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AssigneeThe UAB Research Foundation
InventorsDonald J. Buchsbaum, C. Ryan Miller, G. Yancey Gillespie, Robert J. Garver, Jr.
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The present invention provides a new approach for cancer treatment by utilizing gene therapy combined with radiation therapy to enhance cytotoxicity in malignant cells. Specifically, the present invention demonstrates that molecular chemotherapy with the cytosine deaminase gene and 5-fluorocytosine is an effective radiosensitizing strategy which may lead to substantial improvement in tumor control, with less normal tissue toxicity than conventional systemic administration of 5-fluorouracil, that would translate into improved cure rates and better survival. A noninvasive method is described for continuous in vivo monitoring of 5-fluorouracil production via magnetic resonance spectroscopy. An adenovirus encoding cytosine deaminase gene which selectively replicates in tumor cells with a defective p53 pathway was constructed. Also provided is an adenovirus which encodes a fusion protein of cytosine deaminase and uracil phosphoribosyltransferase.
A method of treating an individual having a solid tumor, wherein cells comprising said tumor are capable of infection by an adenovirus encoding a cytosine deaminase gene and a uracil phosphoribosyltransferase gene and are capable of coexpression said genes, comprising the steps of:
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