Claims
- 1. A method for treating an autoimmune disease in a subject which comprises administering to the subject an effective amount of (a) at least one interferon antagonist that reduces activity of a type I interferon, and (b) at least one Flt3 ligand (Flt3L) antagonist that reduces activity of a Flt3L to thereby treat the autoimmune disease.
- 2. The method of claim 1, wherein the autoimmune disease is selected from the group consisting of acquired immune deficiency syndrome (AIDS), ankylosing spondylitis, arthritis, aplastic anemia, Behcet's disease, diabetes, graft-versus-host disease, Graves' disease, hemolytic anemia, hypogammaglobulinemia, hyper IgE syndrome, idiopathic thrombocytopenia purpura (ITP), multiple sclerosis (MS), Myasthenia gravis, psoriasis, lupus and any combination thereof.
- 3. The method of claim 2, wherein the lupus is systemic lupus erythematosus (SLE) or drug-induced lupus.
- 4. The method of claim 2, wherein the diabetes is diabetes mellitus, Type I diabetes, Type II diabetes, juvenile on-set diabetes or any combination thereof.
- 5. The method of claim 2, wherein the arthritis is rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis or any combination thereof.
- 6. The method of claim 1, wherein the autoimmune disease is SLE.
- 7. The method of claim 1, wherein the subject is a mammal.
- 8. The method of claim 7, wherein the mammal is a human, a primate, a rat, a dog, a cat or a mouse.
- 9. The method of claim 1, wherein the interferon antagonist is selected from the group consisting of an antibody, an antigen-binding fragment of an antibody, a polypeptide, a peptidomimetic, a nucleic acid encoding a peptide, an organic molecule and any combination thereof.
- 10. The method of claim 1, wherein the interferon antagonist comprises soluble receptor for IFN-α.
- 11. The method of claim 1, wherein the interferon antagonist comprises a anti-IFN-α antibody or an antigen-binding fragment thereof.
- 12. The method of claim 1, wherein the Flt3L antagonist is selected from the group consisting of an antibody, an antigen-binding fragment of an antibody, a polypeptide, a peptidomimetic, a nucleic acid encoding a polypeptide, an organic molecule and any combination thereof.
- 13. The method of claim 1, wherein the Flt3L antagonist comprises a soluble Flt3 receptor.
- 14. The method of claim 1, wherein the Flt3L antagonist comprises a anti-Flt3L antibody or an antigen-binding fragment thereof.
- 15. The method of any one of claims 9, 11, 12 or 14, wherein the antibody comprises a monoclonal antibody, a chimeric antibody, an anti-idiotypic antibody, a humanized antibody, a primatized antibody and any combination thereof.
- 16. The method of claim 1, wherein the interferon antagonist and the Flt3L antagonist are part of one molecule.
- 17. The method of claim 1, wherein the effective amount of the interferon antagonist comprises from about 1 to about 10 fold molar excess of interferon.
- 18. The method of claim 1, wherein the effective amount of the Flt3L antagonist comprises from about 1 to about 10 molar excess of Flt3L.
- 19. The method of claim 1, wherein the administration of the composition is by intralesional, intraperitoneal, intramuscular or intravenous injection; infusion; liposome-mediated delivery; or topical, nasal, oral, ocular or otic delivery.
- 20. The method of claim 1, wherein the type I interferon is an interferon-a (IFN-α) or an IFN-β.
- 21. The method of claim 1, wherein the interferon antagonist reduces binding of a type I interferon with its receptor.
- 22. The method of claim 1, wherein the interferon antagonist reduces interferon-dependent signal transduction.
- 23. The method of claim 1, wherein the interferon antagonist reduces interferon serum levels.
- 24. The method of claim 1, wherein the interferon antagonist reduces interferon secretion from cells as measured by an interferon receptor binding assay.
- 25. The method of claim 1, wherein the interferon antagonist reduces bioavailability of interferon in serum as measured by an interferon receptor binding assay.
- 26. The method of claim 1, wherein the interferon antagonist reduces development of cells which produce type I interferon in the subject as measured by a monocyte differentiation assay.
- 27. The method of claim 1 or 11, wherein the interferon antagonist is TNF.
- 28. A therapeutic composition to inhibit monocyte differentiation into dendritic cells capable of antigen presentation which comprises:
(a) at least one interferon antagonist that reduces activity of a type I interferon, and (b) at least one FIt3 ligand (Flt3L) antagonist that reduces activity of Flt3L.
- 29. The composition of claim 28, wherein the type I interferon is an interferon-α (IFN-α) or an IFN-β.
- 30. The composition of claim 28, wherein the composition further comprises a carrier.
- 31. The composition of claim 28, wherein the interferon antagonist is selected from the group consisting of an antibody, an antigen-binding fragment of an antibody, a polypeptide, a peptidomimetic, a nucleic acid encoding a polypeptide, an organic molecule and any combination thereof.
- 32. The composition of claim 28, wherein the interferon antagonist comprises a soluble receptor for IFN-α.
- 33. The composition of claim 28, wherein the interferon antagonist comprises an anti-IFN-α antibody or an antigen-binding fragment thereof.
- 34. The composition of claim 28, wherein the interferon antagonist is TNF.
- 35. The composition of claim 28, wherein the Flt3L antagonist is selected from the group consisting of an antibody, an antigen-binding fragment of an antibody, a peptide, a peptidomimetic, a nucleic acid encoding a peptide, an organic molecule and any combination thereof.
- 36. The composition of claim 28, wherein the Flt3L antagonist comprises a soluble Flt3 receptor.
- 37. The composition of claim 28, wherein the Flt3L antagonist comprises an anti-Flt3L antibody or an antigen-binding fragment thereof.
- 38. The composition of any one of claims 31, 33, 35 and 37, wherein the antibody is a monoclonal antibody, a chimeric antibody, an anti-idiotypic antibody, a humanized antibody, or a primatized antibody.
- 39. The composition of claim 28, wherein the interferon antagonist and the Flt3L antagonist are part of one molecule.
- 40. The composition of claim 28, wherein the composition comprises two or more interferon antagonists and a Flt3L antagonist.
- 41. The composition of claim 40, wherein one interferon antagonist is TNF.
- 42. The composition of claim 40, wherein the composition comprises an anti-IFN-α antibody, an anti-Flt3L antibody and TNF.
- 43. An in vitro assay for determining a subject's risk for developing an autoimmune disease which comprises:
(a) obtaining a serum sample from the subject; (b) quantifying IFN-α and Flt3 ligand (Flt3L) in the serum sample; and (c) comparing the quantity of IFN-α and Flt3L with the quantities of IFN-α and Flt3L in serum from subjects with an autoimmune disease, thereby determining the subject's risk for developing an autoimmune disease.
- 44. The method of claim 43, wherein a risk of developing an autoimmune disease occurs when the quantities of IFN-α and Flt3L are within about a 30% range of those quantities for subjects with an autoimmune disease.
- 45. The method of claim 44, wherein said risk increases when said range is about 20%.
- 46. The method of claim 43, wherein said comparison is made for age-matched subjects.
- 47. A kit for determining a subject's risk for developing an autoimmune disease or for monitoring the status of an autoimmune disease in a subject which comprises a composition which specifically binds to Flt3L and to IFN-α in an amount effective to detect Flt3L and IFN-α in a biological sample of a subject.
- 48. The kit of claim 47, wherein the biological sample is a blood sample or a serum sample.
- 49. The kit of claim 47, wherein the composition comprises a monoclonal antibody that binds Flt3L and a monoclonal antibody that binds IFN-α.
- 50. The kit of claim 47, wherein the kit further comprises one or more reagents for detecting amounts of the composition bound to one or more samples.
- 51. The kit of claim 47, wherein the composition is labeled with a detectable marker.
- 52. The kit of claim 51, wherein the detectable marker is selected from the group consisting of a fluorescent marker, a radioactive marker, an enzymatic marker, a calorimetric marker, a chemiluminescent marker and any combination thereof.
CROSS-REFERENCES TO RELATED APPLICATIONS
[0001] This application claims the priority to U.S. Provisional Patent Application Serial No. 60/260,541, fied Jan. 9, 2001, the entire contents of which are hereby incorporated by reference.
Provisional Applications (1)
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Number |
Date |
Country |
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60260541 |
Jan 2001 |
US |