Document Detail


Cytotoxic T-lymphocyte clones, established by stimulation with the HLA-A2 binding p5365-73 wild type peptide loaded on dendritic cells In vitro, specifically recognize and lyse HLA-A2 tumour cells overexpressing the p53 protein.
MedLine Citation:
PMID:  10652158     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mutations in the tumour suppressor gene p53 are among the most frequent genetic alterations in human malignancies, often associated with an accumulation of the p53 protein in the cytoplasm. We have generated a number of cytotoxic T lymphocyte (CTL) clones that specifically recognize the HLA-A*0201 p53 wild type peptide RMPEAAPPV [65-73], designated R9V, by the in vitro stimulation of CD8 enriched peripheral blood lymphocytes from a healthy HLA-A*0201 donor using peptide loaded autologous dendritic cells. A total of 22 CTL clones were generated from the same bulk culture and demonstrated to carry identical T-cell receptors. The CTL clone, 2D9, was shown to specifically lyse the HLA-A*0201+ squamous carcinoma cell line SCC9 and the breast cancer cell line MDA-MB-468. Our data demonstrate that human peripheral blood lymphocytes from normal healthy individuals comprise T cells capable of recognizing p53 derived wild type (self) peptides. Furthermore, the capacity of R9V specific T cell clones to exert HLA restricted cytotoxicity, argues that the R9V peptide is naturally presented on certain cancer cells. This supports the view that p53 derived wild type peptides might serve as candidate target antigens for the immunotherapeutic treatment of cancer.
Authors:
A M Barfoed; T R Petersen; A F Kirkin; P Thor Straten; M H Claesson; J Zeuthen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Scandinavian journal of immunology     Volume:  51     ISSN:  0300-9475     ISO Abbreviation:  Scand. J. Immunol.     Publication Date:  2000 Feb 
Date Detail:
Created Date:  2000-03-15     Completed Date:  2000-03-15     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0323767     Medline TA:  Scand J Immunol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  128-33     Citation Subset:  IM    
Affiliation:
Department of Tumour Cell Biology, Institute of Cancer Biology, Danish Cancer Society, DK-2100 Copenhagen, Denmark.
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MeSH Terms
Descriptor/Qualifier:
Cell Line, Transformed
Cells, Cultured
Clone Cells
Coculture Techniques
Cytotoxicity, Immunologic / immunology
Dendritic Cells / immunology*
Gene Expression
HLA-A2 Antigen / immunology*
Humans
K562 Cells
Male
Mutation
Peptides / immunology,  metabolism
Receptors, Antigen, T-Cell / genetics
T-Lymphocytes, Cytotoxic / cytology,  immunology*
Tumor Cells, Cultured
Tumor Suppressor Protein p53 / biosynthesis,  genetics,  immunology*
Chemical
Reg. No./Substance:
0/HLA-A2 Antigen; 0/Peptides; 0/Receptors, Antigen, T-Cell; 0/Tumor Suppressor Protein p53

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


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