論文 - 詳細
| RRC ID | 38437 |
|---|---|
| 著者 | Yao X, Yoshioka Y, Morishige T, Eto Y, Narimatsu S, Kawai Y, Mizuguchi H, Gao JQ, Mukai Y, Okada N, Nakagawa S. |
| タイトル | Tumor vascular targeted delivery of polymer-conjugated adenovirus vector for cancer gene therapy. |
| ジャーナル | Mol Ther |
| Abstract |
Previously, we generated a cancer-specific gene therapy system using adenovirus vectors (Adv) conjugated to polyethylene glycol (Adv-PEG). Here, we developed a novel Adv that targets both tumor tissues and tumor vasculatures after systemic administration by conjugating CGKRK tumor vasculature homing peptide to the end of a 20-kDa PEG chain (Adv-PEG(CGKRK)). In a primary tumor model, systemic administration of Adv-PEG(CGKRK) resulted in ~500- and 100-fold higher transgene expression in tumor than that of unmodified Adv and Adv-PEG, respectively. In contrast, the transgene expression of Adv-PEG(CGKRK) in liver was about 400-fold lower than that of unmodified Adv, and was almost the same as that of Adv-PEG. We also demonstrated that transgene expression with Adv-PEG(CGKRK) was enhanced in tumor vessels. Systemic administration of Adv-PEG(CGKRK) expressing the herpes simplex virus thymidine kinase (HSVtk) gene (Adv-PEG(CGKRK)-HSVtk) showed superior antitumor effects against primary tumors and metastases with negligible side effects by both direct cytotoxic effects and inhibition of tumor angiogenesis. These results indicate that Adv-PEG(CGKRK) has potential as a prototype Adv with suitable efficacy and safety for systemic cancer gene therapy against both primary tumors and metastases. |
| 巻・号 | 19(9) |
| ページ | 1619-25 |
| 公開日 | 2011-9-1 |
| DOI | 10.1038/mt.2011.112 |
| PII | S1525-0016(16)32747-2 |
| PMID | 21673661 |
| PMC | PMC3182347 |
| MeSH | Adenoviridae / genetics* Animals Cell Line, Tumor Gene Expression Regulation Gene Transfer Techniques Genes, Viral Genetic Therapy / methods* Genetic Vectors* Mice Mice, Inbred BALB C Mice, Inbred C57BL Polyethylene Glycols / chemistry Polyethylene Glycols / therapeutic use Simplexvirus / genetics Simplexvirus / metabolism Thymidine Kinase / genetics Thymidine Kinase / metabolism Transduction, Genetic Transgenes Vascular Neoplasms / therapy* |
| IF | 8.986 |
| 引用数 | 25 |
| WOS 分野 | MEDICINE, RESEARCH & EXPERIMENTAL BIOTECHNOLOGY & APPLIED MICROBIOLOGY GENETICS & HEREDITY |
| 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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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | B16/BL6(RCB2638) |