Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
170
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2186-94
pubmed:dateRevised
2010-11-18
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
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.
pubmed:affiliation
Clinical and Tumor Immunology, Department of Medical Oncology, Erasmus Medical Center-Daniel den Hoed, Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't