Protein Transduction Based Therapies for Breast Cancer
Annual rept. 23 Jun 2004-22 Jun 2005
PITTSBURGH UNIV PA
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We have demonstrated that certain transduction peptides such as 12 lysines and 12 arginines can facilitate internalization into breast tumor lines with higher efficiency than smaller polymers of cationic amino acids. In addition, we have demonstrated that PTD-Sma34 worked in conjunction with Ad.TRAIL gene transfer to induce breast tumor apoptosis. We also have demonstrated that membrane bound TRAIL worked more effectively than soluble secreted TRAIL to induce breast cancer apoptosis. Moreover, we have demonstrated that co-administration of Ad.TRAIL with PTD-Smac34 resulted in not only enhanced adenoviral transduction of the tumors, but resulted in a stronger apoptotic effect. Finally, we have initiated studies to identify breast cancer specific tumor lines by screening a peptide phage display library both in cell culture as well as in nude mice bearing xenografts. Initial results in prostate tumors has demonstrated the feasibility of this approach and suggests breast tumor specific internalization peptides can be identified.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research