Claims
- 1. A method for expressing gene product in a cell type-preferential manner comprising:
(a) providing a first expression cassette comprising a cell type-preferential promoter that directs the expression of a nucleic acid encoding a transcription factor; (b) providing a second expression cassette comprising an inducible promoter, responsive to said transcription factor, that directs the expression of a nucleic acid encoding a selected polypeptide; and (c) transferring said first and second expression cassettes into a cell in which said cell type-specific preferential promoter is active, wherein said transcription factor is expressed and directs expression of said selected polypeptide.
- 2. The method of claim 1, wherein said cell type-preferential promoter is hTERT, CEA, PSA, probasin, ARR2PB or AFP.
- 3. The method of claim 1, wherein said transcription factor is GAL4-VP16 fusion and said inducible promoter is GAL4/TATA.
- 4. The method of claim 1, wherein said transcription factor is tetR-VP16 fusion and said inducible promoter is tet operator.
- 5. The method of claim 1, wherein said first and second expression cassettes are located in different expression constructs.
- 6. The method of claim 1, wherein said first and second expression cassettes are located in the same expression construct.
- 7. The method of claim 1, wherein at least one of said expression cassettes is located in a viral expression construct.
- 8. The method of claim 1, wherein at least one of said expression cassettes is located in a non-viral expression construct.
- 9. The method of claim 1, wherein said cell is a tumor cell.
- 10. The method of claim 1, wherein said selected polypeptide is a tumor suppressor, an inducer of apoptosis, a cytokine, an enzyme or a toxin.
- 11. The method of claim 1, wherein said tumor suppressor is p53, Rb, PTEN, BRCA1 and BRCA2.
- 12. The method of claim 1, wherein said inducer of apoptosis is Bax, Bad, Bid, Bik, Bak, TRAIL, FasL, Noxa, PUMA, p53AIP1, TGF-β, Granzyme A or Granzyme B.
- 13. The method of claim 10, wherein said cytokine is IL-2, IL-4, IL-10, IL-12, GM-CSF, MCP-3, TNF-α, or INF-β.
- 14. The method of claim 10, wherein said enzyme is cytosine deaminase.
- 15. The method of claim 10, wherein said toxin in ricin A chain, cholera toxin and pertussis toxin.
- 16. The method of claim 9, wherein said tumor cell is selected from the group consisting of a brain tumor cell, a head & neck tumor cell, an esophageal tumor cell, a lung tumor cell, a thyroid tumor cell, a stomach tumor cell, a colon tumor cell, a liver tumor cell, a kidney tumor cell, a prostate tumor cell, a breast tumor cell, a cervical tumor cell, an ovarian tumor cell, a testicular tumor cell, a rectal tumor cell, a skin tumor cell or a blood tumor cell.
- 17. A method of treating a human subject having cancer comprising:
(a) providing a first expression cassette comprising a CEA or hTERT promoter that directs the expression of a nucleic acid encoding a transcription factor; (b) providing a second expression cassette comprising an inducible promoter, responsive to said transcription factor, that directs the expression of a nucleic acid encoding a therapeutic polypeptide; and (c) transferring said first and second expression constructs into a cancer cell in said subject, wherein said transcription factor is expressed and directs expression of said therapeutic polypeptide.
- 18. The method of claim 17, wherein (i) said transcription factor is GAL4-VP16 fusion and said inducible promoter is GAL4/TATA, or (ii) said transcription factor is tetR-VP 16 fusion and said inducible promoter is tet operator.
- 19. The method of claim 17, wherein said first and second expression cassettes are located in different expression constructs.
- 20. The method of claim 17, wherein said first and second expression cassettes are located in the same expression construct.
- 21. The method of claim 17, wherein at least one of said expression cassettes is located in a viral expression construct.
- 22. The method of claim 17, wherein at least one of said expression cassettes is located in a non-viral expression construct.
- 23. The method of claim 21, wherein said viral expression construct is an adenoviral expression construct, a herpesviral expression construct, a retroviral expression construct, a vaccinia viral expression construct, an adeno-associated viral expression construct or a polyoma viral expression construct.
- 24. The method of claim 1, wherein said selected polypeptide is a tumor suppressor, an inducer of apoptosis, a cytokine, an enzyme or a toxin.
- 25. The method of claim 24, wherein said tumor suppressor is p53, Rb, PTEN, BRCA1 and BRCA2.
- 26. The method of claim 24, wherein said inducer of apoptosis is Bax, Bad, Bid, Bik, Bak, TRAIL, FasL, Noxa, PUMA, p53AIP1, TGF-β, Granzyme A or Granzyme B.
- 27. The method of claim 24, wherein said cytokine is IL-2, IL-4, IL-10, IL-12, GM-CSF, MCP-3, TNF-β or INF-β.
- 28. The method of claim 24, wherein said enzyme is cytosine deaminase.
- 29. The method of claim 24, wherein said toxin in ricin A chain, cholera toxin and pertussis toxin.
- 30. The method of claim 17, wherein said cancer is selected from the group consisting of brain cancer, head & neck cancer, esophageal cancer, lung cancer, thyroid cancer, stomach cancer, colon cancer, liver cancer, kidney cancer, prostate cancer, breast cancer, cervical cancer, ovarian cancer, testicular cancer, rectal cancer, skin cancer or blood cancer.
- 31. The method of claim 17, further comprising administering a second cancer therapy comprising surgery, immunotherapy, chemotherapy or radiation therapy.
- 32. A method for treating a human cancer patient comprising:
(a) providing a non-viral expression cassette comprising an hTERT promoter that directs the expression of a nucleic acid encoding a tumor suppressor or an inducer of apoptosis; and (b) administering said expression cassette into said subject, wherein said tumor suppressor or inducer of apoptosis is expressed and inhibits growth of cancer cells, thereby treating said cancer.
- 33. The method of claim 32, wherein said tumor suppressor is p53, Rb, PTEN, BRCA1 and BRCA2.
- 34. The method of claim 32, wherein said inducer of apoptosis is Bax, Bad, Bid, Bik, Bak, TRAIL, FasL, Noxa, PUMA, p53AIP1, TGF-β, Granzyme A or Granzyme B.
- 35. The method of claim 32, wherein said cancer cells are killed.
- 36. The method of claim 32, wherein at least one of said expression cassettes is located in a viral expression construct.
- 37. The method of claim 36, wherein said nucleic acid encoding a tumor suppressor or an inducer of apoptosis further encodes a screenable marker fused to said tumor suppressor or said inducer of apoptosis.
- 38. The method of claim 32, wherein at least one of said expression cassettes is located in a non-viral expression construct.
- 39. The method of claim 32, further comprising administering a second cancer therapy comprising surgery, immunotherapy, chemotherapy or radiation therapy.
- 40. The method of claim 32, wherein said cancer is selected from the group consisting of brain cancer, head & neck cancer, esophageal cancer, lung cancer, thyroid cancer, stomach cancer, colon cancer, liver cancer, kidney cancer, prostate cancer, breast cancer, cervical cancer, ovarian cancer, testicular cancer, rectal cancer, skin cancer or blood cancer.
Parent Case Info
[0001] The present application claims priority to co-pending U.S. Provisional Patent Application Serial No. 60/310,905 filed on Aug. 8, 2001. The entire text of the above-referenced disclosure is specifically incorporated herein by reference without disclaimer.
Government Interests
[0002] The government owns rights in the present invention pursuant to grant number P50CA70907-01 from the National Institutes of Health (University of Texas SPORE in Lung Cancer).
Provisional Applications (1)
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Number |
Date |
Country |
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60310905 |
Aug 2001 |
US |