New polycomb group protein enhancer of zeste homolog (EZH) 2-derived peptide with the potential to induce cancer-reactive cytotoxic T lymphocytes in prostate cancer patients with HLA-A3 supertype alleles.

Abstract

Analyses on reactivity of anti-cancer cytotoxic T lymphocytes (CTLs) and clinical application of peptide-based anti-cancer vaccine have been mainly focused on patients with HLA-A2 or -A24 alleles. In this study, we identified an enhancer of zeste homolog (EZH) 2-derived peptide applicable for anti-cancer vaccine for prostate cancer patients with HLA-A3 supertype alleles. Five EZH2-derived peptides that were prepared based on the binding motif to the HLA-A3 supertype alleles (HLA-A11, -A31, and -A33) were functionally screened for their potential to induce peptide-specific CTLs from peripheral blood mononuclear cells (PBMCs) of HLA-A3 supertype allele(+) prostate cancer patients. As a result, EZH2733-741 peptide was found to efficiently induce peptide-specific CTLs. The EZH2733-741 peptide-stimulated and purified CD8(+) T cells from PBMCs of HLA-A3 supertype allele(+) prostate cancer patients showed higher cytotoxicity against HLA-A3 supertype allele-expressing LNCaP prostate cancer cells than against parental LNCaP cells. This cytotoxicity against HLA-A3 supertype allele-expressing LNCaP cells was partially but significantly inhibited by the addition of EZH2733-741 peptide-pulsed competitive cells. These results indicate that the EZH2733-741 peptide could be a promising candidate for peptide-based immunotherapy for HLA-A3 supertype allele(+) prostate cancer patients.

• Authors: Takafumi Minami, Tomoko Minami, Nobutaka Shimizu, Yutaka Yamamoto, Marco A De Velasco, Masahiro Nozawa, Kazuhiro Yoshimura, Nanae Harashima, Mamoru Harada, Hirotsugu Uemura
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 26 Issue 1 Pg. 133-8 (May 2015) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 25819666 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Cancer Vaccines
• HLA-A3 Antigen
• Peptide Fragments
• EZH2 protein, human
• Enhancer of Zeste Homolog 2 Protein
• Polycomb Repressive Complex 2

Topics

• Alleles
• Cancer Vaccines (chemistry, immunology, therapeutic use)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Enhancer of Zeste Homolog 2 Protein
• Flow Cytometry
• HLA-A3 Antigen (genetics, immunology)
• Humans
• Leukocytes, Mononuclear (immunology)
• Male
• Peptide Fragments (chemistry, immunology, therapeutic use)
• Polycomb Repressive Complex 2 (immunology)
• Prostatic Neoplasms (immunology, pathology)
• T-Lymphocytes, Cytotoxic (drug effects, immunology)
• Transfection