Human CDR-grafted antibody and antibody fragment thereof
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 human CDR-grafted antibody or antibody fragment thereof which comprises
complementarity determining regions (CDRs) 1-3 of a heavy chain variable region which comprise the amino acid sequences of SEQ ID NOs: 1-3, respectively, and CDRs 1-3 of a light chain variable region which comprise the amino acid sequences of SEQ ID NOs: 5-7, respectively.
2. The human CDR-grafted antibody or antibody fragment thereof according to claim 1 , which specifically reacts with a cell expressing an extracellular region of human CC chemokine receptor 4 (CCR4).
3. The human CDR-grafted antibody or the antibody fragment thereof according to claim 1 , wherein the antibody has a cytotoxic activity against a cell expressing an extracellular region of human CC chemokine receptor 4 (CCR4).
4. A composition comprising at least one human CDR-grafted antibody or antibody fragment thereof according to claim 1 as an active ingredient, together with a pharmaceutically acceptable carrier.
5. A human CDR-grafted antibody or antibody fragment thereof which comprises:
(i) a heavy chain variable region of SEQ ID NO: 4, 9, 10, 11, 38, 39, 40 or 41, and a light chain variable region of SEQ ID NO: 8, 12, 13 or 14, or
(ii) a heavy chain variable region encoded by SEQ ID NO: 49, 50, 51, 52, 57, 58, 59, or 60, and a light chain variable region encoded by SEQ ID NO: 53, 54, 55 or 56.
6. The human CDR-grafted antibody or antibody fragment thereof according to claim 5 , which specifically reacts with a cell expressing an extracellular region of human CC chemokine receptor 4 (CCR4).
7. The human CDR-grafted antibody or the antibody fragment thereof according to claim 5 , wherein the antibody has a cytotoxic activity against a cell expressing an extracellular region of human CCR4.
8. A composition comprising at least one human CDR-grafted antibody or antibody fragment thereof according to claim 5 as an active ingredient, together with a pharmaceutically acceptable carrier.
9. A process for producing a human CDR-grafted antibody or antibody fragment thereof, comprising the steps of: culturing a transformant which produces the antibody or antibody fragment thereof according to claim 5 in a medium to form and accumulate the antibody or antibody fragment in the culture; and recovering the antibody or antibody fragment from the culture.
10. A method for depleting CCR4-positive tumor cells in a patient, comprising administering an effective dose of the antibody of claim 5 to a patient in need thereof.