Vasculature-Specific Adenovirus Vectors for Gene Therapy of Prostate Cancer
Final rept. 1 Feb 2004-31 Jan 2008
M D ANDERSON CANCER CENTER HOUSTON TX
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The goal of this project was to use the previously identified peptides with the reported specificity for neovasculature of prostate tumors to genetically modify the natural tropism of human adenovirus type 5 towards designing of tumor-selective gene therapy vectors. The study involved the design of peptide-modified Ad fiber proteins, their expression and characterization in vitro. A panel of recombinant adenovirus vector incorporating the most promising of these protein chimeras has been developed. These new vectors have been tested in vivo using human prostate xenografts established in nude mice as a model of target tumors. Biodistribution of the control and modified adenoviral vectors in these animals has been studied using non-invasive whole body imaging measurements of the vector-encoded reporter activity in isolated organs and tumors and also by qPCR-based detection of vector particles. This work showed, however, that none of the designed vectors possessed the tumor specificity expected based on the reported performance of chosen peptide ligands. Potential reasons for these unexpected findings are discussed.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research