Source:http://linkedlifedata.com/resource/pubmed/id/17414326
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2007-4-6
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pubmed:abstractText |
The carcinoembryonic antigen (CEA)-derived peptide CAP1 and heteroclitic peptide CAP1-6D are stimulators of HLA-A*A0201 restricted CEA-specific T cells in vivo and in vitro. The goal of this study was to evaluate differences in T cell responses to peptide and modified peptide antigens from CEA. The heterogeneity of responses among individuals is potentially important for the design of future CEA-directed immunotherapy trials. Peripheral blood mononuclear cells from blood donors were stimulated with peptide, IL-2, and IL-7. Weekly, microcultures were restimulated with irradiated, autologous peptide-loaded peripheral blood mononuclear cells and expanded in IL-2. Established T cell lines were tested by cytokine release assays using peptide-loaded T2 targets. T cell avidity was measured by cytokine release using targets expressing diminishing concentrations of peptide. Fine specificities were measured using targets loaded with alanine-substituted CAP1 peptide. Tumor recognition was measured using HLA-A*A0201/CAP1-transduced COS tumor targets. Varied responses to CAP1 and CAP1-6D were seen among individuals. The immunogenicity of CAP1 or CAP1-6D was donor dependent. Many T cells recognized one peptide but did not cross-recognize the altered peptide. The avidities of T cell lines were moderate to low, and fine specificities were consistent with a narrow antigen-specific repertoire. CAP1-6D-based immune therapy may not be optimal in some patients with CAP1-specific precursors. The T cell repertoire may be a central contributor to the limited responses seen with CEA-directed immunotherapy to date. Treatment strategies designed to alter or expand the T cell repertoire against CEA should be considered for trials.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CAP1-6D,
http://linkedlifedata.com/resource/pubmed/chemical/Carcinoembryonic Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-7,
http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1524-9557
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
30
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
350-8
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pubmed:dateRevised |
2008-3-18
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pubmed:meshHeading |
pubmed-meshheading:17414326-Carcinoembryonic Antigen,
pubmed-meshheading:17414326-Cross Reactions,
pubmed-meshheading:17414326-Humans,
pubmed-meshheading:17414326-Immunotherapy,
pubmed-meshheading:17414326-Interleukin-2,
pubmed-meshheading:17414326-Interleukin-7,
pubmed-meshheading:17414326-Neoplasms,
pubmed-meshheading:17414326-Oligopeptides,
pubmed-meshheading:17414326-Receptors, Antigen, T-Cell,
pubmed-meshheading:17414326-T-Lymphocytes
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pubmed:year |
2007
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pubmed:articleTitle |
Recognition of carcinoembryonic antigen peptide and heteroclitic peptide by peripheral blood T lymphocytes.
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pubmed:affiliation |
Department of Surgery, University of Chicago, IL, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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