Abstract: Methods and compositions for substantially and selectively ablating cancer cells and dividing endothelial cells while substantially sparing quiescent normal cells are described consisting of replication competent adenoviral mutants that are mutant in E1A RB family member binding site region of the virus, and preferably in the E1A-CR2 region, which mutants show superior replication and efficacy compared to wild-type adenovirus in multiple tumor cell lines and in proliferating microvascular endothelial cells.

Abstract: Methods and compositions for treating neoplastic conditions by viral-based therapy are provided. Mutant virus lacking viral proteins which bind and/or inactivate p53 or RB are administered to a patient having a neoplasm which comprises cells lacking p53 and/or RB function. The mutant virus is able to substantially produce a replication phenotype in neoplastic cells but is substantially unable to produce a replication phenotype in non-replicating, non-neoplastic cells having essentially normal p53 and/or RB function. The preferential generation of replication phenotype in neoplastic cells results in a preferential killing of the neoplastic cells, either directly or by expression of a cytotoxic gene in cells expressing a viral replication phenotype.