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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 (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 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 HighWire 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 30, 2007 Accepted May 12, 2007 DKK1 is a widely expressed and potent tumor-associated antigen in multiple myeloma Jianfei Qian, Jin Xie, Sungyoul Hong, Jing Yang, Liang Zhang, Xiaohong Han, Michael Wang, Fenghuang Zhan, John D Shaughnessy Jr, Joshua Epstein, Larry W Kwak, and Qing Yi* Dept of Lymphoma & Myeloma, Division of Cancer Medicine, & the Center for Cancer Immunology Research, University of Texas MD Anderson Cancer Center, Houston, TX, United States Myeloma Institute for Research and Therapy, Arkansas Cancer Research Center, University of Arkansas for Medical Sciences, Little Rock, AR, United States * Corresponding author; email: qyi{at}mdanderson.org. 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 by the tumor cells from almost all myeloma patients, could be a good candidate. We identified and synthesized DKK1 peptides for HLA-A*0201 and confirmed their immunogenicity by in vivo immunization in HLA-A*0201 transgenic mice. We detected, using peptide-tetramers, low frequencies of DKK1 peptide-specific CD8+ T cells in myeloma patients and generated peptide-specific T-cell lines and clones from HLA-A*0201+ blood donors and myeloma patients. These T cells efficiently lysed peptide-pulsed but not unpulsed T2 or autologous dendritic cells, 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- 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? This article has been cited by other articles: J. Qian, S. Hong, S. Wang, L. Zhang, L. Sun, M. Wang, J. Yang, L. W. Kwak, J. Hou, and Q. Yi Myeloma cell line-derived, pooled heat shock proteins as a universal vaccine for immunotherapy of multiple myeloma Blood, October 29, 2009; 114(18): 3880 - 3889. [Abstract] [Full Text] [PDF] J. J. Pinzone, B. M. Hall, N. K. Thudi, M. Vonau, Y.-W. Qiang, T. J. Rosol, and J. D. Shaughnessy Jr The role of Dickkopf-1 in bone development, homeostasis, and disease Blood, January 15, 2009; 113(3): 517 - 525. [Abstract] [Full Text] [PDF]

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