Human cdr-grafted antibody and antibody fragment thereof

Abstract

A human CDR-grafted antibody or the antibody fragment thereof which specifically reacts with the extracellular region of human CC chemokine receptor 4 (CCR4) but does not react with a human blood platelet; a human CDR-grafted antibody or the antibody fragment thereof which specifically reacts with the extracellular region of CCR4 and has a cytotoxic activity against a CCR4-expressing cell; and a medicament, a therapeutic agent or a diagnostic agent comprising at least one of the antibodies and the antibody fragments thereof as an active ingredient.

1 . A method for reducing or depleting a cell expressing human CC chemokine receptor 4 (CCR4) on its cell surface, comprising administering to the cell a human CDR-grafted antibody or antibody fragment thereof which reacts with an extracellular region of human CCR4 but does not specifically react with a human platelet, wherein said extracellular region is an epitope present in SEQ ID NO: 37, and wherein the human CDR-grafted antibody, or antibody fragment thereof, comprises an antibody heavy chain variable region comprising the amino acid sequence of SEQ ID NO:4, 9, 10, 11, 38, 39, 40 or 41, and an antibody light chain variable region comprising the amino acid sequence of SEQ ID NO:8, 12, 13 or 14. 
     
     
         2 . A method for inhibiting cytokine production of a Th2 cell, comprising administering to the cell a human CDR-grafted antibody or antibody fragment thereof which reacts with an extracellular region of human CC chemokine receptor 4 (CCR4) but does not specifically react with a human platelet, wherein said extracellular region is an epitope present in SEQ ID NO: 37, and wherein the human CDR-grafted antibody, or antibody fragment thereof, comprises an antibody heavy chain variable region comprising the amino acid sequence of SEQ ID NO:4, 9, 10, 11, 38, 39, 40 or 41, and an antibody light chain variable region comprising the amino acid sequence of SEQ ID NO:8, 12, 13 or 14. 
     
     
         3 . The method of  claim 1  or  claim 2 , wherein the antibody heavy chain variable region comprises the amino acid sequence of SEQ ID NO:9 or 10; and the antibody light chain variable region comprises the amino acid sequence of SEQ ID NO: 12 or 14. 
     
     
         4 . The method of  claim 3 , wherein the antibody heavy chain variable region comprises the amino acid sequence of SEQ ID NO:9; and the antibody light chain variable region comprises the amino acid sequence of SEQ ID NO: 14. 
     
     
         5 . The method of  claim 1  or  claim 2 , wherein the human CDR-grafted antibody or antibody fragment thereof, is produced by a transformant KM8759 (FERM BP-8129) or KM8760 (FERM BP-8130).