449. Evaluation of New Generation of Prostate Specific Replication Competent Adenoviruses with E1A-AR Chimera

Adenoviral vector-based gene therapy has been evaluated as a potential therapeutic for prostate cancer. The prostate specific conditionally replication competent adenoviruses (CRADs) are designed to replicate and lyse the prostate epithelium under the control of the E1A gene expression by a prostate specific promoter. Recently we have determined that E1A inhibits the androgen receptor (AR) function, resulting in the attenuation of prostate specific CRAD vectors. We designed E1A-AR fusion chimeras in a new generation of prostate specific replication competent adenoviruses to overcome the inhibition of AR and restore efficient ARE-dependent E1A expression. A series of CRADs with chimeric E1A-AR were constructed and evaluated in prostate cancer cells and non-prostate cancer cells. Here, we describe the function of recombinant adenoviruses with E1A-AR chimeric expression in in vitro study.