Author/Authors :
Johnson، نويسنده , , Leisa and Shen، نويسنده , , Annie and Boyle، نويسنده , , Larry and Kunich، نويسنده , , John and Pandey، نويسنده , , Kusum and Lemmon، نويسنده , , Marilyn and Hermiston، نويسنده , , Terry and Giedlin، نويسنده , , Marty and McCormick، نويسنده , , Frank and Fattaey، نويسنده , , Ali، نويسنده ,
Abstract :
We have engineered a human adenovirus, ONYX-411, that selectively replicates in human tumor cells, but not normal cells, depending upon the status of their retinoblastoma tumor suppressor protein (pRB) pathway. Early and late viral gene expression as well as DNA replication were significantly reduced in a functional pRB-pathway-dependent manner, resulting in a restricted replication profile similar to that of nonreplicating adenoviruses in normal cells both in vitro and in vivo. In contrast, the viral life cycle and tumor cell killing activity of ONYX-411 was comparable to that of wild-type adenovirus following infection of human tumor cells in vitro as well as after systemic administration in tumor-bearing animals.
