PSES - A Novel Prostate Specific Chimeric Enhancer for Prostate Cancer Gene Therapy
Abstract
Recently we identified two prostate-specific enhancers, AREc3 and PSME(del2), from PSA gene and PSMA gene respectively, and generated a chemic promoter, called PSES, by combining AREc3 and PSME(del2). The goal of this research is to use AREc3/PSME(del2)or PSES to develop a prostate-restricted replicative adenovirus (PRRA) and to arm PrRRA with an apoptosis inducer, TRAIL (tumor necrosis factor-related apoptosis-inducing ligand). We constructed 3 PRRAs-according to our original proposal. None of them demonstrated a good prostate specificity. We, then, constructed another PRRA, called AdE4PSESE1a, using a different strategy. AdE4PSESE1a only replicated in PSAIPSMA positive prostate cancer cells or cells expressing adenoviral El and E4 proteins. Then, we armed AdE4PSESE1a with TRAIL to make AD-IU-2 as our original plan. Ad-IU-2 retains prostate specificity of AdE4PSESE1a and expresses TRAIL on in PSAIPSMA positive cells. Ad-IU-2 demonstrated a better in vitro cell killing activity and tumor killing activity in vivo than AdE4PSESE1a against PSAIPSMA positive prostate cancers. We are on the process of arming AdE4PSESE1a with a soluble TRAIL and creating a hybrid tumor model containing both PSNPSMA-positive and negative prostate cancer cells to test the therapeutic advantage of TRAIL-armed PRRA.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2005
- Accession Number
- ADA447539
Entities
People
- Chinghai Kao
Organizations
- Indiana University