Methods and Compositions for the Treatment of Immune Disorders

Abstract

The present invention provides a method of treating an immune-related disorder in a subject, comprising administering to the subject an effective amount of an inhibitor of plexin-A4 activity, which results in reducing the plexin-A4 activity in the subject, and thereby treating the immune-related disorder. Inhibitors of plexin-A4 activity include, for example, plexin-A4 antibodies and plexin-A4 fusion proteins. The present invention further provides a method of treating an immune-related disorder in a subject, comprising administering to the subject an effective amount of an inhibitor of semaphorin-3A (Sema3A) activity, which results in reducing the Sema3A activity in the subject, thereby treating the immune-related disorder. Inhibitors of Sema3A activity include, for example, Sema3A antibodies and Sema3A fusion proteins.

1 . A method of treating an immune-related and/or inflammatory disorder in a subject, comprising administering to the subject an effective amount of an inhibitor of plexin-A4 activity, whereby the plexin-A4 activity in said subject is reduced, thereby treating the immune-related disorder and/or inflammatory disorder. 
     
     
         2 . A method of reducing cytokine production in a subject, comprising administering to the subject an effective amount of an inhibitor of plexin-A4 activity, thereby reducing the cytokine production the subject. 
     
     
         3 . The method of  claim 1 , wherein the inhibitor of plexin-A4 activity is selected from the group consisting of a plexin-A4 fusion protein, a plexin-A4 antibody or an active fragment thereof, or any combination thereof. 
     
     
         4 . The method of  claim 3 , wherein the plexin-A4 antibody or active fragment thereof is a monoclonal antibody or is derived from a monoclonal antibody. 
     
     
         5 . The method of  claim 3 , wherein the plexin-A4 fusion protein comprises the extracellular domain of plexin-A4 and the Fc region of IgG. 
     
     
         6 . The method of  claim 5 , wherein the extracellular domain of plexin-A4 and the IgG1 Fc region is human. 
     
     
         7 . The method of  claim 5 , wherein the extracellular domain of plexin-A4 comprises the amino acid sequence of SEQ ID NO:7 and the IgG Fc region comprises the amino acid sequence of SEQ ID NO:8. 
     
     
         8 . The method of  claim 3 , wherein the plexin-A4 fusion protein comprises the amino acid sequence of SEQ ID NO:6. 
     
     
         9 . The method of  claim 1 , wherein the immune-related and/or inflammatory disorder is selected from the group consisting of sepsis, arthritis, hepatitis, systemic lupus erythematosus (SLE), multiple sclerosis, Guillain-Barre syndrome, Alzheimer's disease, colitis, psoriasis, contact hypersensitivity, retinitis, uveitis, malignancies, systemic lupus erythematosis, asthma, myocarditis, hepatitis, kidney diseases, diabetes, obesity, cardiovascular diseases, and inflammatory bowel disease, or any combination thereof. 
     
     
         10 . The method of  claim 3 , wherein the inhibitor is administered subcutaneously, intramuscularly, intraperitoneally, topically, intravenously, and any combination thereof. 
     
     
         11 . (canceled) 
     
     
         12 . A method of treating an immune-related and/or inflammatory disorder in a subject, comprising administering to the subject an effective amount of an inhibitor of semaphorin-3A (Sema3A) activity, whereby the Sema3A activity in said subject is reduced, thereby treating the immune-related disorder and/or inflammatory disorder. 
     
     
         13 . A method of reducing cytokine production in a subject, comprising administering to the subject an effective amount of an inhibitor of Sema3A activity, thereby reducing the cytokine production the subject. 
     
     
         14 . The method of  claim 12 , wherein the inhibitor of Sema3A activity is selected from the group consisting of a Sema3A fusion protein, a Sema3A antibody or an active fragment thereof, or any combination thereof. 
     
     
         15 . The method of  claim 14 , wherein the plexin-A4 antibody or active fragment thereof is a monoclonal antibody or is derived from a monoclonal antibody. 
     
     
         16 . The method of  claim 14 , wherein the Sema3A fusion protein comprises the amino acid sequence encoding Sema3A and the Fe region of IgG. 
     
     
         17 . The method of  claim 16 , wherein the amino acid sequence encoding Sema3A and the IgG1 Fc region is human. 
     
     
         18 . The method of  claim 16 , wherein the amino acid sequence encoding Sema3A comprises the amino acid sequence of SEQ ID NO:13 and the IgG Fe region comprises the amino acid sequence of SEQ ID NO:8. 
     
     
         19 . The method of  claim 14 , wherein the Sema3A fusion protein comprises the amino acid sequence of SEQ ID NO:16. 
     
     
         20 . The method of  claim 12 , wherein the immune-related and/or inflammatory disorder is selected from the group consisting of sepsis, arthritis, hepatitis, systemic lupus erythematosus (SLE), multiple sclerosis, Guillain-Barre syndrome, Alzheimer's disease, colitis, psoriasis, contact hypersensitivity, retinitis, uveitis, malignancies, systemic lupus erythematosis, asthma, myocarditis, hepatitis, kidney diseases, diabetes, obesity, cardiovascular diseases, and inflammatory bowel disease, or any combination thereof. 
     
     
         21 . The method of  claim 14 , wherein the inhibitor is administered subcutaneously, intramuscularly, intraperitoneally, topically, intravenously, and any combination thereof. 
     
     
         22 . (canceled)