HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

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

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.
AuthorsLisa 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
JournalCancer research (Cancer Res) Vol. 69 Issue 3 Pg. 1046-54 (Feb 01 2009) ISSN: 1538-7445 [Electronic] United States
PMID19176376 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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
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

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: