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Melanoma gene therapy by conditional replicative adenovirus delivering PUMA

Gang Li, MD, University of British Columbia, Vancouver, BC

Cutaneous malignant melanoma is a severe and life-threatening skin cancer. Currently there is no cure for metastatic melanoma. One of the obstacles in melanoma treatment is its resistance to conventional therapy. Recently, we have demonstrated that reduced expression of a mitochondrial protein called PUMA (or the p53 upregulated modulator of apoptosis) is the most important factor involved in melanoma progression and poor patient survival. To test the feasibility of targeting this molecule for gene therapy, we have used adenovirus to deliver the PUMA gene into melanoma cells and found that overexpression of PUMA can significantly induce cell death and inhibit tumor growth in mice. In this project, we will construct an adenovirus to specifically deliver the PUMA gene into pigmented melanoma cells with enhanced infectivity. Therefore, we expect to observe a complete tumor regression using this viral vector targeting PUMA. Our research will provide first hand information on the efficacy of tissue-specific gene therapy. This project may lead to a more effective treatment of patients with malignant melanoma.

(C2006)