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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2003-4-16
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pubmed:abstractText |
Chimeric receptors comprising of the T-cell receptor-zeta cytoplasmic signalling chain fused to an extracellular ligand-binding domain of a single-chain antibody (scFv) have served as effective tools for redirecting cytotoxic T lymphocytes (CTL) against tumour cells. In this report, we constructed a chimeric scFv/zeta gene composed of the variable regions of an HER-2/neu-specific monoclonal antibody (MAb) joined to the TCR-zeta chain. The scFv(anti-HER-2/neu)/zeta chimeric gene was successfully expressed as a functional surface receptor in the MD.45 CTL hybridoma (MD.45-HER/zeta). More importantly, the scFv(anti-HER-2/neu)/zeta receptor was functionally active, since it triggered cytokine secretion by the MD.45-HER/zeta cells upon recognition of HER-2/neu-positive (+) tumour cell lines, or primary tumour cells from patients with HER-2/neu(+) cancers. The MD.45-HER/zeta-transduced cells also lysed HER-2/neu(+) target cells in vitro with high specificity. We tested the antitumour efficacy of scFv(anti-HER-2/neu)/zeta expressing MD.45 cells in severe combined immunodeficiency disease mice/human and murine tumour models. The adoptively transferred MD.45-HER/zeta cells both slowed significantly the growth of human FM3 melanoma or murine ALC leukaemic cells both transfected to express HER-2/neu. Our data demonstrate the feasibility of redirecting MD.45 CTL with the scFv(anti-HER-2/neu)/zeta chimeric receptor to respond specifically against HER-2/neu expressing tumour cells in vitro and in vivo. Moreover, they make it likely that T cells transduced with the same chimeric gene might be utilised in the treatment of patients with HER-2/neu(+) tumours.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/12698199-10376932,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12698199-10395702,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12698199-10725753,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12698199-11016652,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12698199-11123291,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/12698199-9647246
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0007-0920
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
22
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pubmed:volume |
88
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1292-300
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12698199-Amino Acid Sequence,
pubmed-meshheading:12698199-Animals,
pubmed-meshheading:12698199-Base Sequence,
pubmed-meshheading:12698199-Breast Neoplasms,
pubmed-meshheading:12698199-Cell Line, Tumor,
pubmed-meshheading:12698199-Cytotoxicity, Immunologic,
pubmed-meshheading:12698199-Female,
pubmed-meshheading:12698199-Flow Cytometry,
pubmed-meshheading:12698199-Humans,
pubmed-meshheading:12698199-Hybridomas,
pubmed-meshheading:12698199-Interferon-gamma,
pubmed-meshheading:12698199-Mice,
pubmed-meshheading:12698199-Mice, SCID,
pubmed-meshheading:12698199-Molecular Sequence Data,
pubmed-meshheading:12698199-Ovarian Neoplasms,
pubmed-meshheading:12698199-Receptor, erbB-2,
pubmed-meshheading:12698199-T-Lymphocytes,
pubmed-meshheading:12698199-T-Lymphocytes, Cytotoxic,
pubmed-meshheading:12698199-Transfection
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pubmed:year |
2003
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pubmed:articleTitle |
Redirecting mouse T hybridoma against human breast and ovarian carcinomas: in vivo activity against HER-2/neu expressing cancer cells.
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pubmed:affiliation |
Saint Savas Cancer Hospital, Cancer Immunology and Immunotherapy Center, Athens, Greece.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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