Anti-αβTCR antibody
The present invention relates to humanized monoclonal antibodies comprising the CDRs of murine antibody BMA031, which bind to the apTCR.CD3 complex and possess improved biological properties.
1. A method of suppressing a T cell-mediated response in a subject, the method comprising administering to a subject in need thereof an effective amount of a humanized monoclonal antibody specific for human αβTCR/CD3 complex, wherein the humanized monoclonal antibody comprises:
(a) a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 7, 12, 13, 15, and 16,
(b) a light chain variable region comprising the amino acid sequence set forth as SEQ ID NO: 14, and
wherein the T cell-mediated response is involved in a condition selected from the group consisting of tissue transplantation, tissue grafting, multiple sclerosis, and type 1 diabetes,
thereby suppressing the T cell-mediated response in the subject.
2. The method according to claim 1 , wherein the humanized monoclonal antibody further comprises a constant region of human origin.
3. The method according to claim 2 , wherein the humanized monoclonal antibody further comprises an Fc modification which reduces Fcγ receptor binding.
4. The method according to claim 3 , wherein the Fc modification comprises multiple mutations selected from the group consisting of N297Q/S298N/Y300S, S298N/T299A/Y300S and S298N/Y300S.
5. The method according to claim 1 , wherein the heavy chain variable region comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 15 and 16.
6. The method according to claim 1 , wherein the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 16.
7. The method according to claim 3 , wherein the Fcγ receptor is selected from the group consisting of FcγRIIIa and FcγRI.
8. The method according to claim 7 , wherein the Fc modification is selected from the group consisting of N297Q/S298N/Y300S, S298N/T299A/Y300S and S298N/Y300S.
9. The method according to claim 8 , wherein the Fc modification is S297N/T299A/Y300S.
10. The method according to claim 8 , wherein the Fc modification is S298N/T299A/Y300S.
11. The method according to claim 8 , wherein the Fc modification is S298N/Y300S.