AN ADENOVIRUS MUTANT THAT REPLICATES SELECTIVELY IN P53-DEFICIENT HUMAN TUMOR-CELLS

The human adenovirus E1B gene encodes a 55-kilodalton protein that ina ctivates the cellular tumor suppressor protein p53, Here it is shown t hat a mutant adenovirus that does not express this viral protein can r eplicate in and lyse p53-deficient human tumor cells but not cells wit h functional p53. Ectopic expression of the 55-kilodalton E1B protein in the latter cells rendered them sensitive to infection with the muta nt virus. Injection of the mutant virus into p53-deficient human cervi cal carcinomas grown in nude mice caused a significant reduction in tu mor size and caused complete regression of 60 percent of the tumors. T hese data raise the possibility that mutant adenoviruses can be used t o treat certain human tumors.