Identification of cytotoxic T-lymphocyte epitope(s) and its agonist epitope(s) of a novel target for vaccine therapy (PAGE4)

✍ Scribed by Junko Yokokawa; Tapan K. Bera; Claudia Palena; Vittore Cereda; Cinzia Remondo; James L. Gulley; Philip M. Arlen; Ira Pastan; Jeffrey Schlom; Kwong Y. Tsang

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: French
• Weight: 431 KB
• Volume: 121
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.22698

✦ Synopsis

Abstract

PAGE4 is an X chromosome‐linked cancer testis antigen and is a potential new tumor‐associated antigen that is overexpressed in prostate and uterine cancers. The purpose of this study was to identify a human CTL epitope and a corresponding agonist epitope of PAGE4 to determine if PAGE4 is a potential target for vaccine‐mediated immunotherapy against PAGE4‐expressing tumors. A class I PAGE4 epitope was identified with a high level of binding to HLA‐A2. PAGE4 peptide‐pulsed dendritic cells were then used to generate human PAGE4‐specific T‐cell lines. Further studies demonstrated the generation of an enhancer agonist epitope. Compared with the native peptide, the agonist (i) bound to HLA‐A2 molecules at lower peptide concentrations, (ii) demonstrated a higher stability of the peptide HLA‐A2 complex, (iii) induced higher levels of production of IFN‐γ, Granzyme B, TNF‐α, IL‐2 and lymphotactin by PAGE4‐specific T‐cell lines and (iv) T‐cell lines generated against the agonist peptide were more efficient to lyse HLA‐A2 human tumor cells expressing native PAGE4. The studies reported here are the first to describe a PAGE4 CTL epitope and its agonist epitope, and thus identify PAGE4 as a potentially useful target for vaccine‐mediated therapy of prostate cancer. © 2007 Wiley‐Liss, Inc.