Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/10234
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dc.contributor.authorDavis, Ian Den
dc.contributor.authorChen, Qiyuanen
dc.contributor.authorMorris, Leoneen
dc.contributor.authorQuirk, Julieten
dc.contributor.authorStanley, Maureenen
dc.contributor.authorTavarnesi, Maria Len
dc.contributor.authorParente, Phillipen
dc.contributor.authorCavicchiolo, Tinaen
dc.contributor.authorHopkins, Wendieen
dc.contributor.authorJackson, Heather Men
dc.contributor.authorDimopoulos, Nektariaen
dc.contributor.authorTai, Tsin Yeeen
dc.contributor.authorMacGregor, Duncanen
dc.contributor.authorBrowning, Judyen
dc.contributor.authorSvobodova, Suzanneen
dc.contributor.authorCaron, Daniaen
dc.contributor.authorMaraskovsky, Eugeneen
dc.contributor.authorOld, Lloyd Jen
dc.contributor.authorChen, Weisanen
dc.contributor.authorCebon, Jonathan Sen
dc.date.accessioned2015-05-15T23:37:10Z
dc.date.available2015-05-15T23:37:10Z
dc.date.issued2006-09-10en
dc.identifier.citationJournal of Immunotherapy (hagerstown, Md. : 1997); 29(5): 499-511en
dc.identifier.govdoc16971806en
dc.identifier.otherPUBMEDen
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/10234en
dc.description.abstractFlt3 ligand mobilizes dendritic cells (DCs) into blood, allowing generation in vivo of large numbers of DCs for immunotherapy. These immature DCs can be rapidly activated by soluble CD40 ligand (CD40L). We developed a novel overnight method using these cytokines to produce DCs for cancer immunotherapy. Flt3 ligand-mobilized DCs (FLDCs) were isolated, activated with CD40L, loaded with antigenic peptides from influenza matrix protein, hepatitis B core antigen, NY-ESO-1, MAGE-A4, and MAGE-A10, and injected into patients with resected melanoma. Three injections were given at 4-week intervals. Study end points included antigen-specific immune responses (skin reactions to peptides alone or peptide-pulsed FLDCs; circulating T-cell responses), safety, and toxicity. No patient had a measurable tumor. Six patients were entered. FLDCs were obtained, enriched, and cultured under Good Manufacturing Practice grade conditions. Overnight culture with soluble CD40L caused marked up-regulation of activation markers (CD83 and HLA-DR). These FLDCs were functional and able to stimulate antigen-specific T cells in vitro. No significant adverse events were attributable to FLDCs. Peptide-pulsed FLDCs caused strong local skin reactions up to 60 mm diameter with intense perivascular infiltration of T cells, exceeding those seen in our previous peptide-based protocols. Antigen-specific blood T-cell responses were induced, including responses to an antigen for which the patients were naive (hepatitis B core antigen) and MAGE-A10. MAGE-A10-specific T cells with a skewed T-cell receptor repertoire were detected in 1 patient in blood ex vivo and from tumor biopsies. Vaccination with FLDCs pulsed with peptides is safe and primes immune responses to cancer antigens.en
dc.language.isoenen
dc.subject.otherAdulten
dc.subject.otherAntigen Presentationen
dc.subject.otherAntigens, CD8.immunologyen
dc.subject.otherCD40 Ligand.immunologyen
dc.subject.otherCD8-Positive T-Lymphocytes.immunologyen
dc.subject.otherCancer Vaccines.adverse effects.immunology.therapeutic useen
dc.subject.otherCells, Cultureden
dc.subject.otherCytotoxicity, Immunologicen
dc.subject.otherDendritic Cells.immunologyen
dc.subject.otherFemaleen
dc.subject.otherHumansen
dc.subject.otherImmunotherapy, Adoptiveen
dc.subject.otherLeukapheresisen
dc.subject.otherLymphocyte Activationen
dc.subject.otherMaleen
dc.subject.otherMelanoma.immunology.therapyen
dc.subject.otherMembrane Proteins.immunologyen
dc.subject.otherMiddle Ageden
dc.subject.otherPeptides.immunology.therapeutic useen
dc.subject.otherPilot Projectsen
dc.subject.otherReceptors, Antigen, T-Cell.metabolismen
dc.subject.otherSkin Neoplasms.immunology.therapyen
dc.titleBlood dendritic cells generated with Flt3 ligand and CD40 ligand prime CD8+ T cells efficiently in cancer patients.en
dc.typeJournal Articleen
dc.identifier.journaltitleJournal of immunotherapy (Hagerstown, Md. : 1997)en
dc.identifier.affiliationLudwig Institute for Cancer Research, Austin Health, Studley Road, Heidelberg, Victoria 3084, Australiaen
dc.identifier.doi10.1097/01.cji.0000211299.29632.8cen
dc.description.pages499-511en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/16971806en
dc.type.austinJournal Articleen
local.name.researcherCebon, Jonathan S
item.openairetypeJournal Article-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.grantfulltextnone-
item.fulltextNo Fulltext-
item.cerifentitytypePublications-
item.languageiso639-1en-
crisitem.author.deptOlivia Newton-John Cancer Research Institute-
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