Immune regulation

• US 20080124348A1
• Filed: 04/06/2007
• Published: 05/29/2008
• Est. Priority Date: 03/01/2002
• Status: Active Grant

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Leguern, Christian A.
• Granted Patent: US 8,652,462 B2
• Time in Patent Office: Days
• US Class Current: 424/184.1
• CPC Class Codes: A61K 39/001 Preparations to induce tolerance to non-self, e.g. prior to transplantation
• CPC Class Codes: A61K 39/4611 T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61K 39/4622 Antigen presenting cells
• CPC Class Codes: A61K 39/464411 Immunoglobulin superfamily
• CPC Class Codes: A61K 39/464429 Molecules with a "CD" designation not provided for elsewhere
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: C07K 16/2833 against MHC-molecules, e.g. HLA-molecules
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C12N 5/0639 Dendritic cells, e.g. Langherhans cells in the epidermis

Abstract

A method of regulating the immune system of a subject that involves removing antigen presenting cells from subject and loading preselected class II peptide fragments onto the subjects APC'"'"'s outside the body of the subject.

Claims

1. A method of regulating the immune system of a subject comprising:

providing antigen presenting cells (APC) from the subject;

loading preselected class II peptide fragments onto the subjects APC'"'"'s outside the body of the subject;

introducing the loaded cells into the subject, thereby regulating the immune response of the subject.

2. The method of claim 1, comprising evaluating the extent to which the cells are loaded with the peptide.

3. The method of claim 1, further comprising introducing a graft that expresses the preselected class II molecule into the subject.

4. The method according to claim 3, wherein the graft is vascularized.

5. The method of claim 1, wherein the preselected class II molecule is autogenic, allogenic, or xenogenic.

6. The method of claim 1, wherein the tissue is autogenic, allogenic, or xenogenic.

7. The method of claim 1, wherein the donor and recipient class II molecules match, or partially match.

8. The method of claim 1, wherein the subject is human.

9. The method of claim 1, wherein the MHC class II molecule and the MHC class II peptide are synthesized in the same cell.

10. The method of claim 1, wherein the MHC class II peptide is processed by an endogenous pathway.

11. The method of claim 1, wherein the regulating of the immune system comprises regulating T cells.

12. The method of claim 11, wherein the T cells comprises autogenous T regulatory T cells and autogenous alloreactive cytotoxic T cells.

13. The method of claim 12, wherein the thymic T regulatory T cells undergo thymic differentiation and peripheral T regulatory T cells undergo activation.

14. The method of claim 12, wherein the alloreactive cytotoxic T cells undergo suppression.

15. The method of claim 12, wherein the T regulatory cell population comprises CD4+CD25+ cells.

16. A method of claim 1, wherein a nucleic acid encoding the class II protein to be presented as a fragment has been introduced into the APC.

17. A method of claim 16, wherein the nucleic acid is expressed as a protein.

18. The method of claim 1, wherein the method is used for graft survival.

19. A method of claim 18, wherein the method is used as a treatment for a malady.

20. A method of claim 19, wherein the malady is an autoimmune disease.

21. A method of claim 20, wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, diabetes mellitus, multiple sclerosis, and lupus erythematosus.