Claims
- 1. An isolated nucleic acid composition comprising at least a first set of nucleic acid molecules and a second set of nucleic acid molecules, wherein
(a) each nucleic acid molecule of the first set comprises a sequence encoding a first cytokine or functional fragment thereof and each nucleic acid molecule of the second set comprises a sequence encoding a second cytokine or functional fragment thereof, (b) each nucleic acid molecule of the first set comprises a sequence encoding a first cytokine or functional fragment thereof and each nucleic acid molecule of the second set comprises a sequence encoding a first non-cytokine, anti-tumor protein or functional fragment thereof, or (c) each nucleic acid molecule of the first set comprises a sequence encoding a first non-cytokine, anti-tumor protein or functional fragment thereof and each nucleic acid molecule of the second set comprises a sequence encoding a second non-cytokine anti-tumor protein or functional fragment thereof.
- 2. The nucleic acid composition of claim 1, wherein the nucleic acid molecules comprise DNA vectors.
- 3. The nucleic acid composition of claim 1, wherein the cytokines of (a) or (b) are selected from the group consisting of IL-2, IL-4, IL-5, IL-10, IL-12, IL-15, IL-18, GM-CSF, TGF-β, TNF-α, and IFN-γ.
- 4. The nucleic acid composition of claim 1, wherein the cytokines of (a) or (b) are human cytokines.
- 5. The nucleic acid composition of claim 1, wherein the non-cytokine, anti-tumor proteins of (b) or (c) are selected from the group consisting of an apoptotic protein, an anti-angiogenic protein, and a cell cycle arrest protein.
- 6. The nucleic acid composition of claim 1, wherein the non-cytokine, anti-tumor proteins of (b) or (c) are selected from the group consisting of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), phosphatase and tensin homolog (PTEN), suppressor of high-copy phosphoprotein phosphatase 1 (SHP1), and SHP2.
- 7. The nucleic acid composition of claim 1, wherein the non-cytokine, anti-tumor proteins of (b) or (c) are human non-cytokine anti-tumor proteins.
- 8. The nucleic acid composition of claim 1, wherein each nucleic acid molecule of the first set comprises a sequence encoding a first cytokine or functional fragment thereof and each nucleic acid molecule of the second set of the plurality comprises a sequence encoding a second cytokine or functional fragment thereof.
- 9. The nucleic acid composition of claim 8, wherein each nucleic acid molecule of the first set comprises a sequence encoding IL-2 or a functional fragment thereof.
- 10. The nucleic acid composition of claim 9, wherein the sequence encoding IL-2 is at least 80% identical to SEQ ID NO:1.
- 11. The nucleic acid composition of claim 8, wherein each nucleic acid molecule of the first set comprises a sequence encoding IL-10 or a functional fragment thereof.
- 12. The nucleic acid composition of claim 11, wherein the sequence encoding IL-10 is at least 80% identical to SEQ ID NO:2.
- 13. The nucleic acid composition of claim 9, wherein each nucleic acid molecule of the second set comprises a sequence encoding IL-10 or a functional fragment thereof.
- 14. The nucleic acid composition of claim 8, further comprising a third set of nucleic acid molecules, wherein each nucleic acid molecule of the third set comprises a sequence encoding a non-cytokine anti-tumor protein or functional fragment thereof.
- 15. The nucleic acid composition of claim 14, wherein the non-cytokine, anti-tumor protein is TRAIL or a functional fragment thereof.
- 16. The nucleic acid composition of claim 15, wherein the sequence encoding TRAIL is at least 80% identical to SEQ ID NO:3.
- 17. The nucleic acid composition of claim 14, wherein the non-cytokine, anti-tumor protein is PTEN or a functional fragment thereof.
- 18. The nucleic acid composition of claim 17, wherein the sequence encoding PTEN is at least 80% identical to SEQ ID NO:4.
- 19. The nucleic acid composition of claim 1, wherein each nucleic acid molecule of the first set comprises a sequence encoding a first cytokine or functional fragment thereof and each nucleic acid molecule of the second set comprises a sequence encoding a first non-cytokine, anti-tumor protein or functional fragment thereof.
- 20. The nucleic acid composition of claim 19, wherein each nucleic acid molecule of the first set comprises a sequence encoding IL-2 or a functional fragment thereof.
- 21. The nucleic acid composition of claim 20, wherein the sequence encoding IL-2 is at least 80% identical to SEQ ID NO:1.
- 22. The nucleic acid composition of claim 19, wherein each molecule of the first set comprises a sequence encoding IL-10 or a functional fragment thereof.
- 23. The nucleic acid composition of claim 22, wherein the sequence encoding IL-10 is at least 80% identical to SEQ ID NO:2.
- 24. The nucleic acid composition of claim 19, wherein the non-cytokine, anti-tumor protein is TRAIL or a functional fragment thereof.
- 25. The nucleic acid composition of claim 24, wherein the sequence encoding TRAIL is at least 80% identical to SEQ ID NO:3.
- 26. The nucleic acid composition of claim 19, wherein the non-cytokine anti-tumor protein is PTEN or a functional fragment thereof.
- 27. The nucleic acid composition of claim 26, wherein the sequence encoding PTEN is at least 80% identical to SEQ ID NO:4.
- 28. The nucleic acid composition of claim 1, wherein each nucleic acid molecule of the first set comprises a sequence encoding a first non-cytokine, anti-tumor protein or functional fragment thereof and each nucleic acid molecule of the second set comprises a sequence encoding a second non-cytokine, anti-tumor protein or functional fragment thereof.
- 29. The nucleic acid composition of claim 28, wherein the first non-cytokine anti-tumor protein is TRAIL or a functional fragment thereof.
- 30. The nucleic acid composition of claim 29, wherein the sequence encoding TRAIL is at least 80% identical to SEQ ID NO:3.
- 31. The nucleic acid composition of claim 30, further comprising a third set of nucleic acid molecules, each nucleic acid molecule of the third set comprising a sequence encoding a cytokine or functional fragment thereof
- 32. A nucleic acid composition comprising a first set of nucleic acid vectors, each vector of the first set comprising a sequence encoding IL-2 or a functional fragment thereof, a second set of nucleic acid vectors, each vector of the second set comprising a sequence encoding IL-10 or a functional fragment thereof, and a third set of nucleic acid vectors, each vector of the third set comprising a sequence encoding TNF-related apoptosis-inducing ligand (TRAIL) or a functional fragment thereof.
- 33. A pharmaceutical composition consisting essentially of the nucleic acid composition of claim 1 and a pharmaceutically acceptable carrier.
- 34. The composition of claim 33, wherein the pharmaceutically acceptable carrier comprises saline or buffered saline.
- 35. A method of treating a solid tumor in a subject, the method comprising locally administering the composition of claim 33 to the solid tumor of the subject.
- 36. The method of claim 35, wherein the composition is administered by intratumoral injection.
- 37. The method of claim 35, wherein the composition is administered by subcutaneous injection, intramuscular injection, endoscopic percutaneous injection, injection into a vessel supplying blood flow to the solid tumor, injection into a vessel supplying blood flow to a tumor-containing organ, inhalation, localized topical administration, mucosal administration, injection into cerebral spinal fluid, by osmotic pump, or by lymphoid injecting into circulation.
- 38. The method of claim 35, wherein the composition lacks an adjuvant or facilitating agent.
- 39. The method of claim 35, wherein the tumor is a prostate tumor or a head and neck tumor.
- 40. The method of claim 35, wherein the composition is administered in combination with a second agent or treatment modality.
- 41. The method of claim 40, wherein the second agent or treatment modality is a chemotherapeutic agent, radiation, or surgery.
- 42. The pharmaceutical composition of claim 33, wherein the pharmaceutically acceptable carrier lacks an adjuvant or facilitating agent.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of priority of U.S. Ser. No. 60/464,700, filed Apr. 23, 2003, the contents of which are hereby incorporated by reference in their entirety.
Provisional Applications (1)
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Number |
Date |
Country |
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60464700 |
Apr 2003 |
US |