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dc.contributor.authorIversen, Per Oleen_US
dc.contributor.authorSemaeva, Elviraen_US
dc.contributor.authorSørensen, Dag R.en_US
dc.contributor.authorWiig, Helgeen_US
dc.contributor.authorSioud, Mouldyen_US
dc.description.abstractVaccines using dendritic cells (DCs) harboring leukemic antigens to stimulate T cells is a possible treatment of acute myeloid leukemia (AML). Limitations of breaking tolerance to leukemic cells and lack of specific activation of T cell-mediated cytotoxicity may explain the discouraging clinical results with this approach. To break self-tolerance against AML cells, we loaded DCs with AML antigens and a bifunctional small interference (si) RNA targeting interleukin (IL) 10 and simultaneously activating toll-like receptors (TLRs). In vitro, this active siRNA inhibited (P < .05) IL-10 production by silencing the IL-10 gene in DCs. The active siRNA stimulated production of tumor necrosis factor α, implying activation of TLRs. Vaccination in a nonimmunogenic rat model mimicking human AML with the loaded DCs induced a substantial and specific T-cell cytotoxicity. Leukemic rats treated with the active siRNA lived longer and had markedly less leukemic cell mass infiltrating their bone marrow compared with rats given inactive siRNA (P < .05). Furthermore, compared with inactive siRNA treatment, the active siRNA led to significantly less extramedullar leukemic dissemination, evidenced by reduced matrix metalloproteinase activity and smaller spleens. Our data demonstrate that this bifunctional siRNA may work as an immunomodulatory drug with antileukemic properties.en_US
dc.rightsAttribution-NonCommercial-NoDerivs CC BY-NC-NDeng
dc.titleDendritic cells loaded with tumor antigens and a dual immunostimulatory and anti-IL-10 specific siRNA can prime T lymphocytes against leukemic cellsen_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2009 Neoplasia Press, Inc. Open access under CC BY-NC-ND license.
dc.source.journalTranslational Oncology
dc.subject.nsiVDP::Medical sciences: 700::Clinical medical sciences: 750::Haematology: 775eng
dc.subject.nsiVDP::Medical sciences: 700::Basic medical, dental and veterinary sciences: 710::Medical immunology: 716eng
dc.subject.nsiVDP::Medical sciences: 700::Clinical medical sciences: 750::Oncology: 762eng
dc.subject.nsiVDP::Medisinske fag: 700::Klinisk medisinske fag: 750::Hematologi: 775nob
dc.subject.nsiVDP::Medisinske fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk immunologi: 716nob
dc.subject.nsiVDP::Medisinske fag: 700::Klinisk medisinske fag: 750::Onkologi: 762nob

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Attribution-NonCommercial-NoDerivs CC BY-NC-ND
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