Methods and compositions for treating multiple sclerosis and related disorders
This disclosure provides therapeutic compositions and methods for treating multiple sclerosis or a multiple sclerosis-related disorder in a subject in need thereof comprising administering an effective amount of an antigen-MHC-nanoparticle complex to the subject, wherein the antigen is a multiple sclerosis-related antigen.
1. A method for expanding or developing anti-inflammatory T-cells specific for a multiple sclerosis related-antigen in a subject comprising administering to the subject an effective amount of a nanoparticle complex comprising: a nanoparticle core and multiple sclerosis-related antigen-MHC class II protein (pMHCII) complexes operatively coupled to the nanoparticle core, wherein the nanoparticle core has a diameter from about 1 nm to about 100 nm and wherein the pMHCII density on the nanoparticle core comprises from about 0.005 pMHCII/100 nm 2 to about 25 pMHCII/100 nm 2 .
2. The method of claim 1 , wherein the nanoparticle core has a biodegradable layer on the outer surface of the nanoparticle core and the pMHCII complexes are operatively coupled to the nanoparticle core or the biodegradable layer on the nanoparticle core.
3. The method of claim 1 or 2 , wherein the multiple sclerosis-related antigen of the pMHCII complexes is an antigen derived from a protein selected from the group of myelin basic protein, myelin associated glycoprotein, myelin oligodendrocyte protein, proteolipid protein, oligodendrocyte myelin oligoprotein, myelin associated oligodendrocyte basic protein, oligodendrocyte specific protein, heat shock proteins, oligodendrocyte specific proteins NOGO A, glycoprotein Po, peripheral myelin protein 22, and 2′3′-cyclic nucleotide 3′-phosphodiesterase and myelin oligodendrocyte glycoprotein (MOG) or an antigen corresponding to a peptide
having at least 80% identity to a peptide comprising the sequence of SEQ ID NO: 1, 4, or 5.
4. The method of claim 1 or 2 , wherein the nanoparticle core is non-liposomal.
5. The method of claim 1 or 2 , wherein the nanoparticle core comprises a metal, a metal oxide, a metal sulfide, a metal selenide, a magnetic material, a polymer, iron, iron oxide, or gold.
6. The method of claim 2 , wherein the biodegradable layer comprises one or more of dextran, mannitol, or poly(ethylene glycol).
7. The method of claim 1 , wherein the pMHCII complexes are covalently linked or non-covalently linked to the nanoparticle core.
8. The method of claim 2 , wherein the pMHCII complexes are covalently linked or non-covalently linked to the nanoparticle core or the biodegradable layer.
9. The method of claim 1 , wherein the pMHCII complexes are covalently linked to the nanoparticle core through a linker less than 5 kD in size.
10. The method of claim 2 , wherein the pMHCII complexes are covalently linked to the nanoparticle core or the biodegradable layer through a linker less than 5 kD in size.
11. The method of claim 9 or 10 , wherein the linker comprises polyethylene glycol.
12. The method of claim 1 or 2 , wherein the nanoparticle core is bioabsorbable and/or biodegradable.
13. The method of claim 1 , wherein the MHCII protein of the pMHCII complexes comprises all or part of a HLA-DR, HLA-DQ, or HLA-DP protein.
14. The method of claim 1 or 2 , wherein the ratio of the number of pMHCII complexes to the nanoparticle core is from about 10:1 to about 500:1.
15. The method of claim 1 or 2 , wherein the nanoparticle core has a diameter from about 1 nm to about 50 nm.
16. The method of claim 1 or 2 , wherein the nanoparticle core has a diameter from about 1 nm to about 20 nm.
17. The method of claim 1 or 2 , wherein the nanoparticle core has a diameter from about 5 nm to about 20 nm.
18. The method of claim 1 , wherein the subject is a mammal.
19. The method of claim 3 , wherein the multiple sclerosis-related antigen comprises a polypeptide sequence identical to that set-forth in any one of SEQ ID NOs: 1, 4, or 5.
20. The method of claim 1 , wherein the anti-inflammatory T-cells are CD4+ T cells.