An Adenovirus Mutant That Replicates Selectively in
p53- Deficient Human Tumor Cells
James R. Bischoff,
*
David H. Kirn,
Angelica Williams,
Carla Heise,
Sharon Horn,
Mike Muna,
Lelia Ng,
*
Julie A. Nye,
Adam Sampson-Johannes,
Ali Fattaey,
Frank McCormick
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.
The authors are with ONYX Pharmaceuticals, 3031 Research Drive,
Richmond, CA 94806, USA.
*
Present address: Sugen, Incorporated, 515 Galveston Drive,
Redwood City CA 94063, USA.
To whom correspondence should be addressed.
