Treatment method

Abstract

A method is provided for reducing the occurrence of fever, headache, nausea and/or vomiting associated with administration of a therapeutic compound to a mammal in need thereof, comprising administering to the mammal a first conditioning dose of a non-target cell depleting compound which binds to a cell surface receptor on a target mammalian cell; and administering a second therapeutic dose of the compound, wherein the second dose is higher than the first dose.

1 . A method for reducing the occurrence of fever, headache, nausea and/or vomiting associated with administration of a therapeutic compound to a mammal in need thereof, comprising: 
 administering to the mammal a first conditioning dose of a non-target cell-depleting compound which binds to a cell surface receptor on a target mammalian cell; and    administering a second therapeutic dose of the compound, wherein the second dose is higher than the first dose.    
     
     
         2 . The method of  claim 1 , wherein the therapeutic compound comprises a polypeptide which binds to an extracellular domain of the receptor molecule.  
     
     
         3 . The method of  claim 2 , wherein the polypeptide is an antibody or a fragment thereof.  
     
     
         4 . The method of  claim 1 , wherein the target mammalian cell is a lymphocyte.  
     
     
         5 . The method of  claim 4 , wherein the lymphocyte is a T-cell.  
     
     
         6 . The method of  claim 5 , wherein the cell surface receptor on the T cell is LFA-1.  
     
     
         7 . The method of  claim 6 , wherein the therapeutic compound is anti-CD11a antibody hu1124.  
     
     
         8 . The method of  claim 1 , further comprising administering a third therapeutic dose, wherein the third dose is higher than the second dose.  
     
     
         9 . The method of  claim 1 , wherein administration is intravenous or subcutaneous.  
     
     
         10 . The method of  claim 1 , wherein administration is not more than once per week.  
     
     
         11 . A method for treating an LFA-1 mediated disorder, comprising 
 administering to a mammal in need thereof a first conditioning dose of a compound which binds to the lymphocyte surface receptor LFA-1; and    administering a second therapeutic dose of the compound, wherein the second dose is higher than the first dose.    
     
     
         12 . The method of  claim 11 , wherein the compound comprises a polypeptide which binds to an extracellular domain of the receptor molecule.  
     
     
         13 . The method of  claim 12 , wherein the polypeptide is an antibody or a fragment thereof.  
     
     
         14 . The method of  claim 13 , wherein the antibody or fragment thereof binds to CD11a.  
     
     
         15 . The method of  claim 14 , wherein the antibody is antibody hu1124.  
     
     
         16 . The method of any one of claims  11 - 15 , wherein the LFA-1 mediated disorder is selected from the group consisting of psoriasis, asthma, rheumatoid arthritis, multiple sclerosis, rejection of a transplanted graft or rejection by a transplanted graft.  
     
     
         17 . The method of  claim 16 , wherein the transplant is a renal transplant.  
     
     
         18 . The method of  claim 11 , further comprising administering a third therapeutic dose, wherein the third dose is higher than the second dose.  
     
     
         19 . The method of  claim 11 , further comprising administering a fourth therapeutic dose, wherein the fourth dose is higher than or equal to the third dose.  
     
     
         20 . The method of  claim 11 , wherein administration is intravenous or subcutaneous.  
     
     
         21 . The method of  claim 11 , wherein administration is not more than once per week.  
     
     
         22 . The method of  claim 11 , wherein the compound is non-lymphocyte depleting.  
     
     
         23 . A method for conditioning a mammal to tolerate high doses of a therapeutic compound, comprising 
 administering to the mammal a first conditioning dose of a non-target cell depleting compound which binds to a cell surface receptor on a target mammalian cell; and    administering a second therapeutic dose of the compound, wherein the second dose is higher than the first dose.    
     
     
         24 . A method for down modulating a cell surface receptor in a cell population in a mammal, comprising 
 contacting a target mammalian cell displaying a receptor molecule on the surface thereof with a first dose of a ligand which binds to the receptor molecule and does not deplete the target mammalian cell population; and then    further contacting the target mammalian cell population with a second dose of the ligand, wherein the second dose is higher than the first dose.    
     
     
         25 . The method of  claim 24 , wherein the ligand comprises a polypeptide which binds to an extracellular domain of the receptor molecule.  
     
     
         26 . The method of  claim 25 , wherein the polypeptide is an antibody or a fragment thereof.  
     
     
         27 . The method of any one of claims  24 - 26 , wherein the target mammalian cell is a lymphocyte.  
     
     
         28 . The method of  claim 27 , wherein the lymphocyte is a T-cell.  
     
     
         29 . The method of  claim 28 , wherein the cell surface receptor is CD11a and the ligand is antibody hu1124.  
     
     
         30 . The method of  claim 24 , further comprising contacting the mammalian cell population with a third dose of the ligand, wherein the third dose is higher than the second dose.  
     
     
         31 . The method of  claim 24 , wherein the contacting is by administration to a mammal.  
     
     
         32 . The method of  claim 31 , wherein administration is not more than once per week.