A prodrug strategy using ONYX-015-based replicating adenoviruses to deliver rabbit carboxylesterase to tumor cells for conversion of CPT-11 to SN-38.

ONYX-015 has been used successfully in the clinic as a cancer therapeutic in combination with chemotherapy. The combination of ONYX-015 and chemotherapy appears to be more efficacious than either regimen alone. In this study, we try to enhance this combination by "arming" ONYX-015 with a therapeutic transgene, an approach more commonly used with nonreplicating viruses in the context of gene therapy.