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Identification of Peptide Vaccine Candidates for Prostate Cancer Patients with HLA-A3 Supertype Alleles

Authors' Affiliations: Departments of ¹ Immunology and ² Urology, Kurume University School of Medicine and ³ Center of the 21st Century COE Program for Medical Science, Kurume University, Kurume, Fukuoka, Japan

Requests for reprints: Mamoru Harada, Department of Immunology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan. Phone: 81-942-31-7744; Fax: 81-942-31-7745; E-mail: haramamo{at}med.kurume-u.ac.jp.

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_431-440 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.

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