期刊
JOURNAL OF GENE MEDICINE
卷 11, 期 11, 页码 1005-1011出版社
WILEY
DOI: 10.1002/jgm.1385
关键词
adenovirus; brain tumor; glioma; survivin; virotherapy
资金
- National Cancer Institute [R01-CA122930]
- National Institute of Neurological Disorders and Stroke [K08-NS046430]
- Alliance for Cancer Gene Therapy Young Investigator Award
- American Cancer Society [RSG-07-276-01-MGO]
Background Malignant gliomas remain refractory to treatment despite advances in chemotherapy and surgical techniques. Viral vectors developed to treat gliomas have had low transduction capabilities, limiting their use. Gliomas over-express CD46, CD80, and CD86, all of which bind adenovirus serotype 3. Methods To increase the infectivity and replication of oncolytic vectors in malignant brain tumors, we created a conditionally replicating adenovirus, CRAd-Survivin-5/3, which contains a survivin promoter-driving E1A and a chimeric fiber consisting of adenovirus serotype 3 knob. Results In vitro, this modified CRAd showed ten- to 100-fold increased cyrotoxicity against glioma cells. Ex vivo analysis of primary glioblastoma multiforme samples infected with CRAd-Survivin-5/3 showed an increase in cytotoxicity of 20-30% compared to adenovirus wild-type (AdWT). In normal human astrocytes and normal brain tissues, CRAd-Survivin-5/3 exhibited 30-40% and 10-15% lower cytotoxicity than AdWT, respectively. In an intracranial xenograft model of glioma, this oncolytic virus increased tumor-free survival and overall lifespan by 50% compared to controls (P < 0.05). Conclusions CRAd-Survivin-5/3 represents an attractive alternative to existing vectors and should be tested further in the pre-clinical setting. Copyright (C) 2009 John Wiley & Sons, Ltd.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据