Anti-TIGIT antibody, and pharmaceutical composition and use thereof
An ant-TIGIT antibody, and a pharmaceutical composition and the use thereof. The present invention relates to an anti-TIGIT antibody or an antigen-binding fragment thereof, wherein a heavy chain variable region of the antibody comprises HCDR1-HCDR3 having amino acid sequences as shown in SEQ ID NOs: 3-5, respectively; and a light chain variable region of the antibody comprises LCDR1-LCDR3 having amino acid sequences as shown in SEQ ID NOs: 8-10, respectively. The antibody can effectively bind to TIGIT and has the potential for use in tumor prevention and treatment.
1 . An anti-TIGIT antibody or an antigen-binding fragment thereof,
wherein the anti-TIGIT antibody comprises a heavy chain variable region and a light chain variable region,
wherein the heavy chain variable region of the antibody comprises HCDR1-HCDR3 with amino acid sequences set forth in SEQ ID NOs: 3-5, respectively, and the light chain variable region of the antibody comprises LCDR1-LCDR3 with amino acid sequences set forth in SEQ ID NOs: 8-10, respectively.
2 . The anti-TIGIT antibody or the antigen-binding fragment thereof according to claim 1 , wherein the heavy chain variable region of the antibody comprises an amino acid sequence selected from SEQ ID NO: 1, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, and SEQ ID NO: 17; and
the light chain variable region of the antibody comprises an amino acid sequence selected from SEQ ID NO: 6, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, and SEQ ID NO: 25.
3 . The anti-TIGIT antibody or the antigen-binding fragment thereof according to claim 1 , wherein
the heavy chain variable region of the antibody comprises an amino acid sequence set forth in SEQ ID NO: 1, and the light chain variable region of the antibody comprises an amino acid sequence set forth in SEQ ID NO: 6;
the heavy chain variable region of the antibody comprises an amino acid sequence set forth in SEQ ID NO: 11, and the light chain variable region of the antibody comprises an amino acid sequence set forth in SEQ ID NO: 19;
the heavy chain variable region of the antibody comprises an amino acid sequence set forth in SEQ ID NO: 17, and the light chain variable region of the antibody comprises an amino acid sequence set forth in SEQ ID NO: 19;
the heavy chain variable region of the antibody comprises an amino acid sequence set forth in SEQ ID NO: 13, and the light chain variable region of the antibody comprises an amino acid sequence set forth in SEQ ID NO: 21;
the heavy chain variable region of the antibody comprises an amino acid sequence set forth in SEQ ID NO: 13, and the light chain variable region of the antibody comprises an amino acid sequence set forth in SEQ ID NO: 23;
the heavy chain variable region of the antibody comprises an amino acid sequence set forth in SEQ ID NO: 15, and the light chain variable region of the antibody comprises an amino acid sequence set forth in SEQ ID NO: 21;
the heavy chain variable region of the antibody comprises an amino acid sequence set forth in SEQ ID NO: 15, and the light chain variable region of the antibody comprises an amino acid sequence set forth in SEQ ID NO: 23;
the heavy chain variable region of the antibody comprises an amino acid sequence set forth in SEQ ID NO: 11, and the light chain variable region of the antibody comprises an amino acid sequence set forth in SEQ ID NO: 25; or
the heavy chain variable region of the antibody comprises an amino acid sequence set forth in SEQ ID NO: 17, and the light chain variable region of the antibody comprises an amino acid sequence set forth in SEQ ID NO: 25.
4 . The anti-TIGIT antibody or the antigen-binding fragment thereof according to claim 1 , wherein the anti-TIGIT antibody or the antigen-binding fragment thereof is selected from Fab, Fab′, F(ab′) 2 , Fv, a single chain antibody, a humanized antibody, a chimeric antibody, and a diabody.
5 . The anti-TIGIT antibody or the antigen-binding fragment thereof according to claim 1 , wherein
the antibody comprises a one or more human framework region.
6 . The anti-TIGIT antibody or the antigen-binding fragment thereof according to claim 1 , wherein the anti-TIGIT antibody comprises a heavy chain constant region and a light chain constant region, wherein the heavy chain constant region of the antibody is Ig gamma-1 chain C region or Ig gamma-4 chain C region; and the light chain constant region of the antibody is Ig kappa chain C region.
7 . The anti-TIGIT antibody or the antigen-binding fragment thereof according to claim 1 , wherein the antibody binds to TIGIT-mFc with a K D of less than 4E-10 or less than 4E-11; wherein the K D is measured by a Fortebio molecular interaction instrument.
8 . The anti-TIGIT antibody or the antigen-binding fragment thereof according to claim 1 , wherein the antibody binds to TIGIT-mFc with an EC 50 of less than 1.5 nM, less than 1.2 nM, or less than 1 nM; wherein the EC 50 is measured by a flow cytometer.
9 . The anti-TIGIT antibody or the antigen-binding fragment thereof according to claim 1 , wherein the anti-TIGIT antibody is an antibody produced by a hybridoma cell line LT019 deposited at China Center for Type Culture Collection (CCTCC) under CCTCC NO. C2020208.
10 . An isolated nucleic acid molecule, encoding the anti-TIGIT antibody or the antigen-binding fragment according to claim 1 .
11 . A vector, comprising the isolated nucleic acid molecule according to claim 10 .
12 . A host cell, comprising the isolated nucleic acid molecule according to claim 10 .
13 . A hybridoma cell line LT019 deposited at China Center for Type Culture Collection (CCTCC) under CCTCC NO. C2020208.
14 . A conjugate, comprising an antibody and a conjugated moiety, wherein the antibody is the anti-TIGIT antibody or the antigen-binding fragment thereof according to claim 1 , and the conjugated moiety is a detectable label.
15 . A kit, comprising the anti-TIGIT antibody or the antigen-binding fragment thereof according to claim 1 ;
wherein the kit further comprises a secondary antibody specifically recognizing the anti-TIGIT antibody; wherein the secondary antibody further comprises a detectable label.
16 . A bispecific antibody, comprising a first protein functional region and a second protein functional region, wherein
the first protein functional region targets TIGIT;
the second protein functional region targets a target other than TIGIT;
wherein the first protein functional region is the antibody or the antigen-binding fragment according to claim 1 .
17 . The bispecific antibody according to claim 16 , wherein the first protein functional region and the second protein functional region are linked directly or via a linker fragment.
18 . The bispecific antibody according to claim 16 , comprising 1, 2, or more first protein functional region and, independently, 1, 2 or more second protein functional region.
19 . A pharmaceutical composition, comprising the anti-TIGIT antibody or the antigen-binding fragment thereof according to claim 1 , and a pharmaceutically acceptable carrier and/or excipient.
20 . The pharmaceutical composition according to claim 19 , further comprising one or more anti-PD-1 antibodies, or one or more anti-PD-L1 antibodies.
21 . The pharmaceutical composition according to claim 19 , wherein a mass ratio of the anti-TIGIT antibody or the antigen-binding fragment thereof to the anti-PD-1 antibody or the anti-PD-L1 antibody is (1:5)-(5:1), based on the mass of the antibodies.
22 . A combination product, comprising a first product and a second product in separate packages, wherein
the first product comprises the anti-TIGIT antibody or the antigen-binding fragment thereof according to claim 1 ;
the second product comprises at least one anti-PD-1 antibody or at least one anti-PD-L1 antibody;
wherein the first product and the second product further independently comprise one or more pharmaceutically acceptable adjuvants.
23 . The combination product according to claim 22 , wherein a mass ratio of the anti-TIGIT antibody or the antigen-binding fragment thereof to the anti-PD-1 antibody or the anti-PD-L1 antibody is (1:5)-(5:1), based on the mass of the antibodies.
24 . A method for treating a cancer, comprising a step of administering to a subject in need an effective amount of the antibody or the antigen-binding fragment thereof according to claim 1 ,
wherein
the cancer is selected from one or more of ovarian cancer, colorectal cancer and multiple myeloma.
25 . A method for treating a cancer, comprising a step of administering to a subject in need an effective amount of the antibody or the antigen-binding fragment thereof according to claim 16 ,
wherein
the cancer is selected from one or more of ovarian cancer, colorectal cancer and multiple myeloma.
26 . The bispecific antibody according to claim 16 , wherein the second protein functional region targets PD-1.
27 . The bispecific antibody according to claim 16 , wherein the bispecific antibody is in an IgG-scFv format.
28 . The bispecific antibody according to claim 16 , wherein the first protein functional region is an immunoglobulin, and the second protein functional region is a single chain antibody; or
the first protein functional region is a single chain antibody, and the second protein functional region is an immunoglobulin.
29 . The bispecific antibody according to claim 28 , wherein
(a) the first protein functional region is an immunoglobulin comprising two heavy chains and the second protein functional region is a single chain antibody linked to C-termini of two heavy chains; or
(b) the second protein functional region is an immunoglobulin comprising two heavy chains and the first protein functional region is a single chain antibody linked to C-termini of two heavy chains.