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dc.contributor.authorEbert, Lisa Men
dc.contributor.authorLiu, Yu Chihen
dc.contributor.authorClements, Craig Sen
dc.contributor.authorRobson, Neil Cen
dc.contributor.authorJackson, Heather Men
dc.contributor.authorMarkby, Jessica Len
dc.contributor.authorDimopoulos, Nektariaen
dc.contributor.authorTan, Bee Shinen
dc.contributor.authorLuescher, Immanuel Fen
dc.contributor.authorDavis, Ian Den
dc.contributor.authorRossjohn, Jamieen
dc.contributor.authorCebon, Jonathan Sen
dc.contributor.authorPurcell, Anthony Wen
dc.contributor.authorChen, Weisanen
dc.identifier.citationCancer Research 2009; 69(3): 1046-54en
dc.description.abstractThe tumor antigen NY-ESO-1 is a promising cancer vaccine target. We describe here a novel HLA-B7-restricted NY-ESO-1 epitope, encompassing amino acids 60-72 (APRGPHGGAASGL), which is naturally presented by melanoma cells. The tumor epitope bound to HLA-B7 by bulging outward from the peptide-binding cleft. This bulged epitope was not an impediment to T-cell recognition, however, because four of six HLA-B7(+) melanoma patients vaccinated with NY-ESO-1 ISCOMATRIX vaccine generated a potent T-cell response to this determinant. Moreover, the response to this epitope was immunodominant in three of these patients and, unlike the T-cell responses to bulged HLA class I viral epitopes, the responding T cells possessed a remarkably broad TCR repertoire. Interestingly, HLA-B7(+) melanoma patients who did not receive the NY-ESO-1 ISCOMATRIX vaccine rarely generated a spontaneous T-cell response to this cryptic epitope, suggesting a lack of priming of such T cells in the natural anti-NY-ESO-1 response, which may be corrected by vaccination. Together, our results reveal several surprising aspects of antitumor immunity and have implications for cancer vaccine design.en
dc.subject.otherAmino Acid Sequenceen
dc.subject.otherAmino Acid Substitutionen
dc.subject.otherAntigen Presentationen
dc.subject.otherAntigens, Neoplasm.immunologyen
dc.subject.otherCD8-Positive T-Lymphocytes.immunologyen
dc.subject.otherCancer Vaccines.immunology.therapeutic useen
dc.subject.otherCell Line, Tumoren
dc.subject.otherHLA-B Antigens.immunologyen
dc.subject.otherHLA-B7 Antigenen
dc.subject.otherImmunodominant Epitopes.immunologyen
dc.subject.otherLymphocyte Activationen
dc.subject.otherMembrane Proteins.immunologyen
dc.subject.otherModels, Molecularen
dc.subject.otherMolecular Sequence Dataen
dc.subject.otherPeptide Fragments.immunologyen
dc.subject.otherProtein Conformationen
dc.titleA long, naturally presented immunodominant epitope from NY-ESO-1 tumor antigen: implications for cancer vaccine design.en
dc.typeJournal Articleen
dc.identifier.journaltitleCancer researchen
dc.identifier.affiliationLudwig Institute for Cancer Research, Melbourne Centre for Clinical Sciences, Austin Health, Heidelberg, Victoria, Australiaen
Appears in Collections:Journal articles

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