In:
Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 11, No. 19 ( 2005-10-01), p. 6933-6943
Abstract:
Purpose: The peptide vaccine candidates identified to date have been focused on the HLA-A2 and HLA-A24 alleles. The HLA-A11, HLA-A31, and HLA-A33 alleles share binding motifs and belong to an HLA-A3 supertype family. In this study, we attempted to identify CTL-directed peptide candidates, derived from prostate-related antigens and shared by HLA-A11+, HLA-A31+, and HLA-A33+ prostate cancer patients. Experimental Design: Based on the binding motif to the HLA-A3 supertype alleles, 42 peptides were prepared from prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA), and prostatic acid phosphatase (PAP). These peptides were first screened for their ability to be recognized by immunoglobulin G (IgG) of prostate cancer patients and subsequently for the potential to induce peptide-specific and prostate cancer–reactive CTLs from peripheral blood mononuclear cells (PBMC) of cancer patients with the HLA-A11, HLA-A31, and HLA-A33 alleles. Results: Five peptide candidates, including the PSA16-24, PAP155-163, PAP248-257, PSMA207-215, and PSMA431-440 peptides, were frequently recognized by IgGs of prostate cancer patients. These peptides efficiently induced peptide-specific and prostate cancer–reactive CTLs from PBMCs of cancer patients with the HLA-A11, HLA-A31, and HLA-A33 alleles. Antibody blocking and cold inhibition experiments revealed that the HLA-A3 supertype–restricted cytotoxicity against prostate cancer cells could be ascribed to peptide-specific and CD8+ T cells. Conclusions: We identified prostate-related antigen-derived new peptide candidates for HLA-A11-, HLA-A31-, and HLA-A33-positive prostate cancer patients. This information could facilitate the development of a peptide-based anticancer vaccine for patients with alleles other than HLA-A2 and HLA-A24.
Type of Medium:
Online Resource
ISSN:
1078-0432
,
1557-3265
DOI:
10.1158/1078-0432.CCR-05-0682
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2005
detail.hit.zdb_id:
1225457-5
detail.hit.zdb_id:
2036787-9
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