A long, naturally presented immunodominant epitope from NY-ESO-1 tumor antigen: implications for cancer vaccine design

Lisa M Ebert, Yu Chih Liu, Craig Steven Clements, Neil C Robson, Heather M Jackson, Jessica L Markby, Nektaria Dimopoulos, Bee Shin Tan, Immanuel F Luescher, Ian D Davis, Jamie Rossjohn, Jonathan Cebon, Anthony Wayne Purcell, Weisan Chen

Research output: Contribution to journalArticleResearchpeer-review

45 Citations (Scopus)

Abstract

The 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. [Cancer Res 2009;69(3):1046-54].
Original languageEnglish
Pages (from-to)1046 - 1054
Number of pages9
JournalCancer Research
Volume69
Issue number3
DOIs
Publication statusPublished - 2009

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