HLA class i-associated immunodominance affects CTL responsiveness to an ESO recombinant protein tumor antigen vaccine Journal Article
| Authors: | Bioley, G.; Guillaume, P.; Luescher, I.; Yeh, A.; Dupont, B.; Bhardwaj, N.; Mears, G.; Old, L. J.; Valmori, D.; Ayyoub, M. |
| Article Title: | HLA class i-associated immunodominance affects CTL responsiveness to an ESO recombinant protein tumor antigen vaccine |
| 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 Tcell 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 l/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. © 2009 American Association for Cancer Research. |
| Keywords: | clinical article; unclassified drug; human cell; neoplasm; neoplasms; antigen expression; allele; membrane proteins; peptide; tumor antigen; cellular immunity; antigen; antigens, neoplasm; cancer vaccine; cancer vaccines; gene identification; cpg oligodeoxynucleotide; montanide isa 51; antigen recognition; cancer immunization; immunodominant epitopes; epitope; recombinant protein; cytotoxic t lymphocyte; t-lymphocytes, cytotoxic; hla antigen class 1; hla b35 antigen; hla cw3 antigen; recombinant eso protein; drug response; molecular typing; histocompatibility antigens class i; hla-b35 antigen; hla-c antigens; vaccines, synthetic |
| Journal Title: | Clinical Cancer Research |
| Volume: | 15 |
| Issue: | 1 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2009-01-01 |
| Start Page: | 299 |
| End Page: | 306 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-08-1747 |
| PUBMED: | 19118058 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 2" - "Export Date: 30 November 2010" - "CODEN: CCREF" - "Source: Scopus" |
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