Compositions and methods for the prevention and treatment of autoimmune conditions
View Patent ↗The methods include selectively reducing or expanding T cells according to the antigenic specificity of the T cells. Therefore, the present invention can be used to reduce or eliminate pathogenic T cells that recognize autoantigens, such as beta cell specific T cells. As such, the present invention can be used to prevent, treat or ameliorate autoimmune diseases such as IDDM. Furthermore, the present invention can be used to expand desirable T cells, such as anti-pathogenic T cells to prevent, treat and/or ameliorate autoimmune diseases.
1. A method of treating type I diabetes or prediabetes, in a patient which method comprises:
identifying a patient having type I diabetes or prediabetes; and
administering to said patient an antigen-MHC complex operatively coupled to a non-liposomal nanoparticle in an amount sufficient to expand low avidity anti-pathogenic autoreactive T cells;
wherein the antigen is a type I diabetes relevant; and
further wherein said nanoparticle has a diameter of less than 1 μm.
2. The method of claim 1 , wherein the MHC component is a MHC class I component.
3. The method of claim 2 , wherein the MHC class I component comprises all or part of a HLA-A, HLA-B, HLA-C, HLA-E, HLA-F, HLA-G or CD-1 molecule.
4. The method of claim 2 , wherein, the MHC class I component comprises all or part of a HLA-A molecule.
5. The method of claim 2 , wherein the MHC class I component comprises all or part of a HLA-A*0201 MHC class I molecule.
6. The method of claim 1 , wherein the nanoparticle comprises a metal ion.
7. The method of claim 6 , wherein the metal ion is iron (III).
8. The method of claim 1 , wherein the antigen-MHC complex is covalently bound to the nanoparticle.
9. The method of claim 8 , wherein the complex is bound to the nanoparticle via a linker.
10. The method of claim 9 , wherein the linker is one or more of the group a peptide linker, ethylene glycol, biotin, and strepdavidin.
11. The method of claim 1 , wherein the T cells expanded by the treatment have been preactivated by type I diabetes and have a memory phenotype.
12. The method of claim 1 , wherein the T cell is a CD4 + or CD8 + T cell.
13. A method of treating type I diabetes or prediabetes in a patient in need thereof which method comprises:
identifying a patient having type I diabetes or prediabetes; and
administering to said patient a peptide-MHC complex operatively coupled to a non-liposomal nanoparticle in an amount sufficient to expand low avidity anti-pathogenic autoreactive T cells;
wherein the peptide is a type I diabetes relevant and the MHC is a classical MHC molecule;
wherein said nanoparticle has a diameter of less than 1 μm; and
further wherein the peptide is an epitope from an autoantigen expressed by pancreatic beta cells.
14. The method of claim 13 , wherein the autoantigen is islet-specific glucose-6-phosphatase catalytic subunit-related protein, insulin, glutamic acid decarboxylase or IA-2 protein.
15. The method of claim 13 , wherein the autoantigen is an epitope derived from an endocrine or neurocrine component.
16. The method of claim 15 wherein the endocrine or neuroendocrine component is peri-islet Schwann cells.
17. The method of claim 1 or 13 , wherein the method treats type I diabetes.
18. The method of claim 1 or 13 , wherein the method treats prediabetes.
19. A method of treating type I diabetes or prediabetes in a patient which method comprises:
identifying a patient having type I diabetes or prediabetes; and
administering to said patient an antigen-MHC class II complex operatively coupled to a non-liposomal nanoparticle in an amount sufficient to expand low avidity anti-pathogenic autoreactive T cells;
wherein the antigen is a type I diabetes relevant antigen; and
wherein said nanoparticle has a diameter of less than 1 μm.
20. The method of claim 19 , wherein the MHC class II component comprises all or part of a HLA-DR, HLA-DQ, or HLA-DP.
21. The method of any one of claims 1 , 13 and 19 , wherein the non-liposomal nanoparticle comprises a solid core.