Treatment and prophylaxis with 4-1BB-binding agents

• US 20040109847A1
• Filed: 07/14/2003
• Published: 06/10/2004
• Est. Priority Date: 07/15/2002
• Status: Abandoned Application

• Current Assignee: Mayo Foundation For Medical Education And Research (Mayo Clinic), University of Chicago
• Original Assignee: University of Chicago
• Inventors: Fu, Yang-Xin, Chen, Lieping
• Application Number:
  US10/619,824
• Publication Number:
  US 20040109847A1
• Time in Patent Office: Days
• US Class Current: 424/85.4
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 39/39541 against normal tissues, cells
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/14 of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: C07K 16/2878 against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
• CPC Class Codes: C07K 2317/73 : Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2319/30 : Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

Abstract

Materials and methods for using 4-1BB agonists to treat or prevent autoimmune disorders, lymphoproliferative diseases, and allergies are provided.

Claims

1. A method for depleting double negative T cells in a subject, said method comprising:

(a) identifying a subject as having, or at risk of having, an autoimmune disease, a lymphoproliferative disease, or an allergy; and

(b) administering to said subject an effective amount of a 4-1BB agonist.

2. The method of claim 1, wherein said subject is a human.

3. The method of claim 1, further comprising depleting autoreactive B cells in said subject, wherein said 4-1BB agonist is effective to deplete said autoreactive B cells.

4. The method of claim 1, wherein said 4-1BB agonist is an antibody that binds to 4-1BB.

5. The method of claim 4, wherein said antibody is a monoclonal antibody.

6. The method of claim 4, wherein said antibody is 2A.

7. The method of claim 1, further comprising administering interferon-K to said subject.

8. The method of claim 1, further comprising administering a Gr-1-binding agent to said subject.

9. The method of claim 8, wherein said Gr-1-binding agent is an antibody that binds to Gr-1.

10. The method of claim 1, wherein said autoimmune disease or said lymphoproliferative disease is systemic lupus erythematosus.

11. The method of claim 1, wherein said autoimmune disease is insulin-dependent diabetes mellitus.

12. The method of claim 1, wherein said autoimmune disease or said lymphoproliferative disease is selected from the group consisting of an inflammatory bowel disease, a celiac disease, an autoimmune thyroid disease, Sjogren'"'"'s Syndrome, autoimmune gastritis, pernicious anemia, autoimmune hepatitis, cutaneous autoimmune diseases, autoimmune dilated cardiomyopathy, myocarditis, myasthenia gravis, vasculitis, autoimmune diseases of the muscle, autoimmune diseases of the testis, autoimmune diseases of the ovary, and autoimmune diseases of the eye.

13. The method of claim 1, wherein said allergy is to pollen antigens, fungal antigens, insect antigens, bacterial antigens, mammalian antigens, or insect venom antigens.

14. The method of claim 1, wherein said 4-1BB-binding agent is 4-1BB ligand or a fragment thereof.

15. The method of claim 1, wherein said administering comprises delivering to said subject a nucleic acid comprising a polynucleotide encoding said 4-1BB agonist, wherein said polynucleotide is operably linked to a transcriptional regulatory element.

16. The method of claim 1, wherein said administering comprises:

(i) providing a cell from said subject;

(ii) transfecting or transducing said cell, or a progeny of said cell, with a nucleic acid comprising a polynucleotide encoding said 4-1BB-agonist, wherein said polynucleotide is operably linked to a transcriptional regulatory element; and

(iii) administering said transfected or transduced cell, or a progeny of said transfected or transduced cell, to said subject.

17. The method of claim 1, further comprising:

(c) monitoring said subject for symptoms of said autoimmune disease, lymphoproliferative disease, or allergy.

18. A method for inducing death of a double negative T cell, said method comprising contacting said double negative T cell with an effective amount of a 4-1BB agonist.

19. The method of claim 18, wherein said 4-1BB agonist is an antibody that binds to 4-1BB.

20. The method of claim 19, wherein said antibody is a monoclonal antibody.

21. The method of claim 19, wherein said antibody is 2A.

22. The method of claim 18, wherein said 4-1BB agonist is 4-1BB ligand or a fragment thereof.

23. The method of claim 18, further comprising inducing death-of an autoreactive B cell, wherein said autoreactive B cell is contacted with said effective amount of said 4-1BB agonist.

24. The method of claim 18, wherein said double negative T cell is in vitro.

25. The method of claim 18, wherein said double negative T cell is in a subject.

26. The method of claim 25, wherein said subject is a human.

27. The method of claim 25, wherein said subject has or is at risk for having an autoimmune disease, a lymphoproliferative disease, or an allergy.

28. The method of claim 27, wherein said autoimmune disease or said lymphoproliferative disease is systemic lupus erythematosus.

29. The method of claim 27, wherein said autoimmune disease is insulin-dependent diabetes mellitus.

30. The method of claim 27, wherein said autoimmune disease or said lymphoproliferative disease is selected from the group consisting of an inflammatory bowel disease, a celiac disease, an autoimmune thyroid disease, Sjogren'"'"'s Syndrome, autoimmune gastritis, pernicious anemia, autoimmune hepatitis, cutaneous autoimmune diseases, autoimmune dilated cardiomyopathy, myocarditis, myasthenia gravis, vasculitis, autoimmune diseases of the muscle, autoimmune diseases of the testis, autoimmune-diseases of the ovary, and autoimmune diseases of the eye.

31. The method of claim 27, wherein said allergy is to pollen antigens, fungal antigens, insect antigens, bacterial allergens, mammalian antigens, or insect venom antigens.

32. The method of claim 25, wherein said contacting comprises administering to said subject said 4-1BB agonist.

33. The method of claim 25, wherein said contacting comprises administering to said subject a nucleic acid comprising a polynucleotide encoding said 4-1BB agonist, wherein said polynucleotide is operably linked to a transcriptional regulatory element.

34. The method of claim 25, wherein said contacting comprises:

(a) providing a cell from said subject;

(b) transfecting or transducing said cell, or a progeny cell of the cell, with a nucleic acid comprising a polynucleotide encoding said 4-1BB agonist, wherein said polynucleotide is operably linked to a transcriptional regulatory element; and

(c) administering said transfected or transduced cell, or a progeny of said transfected or transduced cell, to said subject.