PMID- 17515399
OWN - NLM
STAT- MEDLINE
DCOM- 20071019
LR  - 20220311
IS  - 0006-4971 (Print)
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 110
IP  - 5
DP  - 2007 Sep 1
TI  - Dickkopf-1 (DKK1) is a widely expressed and potent tumor-associated antigen in 
      multiple myeloma.
PG  - 1587-94
AB  - 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.
FAU - Qian, Jianfei
AU  - Qian J
AD  - 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 77030, USA.
FAU - Xie, Jin
AU  - Xie J
FAU - Hong, Sungyoul
AU  - Hong S
FAU - Yang, Jing
AU  - Yang J
FAU - Zhang, Liang
AU  - Zhang L
FAU - Han, Xiaohong
AU  - Han X
FAU - Wang, Michael
AU  - Wang M
FAU - Zhan, Fenghuang
AU  - Zhan F
FAU - Shaughnessy, John D Jr
AU  - Shaughnessy JD Jr
FAU - Epstein, Joshua
AU  - Epstein J
FAU - Kwak, Larry W
AU  - Kwak LW
FAU - Yi, Qing
AU  - Yi Q
LA  - eng
GR  - R01 CA096569/CA/NCI NIH HHS/United States
GR  - R01 CA103978/CA/NCI NIH HHS/United States
GR  - R01-CA103978/CA/NCI NIH HHS/United States
GR  - R01-CA96569/CA/NCI NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070521
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (DKK1 protein, human)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-A*02:01 antigen)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Peptides)
SB  - IM
MH  - Animals
MH  - Antigen Presentation/drug effects/immunology
MH  - Antigens, Neoplasm/biosynthesis/*immunology/pharmacology
MH  - B-Lymphocytes/immunology
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Dendritic Cells/immunology
MH  - Gene Expression Regulation, Neoplastic/*immunology
MH  - HLA-A Antigens/*immunology
MH  - HLA-A2 Antigen
MH  - Humans
MH  - Intercellular Signaling Peptides and 
      Proteins/biosynthesis/*immunology/pharmacology
MH  - K562 Cells
MH  - Mice
MH  - Mice, Transgenic
MH  - Multiple Myeloma/*immunology/therapy
MH  - Peptides/*immunology/pharmacology
MH  - Vaccination
PMC - PMC1975842
EDAT- 2007/05/23 09:00
MHDA- 2007/10/20 09:00
PMCR- 2008/09/01
CRDT- 2007/05/23 09:00
PHST- 2007/05/23 09:00 [pubmed]
PHST- 2007/10/20 09:00 [medline]
PHST- 2007/05/23 09:00 [entrez]
PHST- 2008/09/01 00:00 [pmc-release]
AID - S0006-4971(20)49450-9 [pii]
AID - 2007/082529 [pii]
AID - 10.1182/blood-2007-03-082529 [doi]
PST - ppublish
SO  - Blood. 2007 Sep 1;110(5):1587-94. doi: 10.1182/blood-2007-03-082529. Epub 2007 
      May 21.