Document Detail


Identification of an immunogenic HLA-A*0201-binding T-cell epitope of the transcription factor PAX2.
MedLine Citation:
PMID:  19342968     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PAX2 is a transcription factor and member of the highly conserved family of paired box genes. PAX2 is aberrantly expressed in a variety of solid and hematologic malignancies. PAX2 regulates the transcription factor Wilms tumor gene 1, which is a promising target of cancer immunotherapy. The aim of this study was to apply a modified reverse immunology strategy to identify immunogenic epitopes of PAX2 which could be useful for cancer immunotherapy. Thirteen potential HLA-A*0201 epitopes were predicted by a major histocompatibility complex binding algorithm (SYFPEITHI) and a proteasome cleavage algorithm (PAProC) and screened for recognition by T cells from HLA-A*02-positive cancer patients using intracellular cytokine cytometry. Epitope-specific T cells were generated from CD4CD25 regulatory T-cell-depleted peripheral blood mononuclear cell. Nine of 20 colorectal cancer patients, 1 of 13 renal cell carcinoma patients, and 2 of 17 lymphoma patients had a spontaneous CD8 T-cell response toward at least 1 of 6 PAX2 peptide pools. None of the 20 healthy subjects showed reactivity toward PAX2. PAX2.337-345 (TLPGYPPHV)-specific T cells could repeatedly be generated, which specifically lysed the PAX2 expressing colorectal tumor cell line SW480. In this study, a modified reverse immunology strategy was employed to identify a first immunogenic HLA-A*0201 restricted T-cell epitope and natural ligand of the tumor antigen PAX2. Thus, PAX2 is another embryonic transcription factor, which is of potential interest as immunotherapy target antigen.
Authors:
Anne Marie Asemissen; Doreen Haase; Stefan Stevanovic; Sandra Bauer; Antonia Busse; Eckhard Thiel; Hans-Georg Rammensee; Ulrich Keilholz; Carmen Scheibenbogen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of immunotherapy (Hagerstown, Md. : 1997)     Volume:  32     ISSN:  1537-4513     ISO Abbreviation:  J. Immunother.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-04-30     Completed Date:  2009-06-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9706083     Medline TA:  J Immunother     Country:  United States    
Other Details:
Languages:  eng     Pagination:  370-5     Citation Subset:  IM    
Affiliation:
Hämatologie und Onkologie, Charité Campus Benjamin Franklin, Hindenburgdamm, Germany.
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MeSH Terms
Descriptor/Qualifier:
Algorithms
Amino Acid Sequence
CD8-Positive T-Lymphocytes / immunology*,  metabolism
Carcinoma, Renal Cell / immunology,  metabolism
Cell Line, Tumor
Colorectal Neoplasms / immunology,  metabolism
Epitopes, T-Lymphocyte / immunology*,  metabolism
HLA-A Antigens / immunology*,  metabolism
Humans
Lymphoma / immunology,  metabolism
Molecular Sequence Data
Nuclear Proteins / genetics,  immunology
PAX2 Transcription Factor / immunology*,  metabolism
Peptides / immunology,  metabolism
Chemical
Reg. No./Substance:
0/Epitopes, T-Lymphocyte; 0/HLA-A Antigens; 0/HLA-A*0201 antigen; 0/Nuclear Proteins; 0/PAX2 Transcription Factor; 0/PAX2 protein, human; 0/Peptides; 0/WTAP protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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