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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, comprising the steps of:
A method of treating an individual having a cancer, comprising the steps of:
A method of monitoring continuous conversion of 5-fluorocytosine to 5-fluorouracil in a tumor, wherein said tumor is treated with multiple doses of 5-fluorocytosine and multiple doses of adenovirus encoding a cytosine deaminase gene, comprising the steps of:
A method of monitoring continuous conversion of 5-fluorocytosine to 5-fluorouracil in a tumor, wherein said tumor is treated with multiple doses of 5-fluorocytosine and multiple doses of cytosine deaminase gene encoding adenovirus targeted by a ligand to a tumor cellular receptor, comprising the steps of:
An adenovirus encoding a cytosine deaminase gene, wherein said adenovirus selectively replicates in tumor cells.
An adenovirus coexpressing cytosine deaminase and uracil phosphoribosyltransferase.
Dependencies are inferred from the claim text.