PSES-A Novel Prostate Specific Chimeric Enhancer for Prostate Cancer Gene Therapy
Abstract
Recently we generated a chemic prostate specific promoter, called PSES, by combining the enhancer elements from the PSA and PSMA genes. Based on PSES, we develop a prostate restricted replicative adenovirus (PRRA), called AdE4PSESE1a. AdE4PSESE1a only replicated in PSA/PSMA positive prostate cancer cells or cells expressing adenoviral E1 and E4 proteins. Then, we armed AdE4PSESE1a with TRAIL to make AD-IU-2. Ad-IU-2 retains prostate specificity of AdE4PSESE1a and expresses TRAIL only in PSA/PSMA positive cells. Ad-IU-2 demonstrated a better in vitro cell killing activity and tumor killing activity in vivo than AdE4PSESE1a against PSA/PSMA positive prostate cancers. The tumors cell killing activity of soluble TRAIL could be further enhanced by an apoptosis inducer, BH3 domain and ADP (encoded in the E3 region of adenovirus). We are testing whether we can fuse a cell-permeable peptide to BH3 and ADP, so that we can further improve Ad-IU-2s cell killing activity. We are also on the process of arming AdE4PSESE1a with a soluble TRAIL and creating a hybrid tumor model containing both PSA/PSMA-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, 2006
- Accession Number
- ADA454853
Entities
People
- Chinghai Kao
Organizations
- Indiana University Bloomington