HLA class I - associated immunodominance affects CTL responsiveness to an ESO recombinant protein tumor antigen vaccine.

Details

Serval ID
serval:BIB_E10AFD5F9310
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
HLA class I - associated immunodominance affects CTL responsiveness to an ESO recombinant protein tumor antigen vaccine.
Journal
Clinical cancer research
Author(s)
Bioley G., Guillaume P., Luescher I., Yeh A., Dupont B., Bhardwaj N., Mears G., Old L.J., Valmori D., Ayyoub M.
ISSN
1078-0432
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
15
Number
1
Pages
299-306
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
PURPOSE: Vaccination with full-length human tumor antigens aims at inducing or increasing antitumor immune responses, including CD8 CTL in cancer patients across the HLA barrier. We have recently reported that vaccination with a recombinant tumor-specific NY-ESO-1 (ESO) protein, administered with Montanide and CpG resulted in the induction of specific integrated antibody and CD4 T cell responses in all vaccinated patients examined, and significant CTL responses in half of them. Vaccine-induced CTL mostly recognized a single immunodominant region (ESO 81-110). The purpose of the present study was to identify genetic factor(s) distinguishing CTL responders from nonresponders. EXPERIMENTAL DESIGN: We determined the HLA class I alleles expressed by CTL responders and nonresponders using high-resolution molecular typing. Using short overlapping peptides spanning the ESO immunodominant CTL region and HLA class I/ESO peptide tetramers, we determined the epitopes recognized by the majority of vaccine-induced CTL. RESULTS: CTL induced by vaccination with ESO protein mostly recognized distinct but closely overlapping epitopes restricted by a few frequently expressed HLA-B35 and HLA-Cw3 alleles. All CTL responders expressed at least one of the identified alleles, whereas none of the nonresponders expressed them. CONCLUSIONS: Expression of HLA-B35 and HLA-Cw3 is associated with the induction of immunodominant CTL responses following vaccination with recombinant ESO protein. Because recombinant tumor-specific proteins are presently among the most promising candidate anticancer vaccines, our findings indicate that the monitoring of cancer vaccine trials should systematically include the assessment of HLA association with responsiveness.
Keywords
Antigens, Neoplasm/immunology, Cancer Vaccines/immunology, Cancer Vaccines/therapeutic use, HLA-B35 Antigen/genetics, HLA-C Antigens/genetics, Histocompatibility Antigens Class I/genetics, Histocompatibility Antigens Class I/immunology, Humans, Immunodominant Epitopes/immunology, Membrane Proteins/immunology, Neoplasms/immunology, Neoplasms/therapy, T-Lymphocytes, Cytotoxic/immunology, Vaccines, Synthetic/immunology
Pubmed
Web of science
Open Access
Yes
Create date
15/01/2010 16:14
Last modification date
20/08/2019 17:05
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