Identification of polycomb group protein enhancer of zeste homolog 2 (EZH2)-derived peptides immunogenic in HLA-A24+ prostate cancer patients

• Published in: The Prostate 2004-09, Vol.60 (4), p.273-281
• Main Authors: Ogata, Rika, Matsueda, Satoko, Yao, Akihisa, Noguchi, Masanori, Itoh, Kyogo, Harada, Mamoru
• Format: Article
• Language: English
• Subjects: Antibodies; antibody; Biological and medical sciences; cytotoxic T lymphocyte; DNA-Binding Proteins; Enhancer of Zeste Homolog 2 Protein; EZH2; Gynecology. Andrology. Obstetrics; HLA-A Antigens - immunology; HLA-A24; HLA-A24 Antigen; Humans; Immunoglobulin G - analysis; Male; Male genital diseases; Medical sciences; Nephrology. Urinary tract diseases; peptide; Peptides; Polycomb Repressive Complex 2; prostate cancer; Prostatic Neoplasms - immunology; Prostatic Neoplasms - physiopathology; Proteins - analysis; Proteins - immunology; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes, Cytotoxic - immunology; Transcription Factors; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.20078

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. © 2004 Wiley‐Liss, Inc.