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dc.date.accessioned2015-04-23T09:40:54Z
dc.date.available2015-04-23T09:40:54Z
dc.date.created2010-01-20T10:32:03Z
dc.date.issued2009
dc.identifier.citationIversen, Per Ole Semaeva, Elvira Sørensen, Dag R. Wiig, Helge Sioud, Mouldy . Dendritic cells loaded with tumor antigens and a dual immunostimulatory and anti-IL-10 specific siRNA can prime T lymphocytes against leukemic cells. Translational Oncology. 2009, 2(4), 242-246
dc.identifier.urihttp://hdl.handle.net/10852/43671
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.languageEN
dc.language.isoenen_US
dc.publisherTranslational Oncology, University of Michigan Medical Center, Ann Arbor, MI
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Unported
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/
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.typeJournal articleen_US
dc.creator.authorIversen, Per Ole
dc.creator.authorSemaeva, Elvira
dc.creator.authorSørensen, Dag R.
dc.creator.authorWiig, Helge
dc.creator.authorSioud, Mouldy
cristin.unitcode185,13,10,0
cristin.unitnameInstitutt for medisinske basalfag
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1
dc.identifier.cristin341650
dc.identifier.bibliographiccitationinfo:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Translational Oncology&rft.volume=2&rft.spage=242&rft.date=2009
dc.identifier.jtitleTranslational Oncology
dc.identifier.volume2
dc.identifier.issue4
dc.identifier.startpage242
dc.identifier.endpage246
dc.identifier.doihttp://dx.doi.org/10.1593/tlo.09154
dc.identifier.urnURN:NBN:no-48043
dc.subject.nviVDP::Onkologi: 762VDP::Hematologi: 775VDP::Medisinsk immunologi: 716
dc.type.documentTidsskriftartikkelen_US
dc.type.peerreviewedPeer reviewed
dc.source.issn1936-5233
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/43671/2/1-s2.0-S1936523309800314-main.pdf
dc.type.versionPublishedVersion


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