Available data indicate that adenoviral cancer gene therapy, using tumor suppressor or other genes, is safe and could be highly effective for many types of cancer. In cell culture experiments, cancer cells can easily be eliminated with adenoviral vectors. However, in solid tumors, efficient viral gene transfer has been extremely difficult to achieve, and results from human trials show only modest response rates. Limited distribution of the virus, even with replication-competent viruses, has emerged as one of the main obstacles for adenoviral-mediated cancer gene therapy. We are testing the hypothesis that protein transduction technology can improve adenoviral vectors for the treatment of cancer. Protein transduction domains are short peptides that can penetrate intact cell membranes. We are investigating if adenoviral expression of therapeutic peptides fused to a protein transduction domain will mediate wider intratumoral distribution of the therapeutic agent and lead to more efficient cancer therapy. Delivery of transducible peptides with adenoviral vectors is a new strategy that could find broad application for cancer gene therapy.

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