ONYX-015, AN E1B GENE-ATTENUATED ADENOVIRUS, CAUSES TUMOR-SPECIFIC CYTOLYSIS AND ANTITUMORAL EFFICACY THAT CAN BE AUGMENTED BY STANDARD CHEMOTHERAPEUTIC-AGENTS

The 55-kilodalton (kDa) protein from the E1B-region of adenovirus bind s to and inactivates the p53 gene, which is mutated in half of human c ancers. We have previously shown that the replication and cytopathogen icity of an E1B, 55-kDa gene-attenuated adenovirus, ONYX-015, is block ed by functional p53 in RKO and U2OS carcinoma lines. We now report th at normal human cells were highly resistant to ONYX-015-mediated, repl ication-dependent cytolysis. In contrast, a wide range of human tumor cells, including numerous carcinoma lines with either mutant or normal p53 gene sequences (exons 5-9), were efficiently destroyed. Antitumor al efficacy was documented following intratumoral or intravenous admin istration of ONYX-015 to nude mouse-human tumor xenografts; efficacy w ith ONYX-015 plus chemotherapy (cisplatin, 5-fluorouracil) was signifi cantly greater than with either agent alone.