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

Ebert, L.M. et al. (2009) A long, naturally presented immunodominant epitope from NY-ESO-1 tumor antigen: implications for cancer vaccine design. Cancer Research, 69(3), pp. 1046-1054. (doi: 10.1158/0008-5472.CAN-08-2926)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Robson, Dr Neil
Authors: Ebert, L.M., Liu, Y.C., Clements, C.S., Robson, N.C., Jackson, H.M., Markby, J. L., Dimopoulos, N., Tan, B.S., Luescher, I.F., Davis, I.D., Rossjohn, J., Cebon, J., Purcell, A.W., and Chen, W.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Cancer Research
ISSN:0008-5472

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