Programming of cells for tolerogenic therapies

Abstract

Biomaterial systems, e.g., gel scaffolds, are used in vivo to recruit immune cells and promote their activation towards a non-inflammatory phenotype, thereby leading suppression of inflammation. The compositions and methods are useful to reduce the severity of autoimmunity, chronic inflammation, allergy, and periodontal disease.

1 - 23 . (canceled) 
     
     
         24 . A scaffold composition comprising:
 an antigen;   a recruitment composition;   and a tolerogen.   
     
     
         25 . The composition of  claim 24 , wherein the antigen is derived from a cell to which a pathologic autoimmune response associated with an autoimmune disorder is directed. 
     
     
         26 . The composition of  claim 24 , wherein the tolerogen induces immune tolerance or a reduction in an immune response. 
     
     
         27 . The composition of  claim 25 , wherein the autoimmune disorder is type 1 diabetes. 
     
     
         28 . The composition of  claim 27 , wherein the antigen comprises a pancreatic cell antigen. 
     
     
         29 . The composition of  claim 28 , wherein the antigen is selected from the group consisting of insulin, proinsulin, glutamic acid decarboxylase-65 (GAD65), insulinoma-associated protein 2, heat shock protein 60, ZnT8, and islet-specific glucose-6-phosphatase catalytic subunit. 
     
     
         30 . The composition of  claim 25 , wherein the autoimmune disorder is multiple sclerosis. 
     
     
         31 . The composition of  claim 30 , wherein the antigen is selected from the group consisting of myelin basic protein, myelin proteolipid protein, myelin-associated oligodendrocyte basic protein, and myelin oligodendrocyte glycoprotein. 
     
     
         32 . The composition of  claim 25 , where the autoimmune disorder is selected from the group consisting of Crohn's disease, rheumatoid arthritis, Systemic lupus erythematosus, Scleroderma, Alopecia areata, Antiphospholipid antibody syndrome, Autoimmune hepatitis, Celiac disease, Graves' disease, Guillain-Barre syndrome, Hashimoto's disease, Hemolytic anemia, Idiopathic thrombocytopenic purpura, inflammatory bowel disease, ulcerative colitis, inflammatory myopathies, Polymyositis, Myasthenia gravis, Primary biliary cirrhosis, Psoriasis, Sjögren's syndrome, Vitiligo, gout, celiac disease, atopic dermatitis, acne vulgaris, autoimmune hepatitis, and autoimmune pancreatitis. 
     
     
         33 . The composition of  claim 24 , wherein the tolerogen is selected from the group consisting of thymic stromal lymphopoietin, dexamethasone, vitamin D, retinoic acid, rapamycin, aspirin, transforming growth factor beta, interleukin-10, vasoactive intestinal peptide, and vascular endothelial growth factor. 
     
     
         34 . The composition of  claim 24 , wherein the recruitment composition is selected from the group consisting of GM-CSF, FMS-like tyrosine kinase 3 ligand, N-formyl peptides, fractalkine, and monocyte chemotactic protein-1. 
     
     
         35 . The composition of  claim 24 , wherein the recruitment composition comprises GM-CSF. 
     
     
         36 . The composition of  claim 24 , further comprising a non-inflammatory polymer. 
     
     
         37 . The composition of  claim 36 , wherein the non-inflammatory polymer is selected from the group consisting of alginate, poly(ethylene glycol), hyaluronic acid, collagen, gelatin, poly (vinyl alcohol), fibrin, poly (glutamic acid), peptide amphiphiles, silk, fibronectin, chitin, poly(methyl methacrylate), poly(ethylene terephthalate), poly(dimethylsiloxane), poly(tetrafluoroethylene), polyethylene, polyurethane, poly(glycolic acid), poly(lactic acid), poly(caprolactone), poly(lactide-co-glycolide), polydioxanone, polyglyconate, BAK, poly(ortho ester I), poly(ortho ester) II, poly(ortho ester) III, poly(ortho ester) IV, polypropylene fumarate, poly[(carboxy phenoxy)propane-sebacic acid], poly[pyromellitylimidoalanine-co-1,6-bis(p-carboxy phenoxy)hexane], polyphosphazene, starch, cellulose, albumin, and polyhydroxyalkanoates. 
     
     
         38 . The composition of  claim 24 , comprising a hydrogel. 
     
     
         39 . The composition of  claim 38 , wherein the hydrogel comprises an alginate gel polymer. 
     
     
         40 . The composition of  claim 39 , wherein the hydrogel comprises 1-5% alginate gel polymer. 
     
     
         41 . The composition of  claim 24 , wherein the tolerogen is encapsulated in poly(lactide-co-glycolide) (PLGA) microspheres. 
     
     
         42 . A method of reducing the severity of an autoimmune disorder, comprising administering to a subject a scaffold composition comprising:
 an antigen;   a recruitment composition;   and a tolerogen;   thereby reducing the severity of the autoimmune disorder.   
     
     
         43 . The method of  claim 42 , wherein the antigen is derived from a cell to which a pathologic autoimmune response associated with an autoimmune disorder is directed. 
     
     
         44 . The method of  claim 42 , wherein the tolerogen induces immune tolerance or a reduction in an immune response. 
     
     
         45 . The method of  claim 42 , wherein the autoimmune disorder is type 1 diabetes and the antigen comprises a pancreatic cell antigen. 
     
     
         46 . The method of  claim 42 , wherein the autoimmune disorder is multiple sclerosis and the antigen is selected from the group consisting of myelin basic protein myelin basic protein, myelin proteolipid protein, myelin-associated oligodendrocyte basic protein, or myelin oligodendrocyte glycoprotein. 
     
     
         47 . The method of  claim 42 , wherein the autoimmune disorder is selected from the group consisting of Crohn's disease, rheumatoid arthritis, Systemic lupus erythematosus, Scleroderma, Alopecia areata, Antiphospholipid antibody syndrome, Autoimmune hepatitis, Celiac disease, Graves' disease, Guillain-Barre syndrome, Hashimoto's disease, Hemolytic anemia, Idiopathic thrombocytopenic purpura, inflammatory bowel disease, ulcerative colitis, inflammatory myopathies, Polymyositis, Myasthenia gravis, Primary biliary cirrhosis, Psoriasis, Sjögren's syndrome, Vitiligo, gout, celiac disease, atopic dermatitis, acne vulgaris, autoimmune hepatitis, and autoimmune pancreatitis.