論文 - 詳細
| RRC ID | 38481 |
|---|---|
| 著者 | Hayashi S, Kumai T, Matsuda Y, Aoki N, Sato K, Kimura S, Kitada M, Tateno M, Celis E, Kobayashi H. |
| タイトル | Six-transmembrane epithelial antigen of the prostate and enhancer of zeste homolog 2 as immunotherapeutic targets for lung cancer. |
| ジャーナル | J Transl Med |
| Abstract |
BACKGROUND:T-cell based immunotherapy for lung cancer (LC) could be a promising and novel therapeutic approach. Six-transmembrane epithelial antigen of the prostate (STEAP) and the polycomb group protein enhancer of zeste homolog 2 (EZH2) are highly expressed in LC and since the expression of molecules in normal tissue is significantly lower as compared to tumor cells, these proteins are considered as potential tumor-associated antigens (TAAs) for developing T-cell based immunotherapy. METHODS:We assessed the capacity of predicted CD4 T-cell epitopes from STEAP and EZH2 to induce anti-tumor immune responses to LC cell lines. RESULTS:Out of several predicted epitopes, two synthetic peptides, STEAP281-296 and EZH295-109, were effective in inducing CD4 T-cell responses that were restricted by HLA-DR1, DR15, or DR53 molecules, indicating that the peptides function as promiscuous T-cell epitopes. Moreover, STEAP281-296 and EZH295-109-reactive T-cells could directly recognize STEAP or EZH2 expressing LC cells in an HLA-DR restricted manner. In addition, some STEAP-reactive T-cells responded to STEAP+ tumor cell lysates presented by autologous dendric cells. Most significantly, both of these peptides were capable of stimulating in vitro T-cell responses in patients with LC. CONCLUSIONS:Peptides STEAP281-296 and EZH295-109 function as strong CD4 T-cell epitopes that can elicit effective anti-tumor T-cell responses against STEAP or EZH2 expressing LC. These observations may facilitate the translation of T-cell based immunotherapy into the clinic for the treatment of LC. |
| 巻・号 | 9 |
| ページ | 191 |
| 公開日 | 2011-11-5 |
| DOI | 10.1186/1479-5876-9-191 |
| PII | 1479-5876-9-191 |
| PMID | 22053850 |
| PMC | PMC3219573 |
| MeSH | Adenocarcinoma / blood Adenocarcinoma / immunology Adenocarcinoma / pathology Adenocarcinoma / therapy Adult Aged Aged, 80 and over Alleles Animals Antigen Presentation / immunology Antigens, Neoplasm / immunology* Antigens, Neoplasm / metabolism CD4-Positive T-Lymphocytes / immunology Cell Line Clone Cells Cytotoxicity, Immunologic DNA-Binding Proteins / immunology* DNA-Binding Proteins / metabolism Enhancer of Zeste Homolog 2 Protein Epitopes / immunology Female Granzymes / metabolism HLA-DR Antigens / immunology Humans Immunotherapy* Lung Neoplasms / blood Lung Neoplasms / immunology* Lung Neoplasms / pathology Lung Neoplasms / therapy* Male Mice Middle Aged Molecular Targeted Therapy Oxidoreductases / immunology* Oxidoreductases / metabolism Peptides / immunology Polycomb Repressive Complex 2 Transcription Factors / immunology* Transcription Factors / metabolism |
| IF | 4.124 |
| 引用数 | 24 |
| WOS 分野 | MEDICINE, RESEARCH & EXPERIMENTAL |
| リソース情報 | |
| ヒト・動物細胞 | PC-14(RCB0446) A549(RCB0098) LC-2/ad(RCB0440) LCAM1(RCB1425) LK-2(RCB1970) RERF-LC-AI(RCB0444) EBC-1(RCB1965) LU65(RCB1967) Lu99(RCB1900) |