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

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

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)1046-1054
Number of pages9
JournalCancer Research
Volume69
Issue number3
Early online date27 Jan 2009
DOIs
Publication statusPublished - 1 Feb 2009

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