PROSTATE ATTENUATED REPLICATION COMPETENT ADENOVIRUS (ARCA) CN706 - ASELECTIVE CYTOTOXIC FOR PROSTATE-SPECIFIC ANTIGEN-POSITIVE PROSTATE-CANCER CELLS

Prostate-specific antigen (PSA) is a widely used marker for the diagno sis and management of prostate cancer. Minimal enhancer/promoter const ructs derived from the 5' flank of the human PSA gene (prostate-specif ic enhancer) were inserted into adenovirus type 5 DNA so as to drive t he EIA gene, thereby creating a prostate-specific enhancer-containing virus, CN706. EIA was expressed at high levels in CN706-infected human PSA-producing LNCaP cells but not in CN706-infected DU145 cells, whic h are human prostate cells that do not express PSA. The titer of CN706 was significantly higher in LNCaP cells compared to several human cel l lines that do not produce PSA (HBL100, PANC-1, MCF-7, DU145, and OVC AR3). Furthermore, in LNCaP cells, the yield of CN706 was dependent on exogenous androgen (R1881). CN706 destroyed large LNCaP tumors (1 x 1 0(9) cells) and abolished PSA production in nu/nu mouse xenograft mode ls with a single intratumoral injection.