Immunosuppressive composition for use in treating immunological disorders

Abstract

The present disclosure describes a pharmaceutical composition comprising at least one antibody and at least one mesenchymal stromal cell-derived protein. Disclosed herein is also the use of said pharmaceutical composition for treating immunological diseases, for example alloimmune and autoimmune diseases. Further disclosed herein is the use of the pharmaceutical composition for immunomodulation.

1 . (canceled) 
     
     
         2 . (canceled) 
     
     
         3 . (canceled) 
     
     
         4 . (canceled) 
     
     
         5 . (canceled) 
     
     
         6 . (canceled) 
     
     
         7 . (canceled) 
     
     
         8 . A method of treating an immunological disorder, the method comprising administration of a pharmaceutical composition comprising at least one antibody and/or at least one mesenchymal stromal cell-derived protein,
 wherein the antibody targets one or more of the cytokines selected from the group consisting of macrophage colony-stimulating factor (M-CSF), Interleukin-1beta (IL-1β), CCL-1 (I-309) and CCL24 (Eotaxin-2);   wherein the mesenchymal stromal cell-derived protein is selected from the group consisting of PGE2 (prostaglandin E2), OPG, CCL7 (MCP-2), CCL8 (MCP-3), CCL20 (MIP-3α), CXCL5 (ENA-78), IL-10 and CXCL6 (GCP-2).   
     
     
         9 . (canceled) 
     
     
         10 . The method of  claim 8 , wherein the pharmaceutical composition is as shown in the table below: 
       
         
           
                 
                 
               
                   Composition 
                     
                 
                   C2a 
                   CXCL5; anti-CCL1; anti-IL1b; anti-M-CSF; anti-CCL24 
                 
                   C3a 
                   CCL8; CCL7; OPG; IL-10; anti-CCL24 
                 
                   C4a 
                   CCL8; CCL7; OPG; IL-10; CXCL5;anti-CCL1; anti-lL1b; anti-M-CSF 
                 
                   C5a 
                   CCL20; CXCL6; OPG; IL-10; anti-IL1b; anti-M-CSF 
                 
                   C6a 
                   CCL20; CXCL6; OPG; IL-10; CXCL5; anti-CCL1; anti-CCL24 
                 
                   C7a 
                   CCL20; CXCL6; CCL8; CCL7; anti-IL1b; anti-M-CSF; anti-CCL24 
                 
                   C8a 
                   CCL20; CXCL6; CCL8; CCL7; CXCL5; anti-CCL1 
                 
                   C9a 
                   PGE2; CXCL6; CCL7; IL-10; anti-CCL1; anti-M-CSF 
                 
                   C10a 
                   PGE2; CXCL6; CCL7; IL-10; CXCL5; anti-IL1b; anti-CCL24 
                 
                   C11a 
                   PGE2; CXCL6; CCL8; OPG; anti-CCL1; anti-M-CSF; anti-CCL24 
                 
                   C12a 
                   PGE2; CXCL6; CCL8; OPG; CXCL5; anti-IL1b 
                 
                   C13a 
                   PGE2; CCL20; CCL7; OPG; anti-CCL1; anti-IL1b 
                 
                   C14a 
                   PGE2; CCL20; CCL7; OPG; CXCL5; anti-M-CSF; anti-CCL24 
                 
                   C15a 
                   PGE2; CCL20; CCL8; IL-10; anti-CCL1; anti-IL1b; anti-CCL24 
                 
                   C16a 
                   PGE2; CCL20; CCL8; IL-10; CXCL5; anti-M-CSF 
                 
                   C17a 
                   CXCL5; CXCL6; anti-CCL1; CCL20 
                 
                   C18a 
                   IL-10; OPG; anti-CCL1; CCL20 
                 
                   C19a 
                   IL-10; OPG; CXCL5; CXCL6 
                 
                   C20a 
                   anti-CCL24; OPG; CXCL6; CCL20 
                 
                   C21a 
                   anti-CCL24; OPG; CXCL5; anti-CCL1 
                 
                   C22a 
                   anti-CCL24; IL-10; CXCL6; anti-CCL1 
                 
                   C23a 
                   anti-CCL24; IL-10; CXCL5; CCL20 
                 
                   C24a 
                   anti-CCL1 
                 
                   C25a 
                   anti-CCL24 
                 
                   C26a 
                   OPG 
                 
                   C27a 
                   CXCL5 
                 
                   C28a 
                   anti-CCL1; anti-CCL24 
                 
                   C29a 
                   anti-CCL1; OPG 
                 
                   C30a 
                   anti-CCL1; CXCL5 
                 
                   C31a 
                   anti-CCL24; OPG 
                 
                   C32a 
                   anti-CCL24; CXCL5 
                 
                   C33a 
                   OPG; CXCL5 
                 
                   C34a 
                   anti-CCL1; anti-CCL24; OPG 
                 
                   C35a 
                   anti-CCL1; anti-CCL24; CXCL5 
                 
                   C36a 
                   anti-CCL1; OPG; CXCL5 
                 
                   C37a 
                   anti-CCL24; OPG; CXCL5 
                 
                   C38a 
                   anti-CCL1; anti-CCL24; OPG; CXCL5 
                 
             
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
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         11 . The method of  claim 8 , wherein the pharmaceutical composition comprises CXCL5 and an anti-CCL24 antibody (C32a). 
     
     
         12 . The method of  claim 8 , wherein the immunological disorder is an alloimmune disease or an autoimmune disease. 
     
     
         13 . The method of  claim 12 , wherein the alloimmune disease is selected from the group consisting of graft versus host disease (GVHD) after allogeneic hematopoietic cell transplantations, alloimmune disease resulting from skin transplant, alloimmune disease resulting from kidney transplant, alloimmune disease resulting from liver transplant, and hemolytic disease of the foetus and newborn. 
     
     
         14 . The method of  claim 12 , wherein the autoimmune disease is selected from the group consisting of systemic lupus erythematosus (SLE), lupus nephritis, type-I diabetes mellitus, systemic sclerosis, inflammatory bowel disease (IBD) and Crohn’s disease. 
     
     
         15 . The method of  claim 8 , wherein the pharmaceutical composition results in a decrease in the concentration of one or more of the circulating pro-inflammatory cytokines selected from the group consisting of IFN-y, IL-6, IL-17A, IL-8, MIP-1β and MCP-1 in the subject. 
     
     
         16 . The method of  claim 8 , wherein the pharmaceutical composition results an increase or a decrease in the concentration of at least one mesenchymal stromal cell-derived protein in a subject results in an immunosuppressive effect, wherein the mesenchymal stromal cell-derived protein is selected from the group consisting of PGE2 (prostaglandin E2), OPG, CCL7, CCL8, IL-10, CCL20, CXCL5, CXCL6, M-CSF, IL-1β, CCL-1 and CCL24. 
     
     
         17 . (canceled) 
     
     
         18 . The method of  claim 8 , wherein the wherein the antibody is present in a concentration of about 0.05 µg/ml to about 5 µg/ml. 
     
     
         19 . The method of  claim 18 , wherein the antibody is present in a concentration of about 1 µg/ml or about 2 µg/ml. 
     
     
         20 . The method of  claim 8 , wherein the mesenchymal stromal cell-derived protein is present in a concentration of about 0.5 ng/ml to about 75 ng/ml. 
     
     
         21 . The method of  claim 20 , wherein the mesenchymal stromal cell-derived protein is present in a concentration of about 10 ng/ml or 50 ng/ml.