Prostate attenuated replication competent adenovirus (ARCA) CN706: a selective cytotoxic for prostate-specific antigen-positive prostate cancer cells

R Rodriguez, ER Schuur, HY Lim, GA Henderson… - Cancer research, 1997 - AACR
R Rodriguez, ER Schuur, HY Lim, GA Henderson, JW Simons, DR Henderson
Cancer research, 1997AACR
Prostate-specific antigen (PSA) is a widely used marker for the diagnosis and management
of prostate cancer. Minimal enhancer/promoter constructs derived from the 5′ flank of the
human PSA gene (prostatespecific enhancer) were inserted into adenovirus type 5 DNA so
as to drive the E1A gene, thereby creating a prostate-specific enhancer-containing virus,
CN706. E1A was expressed at high levels in CN706-infected human PSA-producing LNCaP
cells but not in CN706-infected DU145 cells, which are human prostate cells that do not …
Abstract
Prostate-specific antigen (PSA) is a widely used marker for the diagnosis and management of prostate cancer. Minimal enhancer/promoter constructs derived from the 5′ flank of the human PSA gene (prostatespecific enhancer) were inserted into adenovirus type 5 DNA so as to drive the E1A gene, thereby creating a prostate-specific enhancer-containing virus, CN706. E1A was expressed at high levels in CN706-infected human PSA-producing LNCaP cells but not in CN706-infected DU145 cells, which are human prostate cells that do not express PSA. The titer of CN706 was significantly higher in LNCaP cells compared to several human cell lines that do not produce PSA (HBL100, PANC-1, MCF-7, DU145, and OVCAR3). Furthermore, in LNCaP cells, the yield of CN706 was dependent on exogenous androgen (R1881). CN706 destroyed large LNCaP tumors (1 × 109 cells) and abolished PSA production in nu/nu mouse xenograft models with a single intratumoral injection.
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