Method for in vivo expansion of T regulatory cells

• US 9,499,627 B2
• Filed: 08/03/2010
• Issued: 11/22/2016
• Est. Priority Date: 08/03/2009
• Status: Active Grant

• Current Assignee: University of Miami
• Original Assignee: University of Miami
• Inventors: Podack, Eckhard R., Schreiber, Taylor, Wolf, Dietlinde-Maria
• Primary Examiner(s): Bunner, Bridget E
• Application Number:
  US13/388,722
• Publication Number:
  US 20120135011A1
• Time in Patent Office: 2,303 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 38/17 from animals; from humans enzyme inhibitors A61K38/005
• CPC Class Codes: A61K 38/19 Cytokines; Lymphokines; Interferons
• CPC Class Codes: A61K 38/191 Tumor necrosis factors [TNF], e.g. lymphotoxin [LT], i.e. TNF-beta
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• 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 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• 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 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 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: C07K 14/525 Tumour necrosis factor [TNF]
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C07K 14/7151 for tumor necrosis factor [TNF], for lymphotoxin [LT]
• CPC Class Codes: C07K 16/28 : against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 16/2863 : against receptors for growth factors, growth regulators
• CPC Class Codes: C07K 16/2878 : against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
• CPC Class Codes: C07K 2317/75 : Agonist effect on antigen

Abstract

Compositions specific for TNF-receptor superfamily member 25 (TNFRSF25, DR3) modulate the immune response by regulating T regulatory cells.

Claims

1. A method of delaying acute rejection of a transplanted allograft in a subject, the method comprising the step of administering to the subject, prior to the subject receiving the transplanted allograft, a sufficient amount of a tumor necrosis factor receptor superfamily member 25 (TNFRSF25) agonist to increase the frequency of thymically-derived, natural T regulatory cells (nTreg) and for delaying rejection of the transplanted allograft, wherein the agonist is selected from the group consisting of:

an agonistic anti-TNFRSF25 antibody and a soluble form of TL1A.

2. The method of claim 1, wherein the TNFRSF25 agonist is an antibody that specifically binds TNFRSF25.

3. The method of claim 2, wherein the antibody is a monoclonal antibody.

4. The method of claim 3, wherein the monoclonal antibody is of the IgG isotype.

5. The method of claim 1, wherein the administration is by injection.

6. The method of claim 1, wherein the method further comprises the step of assessing the function of the allograft following transplant.

7. The method of claim 1, wherein the method further comprises the step of monitoring CD4+FoxP3+ regulatory T (Treg) cell levels in the subject'"'"'s blood.

8. The method of claim 1, wherein the method comprises monitoring Treg cell levels in the subject'"'"'s blood prior to or at the time of transplant of the allograft.

9. The method of claim 1, wherein the method comprises monitoring the frequency of the nTreg in the subject'"'"'s blood prior to or at the time of transplant of the allograft.

10. A method of delaying acute rejection of a transplanted allograft in a subject, the method comprising administering to the subject a sufficient amount of a TNFRSF25 agonist to delay rejection of the transplanted allograft, wherein the TNFRSF25 agonist is a soluble form of TL1A.

11. The method of claim 10, wherein the soluble form of TL1A is a TL1A fusion protein.

12. The method of claim 10, wherein the soluble form of TL1A is administered to the subject prior to the subject receiving the transplanted allograft.

13. The method of claim 12, wherein the administration of the soluble form of TL1A is effective for expanding nTreg in the subject.

14. The method of claim 13, wherein the method comprises monitoring the frequency of the nTreg in the subject'"'"'s blood prior to or at the time of transplant of the allograft.

15. The method of claim 12, wherein the method comprises monitoring Treg cell levels in the subject'"'"'s blood prior to or at the time of transplant of the allograft.