An adenovirus mutant that replicates selectively in p53-deficient human tumor cells.
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.
Bischoff
J R
JR
ONYX Pharmaceuticals, 3031 Research Drive, Richmond, CA 94806, USA.
Kirn
D H
DH
Williams
A
A
Heise
C
C
Horn
S
S
Muna
M
M
Ng
L
L
Nye
J A
JA
Sampson-Johannes
A
A
Fattaey
A
A
McCormick
F
F
D017501:Adenovirus E1B Proteins / Q000235:genetics* / Q000378:metabolism; D000260:Adenoviruses, Human / Q000235:genetics / Q000502:physiology*; D000818:Animals; D003588:Cytopathogenic Effect, Viral; D017353:Gene Deletion; D016158:Genes, p53; D006258:Head and Neck Neoplasms / Q000628:therapy* / Q000821:virology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000473:pathology / Q000628:therapy* / Q000821:virology; D016205:Sigmodontinae; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014779:Virus Replication
D017501:Adenovirus E1B Proteins; D016159:Tumor Suppressor Protein p53