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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
24
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pubmed:dateCreated |
1997-1-23
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pubmed:abstractText |
Dendritic cells (DCs) are potent antigen-presenting cells that can activate quiescent T lymphocytes. When pulsed with tumor-associated antigen (TAA) peptide or protein, murine DCs can provide antitumor immunity. We reasoned that DCs retrovirally transduced with TAA genes might have important advantages over peptide- or protein-pulsed DCs, including long-term TAA presentation in vivo, and presentation of important but undefined epitopes. Therefore, we attempted to retrovirally transduce human DCs with a melanoma TAA gene (MART-1) and determine whether these transduced DCs could raise a specific antitumor response from quiescent autologous T lymphocytes. After retroviral transduction, human CD34+ cells were differentiated into DCs in vitro using granulocyte macrophage colony-stimulating factor, tumor necrosis factor alpha, and stem cell factor. This method consistently yielded a population of DCs as analyzed by morphology, phenotype, and MLR. Flow cytometric analysis revealed that 22-28% of cells expressing the DC phenotype also expressed a transduced marker gene. When DCs were transduced with the gene encoding MART-1, they stimulated much higher levels of cytokine release by MART-1-specific tumor-infiltrating lymphocytes than control DCs transduced with an irrelevant gene. In vitro stimulation using MART-1-transduced DCs but not control-transduced DCs raised specific antitumor CTLs from autologous quiescent T cells. These results provide evidence that human DCs can be retrovirally transduced with a TAA gene and that these transduced cells can raise a specific antitumor immune response in vitro. Transduced DCs may be useful for in vivo immunization against TAA.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0008-5472
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
56
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5672-7
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:8971174-Antigens, Neoplasm,
pubmed-meshheading:8971174-Dendritic Cells,
pubmed-meshheading:8971174-Epitopes,
pubmed-meshheading:8971174-Genetic Vectors,
pubmed-meshheading:8971174-Humans,
pubmed-meshheading:8971174-Immunity, Cellular,
pubmed-meshheading:8971174-Lymphocytes, Tumor-Infiltrating,
pubmed-meshheading:8971174-Melanoma,
pubmed-meshheading:8971174-Retroviridae,
pubmed-meshheading:8971174-Transfection
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pubmed:year |
1996
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pubmed:articleTitle |
Retroviral transduction of human dendritic cells with a tumor-associated antigen gene.
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pubmed:affiliation |
Surgery Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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