Monoclonal antibodies against nkg2a

Abstract

The present invention relates to methods of treating immune disorders, particularly autoimmune or inflammatory disorders, and methods of producing antibodies and other compounds for use in therapeutic strategies for treating such disorders. Generally, the present methods involve the use of antibodies or other compounds that prevent the stimulation of NKG2A receptors on NK cells, leading to the lysis of dendritic cells that contribute to the pathology of the disorders.

We claim: 
     
         1 . A monoclonal antibody or a fragment thereof characterized by:
 a) specifically binding to NKG2A and not specifically binding to NKG2C or NKG2E;   b) a human constant region that does not substantially bind human FcγIIIa receptor (CD16); and   c) when bound to NKG2A on a human NK cell, causing said NK cell to lyse a target human cell bearing HLA-E on the target cell surface, when said target cell comes into contact with said NK cell.   
     
     
         2 . A composition comprising:
 a) an effective amount of a monoclonal antibody or a fragment thereof according to  claim 1 ; and   b) a pharmaceutically acceptable carrier or excipient.   
     
     
         3 . A method of reconstituting NK cell-mediated lysis of a target cell in a population comprising a NK cell and said target cell, wherein said NK cell is characterized by NKG2A on its surface, and said target cell is characterized by the presence of HLA-E on its surface, said method comprising the step of contacting said NK cell with a monoclonal antibody or a fragment thereof according to  claim 1 . 
     
     
         4 . The method according to  claim 3 , wherein said NK cell is a human cell and said target cell is a human cell selected from a dendritic cell, a cancer cell, a virally infected cell. 
     
     
         5 . A method of treating a cancer in a patient, wherein said cancer is characterized by the presence of a cancer cell expressing HLA-E on its cell surface, said method comprising the step of administering to said patient a composition according to  claim 2 . 
     
     
         6 . The method according to  claim 5 , comprising the additional step of administering to said patient a second therapeutic agent selected from: an anticancer agent or an antiemetic, wherein said second therapeutic agent is administered either as a separate dosage form or as part of said composition. 
     
     
         7 . The method according to  claim 5 , wherein the cancer is a cancer of the bladder, breast, colon, kidney, liver, lung, ovary, prostate, pancreas, stomach, cervix, thyroid and skin, including squamous cell carcinoma. 
     
     
         8 . The method according to  claim 5 , wherein the cancer is a hematopoietic tumor of lymphoid lineage. 
     
     
         9 . A method of treating a viral disease in a patient, wherein said viral disease is characterized by the presence of a virally-infected cell expressing HLA-E on its cell surface, said method comprising the step of administering to said patient a composition according to  claim 2 . 
     
     
         10 . The method according to  claim 9 , comprising the addition step of administering to said patient an antiviral agent, wherein said antiviral agent is administered either as a separate dosage form or as part of said composition. 
     
     
         11 . A method of improving the engraftment of hematopoietic cells in a patient, said method comprising the step of administering to said patient a composition according to  claim 2 . 
     
     
         12 . The method according to  claim 11 , comprising the additional step of administering to said patient a second therapeutic agent selected from an anticancer agent, or a hematopoietic growth factor, wherein said second therapeutic agent is administered either as a separate dosage form or as part of said composition. 
     
     
         13 . The method according to  claim 11 , wherein said patient is suffering from leukemia.