Methods of using cytochrome P450 reductase for the enhancement of P450-based anti-cancer gene therapy
AssigneeTrustees of Boston University
InventorsDavid J. Waxman, Ling Chen
Life of this patent
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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.
Claims54
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.
A method for killing neoplastic cells in a mammal, said method comprising:
- (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.
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 bioreductive drug;
- and
- (c) killing said neoplastic cells.
A method for killing neoplastic cells in a mammal, said method comprising:
- (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.
Dependencies are inferred from the claim text.