Method for treating the Th2-mediated disease
View Patent ↗A recombinant antibody or the antibody fragment thereof which specifically reacts with an extracellular domain of human CCR4; a DNA which encodes the recombinant antibody or the antibody fragment thereof; a method for producing the recombinant antibody or the antibody fragment thereof; a method for immunologically detecting CCR4, a method for immunologically detecting a cell which expressed CCR4 on the cell surface, a method for depleting a cell which expresses CCR4 on the cell surface, and a method for inhibiting production of Th2 cytokine, which comprise using the recombinant antibody according or antibody fragment thereof; a therapeutic or diagnostic agent for Th2-mediated immune diseases; and a therapeutic or diagnostic agent for a blood cancer.
1. A method for treating asthma which comprises: administering to a patient in need thereof a therapeutically effective amount of a monoclonal antibody or an antibody fragment thereof that specifically binds to the epitope recognized by mouse antibody KM2160 produced by FERM BP-10090, wherein the antibody or antibody fragment exhibits antibody-dependent cell-mediated cytotoxic activity against a cell which expresses CCR4.
2. The method according to claim 1 , wherein the antibody or the antibody fragment thereof specifically binds a CCR4-expressing cell.
3. The method according to claim 1 , wherein the antibody or the antibody fragment has an activity of inducing apoptosis of a Th2 cell.
4. The method according to claim 1 , wherein the antibody or the antibody fragment has an activity of depleting a Th2 cell.
5. The method according to claim 1 , wherein the antibody or the antibody fragment has an activity of inhibiting production of Th2 cytokines.
6. The method according to claim 5 , wherein the Th2 cytokines are IL-4, IL-5 and IL-13.
7. The method according to claim 1 , wherein the antibody is selected from a humanized antibody and a human antibody.
8. The method according to claim 7 , wherein the humanized antibody is a human chimeric antibody or a human CDR-grafted antibody.
9. The method according to claim 1 , wherein the antibody is a human IgG antibody.
10. The method according to claim 7 , wherein the humanized antibody comprises: CDR1, CDR2 and CDR3 of an antibody H chain V region having the amino acid sequences set forth in SEQ ID NOS: 5, 6 and 7, respectively; and CDR1, CDR2 and CDR3 of an antibody L chain V region having the amino acid sequences set forth in SEQ ID, NOS: 8, 9 and 10, respectively.
11. The method according to claim 8 , wherein the human chimeric antibody comprises: an antibody H chain V region and antibody L chain V region of a monoclonal antibody which specifically binds CCR4; and an H chain C region and L chain C region of a human antibody.
12. The method according to claim 11 , wherein the human chimeric antibody comprises: a CDR1, CDR2 and CDR3 of an H chain V region having the amino acid sequence set forth in SEQ ID NOs: 5, 6 and 7, respectively; and CDR1, CDR2 and CDR3 of an L chain V region having the amino acid sequences set forth in SEQ ID NOS: 8, 9 and 10, respectively.
13. The method according to claim 8 , wherein the human chimeric antibody comprises: an H chain V region having amino acids of positions 20-138 in the amino acid sequence set forth in SEQ ID NO: 15; and an L chain V region having amino acids of positions 20-132 in the amino acid sequence set forth in SEQ ID NO: 16.
14. The method according to claim 8 , wherein the human chimeric antibody is an antibody KM2760 produced by a transformant KM2760 (FERM BP-70541), and wherein its antibody H chain C region belongs to human IgG1 subclass.
15. The method according to claim 8 , wherein the human CDR-grafted antibody comprises: CDRs of an antibody H chain V region and an antibody L chain V region of a monoclonal antibody which specifically reacts with binds CCR4; and C regions of an H chain and an L chain and a V region framework region of a human antibody.
16. The method according to claim 15 , wherein the human CDR-grafted antibody comprises: CDR1, CDR2 and CDR3 of an H chain V region having the amino acid sequences set forth in SEQ ID NOS: 5, 6 and 7, respectively; and CDR1, CDR2 and CDR3 of an L chain V region having the amino acid sequences set forth in SEQ ID NOS: 8, 9 and 10, respectively.
17. The method according to claim 7 , wherein the human antibody comprises an antibody H chain V region and an antibody L chain V region.
18. The method according to claim 17 , wherein CDRs of the H chain V region and L chain V region of the human antibody comprise amino acid sequences which are the same as amino acid sequences of CDRs of an H chain V region and an L chain V region, respectively, of a monoclonal antibody which specifically binds CCR4.
19. The method according to claim 18 , wherein the human antibody comprise CDR1, CDR2 and CDR3 of an H chain V region having the amino acid sequences set forth in SEQ ID NOS: 5, 6 and 7, respectively, and CDR1, CDR2 and CDR3 of an L chain V region having the amino acid sequences set forth in SEQ ID NOS: 8, 9 and 10, respectively.
20. The method according to claim 17 , wherein the human antibody comprise amino acid sequences which are the same as amino acid sequences of an H chain V region and an L chain V region, respectively, of a monoclonal antibody which specifically binds CCR4.
21. The method according to claim 20 , wherein the human antibody comprises: an H chain V region having amino acids of positions 20-138 in the amino acid sequence set forth in SEQ ID NO: 15; and an L chain V region having amino acids of positions 20-132 in the amino acid sequence set forth in SEQ ID NO: 16.
22. The method according to claim 17 , wherein the human antibody is an antibody obtained from a human antibody phage library or a transgenic animal which produces a human antibody.
23. The method according to claim 1 , wherein the antibody fragment is selected from Fab, Fab′, F(ab′) 2 , a single chain antibody, and a disulfide stabilized V region fragment.
24. The method according to claim 23 , wherein the antibody fragment comprises the antibody H chain V region and an antibody L chain V region of an antibody.
25. The method according to claim 24 , wherein CDRs of the H chain V region and L chain V region of the antibody fragment comprise amino acid sequences which are the same as amino acid sequences of CDRs of an H chain V region and an L chain V region, respectively, of a monoclonal antibody which specifically binds CCR4.
26. The method according to claim 25 , wherein the antibody fragment comprises CDR1, CDR2 and CDR3 of the H chain V region having the amino acid sequences set forth in SEQ ID NOS: 5, 6 and 7, respectively; and CDR1, CDR2 and CDR3 of the L chain V region having the amino acid sequences set forth in SEQ ID NOS: 8, 9 and 10, respectively.
27. The method according to claim 24 , wherein the H chain V region and L chain V region of the antibody fragment comprise amino acid sequences which are the same as amino acid sequences of an H chain V region and an L chain V region, respectively, of a monoclonal antibody which specifically binds CCR4.
28. The method according to claim 27 , wherein the antibody fragment comprises: an H chain V region having amino acids of positions 20-138 in the amino acid sequence set forth in SEQ ID NO: 15; and an L chain V region having amino acids of positions of 20-132 in the amino acid sequence set forth in SEQ ID NO: 16.
29. The method according to claim 1 , wherein the antibody or the antibody fragment is chemically or genetically conjugated with a radioisotope, a protein, an anticancer agent or an anti-inflammatory agent.
30. The method according to claim 15 , wherein the human CDR-grafted antibody comprises: CDR1, CDR2 and CDR3 of an H chain V region, and CDR1, CDR2 and CDR3 of an L chain V region having the amino acid sequences set forth in SEQ ID NOS:5-10, respectively.
31. The method according to claim 18 , wherein the human antibody comprises: CDR1, CDR2 and CDR3 of an H chain V region, and CDR1, CDR2 and CDR3 of an L chain V region having the amino acid sequences set forth in SEQ ID NOS: 5-10, respectively.
32. The method according to claim 25 , wherein the antibody fragment comprises: CDR1, CDR2 and CDR3 of an H chain V region, and CDR1, CDR2 and CDR3 of an L chain V region having the amino acid sequences set forth in SEQ ID NOS: 5-10, respectively.