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Peptide Transduction-Based Therapies for Prostate Cancer

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Annual rept. 1 May 2003-30 Apr 2004

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One approach for the efficient intra-cellular delivery of proteins involves the use of protein transduction. We have demonstrated the feasibility of use PTDs for the treatment of cancer in murine tumor models, where a specific cationic peptide was able to transduce tumor cells efficiently following intra-tumoral injection. Intra-tumoral injection of a mitochondrial disruption peptide, KLAK, fused to a cationic transduction domain resulted in significant murine tumor apoptosis and complete tumor regression. Moreover, we have now shown that a peptide derived from the amino terminus of Smac, a protein able to block the anti-apoptotic effect of IAPs Inhibitors of Apoptosis, induced apoptosis of DU145 and LNCaP cells following PTD-mediated internalization. Treatment with the PTD-Smac fusion increased the sensitivity of cells to apoptosis induced by TRAIL and etoposide treatment. In addition to the cationic, non-specific transduction peptides, we also have developed a method for screening for tissue-targeted transduction peptides using an M13 peptide phage display library. Initial screening of the library for transduction of tumors in vivo has identified peptides able to facilitate transduction of prostate tumors in vivo. These peptides will be developed for efficient delivery of therapeutic peptides and eventually proteins into prostate tumor cells for treatment of metastatic disease.

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  • Biochemistry
  • Medicine and Medical Research

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