Identification of polycomb group protein enhancer of zeste homolog 2 (EZH2)-derived peptides immunogenic in HLA-A24+ prostate cancer patients.
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.
Ogata
Rika
R
Department of Immunology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
Matsueda
Satoko
S
Yao
Akihisa
A
Noguchi
Masanori
M
Itoh
Kyogo
K
Harada
Mamoru
M
D000906:Antibodies; D004268:DNA-Binding Proteins; D000071221:Enhancer of Zeste Homolog 2 Protein; D015234:HLA-A Antigens / Q000276:immunology*; D059871:HLA-A24 Antigen; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D008297:Male; D010455:Peptides; D063151:Polycomb Repressive Complex 2; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000503:physiopathology*; D011506:Proteins / Q000032:analysis* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014157:Transcription Factors
D000906:Antibodies; D004268:DNA-Binding Proteins; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D007074:Immunoglobulin G; D010455:Peptides; D011506:Proteins; D014157:Transcription Factors; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2