TIGIT antibody, antigen-binding fragment thereof, and medical use thereof
A TIGIT antibody, an antigen-binding fragment thereof, and a medical use thereof. The present invention relates to a murine antibody, a chimeric antibody, and a humanized antibody comprising a CDR region of the TIGIT antibody, and a pharmaceutical composition comprising the TIGIT antibody and the antigen-binding fragment thereof, and a use thereof as a medicament. In particular, the present invention also relates to a use of a humanized TIGIT antibody for preparing a medicament for the treatment of TIGIT-associated diseases or conditions.
1. A monoclonal antibody or antigen-binding fragment thereof, specifically binding to human TIGIT, comprising a heavy chain variable region and a light chain variable region, wherein
the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 as set comprising sequences of SEQ ID NOs: 21, 22 and 23, respectively; and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 comprising sequences of SEQ ID NOs: 24, 25 and 26, respectively.
2. The monoclonal antibody or antigen-binding fragment thereof according to claim 1 , wherein the monoclonal antibody is a recombinant antibody.
3. The monoclonal antibody or antigen-binding fragment thereof according to claim 2 , wherein the recombinant antibody is a humanized antibody comprising light and heavy chain framework region (FR) sequences derived from human germline light and heavy chain, or mutated sequences thereof, respectively.
4. The monoclonal antibody or antigen-binding fragment thereof according to claim 3 , wherein the heavy chain variable region of the humanized antibody comprises a sequence of SEQ ID NO: 51, or a variant thereof having 1-3 back mutations on the FR of the heavy chain variable region of SEQ ID NO: 51, wherein the back mutations are selected from the group consisting of M48I, R72V and V79A.
5. The monoclonal antibody or antigen-binding fragment thereof according to claim 3 , wherein the heavy chain variable region sequence of the humanized antibody is selected from the group consisting of: SEQ ID NO: 51, SEQ ID NO: 54 and SEQ ID NO: 55.
6. The monoclonal antibody or antigen-binding fragment thereof according to claim 3 , wherein the light chain variable region of the humanized antibody comprises a sequence of SEQ ID NO: 52, or a variant thereof having the back mutation A43S.
7. The monoclonal antibody or antigen-binding fragment thereof according to claim 3 , wherein the light chain variable region sequence of the humanized antibody is selected from the group consisting of SEQ ID NO: 52 and SEQ ID NO:53.
8. The monoclonal antibody or antigen-binding fragment thereof according to claim 3 , wherein the humanized antibody comprises: a heavy chain variable region of any one of SEQ ID NOs: 51, 54 and 55, and a light chain variable region of SEQ ID NO: 52 or 53.
9. The monoclonal antibody or antigen-binding fragment thereof according to claim 8 , wherein the humanized antibody comprises a heavy chain variable region of SEQ ID NO: 51 and a light chain variable region of SEQ ID NO: 53.
10. The monoclonal antibody or antigen-binding fragment thereof according to claim 1 , wherein the antibody is a full-length antibody, further comprising a human antibody heavy chain constant region comprising a sequence of SEQ ID NO: 78 and a human light chain constant region comprising a sequence of SEQ ID NO: 79.
11. The monoclonal antibody or antigen-binding fragment thereof according to claim 1 , wherein the antigen-binding fragment is selected from the group consisting of Fab, Fab′, F(ab′) 2, single-chain antibody (scFv), dimerized V region (diabody), disulfide-stabilized V region (dsFv) and a peptide comprising CDRs.
12. A pharmaceutical composition comprising a therapeutically effective amount of the monoclonal antibody or antigen-binding fragment thereof according to claim 1 , and one or more pharmaceutically acceptable carriers, diluents, buffers or excipients.
13. An isolated nucleic acid molecule encoding the monoclonal antibody or antigen-binding fragment thereof according to claim 1 .
14. A recombinant vector comprising the nucleic acid molecule of claim 13 .
15. A host cell transformed with the recombinant vector of claim 14 , wherein the host cell is selected from the group consisting of prokaryotic cell and eukaryotic cell.
16. A method comprising cultivating the host cell of claim 15 in culture to form and accumulate the monoclonal antibody or antigen-binding fragment thereof, and recovering the monoclonal antibody or antigen-binding fragment thereof from the culture.
17. A method for detecting or measuring human TIGIT, comprising the step contacting the human TIGIT with the monoclonal antibody or antigen-binding fragment thereof according to claim 1 .
18. A method for treating a disease associated with human TIGIT, comprising administering to a subject a pharmaceutically effective amount of the pharmaceutical composition of claim 12 , wherein the disease associated with human TIGIT is tumor, cancer, or immune disease.
19. The method of claim 18 , wherein the disease associated with human TIGIT is tumor or cancer.