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rdf:type |
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lifeskim:mentions |
umls-concept:C0001483,
umls-concept:C0039195,
umls-concept:C0085358,
umls-concept:C0205263,
umls-concept:C0439677,
umls-concept:C0439859,
umls-concept:C0679058,
umls-concept:C1332717,
umls-concept:C1413244,
umls-concept:C1456820,
umls-concept:C1517806,
umls-concept:C1547699,
umls-concept:C1706438,
umls-concept:C2698600,
umls-concept:C2700640
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pubmed:issue |
6
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pubmed:dateCreated |
2005-5-30
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|
pubmed:abstractText |
Acute myeloid leukemia (AML) cells can be differentiated into dendritic cells (DCs) using appropriate combinations of cytokines but generation of autologous antileukemic cytotoxic T cells using leukemic DCs remains difficult. Transduction by adenoviral vectors has been reported to induce efficient maturation of monocyte-derived DCs but AML cells are generally resistant to adenoviral gene transfer. In this study we tested the effects of adenoviral TNF-alpha gene transfer on maturation of AML cells using the fiber-modified AdTNF.F(pK7) adenovirus. All samples expressed high and sustained levels of TNF-alpha following transduction. AdTNF.F(pK7) induced significantly greater maturation of AML cells into antigen-presenting cells (APC) than did recombinant TNF-alpha or control adenoviral vector. Maturation of leukemic cells into APCs was mediated at least partially via a PI3K/mTOR pathway, as the inhibitors LY294002, wortmannin, and rapamycin inhibited the maturation effect induced by the AdTNF.F(pK7) adenovirus. In addition, CD8+ T cells expanded with AdTNF.F(pK7)-transduced AML cells showed greater expansion and specific CD8+ CTL activity against autologous AML cells than T cells expanded by other means. Thus, fiber-modified adenoviral vectors encoding TNF-alpha are able to maturate AML cells into APCs with high efficacy and reproducibility, providing a useful tool to generate efficiently specific CD8+ CTLs against leukemic disease.
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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 |
Jun
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pubmed:issn |
1525-0016
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
11
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
950-9
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:15922966-Acute Disease,
pubmed-meshheading:15922966-Adenoviridae,
pubmed-meshheading:15922966-Antigen-Presenting Cells,
pubmed-meshheading:15922966-Capsid Proteins,
pubmed-meshheading:15922966-Cell Differentiation,
pubmed-meshheading:15922966-Coculture Techniques,
pubmed-meshheading:15922966-Cytotoxicity, Immunologic,
pubmed-meshheading:15922966-Humans,
pubmed-meshheading:15922966-Leukemia, Myeloid,
pubmed-meshheading:15922966-Phenotype,
pubmed-meshheading:15922966-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:15922966-Protein Kinase Inhibitors,
pubmed-meshheading:15922966-Protein Kinases,
pubmed-meshheading:15922966-Signal Transduction,
pubmed-meshheading:15922966-T-Lymphocytes, Cytotoxic,
pubmed-meshheading:15922966-TOR Serine-Threonine Kinases,
pubmed-meshheading:15922966-Transduction, Genetic,
pubmed-meshheading:15922966-Tumor Necrosis Factor-alpha
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pubmed:year |
2005
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pubmed:articleTitle |
Induction of leukemia-specific CD8+ cytotoxic T cells with autologous myeloid leukemic cells maturated with a fiber-modified adenovirus encoding TNF-alpha.
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pubmed:affiliation |
Unité INSERM 524, Institut de Recherche sur le Cancer de Lille, 59037 Lille, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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