BACKGROUND: Antigens overexpressed in metastatic prostate cancer are appropriate 
targets in anti-cancer immunotherapy, and one candidate is the polycomb group 
protein enhancer of zeste homolog 2 (EZH2).
METHODS: Eleven EZH2-derived peptides were prepared based on the HLA-A24 binding 
motif. These peptide candidates were screened first by their ability to be 
recognized by immunoglobulin G (IgG), and then by their ability to induce 
peptide-specific cytotoxic T lymphocytes (CTLs).
RESULTS: IgGs reactive to three EZH2 peptides (EZH2-243 to -252, EZH2-291 to 
-299, and EZH2-735 to -;742) were detected in the plasma of almost half of 
prostate cancer patients. Among them, the EZH2-291 to -299 and EZH2-735 to -742 
peptides effectively induced HLA-A24-restricted and prostate cancer-reactive 
CTLs from prostate cancer patients. The cytotoxicity was mainly dependent on 
EZH2 peptide-specific and CD8+ T cells.
CONCLUSIONS: These EZH2-291 to -299 and EZH2-735 to -742 peptides could be 
promising candidates for peptide-based immunotherapy for HLA-A24+ prostate 
cancer patients with metastases.