Methods of using cytochrome P450 reductase for the enhancement of P450-based anti-cancer gene therapy
First Claim
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1. A method for killing neoplastic cells in a mammal, said method comprising:
- (a) delivering a vector to said neoplastic cells, said vector comprising the nucleotide coding sequence of a gene encoding cytochrome P450 and the nucleotide coding sequence of a gene encoding NADPH-P450 reductase (RED);
(b) treating said neoplastic cells with a chemotherapeutic agent that is activated by the product of said cytochrome P450 gene; and
(c) killing said neoplastic cells.
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Abstract
Methods of killing neoplastic cells are provided. The invention relates to the use of NADPH-cytochrome P450 reductase (RED) gene transfer in combination with cytochrome P450 gene transfer to enhance the sensitivity of tumor cells to anti-cancer drugs that are activated by P450 enzymes. The use of bioreductive drugs that are activated by RED and/or cytochrome P450, in this paradigm, is also provided.
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Citations
54 Claims
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1. A method for killing neoplastic cells in a mammal, said method comprising:
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(a) delivering a vector to said neoplastic cells, said vector comprising the nucleotide coding sequence of a gene encoding cytochrome P450 and the nucleotide coding sequence of a gene encoding NADPH-P450 reductase (RED);
(b) treating said neoplastic cells with a chemotherapeutic agent that is activated by the product of said cytochrome P450 gene; and
(c) killing said neoplastic cells. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24)
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25. A method for killing neoplastic cells in a mammal, said method comprising:
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(a) delivering two vectors to said neoplastic cells;
one vector comprising the nucleotide coding sequence of a gene encoding cytochrome P450, the other vector comprising the nucleotide coding sequence of a gene encoding NADPH-P450 reductase (RED);
(b) treating said neoplastic cells with a chemotherapeutic agent that is activated by the product of said cytochrome P450 gene; and
(c) killing said neoplastic cells. - View Dependent Claims (26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43)
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44. A method for killing neoplastic cells in a mammal, said method comprising:
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(a) delivering a vector to said neoplastic cells, said vector comprising the nucleotide coding sequence of a gene encoding cytochrome P450 and the nucleotide coding sequence of a gene encoding NADPH-P450 reductase (RED);
(b) treating said neoplastic cells with a bioreductive drug; and
(c) killing said neoplastic cells. - View Dependent Claims (45, 46, 47, 48)
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49. A method for killing neoplastic cells in a mammal, said method comprising:
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(a) administering to said mammal an agent that will decrease the activity or expression level of hepatic P450 reductase (RED) in said mammal;
(b) delivering a vector to said neoplastic cells, said vector comprising the nucleotide coding sequence of a gene encoding cytochrome P450 and the nucleotide coding sequence of a gene encoding RED;
(c) treating said neoplastic cells with a chemotherapeutic agent that is activated by the gene product of said cytochrome P450 gene; and
(d) killing said neoplastic cells. - View Dependent Claims (50, 51, 52, 53, 54)
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Specification