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A Long, Naturally Presented Immunodominant Epitope from NY-ESO-1 Tumor Antigen: Implications for Cancer Vaccine Design

¹ Ludwig Institute for Cancer Research (Melbourne Centre for Clinical Sciences), Austin Health, Heidelberg, and ² The Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, ³ Department of Biochemistry and Molecular Biology, The Bio21 Molecular Science and Biotechnology Institute, Melbourne University, Victoria, Australia; and ⁴ Ludwig Institute for Cancer Research (Lausanne Branch), Lausanne, Switzerland

Requests for reprints: Weisan Chen, Ludwig Institute for Cancer Research, Melbourne Centre for Clinical Sciences, Austin Health, Heidelberg, VIC, 3084 Australia. Phone: 613-949-63700; Fax: 613-949-65334; E-mail: weisan.chen{at}ludwig.edu.au.

Key Words: epitope • immunodominance • vaccine

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]

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				Correction: Article on Vaccination Reveals a Long Dominant CTL Epitope Cancer Res., May 15, 2009; 69(10): 4553 - 4553. [Full Text] [PDF]