WO2025002151A1 - 抗tigit抗体及其应用 - Google Patents

抗tigit抗体及其应用 Download PDF

Info

Publication number
WO2025002151A1
WO2025002151A1 PCT/CN2024/101505 CN2024101505W WO2025002151A1 WO 2025002151 A1 WO2025002151 A1 WO 2025002151A1 CN 2024101505 W CN2024101505 W CN 2024101505W WO 2025002151 A1 WO2025002151 A1 WO 2025002151A1
Authority
WO
WIPO (PCT)
Prior art keywords
seq
amino acid
sequence shown
acid sequence
variable region
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/CN2024/101505
Other languages
English (en)
French (fr)
Inventor
甄子朋
黄梁敏
马元婧
黄颖
王亮亮
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Chia Tai Tianqing Pharmaceutical Group Co Ltd
Original Assignee
Chia Tai Tianqing Pharmaceutical Group Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Chia Tai Tianqing Pharmaceutical Group Co Ltd filed Critical Chia Tai Tianqing Pharmaceutical Group Co Ltd
Priority to CN202480031403.4A priority Critical patent/CN121219319A/zh
Publication of WO2025002151A1 publication Critical patent/WO2025002151A1/zh
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the present disclosure relates to anti-TIGIT antibodies. More specifically, the present disclosure relates to antibodies or antigen-binding portions thereof that specifically bind to TIGIT, and methods of making and using the antibodies or antigen-binding portions thereof.
  • TIGIT T cell immunoreceptor with Ig and ITIM domains
  • WUCAM WUCAM
  • Vstm3 VSIG9
  • ITIM immunoglobulin tyrosine-based inhibitory motif
  • ITT immunoglobulin tyrosine-based tail motif.
  • TIGIT is an inhibitory immune checkpoint that is primarily expressed on activated T cells and natural killer (NK) cells.
  • CD155 also known as PVR, Necl5 or Tage4
  • CD112 also known as PVRL2/nectin 2
  • CD113 also known as PVRL3
  • CD155 is a high-affinity ligand of TIGIT. After TIGIT binds to the ligand, it transmits the inhibitory signal to the cell through its inhibitory motif, effectively inhibiting innate immunity and adaptive immunity.
  • TIGIT exerts its inhibitory effects include: binding to CD155 on dendritic cells (DCs), promoting the formation of immune-tolerant DCs, reducing the production of IL-12 and leading to an increase in IL-10, indirectly hindering the function of T cells; inhibiting NK cell degranulation and cytokine production, and reducing NK cell-mediated cytotoxicity of CD155 + tumor cells; binding to CD155 with a higher affinity than CD226, resulting in dephosphorylation of its intracellular tyrosine segment, limiting CD226-mediated immune cell activation; acting on Tregs to enhance their immunosuppressive function.
  • DCs dendritic cells
  • TIGIT is expressed in tumor-infiltrating CD8 + T cells, NK cells, helper T cells, and Tregs in solid tumors and hematological malignancies such as melanoma, non-small cell lung cancer, colon cancer, hepatocellular carcinoma, gastric cancer, and glioblastoma.
  • Anti-TIGIT antibodies have been shown to be useful for the treatment of cancer. As an attractive target for cancer immunotherapy, there is a need in the field to develop new TIGIT antibodies.
  • the present disclosure provides a new anti-TIGIT antibody or an antigen-binding portion thereof, providing a solution for TIGIT-targeted therapy.
  • the present disclosure provides an anti-TIGIT antibody or an antigen-binding portion thereof, wherein the anti-TIGIT antibody or the antigen-binding portion thereof comprises:
  • HCDR1 which comprises the amino acid sequence shown in SEQ ID NO: 1, 2, 3 or 4;
  • HCDR2 comprising the amino acid sequence shown in SEQ ID NO:5, 6, 7 or 8;
  • HCDR3 comprising the amino acid sequence shown in SEQ ID NO:9, 10, 11, 12, 13, 14 or 15;
  • LCDR1 which comprises the amino acid sequence shown in SEQ ID NO:16, 17 or 18;
  • LCDR2 which comprises the amino acid sequence shown in SEQ ID NO:19;
  • LCDR3 which comprises the amino acid sequence shown in SEQ ID NO:20, 21, 22, 23 or 24.
  • the present disclosure provides an anti-TIGIT antibody or an antigen binding portion thereof, wherein the anti-TIGIT antibody or the antigen binding portion thereof comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 of the sequence shown in SEQ ID NO: 25, 27, 29, 31, 33, 35, 37, 38, 39, 40, 42, 44, 46, 47, 48, 50, 51, 52, 54, 55, 57, 59, 61 or 63, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 of the sequence shown in SEQ ID NO: 26, 28, 30, 32, 34, 36, 41, 43, 45, 49, 53, 56, 58, 60, 62 or 64.
  • the present disclosure provides an anti-TIGIT antibody or an antigen binding portion thereof, wherein the anti-TIGIT antibody or the antigen binding portion thereof comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO: 25, 27, 29, 31, 33, 35, 37, 38, 39, 40, 42, 44, 46, 47, 48, 50, 51, 52, 54, 55, 57, 59, 61 or 63, and the light chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO: 26, 28, 30, 32, 34, 36, 41, 43, 45, 49, 53, 56, 58, 60, 62 or 64.
  • the present disclosure provides an anti-TIGIT antibody or an antigen-binding portion thereof, wherein the anti-TIGIT antibody or antigen-binding portion thereof is Any of the exemplary anti-TIGIT antibodies, or antigen-binding portions thereof, provided herein bind to the same epitope on human TIGIT.
  • the present disclosure provides an anti-TIGIT antibody, or an antigen-binding portion thereof, wherein the anti-TIGIT antibody, or an antigen-binding portion thereof, competes with any of the exemplary anti-TIGIT antibodies, or antigen-binding portions thereof provided herein for binding to human TIGIT, wherein the competition is measured by ELISA, flow cytometry, or surface plasmon resonance assay.
  • the antigen binding portion may be selected from a Fab portion, a Fab' portion, a F(ab') 2 portion, a Fd portion, a Fv portion, a dAb portion, an isolated CDR region or a scFv, but is not limited thereto.
  • the present disclosure provides an antibody drug conjugate comprising an anti-TIGIT antibody or an antigen-binding portion thereof described herein, and a therapeutic agent conjugated to the anti-TIGIT antibody or the antigen-binding portion thereof.
  • the anti-TIGIT antibody or antigen-binding portion thereof can be connected to the therapeutic agent via a linker.
  • the linker can be cleavable or non-cleavable.
  • the therapeutic agent can be selected from cytotoxic drugs, radioisotopes or immunomodulators, such as chemotherapeutic agents, immunosuppressants, immunostimulants, antimetabolites, alkylating agents, antibiotics, anti-angiogenic agents, anti-mitotic agents, toxins, apoptotic agents, etc.
  • cytotoxic drugs such as chemotherapeutic agents, immunosuppressants, immunostimulants, antimetabolites, alkylating agents, antibiotics, anti-angiogenic agents, anti-mitotic agents, toxins, apoptotic agents, etc.
  • the present disclosure provides a fusion protein comprising an anti-TIGIT antibody or antigen-binding portion thereof as described herein.
  • the present disclosure provides a pharmaceutical composition
  • a pharmaceutical composition comprising an anti-TIGIT antibody or antigen-binding portion thereof, an antibody drug conjugate, or a fusion protein described herein.
  • the present disclosure provides an isolated nucleic acid encoding an anti-TIGIT antibody, or an antigen-binding portion thereof, described herein.
  • the present disclosure provides a vector comprising the isolated nucleic acid described herein.
  • the present disclosure provides a host cell comprising a vector as described herein or an isolated nucleic acid as described herein.
  • the vector is an expression vector.
  • the present disclosure provides a method for preparing an anti-TIGIT antibody or an antigen-binding portion thereof, comprising: culturing the host cell described herein, and isolating the expressed anti-TIGIT antibody or the antigen-binding portion thereof.
  • the present disclosure provides a method for treating cancer in a subject, wherein the method comprises administering to the subject a therapeutically effective amount of an anti-TIGIT antibody or antigen-binding portion thereof described herein, an antibody-drug conjugate described herein, a fusion protein described herein, or a pharmaceutical composition described herein.
  • the present disclosure provides a method for treating an immune-related disease in a subject, wherein the method comprises administering to the subject a therapeutically effective amount of the anti-TIGIT antibody or antigen-binding portion thereof described herein, the antibody-drug conjugate described herein, the fusion protein described herein, or the pharmaceutical composition described herein.
  • the present disclosure provides a method for enhancing an immune response in a subject, wherein the method comprises administering to the subject a therapeutically effective amount of an anti-TIGIT antibody or antigen-binding portion thereof described herein, an antibody-drug conjugate described herein, a fusion protein described herein, or a pharmaceutical composition described herein.
  • the anti-TIGIT antibody or antigen-binding portion thereof, antibody drug conjugate, fusion protein or pharmaceutical composition is administered to a subject alone or together with a PD ⁇ 1 axis binding antagonist.
  • the present disclosure provides a kit comprising the anti-TIGIT antibody or antigen-binding portion thereof described herein, the antibody-drug conjugate described herein, the fusion protein described herein, or the pharmaceutical composition described herein.
  • FIG1 shows the effect of anti-TIGIT antibodies on NK cell cytotoxicity.
  • Figure 2 shows the effect of anti-TIGIT antibodies on NK cell-to-Treg ADCC.
  • FIG3 shows the effect of anti-TIGIT antibody alone on CD8 + T cell function.
  • antibody refers to a binding protein having at least one antigen (eg, TIGIT) binding domain, and thus, The antibodies of the present disclosure encompass polyclonal antibodies, monoclonal antibodies, monospecific antibodies, multispecific antibodies (eg, bispecific antibodies, trispecific antibodies), monovalent antibodies, multivalent antibodies, single-chain antibodies, or fusion proteins.
  • the "antigen binding portion" of an antibody refers to one or more portions of an antibody that retain the function of specifically binding to an antigen (e.g., TIGIT). It has been demonstrated that the antigen binding function of an antibody can be achieved by a portion of a full-length antibody.
  • an antigen e.g., TIGIT
  • an antibody examples encompassed within the term "antigen binding portion" of an antibody include: (i) a Fab fragment, a monovalent fragment consisting of a VL, VH, CL, and CH1 domain; (ii) a Fab' fragment, which differs from a Fab fragment in that several residues are added to the carboxyl terminus of the heavy chain CH1 domain, including one or more cysteines from the hinge region of the antibody; (iii) a F(ab') 2 fragment, a bivalent fragment comprising two Fab fragments connected by a hinge region disulfide bridge; (iv) an Fd fragment, consisting of a VH and CH1 domain; (v) an Fv fragment, consisting of a VL and VH domain of a single-arm antibody; (vi) a dAb fragment, consisting of a VH domain; (vii) a separated complementary determining region (CDR); and (viii) a nanobody, comprising a heavy chain variable region and two constant domains of
  • the two domains VL and VH of the Fv fragment are encoded by different genes, they can be connected by a recombinant method through a synthetic linker to prepare a single protein chain, in which VL and VH are paired to form a monovalent molecule (called single-chain Fv (scFv).
  • the antigen-binding portion herein can be obtained using conventional techniques known to those skilled in the art, and can be functionally screened by the same method as the full-length antibody.
  • anti-TIGIT antibodies and antigen-binding fragments thereof disclosed herein can be derived from any species, including but not limited to mice, rats, rabbits, non-human primates (such as chimpanzees, cynomolgus monkeys, spider monkeys, macaques), llamas and humans.
  • Anti-TIGIT antibodies can be murine antibodies, chimeric antibodies, humanized antibodies or fully human antibodies.
  • anti-TIGIT antibodies are antibodies produced by hybridoma cell lines derived from mice. Therefore, in some embodiments, anti-TIGIT antibodies are murine antibodies.
  • anti-TIGIT antibodies are chimeric antibodies. In some embodiments, chimeric antibodies are mouse-human chimeric antibodies. In other embodiments, anti-TIGIT antibodies are humanized antibodies. In other embodiments, anti-TIGIT antibodies are derived from murine antibodies and are humanized.
  • chimeric antibody is an antibody having at least a portion of an antibody heavy chain variable region and at least a portion of an antibody light chain variable region derived from one species; and at least a portion of an antibody constant region derived from another species.
  • a chimeric antibody may comprise a variable region of a murine antibody and a constant region of a human antibody.
  • Humanized antibodies are antibodies that contain complementary determining regions (CDRs) derived from non-human antibodies and framework regions and constant regions derived from human antibodies.
  • the humanized antibodies provided herein that bind to TIGIT may include CDRs derived from one or more murine antibodies and framework regions and constant regions of human antibodies. Therefore, in some embodiments, the humanized antibodies provided herein bind to the same epitope on TIGIT as the murine antibodies from which the CDRs of the antibodies are derived.
  • Exemplary humanized antibodies are provided herein. Additional humanized antibodies or variants thereof that bind to TIGIT comprising the heavy chain CDRs and light chain CDRs provided herein can be produced using any human antibody framework sequence and are also included in the present disclosure.
  • framework sequences suitable for use in the present disclosure include those that are structurally similar to the framework sequences provided herein. Additional modifications may be made in the framework region to improve the properties of the antibodies provided herein. Such additional framework modifications may include chemical modifications, point mutations to reduce immunogenicity or remove T cell epitopes, or back mutations to residues in the original germline sequence.
  • multi-specific means that the antibody can specifically bind to a variety of different antigenic determinants, for example, it can specifically bind to two (i.e., "bispecific") or more different antigenic determinants.
  • Antigenic determinants in this article are synonymous with antigenic epitopes.
  • bispecific antibodies contain two antigen binding sites, each of which is specific for a different antigenic determinant.
  • Different antigenic determinants can be expressed on the same or different cells.
  • Different antigenic determinants can be different due to different antigen types, or they can exist on the same antigen.
  • Antigenic determinants are special chemical groups with a certain composition and structure on the surface of antigenic molecules or other parts, which can specifically bind to their corresponding antibodies or sensitized lymphocytes.
  • variable domain refers to the domain of an antibody that is involved in binding the antibody to an antigen.
  • a natural four-chain antibody e.g., derived from humans, mice, etc.
  • has a heavy chain variable region also referred to as a heavy chain variable domain, VH or VH domain
  • a light chain variable region also referred to as a light chain variable domain, VL or VL domain.
  • each variable domain of a natural antibody is essentially composed of four "framework regions (FR)" and three "complementarity determining regions (CDR)".
  • the four framework regions are respectively referred to as framework region 1 (or FR1), framework region 2 (or FR2), framework region 3 (or FR3), and framework region 4 (or FR4); the framework region is separated by three complementary determining regions, which are respectively referred to as complementary determining region 1 (or CDR1), complementary determining region 2 (or CDR2), and complementary determining region 3 (or CDR3) in the art and hereinafter. Therefore, the general structure of the variable domain can be expressed as follows: FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4. The variable domain confers specificity to the antibody for the antigen by providing the antigen binding site.
  • CDR complementarity determining region
  • HVR hypervariable region
  • Natural four-chain antibodies usually contain six CDRs, three In the heavy chain variable region, namely, heavy chain CDR1 (HCDR1), heavy chain CDR2 (HCDR2) and heavy chain CDR3 (HCDR3); three in the light chain variable region, namely, light chain CDR1 (LCDR1), light chain CDR2 (LCDR2) and light chain CDR3 (LCDR3).
  • isolated means that the compound of interest (eg, antibody or nucleic acid) has been separated from its natural environment.
  • EC50 refers to the half effective concentration, which refers to the antibody concentration that achieves 50% of the maximum effect after a specific exposure event.
  • IC50 refers to the half inhibitory concentration, which refers to the antibody concentration that inhibits a specific biological or biochemical function by 50% relative to the absence of the antibody. Both EC50 and IC50 can be measured by ELISA or FACS analysis or any other method known in the art.
  • KD refers to the equilibrium dissociation constant, which is obtained from the ratio of kd to ka (i.e., kd/ka), expressed as molar concentration (M).
  • M molar concentration
  • the KD value of an antibody can be determined using methods known in the art.
  • a preferred method for determining the KD of an antibody is to use surface plasmon resonance, more preferably using a biosensor system, such as a Biacore system.
  • treatment refers to measures used to cure, heal, alleviate, relieve, alter, remedy, improve, improve or affect a condition (e.g., a disease), the symptoms of a condition, or to prevent or delay the onset of symptoms, complications, biochemical indicators, or otherwise block or inhibit the further development of a disease, condition or disorder.
  • a condition e.g., a disease
  • the term “subject” includes any human or non-human animal.
  • the term “non-human animal” includes all vertebrates, e.g., mammals and non-mammals, such as non-human primates, sheep, dogs, cats, horses, cows, chickens, amphibians, reptiles, etc.
  • the subject according to the present disclosure is a human.
  • the terms “patient” or “subject” can be used interchangeably.
  • “about” means within the acceptable error range for a particular value as determined by one of ordinary skill in the art, which depends in part on how the value is measured or determined, i.e., the limitations of the measurement system. For example, “about” may mean within 1 or more than 1 standard deviation as practiced in the art. Alternatively, “about” may mean a range of up to ⁇ 5%, such as fluctuations within ⁇ 2%, within ⁇ 1%, or within ⁇ 0.5% of a given specific numerical range. When a specific value is given in the application or claims, unless otherwise indicated, the meaning of "about” should be considered to be within the acceptable error range for that specific value. In this document, unless otherwise indicated, the values of step parameters or conditions are modified by "about” by default.
  • identity is also called consistency.
  • a mathematical algorithm can be used to complete the comparison of sequences and the determination of the percentage identity between two sequences.
  • the percentage identity between two amino acid sequences can be determined using the algorithm of E.Meyers and W.Miller (Comput.Appl.Biosci., 4:11-17 (1988)), which has been incorporated into the ALIGN program (version 2.0), which uses the PAM120 residue weight table, a gap length penalty of 12, and a gap penalty of 4.
  • the percent identity of two amino acid sequences can be determined using the algorithm of Needleman and Wunsch (J. Mol. Biol.
  • Xn is equivalent to "Xaa” and refers to an unspecified amino acid, and its scope is specified by the subsequent definition in the relevant statement.
  • Anti-TIGIT antibodies or antigen-binding portions thereof are provided.
  • TIGIT T cell immunoreceptor with Ig and ITIM domains
  • WUCAM WUCAM
  • Vstm3 WUCAM
  • Vstm3 WUCAM
  • Vstm3 WUCAM
  • Vstm3 Vstm3
  • VSIG9 VSIG9
  • human TIGIT and “human TIGIT”, “hTIGIT”, etc. are used interchangeably herein.
  • anti-TIGIT antibody and “antibody that binds to TIGIT” are used interchangeably.
  • the present disclosure provides anti-TIGIT antibodies or antigen-binding portions thereof, providing new solutions for the treatment of TIGIT targeting.
  • the antibodies provided herein also show many other desirable features for targeted therapy. Specifically, these desirable features can be, for example, binding to human TIGIT with a KD value of 1.38E-09M or less, blocking TIGIT from binding to CD155, promoting NK cell killing activity, promoting the ADCC effect of NK cells on Tregs, promoting T cell function, etc. At least one of the above.
  • the present disclosure provides an anti-TIGIT antibody or an antigen-binding portion thereof comprising a specific sequence.
  • the present disclosure provides an anti-TIGIT antibody, or an antigen-binding portion thereof, comprising one or more CDRs selected from the group consisting of SEQ ID NOs: 1-24.
  • an anti-TIGIT antibody or an antigen-binding portion thereof is provided, wherein the anti-TIGIT antibody or the antigen-binding portion thereof comprises:
  • HCDR1 which comprises the amino acid sequence shown in SEQ ID NO: 1, 2, 3 or 4;
  • HCDR2 comprising the amino acid sequence shown in SEQ ID NO:5, 6, 7 or 8;
  • HCDR3 comprising the amino acid sequence shown in SEQ ID NO:9, 10, 11, 12, 13, 14 or 15;
  • LCDR1 which comprises the amino acid sequence shown in SEQ ID NO:16, 17 or 18;
  • LCDR2 which comprises the amino acid sequence shown in SEQ ID NO:19;
  • LCDR3 which comprises the amino acid sequence shown in SEQ ID NO:20, 21, 22, 23 or 24.
  • the anti-TIGIT antibody or its antigen-binding portion comprises: HCDR1 comprising the amino acid sequence shown in SEQ ID NO:1; HCDR2 comprising the amino acid sequence shown in SEQ ID NO:5; HCDR3 comprising the amino acid sequence shown in SEQ ID NO:9; LCDR1 comprising the amino acid sequence shown in SEQ ID NO:16; LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19; and LCDR3 comprising the amino acid sequence shown in SEQ ID NO:20.
  • the anti-TIGIT antibody or its antigen-binding portion comprises: HCDR1 comprising the amino acid sequence shown in SEQ ID NO:2; HCDR2 comprising the amino acid sequence shown in SEQ ID NO:5; HCDR3 comprising the amino acid sequence shown in SEQ ID NO:10; LCDR1 comprising the amino acid sequence shown in SEQ ID NO:17; LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19; and LCDR3 comprising the amino acid sequence shown in SEQ ID NO:21.
  • the anti-TIGIT antibody or its antigen-binding portion comprises: HCDR1 comprising the amino acid sequence shown in SEQ ID NO:3; HCDR2 comprising the amino acid sequence shown in SEQ ID NO:6; HCDR3 comprising the amino acid sequence shown in SEQ ID NO:11; LCDR1 comprising the amino acid sequence shown in SEQ ID NO:16; LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19; and LCDR3 comprising the amino acid sequence shown in SEQ ID NO:22.
  • the anti-TIGIT antibody or its antigen-binding portion comprises: HCDR1 comprising the amino acid sequence shown in SEQ ID NO:4; HCDR2 comprising the amino acid sequence shown in SEQ ID NO:7; HCDR3 comprising the amino acid sequence shown in SEQ ID NO:12; LCDR1 comprising the amino acid sequence shown in SEQ ID NO:16; LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19; and LCDR3 comprising the amino acid sequence shown in SEQ ID NO:23.
  • the anti-TIGIT antibody or its antigen-binding portion comprises: HCDR1 comprising the amino acid sequence shown in SEQ ID NO:4; HCDR2 comprising the amino acid sequence shown in SEQ ID NO:8; HCDR3 comprising the amino acid sequence shown in SEQ ID NO:13; LCDR1 comprising the amino acid sequence shown in SEQ ID NO:18; LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19; and LCDR3 comprising the amino acid sequence shown in SEQ ID NO:24.
  • the anti-TIGIT antibody or its antigen-binding portion comprises: HCDR1 comprising the amino acid sequence shown in SEQ ID NO:1; HCDR2 comprising the amino acid sequence shown in SEQ ID NO:5; HCDR3 comprising the amino acid sequence shown in SEQ ID NO:14; LCDR1 comprising the amino acid sequence shown in SEQ ID NO:16; LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19; and LCDR3 comprising the amino acid sequence shown in SEQ ID NO:20.
  • the anti-TIGIT antibody or its antigen-binding portion comprises: HCDR1 comprising the amino acid sequence shown in SEQ ID NO:2; HCDR2 comprising the amino acid sequence shown in SEQ ID NO:5; HCDR3 comprising the amino acid sequence shown in SEQ ID NO:15; LCDR1 comprising the amino acid sequence shown in SEQ ID NO:17; LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19; and LCDR3 comprising the amino acid sequence shown in SEQ ID NO:21.
  • an anti-TIGIT antibody or an antigen binding portion thereof comprises a heavy chain variable region and a light chain variable region
  • the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 of the sequence shown in SEQ ID NO: 25, 27, 29, 31, 33, 35, 37, 38, 39, 40, 42, 44, 46, 47, 48, 50, 51, 52, 54, 55, 57, 59, 61 or 63
  • the light chain variable region comprises LCDR1, LCDR2 and LCDR3 of the sequence shown in SEQ ID NO: 26, 28, 30, 32, 34, 36, 41, 43, 45, 49, 53, 56, 58, 60, 62 or 64.
  • the anti-TIGIT antibody or its antigen-binding portion provided comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 of the sequence shown in SEQ ID NO:25, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 of the sequence shown in SEQ ID NO:26.
  • an anti-TIGIT antibody or antigen-binding portion thereof comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain
  • the variable region comprises HCDR1, HCDR2 and HCDR3 of the sequence shown in SEQ ID NO: 27, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 of the sequence shown in SEQ ID NO: 28;
  • the anti-TIGIT antibody or antigen-binding portion thereof provided comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 of the sequence shown in SEQ ID NO: 29, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 of the sequence shown in SEQ ID NO: 30;
  • the anti-TIGIT antibody or antigen-binding portion thereof provided comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 of the sequence shown in SEQ ID NO: 31, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 of the sequence shown in SEQ ID NO: 32;
  • the anti-TIGIT antibody or antigen-binding portion thereof provided comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 of the sequence shown in SEQ ID NO: 33, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 of the sequence shown in SEQ ID NO: 34;
  • the anti-TIGIT antibody or antigen-binding portion thereof provided comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 of the sequence shown in SEQ ID NO:55, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 of the sequence shown in SEQ ID NO:56;
  • the anti-TIGIT antibody or antigen-binding portion thereof provided comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 of the sequence shown in SEQ ID NO:57, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 of the sequence shown in SEQ ID NO:58;
  • the anti-TIGIT antibody or antigen-binding portion thereof provided comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 of the sequence shown in SEQ ID NO:59, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 of the sequence shown in SEQ ID NO:60;
  • the anti-TIGIT antibody or antigen-binding portion thereof provided comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 of the sequence shown in SEQ ID NO:61, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 of the sequence shown in SEQ ID NO:62; or
  • the anti-TIGIT antibody or its antigen-binding portion provided comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 of the sequence shown in SEQ ID NO:63, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 of the sequence shown in SEQ ID NO:64.
  • the anti-TIGIT antibody or its antigen binding portion comprises a heavy chain variable region
  • the heavy chain variable region comprises a sequence shown in SEQ ID NO: 25, 27, 29, 31, 33, 35, 37, 38, 39, 40, 42, 44, 46, 47, 48, 50, 51, 52, 54, 55, 57, 59, 61 or 63.
  • the present invention relates to an amino acid sequence that is 100% identical to an amino acid sequence of at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least 89% identical, at least 90% identical, at least 91% identical, at least 92% identical, at least 93% identical, at least 94% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, at least 99% identical, or 100% identical.
  • the anti-TIGIT antibody or its antigen binding portion comprises a light chain variable region, which comprises an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least 89% identical, at least 90% identical, at least 91% identical, at least 92% identical, at least 93% identical, at least 94% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, at least 99% identical or 100% identical to the sequence shown in SEQ ID NO:26, 28, 30, 32, 34, 36, 41, 43, 45, 49, 53, 56, 58, 60, 62 or 64.
  • the anti-TIGIT antibody or antigen-binding portion thereof comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises NO:25, 27, 29, 31, 33, 35, 37, 38, 39, 40, 42, 44, 46, 47, 48, 50, 51, 52, 54, 55, 57, 59, 61 or 63 has an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least 89% identical, at least 90% identical, at least 91% identical, at least 92% identical, at least 93% identical, at least 94% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, at least 99% identical or 100% identical to the sequence shown in SEQ ID NO:25, 27, 29, 31, 33, 35, 37, 38, 39, 40, 42, 44, 46, 47, 48, 50
  • the anti-TIGIT antibody or its antigen-binding portion provided comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a sequence shown in SEQ ID NO:25 having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, at least 100% identity, at least 101% identity, at least 102% identity, at least 103% identity, at least 104% identity, at least 105% identity, at least 106% identity, at least 107% identity, at least 108% identity, at least 109% identity
  • the light chain variable region comprises an amino acid sequence that is at least 80% identical, at least 81%, at
  • the anti-TIGIT antibody or antigen-binding portion thereof comprises: a HCDR1 comprising the amino acid sequence shown in SEQ ID NO:1; a HCDR2 comprising the amino acid sequence shown in SEQ ID NO:5; a HCDR3 comprising the amino acid sequence shown in SEQ ID NO:9; a LCDR1 comprising the amino acid sequence shown in SEQ ID NO:16; a LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19; and a LCDR3 comprising the amino acid sequence shown in SEQ ID NO:20.
  • the anti-TIGIT antibody or its antigen-binding portion provided comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a sequence shown in SEQ ID NO:27 having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, at least 100% identity, at least 101% identity, at least 102% identity, at least 103% identity, at least 104% identity, at least 105% identity, at least 106% identity, at least 107% identity, at least 108% identity, at least 109% identity
  • the light chain variable region comprises an amino acid sequence that is at least 80% identical, at least 81%, at
  • the anti-TIGIT antibody or antigen-binding portion thereof comprises: a HCDR1 comprising the amino acid sequence shown in SEQ ID NO:2; a HCDR2 comprising the amino acid sequence shown in SEQ ID NO:5; a HCDR3 comprising the amino acid sequence shown in SEQ ID NO:10; a LCDR1 comprising the amino acid sequence shown in SEQ ID NO:17; a LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19; and a LCDR3 comprising the amino acid sequence shown in SEQ ID NO:21.
  • the anti-TIGIT antibody or its antigen-binding portion provided comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a sequence shown in SEQ ID NO:29 having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, at least 100% identity, at least 101% identity, at least 102% identity, at least 103% identity, at least 104% identity, at least 105% identity, at least 106% identity, at least 107% identity, at least 108% identity, at least 109% identity
  • the light chain variable region comprises an amino acid sequence that is at least 80% identical, at least 81%, at
  • the anti-TIGIT antibody or antigen-binding portion thereof comprises: a HCDR1 comprising the amino acid sequence shown in SEQ ID NO:3; a HCDR2 comprising the amino acid sequence shown in SEQ ID NO:6; a HCDR3 comprising the amino acid sequence shown in SEQ ID NO:11; a LCDR1 comprising the amino acid sequence shown in SEQ ID NO:16; a LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19; and a LCDR3 comprising the amino acid sequence shown in SEQ ID NO:22.
  • an anti-TIGIT antibody or antigen-binding portion thereof comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a sequence having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, or at least 85% identity to the sequence shown in SEQ ID NO: 31.
  • the sequence shown in NO:32 has an amino acid sequence with at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity or 100% identity.
  • the anti-TIGIT antibody or antigen-binding portion thereof comprises: a HCDR1 comprising the amino acid sequence shown in SEQ ID NO:4; a HCDR2 comprising the amino acid sequence shown in SEQ ID NO:7; a HCDR3 comprising the amino acid sequence shown in SEQ ID NO:12; a LCDR1 comprising the amino acid sequence shown in SEQ ID NO:16; a LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19; and a LCDR3 comprising the amino acid sequence shown in SEQ ID NO:23.
  • the anti-TIGIT antibody or its antigen-binding portion provided comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a sequence shown in SEQ ID NO:33 having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, at least 100% identity, at least 101% identity, at least 102% identity, at least 103% identity, at least 104% identity, at least 105% identity, at least 106% identity, at least 107% identity, at least 108% identity, at least 109% identity
  • the light chain variable region comprises an amino acid sequence that is at least 80% identical, at least 81%, at
  • the anti-TIGIT antibody or antigen-binding portion thereof comprises: a HCDR1 comprising the amino acid sequence shown in SEQ ID NO:4; a HCDR2 comprising the amino acid sequence shown in SEQ ID NO:8; a HCDR3 comprising the amino acid sequence shown in SEQ ID NO:13; a LCDR1 comprising the amino acid sequence shown in SEQ ID NO:18; a LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19; and a LCDR3 comprising the amino acid sequence shown in SEQ ID NO:24.
  • the anti-TIGIT antibody or its antigen-binding portion provided comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a sequence shown in SEQ ID NO:35 having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, at least 100% identity, at least 101% identity, at least 102% identity, at least 103% identity, at least 104% identity, at least 105% identity, at least 106% identity, at least 107% identity, at least 108% identity, at least 109% identity
  • the light chain variable region comprises an amino acid sequence that is at least 80% identical, at least 81%, at
  • the anti-TIGIT antibody or antigen-binding portion thereof comprises: a HCDR1 comprising the amino acid sequence shown in SEQ ID NO:1; a HCDR2 comprising the amino acid sequence shown in SEQ ID NO:5; a HCDR3 comprising the amino acid sequence shown in SEQ ID NO:14; a LCDR1 comprising the amino acid sequence shown in SEQ ID NO:16; a LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19; and a LCDR3 comprising the amino acid sequence shown in SEQ ID NO:20.
  • an anti-TIGIT antibody or antigen-binding portion thereof comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least 89% identical, at least 90% identical, at least 91% identical, at least 92% identical, at least 93% identical, at least 94% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, at least 99% identical, or 100% identical to the sequence shown in SEQ ID NO: 37, and the light chain variable region comprises an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least
  • sequence shown in NO:36 has at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity.
  • the anti-TIGIT antibody or antigen-binding portion thereof comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO: 1; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 5; a HCDR3 comprising the amino acid sequence of SEQ ID NO: 14; a LCDR1 comprising the amino acid sequence of SEQ ID NO: 16; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 19; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 20.
  • the anti-TIGIT antibody or its antigen-binding portion provided comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a sequence shown in SEQ ID NO:38 having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, at least 100% identity, at least 101% identity, at least 102% identity, at least 103% identity, at least 104% identity, at least 105% identity, at least 106% identity, at least 107% identity, at least 108% identity, at least 109% identity
  • the light chain variable region comprises an amino acid sequence that is at least 80% identical, at least 81%, at
  • the anti-TIGIT antibody or antigen-binding portion thereof comprises: a HCDR1 comprising the amino acid sequence shown in SEQ ID NO:1; a HCDR2 comprising the amino acid sequence shown in SEQ ID NO:5; a HCDR3 comprising the amino acid sequence shown in SEQ ID NO:14; a LCDR1 comprising the amino acid sequence shown in SEQ ID NO:16; a LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19; and a LCDR3 comprising the amino acid sequence shown in SEQ ID NO:20.
  • the anti-TIGIT antibody or its antigen-binding portion provided comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a sequence shown in SEQ ID NO:39 having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, at least 100% identity, at least 101% identity, at least 102% identity, at least 103% identity, at least 104% identity, at least 105% identity, at least 106% identity, at least 107% identity, at least 108% identity, at least 109% identity
  • the light chain variable region comprises an amino acid sequence that is at least 80% identical, at least 81%, at
  • the anti-TIGIT antibody or antigen-binding portion thereof comprises: a HCDR1 comprising the amino acid sequence shown in SEQ ID NO:1; a HCDR2 comprising the amino acid sequence shown in SEQ ID NO:5; a HCDR3 comprising the amino acid sequence shown in SEQ ID NO:14; a LCDR1 comprising the amino acid sequence shown in SEQ ID NO:16; a LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19; and a LCDR3 comprising the amino acid sequence shown in SEQ ID NO:20.
  • the anti-TIGIT antibody or its antigen-binding portion provided comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a sequence shown in SEQ ID NO:40 having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, at least 100% identity, at least 101% identity, at least 102% identity, at least 103% identity, at least 104% identity, at least 105% identity, at least 106% identity, at least 107% identity, at least 108% identity, at least 109% identity
  • the light chain variable region comprises an amino acid sequence that is at least 99% identical or 100% identical to the light chain
  • the anti-TIGIT antibody or its antigen-binding portion comprises: a HCDR1 comprising the amino acid sequence shown in SEQ ID NO:2; a HCDR2 comprising the amino acid sequence shown in SEQ ID NO:5; a HCDR3 comprising the amino acid sequence shown in SEQ ID NO:15; a LCDR1 comprising the amino acid sequence shown in SEQ ID NO:17; a LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19; and a LCDR3 comprising the amino acid sequence shown in SEQ ID NO:21.
  • an anti-TIGIT antibody or antigen-binding portion thereof comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region
  • the light chain variable region comprises an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least 89% identical, at least 90% identical, at least 91% identical, at least 92% identical, at least 93% identical, at least 94% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, at least 99% identical, or 100% identical to the sequence of SEQ ID NO:42, wherein the light chain variable region comprises an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 8
  • the sequence shown in NO:41 has an amino acid sequence with at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity or 100% identity.
  • the anti-TIGIT antibody or antigen-binding portion thereof comprises: a HCDR1 comprising the amino acid sequence shown in SEQ ID NO:2; a HCDR2 comprising the amino acid sequence shown in SEQ ID NO:5; a HCDR3 comprising the amino acid sequence shown in SEQ ID NO:15; a LCDR1 comprising the amino acid sequence shown in SEQ ID NO:17; a LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19; and a LCDR3 comprising the amino acid sequence shown in SEQ ID NO:21.
  • the anti-TIGIT antibody or its antigen-binding portion provided comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a sequence shown in SEQ ID NO:40 having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, at least 100% identity, at least 101% identity, at least 102% identity, at least 103% identity, at least 104% identity, at least 105% identity, at least 106% identity, at least 107% identity, at least 108% identity, at least 109% identity
  • the light chain variable region comprises an amino acid sequence that is at least 80% identical, at least 81%, at
  • the anti-TIGIT antibody or its antigen-binding portion comprises: a HCDR1 comprising the amino acid sequence shown in SEQ ID NO:2; a HCDR2 comprising the amino acid sequence shown in SEQ ID NO:5; a HCDR3 comprising the amino acid sequence shown in SEQ ID NO:15; a LCDR1 comprising the amino acid sequence shown in SEQ ID NO:17; a LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19; and a LCDR3 comprising the amino acid sequence shown in SEQ ID NO:21.
  • the anti-TIGIT antibody or its antigen-binding portion provided comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a sequence shown in SEQ ID NO:42 having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, at least 100% identity, at least 101% identity, at least 102% identity, at least 103% identity, at least 104% identity, at least 105% identity, at least 106% identity, at least 107% identity, at least 108% identity, at least 109% identity
  • the light chain variable region comprises an amino acid sequence that is at least 80% identical, at least 81%, at
  • the anti-TIGIT antibody or its antigen-binding portion comprises: a HCDR1 comprising the amino acid sequence shown in SEQ ID NO:2; a HCDR2 comprising the amino acid sequence shown in SEQ ID NO:5; a HCDR3 comprising the amino acid sequence shown in SEQ ID NO:15; a LCDR1 comprising the amino acid sequence shown in SEQ ID NO:17; a LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19; and a LCDR3 comprising the amino acid sequence shown in SEQ ID NO:21.
  • an anti-TIGIT antibody or antigen-binding portion thereof comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least 89% identical, at least 90% identical, at least 91% identical, at least 92% identical, at least 93% identical, at least 94% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, at least 99% identical, or 100% identical to the sequence shown in SEQ ID NO:44, and the light chain variable region comprises an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least
  • the anti-TIGIT antibody or antigen-binding portion thereof comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO: 3; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 6; a HCDR3 comprising the amino acid sequence of SEQ ID NO: 11; a LCDR1 comprising the amino acid sequence of SEQ ID NO: 16; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 19; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 22.
  • the anti-TIGIT antibody or its antigen-binding portion provided comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a sequence shown in SEQ ID NO:46 having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, at least 100% identity, at least 101% identity, at least 102% identity, at least 103% identity, at least 104% identity, at least 105% identity, at least 106% identity, at least 107% identity, at least 108% identity, at least 109% identity
  • the light chain variable region comprises an amino acid sequence that is at least 80% identical, at least 81%, at
  • the anti-TIGIT antibody or antigen-binding portion thereof comprises: a HCDR1 comprising the amino acid sequence shown in SEQ ID NO:3; a HCDR2 comprising the amino acid sequence shown in SEQ ID NO:6; a HCDR3 comprising the amino acid sequence shown in SEQ ID NO:11; a LCDR1 comprising the amino acid sequence shown in SEQ ID NO:16; a LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19; and a LCDR3 comprising the amino acid sequence shown in SEQ ID NO:22.
  • the anti-TIGIT antibody or its antigen-binding portion provided comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a sequence shown in SEQ ID NO:47 having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, at least 100% identity, at least 101% identity, at least 102% identity, at least 103% identity, at least 104% identity, at least 105% identity, at least 106% identity, at least 107% identity, at least 108% identity, at least 109% identity
  • the light chain variable region comprises an amino acid sequence that is at least 80% identical, at least 81%, at
  • the anti-TIGIT antibody or antigen-binding portion thereof comprises: a HCDR1 comprising the amino acid sequence shown in SEQ ID NO:3; a HCDR2 comprising the amino acid sequence shown in SEQ ID NO:6; a HCDR3 comprising the amino acid sequence shown in SEQ ID NO:11; a LCDR1 comprising the amino acid sequence shown in SEQ ID NO:16; a LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19; and a LCDR3 comprising the amino acid sequence shown in SEQ ID NO:22.
  • an anti-TIGIT antibody or antigen-binding portion thereof comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least 89% identical, at least 90% identical, at least 91% identical, at least 92% identical, at least 93% identical, at least 94% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, at least 99% identical, or 100% identical to the sequence shown in SEQ ID NO:48, and the light chain variable region comprises an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least
  • sequence shown in NO:49 has an amino acid sequence with at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity or 100% identity.
  • the anti-TIGIT antibody or antigen-binding portion thereof comprises: a HCDR1 comprising the amino acid sequence shown in SEQ ID NO:4; a HCDR2 comprising the amino acid sequence shown in SEQ ID NO:7; a HCDR3 comprising the amino acid sequence shown in SEQ ID NO:12; a LCDR1 comprising the amino acid sequence shown in SEQ ID NO:16; a LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19; and a LCDR3 comprising the amino acid sequence shown in SEQ ID NO:23.
  • the anti-TIGIT antibody or its antigen-binding portion provided comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a sequence shown in SEQ ID NO:50 having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, at least 100% identity, at least 101% identity, at least 102% identity, at least 103% identity, at least 104% identity, at least 105% identity, at least 106% identity, at least 107% identity, at least 108% identity, at least 109% identity
  • the light chain variable region comprises an amino acid sequence that is at least 80% identical, at least 81%, at
  • the anti-TIGIT antibody or antigen-binding portion thereof comprises: a HCDR1 comprising the amino acid sequence shown in SEQ ID NO:4; a HCDR2 comprising the amino acid sequence shown in SEQ ID NO:7; a HCDR3 comprising the amino acid sequence shown in SEQ ID NO:12; a LCDR1 comprising the amino acid sequence shown in SEQ ID NO:16; a LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19; and a LCDR3 comprising the amino acid sequence shown in SEQ ID NO:23.
  • the anti-TIGIT antibody or its antigen-binding portion provided comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a sequence shown in SEQ ID NO:51 having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, at least 100% identity, at least 101% identity, at least 102% identity, at least 103% identity, at least 104% identity, at least 105% identity, at least 106% identity, at least 107% identity, at least 108% identity, at least 109% identity
  • the light chain variable region comprises an amino acid sequence that is at least 80% identical, at least 81%, at
  • the anti-TIGIT antibody or antigen-binding portion thereof comprises: a HCDR1 comprising the amino acid sequence shown in SEQ ID NO:4; a HCDR2 comprising the amino acid sequence shown in SEQ ID NO:7; a HCDR3 comprising the amino acid sequence shown in SEQ ID NO:12; a LCDR1 comprising the amino acid sequence shown in SEQ ID NO:16; a LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19; and a LCDR3 comprising the amino acid sequence shown in SEQ ID NO:23.
  • the anti-TIGIT antibody or its antigen-binding portion provided comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a sequence shown in SEQ ID NO:52 having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, at least 100% identity, at least 101% identity, at least 102% identity, at least 103% identity, at least 104% identity, at least 105% identity, at least 106% identity, at least 107% identity, at least 108% identity, at least 109% identity
  • the light chain variable region comprises an amino acid sequence that is at least 80% identical, at least 81%, at
  • the anti-TIGIT antibody or antigen-binding portion thereof comprises: a HCDR1 comprising the amino acid sequence shown in SEQ ID NO:4; a HCDR2 comprising the amino acid sequence shown in SEQ ID NO:8; a HCDR3 comprising the amino acid sequence shown in SEQ ID NO:13; a LCDR1 comprising the amino acid sequence shown in SEQ ID NO:18; a LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19; and a LCDR3 comprising the amino acid sequence shown in SEQ ID NO:24.
  • an anti-TIGIT antibody or antigen-binding portion thereof provided comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises an amino acid sequence having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, or 100% identity to the sequence shown in SEQ ID NO:54, and the light chain variable region comprises an amino acid sequence having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity,
  • the anti-TIGIT antibody or antigen-binding portion thereof comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO:4; a HCDR2 comprising the amino acid sequence of SEQ ID NO:8; a HCDR3 comprising the amino acid sequence of SEQ ID NO:13; a LCDR1 comprising the amino acid sequence of SEQ ID NO:18; a LCDR2 comprising the amino acid sequence of SEQ ID NO:19; and a LCDR3 comprising the amino acid sequence of SEQ ID NO:24.
  • the anti-TIGIT antibody or its antigen-binding portion provided comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a sequence shown in SEQ ID NO:55 having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, at least 100% identity, at least 101% identity, at least 102% identity, at least 103% identity, at least 104% identity, at least 105% identity, at least 106% identity, at least 107% identity, at least 108% identity, at least 109% identity
  • the light chain variable region comprises an amino acid sequence that is at least 80% identical, at least 81%, at
  • the anti-TIGIT antibody or antigen-binding portion thereof comprises: a HCDR1 comprising the amino acid sequence shown in SEQ ID NO:1; a HCDR2 comprising the amino acid sequence shown in SEQ ID NO:5; a HCDR3 comprising the amino acid sequence shown in SEQ ID NO:14; a LCDR1 comprising the amino acid sequence shown in SEQ ID NO:16; a LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19; and a LCDR3 comprising the amino acid sequence shown in SEQ ID NO:20.
  • the anti-TIGIT antibody or its antigen-binding portion provided comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a sequence shown in SEQ ID NO:57 having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, at least 100% identity, at least 101% identity, at least 102% identity, at least 103% identity, at least 104% identity, at least 105% identity, at least 106% identity, at least 107% identity, at least 108% identity, at least 109% identity
  • the light chain variable region comprises an amino acid sequence that is at least 80% identical, at least 81%, at
  • the anti-TIGIT antibody or its antigen-binding portion comprises: a HCDR1 comprising the amino acid sequence shown in SEQ ID NO:2; a HCDR2 comprising the amino acid sequence shown in SEQ ID NO:5; a HCDR3 comprising the amino acid sequence shown in SEQ ID NO:15; a LCDR1 comprising the amino acid sequence shown in SEQ ID NO:17; a LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19; and a LCDR3 comprising the amino acid sequence shown in SEQ ID NO:21.
  • an anti-TIGIT antibody or antigen-binding portion thereof comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least 89% identical, at least 90% identical, at least 91% identical, at least 92% identical, at least 93% identical, at least 94% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, at least 99% identical, or 100% identical to the sequence shown in SEQ ID NO:59, and the light chain variable region comprises an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least
  • NO:60 has an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least 89% identical, at least 90% identical, at least 91% identical, at least 92% identical, at least 93% identical, at least 94% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, at least 99% identical, or 100% identical.
  • the anti-TIGIT antibody or antigen-binding portion thereof comprises: a HCDR1 comprising the amino acid sequence of SEQ ID NO:3; a HCDR2 comprising the amino acid sequence of SEQ ID NO:6; a HCDR3 comprising the amino acid sequence of SEQ ID NO:11; a LCDR1 comprising the amino acid sequence of SEQ ID NO:16; a LCDR2; and LCDR3 comprising the amino acid sequence shown in SEQ ID NO:22.
  • the anti-TIGIT antibody or its antigen-binding portion provided comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a sequence shown in SEQ ID NO:61 having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, at least 100% identity, at least 101% identity, at least 102% identity, at least 103% identity, at least 104% identity, at least 105% identity, at least 106% identity, at least 107% identity, at least 108% identity, at least 109% identity
  • the light chain variable region comprises an amino acid sequence that is at least 80% identical, at least 81%, at
  • the anti-TIGIT antibody or antigen-binding portion thereof comprises: a HCDR1 comprising the amino acid sequence shown in SEQ ID NO:4; a HCDR2 comprising the amino acid sequence shown in SEQ ID NO:7; a HCDR3 comprising the amino acid sequence shown in SEQ ID NO:12; a LCDR1 comprising the amino acid sequence shown in SEQ ID NO:16; a LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19; and a LCDR3 comprising the amino acid sequence shown in SEQ ID NO:23.
  • the anti-TIGIT antibody or its antigen-binding portion provided comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a sequence shown in SEQ ID NO:63 having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, at least 100% identity, at least 101% identity, at least 102% identity, at least 103% identity, at least 104% identity, at least 105% identity, at least 106% identity, at least 107% identity, at least 108% identity, at least 109% identity
  • the light chain variable region comprises an amino acid sequence that is at least 99% identical or 100% identical to the light chain
  • the anti-TIGIT antibody or antigen-binding portion thereof comprises: a HCDR1 comprising the amino acid sequence shown in SEQ ID NO:4; a HCDR2 comprising the amino acid sequence shown in SEQ ID NO:8; a HCDR3 comprising the amino acid sequence shown in SEQ ID NO:13; a LCDR1 comprising the amino acid sequence shown in SEQ ID NO:18; a LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19; and a LCDR3 comprising the amino acid sequence shown in SEQ ID NO:24.
  • an anti-TIGIT antibody or antigen-binding portion thereof comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises or consists of an amino acid sequence as shown in SEQ ID NO: 25, 27, 29, 31, 33, 35, 37, 38, 39, 40, 42, 44, 46, 47, 48, 50, 51, 52, 54, 55, 57, 59, 61 or 63, and the light chain variable region comprises an amino acid sequence as shown in SEQ ID NO: 25, 27, 29, 31, 33, 35, 37, 38, 39, 40, 42, 44, 46, 47, 48, 50, 51, 52, 54, 55, 57, 59, 61 or 63.
  • the anti-TIGIT antibody provided comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO:25, and the light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO:26.
  • the anti-TIGIT antibody provided comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 27, and the light chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 28.
  • the anti-TIGIT antibody provided comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 29, and the light chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 30.
  • the anti-TIGIT antibody provided comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 31, and the light chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 32.
  • the anti-TIGIT antibody provided comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 33 or the amino acid sequence shown in SEQ ID NO: 33.
  • the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 34 or consists of the amino acid sequence shown in SEQ ID NO: 34.
  • the anti-TIGIT antibody provided comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 35, and the light chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 36.
  • the anti-TIGIT antibody provided comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 37, and the light chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 36.
  • the anti-TIGIT antibody provided comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 38, and the light chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 36.
  • the anti-TIGIT antibody provided comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 39, and the light chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 36.
  • the anti-TIGIT antibody provided comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO:40, and the light chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO:41.
  • the anti-TIGIT antibody provided comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO:42, and the light chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO:41.
  • the anti-TIGIT antibody provided comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 40, and the light chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 43.
  • the anti-TIGIT antibody provided comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 42, and the light chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 43.
  • the anti-TIGIT antibody provided comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 44, and the light chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 45.
  • the anti-TIGIT antibody provided comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 46, and the light chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 45.
  • the anti-TIGIT antibody provided comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 47, and the light chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 45.
  • the anti-TIGIT antibody provided comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 48, and the light chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 49.
  • the anti-TIGIT antibody provided comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 50, and the light chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 49.
  • the anti-TIGIT antibody provided comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 51, and the light chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 49.
  • an anti-TIGIT antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises SEQ ID NO:52 or consists of the amino acid sequence shown in SEQ ID NO:52, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:53 or consists of the amino acid sequence shown in SEQ ID NO:53.
  • the anti-TIGIT antibody provided comprises a heavy chain variable region and a light chain variable region
  • the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:54 or consists of the amino acid sequence shown in SEQ ID NO:54
  • the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:53 or consists of the amino acid sequence shown in SEQ ID NO:53.
  • the anti-TIGIT antibody provided comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 55, and the light chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 56.
  • the anti-TIGIT antibody provided comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 57, and the light chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 58.
  • the anti-TIGIT antibody provided comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 59, and the light chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 60.
  • the anti-TIGIT antibody provided comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 61, and the light chain variable region comprises or consists of the amino acid sequence shown in SEQ ID NO: 62.
  • the anti-TIGIT antibody provided comprises a heavy chain variable region and a light chain variable region
  • the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:63 or consists of the amino acid sequence shown in SEQ ID NO:63
  • the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:64 or consists of the amino acid sequence shown in SEQ ID NO:64.
  • the anti-TIGIT antibodies provided herein comprise heavy chains and light chains, and the heavy chains and light chains include a constant region in addition to the heavy chain variable region and light chain variable region described herein.
  • the heavy chain constant region of the anti-TIGIT antibody may be from any type of constant region, such as IgG, IgM, IgD, IgA and IgE or variants thereof; and any isotype, such as IgG1, IgG2, IgG3 and IgG4 or variants thereof.
  • the heavy chain constant region of the anti-TIGIT antibody is a human IgG1 isotype or a variant thereof.
  • the light chain constant region of the isolated anti-TIGIT antibody is a human ⁇ light chain constant region or a variant thereof. In some embodiments, the light chain constant region of the isolated anti-TIGIT antibody is a human ⁇ light chain constant region or a variant thereof.
  • the constant region variant refers to an amino acid sequence having 1, 2, 3, 4 or 5 amino acid substitutions, deletions and additions relative to the constant region. In some embodiments, the substitution may be a conservative amino acid substitution.
  • the anti-TIGIT antibody provided comprises a heavy chain and a light chain, wherein the heavy chain comprises a sequence shown in SEQ ID NO:65, 67, 69, 71, 73, 75, 77, 78, 79, 80, 82, 84, 86, 87, 88, 90, 91, 92 or 94 having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity
  • the light chain comprises an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86%
  • an anti-TIGIT antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises a sequence having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, or An amino acid sequence with 100% identity, wherein the light chain comprises an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least 89% identical, at least 90% identical, at least 91% identical, at least 92% identical, at least
  • an anti-TIGIT antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the sequence shown in SEQ ID NO: 67. having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity or 100% identity to an amino acid sequence of SEQ ID NO: 1.
  • the sequence shown in NO:68 has an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least 89% identical, at least 90% identical, at least 91% identical, at least 92% identical, at least 93% identical, at least 94% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, at least 99% identical or 100% identical.
  • an anti-TIGIT antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises a sequence having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, or An amino acid sequence with 100% identity, wherein the light chain comprises an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least 89% identical, at least 90% identical, at least 91% identical, at least 92% identical, at least
  • an anti-TIGIT antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises a sequence having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, or An amino acid sequence with 100% identity, wherein the light chain comprises an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least 89% identical, at least 90% identical, at least 91% identical, at least 92% identical, at least
  • an anti-TIGIT antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises a sequence having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, or An amino acid sequence with 100% identity, wherein the light chain comprises an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least 89% identical, at least 90% identical, at least 91% identical, at least 92% identical, at least
  • the anti-TIGIT antibody provided comprises a heavy chain and a light chain, wherein the heavy chain comprises a sequence having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, or An amino acid sequence with 100% identity, wherein the light chain comprises an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least 89% identical, at least 90% identical, at least 91% identical, at least 92% identical, at least 93%
  • an anti-TIGIT antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the sequence shown in SEQ ID NO: 77. having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity or 100% identity to an amino acid sequence of SEQ ID NO: 1.
  • the sequence shown in NO:76 has an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least 89% identical, at least 90% identical, at least 91% identical, at least 92% identical, at least 93% identical, at least 94% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, at least 99% identical or 100% identical.
  • an anti-TIGIT antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises a sequence having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, or An amino acid sequence with 100% identity, wherein the light chain comprises an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least 89% identical, at least 90% identical, at least 91% identical, at least 92% identical, at least
  • an anti-TIGIT antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises a sequence having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, or An amino acid sequence with 100% identity, wherein the light chain comprises an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least 89% identical, at least 90% identical, at least 91% identical, at least 92% identical, at least
  • an anti-TIGIT antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises a sequence having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, or An amino acid sequence with 100% identity, wherein the light chain comprises an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least 89% identical, at least 90% identical, at least 91% identical, at least 92% identical, at least
  • an anti-TIGIT antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises a sequence having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, or An amino acid sequence with 100% identity, wherein the light chain comprises an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least 89% identical, at least 90% identical, at least 91% identical, at least 92% identical, at least
  • an anti-TIGIT antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises a sequence as shown in SEQ ID NO: 80. having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity or 100% identity to an amino acid sequence of SEQ ID NO: 1.
  • the sequence shown in NO:83 has an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least 89% identical, at least 90% identical, at least 91% identical, at least 92% identical, at least 93% identical, at least 94% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, at least 99% identical or 100% identical.
  • an anti-TIGIT antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises a sequence having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, or An amino acid sequence with 100% identity, wherein the light chain comprises an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least 89% identical, at least 90% identical, at least 91% identical, at least 92% identical, at least
  • an anti-TIGIT antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises a sequence having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, or An amino acid sequence with 100% identity, wherein the light chain comprises an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least 89% identical, at least 90% identical, at least 91% identical, at least 92% identical, at least
  • an anti-TIGIT antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises a sequence having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, or An amino acid sequence with 100% identity, wherein the light chain comprises an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least 89% identical, at least 90% identical, at least 91% identical, at least 92% identical, at least
  • an anti-TIGIT antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises a sequence having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, or An amino acid sequence with 100% identity, wherein the light chain comprises an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least 89% identical, at least 90% identical, at least 91% identical, at least 92% identical, at least
  • an anti-TIGIT antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises a sequence as shown in SEQ ID NO: 88. having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity or 100% identity to an amino acid sequence of SEQ ID NO: 1.
  • sequence shown in NO:89 has an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least 89% identical, at least 90% identical, at least 91% identical, at least 92% identical, at least 93% identical, at least 94% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, at least 99% identical or 100% identical.
  • an anti-TIGIT antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises a sequence having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, or An amino acid sequence with 100% identity, wherein the light chain comprises an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least 89% identical, at least 90% identical, at least 91% identical, at least 92% identical, at least
  • an anti-TIGIT antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises a sequence having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, or An amino acid sequence with 100% identity, wherein the light chain comprises an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least 89% identical, at least 90% identical, at least 91% identical, at least 92% identical, at least
  • an anti-TIGIT antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises a sequence having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, or An amino acid sequence with 100% identity, wherein the light chain comprises an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least 89% identical, at least 90% identical, at least 91% identical, at least 92% identical, at least
  • an anti-TIGIT antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises a sequence having at least 80% identity, at least 81% identity, at least 82% identity, at least 83% identity, at least 84% identity, at least 85% identity, at least 86% identity, at least 87% identity, at least 88% identity, at least 89% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, or An amino acid sequence with 100% identity, wherein the light chain comprises an amino acid sequence that is at least 80% identical, at least 81% identical, at least 82% identical, at least 83% identical, at least 84% identical, at least 85% identical, at least 86% identical, at least 87% identical, at least 88% identical, at least 89% identical, at least 90% identical, at least 91% identical, at least 92% identical, at least
  • an anti-TIGIT antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises SEQ ID NO: 65, 67, 69, 71, 73, 75, 77, 78, 79, 80, 82, 84, 86, 87, 88, 90, 91, 92 or 94, or consist of the amino acid sequence shown in SEQ ID NO:65, 67, 69, 71, 73, 75, 77, 78, 79, 80, 82, 84, 86, 87, 88, 90, 91, 92 or 94, and the light chain comprises the amino acid sequence shown in SEQ ID NO:66, 68, 70, 72, 74, 76, 81, 83, 85, 89 or 93, or consists of the amino acid sequence shown in SEQ ID NO:66, 68, 70, 72, 74, 76, 81, 83, 85, 89 or 93.
  • an anti-TIGIT antibody provided comprises a heavy chain and a light chain, the heavy chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 65, and the light chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 66.
  • an anti-TIGIT antibody provided comprises a heavy chain and a light chain, the heavy chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 67, and the light chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 68.
  • an anti-TIGIT antibody provided comprises a heavy chain and a light chain, the heavy chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 69, and the light chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 70.
  • an anti-TIGIT antibody provided comprises a heavy chain and a light chain, the heavy chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 71, and the light chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 72.
  • an anti-TIGIT antibody provided comprises a heavy chain and a light chain, the heavy chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 73, and the light chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 74.
  • an anti-TIGIT antibody provided comprises a heavy chain and a light chain, the heavy chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 75, and the light chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 76.
  • an anti-TIGIT antibody provided comprises a heavy chain and a light chain, the heavy chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 77, and the light chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 76.
  • an anti-TIGIT antibody provided comprises a heavy chain and a light chain, the heavy chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 78, and the light chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 76.
  • an anti-TIGIT antibody provided comprises a heavy chain and a light chain, the heavy chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 79, and the light chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 76.
  • an anti-TIGIT antibody provided comprises a heavy chain and a light chain, the heavy chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 80, and the light chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 81.
  • an anti-TIGIT antibody provided comprises a heavy chain and a light chain, the heavy chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 82, and the light chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 81.
  • an anti-TIGIT antibody provided comprises a heavy chain and a light chain, the heavy chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 80, and the light chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 83.
  • an anti-TIGIT antibody provided comprises a heavy chain and a light chain, the heavy chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 82, and the light chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 83.
  • an anti-TIGIT antibody provided comprises a heavy chain and a light chain, the heavy chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 84, and the light chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 85.
  • an anti-TIGIT antibody provided comprises a heavy chain and a light chain, the heavy chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 86, and the light chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 85.
  • the anti-TIGIT antibody provided comprises a heavy chain and a light chain, the heavy chain comprising or consisting of the amino acid sequence shown in SEQ ID NO:87, and the light chain comprising or consisting of the amino acid sequence shown in SEQ ID NO:85.
  • the anti-TIGIT antibody provided comprises a heavy chain and a light chain, the heavy chain comprising or consisting of the amino acid sequence shown in SEQ ID NO:88, and the light chain comprising or consisting of the amino acid sequence shown in SEQ ID NO:89.
  • the anti-TIGIT antibody provided comprises a heavy chain and a light chain, the heavy chain comprising or consisting of the amino acid sequence shown in SEQ ID NO:90, and the light chain comprising or consisting of the amino acid sequence shown in SEQ ID NO:89.
  • the anti-TIGIT antibody provided comprises a heavy chain and a light chain, the heavy chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 91, and the light chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 89. In some embodiments, the anti-TIGIT antibody provided comprises a heavy chain and a light chain, the heavy chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 92, and the light chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 93.
  • the anti-TIGIT antibody provided comprises a heavy chain and a light chain, the heavy chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 94, and the light chain comprising or consisting of the amino acid sequence shown in SEQ ID NO: 93.
  • the anti-TIGIT antibody, or an antigen binding portion thereof binds to human TIGIT. In some embodiments, the anti-TIGIT antibody, or an antigen binding portion thereof, binds to cynomolgus monkey TIGIT. In some embodiments, the anti-TIGIT antibody, or an antigen binding portion thereof, binds to rat TIGIT. In some embodiments, the antibody, or an antigen binding portion thereof, binds to human TIGIT with a K value of 1.38E-09M or less.
  • the antibody, or antigen-binding portion thereof has a binding affinity ( KD ) for human TIGIT in the range of about 1E-12M to about 1E-05M, about 1E-12M to about 1.38E-07M, about 1E-12M to about 1.38E-06M, about 1E-12M to about 1.38E-05M, about 1E-11M to about 1.38E-08M, about 9.68E-10M to about 1.38E-08M, about 9.68E-10M to about 1.38E-09M, about 1.10E-10M to about 1.38E-08M, or about 1.10E-10M to about 1.38E-09M.
  • KD binding affinity for human TIGIT in the range of about 1E-12M to about 1E-05M, about 1E-12M to about 1.38E-07M, about 1E-12M to about 1.38E-06M, about 1E-12M to about 1.38E-05M, about 1E-11M to about 1.38E-08M, about 9.68E-10M to about 1.38
  • the antibody, or antigen-binding portion thereof has a binding affinity ( KD ) for human TIGIT of about 1E-05M or less, about 1.38E-07M or less, about 1.38E-08M or less, about 1.38E-09M or less, about 9.36E-10M or less, about 4.44E-10M or less, about 2.55E-10M or less, about 2.15E-10M or less, or about 1.10E-10M or less.
  • KD binding affinity for human TIGIT of about 1E-05M or less, about 1.38E-07M or less, about 1.38E-08M or less, about 1.38E-09M or less, about 9.36E-10M or less, about 4.44E-10M or less, about 2.55E-10M or less, about 2.15E-10M or less, or about 1.10E-10M or less.
  • the antibody, or antigen-binding portion thereof has a binding affinity (KD) for human TIGIT of about 1E-05M or less, about 1.38E-07M or less, about 1.38E-08M or less, about 1.38E-09M or less, about 9.36E-10M or less, about 4.44E-10M or less, about 2.55E-10M or less, about 2.15E-10M or less, or about 1.10E-10M or less.
  • KD binding affinity
  • the binding affinity, KD, of an anti-TIGIT antibody, or antigen-binding portion thereof, provided herein for human TIGIT is measured by Biacore.
  • the anti-TIGIT antibody has a binding EC50 of about 0.01 nM to about 2 nM, about 0.01 nM to about 1.5 nM, about 0.01 nM to about 1 nM, about 0.01 nM to about 0.5 nM, about 0.01 nM to about 0.25 nM, about 0.05 nM to about 0.25 nM, or about 0.05 nM to about 0.15 nM for human TIGIT.
  • the anti-TIGIT antibody, or an antigen-binding portion thereof has a binding EC50 of about 2 nM or less, about 1.5 nM or less, about 1 nM or less, about 0.5 nM or less, about 0.25 nM or less, about 0.15 nM or less, about 0.12 nM or less, about 0.09 nM or less, or about 0.07 nM or less for human TIGIT.
  • the EC50 of the anti-TIGIT antibodies, or antigen-binding portions thereof, provided herein are measured by ELISA or FACS.
  • the anti-TIGIT antibody, or an antigen-binding portion thereof blocks the binding of TIGIT to CD 155. In some embodiments, the anti-TIGIT antibody, or an antigen-binding portion thereof, blocks the binding of TIGIT to CD 155 with an IC50 of about 0.01 nM to about 2 nM, about 0.01 nM to about 1.5 nM, about 0.01 nM to about 1 nM, about 0.01 nM to about 0.5 nM, about 0.01 nM to about 0.25 nM, about 0.05 nM to about 0.25 nM, or about 0.05 nM to about 0.15 nM.
  • the IC50 of the anti-TIGIT antibody or its antigen-binding portion blocking the binding of TIGIT to CD155 is about 2nM or less, about 1.5nM or less, about 1nM or less, about 0.5nM or less, about 0.25nM or less, about 0.15nM or less, about 0.11nM or less, about 0.10nM or less, or about 0.09nM or less. In some embodiments, the IC50 of the anti-TIGIT antibody or its antigen-binding portion provided herein blocking the binding of TIGIT to CD155 is measured by ELISA or FACS.
  • anti-TIGIT antibodies or antigen-binding portions thereof promote the killing activity of NK cells.
  • TIGIT is expressed on the surface of activated NK cells.
  • target cells such as tumor cells
  • the killing activity of NK cells against target cells is inhibited.
  • the binding of TIGIT to CD155 is blocked by anti-TIGIT antibodies, the immunosuppressive effect brought by TIGIT is relieved, and the killing activity of NK cells against target cells (specific examples such as Widr cells, etc.) is promoted.
  • the EC50 of anti-TIGIT antibodies or antigen-binding portions thereof in promoting the killing activity of NK cells is about 0.01pM to about 20pM, about 0.01pM to about 15pM, about 0.01pM to about 10pM, about 0.1pM to about 10pM, about 0.1pM to about 5pM, about 0.1pM to about 3pM, or about 0.5pM to about 3pM.
  • the EC50 of the anti-TIGIT antibody or its antigen-binding portion in promoting NK cell killing activity is about 20 pM or less, about 15 pM or less, about 10 pM or less, about 9.155 pM or less, about 8.952 pM or less, about 6.118 pM or less, about 5.029 pM or less, about 3.375 pM or less, about 2.842 pM or less, about 2.785 pM or less, about 2.122 pM or less, about 1.743 pM or less, about 0.7557 pM or less, about 0.5832 pM or less, about 0.2675 pM or less, or about 0.2406 pM or less.
  • anti-TIGIT antibodies or antigen-binding portions thereof promote ADCC of NK cells against Tregs.
  • TIGIT is also expressed on the surface of activated Treg cells at relatively high abundance.
  • ADCC of NK cells against Treg cells can be mediated by anti-TIGIT antibodies (hIgG1 subtype).
  • the EC50 of anti-TIGIT antibodies or antigen-binding portions thereof in promoting ADCC of NK cells against Tregs is about 0.001 pM to about 20 pM, about 0.001 pM to about 15 pM, about 0.001 pM to about 12 pM, about 0.01 pM to about 12 pM, about 0.01 pM to about 10 pM, about 0.01 pM to about 5 pM, about 0.02 pM to about 5 pM, about 0.02 pM to about 3 pM, or about 0.5 pM to about 3 pM.
  • the EC50 of the anti-TIGIT antibody or its antigen-binding portion for promoting NK cell ADCC on Treg is about 20 pM or less, about 15 pM or less, about 12 pM or less, about 11.84 pM or less, about 10 pM or less, about 4.696 pM or less, about 3.907 pM or less, about 2.53 pM or less, about 1.74 pM or less, about 0.9652 pM or less, about 0.79 pM or less, about 0.6992 pM or less, about 0.5121 pM or less, about 0.2905 pM or less, about 0.09273 pM or less, about 0.06101 pM or less, or about 0.02187 pM or less.
  • anti-TIGIT antibodies or antigen-binding portions thereof promote T cell function.
  • Activated CD8 + T cells express relatively high abundance of TIGIT on their surface, and TIGIT interacts with its ligand to mediate CD8 + T cell inhibitory signal transduction, leading to cell exhaustion.
  • Anti-TIGIT antibodies can reverse the exhausted state of CD8 + T cells and increase factor release and immune activity of CD8 + T cells.
  • the concentration of IFN ⁇ secreted by CD8 + T cells is about 40 pg/mL to about 2000 pg/mL, about 40 pg/mL to about 1500 pg/mL, about 60 pg/mL to about 1500 pg/mL, about 60 pg/mL to about 1300 pg/mL, about 80 pg/mL to about 1300 pg/mL, about 80 pg/mL to about 1000 pg/mL, about 80 pg/mL to about 600 pg/mL, or about 200 pg/mL to about 600 pg/mL.
  • the present disclosure provides an anti-TIGIT antibody or antigen-binding portion thereof that exhibits one or a combination of the following properties:
  • the anti-TIGIT antibody and/or its antigen binding portion has one, two, three, four or five of the properties (i)-(v). In some embodiments, the antibody or its antigen binding portion has the properties (i), (ii) and (iii). In some embodiments, the antibody or its antigen binding portion has the properties (i), (ii) and (iv). In some embodiments, the antibody or its antigen binding portion has the properties (i), (ii) and (v). In some embodiments, the antibody or its antigen binding portion has the properties (i), (ii), (iii) and (iv). In some embodiments, the antibody or its antigen binding portion has the properties (i), (ii), (iii) and (v). In some embodiments, the antibody or its antigen binding portion has the properties (i), (ii), (iii) and (v).
  • the antibody or its antigen binding portion has the properties (i), (ii), (iii) and (v). In some embodiments, the antibody or its antigen binding portion has the properties (i), (ii), (iv) and (v). In some embodiments, the antibody or its antigen binding portion has the properties (i), (ii), (iii), (iv) and (v). In some embodiments, the antibody or its antigen binding portion has the properties (i), (ii), (iii), (iv) and (v).
  • the anti-TIGIT antibodies provided herein are monoclonal antibodies.
  • the present disclosure provides an anti-TIGIT antibody, or antigen-binding portion thereof, that binds to the same epitope on TIGIT as any of the exemplary antibodies provided herein, such as a chimeric antibody or humanized antibody that binds to the same epitope as Ab1, such as a chimeric antibody or humanized antibody that binds to the same epitope as Ab2, such as a chimeric antibody or humanized antibody that binds to the same epitope as Ab19, such as a chimeric antibody or humanized antibody that binds to the same epitope as Ab23, such as a chimeric antibody or humanized antibody that binds to the same epitope as Ab30.
  • a chimeric antibody or humanized antibody that binds to the same epitope as Ab1 such as a chimeric antibody or humanized antibody that binds to the same epitope as Ab2
  • a chimeric antibody or humanized antibody that binds to the same epitope as Ab19 such as a
  • an anti-TIGIT antibody or an antigen-binding portion thereof competes with any of the exemplary antibodies provided herein for binding to TIGIT, such as a chimeric or humanized antibody of Abl for binding to TIGIT, such as a chimeric or humanized antibody of Ab2 for binding to TIGIT, such as a chimeric or humanized antibody of Ab19 for binding to TIGIT, such as a chimeric or humanized antibody of Ab23 for binding to TIGIT, such as a chimeric or humanized antibody of Ab30 for binding to TIGIT.
  • Binding to TIGIT can be measured by ELISA, flow cytometry, surface plasmon resonance (SPR) assay, or any other method known in the art.
  • the present disclosure provides some exemplary anti-TIGIT monoclonal antibodies, including chimeric versions of Ab1, Ab2, Ab19, Ab23 and Ab30 antibodies (ch-Ab1, ch-Ab2, ch-Ab19, ch-Ab23 and ch-Ab30) and humanized variants of Ab1, Ab2, Ab19, Ab23 and Ab30.
  • the amino acid sequences of the heavy chain CDRs (HCDR1, HCDR2 and HCDR3) of the exemplary anti-TIGIT antibodies provided herein are provided in Table S1 below, and the amino acid sequences of the light chain CDRs (LCDR1, LCDR2 and LCDR3) are provided in Table S2 below.
  • CDRs complementary determining regions
  • Kabat Kabat (Kabat et al., Proteins of Immunology) based on the heavy/light chain variable region sequences. Protein sequences, fifth edition, National Institutes of Health, Bethesda, Maryland (1991)), Chothia (J Mol Biol 273:927-48, 1997), IMGT (Lefranc MP, Immunologist, 7, 132-136 (1999); Lefranc, MP et al., Dev. Comp.
  • CDR regions can also be determined based on a combination of two or more of the Kabat, Chothia, IMGT, AbM and Contact definition rules.
  • the CDR regions shown in Tables S1 and S2 are defined by the IMGT numbering system. It will be understood by those skilled in the art that, unless otherwise specified, the term "CDR" of a given antibody or region thereof (e.g., a variable region) should be understood to encompass CDRs defined by any known scheme.
  • the scope of the antibodies also covers antibodies defined by CDR sequences converted to other arbitrary numbering system definitions (e.g., a combination of one or more of the definitions of Kabat, Chothia, IMGT, AbM or Contact, etc., which are well known in the art).
  • the amino acid sequences of the variable regions and full-length heavy and light chains of the exemplary anti-TIGIT antibodies provided herein are provided in Tables S3 and S4 below, respectively, and the nucleotide sequences encoding the variable regions and full-length heavy and light chains of the anti-TIGIT antibodies are provided in Tables S5 and S6 below, respectively.
  • the present disclosure provides an antibody drug conjugate comprising an anti-TIGIT antibody or an antigen binding portion thereof.
  • the therapeutic agent that can be coupled to the anti-TIGIT antibody or its antigen binding portion may include, but is not limited to, a cytotoxic drug, a radioisotope, an immunomodulator, or an antibody.
  • the anti-TIGIT antibody or its antigen binding portion is directly coupled to the therapeutic agent.
  • the anti-TIGIT antibody or its antigen binding portion is coupled to the therapeutic agent via a linker.
  • the present disclosure comprises a fusion protein of an anti-TIGIT antibody of the present disclosure, or an antigen-binding portion thereof.
  • the present disclosure provides a pharmaceutical composition
  • a pharmaceutical composition comprising an anti-TIGIT antibody or an antigen-binding portion thereof, or an antibody-drug conjugate as described herein, or a fusion protein as described herein, and further comprising one or more pharmaceutically acceptable carriers.
  • the pharmaceutical composition comprises any monoclonal antibody of chimeric antibodies and humanized antibodies of Ab1, Ab2, Ab19, Ab23, and Ab30 antibodies, and a pharmaceutically acceptable carrier.
  • Pharmaceutically acceptable carriers include, for example, excipients, diluents, encapsulating materials, fillers, buffers, or Other agents.
  • the pharmaceutical composition is injectable.
  • the pharmaceutical composition is sterile.
  • the present disclosure provides an isolated nucleic acid comprising a sequence encoding an anti-TIGIT antibody or an antigen-binding portion thereof as described herein, in some embodiments, the nucleic acid may encode an amino acid sequence comprising an antibody heavy chain variable region and/or a light chain variable region as described herein. In other embodiments, the nucleic acid may encode an amino acid sequence comprising an antibody heavy chain and/or an antibody light chain as described herein.
  • the sequence table exemplifies the nucleotide sequences of some variable regions, antibody heavy chains, and light chains.
  • the present disclosure provides a vector comprising the isolated nucleic acid.
  • the vector is a cloning vector; in other embodiments, the vector is an expression vector.
  • the expression vector can optionally be any expression vector capable of expressing the anti-TIGIT antibody or antigen-binding portion thereof described herein.
  • the present disclosure provides a host cell comprising the vector, the host cell being a suitable host cell for cloning or encoding an anti-TIGIT antibody or its antigen binding portion.
  • the host cell is a prokaryotic cell.
  • the host cell is a eukaryotic cell.
  • the host cell is selected from yeast cells, mammalian cells, or other cells suitable for preparing antibodies or their antigen binding portions. Mammalian cells are, for example, Chinese hamster ovary (CHO) cells.
  • the present disclosure provides a method for preparing an anti-TIGIT antibody or an antigen-binding portion thereof, the method comprising: isolating a nucleic acid encoding an anti-TIGIT antibody or an antigen-binding portion thereof, and inserting it into one or more vectors for further cloning and/or expression in a host cell.
  • the nucleic acid can be obtained by various methods known in the art, such as gene cloning, gene splicing, and chemical synthesis. Under conditions suitable for host cells containing nucleic acids encoding the antibody or its antigen-binding portion, the host cell is cultured, and the antibody or its antigen-binding portion is recovered from the host cell or the host cell culture medium.
  • the present disclosure provides a method for treating cancer in a subject, wherein the method comprises administering to the subject a therapeutically effective amount of the anti-TIGIT antibody or its antigen-binding portion, the antibody-drug conjugate, the fusion protein, or the pharmaceutical composition.
  • the present disclosure provides a method for treating an immune-related disease in a subject, wherein the method comprises administering to the subject a therapeutically effective amount of the anti-TIGIT antibody or its antigen-binding portion, the antibody-drug conjugate, the fusion protein, or the pharmaceutical composition.
  • the immune-related disease includes, but is not limited to, cancer, inflammatory diseases, infectious diseases, or immunodeficiency diseases.
  • the immune-related disease is associated with a T cell dysfunction disorder.
  • the T cell dysfunction disorder is T cell exhaustion.
  • the present disclosure provides a method for enhancing an immune response in a subject, wherein the method comprises administering to the subject a therapeutically effective amount of the anti-TIGIT antibody or its antigen-binding portion, the antibody-drug conjugate, the fusion protein, or the pharmaceutical composition.
  • treating an immune-related disease in a subject, or enhancing an immune response in a subject the anti-TIGIT antibody or its antigen-binding portion, the antibody-drug conjugate, the fusion protein, or the pharmaceutical composition can be administered alone to a subject in need, and one or more additional therapeutic agents can be further administered.
  • the present disclosure provides use of the anti-TIGIT antibody or its antigen-binding portion, the antibody-drug conjugate, the fusion protein or the pharmaceutical composition in the preparation of a medicament for treating immune-related diseases.
  • the present disclosure provides use of the anti-TIGIT antibody or its antigen-binding portion, the antibody-drug conjugate, the fusion protein or the pharmaceutical composition in the preparation of a medicament for enhancing an immune response.
  • the anti-TIGIT antibody or its antigen-binding portion, the antibody-drug conjugate, the fusion protein or the pharmaceutical composition is combined with one or more additional therapeutic agents to prepare the drug.
  • the above-mentioned additional therapeutic agent can be, for example, a PD ⁇ 1 axis binding antagonist.
  • the PD ⁇ 1 axis binding antagonist is administered before or after the anti-TIGIT antibody or its antigen binding portion, the antibody-drug conjugate, the fusion protein or the pharmaceutical composition.
  • the PD ⁇ 1 axis binding antagonist is administered simultaneously with the anti-TIGIT antibody or its antigen binding portion.
  • the PD ⁇ 1 axis binding antagonist is a PD-1 binding antagonist, a PD-L1 binding antagonist or a PD-L2 binding antagonist.
  • the PD ⁇ 1 axis binding antagonist is a PD-L1 binding antagonist.
  • the PD ⁇ 1 axis binding antagonist is a PD-1 binding antagonist.
  • the PD ⁇ 1 axis binding antagonist includes but is not limited to: Atezolizumab Atezolizumab, Durvalumab, Envafolimab, Socazolimab, Avelumab, Teterizumab, Adebrelimab, Benmelstobart, Sugemalimab, Tagitanlimab, LP002 of Lepu Bio, RC98 of Rongchang Bio, MSB2311 of Maibos Bio, BC003 of Baochuan Bio, IBI318 of Innovent Biologics, Nivolumab, Pembrolizumab, Toripalimab, Sintilimab, Camrelizumab, Tislelizumab, Penpulimab enpulimab), Zimberelimab, Balstilimab, Geptanolimab, Livzon Pharmaceutical's LZM
  • the cancer is lung cancer, small cell lung cancer, non-small cell lung cancer, esophageal cancer, gastric cancer, esophageal junction cancer, liver cancer, bile duct cancer, pancreatic cancer, colorectal cancer, prostate cancer, breast cancer, endometrial cancer, ovarian cancer, fallopian tube cancer, peritoneal cancer, cervical cancer, kidney cancer, bladder cancer, urothelial carcinoma, mesothelioma, melanoma, mycosis fungoides, Merkel cell carcinoma, head and neck cancer, thyroid cancer, sarcoma, glioblastoma, thymic carcinoma, leukemia, lymphoma, or myeloma.
  • the present disclosure provides a kit comprising an anti-TIGIT antibody or antigen binding portion thereof as described herein, an antibody drug conjugate as described herein, a fusion protein as described herein, or a pharmaceutical composition as described herein.
  • the kit also comprises a container for loading the anti-TIGIT antibody or antigen binding portion thereof, antibody drug conjugate, fusion protein or pharmaceutical composition and/or instructions for administering the anti-TIGIT antibody or antigen binding portion thereof, antibody drug conjugate, fusion protein or pharmaceutical composition to a subject in need.
  • Embodiment 1 An anti-TIGIT antibody or an antigen-binding portion thereof, wherein the anti-TIGIT antibody or the antigen-binding portion thereof comprises:
  • HCDR1 which comprises the amino acid sequence shown in SEQ ID NO: 1, 2, 3 or 4;
  • HCDR2 comprising the amino acid sequence shown in SEQ ID NO:5, 6, 7 or 8;
  • HCDR3 comprising the amino acid sequence shown in SEQ ID NO:9, 10, 11, 12, 13, 14 or 15;
  • LCDR1 which comprises the amino acid sequence shown in SEQ ID NO:16, 17 or 18;
  • LCDR2 which comprises the amino acid sequence shown in SEQ ID NO:19;
  • LCDR3 which comprises the amino acid sequence shown in SEQ ID NO:20, 21, 22, 23 or 24.
  • Embodiment 2 The anti-TIGIT antibody or antigen-binding portion thereof according to embodiment 1, wherein the anti-TIGIT antibody or antigen-binding portion thereof comprises:
  • HCDR1 comprising the amino acid sequence shown in SEQ ID NO:1;
  • HCDR2 comprising the amino acid sequence shown in SEQ ID NO:5;
  • HCDR3 comprising the amino acid sequence shown in SEQ ID NO:9;
  • LCDR1 comprising the amino acid sequence shown in SEQ ID NO:16;
  • LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19;
  • LCDR3 comprising the amino acid sequence shown in SEQ ID NO:20;
  • HCDR1 comprising the amino acid sequence shown in SEQ ID NO:2;
  • HCDR2 comprising the amino acid sequence shown in SEQ ID NO:5;
  • HCDR3 comprising the amino acid sequence shown in SEQ ID NO:10;
  • LCDR1 comprising the amino acid sequence shown in SEQ ID NO:17;
  • LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19;
  • LCDR3 comprising the amino acid sequence shown in SEQ ID NO:21;
  • HCDR2 comprising the amino acid sequence shown in SEQ ID NO:6;
  • HCDR3 comprising the amino acid sequence shown in SEQ ID NO:11;
  • LCDR1 comprising the amino acid sequence shown in SEQ ID NO:16;
  • LCDR2 comprising the amino acid sequence shown in SEQ ID NO: 19;
  • LCDR3 comprising the amino acid sequence shown in SEQ ID NO:22;
  • HCDR1 comprising the amino acid sequence shown in SEQ ID NO:4;
  • HCDR2 comprising the amino acid sequence shown in SEQ ID NO:7;
  • HCDR3 comprising the amino acid sequence shown in SEQ ID NO:12;
  • LCDR1 comprising the amino acid sequence shown in SEQ ID NO:16;
  • LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19;
  • LCDR3 comprising the amino acid sequence shown in SEQ ID NO:23;
  • HCDR1 comprising the amino acid sequence shown in SEQ ID NO:4;
  • HCDR2 comprising the amino acid sequence shown in SEQ ID NO:8;
  • HCDR3 comprising the amino acid sequence shown in SEQ ID NO:13;
  • LCDR1 comprising the amino acid sequence shown in SEQ ID NO:18;
  • LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19;
  • LCDR3 comprising the amino acid sequence shown in SEQ ID NO:24;
  • HCDR1 comprising the amino acid sequence shown in SEQ ID NO:1;
  • HCDR2 comprising the amino acid sequence shown in SEQ ID NO:5;
  • HCDR3 comprising the amino acid sequence shown in SEQ ID NO:14;
  • LCDR1 comprising the amino acid sequence shown in SEQ ID NO:16;
  • LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19;
  • LCDR3 comprising the amino acid sequence shown in SEQ ID NO:20;
  • HCDR2 comprising the amino acid sequence shown in SEQ ID NO:5;
  • HCDR3 comprising the amino acid sequence shown in SEQ ID NO:15;
  • LCDR1 comprising the amino acid sequence shown in SEQ ID NO:17;
  • LCDR2 comprising the amino acid sequence shown in SEQ ID NO:19;
  • LCDR3 comprising the amino acid sequence shown in SEQ ID NO:21.
  • Embodiment 3 An anti-TIGIT antibody or an antigen binding portion thereof, wherein the anti-TIGIT antibody or the antigen binding portion thereof comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 of the sequence shown in SEQ ID NO: 25, 27, 29, 31, 33, 35, 37, 38, 39, 40, 42, 44, 46, 47, 48, 50, 51, 52, 54, 55, 57, 59, 61 or 63, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 of the sequence shown in SEQ ID NO: 26, 28, 30, 32, 34, 36, 41, 43, 45, 49, 53, 56, 58, 60, 62 or 64.
  • the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 of the sequence shown in SEQ ID NO: 25, 27, 29, 31, 33, 35, 37, 38, 39, 40, 42, 44, 46, 47, 48, 50, 51, 52, 54, 55,
  • Embodiment 4 The anti-TIGIT antibody or antigen-binding portion thereof according to Embodiment 3, wherein the anti-TIGIT antibody or antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region,
  • the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 of the sequence shown in SEQ ID NO: 25, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 of the sequence shown in SEQ ID NO: 26;
  • the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 of the sequence shown in SEQ ID NO: 27, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 of the sequence shown in SEQ ID NO: 28;
  • the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 of the sequence shown in SEQ ID NO: 29, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 of the sequence shown in SEQ ID NO: 30;
  • the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 of the sequence shown in SEQ ID NO:31, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 of the sequence shown in SEQ ID NO:32;
  • the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 of the sequence shown in SEQ ID NO: 33, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 of the sequence shown in SEQ ID NO: 34;
  • the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 of the sequence shown in SEQ ID NO:55, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 of the sequence shown in SEQ ID NO:56;
  • the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 of the sequence shown in SEQ ID NO:57, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 of the sequence shown in SEQ ID NO:58;
  • the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 of the sequence shown in SEQ ID NO:59, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 of the sequence shown in SEQ ID NO:60;
  • the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 of the sequence shown in SEQ ID NO:61, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 of the sequence shown in SEQ ID NO:62; or
  • the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 of the sequence shown in SEQ ID NO:63, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 of the sequence shown in SEQ ID NO:64.
  • Embodiment 5 An anti-TIGIT antibody or its antigen binding portion according to any one of embodiments 1-4, wherein the anti-TIGIT antibody or its antigen binding portion comprises a heavy chain variable region, and the heavy chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO: 25, 27, 29, 31, 33, 35, 37, 38, 39, 40, 42, 44, 46, 47, 48, 50, 51, 52, 54, 55, 57, 59, 61 or 63.
  • Embodiment 6 An anti-TIGIT antibody or its antigen binding portion according to any one of Embodiments 1-5, wherein the anti-TIGIT antibody or its antigen binding portion comprises a light chain variable region, and the light chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO: 26, 28, 30, 32, 34, 36, 41, 43, 45, 49, 53, 56, 58, 60, 62 or 64.
  • Embodiment 7 An anti-TIGIT antibody or its antigen binding portion according to any one of embodiments 1-6, wherein the anti-TIGIT antibody or its antigen binding portion comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO: 25, 27, 29, 31, 33, 35, 37, 38, 39, 40, 42, 44, 46, 47, 48, 50, 51, 52, 54, 55, 57, 59, 61 or 63, and the light chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO: 26, 28, 30, 32, 34, 36, 41, 43, 45, 49, 53, 56, 58, 60, 62 or 64.
  • Embodiment 8 The anti-TIGIT antibody or antigen-binding portion thereof according to Embodiment 7, wherein
  • the heavy chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:25, and the light chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:26;
  • the heavy chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:27, and the light chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:28;
  • the heavy chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:29, and the light chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:30;
  • the heavy chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:31, and the light chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:32;
  • the heavy chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:33, and the light chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:34;
  • the heavy chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:35, and the light chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:36;
  • the heavy chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:37, and the light chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:36;
  • the heavy chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:38, and the light chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:36;
  • the heavy chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:39, and the light chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:36;
  • the heavy chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:40, and the light chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:41;
  • the heavy chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:42, and the light chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:41;
  • the heavy chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:40, and the light chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:43;
  • the heavy chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:42, and the light chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:43;
  • the heavy chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:44, and the light chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:45;
  • the heavy chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:46, and the light chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:45;
  • the heavy chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:47, and the light chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:45;
  • the heavy chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:48, and the light chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:49;
  • the heavy chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:50, and the light chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:49;
  • the heavy chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:51, and the light chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:49;
  • the heavy chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:52, and the light chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:53;
  • the heavy chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:54, and the light chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:53;
  • the heavy chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:55, and the light chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:56;
  • the heavy chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:57, and the light chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:58;
  • the heavy chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:59, and the light chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:60;
  • the heavy chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:61, and the light chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:62; or,
  • the heavy chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:63, and the light chain variable region comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:64.
  • Embodiment 9 An anti-TIGIT antibody or an antigen-binding portion thereof, wherein the anti-TIGIT antibody or the antigen-binding portion thereof comprises a heavy chain variable region and a light chain variable region, wherein
  • the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:25, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:26;
  • the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:27, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:28;
  • the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:29, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:30;
  • the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:31, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:32;
  • the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:33, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:34;
  • the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:35, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:36;
  • the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:37, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:36;
  • the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 38
  • the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 36
  • the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:39, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:36;
  • the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:40, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:41;
  • the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:42, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:41;
  • the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:40, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:43;
  • the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:42, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:43;
  • the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:44, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:45;
  • the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:46, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:45;
  • the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:47, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:45;
  • the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:48, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:49;
  • the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:50, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:49;
  • the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:51, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:49;
  • the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:52, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:53;
  • the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:54, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:53;
  • the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:55, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:56;
  • the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:57, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:58;
  • the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:59, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:60;
  • the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:61
  • the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:62; or
  • the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:63, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:64.
  • Embodiment 10 An anti-TIGIT antibody or antigen binding portion thereof according to any one of Embodiments 1-9, wherein the antigen binding portion is a Fab fragment, a Fab' fragment, a F(ab') 2 fragment, a Fd fragment, a Fv fragment, a dAb fragment, an isolated CDR region or a scFv.
  • Embodiment 11 An anti-TIGIT antibody or antigen binding portion thereof according to any one of Embodiments 1-10, wherein the anti-TIGIT antibody or antigen binding portion thereof is chimeric, humanized or fully human.
  • Embodiment 12 An anti-TIGIT antibody, or antigen-binding portion thereof, according to any one of Embodiments 1-11, wherein the anti-TIGIT antibody is of IgG1, IgG2, IgG3 or IgG4 isotype.
  • Embodiment 13 An anti-TIGIT antibody, or antigen binding portion thereof, according to any one of Embodiments 1-13, wherein the anti-TIGIT antibody, or antigen binding portion thereof, has at least one property selected from the group consisting of:
  • Embodiment 14 An anti-TIGIT antibody or antigen binding portion thereof according to any one of Embodiments 1-13, wherein the anti-TIGIT antibody comprises a heavy chain and a light chain, wherein
  • the heavy chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:65, and the light chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:66;
  • the heavy chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:67, and the light chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:68;
  • the heavy chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:69, and the light chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:70;
  • the heavy chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:71, and the light chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:72;
  • the heavy chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:73, and the light chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:74;
  • the heavy chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:75, and the light chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:76;
  • the heavy chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:77, and the light chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:76;
  • the heavy chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:78, and the light chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:76;
  • the heavy chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:79, and the light chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:76;
  • the heavy chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:80, and the light chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:81;
  • the heavy chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:82, and the light chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:81;
  • the heavy chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:80, and the light chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:83;
  • the heavy chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:82, and the light chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:83;
  • the heavy chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:84, and the light chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:85;
  • the heavy chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:86, and the light chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:85;
  • the heavy chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:87, and the light chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:85;
  • the heavy chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:88, and the light chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:89;
  • the heavy chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:90, and the light chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:89;
  • the heavy chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:91, and the light chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:89;
  • the heavy chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:92
  • the light chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:93;
  • the heavy chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:94, and the light chain comprises an amino acid sequence that is at least 80% identical to the sequence shown in SEQ ID NO:93.
  • Embodiment 15 An anti-TIGIT antibody or an antigen-binding portion thereof, wherein the anti-TIGIT antibody comprises a heavy chain and a light chain, wherein
  • the heavy chain comprises the amino acid sequence shown in SEQ ID NO:65, and the light chain comprises the amino acid sequence shown in SEQ ID NO:66;
  • the heavy chain comprises the amino acid sequence shown in SEQ ID NO:67, and the light chain comprises the amino acid sequence shown in SEQ ID NO:68;
  • the heavy chain comprises the amino acid sequence shown in SEQ ID NO:69, and the light chain comprises the amino acid sequence shown in SEQ ID NO:70;
  • the heavy chain comprises the amino acid sequence shown in SEQ ID NO:71, and the light chain comprises the amino acid sequence shown in SEQ ID NO:72;
  • the heavy chain comprises the amino acid sequence shown in SEQ ID NO:73, and the light chain comprises the amino acid sequence shown in SEQ ID NO:74;
  • the heavy chain comprises the amino acid sequence shown in SEQ ID NO:75, and the light chain comprises the amino acid sequence shown in SEQ ID NO:76;
  • the heavy chain comprises the amino acid sequence shown in SEQ ID NO:77, and the light chain comprises the amino acid sequence shown in SEQ ID NO:76;
  • the heavy chain comprises the amino acid sequence shown in SEQ ID NO:78, and the light chain comprises the amino acid sequence shown in SEQ ID NO:76;
  • the heavy chain comprises the amino acid sequence shown in SEQ ID NO:79, and the light chain comprises the amino acid sequence shown in SEQ ID NO:76;
  • the heavy chain comprises the amino acid sequence shown in SEQ ID NO:80, and the light chain comprises the amino acid sequence shown in SEQ ID NO:81;
  • the heavy chain comprises the amino acid sequence shown in SEQ ID NO:82, and the light chain comprises the amino acid sequence shown in SEQ ID NO:81;
  • the heavy chain comprises the amino acid sequence shown in SEQ ID NO:80, and the light chain comprises the amino acid sequence shown in SEQ ID NO:83;
  • the heavy chain comprises the amino acid sequence shown in SEQ ID NO:82, and the light chain comprises the amino acid sequence shown in SEQ ID NO:83;
  • the heavy chain comprises the amino acid sequence shown in SEQ ID NO:84, and the light chain comprises the amino acid sequence shown in SEQ ID NO:85;
  • the heavy chain comprises the amino acid sequence shown in SEQ ID NO:86, and the light chain comprises the amino acid sequence shown in SEQ ID NO:85;
  • the heavy chain comprises the amino acid sequence shown in SEQ ID NO:87, and the light chain comprises the amino acid sequence shown in SEQ ID NO:85;
  • the heavy chain comprises the amino acid sequence shown in SEQ ID NO:88, and the light chain comprises the amino acid sequence shown in SEQ ID NO:89;
  • the heavy chain comprises the amino acid sequence shown in SEQ ID NO:90, and the light chain comprises the amino acid sequence shown in SEQ ID NO:89;
  • the heavy chain comprises the amino acid sequence shown in SEQ ID NO:91, and the light chain comprises the amino acid sequence shown in SEQ ID NO:89;
  • the heavy chain comprises the amino acid sequence shown in SEQ ID NO:92, and the light chain comprises the amino acid sequence shown in SEQ ID NO:93; or
  • the heavy chain comprises the amino acid sequence shown in SEQ ID NO:94, and the light chain comprises the amino acid sequence shown in SEQ ID NO:93.
  • Embodiment 16 An anti-TIGIT antibody or antigen-binding portion thereof according to any one of Embodiments 1-15, wherein the anti-TIGIT antibody or antigen-binding portion thereof is a monospecific antibody or a multispecific antibody.
  • Embodiment 17 An isolated nucleic acid encoding the anti-TIGIT antibody or antigen-binding portion thereof according to any one of Embodiments 1-16.
  • Embodiment 18 A vector comprising the nucleic acid according to embodiment 17.
  • Embodiment 19 A host cell comprising the nucleic acid according to embodiment 17 or the vector according to embodiment 18.
  • Embodiment 20 A method for preparing an anti-TIGIT antibody or an antigen-binding portion thereof according to any one of Embodiments 1-16, comprising: culturing the host cell described in Embodiment 19, and recovering the anti-TIGIT antibody or the antigen-binding portion thereof from the host cell or the host cell culture medium.
  • Embodiment 21 An antibody drug conjugate comprising the anti-TIGIT antibody or antigen-binding portion thereof according to any one of Embodiments 1-16.
  • Embodiment 22 A fusion protein comprising the anti-TIGIT antibody or antigen-binding portion thereof according to any one of Embodiments 1-16.
  • Embodiment 23 A pharmaceutical composition comprising the anti-TIGIT antibody or antigen-binding portion thereof according to any one of embodiments 1-16, the antibody drug conjugate according to embodiment 21, or the fusion protein according to embodiment 22.
  • Embodiment 24 A method for treating cancer in a subject, wherein the method comprises administering to the subject a therapeutically effective amount of an anti-TIGIT antibody or antigen-binding portion thereof according to any one of Embodiments 1-16, the antibody-drug conjugate of Embodiment 21, the fusion protein of Embodiment 22, or the pharmaceutical composition of Embodiment 23.
  • Embodiment 25 The method according to embodiment 24, wherein the cancer is lung cancer, small cell lung cancer, non-small cell lung cancer, esophageal cancer, stomach cancer, esophagogastric junction cancer, liver cancer, bile duct cancer, pancreatic cancer, colorectal cancer, prostate cancer, breast cancer, endometrial cancer, ovarian cancer, fallopian tube cancer, peritoneal cancer, cervical cancer, kidney cancer, bladder cancer, urothelial carcinoma, mesothelioma, melanoma, mycosis fungoides, Merkel cell carcinoma, head and neck cancer, thyroid cancer, sarcoma, glioblastoma, thymic carcinoma, leukemia, lymphoma, or myeloma.
  • the cancer is lung cancer, small cell lung cancer, non-small cell lung cancer, esophageal cancer, stomach cancer, esophagogastric junction cancer, liver cancer, bile duct cancer, pancreatic cancer, colorectal cancer,
  • Embodiment 26 A method for treating an immune-related disease in a subject, wherein the method comprises administering to the subject a therapeutically effective amount of an anti-TIGIT antibody or antigen-binding portion thereof according to any one of Embodiments 1-16, the antibody-drug conjugate of Embodiment 21, the fusion protein of Embodiment 22, or the pharmaceutical composition of Embodiment 23.
  • Embodiment 27 A method for enhancing an immune response in a subject, wherein the method comprises administering to the subject a therapeutically effective amount of an anti-TIGIT antibody or antigen-binding portion thereof according to any one of Embodiments 1-16, the antibody-drug conjugate of Embodiment 21, the fusion protein of Embodiment 22, or the pharmaceutical composition of Embodiment 23.
  • Embodiment 28 A method according to any one of Embodiments 24-27, wherein the treatment comprises administering a second therapeutic agent to the subject.
  • Embodiment 29 The method of Embodiment 28, wherein the second therapeutic agent is a PD-1 axis binding antagonist.
  • Embodiment 30 A kit comprising the anti-TIGIT antibody or antigen-binding portion thereof according to any one of embodiments 1-16, the antibody drug conjugate according to embodiment 21, the fusion protein according to embodiment 22, or the pharmaceutical composition according to embodiment 23.
  • the positive control tiragolumab used in the specific embodiments of the present disclosure has a variable region amino acid sequence that is identical to the variable region amino acid sequence of the antibody "4.1D3.Q1E" in Chinese patent CN108290946A (VH is the sequence shown in CN108290946A SEQ ID NO: 34, and VL is the sequence shown in CN108290946A SEQ ID NO: 36).
  • VH is the sequence shown in CN108290946A SEQ ID NO: 34
  • VL is the sequence shown in CN108290946A SEQ ID NO: 36.
  • the VL and VH region gene synthesis parts of "4.1D3.Q1E” were subcloned into the pcDNA3.1 expression vector (Invitrogen, catalog number: V-79020) carrying the human ⁇ light chain constant region and the human IgG1 heavy chain constant region, respectively.
  • SEQ ID NO: 135 shows the heavy chain amino acid sequence of tiragolumab as follows:
  • SEQ ID NO: 136 shows the light chain amino acid sequence of tiragolumab as follows:
  • the open reading frame DNA sequence encoding the extracellular domain of human TIGIT protein (Uniprot: Q495A1) was fused with the human IgG1 Fc tag DNA sequence, and the synthesized DNA sequence was subcloned into the expression vector pcDNA3.1 (Invitrogen, catalog number: V-79020), and the expression vector was transfected into Freestyle293 cells for transient expression, and purified with a protein A column (GE healthcare) to obtain the fusion protein TIGIT-Fc Tag (SEQ ID NO: 137):
  • mice were subcutaneously immunized every 2 weeks with equal volumes of complete (primary immunization)/incomplete (boosting immunization) Freund's adjuvant-emulsified recombinant TIGIT-Fc Tag protein (100 ⁇ g/mouse), and immunization was continued for 4 times for 6 weeks. Three days before cell fusion, mice were boosted by intravenous injection of adjuvant-free TIGIT-Fc Tag protein.
  • Splenocytes (about 1 ⁇ 10 8 ) from immunized mice were fused with SP2/0-Ag14 myeloma cells (about 1 ⁇ 10 7 -3 ⁇ 10 7 ) using an electrofusion instrument (BTX, catalog number: ECM2001). After the fusion was completed, the fused cells were diluted with 500 mL of 1640 culture medium containing 10% fetal bovine serum, and then distributed to 96-well plates at 0.1 mL/well, and incubated in an incubator at 37°C and 5% CO 2 .
  • BTX electrofusion instrument
  • Positive clones were screened by protein- and cell-based binding and ligand competition assays. Positive hybridoma cells in logarithmic growth were counted, 100-200 cells were aspirated and diluted into 20 mL of complete 1640 medium, mixed thoroughly, and inoculated into a 96-well plate at 200 ⁇ L/well, and kept in a 37°C, 5% CO 2 incubator for about 8 days. The supernatant of each visible monoclonal cell well was collected for rescreening to obtain positive hybridoma monoclonal cell lines.
  • VH heavy chain variable region
  • VL light chain variable region
  • the VL region gene synthesis part of the mouse antibody was connected to the human ⁇ light chain constant region to construct a chimeric light chain
  • the VH region gene synthesis part of the mouse antibody was connected to the human IgG1 heavy chain constant region to construct a chimeric heavy chain.
  • the expression plasmid containing the chimeric light chain DNA and the expression plasmid containing the chimeric heavy chain DNA were transfected into ExpiCHO cells (100mL, at a cell density of 6.3 ⁇ 10 6 /mL). After 10-12 days of cell culture, the chimeric antibody in the supernatant was purified using a protein A column (GE healthcare). Five chimeric antibodies were obtained.
  • the variable region sequences of the chimeric antibodies were the same as those of the mouse antibodies.
  • the full-length amino acid sequences of the chimeric heavy chain and chimeric light chain are as follows:
  • Antibody humanization was performed using the CDR grafting approach (see, eg, US Pat. No. 5,225,539).
  • expression plasmids containing humanized antibody heavy chain and light chain were constructed respectively, and 20 ⁇ g of heavy chain expression plasmid and 20 ⁇ g of light chain expression plasmid were transfected into ExpiCHO cells (100 mL, at a cell density of 6.3 ⁇ 10 6 /mL) and cultured in ExpiCHO medium (Gibco, catalog number: A29100-01) for 10-12 days.
  • the cell culture supernatant was collected, and the humanized antibody in the supernatant was purified using a protein A column (GE healthcare).
  • Anti-TIGIT antibodies were affinity captured using a CM5 biosensor chip (GE, catalog number: 29149603) coupled with anti-human IgG antibodies (Human antibody capture kit, GE, catalog number: 29234600), and then human TIGIT-His protein (acrobiosystems, catalog number: TIT-H52H5) was passed through the chip surface.
  • the Biacore 8K instrument was used to detect the reaction signal in real time to obtain the binding and dissociation curves. After each experimental cycle of dissociation was completed, the chip was washed and regenerated with a regeneration buffer Glycine-HCl at pH 1.5.
  • Anti-TIGIT antibodies were captured by affinity using a CM5 biosensor chip coupled with protein A (Sino Biological, catalog number: 10600-P07E), and then antigens cynomolgus monkey TIGIT-His (acrobiosystems, catalog number: TIT-C5223), canine TIGIT-His (acrobiosystems, catalog number: TIT-C52H7) or mouse TIGIT-His (acrobiosystems, catalog number: TIT-M52E6) were passed over the chip surface.
  • the binding and dissociation curves were obtained by real-time detection of the reaction signals using a Biacore 8K instrument. After each experimental cycle of dissociation was completed, the chip was washed and regenerated with a pH 2.0 glycine-HCl regeneration buffer.
  • Rabbit TIGIT-FC (acrobiosystems, catalog number: TIT-R5259) or rat TIGIT-FC (Sino Biological, catalog number: 8A6318-R02H) was amino-coupled to the CM5 biosensor chip, and then anti-TIGIT antibody was passed through the chip surface. The reaction signal was detected in real time using the Biacore 8K instrument to obtain the binding and dissociation curves. After each experimental cycle of dissociation was completed, the chip was washed and regenerated with pH 1.5 glycine-HCl regeneration buffer.
  • the binding and dissociation curves were collected in real time by Biacore 8K Control Software 3.0 and analyzed by Biacore Insight Evaluation Software3.0 to calculate the binding rate constant ka, dissociation rate constant kd, and equilibrium dissociation constant K D.
  • the results are shown in Table 2.
  • hz-Ab1-1.4 and hz-Ab23-1.3 have good binding activity with cynomolgus monkey TIGIT and rat TIGIT, and neither binds to canine TIGIT or mouse TIGIT.
  • the full-length open reading frame DNA sequences of human TIGIT and cynomolgus monkey TIGIT were synthesized and then subcloned into the expression vector pcDNA3.1 (Invitrogen, catalog number: V-79020), respectively.
  • the expression vectors were transfected into CHO-K1 using Lipofectamine 3000 (Gibco, catalog number: L3000001). After 2-3 weeks of geneticin selection, monoclonal cells were isolated by limiting dilution method, and the expression of TIGIT on the cell surface was detected by flow cytometry (FACS), and CHO-K1 cells with high expression of TIGIT were screened (the MFI to background (S/B) ratio of TIGIT detected by flow cytometry was greater than 100).
  • CHO-K1 cells that highly express human and cynomolgus monkey TIGIT were prepared into cell suspensions with a cell density of 0.5-1 ⁇ 10 6 /mL using FACS buffer (Miltenyi Biotec, catalog number: 130-091-221), and 100 ⁇ L/well was added to a 96-well plate (Corning, catalog number: 3894). Then, 100 ⁇ L of different concentrations of anti-TIGIT antibody or human IgG1 control antibody diluted with FACS buffer was added to each well and incubated in a 4°C refrigerator in the dark for 1 hour.
  • the full-length open reading frame DNA sequences of human CD155 and cynomolgus monkey CD155 were synthesized and then subcloned into the expression vector pcDNA3.1 (Invitrogen, catalog number: V-79020), respectively.
  • the expression vectors were transfected into CHO-K1 using Lipofectamine 3000 (Gibco, catalog number: L3000001). After 2-3 weeks of geneticin selection, monoclonal cells were isolated by limiting dilution method. Flow cytometry (FACS) was used to detect the expression of CD155 on the cell surface, and CHO-K1 cells with high expression of CD155 were screened (flow cytometry detection of TIGIT expression, the MFI to background (S/B) ratio was greater than 100).
  • CHO-K1 cells highly expressing human and cynomolgus CD155 were prepared into cell suspensions with a cell density of 0.5-1 ⁇ 10 6 /mL using FACS buffer (Miltenyi Biotec, catalog number: 130-091-221), and 100 ⁇ L/well was added to a 96-well plate (Corning, catalog number: 3894). Then, a mixture of different concentrations of anti-TIGIT antibodies and 100 ng/ml human TIGIT-Fc Tag or cynomolgus TIGIT-hFc (acrobiosystems, catalog number: TIT-C5254) diluted with 100 ⁇ L FACS buffer was added to each well and reacted at 4°C for 30 minutes.
  • PBMC peripheral blood mononuclear cells, Aoneng Biotech, catalog number: FPB004F-C
  • NK cells were sorted out using an NK sorting kit (Miltenyi Biotech, catalog number: 130-092-657)
  • NK cells were resuspended at a density of 1 ⁇ 10 6 /mL in basal medium (RPMI 1640+10% FBS+penicillin-streptomycin), and cytokine human IL-2 (R&D, catalog number: IL-202) was added to the medium at a final concentration of 200 IU/mL, and the cells were activated in a 37°C incubator overnight.
  • basal medium RPMI 1640+10% FBS+penicillin-streptomycin
  • cytokine human IL-2 R&D, catalog number: IL-202
  • the target human colon cancer cell Widr (Nanjing Kebai Biotechnology Co., Ltd.) was labeled and stained using the cell labeling reagent CellTrace TM Violet (Invitrogen, catalog number: C34557A), and then the activated NK cells and labeled Widr cells were resuspended separately, and 50 ⁇ L of anti-TIGIT antibody (starting concentration 280 nM, 10-fold gradient dilution, a total of 7 concentrations), 50 ⁇ L of Widr cells and 100 ⁇ L of NK cells were added to each well of a low-adsorption 96-well plate (Corning, catalog number: 7007), and mixed evenly to make the number of NK cells in each well 20,000 and the number of Widr cells 20,000.
  • the wells containing only Widr target cells were set as background controls: the total volume of each well was 200 ⁇ L, no detection antibody, no NK cells, and the number of Widr was 20,000. After incubation at 37°C for 4 hours, 1 ⁇ L of propidium iodide stain (Invitrogen, catalog number: P3566) was added to each well and mixed evenly. After staining for 5 minutes, flow cytometry was used to detect. The proportion of propidium iodide-positive cells (PI%) in CellTrace TM Violet-positive cells was analyzed, and the cell lysis rate was calculated according to the following formula:
  • Tregs in PBMC were isolated using Treg isolation kit (Stemcell, catalog number: 18063), and the isolated Tregs were expanded using Dynabeads human Treg expander (Gibco, catalog number: 11129D).
  • the target cell Treg marker was stained using the cell labeling reagent CellTrace TM Violet (Invitrogen, catalog number: C34557A).
  • the activated NK cells and labeled Treg cells were then resuspended separately, and 50 ⁇ L of anti-TIGIT antibody (starting concentration was 280 nM, 10-fold gradient dilution, a total of 7 concentrations), 50 ⁇ L of Treg cells and 100 ⁇ L of NK cells were added to each well of the 96-well plate, and mixed evenly to make the number of NK cells in each well 25,000 and the number of Treg cells in each well 25,000.
  • the wells containing only Treg target cells were set as background controls: the total volume of each well was 200 ⁇ L, no detection antibody, no NK cells, and the number of Tregs was 25,000. After the plate is laid, it is placed in a 37°C incubator for 4 hours.
  • PBMCs with HLA-A*02:01 genotype and a history of CMV (cytomegalovirus) infection were selected (Miaoshun Bio, catalog number: PB100C-W), and the cells were resuspended to 2 ⁇ 10 6 cells/mL in complete culture medium (RPMI 1640+5% AB serum+1% P/S+50 ⁇ M 2- ⁇ -mercaptoethanol) containing 1 ⁇ g/mL CMV pp65 (495-503) short peptide (Anaspec, catalog number: AS-28328), 20IU/mL human IL-2 (R&D, catalog number: IL-202), and 10ng/mL human IL-7 (Peprotech, catalog number: 200-07).
  • CMV cytomegalovirus
  • the cells were inoculated in 6 -well plates at 5mL/well and cultured in a 37°C, 5% CO 2 incubator for 6 days. On day 6, cells were collected, the culture medium was removed, and the cells were resuspended in complete culture medium containing 100 IU/mL human IL-2, with a volume twice the original, and inoculated in a new 6-well plate at 5 mL/well and cultured for 2 days. On day 8, the medium was changed and culture continued. On day 11, all cells were collected, CD8 + T cells were isolated as effector cells using a CD8 + T cell sorting kit (Miltenyi Biotec, Cat. No.: 130-045-201), and resuspended with AIM-V (Gibco, Cat.
  • CD8 + T cells were isolated as effector cells using a CD8 + T cell sorting kit (Miltenyi Biotec, Cat. No.: 130-045-201), and resuspended with AIM-V (Gibco, Cat
  • 50 ⁇ L antibody, 50 ⁇ L CD8 + T cells, and 100 ⁇ L pp65-treated Colo205 were added to a low-adsorption 96-well plate (Corning, catalog number: 7007) in sequence, mixed, and incubated overnight at 37°C and 5% CO 2 .
  • the final concentration of the antibody in the system was 70 nM (maximum concentration), the number of CD8 + T cells was 50,000/well, and the number of Colo205 cells was 50,000/well. After the incubation, the level of hIFN ⁇ in the supernatant was detected.
  • the results are shown in AB in Figure 3.
  • the anti-TIGIT chimeric antibody and humanized antibodies hzAb1-1.4 and hzAb23-1.3 can effectively promote CD8 + T cells to release the proinflammatory factor hIFN ⁇ .
  • the humanized antibodies hzAb1-1.4 and hzAb23-1.3 have better promoting functions on CD8 + T cells than tiragolumab.

Landscapes

  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

提供一种抗TIGIT抗体或其抗原结合部分，以及编码抗体或其抗原结合部分的核酸、载体、细胞、药物组合物等，该抗体可治疗癌症、治疗免疫相关疾病、增强免疫应答。

Description

抗TIGIT抗体及其应用 技术领域
本公开涉及抗TIGIT抗体。更具体地，本公开涉及特异性结合TIGIT的抗体或其抗原结合部分，以及制备和使用所述抗体或其抗原结合部分的方法。
背景技术
TIGIT(具有Ig和ITIM结构域的T细胞免疫受体)，也被成为WUCAM，Vstm3，VSIG9，其由细胞外免疫球蛋白可变结构域(IgV)，Ⅰ型跨膜结构域和具有经典免疫受体酪氨酸抑制基序(ITIM)和免疫球蛋白酪氨酸尾(ITT)基序的细胞内结构域组成。TIGIT是一种抑制性免疫检查点，主要在活化的T细胞和自然杀伤(NK)细胞上表达。
CD155(又称为PVR、Necl5或Tage4)、CD112(又称为PVRL2/nectin 2)和CD113(又称为PVRL3)是TIGIT的主要配体，在肿瘤细胞表面高表达，其中CD155是TIGIT的高亲和力配体。TIGIT与配体结合后，通过其抑制性基序将抑制信号传递到细胞中，有效抑制固有免疫和适应性免疫。据认为，TIGIT发挥其抑制性作用的机制包括：与树突状细胞(Dendritic cells,DCs)上的CD155结合，促进形成免疫耐受性DCs，降低IL-12的产生并导致IL-10的增加，间接地阻碍T细胞的功能；抑制NK细胞脱颗粒、细胞因子生成，降低NK细胞介导的CD155+肿瘤细胞的细胞毒性；以比CD226更高的亲和力结合CD155，导致其胞内段酪氨酸的脱磷酸化，限制CD226介导的免疫细胞激活；作用于Treg，增强其免疫抑制功能。
TIGIT在黑色素瘤、非小细胞肺癌、结肠癌、肝细胞癌、胃癌、胶质母细胞瘤等实体肿瘤和血液系统恶性肿瘤中的肿瘤浸润CD8+T细胞、NK细胞、辅助性T细胞和Treg中都有表达。已经证实抗TIGIT抗体可用于治疗癌症。TIGIT作为一个具有吸引力的癌症免疫治疗靶点，本领域存在着开发新的TIGIT抗体的需求。
发明内容
本公开提供了一种新的抗TIGIT抗体或其抗原结合部分，为靶向TIGIT的治疗提供解决方案。
一方面，本公开提供了一种抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体或其抗原结合部分包含：
HCDR1，其包含SEQ ID NO:1、2、3或4所示的氨基酸序列；
HCDR2，其包含SEQ ID NO:5、6、7或8所示的氨基酸序列；
HCDR3，其包含SEQ ID NO:9、10、11、12、13、14或15所示的氨基酸序列；
LCDR1，其包含SEQ ID NO:16、17或18所示的氨基酸序列；
LCDR2，其包含SEQ ID NO:19所示的氨基酸序列；和
LCDR3，其包含SEQ ID NO:20、21、22、23或24所示的氨基酸序列。
另一方面，本公开提供了一种抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述重链可变区包含SEQ ID NO:25、27、29、31、33、35、37、38、39、40、42、44、46、47、48、50、51、52、54、55、57、59、61或63所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:26、28、30、32、34、36、41、43、45、49、53、56、58、60、62或64所示序列的LCDR1、LCDR2和LCDR3。
另一方面，本公开提供了一种抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述重链可变区包含与SEQ ID NO:25、27、29、31、33、35、37、38、39、40、42、44、46、47、48、50、51、52、54、55、57、59、61或63所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:26、28、30、32、34、36、41、43、45、49、53、56、58、60、62或64所示序列具有至少80％同一性的氨基酸序列。
另一方面，本公开提供了抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体或其抗原结合部分与 本文提供的任何示例性抗TIGIT抗体或其抗原结合部分结合人TIGIT上的相同表位。
另一方面，本公开提供了抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体或其抗原结合部分与本文提供的任何示例性抗TIGIT抗体或其抗原结合部分竞争结合人TIGIT，其中所述竞争通过ELISA、流式细胞术或表面等离子体共振测定进行测量。
在本文中，所述抗原结合部分可选自Fab部分、Fab'部分、F(ab')2部分、Fd部分、Fv部分、dAb部分、分离的CDR区或scFv，但不限于此。
另一方面，本公开提供了抗体药物偶联物，其包含本文所述的抗TIGIT抗体或其抗原结合部分，以及与所述抗TIGIT抗体或其抗原结合部分偶联的治疗剂。
在本文中，所述抗TIGIT抗体或其抗原结合部分可通过接头与所述治疗剂连接。接头可以是可裂解的或不可裂解的。
在本文中，所述治疗剂可选自细胞毒性药物、放射性同位素或免疫调节剂，例如化学治疗剂、免疫抑制剂、免疫刺激剂、抗代谢物、烷化剂、抗生素、抗血管生成剂、抗有丝分裂剂、毒素、细胞凋亡剂等。
另一方面，本公开提供了融合蛋白，其包含本文所述的抗TIGIT抗体或其抗原结合部分
另一方面，本公开提供了药物组合物，其包含本文所述的抗TIGIT抗体或其抗原结合部分、抗体药物偶联物或融合蛋白。
另一方面，本公开提供了分离的核酸，其编码本文所述的抗TIGIT抗体或其抗原结合部分。
另一方面，本公开提供了载体，其包含本文所述的分离的核酸。
另一方面，本公开提供了宿主细胞，其包含本文所述的载体或本文所述的分离的核酸。优选地，所述载体为表达载体。
又一方面，本公开提供了制备抗TIGIT抗体或其抗原结合部分的方法，包括：培养本文所述的宿主细胞，分离所表达的所述抗TIGIT抗体或其抗原结合部分。
又一方面，本公开提供了在受试者中治疗癌症的方法，其中所述方法包括向所述受试者施用治疗有效量的本文所述的抗TIGIT抗体或其抗原结合部分、本文所述的抗体药物偶联物、本文所述的融合蛋白或所述的药物组合物。
又一方面，本公开提供了在受试者中治疗免疫相关疾病的方法，其中所述方法包括向所述受试者施用治疗有效量的本文所述的抗TIGIT抗体或其抗原结合部分、本文所述的抗体药物偶联物、本文所述的融合蛋白或所述的药物组合物。
又一方面，本公开提供了在受试者中增强免疫应答的方法，其中所述方法包括向所述受试者施用治疗有效量的本文所述的抗TIGIT抗体或其抗原结合部分、本文所述的抗体药物偶联物、本文所述的融合蛋白或所述的药物组合物。
在本文中，所述抗TIGIT抗体或其抗原结合部分、抗体药物偶联物、融合蛋白或药物组合物单独施用于受试者或与PD□1轴结合拮抗剂一起施用。
又一方面，本公开提供了试剂盒，所述试剂盒包含本文所述的抗TIGIT抗体或其抗原结合部分、本文所述的抗体药物偶联物、本文所述的融合蛋白或所述的药物组合物。
附图说明
图1示出了抗TIGIT抗体对NK细胞杀伤活性的影响。
图2示出了抗TIGIT抗体对NK细胞对Treg ADCC的影响。
图3示出了抗TIGIT抗体单独使用对CD8+T细胞功能的影响。
具体实施方式
术语
为了更容易理解本公开，以下具体定义了某些技术和科学用语。除非在本文中另有明确定义，本公开使用的所有的其他技术和科学术语都具有本公开所属领域的一般技术人员通常理解的含义。
如本文所用，术语“抗体”是指具有至少一个抗原(例如，TIGIT)结合结构域的结合蛋白，因此， 本公开的抗体涵盖多克隆抗体、单克隆抗体、单特异性抗体、多特异性抗体(例如双特异性抗体、三特异性抗体)、单价抗体、多价抗体、单链抗体、或融合蛋白。
抗体的“抗原结合部分”是指抗体中保留特异性结合抗原(例如，TIGIT)功能的一个或多个部分。已证实，抗体的抗原结合功能可以通过全长抗体的部分来实现。涵盖在术语抗体的“抗原结合部分”中的实例包括：(i)Fab片段，由VL、VH、CL和CH1结构域组成的单价片段；(ii)Fab'片段，与Fab片段的不同之处在于在重链CH1结构域的羧基末端添加了几个残基，包括来自抗体铰链区的一个或多个半胱氨酸；(iii)F(ab')2片段，包含通过铰链区二硫桥连接的两个Fab片段的二价片段；(iv)Fd片段，由VH和CH1结构域组成；(v)Fv片段，由抗体单臂的VL和VH结构域组成；(vi)dAb片段，由VH结构域组成；(vii)分离的互补决定区(CDR)；和(viii)纳米抗体，包含单个可变域的重链可变区和两个恒定域。此外，虽然Fv片段的两个结构域VL和VH由不同的基因编码，但可以采用重组的方法通过合成的接头将它们连接制备成单蛋白链，其中VL和VH配对形成单价分子(称为单链Fv(scFv)。本文的抗原结合部分可使用本领域技术人员公知的常规技术获得，且可以通过与全长抗体相同的方法进行功能筛选。
术语“同种型”是指由重链恒定区基因编码的抗体种类。本公开的抗TIGIT抗体和其抗原结合片段可以衍生自任何物种，其包括但不限于小鼠、大鼠、兔、非人灵长类动物(如黑猩猩、食蟹猴、蜘蛛猴、猕猴)、美洲驼和人。抗TIGIT抗体可以是鼠类抗体、嵌合抗体、人源化抗体或全人源抗体。在一些实施方案中，抗TIGIT抗体是由源自小鼠的杂交瘤细胞系产生的抗体。因此，在一些实施方案中，抗TIGIT抗体是鼠类抗体。在另一些实施方案中，抗TIGIT抗体是嵌合抗体。在一些实施方案中，嵌合抗体是小鼠-人嵌合抗体。在另一些实施方案中，抗TIGIT抗体是人源化抗体。在另一些实施方案中，抗TIGIT抗体衍生自鼠类抗体并且是人源化的。
术语“嵌合抗体”是下述抗体：所述抗体具有衍生自一种物种的抗体重链可变区的至少一部分和抗体轻链可变区的至少一部分；以及衍生自另一物种的抗体恒定区的至少一部分。例如，在一些实施方案中，嵌合抗体可以包含鼠类抗体的可变区和人抗体的恒定区。
“人源化抗体”是下述抗体：所述抗体含有衍生自非人抗体的互补决定区(CDR)和衍生自人抗体的框架区以及恒定区。例如，本文提供的结合TIGIT的人源化抗体可以包含衍生自一种或多种鼠类抗体的CDR以及人抗体的框架区和恒定区。因此，在一些实施方案中，本文提供的人源化抗体与所述抗体的CDR所衍生自的鼠类抗体结合TIGIT上的相同表位。本文提供了示例性人源化抗体。包含本文提供的重链CDR和轻链CDR的另外的结合TIGIT的人源化抗体或其变体可以使用任何人抗体框架序列产生，并且也包括在本公开中。在一些实施方案中，适用于在本公开中使用的框架序列包括在结构上与本文提供的框架序列类似的那些框架序列。可以在框架区中进行另外修饰以改进本文提供的抗体的特性。此类另外的框架修饰可以包括化学修饰，点突变以降低免疫原性或去除T细胞表位，或使回复突变为原始种系序列中的残基。
术语“多特异性”意指抗体能够特异性结合多种不同的抗原决定簇，例如能够特异性结合两种(即“双特异性”)或两种以上不同的抗原决定簇。本文中的抗原决定簇与抗原表位同义。通常，双特异性抗体包含两种抗原结合位点，其中每种特异于不同的抗原性决定簇。不同的抗原决定簇可以在相同或不同的细胞上表达。不同的抗原决定簇可以因抗原种类不同而不同，也可以存在同一种抗原上。抗原决定簇是抗原物质分子表面或其他部位，具有一定组成和结构的特殊化学基团，能与其相应抗体或致敏淋巴细胞发生特异性结合的结构。
术语“可变结构域”或“可变区”是指抗体的涉及该抗体与抗原结合的结构域。例如天然四链抗体(例如来源于人、鼠等)具有重链可变区(也可称为重链可变结构域、VH或VH结构域)和轻链可变区(也可称为轻链可变结构域、VL或VL结构域)。大多数情况下，天然抗体的每个可变结构域基本上由四个“框架区(FR)”和三个“互补决定区(CDR)”组成。四个框架区分别称为框架区1(或FR1)、框架区2(或FR2)、框架区3(或FR3)、及框架区4(或FR4)；所述框架区由本领域及下文中分别称为互补决定区1(或CDR1)、互补决定区2(或CDR2)、及互补决定区3(或CDR3)的三个互补决定区间隔开。因此，可变结构域的一般结构可如下表示为：FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4。可变结构域因具有抗原结合位点而赋予抗体对抗原的特异性。
术语“互补决定区”(CDR)，也称为“高变区”(HVR)。天然四链抗体通常包含六个CDR，三个 在重链可变区中，即重链CDR1(HCDR1)、重链CDR2(HCDR2)和重链CDR3(HCDR3)；三个在轻链可变区中，即轻链CDR1(LCDR1)、轻链CDR2(LCDR2)和轻链CDR3(LCDR3)。
术语“分离的”是指目标化合物(例如，抗体或核酸)已经从其天然环境中分离。
术语“EC50”是指半数有效浓度，是指在特定暴露事件后，能达到50％最大效应的抗体浓度。术语“IC50”是指半数抑制浓度，是指相对于不存在抗体的情况，将特异性生物学或生化功能抑制50％的抗体浓度。EC50和IC50两者均可以通过ELISA或FACS分析或本领域已知的任何其他方法进行测量。
术语“KD”在用于本文时指平衡解离常数，其获自kd比ka(即，kd/ka)的比率，以摩尔浓度(M)表示。抗体的KD值可以使用本领域公知的方法测定。一种优选的测定抗体KD的方法是使用表面等离振子共振(surface plasmon resonance)，更优选使用生物传感器系统，例如Biacore系统。
术语“治疗”是指治疗、治愈、减轻、缓解、改变、补救、改善、改进或影响疾患(例如疾病)、疾患的症状，或预防或延缓症状、并发症、生化指标的发作，或以其他方式阻滞或抑制疾病、疾患或病症的进一步发展而使用的措施。
如本文所用，术语“受试者”包括任何人类或非人动物。术语“非人动物”包括所有脊椎动物，例如哺乳动物和非哺乳动物，诸如非人灵长类、绵羊、犬、锚、马、牛、鸡、两栖动物、爬行动物等。优选地，根据本公开的受试者是人。除非标明，术语“患者”或“受试者”可以互换使用。
如本文所用，“约”表示在本领域普通技术人员判定的对特定值可以接受的误差范围内，其部分取决于如何测量或测定该值，即测量系统的限制。例如，“约”按照本领域实践可表示1倍或超过1倍标准偏差以内。或者，“约”可以表示多至±5％的范围，例如在所给定的具体数值范围±2％范围内、±1％范围内或±0.5％范围内波动。当本申请或权利要求中给出特定值时，除非另有说明，“约”的含义应认为是在该特定值的可接受的误差范围内。在本文中，除非另有说明，步骤参数或条件的值默认均由“约”修饰。
术语“同一性(identity)”，也称一致性。两序列间的百分比同一性为序列共有的相同位置数的函数(即％同一性＝相同位置数/位置总数×100)，其中需考虑产生两序列的最优比对需要引入的缺口数和每个缺口的长度。如下述非限制性实施例所示，可以使用数学算法完成序列的比较和两序列间百分比同一性的测定。可以使用E.Meyers和W.Miller的算法(Comput.Appl.Biosci.,4:11-17(1988))测定两氨基酸序列间的百分比同一性，该算法已收入到ALIGN程序(版本2.0)中，其使用PAM120残基权重表，缺口长度罚分为12，缺口罚分为4。此外，可以使用Needleman和Wunsch的算法(J.Mol.Biol.484-453(1970))测定两氨基酸序列的百分比同一性，该算法已掺入到GCG软件包(可在www.gcg.com获得)中的GAP程序中，其使用Blossum 62矩阵或PAM250矩阵，缺口权重为16、14、12、10、8、6或4，长度权重为1、2、3、4、5或6。
术语“Xn”和“Xaa”等同，是指未指定的氨基酸(Unspecified Amino Acid)，通过相关表述中的后续定义来指定其涵盖的范围。
术语“包括”、“含有”或“包含”及其变换形式应理解为“包括但不限于”，意味着除所列出的要素、组分和步骤外，还可涵盖其它未指明的要素、组分和步骤。
在本文中，除非上下文另有明确规定，否则单数术语涵盖复数指代物，反之亦然。“和/或”的使用意指“和”或者“或”。
抗TIGIT抗体或其抗原结合部分
本文中，术语“TIGIT”、“具有Ig和ITIM结构域的T细胞免疫受体”、“WUCAM”、“Vstm3”、“VSIG9”之间彼此可以互换的使用。术语“人TIGIT”和“human TIGIT”、“hTIGIT”等在本文中可互换使用。本文中，“抗TIGIT抗体”与“结合TIGIT的抗体”之间彼此可以互换的使用。
本公开提供了抗TIGIT抗体或其抗原结合部分，为靶向TIGIT的治疗提供新的解决方案。除了与人TIGIT和/或食蟹猴TIGIT结合外，本文提供的抗体还显示了其他诸多用于靶向治疗的期望的特征。具体地，这些期望的特征例如可以是以1.38E-09M或更小的KD值与人TIGIT结合、阻断TIGIT与CD155结合、促进NK细胞杀伤活性、促进NK细胞对Treg的ADCC作用、促进T细胞功能等中的至少一个。
一方面，本公开提供了包含特定序列的抗TIGIT抗体或其抗原结合部分。
在一些实施方案中，本公开提供了包含选自由SEQ ID NOs:1-24组成的组的一个或多个CDR的抗TIGIT抗体或其抗原结合部分。
在一些实施方案中，提供了一种抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体或其抗原结合部分包含：
HCDR1，其包含SEQ ID NO:1、2、3或4所示的氨基酸序列；
HCDR2，其包含SEQ ID NO:5、6、7或8所示的氨基酸序列；
HCDR3，其包含SEQ ID NO:9、10、11、12、13、14或15所示的氨基酸序列；
LCDR1，其包含SEQ ID NO:16、17或18所示的氨基酸序列；
LCDR2，其包含SEQ ID NO:19所示的氨基酸序列；和
LCDR3，其包含SEQ ID NO:20、21、22、23或24所示的氨基酸序列。
在一些具体的实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:1所示氨基酸序列的HCDR1；包含SEQ ID NO:5所示氨基酸序列的HCDR2；包含SEQ ID NO:9所示氨基酸序列的HCDR3；包含SEQ ID NO:16所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的LCDR2；和包含SEQ ID NO:20所示氨基酸序列的LCDR3。
在一些具体的实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:2所示氨基酸序列的HCDR1；包含SEQ ID NO:5所示氨基酸序列的HCDR2；包含SEQ ID NO:10所示氨基酸序列的HCDR3；包含SEQ ID NO:17所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的LCDR2；和包含SEQ ID NO:21所示氨基酸序列的LCDR3。
在一些具体的实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:3所示氨基酸序列的HCDR1；包含SEQ ID NO:6所示氨基酸序列的HCDR2；包含SEQ ID NO:11所示氨基酸序列的HCDR3；包含SEQ ID NO:16所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的LCDR2；和包含SEQ ID NO:22所示氨基酸序列的LCDR3。
在一些具体的实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:4所示氨基酸序列的HCDR1；包含SEQ ID NO:7所示氨基酸序列的HCDR2；包含SEQ ID NO:12所示氨基酸序列的HCDR3；包含SEQ ID NO:16所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的LCDR2；和包含SEQ ID NO:23所示氨基酸序列的LCDR3。
在一些具体的实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:4所示氨基酸序列的HCDR1；包含SEQ ID NO:8所示氨基酸序列的HCDR2；包含SEQ ID NO:13所示氨基酸序列的HCDR3；包含SEQ ID NO:18所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的LCDR2；和包含SEQ ID NO:24所示氨基酸序列的LCDR3。
在一些具体的实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:1所示氨基酸序列的HCDR1；包含SEQ ID NO:5所示氨基酸序列的HCDR2；包含SEQ ID NO:14所示氨基酸序列的HCDR3；包含SEQ ID NO:16所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的LCDR2；和包含SEQ ID NO:20所示氨基酸序列的LCDR3。
在一些具体的实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:2所示氨基酸序列的HCDR1；包含SEQ ID NO:5所示氨基酸序列的HCDR2；包含SEQ ID NO:15所示氨基酸序列的HCDR3；包含SEQ ID NO:17所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的LCDR2；和包含SEQ ID NO:21所示氨基酸序列的LCDR3。
在一些实施方案中，提供了一种抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述重链可变区包含SEQ ID NO:25、27、29、31、33、35、37、38、39、40、42、44、46、47、48、50、51、52、54、55、57、59、61或63所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:26、28、30、32、34、36、41、43、45、49、53、56、58、60、62或64所示序列的LCDR1、LCDR2和LCDR3。
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述重链可变区包含SEQ ID NO:25所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:26所示序列的LCDR1、LCDR2和LCDR3。
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述重链 可变区包含SEQ ID NO:27所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:28所示序列的LCDR1、LCDR2和LCDR3；
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述重链可变区包含SEQ ID NO:29所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:30所示序列的LCDR1、LCDR2和LCDR3；
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述重链可变区包含SEQ ID NO:31所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:32所示序列的LCDR1、LCDR2和LCDR3；
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述重链可变区包含SEQ ID NO:33所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:34所示序列的LCDR1、LCDR2和LCDR3；
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述重链可变区包含SEQ ID NO:55所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:56所示序列的LCDR1、LCDR2和LCDR3；
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述重链可变区包含SEQ ID NO:57所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:58所示序列的LCDR1、LCDR2和LCDR3；
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述重链可变区包含SEQ ID NO:59所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:60所示序列的LCDR1、LCDR2和LCDR3；
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述重链可变区包含SEQ ID NO:61所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:62所示序列的LCDR1、LCDR2和LCDR3；或
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述重链可变区包含SEQ ID NO:63所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:64所示序列的LCDR1、LCDR2和LCDR3。
在一些实施方案中，所述抗TIGIT抗体或其抗原结合部分包含重链可变区，所述重链可变区包含与SEQ ID NO:25、27、29、31、33、35、37、38、39、40、42、44、46、47、48、50、51、52、54、55、57、59、61或63所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。
在一些实施方案中，所述抗TIGIT抗体或其抗原结合部分包含轻链可变区，所述轻链可变区包含与SEQ ID NO:26、28、30、32、34、36、41、43、45、49、53、56、58、60、62或64所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。
在一些实施方案中，所述抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述的重链可变区包含与SEQ ID NO:25、27、29、31、33、35、37、38、39、40、42、44、46、47、48、50、51、52、54、55、57、59、61或63所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:26、28、30、32、34、36、41、43、45、49、53、56、58、60、 62或64所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述的重链可变区包含与SEQ ID NO:25所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:26所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。在一些这些实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:1所示氨基酸序列的HCDR1；包含SEQ ID NO:5所示氨基酸序列的HCDR2；包含SEQ ID NO:9所示氨基酸序列的HCDR3；包含SEQ ID NO:16所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的LCDR2；和包含SEQ ID NO:20所示氨基酸序列的LCDR3。
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述的重链可变区包含与SEQ ID NO:27所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:28所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。在一些这些实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:2所示氨基酸序列的HCDR1；包含SEQ ID NO:5所示氨基酸序列的HCDR2；包含SEQ ID NO:10所示氨基酸序列的HCDR3；包含SEQ ID NO:17所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的LCDR2；和包含SEQ ID NO:21所示氨基酸序列的LCDR3。
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述的重链可变区包含与SEQ ID NO:29所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:30所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。在一些这些实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:3所示氨基酸序列的HCDR1；包含SEQ ID NO:6所示氨基酸序列的HCDR2；包含SEQ ID NO:11所示氨基酸序列的HCDR3；包含SEQ ID NO:16所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的LCDR2；和包含SEQ ID NO:22所示氨基酸序列的LCDR3。
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述的重链可变区包含与SEQ ID NO:31所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％ 同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:32所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。在一些这些实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:4所示氨基酸序列的HCDR1；包含SEQ ID NO:7所示氨基酸序列的HCDR2；包含SEQ ID NO:12所示氨基酸序列的HCDR3；包含SEQ ID NO:16所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的LCDR2；和包含SEQ ID NO:23所示氨基酸序列的LCDR3。
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述的重链可变区包含与SEQ ID NO:33所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:34所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。在一些这些实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:4所示氨基酸序列的HCDR1；包含SEQ ID NO:8所示氨基酸序列的HCDR2；包含SEQ ID NO:13所示氨基酸序列的HCDR3；包含SEQ ID NO:18所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的LCDR2；和包含SEQ ID NO:24所示氨基酸序列的LCDR3。
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述的重链可变区包含与SEQ ID NO:35所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:36所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。在一些这些实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:1所示氨基酸序列的HCDR1；包含SEQ ID NO:5所示氨基酸序列的HCDR2；包含SEQ ID NO:14所示氨基酸序列的HCDR3；包含SEQ ID NO:16所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的LCDR2；和包含SEQ ID NO:20所示氨基酸序列的LCDR3。
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述的重链可变区包含与SEQ ID NO:37所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:36所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％ 同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。在一些这些实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:1所示氨基酸序列的HCDR1；包含SEQ ID NO:5所示氨基酸序列的HCDR2；包含SEQ ID NO:14所示氨基酸序列的HCDR3；包含SEQ ID NO:16所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的LCDR2；和包含SEQ ID NO:20所示氨基酸序列的LCDR3。
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述的重链可变区包含与SEQ ID NO:38所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:36所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。在一些这些实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:1所示氨基酸序列的HCDR1；包含SEQ ID NO:5所示氨基酸序列的HCDR2；包含SEQ ID NO:14所示氨基酸序列的HCDR3；包含SEQ ID NO:16所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的LCDR2；和包含SEQ ID NO:20所示氨基酸序列的LCDR3。
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述的重链可变区包含与SEQ ID NO:39所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:36所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。在一些这些实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:1所示氨基酸序列的HCDR1；包含SEQ ID NO:5所示氨基酸序列的HCDR2；包含SEQ ID NO:14所示氨基酸序列的HCDR3；包含SEQ ID NO:16所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的LCDR2；和包含SEQ ID NO:20所示氨基酸序列的LCDR3。
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述的重链可变区包含与SEQ ID NO:40所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:41所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。在一些这些实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:2所示氨基酸序列的HCDR1；包含SEQ ID NO:5所示氨基酸序列的HCDR2；包含SEQ ID NO:15所示氨基酸序列的HCDR3；包含SEQ ID NO:17所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的LCDR2；和包含SEQ ID NO:21所示氨基酸序列的LCDR3。
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述的重 链可变区包含与SEQ ID NO:42所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:41所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。在一些这些实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:2所示氨基酸序列的HCDR1；包含SEQ ID NO:5所示氨基酸序列的HCDR2；包含SEQ ID NO:15所示氨基酸序列的HCDR3；包含SEQ ID NO:17所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的LCDR2；和包含SEQ ID NO:21所示氨基酸序列的LCDR3。
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述的重链可变区包含与SEQ ID NO:40所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:43所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。在一些这些实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:2所示氨基酸序列的HCDR1；包含SEQ ID NO:5所示氨基酸序列的HCDR2；包含SEQ ID NO:15所示氨基酸序列的HCDR3；包含SEQ ID NO:17所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的LCDR2；和包含SEQ ID NO:21所示氨基酸序列的LCDR3。
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述的重链可变区包含与SEQ ID NO:42所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:43所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。在一些这些实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:2所示氨基酸序列的HCDR1；包含SEQ ID NO:5所示氨基酸序列的HCDR2；包含SEQ ID NO:15所示氨基酸序列的HCDR3；包含SEQ ID NO:17所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的LCDR2；和包含SEQ ID NO:21所示氨基酸序列的LCDR3。
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述的重链可变区包含与SEQ ID NO:44所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:45所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同 一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。在一些这些实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:3所示氨基酸序列的HCDR1；包含SEQ ID NO:6所示氨基酸序列的HCDR2；包含SEQ ID NO:11所示氨基酸序列的HCDR3；包含SEQ ID NO:16所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的LCDR2；和包含SEQ ID NO:22所示氨基酸序列的LCDR3。
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述的重链可变区包含与SEQ ID NO:46所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:45所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。在一些这些实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:3所示氨基酸序列的HCDR1；包含SEQ ID NO:6所示氨基酸序列的HCDR2；包含SEQ ID NO:11所示氨基酸序列的HCDR3；包含SEQ ID NO:16所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的LCDR2；和包含SEQ ID NO:22所示氨基酸序列的LCDR3。
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述的重链可变区包含与SEQ ID NO:47所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:45所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。在一些这些实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:3所示氨基酸序列的HCDR1；包含SEQ ID NO:6所示氨基酸序列的HCDR2；包含SEQ ID NO:11所示氨基酸序列的HCDR3；包含SEQ ID NO:16所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的LCDR2；和包含SEQ ID NO:22所示氨基酸序列的LCDR3。
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述的重链可变区包含与SEQ ID NO:48所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:49所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。在一些这些实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:4所示氨基酸序列的HCDR1；包含SEQ ID NO:7所示氨基酸序列的HCDR2；包含SEQ ID NO:12所示氨基酸序列的HCDR3；包含SEQ ID NO:16所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的LCDR2；和包含SEQ ID NO:23所示氨基酸序列的LCDR3。
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述的重链可变区包含与SEQ ID NO:50所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:49所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。在一些这些实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:4所示氨基酸序列的HCDR1；包含SEQ ID NO:7所示氨基酸序列的HCDR2；包含SEQ ID NO:12所示氨基酸序列的HCDR3；包含SEQ ID NO:16所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的LCDR2；和包含SEQ ID NO:23所示氨基酸序列的LCDR3。
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述的重链可变区包含与SEQ ID NO:51所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:49所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。在一些这些实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:4所示氨基酸序列的HCDR1；包含SEQ ID NO:7所示氨基酸序列的HCDR2；包含SEQ ID NO:12所示氨基酸序列的HCDR3；包含SEQ ID NO:16所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的LCDR2；和包含SEQ ID NO:23所示氨基酸序列的LCDR3。
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述的重链可变区包含与SEQ ID NO:52所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:53所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。在一些这些实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:4所示氨基酸序列的HCDR1；包含SEQ ID NO:8所示氨基酸序列的HCDR2；包含SEQ ID NO:13所示氨基酸序列的HCDR3；包含SEQ ID NO:18所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的LCDR2；和包含SEQ ID NO:24所示氨基酸序列的LCDR3。
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述的重链可变区包含与SEQ ID NO:54所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:53所示序列具有至少80％同一性、至少81％同一性、至少82％同一 性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。在一些这些实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:4所示氨基酸序列的HCDR1；包含SEQ ID NO:8所示氨基酸序列的HCDR2；包含SEQ ID NO:13所示氨基酸序列的HCDR3；包含SEQ ID NO:18所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的LCDR2；和包含SEQ ID NO:24所示氨基酸序列的LCDR3。
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述的重链可变区包含与SEQ ID NO:55所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:56所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。在一些这些实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:1所示氨基酸序列的HCDR1；包含SEQ ID NO:5所示氨基酸序列的HCDR2；包含SEQ ID NO:14所示氨基酸序列的HCDR3；包含SEQ ID NO:16所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的LCDR2；和包含SEQ ID NO:20所示氨基酸序列的LCDR3。
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述的重链可变区包含与SEQ ID NO:57所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:58所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。在一些这些实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:2所示氨基酸序列的HCDR1；包含SEQ ID NO:5所示氨基酸序列的HCDR2；包含SEQ ID NO:15所示氨基酸序列的HCDR3；包含SEQ ID NO:17所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的LCDR2；和包含SEQ ID NO:21所示氨基酸序列的LCDR3。
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述的重链可变区包含与SEQ ID NO:59所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:60所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。在一些这些实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:3所示氨基酸序列的HCDR1；包含SEQ ID NO:6所示氨基酸序列的HCDR2；包含SEQ ID NO:11所示氨基酸序列的HCDR3；包含SEQ ID NO:16所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的 LCDR2；和包含SEQ ID NO:22所示氨基酸序列的LCDR3。
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述的重链可变区包含与SEQ ID NO:61所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:62所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。在一些这些实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:4所示氨基酸序列的HCDR1；包含SEQ ID NO:7所示氨基酸序列的HCDR2；包含SEQ ID NO:12所示氨基酸序列的HCDR3；包含SEQ ID NO:16所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的LCDR2；和包含SEQ ID NO:23所示氨基酸序列的LCDR3。
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述的重链可变区包含与SEQ ID NO:63所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:64所示序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。在一些这些实施方案中，所述抗TIGIT抗体或其抗原结合部分包含：包含SEQ ID NO:4所示氨基酸序列的HCDR1；包含SEQ ID NO:8所示氨基酸序列的HCDR2；包含SEQ ID NO:13所示氨基酸序列的HCDR3；包含SEQ ID NO:18所示氨基酸序列的LCDR1；包含SEQ ID NO:19所示氨基酸序列的LCDR2；和包含SEQ ID NO:24所示氨基酸序列的LCDR3。
在一些实施方案中，提供的抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述的重链可变区包含SEQ ID NO:25、27、29、31、33、35、37、38、39、40、42、44、46、47、48、50、51、52、54、55、57、59、61或63所示的氨基酸序列或由SEQ ID NO:25、27、29、31、33、35、37、38、39、40、42、44、46、47、48、50、51、52、54、55、57、59、61或63所示的氨基酸序列组成，所述轻链可变区包含SEQ ID NO:26、28、30、32、34、36、41、43、45、49、53、56、58、60、62或64所示的氨基酸序列或由SEQ ID NO:26、28、30、32、34、36、41、43、45、49、53、56、58、60、62或64所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链可变区和轻链可变区，所述的重链可变区包含SEQ ID NO:25所示的氨基酸序列或由SEQ ID NO:25所示的氨基酸序列组成，所述轻链可变区包含SEQ ID NO:26所示的氨基酸序列或由SEQ ID NO:26所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链可变区和轻链可变区，所述的重链可变区包含SEQ ID NO:27所示的氨基酸序列或由SEQ ID NO:27所示的氨基酸序列组成，所述轻链可变区包含SEQ ID NO:28所示的氨基酸序列或由SEQ ID NO:28所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链可变区和轻链可变区，所述的重链可变区包含SEQ ID NO:29所示的氨基酸序列或由SEQ ID NO:29所示的氨基酸序列组成，所述轻链可变区包含SEQ ID NO:30所示的氨基酸序列或由SEQ ID NO:30所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链可变区和轻链可变区，所述的重链可变区包含SEQ ID NO:31所示的氨基酸序列或由SEQ ID NO:31所示的氨基酸序列组成，所述轻链可变区包含SEQ ID NO:32所示的氨基酸序列或由SEQ ID NO:32所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链可变区和轻链可变区，所述的重链可变区包含SEQ ID NO:33所示的氨基酸序列或由SEQ ID NO:33所示的氨基酸 序列组成，所述轻链可变区包含SEQ ID NO:34所示的氨基酸序列或由SEQ ID NO:34所示的氨基酸序列组成。
在一些实施方案中，提供的抗TIGIT抗体包含重链可变区和轻链可变区，所述的重链可变区包含SEQ ID NO:35所示的氨基酸序列或由SEQ ID NO:35所示的氨基酸序列组成，所述轻链可变区包含SEQ ID NO:36所示的氨基酸序列或由SEQ ID NO:36所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链可变区和轻链可变区，所述的重链可变区包含SEQ ID NO:37所示的氨基酸序列或由SEQ ID NO:37所示的氨基酸序列组成，所述轻链可变区包含SEQ ID NO:36所示的氨基酸序列或由SEQ ID NO:36所示的氨基酸序列组成。
在一些实施方案中，提供的抗TIGIT抗体包含重链可变区和轻链可变区，所述的重链可变区包含SEQ ID NO:38所示的氨基酸序列或由SEQ ID NO:38所示的氨基酸序列组成，所述轻链可变区包含SEQ ID NO:36所示的氨基酸序列或由SEQ ID NO:36所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链可变区和轻链可变区，所述的重链可变区包含SEQ ID NO:39所示的氨基酸序列或由SEQ ID NO:39所示的氨基酸序列组成，所述轻链可变区包含SEQ ID NO:36所示的氨基酸序列或由SEQ ID NO:36所示的氨基酸序列组成。
在一些实施方案中，提供的抗TIGIT抗体包含重链可变区和轻链可变区，所述的重链可变区包含SEQ ID NO:40所示的氨基酸序列或由SEQ ID NO:40所示的氨基酸序列组成，所述轻链可变区包含SEQ ID NO:41所示的氨基酸序列或由SEQ ID NO:41所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链可变区和轻链可变区，所述的重链可变区包含SEQ ID NO:42所示的氨基酸序列或由SEQ ID NO:42所示的氨基酸序列组成，所述轻链可变区包含SEQ ID NO:41所示的氨基酸序列或由SEQ ID NO:41所示的氨基酸序列组成。
在一些实施方案中，提供的抗TIGIT抗体包含重链可变区和轻链可变区，所述的重链可变区包含SEQ ID NO:40所示的氨基酸序列或由SEQ ID NO:40所示的氨基酸序列组成，所述轻链可变区包含SEQ ID NO:43所示的氨基酸序列或由SEQ ID NO:43所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链可变区和轻链可变区，所述的重链可变区包含SEQ ID NO:42所示的氨基酸序列或由SEQ ID NO:42所示的氨基酸序列组成，所述轻链可变区包含SEQ ID NO:43所示的氨基酸序列或由SEQ ID NO:43所示的氨基酸序列组成。
在一些实施方案中，提供的抗TIGIT抗体包含重链可变区和轻链可变区，所述的重链可变区包含SEQ ID NO:44所示的氨基酸序列或由SEQ ID NO:44所示的氨基酸序列组成，所述轻链可变区包含SEQ ID NO:45所示的氨基酸序列或由SEQ ID NO:45所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链可变区和轻链可变区，所述的重链可变区包含SEQ ID NO:46所示的氨基酸序列或由SEQ ID NO:46所示的氨基酸序列组成，所述轻链可变区包含SEQ ID NO:45所示的氨基酸序列或由SEQ ID NO:45所示的氨基酸序列组成。
在一些实施方案中，提供的抗TIGIT抗体包含重链可变区和轻链可变区，所述的重链可变区包含SEQ ID NO:47所示的氨基酸序列或由SEQ ID NO:47所示的氨基酸序列组成，所述轻链可变区包含SEQ ID NO:45所示的氨基酸序列或由SEQ ID NO:45所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链可变区和轻链可变区，所述的重链可变区包含SEQ ID NO:48所示的氨基酸序列或由SEQ ID NO:48所示的氨基酸序列组成，所述轻链可变区包含SEQ ID NO:49所示的氨基酸序列或由SEQ ID NO:49所示的氨基酸序列组成。
在一些实施方案中，提供的抗TIGIT抗体包含重链可变区和轻链可变区，所述的重链可变区包含SEQ ID NO:50所示的氨基酸序列或由SEQ ID NO:50所示的氨基酸序列组成，所述轻链可变区包含SEQ ID NO:49所示的氨基酸序列或由SEQ ID NO:49所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链可变区和轻链可变区，所述的重链可变区包含SEQ ID NO:51所示的氨基酸序列或由SEQ ID NO:51所示的氨基酸序列组成，所述轻链可变区包含SEQ ID NO:49所示的氨基酸序列或由SEQ ID NO:49所示的氨基酸序列组成。
在一些实施方案中，提供的抗TIGIT抗体包含重链可变区和轻链可变区，所述的重链可变区包含SEQ ID NO:52所示的氨基酸序列或由SEQ ID NO:52所示的氨基酸序列组成，所述轻链可变区包含SEQ ID NO:53所示的氨基酸序列或由SEQ ID NO:53所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链可变区和轻链可变区，所述的重链可变区包含SEQ ID NO:54所示的氨基酸序列或由SEQ ID NO:54所示的氨基酸序列组成，所述轻链可变区包含SEQ ID NO:53所示的氨基酸序列或由SEQ ID NO:53所示的氨基酸序列组成。
在一些实施方案中，提供的抗TIGIT抗体包含重链可变区和轻链可变区，所述的重链可变区包含SEQ ID NO:55所示的氨基酸序列或由SEQ ID NO:55所示的氨基酸序列组成，所述轻链可变区包含SEQ ID NO:56所示的氨基酸序列或由SEQ ID NO:56所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链可变区和轻链可变区，所述的重链可变区包含SEQ ID NO:57所示的氨基酸序列或由SEQ ID NO:57所示的氨基酸序列组成，所述轻链可变区包含SEQ ID NO:58所示的氨基酸序列或由SEQ ID NO:58所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链可变区和轻链可变区，所述的重链可变区包含SEQ ID NO:59所示的氨基酸序列或由SEQ ID NO:59所示的氨基酸序列组成，所述轻链可变区包含SEQ ID NO:60所示的氨基酸序列或由SEQ ID NO:60所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链可变区和轻链可变区，所述的重链可变区包含SEQ ID NO:61所示的氨基酸序列或由SEQ ID NO:61所示的氨基酸序列组成，所述轻链可变区包含SEQ ID NO:62所示的氨基酸序列或由SEQ ID NO:62所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链可变区和轻链可变区，所述的重链可变区包含SEQ ID NO:63所示的氨基酸序列或由SEQ ID NO:63所示的氨基酸序列组成，所述轻链可变区包含SEQ ID NO:64所示的氨基酸序列或由SEQ ID NO:64所示的氨基酸序列组成。
在一些实施方案中，本文提供的抗TIGIT抗体包含重链和轻链，重链和轻链除了包含本文所述的重链可变区和轻链可变区外，还包括恒定区。在一些实施方案中，所述抗TIGIT抗体的重链恒定区可来自任何类型的恒定区，例如IgG、IgM、IgD、IgA和IgE或其变体；以及任何同种型，例如IgG1、IgG2、IgG3和IgG4或其变体。在一些实施方案中，所述抗TIGIT抗体的重链恒定区是人IgG1同种型或其变体。在一些实施方案中，分离的抗TIGIT抗体的轻链恒定区是人κ轻链恒定区或其变体。在一些实施方案中，分离的抗TIGIT抗体的轻链恒定区是人λ轻链恒定区或其变体。所述恒定区变体是指相对于恒定区具有1、2、3、4或5个氨基酸取代、删除和添加的氨基酸序列。在一些实施方案中，所述取代可以是保守氨基酸取代。
在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含与SEQ ID NO:65、67、69、71、73、75、77、78、79、80、82、84、86、87、88、90、91、92或94所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:66、68、70、72、74、76、81、83、85、89或93所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。
在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含与SEQ ID NO:65所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:66所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。
在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含与SEQ ID NO:67所示的序列 具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:68所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。
在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含与SEQ ID NO:69所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:70所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。
在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含与SEQ ID NO:71所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:72所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。
在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含与SEQ ID NO:73所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:74所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。
在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含与SEQ ID NO:75所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:76所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。
在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含与SEQ ID NO:77所示的序列 具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:76所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。
在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含与SEQ ID NO:78所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:76所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。
在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含与SEQ ID NO:79所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:76所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。
在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含与SEQ ID NO:80所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:81所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。
在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含与SEQ ID NO:82所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:81所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。
在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含与SEQ ID NO:80所示的序列 具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:83所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。
在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含与SEQ ID NO:82所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:83所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。
在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含与SEQ ID NO:84所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:85所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。
在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含与SEQ ID NO:86所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:85所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。
在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含与SEQ ID NO:87所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:85所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。
在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含与SEQ ID NO:88所示的序列 具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:89所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。
在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含与SEQ ID NO:90所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:89所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。
在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含与SEQ ID NO:91所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:89所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。
在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含与SEQ ID NO:92所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:93所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。
在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含与SEQ ID NO:94所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:93所示的序列具有至少80％同一性、至少81％同一性、至少82％同一性、至少83％同一性、至少84％同一性、至少85％同一性、至少86％同一性、至少87％同一性、至少88％同一性、至少89％同一性、至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性、至少99％同一性或100％同一性的氨基酸序列。
在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含SEQ ID NO:65、67、69、71、 73、75、77、78、79、80、82、84、86、87、88、90、91、92或94所示的氨基酸序列或由SEQ ID NO:65、67、69、71、73、75、77、78、79、80、82、84、86、87、88、90、91、92或94所示的氨基酸序列组成，所述轻链包含SEQ ID NO:66、68、70、72、74、76、81、83、85、89或93所示的氨基酸序列或由SEQ ID NO:66、68、70、72、74、76、81、83、85、89或93所示的氨基酸序列组成。
在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含SEQ ID NO:65所示的氨基酸序列或由SEQ ID NO:65所示的氨基酸序列组成，所述轻链包含SEQ ID NO:66所示的氨基酸序列或由SEQ ID NO:66所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含SEQ ID NO:67所示的氨基酸序列或由SEQ ID NO:67所示的氨基酸序列组成，所述轻链包含SEQ ID NO:68所示的氨基酸序列或由SEQ ID NO:68所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含SEQ ID NO:69所示的氨基酸序列或由SEQ ID NO:69所示的氨基酸序列组成，所述轻链包含SEQ ID NO:70所示的氨基酸序列或由SEQ ID NO:70所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含SEQ ID NO:71所示的氨基酸序列或由SEQ ID NO:71所示的氨基酸序列组成，所述轻链包含SEQ ID NO:72所示的氨基酸序列或由SEQ ID NO:72所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含SEQ ID NO:73所示的氨基酸序列或由SEQ ID NO:73所示的氨基酸序列组成，所述轻链包含SEQ ID NO:74所示的氨基酸序列或由SEQ ID NO:74所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含SEQ ID NO:75所示的氨基酸序列或由SEQ ID NO:75所示的氨基酸序列组成，所述轻链包含SEQ ID NO:76所示的氨基酸序列或由SEQ ID NO:76所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含SEQ ID NO:77所示的氨基酸序列或由SEQ ID NO:77所示的氨基酸序列组成，所述轻链包含SEQ ID NO:76所示的氨基酸序列或由SEQ ID NO:76所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含SEQ ID NO:78所示的氨基酸序列或由SEQ ID NO:78所示的氨基酸序列组成，所述轻链包含SEQ ID NO:76所示的氨基酸序列或由SEQ ID NO:76所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含SEQ ID NO:79所示的氨基酸序列或由SEQ ID NO:79所示的氨基酸序列组成，所述轻链包含SEQ ID NO:76所示的氨基酸序列或由SEQ ID NO:76所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含SEQ ID NO:80所示的氨基酸序列或由SEQ ID NO:80所示的氨基酸序列组成，所述轻链包含SEQ ID NO:81所示的氨基酸序列或由SEQ ID NO:81所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含SEQ ID NO:82所示的氨基酸序列或由SEQ ID NO:82所示的氨基酸序列组成，所述轻链包含SEQ ID NO:81所示的氨基酸序列或由SEQ ID NO:81所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含SEQ ID NO:80所示的氨基酸序列或由SEQ ID NO:80所示的氨基酸序列组成，所述轻链包含SEQ ID NO:83所示的氨基酸序列或由SEQ ID NO:83所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含SEQ ID NO:82所示的氨基酸序列或由SEQ ID NO:82所示的氨基酸序列组成，所述轻链包含SEQ ID NO:83所示的氨基酸序列或由SEQ ID NO:83所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含SEQ ID NO:84所示的氨基酸序列或由SEQ ID NO:84所示的氨基酸序列组成，所述轻链包含SEQ ID NO:85所示的氨基酸序列或由SEQ ID NO:85所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含SEQ ID NO:86所示的氨基酸序列或由SEQ ID NO:86所示的氨基酸序列组成，所述轻链包含SEQ ID NO:85所示的氨基酸序列或由SEQ ID NO:85所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含SEQ ID NO:87所示的氨基酸序列或由SEQ ID NO:87所示的氨基酸序列组成，所述轻链包含SEQ ID NO:85所示的氨基酸序列或由SEQ ID NO:85所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含SEQ ID NO:88所示的氨基酸序列或由SEQ ID NO:88所示的氨基酸序列组成，所述轻链包含SEQ ID NO:89所示的氨基酸序列或由SEQ ID NO:89所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含SEQ ID NO:90所示的氨基酸序列或由SEQ ID NO:90所示的氨基酸序列组成，所述轻链包含SEQ ID NO:89所示的氨基酸序列或由SEQ ID NO:89所示 的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含SEQ ID NO:91所示的氨基酸序列或由SEQ ID NO:91所示的氨基酸序列组成，所述轻链包含SEQ ID NO:89所示的氨基酸序列或由SEQ ID NO:89所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含SEQ ID NO:92所示的氨基酸序列或由SEQ ID NO:92所示的氨基酸序列组成，所述轻链包含SEQ ID NO:93所示的氨基酸序列或由SEQ ID NO:93所示的氨基酸序列组成。在一些实施方案中，提供的抗TIGIT抗体包含重链和轻链，所述重链包含SEQ ID NO:94所示的氨基酸序列或由SEQ ID NO:94所示的氨基酸序列组成，所述轻链包含SEQ ID NO:93所示的氨基酸序列或由SEQ ID NO:93所示的氨基酸序列组成。
在一些实施方案中，抗TIGIT抗体或其抗原结合部分结合人TIGIT。在一些实施方案中，抗TIGIT抗体或其抗原结合部分结合食蟹猴TIGIT。在一些实施方案中，抗TIGIT抗体或其抗原结合部分结合大鼠TIGIT。在一些实施方案中，所述抗体或其抗原结合部分以1.38E-09M或更小的KD值与人TIGIT结合。在一些实施方案中，所述抗体或其抗原结合部分对人TIGIT具有下述结合亲和力(KD)：在约1E-12M至约1E-05M、约1E-12M至约1.38E-07M、约1E-12M至约1.38E-06M、约1E-12M至约1.38E-05M、约1E-11M至约1.38E-08M、约9.68E-10M至约1.38E-08M、约9.68E-10M至约1.38E-09M、约1.10E-10M至约1.38E-08M或约1.10E-10M至约1.38E-09M的范围内。在一些实施方案中，所述抗体或其抗原结合部分对人TIGIT具有下述结合亲和力(KD)：约1E-05M或更小、约1.38E-07M或更小、约1.38E-08M或更小、约1.38E-09M或更小、约9.36E-10M或更小、约4.44E-10M或更小、约2.55E-10M或更小、约2.15E-10M或更小、或者约1.10E-10M或更小。在一些实施方案中，所述抗体或其抗原结合部分对人TIGIT具有下述结合亲和力(KD)：约1.38E-09M、约1.13E-09M、约9.68E-10M、约9.37E-10M、约9.36E-10M、约7.13E-10M、约7.08E-10M、约6.22E-10M、约5.65E-10M、约5.59E-10M、约4.44E-10M、约3.90E-10M、约3.87E-10M、约3.83E-10M、约2.60E-10M、约2.55E-10M、约2.32E-10M、约2.15E-10M、约1.43E-10M或约1.10E-10M。在一些实施方案中，通过Biacore来测量本文提供的抗TIGIT抗体或其抗原结合部分对人TIGIT的结合亲和力KD。
在一些实施方案中，抗TIGIT抗体或其抗原结合部分对人TIGIT具有约0.01nM至约2nM、约0.01nM至约1.5nM、约0.01nM至约1nM、约0.01nM至约0.5nM、约0.01nM至约0.25nM、约0.05nM至约0.25nM、或约0.05nM至约0.15nM的结合EC50。在一些实施方案中，抗TIGIT抗体或其抗原结合部分对人TIGIT具有约2nM或更小、约1.5nM或更小、约1nM或更小、约0.5nM或更小、约0.25nM或更小、约0.15nM或更小、约0.12nM或更小、约0.09nM或更小、或约0.07nM或更小的结合EC50。在一些实施方案中，通过ELISA或FACS来测量本文提供的抗TIGIT抗体或其抗原结合部分的EC50。
在一些实施方案中，抗TIGIT抗体或其抗原结合部分阻断TIGIT与CD155的结合。在一些实施方案中，抗TIGIT抗体或其抗原结合部分阻断TIGIT与CD155结合的IC50为约0.01nM至约2nM、约0.01nM至约1.5nM、约0.01nM至约1nM、约0.01nM至约0.5nM、约0.01nM至约0.25nM、约0.05nM至约0.25nM、或约0.05nM至约0.15nM。在一些实施方案中，抗TIGIT抗体或其抗原结合部分阻断TIGIT与CD155结合的IC50为约2nM或更小、约1.5nM或更小、约1nM或更小、约0.5nM或更小、约0.25nM或更小、约0.15nM或更小、约0.11nM或更小、约0.10nM或更小、或约0.09nM或更小。在一些实施方案中，通过ELISA或FACS来测量本文提供的抗TIGIT抗体或其抗原结合部分阻断TIGIT与CD155结合的IC50。
在一些实施方案中，抗TIGIT抗体或其抗原结合部分促进NK细胞的杀伤活性。TIGIT表达于活化的NK细胞表面，当TIGIT与靶细胞(如肿瘤细胞)表面的CD155结合后，抑制了NK细胞对靶细胞的杀伤活性。通过抗TIGIT抗体阻断TIGIT与CD155的结合，解除TIGIT带来的免疫抑制效果，促进NK细胞对靶细胞(具体的例子如Widr细胞等)的杀伤活性。在一些实施方案中，抗TIGIT抗体或其抗原结合部分促进NK细胞杀伤活性的EC50为约0.01pM至约20pM、约0.01pM至约15pM、约0.01pM至约10pM、约0.1pM至约10pM、约0.1pM至约5pM、约0.1pM至约3pM、或约0.5pM至约3pM。在一些实施方案中，抗TIGIT抗体或其抗原结合部分促进NK细胞杀伤活性的EC50为约20pM或更小、约15pM或更小、约10pM或更小、约9.155pM或更小、约8.952pM或更小、约6.118pM或更小、约5.029pM或更小、约3.375pM或更小、约2.842pM或更小、约2.785pM或更小、约2.122pM或更小、约1.743pM或更小、约0.7557pM或更小、约0.5832pM或更小、约0.2675pM或更小、或约0.2406pM或更小。
在一些实施方案中，抗TIGIT抗体或其抗原结合部分促进NK细胞对Treg的ADCC作用。TIGIT除了表达于活化的NK细胞表面，还相对高丰度表达在活化的Treg细胞表面。通过抗TIGIT抗体(hIgG1亚型)可以介导NK细胞对Treg细胞的ADCC作用。在一些实施方案中，抗TIGIT抗体或其抗原结合部分促进NK细胞对Treg ADCC作用的EC50为约0.001pM至约20pM、约0.001pM至约15pM、约0.001pM至约12pM、约0.01pM至约12pM、约0.01pM至约10pM、约0.01pM至约5pM、约0.02pM至约5pM、约0.02pM至约3pM、或约0.5pM至约3pM。在一些实施方案中，抗TIGIT抗体或其抗原结合部分促进NK细胞对Treg ADCC作用的EC50为约20pM或更小、约15pM或更小、约12pM或更小、约11.84pM或更小、约10pM或更小、约4.696pM或更小、约3.907pM或更小、约2.53pM或更小、约1.74pM或更小、约0.9652pM或更小、约0.79pM或更小、约0.6992pM或更小、约0.5121pM或更小、约0.2905pM或更小、约0.09273pM或更小、约0.06101pM或更小、或约0.02187pM或更小。
在一些实施方案中，抗TIGIT抗体或其抗原结合部分促进T细胞功能。活化的CD8+T细胞表面表达相对高丰度的TIGIT，TIGIT与其配体相互作用介导CD8+T细胞抑制性信号转导进而导致细胞耗竭。抗TIGIT抗体可以逆转CD8+T细胞的耗竭状态，提高CD8+T细胞的因子释放及免疫活性。在一些实施方案中，在约0.7nM至约70nM的抗TIGIT抗体浓度下，CD8+T细胞分泌IFNγ的浓度为约40pg/mL至约2000pg/mL、约40pg/mL至约1500pg/mL、约60pg/mL至约1500pg/mL、约60pg/mL至约1300pg/mL、约80pg/mL至约1300pg/mL、约80pg/mL至约1000pg/mL、约80pg/mL至约600pg/mL、或约200pg/mL至约600pg/mL。
因此，另一方面，本公开提供了展现出下述性质中的一种或几种组合的抗TIGIT抗体或其抗原结合部分：
(i)以1.38E-09M或更小的KD值与人TIGIT结合；
(ii)阻断TIGIT与CD155结合；
(iii)促进NK细胞杀伤活性；
(iv)促进NK细胞对Treg的ADCC作用；和
(v)促进T细胞功能。
在一些实施方案中，抗TIGIT抗体和/或其抗原结合部分具有所述性质(i)-(v)中的一个、两个、三个、四个或五个。在一些实施方案中，所述抗体或其抗原结合部分具有所述性质(i)、(ii)和(iii)。在一些实施方案中，所述抗体或其抗原结合部分具有所述性质(i)、(ii)和(iv)。在一些实施方案中，所述抗体或其抗原结合部分具有所述性质(i)、(ii)和(v)。在一些实施方案中，所述抗体或其抗原结合部分具有所述性质(i)、(ii)、(iii)和(iv)。在一些实施方案中，所述抗体或其抗原结合部分具有所述性质(i)、(ii)、(iii)和(v)。在一些实施方案中，所述抗体或其抗原结合部分具有所述性质(i)、(ii)、(iv)和(v)。在一些实施方案中，所述抗体或其抗原结合部分具有所述性质(i)、(ii)、(iii)、(iv)和(v)。
在一些实施方案中，本文提供的抗TIGIT抗体是单克隆抗体。
在一些实施方案中，本公开提供了与本文提供的任何示例性抗体结合TIGIT上的相同表位的抗TIGIT抗体或其抗原结合部分，例如与Ab1的嵌合抗体或人源化抗体结合相同表位，例如与Ab2的嵌合抗体或人源化抗体结合相同表位，例如与Ab19的嵌合抗体或人源化抗体结合相同表位，例如与Ab23的嵌合抗体或人源化抗体结合相同表位，例如与Ab30的嵌合抗体或人源化抗体结合相同表位。在一些实施方案中，抗TIGIT抗体或其抗原结合部分与本文提供的用于结合TIGIT的任何示例性抗体竞争，例如与Ab1的嵌合抗体或人源化抗体竞争结合TIGIT，例如与Ab2的嵌合抗体或人源化抗体竞争结合TIGIT，例如与Ab19的嵌合抗体或人源化抗体竞争结合TIGIT，例如与Ab23的嵌合抗体或人源化抗体竞争结合TIGIT，例如与Ab30的嵌合抗体或人源化抗体竞争结合TIGIT。可以通过ELISA、流式细胞术、表面等离子体共振(SPR)测定或本领域已知的任何其他方法测量与TIGIT的结合。
本公开提供了一些示例性的抗TIGIT单克隆抗体，包括Ab1、Ab2、Ab19、Ab23和Ab30抗体的嵌合版本(ch-Ab1、ch-Ab2、ch-Ab19、ch-Ab23和ch-Ab30)以及Ab1、Ab2、Ab19、Ab23和Ab30的人源化变体。本文提供的示例性的抗TIGIT抗体的重链CDR(HCDR1、HCDR2和HCDR3)的氨基酸序列提供于下表S1中，轻链CDR(LCDR1、LCDR2和LCDR3)的氨基酸序列提供于下表S2中。然而，如本领域所公知的，互补决定区(CDR)可以基于重/轻链可变区序列由多种编号系统/方法例如Kabat(Kabat等人，免疫学的蛋 白质序列，第五版，美国国立卫生研究院，贝塞斯达，马里兰州(1991))、Chothia(JMol Biol 273:927-48,1997)、IMGT(Lefranc M.P.,Immunologist,7,132-136(1999)；Lefranc,M.P.等,Dev.Comp.Immunol.,27,55-77(2003))、AbM(Oxford Molecular的AbM抗体建模35软件定义)或Contact(基于对可用复杂晶体结构的分析)确定，CDR区也可以基于Kabat、Chothia、IMGT、AbM和Contact定义规则中的两种或多种组合确定。表S1、S2中所示的CDR区由IMGT编号系统定义。本领域技术人员应当理解的是，除非另有规定，否则术语给定抗体或其区(例如可变区)的“CDR”应了解为涵盖通过任何一种已知方案界定的CDR。在涉及用本公开某些划分定义的具体CDR序列限定抗体时，所述抗体的范围还涵盖了转换为其他任意编号系统定义(例如本领域所公知的Kabat、Chothia、IMGT、AbM或Contact等定义中的一种或几种的结合)的CDR序列限定的抗体。本文提供的示例性的抗TIGIT抗体的可变区以及全长重链、轻链的氨基酸序列分别提供于下表S3、S4中，编码抗TIGIT抗体的可变区以及全长重链、轻链的核苷酸序列分别提供于下表S5、S6中。
表S1：抗TIGIT抗体的重链CDR序列
表S2：抗TIGIT抗体的轻链CDR序列
表S3：抗TIGIT抗体的可变区氨基酸序列



表S4：抗TIGIT抗体的全长重链和全长轻链的氨基酸序列





表S5：抗TIGIT抗体的可变区核苷酸序列

表S6：抗TIGIT抗体的全长重链和全长轻链的核苷酸序列












抗体药物偶联物
在一些实施方案中，本公开提供了包含抗TIGIT抗体或其抗原结合部分的抗体药物偶联物。可以与抗TIGIT抗体或其抗原结合部分偶联的治疗剂可以包括但不限于细胞毒性药物、放射性同位素、免疫调节剂或抗体。在一些实施方案中，抗TIGIT抗体或其抗原结合部分与治疗剂直接偶联。在一些实施方案中，抗TIGIT抗体或其抗原结合部分通过接头与治疗剂偶联。
融合蛋白
在一些实施方案中，本公开包含本公开的抗TIGIT抗体或其抗原结合部分的融合蛋白。
药物组合物
本公开提供了药物组合物，所述药物组合物包含抗TIGIT抗体或其抗原结合部分，或本文所述的抗体药物偶联物，或本文所述的融合蛋白，并且还包含一种或多种药学上可接受的载体。在一些实施方案中，药物组合物包括Ab1、Ab2、Ab19、Ab23和Ab30抗体的嵌合抗体及人源化抗体中的任一单克隆抗体，以及药学上可接受的载体。药学上可接受的载体包括，例如，赋形剂、稀释剂、包封材料、填充剂、缓冲剂或 其他试剂。在一些实施方案中，所述的药物组合物是可注射的。在一些实施方案中，所述的药物组合物是无菌的。
分离的核酸
本公开提供了分离的核酸，其包含编码本文所述抗TIGIT抗体或其抗原结合部分的序列，在一些实施方案中，所述核酸可以编码包含本文所述抗体重链可变区和/或轻链可变区的氨基酸序列。在另一些实施方案中，所述的核酸可以编码包含本文所述的抗体重链和/或抗体轻链的氨基酸序列。序列表中示例性的列举了一些可变区、抗体重链和轻链的核苷酸序列。
载体
本公开提供了包含所述的分离的核酸的载体。在一些实施方案中，所述的载体为克隆载体；在另一些实施方案中，所述的载体为表达载体。所述表达载体可选地为能够表达本文所述抗TIGIT抗体或其抗原结合部分的任意表达载体。
宿主细胞
在一些实施方案中，本公开提供包含所述载体的宿主细胞，宿主细胞为用于克隆或编码抗TIGIT抗体或其抗原结合部分的适当宿主细胞。在一些实施方案中，宿主细胞为原核细胞。在另一些实施方案中，宿主细胞为真核细胞。在一些实施方案中，宿主细胞选自酵母细胞、哺乳细胞或适用于制备抗体或其抗原结合部分的其他细胞。哺乳细胞例如为中国仓鼠卵巢(CHO)细胞。
制备抗TIGIT抗体或其抗原结合部分的方法
在一些实施方案中，本公开提供了制备抗TIGIT抗体或其抗原结合部分的方法，所述方法包括：分离编码抗TIGIT抗体或其抗原结合部分的核酸，并插入一个或多个载体，用于在宿主细胞中进一步克隆和/或表达。所述核酸可以采用基因克隆、基因拼接、化学合成等多种本领域所熟知的方法获取。在适合包含编码所述抗体或其抗原结合部分的核酸的宿主细胞的条件下，培养所述的宿主细胞，从所述宿主细胞或宿主细胞培养基中回收所述抗体或其抗原结合部分。
用途
在一些实施方案中，本公开提供了一种在受试者中治疗癌症的方法，其中所述方法包括向受试者施用治疗有效量的所述的抗TIGIT抗体或其抗原结合部分、所述的抗体药物偶联物、所述的融合蛋白或所述的药物组合物。
在一些实施方案中，本公开提供了一种在受试者中治疗免疫相关疾病的方法，其中所述方法包括向受试者施用治疗有效量的所述的抗TIGIT抗体或其抗原结合部分、所述的抗体药物偶联物、所述的融合蛋白或所述的药物组合物。在一些实施方案中，所述免疫相关疾病包括但不限于：癌症、炎性疾病、传染病、或免疫缺陷病。在一些实施方案中，所述免疫相关疾病与T细胞功能障碍性病症有关。在一些实施方案中，所述T细胞功能障碍性病症为T细胞耗竭。
在一些实施方案中，本公开提供了一种在受试者中增强免疫应答的方法，其中所述方法包括向受试者施用治疗有效量的所述的抗TIGIT抗体或其抗原结合部分、所述的抗体药物偶联物、所述的融合蛋白或所述的药物组合物。
在受试者中治疗癌症、在受试者中治疗免疫相关疾病、或在受试者中增强免疫应答的方法中，所述的抗TIGIT抗体或其抗原结合部分、所述的抗体药物偶联物、所述的融合蛋白或所述的药物组合物可以单独施用于有需要的受试者，还可以进一步施用一种或多种另外的治疗剂。
在一些实施方案中，本公开提供了所述的抗TIGIT抗体或其抗原结合部分、所述的抗体药物偶联物、所述的融合蛋白或所述的药物组合物在制备治疗免疫相关疾病的药物中的用途。
在一些实施方案中，本公开提供了所述的抗TIGIT抗体或其抗原结合部分、所述的抗体药物偶联物、所述的融合蛋白或所述的药物组合物在制备增强免疫应答的药物中的用途。
在一些上述实施方案中，所述的抗TIGIT抗体或其抗原结合部分、所述的抗体药物偶联物、所述的融合蛋白或所述的药物组合物与一种或多种另外的治疗剂制备所述的药物。
上述另外的治疗剂例如可以为PD□1轴结合拮抗剂。在一些实施方案中，所述PD□1轴结合拮抗剂在所述的抗TIGIT抗体或其抗原结合部分、所述的抗体药物偶联物、所述的融合蛋白或所述的药物组合物之前或之后施用。在一些实施方案中，所述PD□1轴结合拮抗剂与抗TIGIT抗体或其抗原结合部分同时施用。在一些实施方案中，所述PD□1轴结合拮抗剂为PD-1结合拮抗剂、PD-L1结合拮抗剂或PD-L2结合拮抗剂。在一些实施方案中，所述PD□1轴结合拮抗剂是PD-L1结合拮抗剂。在一些实施方案中，所述PD□1轴结合拮抗剂是PD-1结合拮抗剂。在一些实施方案中，所述PD□1轴结合拮抗剂包括但不限于：阿替利珠单 抗(Atezolizumab)、度伐利尤单抗(Durvalumab)、恩沃利单抗(Envafolimab)、首克注利单抗(Socazolimab)、Avelumab、泰特利单抗、阿得贝利单抗(Adebrelimab)、贝莫苏拜单抗(Benmelstobart)、舒格利单抗(Sugemalimab)、Tagitanlimab、乐普生物的LP002、荣昌生物的RC98、迈博斯生物的MSB2311、宝船生物的BC003、信达生物的IBI318、纳武利尤单抗(Nivolumab)、帕博利珠单抗(Pembrolizumab)、特瑞普利单抗(Toripalimab)、信迪利单抗(Sintilimab)、卡瑞利珠单抗(Camrelizumab)、替雷利珠单抗(Tislelizumab)、派安普利单抗(Penpulimab)、赛帕利单抗(Zimberelimab)、巴替利单抗(Balstilimab)、杰洛利单抗(Geptanolimab)、丽珠医药的LZM-009、西米普利单抗(Cemiplimab)、斯鲁利单抗(Serplulimab)、帕洛利单抗(Prolgolimab)、普特利单抗、诺法利单抗(Nofazinlimab)、Finotonlimab、多塔利单抗(Dostarlimab)、Cetrelimab、齐鲁制药的QL1604、Spartalizumab、瑞弗利单抗(Retifanlimab)、萨善利单抗(Sasanlimab)、恩朗苏拜单抗、洛奈利单抗、三生国建的SSGJ-609A、恒瑞医药的SHR-1901、百奥泰的BAT1308、大有生物的TY101、或尚健生物的SG001。
在一些上述实施方案中，所述癌症为肺癌，小细胞肺癌，非小细胞肺癌，食管癌，胃癌，食管胃结合部癌，肝癌，胆管癌，胰腺癌，结直肠癌，前列腺癌，乳腺癌，子宫内膜癌，卵巢癌，输卵管癌，腹膜癌，宫颈癌，肾癌，膀胱癌，尿路上皮癌，间皮瘤，黑色素瘤，蕈样肉芽肿，梅克尔细胞癌，头颈癌，甲状腺癌，肉瘤，胶质母细胞瘤，胸腺癌，白血病，淋巴瘤，或骨髓瘤。
试剂盒
在一些实施方案中，本公开提供了试剂盒，所述试剂盒包含本文所述的抗TIGIT抗体或其抗原结合部分、本文所述的抗体药物偶联物、本文所述的融合蛋白或本文所述的药物组合物。所述试剂盒还包含装载所述抗TIGIT抗体或其抗原结合部分、抗体药物偶联物、融合蛋白或药物组合物的容器和/或施用所述抗TIGIT抗体或其抗原结合部分、抗体药物偶联物、融合蛋白或药物组合物于有需要的受试者的说明书。
本公开还提供了一些具体的实施方案，但并不限于此：
实施方案1.一种抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体或其抗原结合部分包含：
HCDR1，其包含SEQ ID NO:1、2、3或4所示的氨基酸序列；
HCDR2，其包含SEQ ID NO:5、6、7或8所示的氨基酸序列；
HCDR3，其包含SEQ ID NO:9、10、11、12、13、14或15所示的氨基酸序列；
LCDR1，其包含SEQ ID NO:16、17或18所示的氨基酸序列；
LCDR2，其包含SEQ ID NO:19所示的氨基酸序列；和
LCDR3，其包含SEQ ID NO:20、21、22、23或24所示的氨基酸序列。
实施方案2.根据实施方案1所述的抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体或其抗原结合部分包含：
(a)包含SEQ ID NO:1所示氨基酸序列的HCDR1；
包含SEQ ID NO:5所示氨基酸序列的HCDR2；
包含SEQ ID NO:9所示氨基酸序列的HCDR3；
包含SEQ ID NO:16所示氨基酸序列的LCDR1；
包含SEQ ID NO:19所示氨基酸序列的LCDR2；和
包含SEQ ID NO:20所示氨基酸序列的LCDR3；
(b)包含SEQ ID NO:2所示氨基酸序列的HCDR1；
包含SEQ ID NO:5所示氨基酸序列的HCDR2；
包含SEQ ID NO:10所示氨基酸序列的HCDR3；
包含SEQ ID NO:17所示氨基酸序列的LCDR1；
包含SEQ ID NO:19所示氨基酸序列的LCDR2；和
包含SEQ ID NO:21所示氨基酸序列的LCDR3；
(c)包含SEQ ID NO:3所示氨基酸序列的HCDR1；
包含SEQ ID NO:6所示氨基酸序列的HCDR2；
包含SEQ ID NO:11所示氨基酸序列的HCDR3；
包含SEQ ID NO:16所示氨基酸序列的LCDR1；
包含SEQ ID NO:19所示氨基酸序列的LCDR2；和
包含SEQ ID NO:22所示氨基酸序列的LCDR3；
(d)包含SEQ ID NO:4所示氨基酸序列的HCDR1；
包含SEQ ID NO:7所示氨基酸序列的HCDR2；
包含SEQ ID NO:12所示氨基酸序列的HCDR3；
包含SEQ ID NO:16所示氨基酸序列的LCDR1；
包含SEQ ID NO:19所示氨基酸序列的LCDR2；和
包含SEQ ID NO:23所示氨基酸序列的LCDR3；
(e)包含SEQ ID NO:4所示氨基酸序列的HCDR1；
包含SEQ ID NO:8所示氨基酸序列的HCDR2；
包含SEQ ID NO:13所示氨基酸序列的HCDR3；
包含SEQ ID NO:18所示氨基酸序列的LCDR1；
包含SEQ ID NO:19所示氨基酸序列的LCDR2；和
包含SEQ ID NO:24所示氨基酸序列的LCDR3；
(f)包含SEQ ID NO:1所示氨基酸序列的HCDR1；
包含SEQ ID NO:5所示氨基酸序列的HCDR2；
包含SEQ ID NO:14所示氨基酸序列的HCDR3；
包含SEQ ID NO:16所示氨基酸序列的LCDR1；
包含SEQ ID NO:19所示氨基酸序列的LCDR2；和
包含SEQ ID NO:20所示氨基酸序列的LCDR3；
或者
(g)包含SEQ ID NO:2所示氨基酸序列的HCDR1；
包含SEQ ID NO:5所示氨基酸序列的HCDR2；
包含SEQ ID NO:15所示氨基酸序列的HCDR3；
包含SEQ ID NO:17所示氨基酸序列的LCDR1；
包含SEQ ID NO:19所示氨基酸序列的LCDR2；和
包含SEQ ID NO:21所示氨基酸序列的LCDR3。
实施方案3.一种抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述重链可变区包含SEQ ID NO:25、27、29、31、33、35、37、38、39、40、42、44、46、47、48、50、51、52、54、55、57、59、61或63所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:26、28、30、32、34、36、41、43、45、49、53、56、58、60、62或64所示序列的LCDR1、LCDR2和LCDR3。
实施方案4.根据实施方案3所述的抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体或其抗原结合片段包含重链可变区和轻链可变区，
所述重链可变区包含SEQ ID NO:25所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:26所示序列的LCDR1、LCDR2和LCDR3；
所述重链可变区包含SEQ ID NO:27所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:28所示序列的LCDR1、LCDR2和LCDR3；
所述重链可变区包含SEQ ID NO:29所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:30所示序列的LCDR1、LCDR2和LCDR3；
所述重链可变区包含SEQ ID NO:31所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:32所示序列的LCDR1、LCDR2和LCDR3；
所述重链可变区包含SEQ ID NO:33所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:34所示序列的LCDR1、LCDR2和LCDR3；
所述重链可变区包含SEQ ID NO:55所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:56所示序列的LCDR1、LCDR2和LCDR3；
所述重链可变区包含SEQ ID NO:57所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:58所示序列的LCDR1、LCDR2和LCDR3；
所述重链可变区包含SEQ ID NO:59所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:60所示序列的LCDR1、LCDR2和LCDR3；
所述重链可变区包含SEQ ID NO:61所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:62所示序列的LCDR1、LCDR2和LCDR3；或
所述重链可变区包含SEQ ID NO:63所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:64所示序列的LCDR1、LCDR2和LCDR3。
实施方案5.根据实施方案1-4中任一项所述的抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体或其抗原结合部分包含重链可变区，所述重链可变区包含与SEQ ID NO:25、27、29、31、33、35、37、38、39、40、42、44、46、47、48、50、51、52、54、55、57、59、61或63所示序列具有至少80％同一性的氨基酸序列。
实施方案6.根据实施方案1-5中任一项所述的抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体或其抗原结合部分包含轻链可变区，所述轻链可变区包含与SEQ ID NO:26、28、30、32、34、36、41、43、45、49、53、56、58、60、62或64所示序列具有至少80％同一性的氨基酸序列。
实施方案7.根据实施方案1-6中任一项所述的抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述重链可变区包含与SEQ ID NO:25、27、29、31、33、35、37、38、39、40、42、44、46、47、48、50、51、52、54、55、57、59、61或63所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:26、28、30、32、34、36、41、43、45、49、53、56、58、60、62或64所示序列具有至少80％同一性的氨基酸序列。
实施方案8.根据实施方案7所述的抗TIGIT抗体或其抗原结合部分，其中，
(a)所述的重链可变区包含与SEQ ID NO:25所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:26所示序列具有至少80％同一性的氨基酸序列；
(b)所述的重链可变区包含与SEQ ID NO:27所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:28所示序列具有至少80％同一性的氨基酸序列；
(c)所述的重链可变区包含与SEQ ID NO:29所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:30所示序列具有至少80％同一性的氨基酸序列；
(d)所述的重链可变区包含与SEQ ID NO:31所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:32所示序列具有至少80％同一性的氨基酸序列；
(e)所述的重链可变区包含与SEQ ID NO:33所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:34所示序列具有至少80％同一性的氨基酸序列；
(f)所述的重链可变区包含与SEQ ID NO:35所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:36所示序列具有至少80％同一性的氨基酸序列；
(g)所述的重链可变区包含与SEQ ID NO:37所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:36所示序列具有至少80％同一性的氨基酸序列；
(h)所述的重链可变区包含与SEQ ID NO:38所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:36所示序列具有至少80％同一性的氨基酸序列；
(i)所述的重链可变区包含与SEQ ID NO:39所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:36所示序列具有至少80％同一性的氨基酸序列；
(j)所述的重链可变区包含与SEQ ID NO:40所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:41所示序列具有至少80％同一性的氨基酸序列；
(k)所述的重链可变区包含与SEQ ID NO:42所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:41所示序列具有至少80％同一性的氨基酸序列；
(l)所述的重链可变区包含与SEQ ID NO:40所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:43所示序列具有至少80％同一性的氨基酸序列；
(m)所述的重链可变区包含与SEQ ID NO:42所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:43所示序列具有至少80％同一性的氨基酸序列；
(n)所述的重链可变区包含与SEQ ID NO:44所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:45所示序列具有至少80％同一性的氨基酸序列；
(o)所述的重链可变区包含与SEQ ID NO:46所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:45所示序列具有至少80％同一性的氨基酸序列；
(p)所述的重链可变区包含与SEQ ID NO:47所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:45所示序列具有至少80％同一性的氨基酸序列；
(q)所述的重链可变区包含与SEQ ID NO:48所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:49所示序列具有至少80％同一性的氨基酸序列；
(r)所述的重链可变区包含与SEQ ID NO:50所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:49所示序列具有至少80％同一性的氨基酸序列；
(s)所述的重链可变区包含与SEQ ID NO:51所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:49所示序列具有至少80％同一性的氨基酸序列；
(t)所述的重链可变区包含与SEQ ID NO:52所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:53所示序列具有至少80％同一性的氨基酸序列；
(u)所述的重链可变区包含与SEQ ID NO:54所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:53所示序列具有至少80％同一性的氨基酸序列；
(v)所述的重链可变区包含与SEQ ID NO:55所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:56所示序列具有至少80％同一性的氨基酸序列；
(w)所述的重链可变区包含与SEQ ID NO:57所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:58所示序列具有至少80％同一性的氨基酸序列；
(x)所述的重链可变区包含与SEQ ID NO:59所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:60所示序列具有至少80％同一性的氨基酸序列；
(y)所述的重链可变区包含与SEQ ID NO:61所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:62所示序列具有至少80％同一性的氨基酸序列；或，
(z)所述的重链可变区包含与SEQ ID NO:63所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:64所示序列具有至少80％同一性的氨基酸序列。
实施方案9.一种抗TIGIT抗体或其抗原结合部分，其中，所述抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，其中
(a)所述的重链可变区包含SEQ ID NO:25所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:26所示的氨基酸序列；
(b)所述的重链可变区包含SEQ ID NO:27所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:28所示的氨基酸序列；
(c)所述的重链可变区包含SEQ ID NO:29所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:30所示的氨基酸序列；
(d)所述的重链可变区包含SEQ ID NO:31所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:32所示的氨基酸序列；
(e)所述的重链可变区包含SEQ ID NO:33所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:34所示的氨基酸序列；
(f)所述的重链可变区包含SEQ ID NO:35所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:36所示的氨基酸序列；
(g)所述的重链可变区包含SEQ ID NO:37所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:36所示的氨基酸序列；
(h)所述的重链可变区包含SEQ ID NO:38所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:36所示 的氨基酸序列；
(i)所述的重链可变区包含SEQ ID NO:39所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:36所示的氨基酸序列；
(j)所述的重链可变区包含SEQ ID NO:40所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:41所示的氨基酸序列；
(k)所述的重链可变区包含SEQ ID NO:42所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:41所示的氨基酸序列；
(l)所述的重链可变区包含SEQ ID NO:40所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:43所示的氨基酸序列；
(m)所述的重链可变区包含SEQ ID NO:42所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:43所示的氨基酸序列；
(n)所述的重链可变区包含SEQ ID NO:44所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:45所示的氨基酸序列；
(o)所述的重链可变区包含SEQ ID NO:46所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:45所示的氨基酸序列；
(p)所述的重链可变区包含SEQ ID NO:47所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:45所示的氨基酸序列；
(q)所述的重链可变区包含SEQ ID NO:48所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:49所示的氨基酸序列；
(r)所述的重链可变区包含SEQ ID NO:50所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:49所示的氨基酸序列；
(s)所述的重链可变区包含SEQ ID NO:51所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:49所示的氨基酸序列；
(t)所述的重链可变区包含SEQ ID NO:52所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:53所示的氨基酸序列；
(u)所述的重链可变区包含SEQ ID NO:54所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:53所示的氨基酸序列；
(v)所述的重链可变区包含SEQ ID NO:55所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:56所示的氨基酸序列；
(w)所述的重链可变区包含SEQ ID NO:57所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:58所示的氨基酸序列；
(x)所述的重链可变区包含SEQ ID NO:59所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:60所示的氨基酸序列；
(y)所述的重链可变区包含SEQ ID NO:61所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:62所示的氨基酸序列；或，
(z)所述的重链可变区包含SEQ ID NO:63所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:64所示的氨基酸序列。
实施方案10.根据实施方案1-9中任一项所述的抗TIGIT抗体或其抗原结合部分，其中所述抗原结合部分为Fab片段、Fab'片段、F(ab')2片段、Fd片段、Fv片段、dAb片段、分离的CDR区或scFv。
实施方案11.根据实施方案1-10中任一项所述的抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体或其抗原结合部分是嵌合的、人源化的或全人源的。
实施方案12.根据实施方案1-11中任一项所述的抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体为IgG1、IgG2、IgG3或IgG4同种型。
实施方案13.根据实施方案1-13中任一项所述的抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体或其抗原结合部分具有至少一种选择以下的性质：
(i)以1.38E-09M或更小的KD值与人TIGIT结合；
(ii)阻断TIGIT与CD155结合；
(iii)促进NK细胞杀伤活性；
(iv)促进NK细胞对Treg的ADCC作用；和
(v)促进T细胞功能。
实施方案14.根据实施方案1-13中任一项所述的抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体包含重链和轻链，其中
(a)所述的重链包含与SEQ ID NO:65所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:66所示序列具有至少80％同一性的氨基酸序列；
(b)所述的重链包含与SEQ ID NO:67所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:68所示序列具有至少80％同一性的氨基酸序列；
(c)所述的重链包含与SEQ ID NO:69所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:70所示序列具有至少80％同一性的氨基酸序列；
(d)所述的重链包含与SEQ ID NO:71所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:72所示序列具有至少80％同一性的氨基酸序列；
(e)所述的重链包含与SEQ ID NO:73所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:74所示序列具有至少80％同一性的氨基酸序列；
(f)所述的重链包含与SEQ ID NO:75所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:76所示序列具有至少80％同一性的氨基酸序列；
(g)所述的重链包含与SEQ ID NO:77所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:76所示序列具有至少80％同一性的氨基酸序列；
(h)所述的重链包含与SEQ ID NO:78所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:76所示序列具有至少80％同一性的氨基酸序列；
(i)所述的重链包含与SEQ ID NO:79所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:76所示序列具有至少80％同一性的氨基酸序列；
(j)所述的重链包含与SEQ ID NO:80所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:81所示序列具有至少80％同一性的氨基酸序列；
(k)所述的重链包含与SEQ ID NO:82所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:81所示序列具有至少80％同一性的氨基酸序列；
(l)所述的重链包含与SEQ ID NO:80所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:83所示序列具有至少80％同一性的氨基酸序列；
(m)所述的重链包含与SEQ ID NO:82所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:83所示序列具有至少80％同一性的氨基酸序列；
(n)所述的重链包含与SEQ ID NO:84所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:85所示序列具有至少80％同一性的氨基酸序列；
(o)所述的重链包含与SEQ ID NO:86所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:85所示序列具有至少80％同一性的氨基酸序列；
(p)所述的重链包含与SEQ ID NO:87所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:85所示序列具有至少80％同一性的氨基酸序列；
(q)所述的重链包含与SEQ ID NO:88所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:89所示序列具有至少80％同一性的氨基酸序列；
(r)所述的重链包含与SEQ ID NO:90所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:89所示序列具有至少80％同一性的氨基酸序列；
(s)所述的重链包含与SEQ ID NO:91所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:89所示序列具有至少80％同一性的氨基酸序列；
(t)所述的重链包含与SEQ ID NO:92所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:93所示序列具有至少80％同一性的氨基酸序列；或者
(u)所述的重链包含与SEQ ID NO:94所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:93所示序列具有至少80％同一性的氨基酸序列。
实施方案15.一种抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体包含重链和轻链，其中
(a)所述的重链包含SEQ ID NO:65所示的氨基酸序列，所述轻链包含SEQ ID NO:66所示的氨基酸序列；
(b)所述的重链包含SEQ ID NO:67所示的氨基酸序列，所述轻链包含SEQ ID NO:68所示的氨基酸序列；
(c)所述的重链包含SEQ ID NO:69所示的氨基酸序列，所述轻链包含SEQ ID NO:70所示的氨基酸序列；
(d)所述的重链包含SEQ ID NO:71所示的氨基酸序列，所述轻链包含SEQ ID NO:72所示的氨基酸序列；
(e)所述的重链包含SEQ ID NO:73所示的氨基酸序列，所述轻链包含SEQ ID NO:74所示的氨基酸序列；
(f)所述的重链包含SEQ ID NO:75所示的氨基酸序列，所述轻链包含SEQ ID NO:76所示的氨基酸序列；
(g)所述的重链包含SEQ ID NO:77所示的氨基酸序列，所述轻链包含SEQ ID NO:76所示的氨基酸序列；
(h)所述的重链包含SEQ ID NO:78所示的氨基酸序列，所述轻链包含SEQ ID NO:76所示的氨基酸序列；
(i)所述的重链包含SEQ ID NO:79所示的氨基酸序列，所述轻链包含SEQ ID NO:76所示的氨基酸序列；
(j)所述的重链包含SEQ ID NO:80所示的氨基酸序列，所述轻链包含SEQ ID NO:81所示的氨基酸序列；
(k)所述的重链包含SEQ ID NO:82所示的氨基酸序列，所述轻链包含SEQ ID NO:81所示的氨基酸序列；
(l)所述的重链包含SEQ ID NO:80所示的氨基酸序列，所述轻链包含SEQ ID NO:83所示的氨基酸序列；
(m)所述的重链包含SEQ ID NO:82所示的氨基酸序列，所述轻链包含SEQ ID NO:83所示的氨基酸序列；
(n)所述的重链包含SEQ ID NO:84所示的氨基酸序列，所述轻链包含SEQ ID NO:85所示的氨基酸序列；
(o)所述的重链包含SEQ ID NO:86所示的氨基酸序列，所述轻链包含SEQ ID NO:85所示的氨基酸序列；
(p)所述的重链包含SEQ ID NO:87所示的氨基酸序列，所述轻链包含SEQ ID NO:85所示的氨基酸序列；
(q)所述的重链包含SEQ ID NO:88所示的氨基酸序列，所述轻链包含SEQ ID NO:89所示的氨基酸序列；
(r)所述的重链包含SEQ ID NO:90所示的氨基酸序列，所述轻链包含SEQ ID NO:89所示的氨基酸序列；
(s)所述的重链包含SEQ ID NO:91所示的氨基酸序列，所述轻链包含SEQ ID NO:89所示的氨基酸序列；
(t)所述的重链包含SEQ ID NO:92所示的氨基酸序列，所述轻链包含SEQ ID NO:93所示的氨基酸序列；或者
(u)所述的重链包含SEQ ID NO:94所示的氨基酸序列，所述轻链包含SEQ ID NO:93所示的氨基酸序列。
实施方案16.根据实施方案1-15中任一项所述的抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体或其抗原结合部分为单特异性抗体或多特异性抗体。
实施方案17.一种分离的核酸，其编码根据实施方案1-16中任一项所述的抗TIGIT抗体或其抗原结合部分。
实施方案18.一种载体，其包含根据实施方案17所述的核酸。
实施方案19.一种宿主细胞，其包含根据实施方案17所述的核酸或实施方案18所述的载体。
实施方案20.一种制备根据实施方案1-16中任一项所述的抗TIGIT抗体或其抗原结合部分的方法，包括：培养实施方案19所述的宿主细胞，从所述宿主细胞或宿主细胞培养基中回收所述抗TIGIT抗体或其抗原结合部分。
实施方案21.一种抗体药物偶联物，其包含实施方案1-16中任一项所述的抗TIGIT抗体或其抗原结合部分。
实施方案22.一种融合蛋白，其包含实施方案1-16中任一项所述的抗TIGIT抗体或其抗原结合部分。
实施方案23.一种药物组合物，其包含根据实施方案1-16中任一项所述的抗TIGIT抗体或其抗原结合部分、实施方案21所述的抗体药物偶联物或实施方案22所述的融合蛋白。
实施方案24.一种在受试者中治疗癌症的方法，其中所述方法包括向受试者施用治疗有效量的根据实施方案1-16中任一项所述的抗TIGIT抗体或其抗原结合部分、实施方案21所述的抗体药物偶联物、实施方案22所述的融合蛋白或实施方案23所述的药物组合物。
实施方案25.根据实施方案24所述的方法，其中所述癌症为肺癌，小细胞肺癌，非小细胞肺癌，食管 癌，胃癌，食管胃结合部癌，肝癌，胆管癌，胰腺癌，结直肠癌，前列腺癌，乳腺癌，子宫内膜癌，卵巢癌，输卵管癌，腹膜癌，宫颈癌，肾癌，膀胱癌，尿路上皮癌，间皮瘤，黑色素瘤，蕈样肉芽肿，梅克尔细胞癌，头颈癌，甲状腺癌，肉瘤，胶质母细胞瘤，胸腺癌，白血病，淋巴瘤，或骨髓瘤。
实施方案26.一种在受试者中治疗免疫相关疾病的方法，其中所述方法包括向受试者施用治疗有效量的根据实施方案1-16中任一项所述的抗TIGIT抗体或其抗原结合部分、实施方案21所述的抗体药物偶联物、实施方案22所述的融合蛋白或实施方案23所述的药物组合物。
实施方案27.一种在受试者中增强免疫应答的方法，其中所述方法包括向受试者施用治疗有效量的根据实施方案1-16中任一项所述的抗TIGIT抗体或其抗原结合部分、实施方案21所述的抗体药物偶联物、实施方案22所述的融合蛋白或实施方案23所述的药物组合物。
实施方案28.根据实施方案24-27中任一项所述的方法，其中所述治疗包括向受试者施用第二治疗剂。
实施方案29.根据实施方案28所述的方法，其中所述第二治疗剂为PD-1轴结合拮抗剂。
实施方案30.一种试剂盒，其包含根据实施方案1-16中任一项所述的抗TIGIT抗体或其抗原结合部分、实施方案21所述的抗体药物偶联物、实施方案22所述的融合蛋白或实施方案23所述的药物组合物。
实施例
尽管为了清楚理解的目的，已经通过举例说明和实施例相当详细地描述了前述本公开，但是根据本公开的教义，本领域的普通技术人员将显而易见的是，可另外对本公开进行某些改变和修改而不背离所附权利要求的精神和范围。以下实施例仅以说明方式提供，而并不起限制作用。本领域的技术人员将容易地识别多种非关键性参数，所述参数可发生改变或修改以产生基本上类似的结果。
实施例中采用的所有试剂，除非另有说明，否则均可以通过商业途径购买获得。
本公开具体实施例中采用的阳性对照tiragolumab，其可变区氨基酸序列与中国专利CN108290946A中的抗体“4.1D3.Q1E”的可变区氨基酸序列(VH为CN108290946A SEQ ID NO:34所示的序列，VL为CN108290946A SEQ ID NO:36所示的序列)相同。将“4.1D3.Q1E”的VL区和VH区基因合成部分分别亚克隆到带有人κ轻链恒定区和人IgG1重链恒定区的pcDNA3.1表达载体(Invitrogen，目录号：V-79020)中，将20μg的重链表达质粒和20μg的轻链表达质粒转染至ExpiCHO细胞(100mL，在6.3×106/mL细胞密度下)，细胞培养10-12天后，用蛋白A柱(GE healthcare)纯化上清液中的抗体。
SEQ ID NO：135示出了tiragolumab的重链氨基酸序列如下：
SEQ ID NO：136示出了tiragolumab的轻链氨基酸序列如下：
实施例1抗TIGIT单克隆抗体的制备
杂交瘤单克隆细胞株筛选：
将编码人TIGIT蛋白(Uniprot：Q495A1)细胞外结构域的开放阅读框DNA序列与人IgG1 Fc标签DNA序列融合，将合成的DNA序列亚克隆到表达载体pcDNA3.1(Invitrogen，目录号：V-79020)中，转染表达载体至Freestyle293细胞中进行瞬时表达，用蛋白A柱(GE healthcare)纯化获得融合蛋白TIGIT-Fc Tag(SEQ ID NO:137)：
为了产生针对人TIGIT的抗体，使用等体积的完全(首次免疫)/不完全(加强免疫)弗氏佐剂乳化的重组TIGIT-Fc Tag蛋白(100μg/小鼠)每2周皮下免疫BALB/c、A/J和SJL小鼠，免疫4次持续6周。细胞融合前3天，通过静脉注射不含佐剂的TIGIT-Fc Tag蛋白对小鼠进行加强免疫。使用电融合仪(BTX，目录号：ECM2001)将来自免疫小鼠的脾细胞(约1×108)与SP2/0-Ag14骨髓瘤细胞(约1×107-3×107)融合。融合结束后，用500mL含有10％胎牛血清的1640培养基稀释融合后的细胞，然后以0.1mL/孔分配到96孔板中，在37℃、5％ CO2的培养箱中孵育培养。第2天，每孔添加另外的0.1mL含有10％血清和2％次黄嘌呤(H)、氨基蝶呤(A)和胸腺嘧啶核苷(T)补充剂(HAT补充剂，lifetechnology，目录号：21060017)的1640培养基继续培养。
通过基于蛋白、细胞的结合和配体竞争测定法筛选阳性克隆。将处于对数生长中的阳性杂交瘤细胞进行计数，吸取100-200个细胞的量稀释至20mL完全1640培养基中，充分混匀后，按200μL/孔接种至1块96孔板中，在37℃、5％ CO2培养箱中保持约8天。收取每个可见的单克隆细胞孔的上清进行再次筛选，以获得阳性杂交瘤单克隆细胞株。
嵌合抗TIGIT抗体的构建和表达：
从阳性杂交瘤克隆中扩增、测序得到五个鼠源单克隆抗体的重链可变区(VH)序列和轻链可变区(VL)序列，序列信息如下：
将小鼠抗体的VL区基因合成部分连接到人κ轻链恒定区构建嵌合轻链，将小鼠抗体的VH区基因合成部分连接到人IgG1重链恒定区构建嵌合重链。将包含嵌合轻链DNA的表达质粒和包含嵌合重链DNA的表达质粒转染至ExpiCHO细胞(100mL，在6.3×106/mL细胞密度下)，细胞培养10-12天后，用蛋白A柱(GE healthcare)纯化上清液中的嵌合抗体。得到5个嵌合抗体，嵌合抗体的可变区序列同鼠抗，其嵌合重链和嵌合轻链的全长氨基酸序列如下：
抗体人源化设计：
使用CDR移植方法进行抗体人源化(参见，例如，美国专利号5,225,539)。
人源化Ab1、Ab2、Ab19、Ab23和Ab30抗体的序列及其编码核酸如下：

人源化Ab1、Ab2、Ab19、Ab23和Ab30抗体的构建和表达：
利用pcDNA3.1表达载体，分别构建含人源化抗体重链和轻链的表达质粒，用20μg重链表达质粒和20μg轻链表达质粒转染至ExpiCHO细胞(100mL，在6.3×106/mL细胞密度下)并且将其在ExpiCHO培养基(Gibco，目录号：A29100-01)培养10-12天。收集细胞培养上清，然后用蛋白A柱(GE healthcare)纯化上清液中的人源化抗体。
实施例2抗TIGIT抗体与人TIGIT的亲和力分析
用偶联有抗人IgG抗体(Human antibody capture kit，GE，目录号：29234600)的CM5生物传感芯片(GE，目录号：29149603)亲和捕获抗TIGIT抗体，然后于芯片表面流经人TIGIT-His蛋白(acrobiosystems，目录号：TIT-H52H5)，用Biacore 8K仪器实时检测反应信号获得结合和解离曲线。在每个实验循环解离完成后，用pH 1.5的再生缓冲液Glycine-HCl将芯片洗净再生。通过Biacore 8K Control Software 3.0实时采集结合解离曲线并使用Biacore Insight Evaluation Software 3.0分析数据，计算结合速率常数ka、解离速率常数kd、平衡解离常数KD值。结果如表1所示，抗TIGIT嵌合及人源化抗体都和人TIGIT蛋白有较高的亲和力。
表1抗TIGIT嵌合及人源化抗体与人TIGIT的结合亲和力

实施例3抗TIGIT人源化抗体与不同种属TIGIT的亲和力分析
用偶联有蛋白A(Sino Biological，目录号：10600-P07E)的CM5生物传感芯片亲和捕获抗TIGIT抗体，然后于芯片表面流经抗原食蟹猴TIGIT-His(acrobiosystems，目录号：TIT-C5223)、犬TIGIT-His(acrobiosystems，目录号：TIT-C52H7)或小鼠TIGIT-His(acrobiosystems，目录号：TIT-M52E6)，用Biacore 8K仪器实时检测反应信号获得结合和解离曲线。在每个实验循环解离完成后，用pH 2.0的甘氨酸-盐酸(Glycine-HCl)再生缓冲液将芯片洗净再生。
氨基偶联兔TIGIT-FC(acrobiosystems，目录号：TIT-R5259)或大鼠TIGIT-FC(Sino Biological，目录号：8A6318-R02H)至CM5生物传感芯片，然后于芯片表面流经抗TIGIT抗体，用Biacore 8K仪器实时检测反应信号获得结合和解离曲线。在每个实验循环解离完成后，用pH 1.5的甘氨酸-盐酸(Glycine-HCl)再生缓冲液将芯片洗净再生。
通过Biacore 8K Control Software 3.0实时采集结合解离曲线并使用Biacore Insight Evaluation Software3.0分析数据，计算结合速率常数ka、解离速率常数kd、平衡解离常数KD值。结果如表2所示，hz-Ab1-1.4、hz-Ab23-1.3与食蟹猴TIGIT和大鼠TIGIT有较好的结合活性，均不与犬TIGIT、小鼠TIGIT结合。
表2抗TIGIT人源化抗体与不同种属TIGIT的结合亲和力

注：NA表示未达检测限
实施例4抗TIGIT抗体基于细胞的结合分析
合成人TIGIT和食蟹猴TIGIT全长开放阅读框DNA序列，然后分别亚克隆到表达载体pcDNA3.1(Invitrogen，目录号：V-79020)中，用Lipofectamine 3000(Gibco，目录号：L3000001)将表达载体转染至CHO-K1中，经遗传霉素筛选2-3周后，通过有限稀释法分离得到单克隆细胞，流式细胞术(FACS)检测细胞表面的TIGIT表达量，筛选出高表达TIGIT的CHO-K1细胞(流式检测TIGIT表达量，其MFI与背景(S/B)比值大于100)。
将高表达人和食蟹猴TIGIT的CHO-K1细胞分别用FACS缓冲液(Miltenyi Biotec，目录号：130-091-221)制备成细胞密度0.5-1×106/mL的细胞悬液，100μL/孔加入96孔板中(Corning，目录号：3894)，然后每孔加入100μL用FACS缓冲液稀释的不同浓度的抗TIGIT抗体或人IgG1对照抗体，放于4℃冰箱中避光孵育1小时。将细胞用FACS缓冲液洗涤3次后，加入100μL每孔1:500稀释的工作浓度的PE标记的山羊抗人IgG(H+L)(Bio-legend，目录号：409304)，放于4℃冰箱中避光孵育40分钟。将细胞用FACS缓冲液洗涤3次后，在Sartorius iQue3流式细胞仪上检测平均荧光强度(MFI)。计算获得抗TIGIT抗体和人或食蟹猴TIGIT高表达细胞系结合的EC50值。结果如表3所示，抗TIGIT嵌合及人源化抗体和人或食蟹猴TIGIT蛋白具有良好的结 合活性。
表3抗TIGIT嵌合及人源化抗体与人或食蟹猴TIGIT基于细胞的结合EC50(nM)
实施例5抗TIGIT抗体基于细胞的阻断分析
合成人CD155和食蟹猴CD155全长开放阅读框DNA序列，然后分别亚克隆到表达载体pcDNA3.1(Invitrogen，目录号：V-79020)中，用Lipofectamine 3000(Gibco，目录号：L3000001)将表达载体转染至CHO-K1中，经遗传霉素筛选2-3周后，通过有限稀释法分离得到单克隆细胞，流式细胞术(FACS)检测细胞表面的CD155表达量，筛选出高表达CD155的CHO-K1细胞(流式检测TIGIT表达量，其MFI与背景(S/B)比值大于100)。
将高表达人和食蟹猴CD155的CHO-K1细胞分别用FACS缓冲液(Miltenyi Biotec，目录号：130-091-221)制备成细胞密度0.5-1×106/mL的细胞悬液，100μL/孔加入96孔板中(Corning，目录号：3894)，然后每孔加入100μL FACS缓冲液稀释的不同浓度的抗TIGIT抗体和100ng/ml人TIGIT-Fc Tag或食蟹猴TIGIT-hFc(acrobiosystems，目录号：TIT-C5254)的混合物，4℃反应30分钟。将细胞用FACS缓冲液洗涤3次后，加入100μL每孔1:500稀释的工作浓度的PE标记的山羊抗人IgG(H+L)(Bio-legend，目录号：409304)，放于4℃冰箱中避光孵育40分钟。将细胞用FACS缓冲液洗涤3次后，在Sartorius iQue3流式细胞仪上检测平均荧光强度(MFI)。分析计算获得抗TIGIT抗体阻断人或食蟹猴TIGIT与人或食蟹猴CD155高表达细胞系结合的IC50值。结果如表4所示，抗TIGIT嵌合及人源化抗体能够有效阻断人或食蟹猴TIGIT蛋白与人或食蟹猴CD155的结合。
表4抗TIGIT嵌合及人源化抗体基于细胞阻断TIGIT与CD155结合的IC50(nM)

实施例6抗TIGIT抗体促进NK细胞杀伤活性的分析
复苏PBMC(外周血单个核细胞，澳能生物，目录号：FPB004F-C)，使用NK分选试剂盒(美天旎，目录号：130-092-657)分选出NK细胞，用基础培养基(RPMI 1640+10％ FBS+青链霉素)按照1×106/mL的密度重悬NK细胞，并在培养基中加入终浓度为200IU/mL的细胞因子human IL-2(R&D，目录号：IL-202)，37℃培养箱过夜激活细胞。使用细胞标记试剂CellTraceTMViolet(Invitrogen，目录号：C34557A)将靶细胞人结肠癌细胞Widr(南京科佰生物科技有限公司)标记染色，随后将激活的NK细胞和标记后的Widr细胞分别重悬，向低吸附96孔板(Corning，货号：7007)每孔加入50μL抗TIGIT抗体(起始浓度280nM，10倍梯度稀释，共7个浓度)、50μL Widr细胞及100μL NK细胞，混合均匀，使每孔NK细胞数量为20000个，Widr细胞数量为20000个。设定只含Widr靶细胞孔作为本底对照：每孔总体积为200μL，无检测抗体，无NK细胞，使Widr数量为20000个。37℃培养箱孵育4小时后，每孔加入1μL碘化丙啶染液(Invitrogen，货号：P3566)混合均匀，染色5分钟后用流式细胞仪检测。分析CellTraceTMViolet阳性细胞中碘化丙啶阳性细胞的占比(PI％)，按照下列公式计算细胞裂解率：
细胞裂解率＝(PI％实验孔-PI％本底对照)/(100％-PI％本底对照)*100％
结果如图1中A-D所示，抗TIGIT嵌合抗体及人源化抗体hzAb1-1.4，hzAb2-2.2，hzAb23-1.3和hzAb30-1.2均能有效促进NK细胞对靶细胞Widr的杀伤，且杀伤促进作用优于tiragolumab或与其相当。
实施例7抗TIGIT抗体促进NK细胞对Treg ADCC的分析
使用Treg isolation kit(Stemcell，目录号：18063)分选出PBMC中的Treg，通过Dynabeads human Treg expander(Gibco，货号：11129D)扩增分选出的Treg。使用细胞标记试剂CellTraceTMViolet(Invitrogen，目录号：C34557A)将靶细胞Treg标记染色。随后将激活的NK细胞和标记后的Treg细胞分别重悬，向96孔板每孔加入50μL抗TIGIT抗体(起始浓度为280nM，10倍梯度稀释，共7个浓度)，50μL Treg细胞及100μLNK细胞，混合均匀，使每孔NK细胞数量为25000个，Treg细胞数量为25000个。设定只含Treg靶细胞孔作为本底对照：每孔总体积为200μL，无检测抗体，无NK细胞，使Treg数量为25000个。铺完板后置于37℃培养箱孵育4小时。孵育结束后每孔加入1μL碘化丙啶染液(Invitrogen，货号：P3566)混合均匀，染色5分钟后用流式细胞仪检测。分析CellTraceTMViolet阳性细胞中碘化丙啶阳性细胞的占比(PI％)，按照下列公式计算细胞裂解率：
细胞裂解率＝(PI％实验孔-PI％本底对照)/(100％-PI％本底对照)*100％
结果如图2中A-F所示，抗TIGIT嵌合抗体及人源化抗体hzAb1-1.4，hzAb2-2.2，hzAb23-1.3和hzAb30-1.2 均能有效促进NK细胞对Treg的ADCC作用，且促进作用优于tiragolumab。
实施例8抗TIGIT抗体促进CD8+T细胞功能的分析
选取HLA-A*02:01基因型并且有CMV(巨细胞病毒)既往感染史的PBMC(妙顺生物，目录号：PB100C-W)，用含有1μg/mL CMV pp65(495-503)短肽(Anaspec，目录号：AS-28328)、20IU/mL人IL-2(R&D，目录号：IL-202)、10ng/mL人IL-7(Peprotech，货号：200-07)的完全培养基(RPMI 1640+5％AB serum+1％ P/S+50μM 2-β巯基乙醇)将细胞重悬至2×106个/mL，以5mL/孔接种于6孔板中，37℃、5％ CO2培养箱中培养6天。第6天，收集细胞，去除培养基，将细胞重悬于含有100IU/mL人IL-2的完全培养基中，体积为原先的2倍，并以5mL/孔接种于新的6孔板中，培养2天。第8天换液继续培养。第11天，收集所有细胞，使用CD8+T细胞分选试剂盒(美天旎，货号：130-045-201)分离出CD8+T细胞作为效应细胞，用AIM-V(Gibco，货号：31035-025)重悬并调整细胞密度至1×106个/mL。以人结肠癌细胞Colo205(上海细胞所)作为靶细胞，经胰酶(Gibco，目录号：12605010)消化，重悬于含有200ng/mL pp65的AIM-V并调整细胞密度至1×106个/mL，37℃孵育3小时，离心弃上清，将细胞重悬至5×105个/mL。抗TIGIT抗体及对照抗体用AIM-V稀释至280nM(和/或更低浓度)。在低吸附96孔板(Corning，货号：7007)中依次加入50μL抗体，50μL CD8+T细胞，100μL pp65处理过的Colo205，混匀，37℃、5％ CO2孵育过夜。体系中抗体终浓度为70nM(最高浓度)，CD8+T细胞为50000个/孔，Colo205为50000个/孔。孵育结束后检测上清中hIFNγ的水平。
结果如图3中A-B所示，抗TIGIT嵌合抗体及人源化抗体hzAb1-1.4，hzAb23-1.3均能有效促进CD8+T细胞释放促炎因子hIFNγ，人源化抗体hzAb1-1.4和hzAb23-1.3对CD8+T细胞的促进功能优于tiragolumab。

Claims (30)

  1. 一种抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体或其抗原结合部分包含：
    HCDR1，其包含SEQ ID NO:1、2、3或4所示的氨基酸序列；
    HCDR2，其包含SEQ ID NO:5、6、7或8所示的氨基酸序列；
    HCDR3，其包含SEQ ID NO:9、10、11、12、13、14或15所示的氨基酸序列；
    LCDR1，其包含SEQ ID NO:16、17或18所示的氨基酸序列；
    LCDR2，其包含SEQ ID NO:19所示的氨基酸序列；和
    LCDR3，其包含SEQ ID NO:20、21、22、23或24所示的氨基酸序列。
  2. 根据权利要求1所述的抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体或其抗原结合部分包含：
    (a)包含SEQ ID NO:1所示氨基酸序列的HCDR1；
    包含SEQ ID NO:5所示氨基酸序列的HCDR2；
    包含SEQ ID NO:9所示氨基酸序列的HCDR3；
    包含SEQ ID NO:16所示氨基酸序列的LCDR1；
    包含SEQ ID NO:19所示氨基酸序列的LCDR2；和
    包含SEQ ID NO:20所示氨基酸序列的LCDR3；
    (b)包含SEQ ID NO:2所示氨基酸序列的HCDR1；
    包含SEQ ID NO:5所示氨基酸序列的HCDR2；
    包含SEQ ID NO:10所示氨基酸序列的HCDR3；
    包含SEQ ID NO:17所示氨基酸序列的LCDR1；
    包含SEQ ID NO:19所示氨基酸序列的LCDR2；和
    包含SEQ ID NO:21所示氨基酸序列的LCDR3；
    (c)包含SEQ ID NO:3所示氨基酸序列的HCDR1；
    包含SEQ ID NO:6所示氨基酸序列的HCDR2；
    包含SEQ ID NO:11所示氨基酸序列的HCDR3；
    包含SEQ ID NO:16所示氨基酸序列的LCDR1；
    包含SEQ ID NO:19所示氨基酸序列的LCDR2；和
    包含SEQ ID NO:22所示氨基酸序列的LCDR3；
    (d)包含SEQ ID NO:4所示氨基酸序列的HCDR1；
    包含SEQ ID NO:7所示氨基酸序列的HCDR2；
    包含SEQ ID NO:12所示氨基酸序列的HCDR3；
    包含SEQ ID NO:16所示氨基酸序列的LCDR1；
    包含SEQ ID NO:19所示氨基酸序列的LCDR2；和
    包含SEQ ID NO:23所示氨基酸序列的LCDR3；
    (e)包含SEQ ID NO:4所示氨基酸序列的HCDR1；
    包含SEQ ID NO:8所示氨基酸序列的HCDR2；
    包含SEQ ID NO:13所示氨基酸序列的HCDR3；
    包含SEQ ID NO:18所示氨基酸序列的LCDR1；
    包含SEQ ID NO:19所示氨基酸序列的LCDR2；和
    包含SEQ ID NO:24所示氨基酸序列的LCDR3；
    (f)包含SEQ ID NO:1所示氨基酸序列的HCDR1；
    包含SEQ ID NO:5所示氨基酸序列的HCDR2；
    包含SEQ ID NO:14所示氨基酸序列的HCDR3；
    包含SEQ ID NO:16所示氨基酸序列的LCDR1；
    包含SEQ ID NO:19所示氨基酸序列的LCDR2；和
    包含SEQ ID NO:20所示氨基酸序列的LCDR3；
    或者
    (g)包含SEQ ID NO:2所示氨基酸序列的HCDR1；
    包含SEQ ID NO:5所示氨基酸序列的HCDR2；
    包含SEQ ID NO:15所示氨基酸序列的HCDR3；
    包含SEQ ID NO:17所示氨基酸序列的LCDR1；
    包含SEQ ID NO:19所示氨基酸序列的LCDR2；和
    包含SEQ ID NO:21所示氨基酸序列的LCDR3。
  3. 一种抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述重链可变区包含SEQ ID NO:25、27、29、31、33、35、37、38、39、40、42、44、46、47、48、50、51、52、54、55、57、59、61或63所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:26、28、30、32、34、36、41、43、45、49、53、56、58、60、62或64所示序列的LCDR1、LCDR2和LCDR3。
  4. 根据权利要求3所述的抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体或其抗原结合片段包含重链可变区和轻链可变区，
    所述重链可变区包含SEQ ID NO:25所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:26所示序列的LCDR1、LCDR2和LCDR3；
    所述重链可变区包含SEQ ID NO:27所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:28所示序列的LCDR1、LCDR2和LCDR3；
    所述重链可变区包含SEQ ID NO:29所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:30所示序列的LCDR1、LCDR2和LCDR3；
    所述重链可变区包含SEQ ID NO:31所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:32所示序列的LCDR1、LCDR2和LCDR3；
    所述重链可变区包含SEQ ID NO:33所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:34所示序列的LCDR1、LCDR2和LCDR3；
    所述重链可变区包含SEQ ID NO:55所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:56所示序列的LCDR1、LCDR2和LCDR3；
    所述重链可变区包含SEQ ID NO:57所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:58所示序列的LCDR1、LCDR2和LCDR3；
    所述重链可变区包含SEQ ID NO:59所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:60所示序列的LCDR1、LCDR2和LCDR3；
    所述重链可变区包含SEQ ID NO:61所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:62所示序列的LCDR1、LCDR2和LCDR3；或
    所述重链可变区包含SEQ ID NO:63所示序列的HCDR1、HCDR2和HCDR3，所述轻链可变区包含SEQ ID NO:64所示序列的LCDR1、LCDR2和LCDR3。
  5. 根据权利要求1-4中任一项所述的抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体或其抗原结合部分包含重链可变区，所述重链可变区包含与SEQ ID NO:25、27、29、31、33、35、37、38、39、40、42、44、46、47、48、50、51、52、54、55、57、59、61或63所示序列具有至少80％同一性的氨基酸序列。
  6. 根据权利要求1-5中任一项所述的抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体或其抗原结合部分包含轻链可变区，所述轻链可变区包含与SEQ ID NO:26、28、30、32、34、36、41、43、45、49、53、56、58、60、62或64所示序列具有至少80％同一性的氨基酸序列。
  7. 根据权利要求1-6中任一项所述的抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，所述重链可变区包含与SEQ ID NO:25、27、29、31、33、35、 37、38、39、40、42、44、46、47、48、50、51、52、54、55、57、59、61或63所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:26、28、30、32、34、36、41、43、45、49、53、56、58、60、62或64所示序列具有至少80％同一性的氨基酸序列。
  8. 根据权利要求7所述的抗TIGIT抗体或其抗原结合部分，其中，
    (a)所述的重链可变区包含与SEQ ID NO:25所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:26所示序列具有至少80％同一性的氨基酸序列；
    (b)所述的重链可变区包含与SEQ ID NO:27所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:28所示序列具有至少80％同一性的氨基酸序列；
    (c)所述的重链可变区包含与SEQ ID NO:29所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:30所示序列具有至少80％同一性的氨基酸序列；
    (d)所述的重链可变区包含与SEQ ID NO:31所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:32所示序列具有至少80％同一性的氨基酸序列；
    (e)所述的重链可变区包含与SEQ ID NO:33所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:34所示序列具有至少80％同一性的氨基酸序列；
    (f)所述的重链可变区包含与SEQ ID NO:35所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:36所示序列具有至少80％同一性的氨基酸序列；
    (g)所述的重链可变区包含与SEQ ID NO:37所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:36所示序列具有至少80％同一性的氨基酸序列；
    (h)所述的重链可变区包含与SEQ ID NO:38所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:36所示序列具有至少80％同一性的氨基酸序列；
    (i)所述的重链可变区包含与SEQ ID NO:39所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:36所示序列具有至少80％同一性的氨基酸序列；
    (j)所述的重链可变区包含与SEQ ID NO:40所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:41所示序列具有至少80％同一性的氨基酸序列；
    (k)所述的重链可变区包含与SEQ ID NO:42所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:41所示序列具有至少80％同一性的氨基酸序列；
    (l)所述的重链可变区包含与SEQ ID NO:40所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:43所示序列具有至少80％同一性的氨基酸序列；
    (m)所述的重链可变区包含与SEQ ID NO:42所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:43所示序列具有至少80％同一性的氨基酸序列；
    (n)所述的重链可变区包含与SEQ ID NO:44所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:45所示序列具有至少80％同一性的氨基酸序列；
    (o)所述的重链可变区包含与SEQ ID NO:46所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:45所示序列具有至少80％同一性的氨基酸序列；
    (p)所述的重链可变区包含与SEQ ID NO:47所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:45所示序列具有至少80％同一性的氨基酸序列；
    (q)所述的重链可变区包含与SEQ ID NO:48所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:49所示序列具有至少80％同一性的氨基酸序列；
    (r)所述的重链可变区包含与SEQ ID NO:50所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:49所示序列具有至少80％同一性的氨基酸序列；
    (s)所述的重链可变区包含与SEQ ID NO:51所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:49所示序列具有至少80％同一性的氨基酸序列；
    (t)所述的重链可变区包含与SEQ ID NO:52所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:53所示序列具有至少80％同一性的氨基酸序列；
    (u)所述的重链可变区包含与SEQ ID NO:54所示序列具有至少80％同一性的氨基酸序列，所述轻链可 变区包含与SEQ ID NO:53所示序列具有至少80％同一性的氨基酸序列；
    (v)所述的重链可变区包含与SEQ ID NO:55所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:56所示序列具有至少80％同一性的氨基酸序列；
    (w)所述的重链可变区包含与SEQ ID NO:57所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:58所示序列具有至少80％同一性的氨基酸序列；
    (x)所述的重链可变区包含与SEQ ID NO:59所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:60所示序列具有至少80％同一性的氨基酸序列；
    (y)所述的重链可变区包含与SEQ ID NO:61所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:62所示序列具有至少80％同一性的氨基酸序列；或，
    (z)所述的重链可变区包含与SEQ ID NO:63所示序列具有至少80％同一性的氨基酸序列，所述轻链可变区包含与SEQ ID NO:64所示序列具有至少80％同一性的氨基酸序列。
  9. 一种抗TIGIT抗体或其抗原结合部分，其中，所述抗TIGIT抗体或其抗原结合部分包含重链可变区和轻链可变区，其中
    (a)所述的重链可变区包含SEQ ID NO:25所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:26所示的氨基酸序列；
    (b)所述的重链可变区包含SEQ ID NO:27所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:28所示的氨基酸序列；
    (c)所述的重链可变区包含SEQ ID NO:29所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:30所示的氨基酸序列；
    (d)所述的重链可变区包含SEQ ID NO:31所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:32所示的氨基酸序列；
    (e)所述的重链可变区包含SEQ ID NO:33所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:34所示的氨基酸序列；
    (f)所述的重链可变区包含SEQ ID NO:35所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:36所示的氨基酸序列；
    (g)所述的重链可变区包含SEQ ID NO:37所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:36所示的氨基酸序列；
    (h)所述的重链可变区包含SEQ ID NO:38所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:36所示的氨基酸序列；
    (i)所述的重链可变区包含SEQ ID NO:39所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:36所示的氨基酸序列；
    (j)所述的重链可变区包含SEQ ID NO:40所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:41所示的氨基酸序列；
    (k)所述的重链可变区包含SEQ ID NO:42所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:41所示的氨基酸序列；
    (l)所述的重链可变区包含SEQ ID NO:40所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:43所示的氨基酸序列；
    (m)所述的重链可变区包含SEQ ID NO:42所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:43所示的氨基酸序列；
    (n)所述的重链可变区包含SEQ ID NO:44所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:45所示的氨基酸序列；
    (o)所述的重链可变区包含SEQ ID NO:46所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:45所示的氨基酸序列；
    (p)所述的重链可变区包含SEQ ID NO:47所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:45所示的氨基酸序列；
    (q)所述的重链可变区包含SEQ ID NO:48所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:49所示的氨基酸序列；
    (r)所述的重链可变区包含SEQ ID NO:50所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:49所示的氨基酸序列；
    (s)所述的重链可变区包含SEQ ID NO:51所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:49所示的氨基酸序列；
    (t)所述的重链可变区包含SEQ ID NO:52所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:53所示的氨基酸序列；
    (u)所述的重链可变区包含SEQ ID NO:54所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:53所示的氨基酸序列；
    (v)所述的重链可变区包含SEQ ID NO:55所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:56所示的氨基酸序列；
    (w)所述的重链可变区包含SEQ ID NO:57所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:58所示的氨基酸序列；
    (x)所述的重链可变区包含SEQ ID NO:59所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:60所示的氨基酸序列；
    (y)所述的重链可变区包含SEQ ID NO:61所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:62所示的氨基酸序列；或，
    (z)所述的重链可变区包含SEQ ID NO:63所示的氨基酸序列，所述轻链可变区包含SEQ ID NO:64所示的氨基酸序列。
  10. 根据权利要求1-9中任一项所述的抗TIGIT抗体或其抗原结合部分，其中所述抗原结合部分为Fab片段、Fab'片段、F(ab')2片段、Fd片段、Fv片段、dAb片段、分离的CDR区或scFv。
  11. 根据权利要求1-10中任一项所述的抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体或其抗原结合部分是嵌合的、人源化的或全人源的。
  12. 根据权利要求1-11中任一项所述的抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体为IgG1、IgG2、IgG3或IgG4同种型。
  13. 根据权利要求1-13中任一项所述的抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体或其抗原结合部分具有至少一种选择以下的性质：
    (i)以1.38E-09M或更小的KD值与人TIGIT结合；
    (ii)阻断TIGIT与CD155结合；
    (iii)促进NK细胞杀伤活性；
    (iv)促进NK细胞对Treg的ADCC作用；和
    (v)促进T细胞功能。
  14. 根据权利要求1-13中任一项所述的抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体包含重链和轻链，其中
    (a)所述的重链包含与SEQ ID NO:65所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:66所示序列具有至少80％同一性的氨基酸序列；
    (b)所述的重链包含与SEQ ID NO:67所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:68所示序列具有至少80％同一性的氨基酸序列；
    (c)所述的重链包含与SEQ ID NO:69所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:70所示序列具有至少80％同一性的氨基酸序列；
    (d)所述的重链包含与SEQ ID NO:71所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:72所示序列具有至少80％同一性的氨基酸序列；
    (e)所述的重链包含与SEQ ID NO:73所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:74所示序列具有至少80％同一性的氨基酸序列；
    (f)所述的重链包含与SEQ ID NO:75所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:76所示序列具有至少80％同一性的氨基酸序列；
    (g)所述的重链包含与SEQ ID NO:77所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:76所示序列具有至少80％同一性的氨基酸序列；
    (h)所述的重链包含与SEQ ID NO:78所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:76所示序列具有至少80％同一性的氨基酸序列；
    (i)所述的重链包含与SEQ ID NO:79所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:76所示序列具有至少80％同一性的氨基酸序列；
    (j)所述的重链包含与SEQ ID NO:80所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:81所示序列具有至少80％同一性的氨基酸序列；
    (k)所述的重链包含与SEQ ID NO:82所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:81所示序列具有至少80％同一性的氨基酸序列；
    (l)所述的重链包含与SEQ ID NO:80所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:83所示序列具有至少80％同一性的氨基酸序列；
    (m)所述的重链包含与SEQ ID NO:82所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:83所示序列具有至少80％同一性的氨基酸序列；
    (n)所述的重链包含与SEQ ID NO:84所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:85所示序列具有至少80％同一性的氨基酸序列；
    (o)所述的重链包含与SEQ ID NO:86所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:85所示序列具有至少80％同一性的氨基酸序列；
    (p)所述的重链包含与SEQ ID NO:87所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:85所示序列具有至少80％同一性的氨基酸序列；
    (q)所述的重链包含与SEQ ID NO:88所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:89所示序列具有至少80％同一性的氨基酸序列；
    (r)所述的重链包含与SEQ ID NO:90所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:89所示序列具有至少80％同一性的氨基酸序列；
    (s)所述的重链包含与SEQ ID NO:91所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:89所示序列具有至少80％同一性的氨基酸序列；
    (t)所述的重链包含与SEQ ID NO:92所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:93所示序列具有至少80％同一性的氨基酸序列；或者
    (u)所述的重链包含与SEQ ID NO:94所示序列具有至少80％同一性的氨基酸序列，所述轻链包含与SEQ ID NO:93所示序列具有至少80％同一性的氨基酸序列。
  15. 一种抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体包含重链和轻链，其中
    (a)所述的重链包含SEQ ID NO:65所示的氨基酸序列，所述轻链包含SEQ ID NO:66所示的氨基酸序列；
    (b)所述的重链包含SEQ ID NO:67所示的氨基酸序列，所述轻链包含SEQ ID NO:68所示的氨基酸序列；
    (c)所述的重链包含SEQ ID NO:69所示的氨基酸序列，所述轻链包含SEQ ID NO:70所示的氨基酸序列；
    (d)所述的重链包含SEQ ID NO:71所示的氨基酸序列，所述轻链包含SEQ ID NO:72所示的氨基酸序列；
    (e)所述的重链包含SEQ ID NO:73所示的氨基酸序列，所述轻链包含SEQ ID NO:74所示的氨基酸序列；
    (f)所述的重链包含SEQ ID NO:75所示的氨基酸序列，所述轻链包含SEQ ID NO:76所示的氨基酸序列；
    (g)所述的重链包含SEQ ID NO:77所示的氨基酸序列，所述轻链包含SEQ ID NO:76所示的氨基酸序列；
    (h)所述的重链包含SEQ ID NO:78所示的氨基酸序列，所述轻链包含SEQ ID NO:76所示的氨基酸序列；
    (i)所述的重链包含SEQ ID NO:79所示的氨基酸序列，所述轻链包含SEQ ID NO:76所示的氨基酸序列；
    (j)所述的重链包含SEQ ID NO:80所示的氨基酸序列，所述轻链包含SEQ ID NO:81所示的氨基酸序列；
    (k)所述的重链包含SEQ ID NO:82所示的氨基酸序列，所述轻链包含SEQ ID NO:81所示的氨基酸序列；
    (l)所述的重链包含SEQ ID NO:80所示的氨基酸序列，所述轻链包含SEQ ID NO:83所示的氨基酸序列；
    (m)所述的重链包含SEQ ID NO:82所示的氨基酸序列，所述轻链包含SEQ ID NO:83所示的氨基酸序列；
    (n)所述的重链包含SEQ ID NO:84所示的氨基酸序列，所述轻链包含SEQ ID NO:85所示的氨基酸序列；
    (o)所述的重链包含SEQ ID NO:86所示的氨基酸序列，所述轻链包含SEQ ID NO:85所示的氨基酸序列；
    (p)所述的重链包含SEQ ID NO:87所示的氨基酸序列，所述轻链包含SEQ ID NO:85所示的氨基酸序列；
    (q)所述的重链包含SEQ ID NO:88所示的氨基酸序列，所述轻链包含SEQ ID NO:89所示的氨基酸序列；
    (r)所述的重链包含SEQ ID NO:90所示的氨基酸序列，所述轻链包含SEQ ID NO:89所示的氨基酸序列；
    (s)所述的重链包含SEQ ID NO:91所示的氨基酸序列，所述轻链包含SEQ ID NO:89所示的氨基酸序列；
    (t)所述的重链包含SEQ ID NO:92所示的氨基酸序列，所述轻链包含SEQ ID NO:93所示的氨基酸序列；或者
    (u)所述的重链包含SEQ ID NO:94所示的氨基酸序列，所述轻链包含SEQ ID NO:93所示的氨基酸序列。
  16. 根据权利要求1-15中任一项所述的抗TIGIT抗体或其抗原结合部分，其中所述抗TIGIT抗体或其抗原结合部分为单特异性抗体或多特异性抗体。
  17. 一种分离的核酸，其编码根据权利要求1-16中任一项所述的抗TIGIT抗体或其抗原结合部分。
  18. 一种载体，其包含根据权利要求17所述的核酸。
  19. 一种宿主细胞，其包含根据权利要求17所述的核酸或权利要求18所述的载体。
  20. 一种制备根据权利要求1-16中任一项所述的抗TIGIT抗体或其抗原结合部分的方法，包括：培养权利要求19所述的宿主细胞，从所述宿主细胞或宿主细胞培养基中回收所述抗TIGIT抗体或其抗原结合部分。
  21. 一种抗体药物偶联物，其包含权利要求1-16中任一项所述的抗TIGIT抗体或其抗原结合部分。
  22. 一种融合蛋白，其包含权利要求1-16中任一项所述的抗TIGIT抗体或其抗原结合部分。
  23. 一种药物组合物，其包含根据权利要求1-16中任一项所述的抗TIGIT抗体或其抗原结合部分、权利要求21所述的抗体药物偶联物或权利要求22所述的融合蛋白。
  24. 一种在受试者中治疗癌症的方法，其中所述方法包括向受试者施用治疗有效量的根据权利要求1-16中任一项所述的抗TIGIT抗体或其抗原结合部分、权利要求21所述的抗体药物偶联物、权利要求22所述的融合蛋白或权利要求23所述的药物组合物。
  25. 根据权利要求23所述的方法，其中所述癌症为肺癌，小细胞肺癌，非小细胞肺癌，食管癌，胃癌，食管胃结合部癌，肝癌，胆管癌，胰腺癌，结直肠癌，前列腺癌，乳腺癌，子宫内膜癌，卵巢癌，输卵管癌，腹膜癌，宫颈癌，肾癌，膀胱癌，尿路上皮癌，间皮瘤，黑色素瘤，蕈样肉芽肿，梅克尔细胞癌，头颈癌，甲状腺癌，肉瘤，胶质母细胞瘤，胸腺癌，白血病，淋巴瘤，或骨髓瘤。
  26. 一种在受试者中治疗免疫相关疾病的方法，其中所述方法包括向受试者施用治疗有效量的根据权利要求1-16中任一项所述的抗TIGIT抗体或其抗原结合部分、权利要求21所述的抗体药物偶联物、权利要求22所述的融合蛋白或权利要求23所述的药物组合物。
  27. 一种在受试者中增强免疫应答的方法，其中所述方法包括向受试者施用治疗有效量的根据权利要求1-16中任一项所述的抗TIGIT抗体或其抗原结合部分、权利要求21所述的抗体药物偶联物、权利要求22所述的融合蛋白或权利要求23所述的药物组合物。
  28. 根据权利要求24-27中任一项所述的方法，其中所述治疗包括向受试者施用第二治疗剂。
  29. 根据权利要求27所述的方法，其中所述第二治疗剂为PD-1轴结合拮抗剂。
  30. 一种试剂盒，其包含根据权利要求1-16中任一项所述的抗TIGIT抗体或其抗原结合部分、权利要求21所述的抗体药物偶联物、权利要求22所述的融合蛋白或权利要求23所述的药物组合物。
PCT/CN2024/101505 2023-06-27 2024-06-26 抗tigit抗体及其应用 Ceased WO2025002151A1 (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202480031403.4A CN121219319A (zh) 2023-06-27 2024-06-26 抗tigit抗体及其应用

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202310764105 2023-06-27
CN202310764105.3 2023-06-27

Publications (1)

Publication Number Publication Date
WO2025002151A1 true WO2025002151A1 (zh) 2025-01-02

Family

ID=93937619

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2024/101505 Ceased WO2025002151A1 (zh) 2023-06-27 2024-06-26 抗tigit抗体及其应用

Country Status (2)

Country Link
CN (1) CN121219319A (zh)
WO (1) WO2025002151A1 (zh)

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20160176963A1 (en) * 2014-12-23 2016-06-23 Bristol-Myers Squibb Company Antibodies to tigit
US20160376365A1 (en) * 2015-05-28 2016-12-29 Oncomed Pharmaceuticals, Inc. Tigit-binding agents and uses thereof
CN108883164A (zh) * 2016-03-04 2018-11-23 Jn生物科学有限责任公司 针对tigit的抗体
CN111196852A (zh) * 2018-11-16 2020-05-26 四川科伦博泰生物医药股份有限公司 抗tigit抗体及其用途
CN111601826A (zh) * 2018-01-15 2020-08-28 南京传奇生物科技有限公司 针对tigit的抗体及其变体
WO2021093849A1 (en) * 2019-11-14 2021-05-20 Wuxi Biologics (Shanghai) Co., Ltd. A novel antibody against tigit
CN111051347B (zh) * 2017-09-29 2021-12-21 江苏恒瑞医药股份有限公司 Tigit抗体、其抗原结合片段及医药用途
WO2022105872A1 (zh) * 2020-11-23 2022-05-27 广东菲鹏制药股份有限公司 抗tigit抗体或其抗原结合片段
WO2022156726A1 (en) * 2021-01-21 2022-07-28 Beigene, Ltd. Methods of cancer treatment using anti-tigit antibodies in combination with anti-pd1 antibodies
CN115698068A (zh) * 2020-06-02 2023-02-03 艾库斯生物科学有限公司 抗tigit抗体

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20160176963A1 (en) * 2014-12-23 2016-06-23 Bristol-Myers Squibb Company Antibodies to tigit
US20160376365A1 (en) * 2015-05-28 2016-12-29 Oncomed Pharmaceuticals, Inc. Tigit-binding agents and uses thereof
CN108883164A (zh) * 2016-03-04 2018-11-23 Jn生物科学有限责任公司 针对tigit的抗体
CN111051347B (zh) * 2017-09-29 2021-12-21 江苏恒瑞医药股份有限公司 Tigit抗体、其抗原结合片段及医药用途
CN111601826A (zh) * 2018-01-15 2020-08-28 南京传奇生物科技有限公司 针对tigit的抗体及其变体
CN111196852A (zh) * 2018-11-16 2020-05-26 四川科伦博泰生物医药股份有限公司 抗tigit抗体及其用途
WO2021093849A1 (en) * 2019-11-14 2021-05-20 Wuxi Biologics (Shanghai) Co., Ltd. A novel antibody against tigit
CN115698068A (zh) * 2020-06-02 2023-02-03 艾库斯生物科学有限公司 抗tigit抗体
WO2022105872A1 (zh) * 2020-11-23 2022-05-27 广东菲鹏制药股份有限公司 抗tigit抗体或其抗原结合片段
WO2022156726A1 (en) * 2021-01-21 2022-07-28 Beigene, Ltd. Methods of cancer treatment using anti-tigit antibodies in combination with anti-pd1 antibodies

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
DAOYUAN LI, SIYI HU, QINGLIN FAN, WENYING BAO, WEI ZHOU, TING XU, TAOHONG YE, HAO LIU, LIHUA SONG: "Phage display screening of TIGIT-specific antibody for antitumor immunotherapy", BIOSCIENCE, BIOTECHNOLOGY, AND BIOCHEMISTRY, vol. 83, no. 9, 2 September 2019 (2019-09-02), JP , pages 1683 - 1696, XP055769359, ISSN: 0916-8451, DOI: 10.1080/09168451.2019.1617107 *
JEONG BO-SEONG, NAM HYEMI, LEE JEEWON, PARK HYE-YOUNG, CHO KI JOON, SHEEN JOONG HYUK, SONG EUNJUNG, OH MEESOOK, LEE SUNGGEUN, CHOI: "Structural and functional characterization of a monoclonal antibody blocking TIGIT", MABS, vol. 14, no. 1, 31 December 2022 (2022-12-31), US , pages 1 - 12, XP093254199, ISSN: 1942-0862, DOI: 10.1080/19420862.2021.2013750 *
KOJIMA MARENORI, SUZUKI KATSUYA, TAKESHITA MASARU, OHYAGI MASAKI, IIZUKA MANA, YAMANE HUMITSUGU, KOGA KEIKO, KOURO TAKU, KASSAI YO: "Anti-human-TIGIT agonistic antibody ameliorates autoimmune diseases by inhibiting Tfh and Tph cells and enhancing Treg cells", COMMUNICATIONS BIOLOGY, vol. 6, no. 1, 1 January 2023 (2023-01-01), pages 1 - 13, XP093203844, ISSN: 2399-3642, DOI: 10.1038/s42003-023-04874-3 *
ROUSSEAU A., PARISI C., BARLESI F.: "Anti-TIGIT therapies for solid tumors: a systematic review", ESMO OPEN : CANCER HORIZONS, vol. 8, no. 2, 1 April 2023 (2023-04-01), London , pages 1 - 9, XP093064346, ISSN: 2059-7029, DOI: 10.1016/j.esmoop.2023.101184 *
SHEN XIAN, FU WENYAN, WEI YONGPENG, ZHU JUNLE, YU YUE, LEI CHANGHAI, ZHAO JIAN, HU SHI: "TIGIT-Fc Promotes Antitumor Immunity", CANCER IMMUNOLOGY RESEARCH, vol. 9, no. 9, 1 September 2021 (2021-09-01), US , pages 1088 - 1097, XP093033275, ISSN: 2326-6066, DOI: 10.1158/2326-6066.CIR-20-0986 *

Also Published As

Publication number Publication date
CN121219319A (zh) 2025-12-26

Similar Documents

Publication Publication Date Title
CN114502591B (zh) 靶向bcma的抗体、双特异性抗体及其用途
CN113412281B (zh) Btn3a结合蛋白及其用途
US12509520B2 (en) Anti-CD3 and anti-CD123 bispecific antibody and use thereof
CN105777906A (zh) 抗pd-l1全人抗体及其应用
US20250145705A1 (en) Gprc5d antibody and application thereof
US20240309087A1 (en) Anti-cd112r antibody and use thereof
TW202302650A (zh) 針對dll3的結合分子及其應用
CN116940598A (zh) 用于治疗表达cldn18.2的实体瘤的cldn18.2/cd3双特异性抗体
CN116685604A (zh) 抗人msln的抗体及其用途
WO2021143914A1 (zh) 一种激活型抗ox40抗体、生产方法及应用
WO2022152282A1 (zh) 抗人cd22的单克隆抗体及其用途
TW202434644A (zh) 三特異性抗原結合分子及其應用
WO2025002151A1 (zh) 抗tigit抗体及其应用
WO2023143322A1 (zh) p95HER2抗体及其应用
CN118165116A (zh) 新型多特异性抗体
EP4663661A1 (en) Anti-cdh6 antibody and use thereof
WO2025146128A1 (zh) 抗liv-1的抗体及其用途
WO2025157244A1 (zh) 抗b7h3抗体及其应用
WO2025025190A1 (zh) 抗cd73抗体及其应用
CN116813786A (zh) 抗cd73抗体及其应用
EP4714974A1 (en) Bispecific antigen binding molecule and use thereof
TW202413414A (zh) 抗ｉｌｔ４抗體及其醫藥用途
JP2024509369A (ja) 抗ｐｄ－ｌ１抗体及びその使用

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 24830790

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE