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.
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Authors | Lisa M Ebert, Yu Chih Liu, Craig S 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 W Purcell, Weisan Chen |
Journal | Cancer research
(Cancer Res)
Vol. 69
Issue 3
Pg. 1046-54
(Feb 01 2009)
ISSN: 1538-7445 [Electronic] United States |
PMID | 19176376
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens, Neoplasm
- CTAG1B protein, human
- Cancer Vaccines
- HLA-B Antigens
- HLA-B*07:02 antigen
- HLA-B7 Antigen
- Immunodominant Epitopes
- Membrane Proteins
- Peptide Fragments
- Alanine
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Topics |
- Alanine
(genetics)
- Amino Acid Sequence
- Amino Acid Substitution
- Antigen Presentation
- Antigens, Neoplasm
(immunology)
- CD8-Positive T-Lymphocytes
(immunology)
- Cancer Vaccines
(immunology, therapeutic use)
- Cell Line, Tumor
- HLA-B Antigens
(immunology)
- HLA-B7 Antigen
- Humans
- Immunodominant Epitopes
(immunology)
- Lymphocyte Activation
- Melanoma
(immunology, therapy)
- Membrane Proteins
(immunology)
- Models, Molecular
- Molecular Sequence Data
- Peptide Fragments
(immunology)
- Protein Conformation
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