Lloyd J. Old
Humoral immunity to human breast cancer: antigen definition and quantitative analysis of mRNA expression
Matthew J. Scanlan1, Ivan Gout2,
Claudia M. Gordon1, Barbara Williamson1,
Elisabeth Stockert1, Ali O. Gure1,
Dirk Jäger3, Yao-Tseng Chen1,4,
Allen Mackay2, Michael J. O'Hare2,
and Lloyd J. Old1
1Ludwig Institute for Cancer Research, New York Branch of Human Cancer Immunology at Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021
2Ludwig Institute for Cancer Research, London Branch at the University College School of Medicine, 91 Riding House Street, London W1P 8BT, England
3II.Medizinische Klinik, Hämatologie-Onkologie, Krankenhaus Nordwest, 60488 Frankfurt, Germany
4Cornell University Medical College, Department of Pathology, 1300 York Avenue, New York, NY 10021
Keywords:
Breast cancer, human, humoral immunity, tumor antigens, SEREX, mRNA, tissue distribution
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Abstract
The ability of the immune system to recognize structurally altered, amplified or aberrantly expressed proteins can be used to identify molecules of etiologic relevance to cancer and to define targets for cancer immunotherapy. In the current study, ninety-four distinct antigens reactive with serum IgG from breast cancer patients were identified by immunoscreening breast cancer-derived cDNA expression libraries (SEREX). A serological profile was generated for each antigen on the basis of reactivity with allogeneic sera from normal individuals and cancer patients, and mRNA expression profiles for coding sequences were assembled based upon the tissue distribution of expressed sequence tags, Northern blots and real-time RT-PCR. Forty antigens reacted exclusively with sera from cancer patients. These included well-characterized tumor antigens, e.g. MAGE-3, MAGE-6, NY-ESO-1, Her2neu and p53, as well as newly-defined breast cancer antigens, e.g. kinesin 2, TATA element modulatory factor 1, tumor protein D52 and MAGE D, and novel gene products, e.g. NY-BR-62, NY-BR-75, NY-BR-85, and NY-BR-96. With regard to expression profiles, two of the novel gene products, NY-BR-62 and NY-BR-85, were characterized by a high level of testicular mRNA expression, and were overexpressed in 60% and 90% of breast cancers, respectively. In addition, mRNA encoding tumor protein D52 was overexpressed in 60% of breast cancer specimens, while transcripts encoding SNT-1 signal adaptor protein were downregulated in 70% of these cases. This study adds to the growing list of breast cancer antigens defined by SEREX and to the ultimate objective of identifying the complete repertoire of immunogenic gene products in human cancer (the cancer immunome).
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