Medicament comprising recombinant antibody against chemokine receptor CCR4
View Patent ↗A medicament having a higher therapeutic effect than that provided by administration of a recombinant antibody against human CC chemokine receptor 4 or an antibody fragment thereof or an agent alone is provided.
1. A method for treating a CCR4-expressing tumor in a patient, comprising administering to said patient a recombinant antibody or antigen-binding fragment thereof which specifically binds to human CC chemokine receptor 4 (CCR4), and at least one agent selected from the group consisting of G-CSF, M-CSF, interferon-α, IL 15, vincristine, cyclophosphamide, etoposide and methotrexate, wherein said agent is not conjugated to said antibody or antigen-binding fragment.
2. The method according to claim 1 , wherein said CCR4-expressing tumor is a hematopoietic organ tumor.
3. The method according to claim 1 , wherein said recombinant antibody or antigen-binding fragment thereof specifically binds to an extracellular region of CCR4, and does not specifically bind to human platelets.
4. The method according to claim 3 , wherein said recombinant antibody or antigen-binding fragment thereof which specifically binds to the extracellular region of CCR4 does not have an activity of inhibiting binding of thymus and activation-regulated chemokine (TARC) or macrophage-derived chemokine (MDC) as a CCR4 ligand to CCR4.
5. The method according to claim 4 , wherein said extracellular region is an extracellular region selected from the group consisting of positions 1 to 39, 98 to 112, 176 to 206 and 271 to 284 of the amino acid sequence as set forth in SEQ ID NO: 1.
6. The method according to claim 4 , wherein said extracellular region is an epitope consisting of positions 2 to 29 of the amino acid sequence as set forth in SEQ ID NO: 1.
7. The method according to claim 4 , wherein said extracellular region is an epitope consisting of positions 13 to 29 of the amino acid sequence as set forth in SEQ ID NO: 1.
8. The method according to claim 4 , wherein said extracellular region is an epitope consisting of positions 13 to 25 of the amino acid sequence as set forth in SEQ ID NO: 1.
9. The method according to claim 8 , wherein said recombinant antibody or antigen-binding fragment thereof which specifically binds to the extracellular region of CCR4 has a binding activity to a polypeptide comprising amino acids 13 to 25 of SEQ ID NO: 1, in which at least one of tyrosine residues 16, 19, 20 and 22 is sulfated, which is lower than a binding activity to a peptide comprising amino acids 13 to 25 of SEQ ID NO: 1.
10. The method according to claim 9 , wherein said recombinant antibody or antigen-binding fragment thereof which specifically binds to the extracellular region of CCR4 specifically reacts with an epitope specifically bound by a monoclonal antibody produced by hybridoma KM 2160 (FERM BP-10090).
11. The method according to claim 10 , wherein said recombinant antibody is a human chimeric antibody or a human CDR-grafted antibody.
12. The method according to claim 11 , wherein said human chimeric antibody comprises complementarity determining regions (CDRs) of a heavy chain (H chain) variable region (V region) and a light chain (L chain) V region of a monoclonal antibody which specifically binds to CCR4.
13. The method according to claim 12 , wherein said human chimeric antibody comprises CDR1, CDR2 and CDR3 domains of a heavy chain (H chain) variable region (V region) comprising the amino acid sequences as set forth in SEQ ID NOs: 5, 6 and 7, respectively, and CDR1, CDR2 and CDR3 domains of a light chain (L chain) variable region (V region) comprising the amino acid sequences as set forth in SEQ ID NOs: 8, 9 and 10, respectively.
14. The method according to claim 13 , wherein said human chimeric antibody comprises a heavy chain (H chain) variable region (V region) comprising the amino acid sequence as set forth in SEQ ID NO: 11, and a light chain (L chain) V region of an antibody molecule comprising the amino acid sequence as set forth in SEQ ID NO: 12.
15. The method according to claim 11 , wherein said human CDR-grafted antibody comprises complementarity determining regions (CDRs) of a heavy chain (H chain) variable region (V region) and a light chain (L chain) V region of a monoclonal antibody which specifically binds to CCR4.
16. The method according to claim 15 , wherein said human CDR-grafted antibody comprises CDR1, CDR2 and CDR3 domains of a heavy chain (H chain) variable region (V region) comprising the amino acid sequences as set forth in SEQ ID NOs: 5, 6 and 7, respectively, and CDR1, CDR2 and CDR3 domains of a light chain (L chain) variable region (V region) comprising the amino acid sequences as set forth in SEQ ID NOs: 8, 9 and 10, respectively.
17. The method according to claim 16 , wherein the human CDR-grafted antibody comprises a heavy chain (H chain) variable region (V region) comprising the amino acid sequence as set forth in SEQ ID NO: 16 or 17, and a light chain (L chain) V region of an antibody molecule comprising the amino acid sequence as set forth in SEQ ID NO: 18.