IN-VIVO REPLICATION-DEFICIENT ADENOVIRUS VECTOR-MEDIATED TRANSDUCTIONOF THE CYTOSINE DEAMINASE GENE SENSITIZES GLIOMA-CELLS TO 5-FLUOROCYTOSINE

Viral vector-mediated transfer of chemosensitization genes represents a promising new approach to the treatment of cancer. Previous reports have demonstrated that transfection of the bacterial cytosine deaminas e (cd) gene into mammalian cells can sensitize them to the otherwise n ontoxic nucleoside, 5-fluorocytosine (5-FC). We now report that a repl ication-deficient adenovirus vector that transduces the ed gene (Ad.CM V-cd) highly sensitizes 9L gliosarcoma cells to 5-FC, and that gene tr ansduction is associated with a potent bystander effect that is not de pendent on direct cell-to-cell contact. Stereotactic injection of Ad.C MV-cd into established rat gliomas, followed by systemic administratio n of 5-FC in vivo, results in prolongation of survival.