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

• We identify a peptide applicable for HLA-A3 supertype+ prostate cancer patients.
• An identified EZH2 peptide can induce prostate cancer-reactive CTLs.
• This peptide is useful as immunotherapy for HLA-A3 supertype+ cancer patients.

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.