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 nanoparticle complex comprising: a nanoparticle core and multiple sclerosis-related antigen-MHC (pMHC) 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 pMHC density on the nanoparticle core comprises from about 0.005 pMHC/100 nm 2 to about 25 pMHC/100 nm 2 .
2. A kit comprising the complex of claim 1 , and instructions for use.
3. The nanoparticle complex of claim 1 , wherein the nanoparticle core has a diameter from about 1 nm to about 50 nm.
4. The nanoparticle complex of claim 1 , wherein the nanoparticle core has a diameter from about 1 nm to about 20 nm.
5. The nanoparticle complex of claim 1 , wherein the nanoparticle core has a diameter from about 5 nm to about 20 nm.
6. The nanoparticle complex of claim 1 , wherein the nanoparticle core has a biodegradable layer on the outer surface of the nanoparticle core and the pMHC complexes are operatively coupled to the nanoparticle core or the biodegradable layer on the nanoparticle core.
7. The nanoparticle complex of claim 6 , wherein the biodegradable layer comprises one or more of dextran, mannitol, or poly(ethylene glycol).
8. The nanoparticle complex of claim 6 , wherein the nanoparticle core has a diameter from about 1 nm to about 50 nm.
9. The nanoparticle complex of claim 6 , wherein the nanoparticle core has a diameter from about 1 nm to about 20 nm.
10. The nanoparticle complex of claim 6 , wherein the nanoparticle core has a diameter from about 5 nm to about 20 nm.
11. The nanoparticle complex of claim 1 or 6 , wherein the multiple sclerosis-related antigen of the pMHC 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 or 4-17, or an equivalent of each thereof.
12. The nanoparticle complex of claim 1 or 6 , wherein the nanoparticle core is non-liposomal.
13. The nanoparticle complex of claim 1 or 6 , wherein the pMHC complexes are covalently or non-covalently linked to the nanoparticle core or the biodegradable layer.
14. The nanoparticle complex of claim 1 or 6 , wherein the pMHC complexes are covalently linked to the nanoparticle core or the biodegradable layer through a linker less than 5 kD in size.
15. The nanoparticle complex of claim 14 , wherein the linker comprises polyethylene glycol.
16. The nanoparticle complex of claim 1 or 6 , wherein the nanoparticle core is bioabsorbable and/or biodegradable.
17. The nanoparticle complex of claim 1 or 6 , wherein the MHC of the pMHC complexes is a MHC class I or II protein.
18. The nanoparticle complex of claim 17 , wherein the MEW class I protein comprises all or part of a HLA-A, HLA-B, HLA-C, HLA-E, HLA-F, HLA-G or CD-1 protein.
19. The nanoparticle complex of claim 17 , wherein the MHC class II protein comprises all or part of a HLA-DR, HLA-DQ, or HLA-DP protein.
20. The nanoparticle complex of claim 1 or 6 , wherein the ratio of the number of pMHC complexes to the nanoparticle core is from about 10:1 to about 500:1.
21. A composition comprising a therapeutically effective amount of the nanoparticle complex of claim 1 or 6 , and a carrier.
22. A method for making, preparing or obtaining the nanoparticle complex of any one of claim 1 - 6 or 3 - 10 , comprising coating or complexing the pMHC complexes onto the nanoparticle core or the biodegradable layer.
23. A method for expanding and/or developing populations of anti-pathogenic autoreactive T-cells in a subject with multiple sclerosis or a multiple sclerosis-related disorder, comprising administering to the subject an effective amount of the nanoparticle complex of any one of claim 1 - 6 or 3 - 10 , thereby expanding and/or developing the populations of anti-pathogenic autoreactive T-cells.
24. The method of claim 23 , wherein the multiple sclerosis-related disorder is selected from the group consisting of neuromyelitis optica (NMO) and neuropathic pain.