Cytokines and neuroantigens for treatment of immune disorders
The present invention provides methods of regulating an immunological disorder comprising administering to a subject an effective amount of (i) an autoimmune antigen in conjunction with (ii) an anti-inflammatory cytokine. Compositions including the same are also provided.
1. A method of treating multiple sclerosis in a subject comprising administering to the subject an effective amount of a composition comprising:
(a) at least one fusion protein comprising, from N-terminal to C-terminal, (i) a cytokine, wherein the cytokine is interferon-β (IFN-β); (ii) optionally an enterokinase linking moiety, wherein the enterokinase linking moiety is (1) an amino acid sequence of SEQ ID NO:1, (2) an amino acid sequence having at least 80% identity or homology with the amino acid sequence of SEQ ID NO:1, (3) an amino acid sequence encoded by a nucleic acid sequence encoding an enterokinase recognition site, or (4) an amino acid sequence encoded by a nucleic acid sequence that hybridizes with the complement of the nucleic acid sequence of (3) under stringent conditions as represented by hybridization conditions of 0.5M NaHPO 4 , 7% sodium dodecyl sulfate (SDS), 1 mM EDTA at 65° C. and wash conditions of 0.1×SSC/0.1% SDS at 68° C.; and (iii) an autoimmune antigen, or portion thereof, wherein the autoimmune antigen is myelin basic protein (MBP);
(b) a cytokine, wherein the cytokine is IFN-β; and
(c) a pharmaceutically acceptable carrier, excipient or diluent.
2. The method of claim 1 , wherein the composition is administered parenterally.
3. The method of claim 1 , wherein the subject is a human subject.
4. The method of claim 1 , wherein the portion of the autoimmune antigen in the composition is an encephalitogenic determinant portion of MBP, wherein the encephalitogenic determinant portion of MBP is (1) an amino acid sequence of SEQ ID NO:2, an amino acid sequence of at least 80% identity with the amino acid sequence of SEQ ID NO:2, (3) an amino acid sequence encoded by a nucleic acid sequence encoding the encephalitogenic determinant portion of MBP, or (4) an amino acid sequence encoded by a nucleic acid sequence that hybridizes with the complement of the nucleic acid sequence of (3) under stringent conditions as represented by hybridization conditions of 0.5M NaHPO 4 , 7% sodium dodecyl sulfate (SDS), 1 mM EDTA at 65° C. and wash conditions of 0.1×SSC/0.1% SDS at 68° C.