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dc.contributor.authorNicholaou, Theoen
dc.contributor.authorEbert, Lisa Men
dc.contributor.authorDavis, Ian Den
dc.contributor.authorMcArthur, Grant Aen
dc.contributor.authorJackson, Heather Men
dc.contributor.authorDimopoulos, Nektariaen
dc.contributor.authorTan, Beeen
dc.contributor.authorMaraskovsky, Eugeneen
dc.contributor.authorMiloradovic, Lenaen
dc.contributor.authorHopkins, Wendieen
dc.contributor.authorPan, Lindaen
dc.contributor.authorVenhaus, Ralphen
dc.contributor.authorHoffman, Eric Wen
dc.contributor.authorChen, Weisanen
dc.contributor.authorCebon, Jonathan Sen
dc.identifier.citationClinical Cancer Research 2009; 15(6): 2166-73en
dc.description.abstractNY-ESO-1 is a highly immunogenic antigen expressed in a variety of malignancies, making it an excellent target for cancer vaccination. We recently developed a vaccine consisting of full-length recombinant NY-ESO-1 protein formulated with ISCOMATRIX adjuvant, which generated strong humoral and T-cell-mediated immune responses and seemed to reduce the risk of disease relapse in patients with fully resected melanoma. This study examines the clinical and immunologic efficacy of the same vaccine in patients with advanced metastatic melanoma.Delayed-type hypersensitivity responses, circulating NY-ESO-1-specific CD4(+) and CD8(+) T cells, and proportions of regulatory T cells (Treg) were assessed in patients.In contrast to patients with minimal residual disease, advanced melanoma patients showed no clinical responses to vaccination. Although strong antibody responses were mounted, the generation of delayed-type hypersensitivity responses was significantly impaired. The proportion of patients with circulating NY-ESO-1-specific CD4(+) T cells was also reduced, and although many patients had CD8(+) T cells specific to a broad range of NY-ESO-1 epitopes, the majority of these responses were preexisting. Tregs were enumerated in the blood by flow cytometric detection of cells with a CD4(+)CD25(+)FoxP3(+) and CD4(+)CD25(+)CD127(-) phenotype. Patients with advanced melanoma had a significantly higher proportion of circulating Treg compared with those with minimal residual disease.Our results point to a tumor-induced systemic immune suppression, showing a clear association between the stage of melanoma progression, the number of Treg in the blood, and the clinical and immunologic efficacy of the NY-ESO-1 ISCOMATRIX cancer vaccine.en
dc.subject.otherAdjuvants, Immunologic.administration & dosageen
dc.subject.otherAged, 80 and overen
dc.subject.otherAntigens, Neoplasm.administration & dosage.immunologyen
dc.subject.otherCancer Vaccines.administration & dosage.immunologyen
dc.subject.otherCholesterol.administration & dosageen
dc.subject.otherDrug Combinationsen
dc.subject.otherHypersensitivity, Delayed.etiologyen
dc.subject.otherMembrane Proteins.administration & dosage.immunologyen
dc.subject.otherMiddle Ageden
dc.subject.otherPhospholipids.administration & dosageen
dc.subject.otherSaponins.administration & dosageen
dc.subject.otherT-Lymphocytes, Regulatory.physiologyen
dc.titleRegulatory T-cell-mediated attenuation of T-cell responses to the NY-ESO-1 ISCOMATRIX vaccine in patients with advanced malignant melanoma.en
dc.typeJournal Articleen
dc.identifier.journaltitleClinical Cancer Researchen
dc.identifier.affiliationLudwig Institute for Cancer Research, Austin Health, Peter MacCallum Cancer Centre, CSL Limited, Melbourne, Victoria, Australiaen
dc.type.austinJournal Articleen, Jonathan S
item.fulltextNo Fulltext-
item.openairetypeJournal Article-
item.languageiso639-1en- Newton-John Cancer Research Institute-
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