Method of sensitizing tumor cells with adenovirus E1A
First Claim
1. A method of reducing viability of a human tumor cell in a subject, comprising the steps of:
- a. introducing into a human tumor cell in a subject nucleic acid encoding a polypeptide having adenovirus E1A activity;
b. expressing said polypeptide in an effective amount in the tumor cell, thereby enhancing sensitivity of the tumor cell expressing said polypeptide to a chemotherapeutic agent; and
c. contacting the tumor cell with said chemotherapeutic agentwherein a nucleic acid encoding functional p53 is not introduced into the tumor cell, said enhanced sensitivity is independent or p53 and viability of the tumor cell is reduced.
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Abstract
The present invention is directed to methods of sensitizing a human tumor cell with adenovirus E1A. The methods involve treating a human tumor cell by, first, introducing into the tumor cell nucleic acid encoding a polypeptide having adenovirus E1A activity, expressing the E1A active polypeptide in the cell, and then either contacting the E1A expressing tumor cell with a chemotherapeutic agent or irradiating the E1A-expressing tumor cell. The invention also provides methods of enhancing a subject'"'"'s response to chemotherapy or irradiation by introducing into a subject'"'"'s tumor cells nucleic acid encoding a polypeptide having adenovirus E1A activity, expressing the E1A active polypeptide in the cells and finally, administering either a chemotherapeutic agent or irradiation. The invention also provides a method of treating cancer.
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Citations
26 Claims
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1. A method of reducing viability of a human tumor cell in a subject, comprising the steps of:
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a. introducing into a human tumor cell in a subject nucleic acid encoding a polypeptide having adenovirus E1A activity; b. expressing said polypeptide in an effective amount in the tumor cell, thereby enhancing sensitivity of the tumor cell expressing said polypeptide to a chemotherapeutic agent; and c. contacting the tumor cell with said chemotherapeutic agent wherein a nucleic acid encoding functional p53 is not introduced into the tumor cell, said enhanced sensitivity is independent or p53 and viability of the tumor cell is reduced. - View Dependent Claims (2, 3, 4, 5)
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6. A method of reducing viability of a human tumor cell in a subject, comprising the steps of:
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a. introducing into a human tumor cell in a subject nucleic acid encoding a polypeptide having adenovirus E1A activity; b. expressing said polypeptide in an effective amount in the tumor cell, thereby enhancing sensitivity of the tumor cell expressing said polypeptide to irradiation; and c. irradiating the tumor cell; wherein a nucleic acid encoding functional p53 is not introduced into the tumor cell, said enhanced sensitivity is independent of p53 and viability of the tumor cell is reduced. - View Dependent Claims (7, 8, 9)
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10. A method of increasing susceptibility to chemotherapy in a subject, comprising the steps of:
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a. introducing into a subject'"'"'s tumor cells nucleic acid encoding a polypeptide having adenovirus E1A activity; b. expressing said polypeptide in an effective amount in said tumor cells, thereby increasing susceptibility of said tumor cells expressing said polypeptide to said chemotherapeutic agent; and c. administering said chemotherapeutic agent to said subject; wherein a nucleic acid encoding functional p53 is not introduced into said tumor cells and said icreased susceptibility is independent of p53. - View Dependent Claims (11, 12, 13)
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14. A method of increasing susceptibility to irradiation in a subject, comprising the steps of:
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a. introducing into a subject'"'"'s tumor cells nucleic acid encoding a polypeptide having adenovirus E1A activity; b. expressing said polypeptide in an effective amount in said tumor cells, thereby increasing susceptibility of said tumor cells expressing said polypeptide to irradiation; and c. administering irradiation to said subject; wherein a nucleic acid encoding functional p53 is not introduced into said tumor cells and said increased susceptibility is independent of p53. - View Dependent Claims (15, 16, 17)
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18. A method of inactivating a tumor in a subject, comprising the steps of:
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a. introducing into a subject'"'"'s tumor cells nucleic acid encoding a polypeptide having adenovirus E1A activity; b. expressing said polypeptide in an effective amount in said tumor cells, thereby enhancing sensitivity of said tumor to a chemotherapeutic agent; and c. contacting said tumor with said chemotherapeutic agent; wherein a nucleic acid encoding functional p53 is not introduced into said tumor cells, said enhanced sensitivity is independent of p53 and said tumor is inactivated. - View Dependent Claims (20, 21, 22, 23)
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19. A method of inactivating a tumor in a subject, comprising the steps of:
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a. introducing into a subject'"'"'s tumor cells nucleic acid encoding a polypeptide having adenovirus E1A activity; b. expressing said polypeptide in an effective amount in said tumor cells, thereby enhancing sensitivity of said tumor to irradiation; and c. irradiating said tumor; wherein a nucleic acid encodina functional p53 is not introduced into said tumor cells, said enhanced sensitivity is independent of p53 and said tumor is inactivated. - View Dependent Claims (24, 25, 26)
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Specification