論文 - 詳細
| RRC ID | 1372 |
|---|---|
| 著者 | Fukui M, Nakano-Hashimoto T, Okano K, Maruta Y, Suehiro Y, Hamanaka Y, Yamashita H, Imai K, Kawano MM, Hinoda Y. |
| タイトル | Therapeutic effect of dendritic cells loaded with a fusion mRNA encoding tyrosinase-related protein 2 and enhanced green fluorescence protein on B16 melanoma. |
| ジャーナル | Tumour Biol |
| Abstract |
Dendritic cells (DCs) loaded with messenger RNA (mRNA) have been proposed to be useful for inducing specific cytotoxic T lymphocytes against tumor antigens. It is now also apparent that tumor antigen-specific T cell tolerance limits the efficacy of active immunotherapy. To improve the efficacy of mRNA-loaded DCs, we constructed a fusion mRNA encoding tyrosinase-related protein 2 (TRP2), which has a late endosomal/lysosomal sorting signal and enhanced green fluorescence protein (EGFP), and evaluated its effect in a murine melanoma model. C57BL/6 mice were challenged subcutaneously (s.c.) with 3 x 10(5) B16 tumor cells, and 3 and 10 days later, 3 x 10(5) DCs loaded with mRNA (DC/mRNA) were injected s.c. in the vicinity of the tumor site. Treatment with DC/TRP2 mRNA or DC/TRP2-EGFP mRNA significantly inhibited tumor growth compared to DC/PBS on day 17 after B16 challenge (DC/PBS vs. DC/TRP2 mRNA, p = 0.0411; DC/PBS vs.DC/TRP2-EGFP mRNA, p = 0.0253), whereas no antitumor effect was observed in mice treated with DC/EGFP mRNA or DC/TRP2 peptide. Moreover, the survival rate in mice immunized with DC/TRP2 mRNA or DC/TRP2-EGFP mRNA was significantly improved as compared with that in mice receiving DC/PBS (DC/PBS vs. DC/TRP2 mRNA, p = 0.0228; DC/PBS vs. DC/TRP2-EGFP mRNA, p = 0.0049). Depletion of CD4+ T cells or CD8+ T cells with antibody administration completely abrogated the therapeutic effectiveness of DC/TRP2-EGFP mRNA, suggesting the induction of a T cell immune response against the B16 tumor. |
| 巻・号 | 25(5-6) |
| ページ | 252-7 |
| 公開日 | 2004-1-1 |
| DOI | 10.1159/000081388 |
| PII | 81388 |
| PMID | 15627888 |
| MeSH | Animals Antibody Formation Antigens, Neoplasm Artificial Gene Fusion Dendritic Cells* Disease Models, Animal Female Green Fluorescent Proteins / genetics* Immunotherapy / methods Intramolecular Oxidoreductases / genetics* Intramolecular Oxidoreductases / pharmacology Melanoma / immunology* Melanoma / pathology Melanoma / therapy* Melanoma / veterinary Mice RNA, Messenger / genetics Signal Transduction Skin Neoplasms / immunology* Skin Neoplasms / pathology Skin Neoplasms / therapy* Skin Neoplasms / veterinary Survival Analysis T-Lymphocytes, Cytotoxic / immunology* Transfection |
| IF | 3.65 |
| 引用数 | 6 |
| WOS 分野 | ONCOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | B16 melanoma 4A5(RCB0557) |