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Generation of an adenovirus vector for gene therapy of pituitary tumor

用于垂体瘤基因治疗的腺病毒载体的产生

基本信息

批准号：
16590915
负责人：
SEKI Toshiro
金额：
$ 2.24万
依托单位：
Tokyo Women's Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590915/
关键词：
Gene therapy Adenovirus vector Pituitary tumor アデノウィルスベクター

项目摘要

Adenovirus vectors (Ads) have been employed for a wide variety of cancer gene therapy applications to date. This utility has derived principally from the unparalleled ability of these agents to accomplish efficient gene delivery to tumor targets. Unfortunately, translation of these advantages has been more difficult to accomplish in human clinical gene therapy trials for cancer. Critical problems to overcome are low efficiency and lack of selectivity of currently available gene transfer systems. Adaptation of Ad for cancer gene therapy applications would thus ideally embody these two mandates-the ability to accomplish adenovirus receptor (CAR)-independent gene delivery as a means to improve vector efficiency for tumor targets and the ability to avoid liver sequestration as a means to limit potential vector related toxicity. Herein, we compared gene transfer efficiencies of Ad serotype 5 (Ad5) capsid-based 'longer-shafted' Ad vector with a somatostatin ligand (SS-14) in the HI-loop of the fiber knob (Ad5longSS-14VEGF) to wild-type Ad vector in vitro. Ad5longSS-14VEGF significantly reduced infectivity in CAR-positive cells (normal organ model). On the other hand, Ad5longSS-14VEGF significantly increased infectivity in SS-14 receptor-positive cells (pituitary tumor model) compared with Ad5. We suggest that Ad vectors with artificial fiber shaft extension in combination with a somatostatin ligand in the HI-loop of the fiber knob may be useful for gene therapy of pituitary tumor.

迄今为止，腺病毒载体（Ads）已用于各种癌症基因治疗应用。这种效用主要来源于这些试剂实现有效基因递送至肿瘤靶点的无与伦比的能力。不幸的是，这些优势的转化在癌症的人类临床基因治疗试验中更难实现。需要克服的关键问题是目前可用的基因转移系统效率低和缺乏选择性。因此，将Ad用于癌症基因治疗应用将理想地体现这两个任务-实现腺病毒受体（CAR）非依赖性基因递送的能力作为提高肿瘤靶向的载体效率的手段，以及避免肝隔离的能力作为限制潜在的载体相关毒性的手段。在本文中，我们比较了Ad血清型5（Ad 5）captyles为基础的“长轴”Ad载体与生长抑素配体（SS-14）在纤维球（Ad 5longSS-14 VEGF）的HI环野生型Ad载体在体外的基因转移效率。Ad 5longSS-14 VEGF显著降低CAR阳性细胞（正常器官模型）中的感染性。另一方面，与Ad 5相比，Ad 5longSS-14 VEGF显著增加了SS-14受体阳性细胞（垂体瘤模型）的感染性。我们认为，Ad载体与人工纤维轴延伸结合生长抑素配体在HI环的纤维球可能是有用的垂体瘤的基因治疗。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

総説 : 癌遺伝子治療に有用なアデノウイノレスベクターの開発戦略

综述：用于癌症基因治疗的腺病毒载体的开发策略

DOI：
发表时间：
2005
期刊：
東京女子医科大学雑誌 75巻・12号
影响因子：
0
作者：
Kasayama;S;Fujita;M;Goya;K;Yamamoto;H;Fujita;K;Morimoto;Y;Kawase;I;Miyatake;A;大中佳三;Tao R-H. et al.;関敏郎
通讯作者：
関敏郎

Effective Strategies for Cancer Gene Therapy using Adenovirus Vector

使用腺病毒载体进行癌症基因治疗的有效策略