Method for sensitizing tumor cells to chemotherapeutic prodrug CPT-11
AssigneesSt. Jude Children's Research Hospital, University of North Carolina
InventorsPhilip M. Potter, Monika Weirdl, Matthew R. Redinbo
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Abstract
Polynucleotides encoding a mutant human carboxylesterase enzyme and polypeptides encoded by the polynucleotides which are capable of metabolizing a prodrug and inactive metabolites thereof to active drug are provided. Compositions and methods for sensitizing cells to a prodrug agent, inhibiting cell growth, treating drug addiction, and facilitating the metabolism of an organophosphate with this enzyme are also provided. In addition, a screening assay for identification of drugs activated by this enzyme is described.
Claims2
A method for sensitizing tumor cells to CPT-11 comprising directly injecting a tumor site comprising tumor cells with a composition comprising an isolated polynucleotide comprising a tumor-specific responsive promoter operably linked to a nucleic acid molecule encoding a mutant human carboxylesterase consisting of the amino acid sequence as set forth in SEQ ID NO:
- 3, wherein the tumor-specific responsive promoter is selected from the group consisting of a carcinoembryonic antigen promoter, a HER-2/neu promoter, a tumor-specific responsive promoter comprising Myc-Max response elements, and a DF3/MUC promoter, so that said tumor cells express the mutant human carboxylesterase and are sensitized to CPT-11.
Dependencies are inferred from the claim text.