An Adenovirus Mutant That Replicates Selectively in p53- Deficient Human Tumor Cells

American Association for the Advancement of Science (AAAS) - Tập 274 Số 5286 - Trang 373-376 - 1996
James R. Bischoff1, David H. Kirn1, Angelica Williams1, Carla Heise1, Sharon T. Horn1, Mike Muna1, Lelia Ng1, J A Nye1, Adam Sampson‐Johannes1, Ali Fattaey1, Frank McCormick1
1The authors are with ONYX Pharmaceuticals, 3031 Research Drive, Richmond, CA 94806, USA.

Tóm tắt

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 EIB 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.

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