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- Title
Identification of an antigenic peptide derived from the cancer-testis antigen NY-ESO-1 binding to a broad range of HLA-DR subtypes.
- Authors
Neumann, Frank; Wagner, Claudia; Kubuschok, Boris; Stevanovic, Stefan; Rammensee, Hans-Georg; Pfreundschuh, Michael
- Abstract
NY-ESO-1 is a SEREX-defined cancer-testis antigen of which several MHC I, but only few MHC II–restricted epitopes have been identified. Searching for highly promiscuous MHC II–restricted peptides that might be suitable as a CD4+ stimulating vaccine for many patients, we used the SYFPEITHI algorithm and identified an NY-ESO-1–derived pentadecamer epitope (p134–148) that induced specific CD4+ T-cell responses restricted to the HLA-DRB1 subtypes *0101, *0301, *0401, and *0701 that have a cumulative prevalence of 40% in the Caucasian population. The DR restriction of the p134–148 pentadecamer was demonstrated by inhibition with an HLA-DR antibody and a functional peptide displacement titration assay with the pan-DR-binding T-helper epitope PADRE as the competitor. The natural processing and presentation of this epitope was demonstrated by recognition of an NY-ESO-1+ melanoma cell line by T cells with specificity for p134–148. The pentadecamer p134–148 was able to induce CD4+ responses in 4/38 cancer patients tested. However, no strict correlation was found between CD4+ T-cell responses against p134–148 reactivity and anti-NY-ESO-1 antibody titers in the serum of patients, suggesting that CD4+ and B-cell responses are regulated independently. In conclusion, p134–148 holds promise as a broadly applicable peptide vaccine for patients with NY-ESO-1–positive neoplasms.
- Publication
Cancer Immunology, Immunotherapy, 2004, Vol 53, Issue 7, p589
- ISSN
0340-7004
- Publication type
Academic Journal
- DOI
10.1007/s00262-003-0492-6