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.
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 cancerpatients. 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 cancerpatients and subsequently for the potential to induce peptide-specific and prostate cancer-reactive CTLs from peripheral blood mononuclear cells (PBMC) of cancerpatients 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 cancerpatients. These peptides efficiently induced peptide-specific and prostate cancer-reactive CTLs from PBMCs of cancerpatients 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 cancerpatients. This information could facilitate the development of a peptide-based anticancer vaccine for patients with alleles other than HLA-A2 and HLA-A24.
Authors: Aleksandr Lazaryan; Tao Wang; Stephen R Spellman; Hai-Lin Wang; Joseph Pidala; Taiga Nishihori; Medhat Askar; Richard Olsson; Machteld Oudshoorn; Hisham Abdel-Azim; Agnes Yong; Manish Gandhi; Christopher Dandoy; Bipin Savani; Gregory Hale; Kristin Page; Menachem Bitan; Ran Reshef; William Drobyski; Steven Ge Marsh; Kirk Schultz; Carlheinz R Müller; Marcelo A Fernandez-Viña; Michael R Verneris; Mary M Horowitz; Mukta Arora; Daniel J Weisdorf; Stephanie J Lee Journal: Haematologica Date: 2016-05-31 Impact factor: 9.941
Authors: M Naito; Y Komohara; Y Ishihara; M Noguchi; Y Yamashita; T Shirakusa; A Yamada; K Itoh; M Harada Journal: Br J Cancer Date: 2007-11-27 Impact factor: 7.640