Re-engineering adenovirus regulatory pathways to enhance oncolytic specificity and efficacy

被引：118

作者：

Ramachandra, M ^{[1
]}

Rahman, A ^{[1
]}

Zou, AH ^{[1
]}

Vaillancourt, M ^{[1
]}

Howe, JA ^{[1
]}

Antelman, D ^{[1
]}

Sugarman, B ^{[1
]}

Demers, GW ^{[1
]}

Engler, H ^{[1
]}

Johnson, D ^{[1
]}

Shabram, P ^{[1
]}

机构：

[1] Canji Inc, San Diego, CA 92121 USA

来源：

NATURE BIOTECHNOLOGY | 2001年 / 19卷 / 11期

关键词：

D O I：

10.1038/nbt1101-1035

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Replicating adenoviruses may prove to be effective anticancer agents if they can be engineered to selectively destroy tumor cells. We have constructed a virus (01/PEME) containing a novel regulatory circuit in which p53-dependent expression of an antagonist of the E2F transcription factor inhibits viral replication in normal cells. In tumor cells, however, the combination of p53 pathway defects and deregulated E2F allows replication of 01/PEME at near wild-type levels. The re-engineered virus also showed significantly enhanced efficacy compared with extensively studied E1b-deleted viruses such as d/1520 in human xenograft tumor models.

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页码：1035 / 1041

页数：7

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