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Blood, 1 September 2007, Vol. 110, No. 5, pp. 1587-1594. Prepublished online as a Blood First Edition Paper on May 21, 2007; DOI 10.1182/blood-2007-03-082529. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-03-082529v1 110/5/1587    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Qian, J. Articles by Yi, Q. Search for Related Content PubMed PubMed Citation Articles by Qian, J. Articles by Yi, Q. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Dickkopf-1 (DKK1) is a widely expressed and potent tumor-associated antigen in multiple myeloma Jianfei Qian1, Jin Xie2, Sungyoul Hong1, Jing Yang1, Liang Zhang1, Xiaohong Han1, Michael Wang1, Fenghuang Zhan2, John D. Shaughnessy, Jr2, Joshua Epstein2, Larry W. Kwak1, and Qing Yi1 1 Department of Lymphoma and Myeloma, Division of Cancer Medicine, and the Center for Cancer Immunology Research, The University of Texas M. D. Anderson Cancer Center, Houston, TX; and 2 Myeloma Institute for Research and Therapy, Arkansas Cancer Research Center, University of Arkansas for Medical Sciences, Little Rock The identification of novel tumor-associated antigens, especially those shared among patients, is urgently needed to improve the efficacy of immunotherapy for multiple myeloma (MM). In this study, we examined whether Dickkopf-1 (DKK1), a protein that is not expressed in most normal tissues but is expressed by tumor cells from almost all patients with myeloma, could be a good candidate. We identified and synthesized DKK1 peptides for human leukocyte antigen (HLA)–A*0201 and confirmed their immunogenicity by in vivo immunization in HLA-A*0201 transgenic mice. We detected, using peptidetetramers, low frequencies of DKK1 peptide-specific CD8-positive (CD8+) T cells in patients with myeloma and generated peptide-specific T-cell lines and clones from HLA-A*0201-positive (HLA-A*0201+) blood donors and patients with myeloma. These T cells efficiently lysed peptide-pulsed but not unpulsed T2 or autologous dendritic cells, DKK1-positive (DKK1+)/HLA-A*0201+ myeloma cell lines U266 and IM-9, and, more importantly, HLA-A*0201+ primary myeloma cells from patients. No killing was observed on DKK1+/HLA-A*0201-negative (HLA-A*0201–) myeloma cell lines and primary myeloma cells or HLA-A*0201+ normal lymphocytes, including B cells. These results indicate that these T cells were potent cytotoxic T cells and recognized DKK1 peptides naturally presented by myeloma cells in the context of HLA-A*0201 molecules. Hence, our study identifies DKK1 as a potentially important antigen for immunotherapy in MM. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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