Dna encoding an anti-system asc amino acid transporter 2 (asct2) antibody

Abstract

An object of the present invention is to provide a monoclonal antibody which is useful for treating or diagnosing a disease relating to system ASC amino acid transporter 2 (hereinafter, referred to as “ASCT2”) or a method using the antibody. The present invention provides a monoclonal antibody which specifically recognizes a native three-dimensional structure of an extracellular region of ASCT2 and binds to the extracellular region, or an antibody fragment thereof; a hybridoma which produces the antibody; a DNA which encodes the antibody; a vector which contains the DNA; a transformant obtainable by introducing the vector; a process for producing an antibody or an antibody fragment thereof using the hybridoma or the transformant; and a therapeutic agent using the antibody or the antibody fragment thereof, and a diagnostic agent using the antibody or the antibody fragment thereof.

1 - 28 . (canceled) 
     
     
         29 . A process for producing a monoclonal antibody or an antigen-binding fragment thereof, comprising:
 (a) culturing a transformant in a medium to form and accumulate the monoclonal antibody or the antigen-binding fragment thereof in the culture; and   (b) collecting the monoclonal antibody or the antigen-binding fragment thereof from the culture,   wherein said transformant comprises a recombinant vector which comprises a DNA sequence encoding the monoclonal antibody or the antigen-binding fragment thereof, and wherein the monoclonal antibody or the antigen-binding fragment thereof specifically binds to a native three-dimensional structure of an extracellular region of human system ASC amino acid transporter 2 (ASCT2), and does not bind to mouse ASCT2.   
     
     
         30 . The process of  claim 29 , wherein the monoclonal antibody or the antigen-binding fragment thereof binds to at least the EL2 region of human ASCT2. 
     
     
         31 . The process of  claim 29 , wherein the monoclonal antibody or the antigen-binding fragment thereof comprises complementarity determining regions (CDRs) of a heavy chain variable region (VH) and a light chain variable region (VL), and wherein (A) CDR1, CDR2 and CDR3 of VH of the antibody comprise the amino acid sequences of SEQ ID NOs: 26, 27 and 28, respectively, and CDR1, CDR2 and CDR3 of VL of the antibody comprise the amino acid sequences of SEQ ID NOs: 29, 30 and 31, respectively; (B) CDR1, CDR2 and CDR3 of VH of the antibody comprise the amino acid sequences of SEQ ID NOs: 32, 33 and 34, respectively, and CDR1, CDR2 and CDR3 of VL of the antibody comprise the amino acid sequences of SEQ ID NOs: 35, 36 and 37, respectively; or (C) CDR1, CDR2 and CDR3 of VH of the antibody comprise the amino acid sequences of SEQ ID NOs: 49, 50 and 51, respectively, and CDR1, CDR2 and CDR3 of VL of the antibody comprise the amino acid sequences of SEQ ID NOs: 52, 53 and 54, respectively. 
     
     
         32 . The process of  claim 29 , wherein the monoclonal antibody or the antigen-binding fragment thereof binds to at least one amino acid residue in SEQ ID NO: 2, wherein said at least one amino acid residue is at a position in SEQ ID NO: 2 selected from the group consisting of positions 154; 159 to 160; 163 to 171; 173 to 174; 177; 188; 204 to 205; 207; 210 to 212; and 214 to 223. 
     
     
         33 . The process of  claim 29 , wherein the monoclonal antibody or the antigen-binding fragment thereof is (A) a monoclonal antibody which binds to an epitope which is recognized by a monoclonal antibody produced from any one of hybridomas selected from a hybridoma KM4008 (FERM BP-10962) and a hybridoma KM4012 (FERM BP-10963); or (B) a monoclonal antibody produced from any one of hybridomas selected from a hybridoma KM4008 (FERM BP-10962) and a hybridoma KM4012 (FERM BP-10963). 
     
     
         34 . The process of  claim 29 , wherein the antigen-binding fragment is selected from the group consisting of a Fab, a Fab′, a F(ab′) 2 , a single chain antibody (scFv), a diabody, and a disulfide stabilized Fv region (dsFv). 
     
     
         35 . The process of  claim 29 , wherein the monoclonal antibody or the antigen-binding fragment thereof is a recombinant antibody or antigen-binding fragment thereof. 
     
     
         36 . The process of  claim 29 , wherein the recombinant antibody or the antigen-binding fragment thereof is a human chimeric antibody or human antibody, or an antigen-binding fragment thereof.