An adenovirus mutant that replicates selectively in p53-deficient human tumor cells

被引:1461
作者
Bischoff, JR [1 ]
Kim, DH [1 ]
Williams, A [1 ]
Heise, C [1 ]
Horn, S [1 ]
Muna, M [1 ]
Ng, L [1 ]
Nye, JA [1 ]
SampsonJohannes, A [1 ]
Fattaey, A [1 ]
McCormick, F [1 ]
机构
[1] ONYX PHARMACEUT,RICHMOND,CA 94806
关键词
D O I
10.1126/science.274.5286.373
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The human adenovirus E1B gene encodes a 55-kilodalton protein that inactivates the cellular tumor suppressor protein p53, Here it is shown that a mutant adenovirus that does not express this viral protein can replicate in and lyse p53-deficient human tumor cells but not cells with functional p53. Ectopic expression of the 55-kilodalton E1B protein in the latter cells rendered them sensitive to infection with the mutant virus. Injection of the mutant virus into p53-deficient human cervical carcinomas grown in nude mice caused a significant reduction in tumor size and caused complete regression of 60 percent of the tumors. These data raise the possibility that mutant adenoviruses can be used to treat certain human tumors.
引用
收藏
页码:373 / 376
页数:4
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