Monoclonal antibodies against the beta chain region of human TRBV9
The invention relates to a monoclonal humanized antibody or antigen-binding fragment thereof that specifically bind to the TRBV9 family of the human T cell receptor. The invention also relates to a nucleic acid encoding said antibody or antigen-binding fragment thereof, an expression vector, a method for preparing said antibody, and use of said antibody in treatment of diseases or disorders associated with the human T cell receptor family. The invention is directed to generation of antibodies that can be used for treating, in particular AS, celiac disease and malignant blood diseases, the pathogenesis of which involves the TRBV9 family TCRs.
1. A monoclonal antibody or antigen-binding fragment thereof that specifically binds to the beta chain region of the human TCR TRBV9, comprising a heavy chain variable domain comprising the amino acid sequence of SEQ ID No: 16 and a light chain variable domain comprising the amino acid sequence of SEQ ID No: 18.
2. The monoclonal antibody according to claim 1 , which includes a heavy chain having the amino acid sequence of SEQ ID No: 20 and a light chain having the amino acid sequence of SEQ ID No: 22.
3. The monoclonal antibody according to claim 1 , which is a full-length IgG antibody.
4. A nucleic acid that encodes the monoclonal antibody or antigen-binding fragment thereof according to claim 2 , wherein the antibody or antigen binding fragment thereof specifically binds to the beta chain region of the human TCR TRBV9.
5. An expression vector containing the nucleic acid according to claim 4 .
6. A method of obtaining a host cell for producing an antibody or antigen-binding fragment thereof, comprising transforming a cell with the vector of claim 5 .
7. A host cell for obtaining an antibody or antigen binding fragment thereof, comprising a nucleic acid according to claim 4 .
8. A method of obtaining an antibody or antigen-binding fragment thereof, comprising culturing the host cell according to claim 7 in a culture medium under conditions ensuring the production of said antibody, followed by isolation and purification of the obtained antibody.
9. A method for inhibiting the biological activity of the beta chain region of the human TCR TRBV9, in a subject in need of such inhibition, comprising administering to the subject an effective amount of an antibody or antigen-binding fragment thereof according to claim 1 .
10. A pharmaceutical composition comprising in a therapeutically effective amount an antibody or antigen-binding fragment thereof according to claim 1 in combination with one or more pharmaceutically acceptable excipients.
11. A pharmaceutical composition comprising in a therapeutically effective amount an antibody or antigen-binding fragment thereof according to claim 1 and at least one other therapeutically active compound in a therapeutically effective amount.
12. The pharmaceutical composition according to claim 11 , wherein the other therapeutically active compound is selected from a small molecule, antibody or steroid hormones.
13. A method for treating a disease or disorder mediated by the human TCR bearing beta chain region of the TRBV9, comprising administering to a subject in need of such treatment a pharmaceutical composition according to claim 10 in a therapeutically effective amount.
14. A method for treating a disease or disorder mediated by the human TCR bearing beta chain region of the TRBV9, comprising administering to a subject in need of such treatment a pharmaceutical composition according to claim 11 in a therapeutically effective amount.
15. The method for treating a disease or disorder according to claim 13 , wherein the disease or disorder is selected from the group consisting of: ankylosing spondylitis, celiac disease, T cell leukemia, and T cell lymphoma.
16. The method for treating a disease or disorder according to claim 14 , wherein the disease or disorder is selected from the group consisting of: ankylosing spondylitis, celiac disease, T cell leukemia, and T cell lymphoma.