Compositions and methods for modulating immune responses
This invention discloses methods and compositions for modulating immune responses, which involve particulate delivery of agents to immune cells, wherein the agents comprise an inhibitor of the NF-κB signaling pathway and an antigen that corresponds to a target antigen. The methods and compositions of the present invention are particularly useful in the treatment or prophylaxis of an undesirable immune response associated with the target antigen, including autoimmune diseases, allergies and transplantation associated diseases.
1. A method for eliciting a tolerogenic immune response to a target antigen in a subject, comprising administering to the subject an NF-κB inhibitor and an antigen that corresponds to at least a portion of the target antigen, wherein the inhibitor and the antigen are contained in at least one particle capable of being taken up by an immune cell and wherein the at least one particle is a liposome or a polymeric microsphere.
2. A method according to claim 1 , wherein the particle is a liposome.
3. A method according to claim 1 , wherein the particle is a polymeric microsphere and comprises a poly(lactide-co-glycolide).
4. A method according to claim 1 , wherein the antigen is selected from allergens, autoantigens and alloantigens.
5. A method according to claim 1 , wherein the antigen is a proteinaceous antigen.
6. A method according to claim 4 , wherein the autoantigen is selected from the group consisting of lupus autoantigen, Smith, Ro, La, U1-RNP, fibrillin; nuclear antigens, histones, glycoprotein gp70 and ribosomal proteins; pyruvate dehydrogenase dehydrolipoamide acetyltransferase (PCD-E2); hair follicle antigens; human tropomyosin isoform 5 (hTM5); proinsulin, insulin, IA2 and GAD65; collagen type II, human cartilage gp 39 (HCgp39) and gp130-RAPS, dnaJp1, citrullinated proteins and peptides, citrullinated type II collagen, citrullinated vimentin and citrullinated fibrinogen; myelin basic protein, proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG); thyroid stimulating factor receptor (TSH-R); acetylcholine receptor (AchR); gliadin; histones, PLP, glucose-6-phosphate isomerase, thyroglobulin, tRNA synthetases, proteinase-3 and myeloperoxidase.
7. A method according to claim 1 , wherein the antigen is in a non-nucleic acid form.
8. A method according to claim 1 , wherein the NF-κB inhibitor decreases the level or functional activity of RelB.
9. A method according to claim 8 , wherein the NF-κB inhibitor is selected from quecertin, curcumin and Bay 11-7082.
10. A method according to claim 1 , wherein the NF-κB inhibitor is in a non-nucleic acid form.
11. A method according to claim 1 , wherein the composition is administered subcutaneously.