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pubmed-article:15922966pubmed:abstractTextAcute 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.lld:pubmed
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pubmed-article:15922966pubmed:pagination950-9lld:pubmed
pubmed-article:15922966pubmed:dateRevised2010-11-18lld:pubmed
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pubmed-article:15922966pubmed:articleTitleInduction of leukemia-specific CD8+ cytotoxic T cells with autologous myeloid leukemic cells maturated with a fiber-modified adenovirus encoding TNF-alpha.lld:pubmed
pubmed-article:15922966pubmed:affiliationUnité INSERM 524, Institut de Recherche sur le Cancer de Lille, 59037 Lille, France.lld:pubmed
pubmed-article:15922966pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:15922966pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed