Methods and compositions for therapies using genes encoding secreted proteins such as interferon-beta
View Patent ↗Methods and pharmaceutical compositions for modifying cells of a mammalian recipient with DNA encoding a secreted protein such as human interferon in situ are provided. The methods include forming a secreted protein expression system in vivo or ex vivo and administering the expression system to the mammalian recipient. The expression system and methods are useful for the localized and systemic delivery of interferons in situ.
1. A method for treating cancer by in vivo interferon-β gene therapy comprising the steps of:
parenterally administering to a subject a viral vector comprising a gene that encodes interferon-β protein, and
allowing said interferon-β protein to be expressed from said gene in said subject in an amount sufficient to cause cancer regression or inhibition of cancer growth,
wherein said viral vector is selected from the group consisting of an adenoviral vector, a lentiviral vector, a baculoviral vector, an Epstein Barr viral vector, a papovaviral vector, a vaccinia viral vector, and a herpes simplex viral vector, and
wherein if said viral vector is an adenoviral vector, then said subject is not exposed to a nucleic acid encoding a selectable marker gene.
2. The method according to claim 1 , wherein said viral vector is selected from the group consisting of an adenoviral vector, a baculoviral vector and a lentiviral vector.
3. The method according to claim 1 , wherein said viral vector is an adenoviral vector.
4. The method according to claim 3 , wherein said adenoviral vector has a deletion in its E3 gene.
5. The method according to claim 3 , wherein said adenoviral vector has a deletion in its E1 gene.
6. The method according to claim 4 , wherein said adenoviral vector has a deletion in its E1 gene.
7. The method according to claim 1 , wherein said parenteral administration is selected from the group consisting of intravenous administration, intramuscular administration, subcutaneous administration and intraperitoneal administration.
8. The method according to claim 1 , wherein said cancer is selected from the group consisting of malignant glioma, melanoma, hemangioma, leukemia, lymphoma, myeloma, colorectal cancer, non-small cell carcinoma, breast cancer and ovarian cancer.
9. The method according to claim 8 , wherein said cancer is malignant glioma.
10. The method according to claim 1 , wherein said gene encodes a human interferon-β protein.
11. The method according to claim 1 , wherein said subject is a human subject.
12. A method for treating cancer by in vivo interferon-β gene therapy comprising the steps of:
parenterally administering to a subject a replication-defective viral vector comprising a gene that encodes interferon-β protein, and
allowing said interferon-β protein to be expressed from said gene in said subject in an amount sufficient to cause cancer regression or inhibition of cancer growth,
wherein said viral vector is selected from the group consisting of an adenoviral vector, a lentiviral vector, a baculoviral vector, an Epstein Barr viral vector, a papovaviral vector, a vaccinia viral vector and a herpes simplex viral vector, and
wherein if said viral vector is an adenoviral vector, then said subject is not exposed to a nucleic acid encoding a selectable marker gene.
13. The method according to claim 12 , wherein said viral vector is selected from the group consisting of an adenoviral vector, a baculoviral vector and a lentiviral vector.
14. The method according to claim 12 , wherein said viral vector is an adenoviral vector.
15. The method according to claim 14 , wherein said adenoviral vector is deficient is one or more essential genes of one or more adenoviral genome regions selected from the group consisting of the E1, E2A and E4 regions of the adenoviral genome.
16. The method according to claim 14 , wherein said adenoviral vector has a deletion in its E3 gene.
17. The method according to claim 14 , wherein said adenoviral vector has a deletion in its E1 gene.
18. The method according to claim 17 , wherein said adenoviral vector is deficient in its E3 gene.
19. The method according to claim 12 , wherein said parenteral administration is selected from the group consisting of intravenous administration, intramuscular administration, subcutaneous administration and intraperitoneal administration.
20. The method according to claim 12 , wherein said cancer is selected from the group consisting of malignant glioma, melanoma, hemangioma, leukemia, lymphoma, myeloma, colorectal cancer, non-small cell carcinoma, breast cancer and ovarian cancer.
21. The method according to claim 20 , wherein said cancer is malignant glioma.
22. The method according to claim 12 , wherein said gene encodes a human interferon-β protein.
23. The method according to claim 12 , wherein said subject is a human subject.
24. A method for treating cancer by in vivo interferon-β gene therapy comprising the steps of:
administering to a subject a viral vector comprising a gene that encodes interferon-β protein, and
allowing said interferon-β protein to be expressed from said gene in said subject in an amount sufficient to cause cancer regression or inhibition of cancer growth by induction of a systemic anti-tumor immune response,
wherein said viral vector is selected from the group consisting of an adenoviral vector, a lentiviral vector, a baculoviral vector, an Epstein Barr viral vector, a papovaviral vector, a vaccinia viral vector and a herpes simplex viral vector, and
wherein if said viral vector is an adenoviral vector, then said subject is not exposed to a nucleic acid encoding a selectable marker gene.
25. The method according to claim 24 , wherein said viral vector is selected from the group consisting of an adenoviral vector, a baculoviral vector and a lentiviral vector.
26. The method according to claim 24 , wherein said viral vector is an adenoviral vector.
27. The method according to claim 26 , wherein said adenoviral vector has a deletion in its E3 gene.
28. The method according to claim 26 , wherein said adenoviral vector has a deletion in its E1 gene.
29. The method according to claim 27 , wherein said adenoviral vector has a deletion in its E1 gene.
30. The method according to claim 24 , wherein said gene encodes a human interferon-β protein.
31. The method according to claim 24 , wherein said subject is a human subject.