Anti-bst2 antibody

Abstract

BST2 antibodies were selected by using as an indicator the binding between BST2 antibodies and various splicing variants of human BST2 antigen. As a result, the present inventors successfully obtained BST2 antibodies that specifically recognize BST2D, which has been reported to be expressed at high levels in cancer cells. The antibodies of the present invention specifically bind to cells expressing BST2D. Non-specific antibody binding to non-target tissues, which results in the decrease of antibody concentration in blood, can be prevented by using the antibodies of the present invention therapeutically. Alternatively, the present invention provides diagnostic agents comprising an antibody of the present invention, which specifically detect tissues expressing BST2D.

1 - 32 . (canceled) 
     
     
         33 . A method for treating a tumor expressing human BST2D antigen in a subject, comprising administering to the subject an anti-human BST2 antibody that binds to human BST2D antigen but does not bind substantially to human BST2H antigen, or a fragment comprising the antigen-binding domain thereof, wherein the antibody recognizes the amino acid sequence of SEQ ID NO: 37 as an epitope. 
     
     
         34 . (canceled) 
     
     
         35 . The method of  claim 33 , wherein the tumor is derived from a cell of bone marrow. 
     
     
         36 . The method of  claim 35 , wherein the tumor is myeloma. 
     
     
         37 . The method of  claim 36 , wherein the myeloma is multiple myeloma. 
     
     
         38 . The method of  claim 33 , wherein the antibody is a monoclonal antibody. 
     
     
         39 . The method of  claim 33 , wherein the heavy-chain and light-chain variable regions of the antibody comprise as CDR1, CDR2, and CDR3 the following amino acid sequences: 
       
         
           
                 
                 
               
                     
                   heavy-chain variable region CDR1: 
                 
                     
                   (SEQ ID NO: 4) 
                 
                     
                   SGYYWN; 
                 
                     
                     
                 
                     
                   heavy-chain variable region CDR2: 
                 
                     
                   (SEQ ID NO: 5) 
                 
                     
                   YISYDGSNNYNPSLKNR; 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   heavy-chain variable region CDR3: 
                 
                     
                   (SEQ ID NO: 6) 
                 
                     
                   ILGRGY; 
                 
                     
                     
                 
                     
                   light-chain variable region CDR1: 
                 
                     
                   (SEQ ID NO: 7) 
                 
                     
                   RASQSVSTSSYSYMH; 
                 
                     
                     
                 
                     
                   light-chain variable region CDR2: 
                 
                     
                   (SEQ ID NO: 8) 
                 
                     
                   YASNLES; 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   light-chain variable region CDR3: 
                 
                     
                   (SEQ ID NO: 9) 
                 
                     
                   QHSWEIPYT; 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         or a fragment comprising the antigen-binding domain thereof. 
       
     
     
         40 . The method of  claim 33 , wherein the antibody comprises the heavy-chain variable region of SEQ ID NO: 11 and the light-chain variable region of SEQ ID NO: 13. 
     
     
         41 . The method of  claim 33 , wherein the antibody has CDC against a cell expressing human BST2D antigen on the cell surface. 
     
     
         42 . The method of  claim 33 , wherein the antibody ADCC against a cell expressing human BST2D antigen on the cell surface. 
     
     
         43 . A method for treating a tumor expressing human BST2D antigen in a subject, comprising administering to the subject a monoclonal antibody produced by hybridoma BST2#4LD deposited under the accession number FERM BP-10964, or a fragment comprising the antigen-binding domain thereof. 
     
     
         44 . A method for treating a tumor expressing human BST2D antigen in a subject, comprising administering to the subject an antibody with a substitution of one amino acid in the antibody of (A) or (B) below, which has an activity equivalent to that of the antibody of (A) or (B) below:
 (A) an antibody whose heavy-chain and light-chain variable regions comprise as CDR1, CDR2, and CDR3 the following amino acid sequences:   
       
         
           
                 
                 
               
                     
                   heavy-chain variable region CDR1: 
                 
                     
                   (SEQ ID NO: 4) 
                 
                     
                   SGYYWN; 
                 
                     
                     
                 
                     
                   heavy-chain variable region CDR2: 
                 
                     
                   (SEQ ID NO: 5) 
                 
                     
                   YISYDGSNNYNPSLKNR; 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   heavy-chain variable region CDR3: 
                 
                     
                   (SEQ ID NO: 6) 
                 
                     
                   ILGRGY; 
                 
                     
                     
                 
                     
                   light-chain variable region CDR1: 
                 
                     
                   (SEQ ID NO: 7) 
                 
                     
                   RASQSVSTSSYSYMH; 
                 
                     
                     
                 
                     
                   light-chain variable region CDR2: 
                 
                     
                   (SEQ ID NO: 8) 
                 
                     
                   YASNLES; 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   light-chain variable region CDR3: 
                 
                     
                   (SEQ ID NO: 9) 
                 
                     
                   QHSWEIPYT; 
                 
                     
                   or 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         (B) an antibody which comprises the heavy-chain variable region of SEQ ID NO: 11 and the light-chain variable region of SEQ ID NO: 13, 
         or a fragment comprising the antigen-binding domain thereof.