Identification of cytotoxic T-lymphocyte epitope(s) and its agonist epitope(s) of a novel target for vaccine therapy (PAGE4)
| Autor: | Philip M. Arlen, Jeffrey Schlom, Tapan K. Bera, Kwong Y. Tsang, Vittore Cereda, Junko Yokokawa, Ira Pastan, Cinzia Remondo, Claudia Palena, James L. Gulley |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Agonist Cancer Research medicine.drug_class medicine.medical_treatment Epitopes T-Lymphocyte Peptide CD8-Positive T-Lymphocytes Biology Transfection Epitope Epitopes Antigen Antigens Neoplasm Cell Line Tumor HLA-A2 Antigen medicine Humans Cytotoxic T cell chemistry.chemical_classification Linear epitope Prostatic Neoplasms Dendritic Cells Immunotherapy Virology Granzyme B Oncology chemistry Cancer research T-Lymphocytes Cytotoxic |
| Zdroj: | International Journal of Cancer. 121:595-605 |
| ISSN: | 1097-0215 0020-7136 |
| DOI: | 10.1002/ijc.22698 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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