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

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...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2009-02, Vol.69 (3), p.1046-1054
Main Authors: EBERT, Lisa M, YU CHIH LIU, ROSSJOHN, Jamie, CEBON, Jonathan, PURCELL, Anthony W, WEISAN CHEN, CLEMENTS, Craig S, ROBSON, Neil C, JACKSON, Heather M, MARKBY, Jessica L, DIMOPOULOS, Nektaria, BEE SHIN TAN, LUESCHER, Immanuel F, DAVIS, Ian D
Format: Article
Language:English
Subjects:
Alanine - genetics
Amino Acid Sequence
Amino Acid Substitution
Antigen Presentation
Antigens, Neoplasm - immunology
Antineoplastic agents
Biological and medical sciences
Cancer Vaccines - immunology
Cancer Vaccines - therapeutic use
CD8-Positive T-Lymphocytes - immunology
Cell Line, Tumor
HLA-B Antigens - immunology
HLA-B7 Antigen
Humans
Immunodominant Epitopes - immunology
Lymphocyte Activation
Medical sciences
Melanoma - immunology
Melanoma - therapy
Membrane Proteins - immunology
Models, Molecular
Molecular Sequence Data
Peptide Fragments - immunology
Pharmacology. Drug treatments
Protein Conformation
Tumors
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Summary: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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-08-2926