Methods and compositions for immunotherapy and detection of inflammatory and immune-dysregulatory disease, infectious disease, pathologic angiogenesis and cancer

Abstract

Methods and compositions for immunotherapy of inflammatory and immune-dysregulatory diseases are disclosed, using multispecific antagonists that target at least two different markers. The different targets are proinflammatory effectors of the innate immune system. The multispecific antagonists can be used to treat sepsis or septic shock.

1 - 18 . (canceled) 
     
     
         19 . A method of treating sepsis or septic shock, comprising administering to a patient that has been diagnosed with sepsis or septic shock a therapeutic composition comprising a therapeutically effective amount of a multispecific antagonist that reacts specifically with at least two different targets on a cell, wherein a first target is MIF and a second target is selected from the group consisting of a second proinflammatory effector cytokine, a proinflammatory effector chemokine, a proinflammatory effector receptor, a coagulation factor, a complement factor, or a complement regulatory protein. 
     
     
         20 . A method according to  claim 19 , wherein said multispecific antagonist is a combination of two separate antibodies. 
     
     
         21 . A method according to  claim 19 , wherein said multispecific antagonist is a multispecific antibody. 
     
     
         22 . A method according to  claim 19 , wherein said multispecific antagonist is a fusion protein. 
     
     
         23 . A method according to  claim 19 , wherein said multispecific antagonist comprises a therapeutic agent. 
     
     
         24 . A method according to  claim 19 , wherein said therapeutic composition additionally comprises a further therapeutic agent. 
     
     
         25 . A method according to  claim 19 , wherein said method of treating additionally comprises administration of activated protein C. 
     
     
         26 . A method according to  claim 19 , wherein said second target is a second proinflammatory effector cytokine. 
     
     
         27 . A method according to  claim 26 , wherein said second target is selected from the group consisting of HMGB-I, TNF-α, IL-1. and IL-6. 
     
     
         28 . A method according to  claim 19 , wherein said second target is a proinflammatory effector chemokine. 
     
     
         29 . A method according to  claim 28 , wherein said second target is selected from the group consisting of MCP-19, RANIES, MIP-1A, and MIP-1B. 
     
     
         30 . A method according to  claim 19 , wherein said second target is a proinflammatory effector receptor. 
     
     
         31 . A method according to  claim 30 , wherein said second target is selected from the group consisting of IL-6R IL-13R, and IL-15R. 
     
     
         32 . A method according to  claim 19 , wherein said second target is a coagulation factor. 
     
     
         33 . A method according to  claim 32 , wherein said second target is selected from the group consisting of TF and thrombin. 
     
     
         34 . A method according to  claim 19 , wherein said second target is a complement factor. 
     
     
         35 . A method according to  claim 34 , wherein said second target is selected from the group consisting of C3, C5, C3a, and C5a. 
     
     
         36 . A method according to  claim 19 , wherein said second target is a complement regulatory protein. 
     
     
         37 . A method according to  claim 36 , wherein said a second target is selected from the group consisting of CD46. CD55, CD59 and mCRP. 
     
     
         38 . A method according to  claim 24 , wherein the further therapeutic agent is an agent for treating an autoimmune disease. 
     
     
         39 . A method according to  claim 24 , wherein the further therapeutic agent is an immunomodulator. 
     
     
         40 . A method according to  claim 39 , wherein the immunomodulator is a cytokine, a stem cell growth factor, a lymphotoxin, a hematopoietic factor, a colony stimulating factor (CSF), an interferon (IFN), a stem cell growth factor, erythropoietin, or thrombopoietin. 
     
     
         41 . A method according to  claim 24 , wherein the further therapeutic agent is a drug or toxin. 
     
     
         42 . A method according to  claim 24 , wherein the further therapeutic agent is an RNase. 
     
     
         43 . A method according to  claim 24 , wherein the further therapeutic agent is an agent used in GVHD or organ transplantation.