A novel hypoxia-inducible factor (HIF) activated oncolytic adenovirus for cancer therapy

被引：101

作者：

Post, DE

Van Meir, EG

机构：

[1] Emory Univ, Winship Canc Ctr, Mol Neurooncol Lab, Dept Neurosurg, Atlanta, GA 30322 USA

[2] Emory Univ, Winship Canc Ctr, Mol Neurooncol Lab, Dept Hematol Oncol, Atlanta, GA 30322 USA

来源：

ONCOGENE | 2003年 / 22卷 / 14期

关键词：

hypoxia; adenovirus; HIF; gene delivery; oncolysis; tumor;

D O I：

10.1038/sj.onc.1206464

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

New therapy targeting the hypoxic fraction of tumors needs to be designed as this population of cells is the most resistant to radio- and chemotherapies. Hypoxia-inducible factor (HIF) mediates transcriptional responses to hypoxia by binding to hypoxia-responsive elements (HRE) in target genes. We developed a <(hyp)under bar>oxia/HIF-dependent replicative <(ad)under bar>enovirus (HYPR-Ad) to target hypoxic cells. HYPR-Ad displays hypoxia-dependent E1A expression and conditional cytolysis of hypoxic but not normoxic cells. This work provides proof-of-principle evidence that an attenuated oncolytic adenovirus that selectively lyses cells under hypoxia can be generated. This therapeutic approach can be used to treat all solid tumors that develop hypoxia, regardless of their tissue origin or genetic alterations.

引用

页码：2065 / 2072

页数：8

共 28 条

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