Monoclonal antibodies that bind TRBV9 and methods for using same for inhibiting the T cell receptor for treatment
The invention relates to monoclonal antibodies which specifically bind to the TRBV9 family of human T-cell receptors. The invention also relates to a nucleic acid which codes for said antibody or for an antigen-binding fragment thereof, to an expression vector, to a method for producing the antibody, and to the use of said antibody for treating diseases or disorders associated with the family of human T-cell receptors. The invention is directed towards producing antibodies that can be used for eliminating T-cells carrying T-cell receptors of the TRBV9 family, in particular for treating ankylosing spondylitis, coeliac disease, and blood cancers, in the pathogenesis of which T-cell receptors of the TRBV9 family are involved.
1. A monoclonal antibody or antigen-binding fragment thereof that specifically binds to the TRBV9 (T Cell Receptor Beta Variable 9) family beta chain region of human T cell receptor, comprising:
1) a heavy chain variable domain comprising HCDR1, HCDR2 and HCDR3, where
the HCDR 1 comprises the amino acid sequence of SEQ ID NO: 1,
the HCDR 2 comprises the amino acid sequence of SEQ ID NO: 2,
the HCDR 3 comprises the amino acid sequence selected from the group of SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6; and
2) a light chain variable domain comprising LCDR1, LCDR2 and LCDR3, where
the LCDR 1 comprises the amino acid sequence of SEQ ID NO: 7,
the LCDR 2 comprises the amino acid sequence of SEQ ID NO: 8, and
the LCDR 3 comprises the amino acid sequence of SEQ ID NO: 9.
2. The monoclonal antibody or antigen-binding fragment thereof according to claim 1 , wherein the heavy chain variable domain comprises an amino acid sequence that is at least 90% identical to an amino acid sequence selected from the group of SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, and SEQ ID NO: 19.
3. The monoclonal antibody or antigen-binding fragment thereof according to claim 2 , wherein the heavy chain variable domain comprises an amino acid sequence selected from the group of SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, and SEQ ID NO: 19.
4. The monoclonal antibody or antigen-binding fragment thereof according to claim 1 , wherein the light chain variable domain comprises an amino acid sequence that is at least 90% identical to the amino acid sequence shown in SEQ ID NO: 11.
5. The monoclonal antibody or antigen-binding fragment thereof according to claim 4 , wherein the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 11.
6. The monoclonal antibody or antigen-binding fragment thereof according to claim 1 , comprising:
1) A heavy chain having an amino acid sequence that is at least 90% identical to a sequence selected from the group SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 25, and SEQ ID NO: 27; and
2) A light chain having an amino acid sequence that is at least 90% identical to the sequence of SEQ ID NO: 29.
7. The monoclonal antibody of claim 6 , comprising:
1) A heavy chain comprising an amino acid sequence selected from the group of SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 25, and SEQ ID NO: 27; and
2) A light chain comprising the amino acid sequence of SEQ ID NO: 29.
8. The monoclonal antibody according to claim 1 , wherein the antibody is a full-length IgG antibody.
9. A nucleic acid that encodes an antibody or antigen-binding fragment thereof according to claim 1 , which specifically binds to the TRBV9 family beta chain region of human T cell receptor.
10. An expression vector comprising the nucleic acid according to claim 9 .
11. A host cell for obtaining an antibody or antigen-binding fragment thereof according to claim 1 , comprising a nucleic add that encodes the antibody or antigen-binding fragment thereof.
12. A method of obtaining an antibody or antigen-binding fragment thereof according to claim 1 , comprising cultivating a host cell that comprises a nucleic add that encodes the antibody or antigen-binding fragment thereof in culture medium under conditions that ensure the production of the antibody, followed by isolation and purification of the obtained antibody.
13. A pharmaceutical composition comprising the antibody or antigen-binding fragment thereof according to claim 1 , in combination with one or several pharmaceutically acceptable excipients.