Combination therapy using antibody to human siglec-9 and antibody to human nkg2a for treating cancer

Abstract

This invention relates to agents that bind human Siglecs having inhibitory activity in immune cells, and that neutralize the inhibitory activity of such Siglec. Such agents can be used for the treatment of cancers.

We claim: 
     
         1 . A pharmaceutical composition comprising an antibody that neutralizes the inhibitory activity of NKG2A, and an antibody that neutralizes the inhibitory activity of Siglec-9, and a pharmaceutically acceptable carrier. 
     
     
         2 . The composition according to  claim 1 , wherein the antibody that binds to Siglec-9 is selected from the group consisting of:
 (a) a monoclonal antibody comprising (i) a heavy chain comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO: 15 and (ii) a light chain comprising CDR 1, 2 and 3 of the light chain variable region of SEQ ID NO: 16;   (b) a monoclonal antibody comprising (i) a heavy chain comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO: 17 and (ii) a light chain comprising CDR 1, 2 and 3 of the light chain variable region of SEQ ID NO: 18;   (c) a monoclonal antibody comprising (i) a heavy chain comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO: 19 and (ii) a light chain comprising CDR 1, 2 and 3 of the light chain variable region of SEQ ID NO: 20;   (d) a monoclonal antibody comprising (i) a heavy chain comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO: 21 and (ii) a light chain comprising CDR 1, 2 and 3 of the light chain variable region of SEQ ID NO: 22;   (e) a monoclonal antibody comprising (i) a heavy chain comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO: 23 and (ii) a light chain comprising CDR 1, 2 and 3 of the light chain variable region of SEQ ID NO: 24; and   (f) a monoclonal antibody comprising (i) a heavy chain comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO: 25 and (ii) a light chain comprising CDR 1, 2 and 3 of the light chain variable region of SEQ ID NO: 26.   
     
     
         3 . The composition according to  claim 1 , wherein the antibody that binds to Siglec-9 is selected from the group consisting of:
 (a) a monoclonal antibody comprising (i) a heavy chain comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO: 3 and (ii) a light chain comprising CDR 1, 2 and 3 of the light chain variable region of SEQ ID NO: 4;   (b) a monoclonal antibody comprising (i) a heavy chain comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO: 5 and (ii) a light chain comprising CDR 1, 2 and 3 of the light chain variable region of SEQ ID NO: 6;   (c) a monoclonal antibody comprising (i) a heavy chain comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO: 7 and (ii) a light chain comprising CDR 1, 2 and 3 of the light chain variable region of SEQ ID NO: 8;   (d) a monoclonal antibody comprising (i) a heavy chain comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO: 9 and (ii) a light chain comprising CDR 1, 2 and 3 of the light chain variable region of SEQ ID NO: 10;   (e) a monoclonal antibody comprising (i) a heavy chain comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO: 11 and (ii) a light chain comprising CDR 1, 2 and 3 of the light chain variable region of SEQ ID NO: 12; and   (f) a monoclonal antibody comprising (i) a heavy chain comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO: 13 and (ii) a light chain comprising CDR 1, 2 and 3 of the light chain variable region of SEQ ID NO: 14.   
     
     
         4 . A kit comprising: (a) a dose of an agent, optionally an antibody, that neutralizes the inhibitory activity of NKG2A, and (b) a dose of an agent, optionally an antibody, that neutralizes the inhibitory activity of Siglec-9. 
     
     
         5 . A method for modulating NKG2A+ Siglec+ lymphocytes, optionally NK cells, optionally CD8+ T cells, in an individual, the method comprising administering to said individual an effective amount of a composition according to  claim 1 . 
     
     
         6 . An in vitro method for modulating the activity of NKG2A+ Siglec+ lymphocytes, optionally NK cells, optionally CD8+ T cells, comprising bringing lymphocytes expressing at their surface NKG2A and Siglec-9 into contact with an antibody that neutralizes the inhibitory activity of NKG2A and an antibody that neutralizes the inhibitory activity of Siglec-9. 
     
     
         7 . A method of treating cancer comprising:
 a) determining the HLA-E polypeptide status of malignant cells within the individual having a cancer, and   b) upon a determination that HLA-E polypeptides are expressed by said malignant cells, administering to the individual a pharmaceutical composition according to  claim 1 .   
     
     
         8 . A method of treating cancer comprising administering a pharmaceutical composition according to  claim 1  to an individual having cancer. 
     
     
         9 . The method according to  claim 8 , wherein the cancer is a solid tumor. 
     
     
         10 . The method according to  claim 8 , wherein the cancer is hematological tumor. 
     
     
         11 . The method according to  claim 8 , wherein the cancer is characterized by malignant cells bearing at their surface sialic acid ligands of Siglec-7 and/or Siglec-9.