Identification of peptide vaccine candidates for prostate cancer patients with HLA-A3 supertype alleles

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 PSA(16-24),, PAP(155-163), PAP(248-257), PSMA(207-215), and PSMA(4311-440) 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(+) Tcells. Conclusions: We identified prostate-related antigen-derived-new peptide candidates for HLAA11-, 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-A12 and,HLA-A24.