rdf:type |
|
lifeskim:mentions |
umls-concept:C0017337,
umls-concept:C0030956,
umls-concept:C0033085,
umls-concept:C0037791,
umls-concept:C0039194,
umls-concept:C0039195,
umls-concept:C0085247,
umls-concept:C0086418,
umls-concept:C0205225,
umls-concept:C0205232,
umls-concept:C0348011,
umls-concept:C1705822
|
pubmed:issue |
4
|
pubmed:dateCreated |
2003-2-7
|
pubmed:abstractText |
TCR with known antitumor reactivity can be genetically introduced into primary human T lymphocytes and provide promising tools for immunogene therapy of tumors. We molecularly characterized two distinct TCRs specific for the same HLA-A2-restricted peptide derived from the melanocyte differentiation Ag gp100, yet exhibiting different stringencies in peptide requirements. The existence of these two distinct gp100-specific TCRs allowed us to study the preservation of peptide fine specificity of native TCRalphabeta when engineered for TCR gene transfer into human T lymphocytes. Retroviral transduction of primary human T lymphocytes with either one of the two sets of TCRalphabeta constructs enabled T lymphocytes to specifically kill and produce TNF-alpha when triggered by native gp100(pos)/HLA-A2(pos) tumor target cells as well as gp100 peptide-loaded HLA-A2(pos) tumor cells. Peptide titration studies revealed that the cytolytic efficiencies of the T lymphocyte transductants were in the same range as those of the parental CTL clones. Moreover, primary human T lymphocytes expressing either one of the two engineered gp100-specific TCRs show cytolytic activities in response to a large panel of peptide mutants that are identical with those of the parental CTL. The finding that two gp100-specific TCR, derived from two different CTL, can be functionally introduced into primary human T lymphocytes without loss of the Ag reactivity and peptide fine specificity, holds great promise for the application of TCR gene transfer in cancer immunotherapy.
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes, T-Lymphocyte,
http://linkedlifedata.com/resource/pubmed/chemical/HLA-A2 Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell...,
http://linkedlifedata.com/resource/pubmed/chemical/SILV protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/gp100 Melanoma Antigen
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
|
pubmed:issn |
0022-1767
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pubmed:author |
|
pubmed:issnType |
Print
|
pubmed:day |
15
|
pubmed:volume |
170
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
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pubmed:pagination |
2186-94
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:12574392-Amino Acid Sequence,
pubmed-meshheading:12574392-Amino Acid Substitution,
pubmed-meshheading:12574392-Base Sequence,
pubmed-meshheading:12574392-Cell Line,
pubmed-meshheading:12574392-Cell Line, Transformed,
pubmed-meshheading:12574392-Cells, Cultured,
pubmed-meshheading:12574392-Clone Cells,
pubmed-meshheading:12574392-Cytotoxicity Tests, Immunologic,
pubmed-meshheading:12574392-Epitopes, T-Lymphocyte,
pubmed-meshheading:12574392-HLA-A2 Antigen,
pubmed-meshheading:12574392-Humans,
pubmed-meshheading:12574392-K562 Cells,
pubmed-meshheading:12574392-Melanoma,
pubmed-meshheading:12574392-Membrane Glycoproteins,
pubmed-meshheading:12574392-Molecular Sequence Data,
pubmed-meshheading:12574392-Neoplasm Proteins,
pubmed-meshheading:12574392-Peptide Fragments,
pubmed-meshheading:12574392-Receptors, Antigen, T-Cell, alpha-beta,
pubmed-meshheading:12574392-T-Lymphocyte Subsets,
pubmed-meshheading:12574392-T-Lymphocytes, Cytotoxic,
pubmed-meshheading:12574392-Transduction, Genetic,
pubmed-meshheading:12574392-Transfection,
pubmed-meshheading:12574392-Tumor Cells, Cultured,
pubmed-meshheading:12574392-gp100 Melanoma Antigen
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pubmed:year |
2003
|
pubmed:articleTitle |
Peptide fine specificity of anti-glycoprotein 100 CTL is preserved following transfer of engineered TCR alpha beta genes into primary human T lymphocytes.
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pubmed:affiliation |
Clinical and Tumor Immunology, Department of Medical Oncology, Erasmus Medical Center-Daniel den Hoed, Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|