Establishment of novel cancer therapy using telomerase-specific replication competent adenovirus

使用具有端粒酶特异性复制能力的腺病毒建立新型癌症疗法

• 批准号: 17390449
• 负责人: KYO Satoru
• 金额: $ 10.44万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390449/
• 关键词: Virotheranv; Replication-competent adenovirus; hTERT nromntnr; telomerase; hTERT; adenovirus; gene therapy

We previously cloned the promoter of human reverse transcriptase (hTERT) gene, a catalytic subunit of human telomerase, which was found to be active only in cancer cells with telomerase activity, while it was silent in most normal cells without telomerase activity. We have planned to insert this promoter into the upstream of the El gene of Adenovirus type 5 genome so that adenovirus El gene is efficiently expressed only in cancer cells. Eventually, this chimera virus can replicate only in cancer cells with high levels of expression of El gene, which is required for viral replication. We named this virus TRAD: telomerase-specific replication adenovirus. In the present project, we examined the in vitro and in vivo efficacy of TARD directly injected into primary site of tumors. We found that TARD was effective to reduce tumor burden without exhibiting any severe adverse effect, such as myelosurpression or liver dysfunction caused by viral toxicity Therefore, we propose the clinical use of this virus.

我们先前克隆了人端粒酶催化亚基hTERT基因的启动子，发现它只在有端粒酶活性的癌细胞中有活性，而在大多数正常细胞中没有端粒酶活性。我们已经计划将该启动子插入到5型腺病毒基因组EL基因的上游，以致腺病毒EL基因只在癌细胞中高效表达。最终，这种嵌合体病毒只能在高水平表达EL基因的癌细胞中复制，这是病毒复制所必需的。我们将这种病毒命名为TRAD：端粒酶特异性复制腺病毒。在本项目中，我们检测了直接注射到肿瘤原发部位的TARD的体内外效果。我们发现TARD可以有效地减轻肿瘤负担，而不会出现任何严重的不良反应，如病毒毒性引起的骨髓抑制或肝功能障碍，因此，我们建议临床使用该病毒。

项目成果

E2F1 and telomerase expression in glioblastomas : mechanistic linkage and prognostic significance.

胶质母细胞瘤中的 E2F1 和端粒酶表达：机制联系和预后意义。

• 发表时间: 2005
• 期刊: J.Natl.Cancer Inst 97
• 作者: Alonso M;Kyo S et al.
• 通讯作者: Kyo S et al.

The function of AP1 on transcription of telomerase reverse transcriptase gene (TERT) in human and mouse cell

AP1对人和小鼠细胞端粒酶逆转录酶基因（TERT）转录的功能

• 发表时间: 2005
• 期刊: Mol.Cell.Biol 18
• 作者: Takakura M;Kyo S et al.
• 通讯作者: Kyo S et al.

Distinct telomere length regulation in uterine cervical and endometrial premalignant lesions ; implication for the roles of telomeres in uterine carcinogenesis

子宫颈和子宫内膜癌前病变中独特的端粒长度调节；

• 发表时间: 2006
• 期刊: J.Pathol. 210(2)
• 作者: Maida Y;et al.
• 通讯作者: et al.

Enhanced oncolysis by OBP-405, a tropism-modified telomerase-specicific replication-selective adenoviral agent

OBP-405（一种向性修饰的端粒酶特异性复制选择性腺病毒药物）增强溶瘤作用

• 发表时间: 2005
• 期刊: Oncogene 24
• 作者: Taki M;Kyo S et al.
• 通讯作者: Kyo S et al.

Recent advances in telomerase-based medicine in gynecologic tumors

端粒酶药物治疗妇科肿瘤的最新进展

• 发表时间: 2007
• 作者: Kyo;S
• 通讯作者: S