Co-administration of a thrombolytic and an anti-CD18 antibody in stroke

Abstract

A method for improving clinical outcome in focal ischemic stroke in a mammal by increasing cerebral blood flow and/or reducing infarct size is described which involves administering an effective amount of an anti-CD18 antibody to the mammal, in the absence of removal of the arterial obstruction.

1 . A method for increasing cerebral blood flow and/or reducing infarct size in focal ischemic stroke caused by obstruction of a main cerebral artery in a human mammal which comprises the step of co-administering effective amounts of tissue plasminogen activator (tPA) and anti-CD18 antibody to the mammal wherein neither the tPA nor the anti-CD18 antibody is administered to the mammal until about three to five hours after the onset of focal ischemic stroke.  
     
     
         2 . The method of  claim 1  that increases cerebral blood flow and reduces infarct size in the mammal.  
     
     
         3 . The method of  claim 1  wherein the anti-CD18 antibody is an antibody fragment.  
     
     
         4 . The method of  claim 3  wherein the anti-CD18 antibody fragment is a F(ab′) 2 .  
     
     
         5 . The method of  claim 1  wherein the anti-CD18 antibody is humanized.  
     
     
         6 . The method of  claim 1  wherein the anti-CD18 antibody is administered to the mammal by bolus dosage.  
     
     
         7 . The method of  claim 1  wherein the anti-CD18 antibody is administered inravenously.  
     
     
         8 . The method of  claim 1  wherein the anti-CD18 antibody is administered via continuous infusion.  
     
     
         9 . The method of  claim 1  wherein the anti-CD18 antibody and the tPA are simultaneously administered to the mammal.  
     
     
         10 . The method of  claim 1  wherein the anti-CD18 antibody is administered before the tPA is administered to the mammal.  
     
     
         11 . The method of  claim 1  wherein the anti-CD18 antibody is humanized H52 antibody comprising heavy chain sequence of SEQ ID NO:10 and light chain sequence of SEQ ID NO:11.  
     
     
         12 . The method of  claim 11  wherein the H52 antibody is a F(ab′) 2 .  
     
     
         13 . The method of  claim 1 , wherein the anti-CD18 antibody binds to an extracellular domain of CD18 and inhibits or reduces the ability of a cell expressing CD18 to bind to endothelium.  
     
     
         14 . The method of  claim 1 , wherein the anti-CD18 antibody binds CD18 with an affinity of 4 nm or less.  
     
     
         15 . The method of  claim 1 , wherein the anti-CD18 antibody binds CD18 with an affinity of 3 nm or less.  
     
     
         16 . The method of  claim 1 , wherein the anti-CD18 antibody binds CD18 with an affinity of 1 nm or less.  
     
     
         17 . The method of  claim 1 , wherein the anti-CD18 antibody dissociates the CD11b/CD18 complex.  
     
     
         18 . The method of  claim 1 , wherein the anti-CD18 antibody binds to the epitope bound by H52 antibody.