COMPOSITIONS AND METHODS FOR STIMULATING AN IMMUNE RESPONSE

• US 20080206235A1
• Filed: 12/27/2007
• Published: 08/28/2008
• Est. Priority Date: 12/27/2006
• Status: Abandoned Application

• Current Assignee: Johns Hopkins University
• Original Assignee: Johns Hopkins University
• Inventors: Chen, Lieping
• Application Number:
  US11/965,611
• Publication Number:
  US 20080206235A1
• Time in Patent Office: Days
• US Class Current: 424/130.1
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61M 1/3413 Diafiltration
• CPC Class Codes: A61M 1/3679 by absorption A61M1/3675 takes precedence
• 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 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• 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 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/16 Otologicals
• 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 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 33/02 : Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/04 : Immunostimulants
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 14/70532 : B7 molecules, e.g. CD80, CD86
• 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
• CPC Class Codes: G01N 2800/102 : Arthritis; Rheumatoid arthritis, i.e. inflammation of peripheral joints
• CPC Class Codes: G01N 2800/104 : Lupus erythematosus [SLE]
• CPC Class Codes: G01N 2800/24 : Immunology or allergic disorders SLE G01N2800/104
• CPC Class Codes: G01N 2800/52 : Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Compositions and methods for the stimulating, enhancing or promoting an immune response in a host are provided. One embodiment provides methods and compositions for stimulating, enhancing, or promoting an immune response in a host by administering an effective amount of a B7-H4 antagonist, preferably sH4 or variant thereof. Compositions of sH4 can be used to enhance an immune response to treat infection, cancer, or as part of a vaccine.

Claims

1. A pharmaceutical composition dosage unit comprising an effective amount of a B7-H4 antagonist to inhibit B7-H4 activity in an individual in need thereof, and a pharmaceutically acceptable carrier.

2. The pharmaceutical composition of claim 1 wherein the B7-H4 antagonist is sH4 or a variant thereof.

3. The pharmaceutical composition of claim 1 wherein the B7-H4 antagonist is selected from the group consisting of anti-B 7-H4 antibody, anti-B7-H4 receptor antibody, inhibitory nucleic acid specific for B7-H4 or B7-H4 receptor, nucleic acid encoding sH4, and combinations thereof.

4. The pharmaceutical composition of claim 3 wherein the inhibitory nucleic acid is selected from the group consisting of antisense DNA, antisense RNA, siRNA, and microRNA.

5. The pharmaceutical composition of claim 1 wherein the B7-H4 activity is B7-H4 binding to cell-surface receptor.

6. The pharmaceutical composition of claim 5 wherein the cell-surface receptor is a receptor on a T cell.

7. The pharmaceutical composition of claim 1 wherein the B7-H4 activity is inhibition of T cell activity.

8. The composition of claim 1 further comprising a second therapeutic agent.

9. The composition of claim 8 wherein the second therapeutic agent is selected from the group consisting of an antibody or antigen binding fragment thereof specific for a growth factor receptor or tumor specific antigen, cytokines, chemokines, proliferation inhibitors and cytotoxic agents.

11. The method of claim 8 wherein the B7-H4 antagonist is sH4 or a variant thereof.

12. The method of claim 8 wherein the B7-H4 antagonist is selected from the group consisting of anti-B7-H4 antibody, anti-B7-H4 receptor antibody, inhibitory nucleic acid specific for B7-H4 or B7-H4 receptor, nucleic acid encoding sH4, and combinations thereof.

13. The method of claim 12 wherein the inhibitory nucleic acid is selected from the group consisting of antisense DNA, antisense RNA, siRNA, and microRNA.

10. A method for stimulating or enhancing an immune response in an individual comprising

administering to the individual an effective amount of a B7-H4 antagonist to inhibit B7-H4 activity in the individual.

14. The method of claim 10 wherein the B7-H4 activity is B7-H4 binding to cell-surface receptor.

15. The method of claim 14 wherein the cell-surface receptor is a receptor on a T cell.

16. The method of claim 10 wherein the B7-H4 activity is inhibition of T cell activity.

17. The method of claim 10 wherein the method is used to treat an infection or cancer in the individual.

18. The method of claim 17 for treating a cancer wherein the cancer is selected from the group consisting of bladder, brain, breast, cervical, colo-rectal, esophageal, kidney, liver, lung, nasopharangeal, pancreatic, prostate, skin, stomach, uterine, ovarian, and testicular cancers.

19. The method of claim 17 for treating an infection wherein the infection is due to a virus, bacteria, fungus, and protozoa.

20. A vaccine composition comprising

an antigen and a B7-H4 antagonist in an amount effective to inhibit B7-H4 activity in a individual.

21. The vaccine composition of claim 20 wherein the antigen is an expression vector encoding the antigen.

22. The vaccine composition of claim 20 wherein the antigen comprises an antigenic polypeptide.

23. The vaccine composition of claim 22 wherein the antigenic polypeptide is viral, fungal, bacterial, or protozoan.

24. The vaccine composition of claim 22 wherein the antigenic polypeptide comprising a tumor specific antigen.

25. A method for treating cancer comprising

administering to a subject an effective amount of a B7-H4 antagonist to bind to a B7-H4 molecule on a tumor cell to inhibit the B7-H4 molecule from binding to a B7-H4 receptor on an immune cell.

26. The method of claim 25 wherein the B7-H4 antagonist is selected from the group consisting of an antibody or antigen binding fragment thereof and sH4.

27. The method of claim 25 further comprising administering to the subject a second therapeutic agent.

28. The method of claim 27, wherein the second therapeutic agent is selected from the group consisting of an antibody or antigen binding fragment thereof specific for a growth factor receptor or tumor specific antigen, cytokines, chemokines, proliferation inhibitors and cytotoxic agents.

29. The method of claim 25 further comprising administering an effective amount of radiation.