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[Cancer Research 57, 2559-2563, July 1, 1997]
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Prostate Attenuated Replication Competent Adenovirus (ARCA) CN706: A Selective Cytotoxic for Prostate-specific Antigen-positive Prostate Cancer Cells1

Ron Rodriguez2, Eric R. Schuur2, Ho Yeong Lim, Gail A. Henderson, Jonathan W. Simons and Daniel R. Henderson3

Brady Urological Institute, Johns Hopkins University Oncology Center, Baltimore, Maryland 21287 [R. R., H. Y. L., J. W. S.]; and Calydon, Inc., Menlo Park, California 94025 [E. R. S., G. A. H., D. R. H.]

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 x 109 cells) and abolished PSA production in nu/nu mouse xenograft models with a single intratumoral injection.

1 R. R., H. Y. L., and J. W. S. have no financial interest in Calydon, Inc., and were supported by NIH Specialized Programs of Research Excellence in Prostate Cancer Grant CA-58230 and the CapCure Foundation.

2 These authors made equal contributions to this work.

3 To whom requests for reprints should be addressed, at Calydon, Inc., 1014 Hamilton Court, Menlo Park, CA 94025.

Received 4/ 7/97. Accepted 5/22/97.




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