Anti-CDH17 antibody or antigen-binding fragment thereof and use thereof

Abstract

An anti-CDH17 antibody or an antigen-binding fragment thereof and the use thereof. The antibody can specifically bind to one or more extracellular domains in extracellular domains 1-7 of CDH17, has an ADCC activity, and can mediate cell endocytosis, thereby providing a new possibility for the treatment and / or prevention of cancers.

Description

Anti-CDH17 antibodies or antigen-binding fragments thereof and their applications

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to the Chinese invention patent application with application number 202311871606.8, filing date November 29, 2023, and invention name “Anti-CDH17 antibodies or antigen-binding fragments thereof and their applications”, the entire contents of which are incorporated herein by reference. Technical Field

[0003] The present disclosure relates to the field of biotechnology, and in particular to an anti-CDH17 antibody or an antigen-binding fragment thereof and applications thereof. Background Art

[0004] Tumor development and progression is a multifactorial, multistep process, in which dysregulation of cell-cell adhesion and motility is a key mechanism of tumor progression. Cadherin-17, a recently discovered member of the cadherin family, is expressed in the mouse liver and small intestine and plays a crucial role in cell adhesion, cell recognition, tissue and organ development, and morphological maintenance. Studies have shown that its expression is closely associated with the development and progression of epithelial tumors of the digestive system, making it a promising new tumor target and marker.

[0005] Cadherin-17 (CDH17) is a new member of the cadherin family. It was first identified from a mouse hepatocyte cDNA library. Because it is exclusively expressed in the mouse liver and small intestine, it is also named liver-intestine cadherin (LI-cadherin). CDH17 is commonly expressed in embryonic and adult intestinal epithelial cells and some pancreatic ductal epithelial cells, but is rarely expressed in hepatocytes, esophageal epithelial cells, or gastric mucosa in healthy individuals.

[0006] Cadherins exert their biological effects by mediating calcium-dependent intercellular junctions. The ligands for classical cadherins are calcatenins, including α-catenin, β-catenin, γ-catenin, and p120. Cadherins regulate intercellular adhesion through interactions with the intracellular cytoskeleton. CDH17 functions as a functional Ca2+-dependent cell adhesion molecule. However, CDH17 does not tightly bind to the actin-mediated cytoskeleton through intracellular calcatenin, but rather directly binds to the cytoskeleton. During tumor progression, CDH17 primarily binds to the integrin α2β1 on adjacent tumor cells through its outer cytoskeleton domain, EC6, which contains an RGD domain (green), leading to enhanced integrin activation, adhesion, proliferation, invasion, tumorigenesis, and metastasis. Studies have also found that CDH17 expression is an independent prognostic factor for patient survival. CDH17 expression has an impact on the prognosis of patients with node-negative gastric cancer, potentially reflecting its role in maintaining polarity and normal intercellular adhesion. Therefore, the development and optimization of anti-CDH17 antibodies are of great significance for the prevention or treatment of tumor-related diseases.

[0007] In view of this, the present disclosure is proposed.

[0008] Application Contents

[0009] One of the objectives of the present disclosure is to provide an antibody or antigen-binding fragment thereof that can specifically bind to CDH17 and its use.

[0010] In order to solve the above technical problems, the present disclosure adopts the following technical solutions:

[0011] In a first aspect, an anti-CDH17 antibody or an antigen-binding fragment thereof is provided. The anti-CDH17 antibody or antigen-binding fragment thereof specifically binds to one or more of CDH17 extracellular domain 1 (D1), CDH17 extracellular domain 2 (D2), CDH17 extracellular domain 3 (D3), CDH17 extracellular domain 4 (D4), CDH17 extracellular domain 5 (D5), CDH17 extracellular domain 6 (D6), and CDH17 extracellular domain 7 (D7).

[0012] In a second aspect, the present disclosure provides an anti-CDH17 antibody or an antigen-binding fragment thereof, which competitively binds to CDH17 with the anti-CDH17 antibody described in the first or second aspect, or the epitope thereof that binds to the CDH17 antigen is the same as the epitope of the anti-CDH17 antibody described in the first or second aspect that binds to the CDH17 antigen.

[0013] In a third aspect, the present disclosure provides a biomaterial comprising any one of the following (i) to (vi):

[0014] (i) a multispecific antibody comprising the anti-CDH17 antibody according to the first or second aspect;

[0015] (ii) a chimeric antigen receptor, comprising an extracellular region, wherein the extracellular region comprises an antigen-binding domain; and wherein the antigen-binding domain comprises the anti-CDH17 antibody or antigen-binding fragment thereof according to the first or second aspect;

[0016] (iii) a nucleic acid molecule encoding the anti-CDH17 antibody or antigen-binding fragment thereof according to the first or second aspect, or the multispecific antibody according to (i), or the chimeric antigen receptor according to (ii);

[0017] (iv) a vector carrying the nucleic acid molecule described in (iii);

[0018] (v) a recombinant cell, characterized in that the recombinant cell expresses the anti-CDH17 antibody or antigen-binding fragment thereof according to the first or second aspect, or expresses the multispecific antibody according to (i), or expresses the chimeric antigen receptor according to (ii), or contains the nucleic acid molecule according to (iii), or contains the vector according to (iv);

[0019] (vi) An engineered immune cell, characterized in that the immune cell expresses the chimeric antigen receptor described in (ii) or contains a nucleic acid molecule encoding the chimeric antigen receptor described in (ii).

[0020] In a fourth aspect, the present disclosure provides a pharmaceutical composition comprising the anti-CDH17 antibody or antigen-binding fragment thereof according to the first or second aspect, or the biomaterial according to the third aspect.

[0021] In a fifth aspect, the present disclosure provides use of the anti-CDH17 antibody or antigen-binding fragment thereof of the first or second aspect, or the biomaterial of the third aspect, or the pharmaceutical composition of the fourth aspect in any of the following:

[0022] (I) Detection of CDH17 or cells expressing CDH17;

[0023] (II) preparing products for detecting CDH17 or cells expressing CDH17;

[0024] (III) for treating, preventing or alleviating diseases, disorders or conditions associated with CDH17

[0025] (IV) Preparing a pharmaceutical composition for treating, preventing or alleviating a disease, disorder or condition associated with CDH17.

[0026] In a sixth aspect, the present disclosure provides a method for producing the aforementioned anti-CDH17 antibody or antigen-binding fragment thereof, comprising the following steps:

[0027] (a) culturing the aforementioned recombinant cell under conditions for expressing an anti-CDH17 antibody or an antigen-binding fragment thereof;

[0028] (b) isolating and purifying the anti-CDH17 antibody or antigen-binding fragment thereof obtained in step (a).

[0029] In a seventh aspect, the present disclosure provides a kit for detecting CDH17, comprising the aforementioned anti-CDH17 antibody or an antigen-binding fragment thereof.

[0030] In an eighth aspect, the present disclosure provides a method for treating a disease, comprising administering to a subject in need thereof a therapeutically effective amount of the anti-CDH17 antibody or antigen-binding fragment thereof of the first or second aspect, or the biomaterial of the third aspect, or the pharmaceutical composition of the fourth aspect; optionally, the disease is a disease associated with overexpression of human CDH17;

[0031] Optionally, the disease is a tumor;

[0032] Optionally, the tumor is selected from lung cancer, prostate cancer, breast cancer, head and neck cancer, esophageal cancer, gastric cancer, colon cancer, rectal cancer, bladder cancer, cervical cancer, uterine cancer, ovarian cancer, liver cancer, melanoma, kidney cancer, squamous cell carcinoma and blood system cancer. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] In order to more clearly illustrate the specific embodiments of the present disclosure or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the specific embodiments or the description of the prior art. Obviously, the drawings described below are some embodiments of the present disclosure. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0034] Figure 1 is a schematic diagram of the extracellular domain of human CDH17;

[0035] FIG2 is a schematic diagram showing the structural relationship between human CDH17 and the extracellular region fragment of human CDH17 in Example 1 of the present disclosure;

[0036] FIG3 shows the binding activity of monoclonal antibodies (F1-87.15, F1-99.29, F1-76.12, and F1-86.9) to CHO-hCDH17 cells detected by flow cytometry in Example 2;

[0037] FIG4 shows the binding activity of monoclonal antibodies (F2-89.7, F2-155.7, F2-238.14, and F2-324.7) to CHO-hCDH17 cells detected by flow cytometry in Example 2;

[0038] Figure 5 shows the binding activity of monoclonal antibodies (F1-124.38, F2-55.10, F2-291.2, F3-1.5, and F3-6.18) to CHO-hCDH17 cells detected by flow cytometry in Example 2;

[0039] Figure 6 shows the binding activity of monoclonal antibodies (F1-87.15, F1-41.16, F2-238.14, F1-111.5, and F2-55.10) to AsPC-1 cells detected by flow cytometry in Example 2;

[0040] FIG7 Flow cytometry analysis of the binding activity of monoclonal antibodies (F1-86.23, F1-99.29, F1-139.6, F1-76.12, F1-124.2, F1-122.19, F1-86.9, F1-143.7, F1-124.38, and F1-143.38) to AsPC-1 cells in Example 2;

[0041] FIG8 Flow cytometry analysis of the binding activity of monoclonal antibodies (F2-71.18, F2-291.2, F2-324.17, F2-89.7, F2-155.7, F2-324.7, F2-186.1, F3-1.5, F3-6.18, and F3-36.14) to AsPC-1 cells in Example 2;

[0042] Figure 9 shows the binding activity of monoclonal antibodies (F1-87.15, F1-99.29, F1-127.8, F1-76.12, F1-111.5, F1-86.9, F1-143.7, F1-41.16, F1-124.38, F2-71.18) to monkey CDH17 detected by ELISA in Example 3;

[0043] Figure 10 shows the binding activity of monoclonal antibodies (F2-89.7, F2-155.7, F2-186.1, F2-238.14, F2-324.7, F2-55.10, F2-291.2, F3-1.5, F3-6.18, and F3-36.14) to monkey CDH17 as detected by ELISA in Example 3;

[0044] Figure 11 shows the binding activity of monoclonal antibodies (F1-87.15, F1-99.29, F1-127.8, F1-76.12, F1-111.5, F1-86.9, F1-143.7, F1-41.16, F1-124.38, and F2-71.18) to mouse CDH17 as detected by ELISA in Example 4;

[0045] Figure 12 shows the binding activity of monoclonal antibodies (F2-89.7, F2-155.7, F2-186.1, F2-238.14, F2-324.7, F2-55.10, F2-291.2, F3-1.5, F3-6.18, and F3-36.14) to mouse CDH17 as detected by ELISA in Example 4;

[0046] Figure 13 shows the binding activity of monoclonal antibodies (F1-87.15, F1-41.16, F2-238.14, F1-111.5, F2-55.10, F1-86.23, F1-99.29, F1-139.6, F1-76.12, F1-124.2, F1-122.19, F1-86.9) to human CDH17 as detected by ELISA in Example 5;

[0047] Figure 14 shows the binding activity of monoclonal antibodies (F1-143.7, F1-124.38, F1-143.38, F2-71.18, F2-291.2, F2-324.17, F2-89.7, F2-155.7, F2-324.7, F2-186.1, F3-1.5, F3-6.18, F3-36.14) to human CDH17 as detected by ELISA in Example 5;

[0048] Figure 15 shows the binding activity of monoclonal antibodies (F1-87.15, F1-41.16, F2-238.14, F1-111.5, F2-55.10, F1-86.23, F1-99.29, F1-139.6, F1-76.12, F1-124.2, F1-122.19, F1-86.9) to mouse CDH17 (D1-D4) detected by ELISA in Example 6;

[0049] Figure 16 shows the binding activity of monoclonal antibodies (F1-143.7, F1-124.38, F1-143.38, F2-71.18, F2-291.2, F2-324.17, F2-89.7, F2-155.7, F2-324.7, F2-186.1, F3-1.5, F3-6.18, F3-36.14) to mouse CDH17 (D1-D4) detected by ELISA in Example 6;

[0050] Figure 17 shows the binding activity of monoclonal antibodies (F1-87.15, F1-41.16, F2-238.14, F1-111.5, F2-55.10, F1-86.23, F1-99.29, F1-139.6, F1-76.12, F1-124.2, F1-122.19, F1-86.9) to mouse CDH17 (D5-D7) detected by ELISA in Example 6;

[0051] Figure 18 shows the binding activity of monoclonal antibodies (F1-143.7, F1-124.38, F1-143.38, F2-71.18, F2-291.2, F2-324.17, F2-89.7, F2-155.7, F2-324.7, F2-186.1, F3-1.5, F3-6.18, F3-36.14) to mouse CDH17 (D5-D7) detected by ELISA in Example 6;

[0052] FIG19 is a flow cytometry analysis of the monoclonal antibody-mediated killing activity against overexpressing CHO-hCDH17 cells in Example 7;

[0053] FIG20 shows the monoclonal antibody-mediated killing activity against AsPC-1 cells endogenously expressing human CDH17 detected by the LDH method in Example 7;

[0054] Figure 21 shows the endocytic activity of AsPC-1 cells in Example 8 towards monoclonal antibodies F1-87.15, F1-99.29, F1-76.12, F1-86.9, F1-143.7, F2-238.14, F2-55.10, F3-1.5, F3-6.18, and F3-36.14;

[0055] Figure 22 shows the binding activity of monoclonal antibodies (R4723, R4709, R4710, R4711, R4712, R4713, and R4714) to CHO-CDH17 cells as detected by flow cytometry in Example 10;

[0056] Figure 23 shows the binding activity of monoclonal antibodies (R4723, R4715, R4716, R4717, R4718) to CHO-CDH17 cells detected by flow cytometry in Example 10;

[0057] Figure 24 shows the binding activity of monoclonal antibodies (R4850, R4832, R4833, R4834, R4835, R4836, and R4837) to CHO-CDH17 cells as detected by flow cytometry in Example 10;

[0058] Figure 25 shows the binding activity of monoclonal antibodies (R4850, R4838, R4839, R4840, R4841, R4842, and R4843) to CHO-CDH17 cells as detected by flow cytometry in Example 10;

[0059] Figure 26 shows the binding activity of monoclonal antibodies (R4723, R4709, R4710, R4711, R4712, R4713, and R4714) to AsPC-1 cells as detected by flow cytometry in Example 10;

[0060] Figure 27 shows the binding activity of monoclonal antibodies (R4723, R4715, R4716, R4717, R4718) to AsPC-1 cells detected by flow cytometry in Example 10;

[0061] Figure 28 shows the binding activity of monoclonal antibodies (R4850, R4832, R4833, R4834, R4835, R4836, and R4837) to AsPC-1 cells as detected by flow cytometry in Example 10;

[0062] Figure 29 shows the binding activity of monoclonal antibodies (R4850, R4838, R4839, R4840, R4841, R4842, and R4843) to AsPC-1 cells as detected by flow cytometry in Example 10;

[0063] FIG30 is a flow cytometry analysis of the binding activity of monoclonal antibodies (R4723, R4709, R4710, R4711, R4712, R4713, and R4714) to OCUM-1 cells in Example 10;

[0064] FIG31 is a flow cytometry analysis of the binding activity of monoclonal antibodies (R4723, R4715, R4716, R4717, and R4718) to OCUM-1 cells in Example 10;

[0065] FIG32 shows the binding activity of monoclonal antibodies (R4850, R4832, R4833, R4834, R4835, R4836, and R4837) to OCUM-1 cells as detected by flow cytometry in Example 10;

[0066] FIG33 shows the binding activity of monoclonal antibodies (R4850, R4838, R4839, R4840, R4841, R4842, and R4843) to OCUM-1 cells as detected by flow cytometry in Example 10;

[0067] Figure 34 shows the binding activity of monoclonal antibodies (R4723, R4709, R4710, R4711, R4712, R4713, and R4714) to monkey CDH17 as detected by ELISA in Example 11;

[0068] Figure 35 shows the binding activity of monoclonal antibodies (R4723, R4715, R4716, R4717, and R4718) to monkey CDH17 as detected by ELISA in Example 11;

[0069] Figure 36 shows the binding activity of monoclonal antibodies (R4850, R4832, R4833, R4834, R4835, R4836, and R4837) to monkey CDH17 as detected by ELISA in Example 11;

[0070] Figure 37 shows the binding activity of monoclonal antibodies (R4850, R4838, R4839, R4840, R4841, R4842, and R4843) to monkey CDH17 detected by ELISA in Example 11. DETAILED DESCRIPTION

[0071] The following will clearly and completely describe the technical solutions of the present disclosure in conjunction with the embodiments. Obviously, the embodiments described are only a part of the embodiments of the present disclosure, not all of them. Based on the embodiments of the present disclosure, all other embodiments obtained by ordinary technicians in this field without making any creative efforts are within the scope of protection of the present disclosure.

[0072] In the present disclosure, the articles "a", "an", and "the" include plural referents unless the context clearly indicates otherwise. For example, "an antibody" refers to one antibody or more than one antibody.

[0073] In this disclosure, the terms "first" and "second" are used for descriptive purposes only and should not be understood to indicate or imply relative importance or implicitly specify the number of the technical features indicated. Therefore, a feature defined as "first" or "second" may explicitly or implicitly include at least one of such features. In the description of this disclosure, "plurality" means at least two, for example, two, three, etc., unless otherwise specifically defined.

[0074] In this disclosure, the terms "CDH17" and "CDH-17" are interchangeable and refer to the cadherin protein Cadherin-17, also known as liver-intestine cadherin (LI-cadherin). It is a member of the non-classical cadherin superfamily and shares some structural homology with classical cadherins. However, CDH17 has its own unique structure: 1) The extracellular region of CDH17 consists of seven repeating sequences (Figure 1), which is different from the five repeating sequences of non-classical cadherins; 2) In the extracellular D1 cell adhesion recognition region, CDH17 contains an AAL sequence that replaces the corresponding HAV sequence of classical cadherin; 3) The cytoplasmic tail of CDH17 has only 20 amino acid residues, while the cytoplasmic tail of classical cadherin has 150-160 amino acid residues. Studies have shown that structural abnormalities and functional disorders of cadherins are closely related to tumor invasion and metastasis. Because CDH17 has a short cytoplasmic tail domain, it cannot interact with the catenin network or the actin cytoskeleton. Therefore, CDH17 is classified as a variant of the classical cadherin. The N-terminus of CDH17 is located outside the cell, and the C-terminus is located inside the cell. CDH17 has seven extracellular domains (i.e., extracellular regions, also known as ECDs (Extra Cellular Domains), including CDH17 D1 to 7, also known as EC1-EC7), a transmembrane region, and a cytoplasmic tail. Its adhesion properties are mainly determined by the extracellular domains. A schematic diagram of the structure of human CDH17 is shown in Figure 2. Unless otherwise specified, the term "CDH17" includes human CDH17, isoforms, and species homologs expressed by cells naturally expressed or transfected with the CDH17 gene. The term also includes artificially modified CDH17, including but not limited to polypeptides or proteins that have been mutated, truncated, or fused with other domains, and retain the necessary antigenic epitopes for antibody binding. The anti-CDH17 antibodies or antigen-binding fragments thereof provided by the present disclosure are capable of specifically binding to CDH17.

[0075] In this disclosure, the term "antibody" includes any immunoglobulin that can bind to a specific antigen. The term "antibody" is used in the broadest sense to encompass various antibody structures, including, but not limited to, monoclonal antibodies, polyclonal antibodies, monospecific antibodies, multispecific antibodies, full-length antibodies, and antigen-binding fragments, as long as they exhibit the desired antigen-binding activity. Typically, a natural, intact antibody comprises two heavy (H) chains and two light (L) chains. Antibodies can be divided into five major classes or isotypes: IgA, IgD, IgE, IgG, and IgM, depending on whether they contain α, δ, ε, γ, and μ heavy chains, respectively. Several major antibody classes are further divided into subclasses, such as IgG1 (γ1 heavy chain), IgG2 (γ2 heavy chain), IgG3 (γ3 heavy chain), IgG4 (γ4 heavy chain), IgA1 (α1 heavy chain), or IgA2 (α2 heavy chain). Each heavy chain consists of a variable region (VH) and first, second, third, and optionally fourth constant regions (CH1, CH2, CH3, and CH4, respectively). The light chains of mammals can be divided into λ or κ, and each light chain consists of a variable region (VL) and a constant region (CL). The variable regions of the light chain and heavy chain determine the binding of the antigen. The variable region of each chain usually contains three hypervariable regions, called "complementarity determining regions (CDRs)", of which the light chain CDR contains LCDR1, LCDR2, LCDR3, and the heavy chain CDR contains HCDR1, HCDR2, and HCDR3. The variable region (VH and VL) is each composed of three complementarity determining regions connected by four framework regions (FRs). Generally, the variable region VL / VH of the heavy chain and light chain can be obtained by connecting the following numbered CDRs and FRs in the following combination: FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4.

[0076] In the present disclosure, the term "antigen-binding fragment" is a substance comprising an antibody CDR that lacks some of the amino acids present in the full-length chain but is still capable of specific binding to an antigen. Such fragments are biologically active because they bind to the target antigen and can compete with other antigen-binding molecules (including intact antibodies) for binding to a given epitope. Examples of antigen-binding fragments include, but are not limited to, Fab, Fab', F(ab')2, Fv fragments, disulfide-stabilized Fv fragments (dsFv), (dsFv)2, bispecific dsFv (dsFv-dsFv'), disulfide-stabilized bifunctional antibodies (ds diabody), single-chain antibody molecules (scFv), scFv dimers (bivalent bifunctional antibodies), and antibody minimum recognition units. The above-mentioned antigen-binding fragments are capable of binding to the same antigen as the parent antibody.

[0077] In the present disclosure, the term "Fab" of an antibody refers to a portion of an antibody composed of a single light chain (including a variable region and a constant region) and the variable region and the first constant region of a single heavy chain bound together by a disulfide bond. A "Fab' fragment" refers to a Fab fragment that includes part of the hinge region. "F(ab')2" refers to a dimer of Fab'. An "Fv fragment" is composed of the variable region of a single light chain and / or the variable region of a single heavy chain. A "single-chain Fv antibody" or "scFv" refers to an antibody fragment formed by directly connecting the light chain variable region and the heavy chain variable region to each other or connected by a peptide linker sequence. The "minimum recognition unit of an antibody" refers to a structure containing only a single CDR in the variable region. Although the minimum recognition unit has a small molecular weight and low affinity, it has the ability to bind to the antigen.

[0078] The CDR boundaries of the antibodies or antigen-binding fragments thereof in the present disclosure can be defined or identified according to the IMGT, Kabat, Chothia, AbM, or Contact definitions. CDRs defined in other ways acceptable in the art also fall within the scope of protection of the present disclosure (Kaas, Q et al. IMGT unique numbering for immunoglobulin and T cell receptor constant domains and Ig superfamily C-like domains. Dev. Comp. Immunol. 29, 185-203, (2005); RM MacCallum et al.. Antibody–antigen interactions: contact analysis and binding site topography J. Mol. Biol. (1996); Martin, A C R Protein sequence and structure analysis of antibody variable domains (Book chapter). In Antibody engineering lab manual Eds. Duebel, S. and Kontermann, R. (2001); Marie-Paule Lefranc et al. IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains,Developmental and Comparative Immunology 27(2003)55–77).

[0079] In this disclosure, the term "amino acid" refers to naturally occurring amino acids and synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function in a manner similar to the naturally occurring amino acids. Naturally occurring amino acids include those encoded by the genetic code and modified amino acids thereof, such as hydroxyproline, γ-carboxyglutamate, and O-phosphoserine. Common naturally occurring amino acids include alanine (Ala; A), arginine (Arg; R), asparagine (Asn; N), aspartic acid (Asp; D), cysteine ​​(Cys; C); glutamic acid (Glu; E), glutamine (Gln; Q), glycine (Gly; G); histidine (His; H), isoleucine (Ile; I), leucine (Leu; L), lysine (Lys; K), methionine (Met; M), phenylalanine (Phe; F), proline (Pro; P), serine (Ser; S), threonine (Thr; T), tryptophan (Trp; W), tyrosine (Tyr; Y), and valine (Val; V). Amino acid analogs are compounds that have the same basic chemical structure as naturally occurring amino acids (i.e., an alpha carbon bonded to a hydrogen, carboxyl, amino, and R groups), such as homoserine, norleucine, methionine sulfoxide, and methionine methylsulfonium. Amino acid analogs typically have modified R groups (e.g., norleucine) or modified peptide backbones, but retain the same basic chemical structure as naturally occurring amino acids. Amino acid mimetics refer to chemical compounds that have a structure that is different from the general chemical structure of an amino acid, but function in a manner similar to naturally occurring amino acids. In the present disclosure, the term "percent identity" refers to the extent to which the amino acids of two polypeptides are identical at equivalent positions when the two sequences are optimally aligned. Comparison of amino acid sequence identity percentages can be performed in various ways known in the art, such as software such as BLAST, BLAST-2, ALIGN, MEGALIGN (DNASTAR), CLUSTALW, or CLUSTAL OMEGA, which are well known in the art. One skilled in the art can determine appropriate parameters for aligning sequences, including any algorithm required to achieve maximum alignment over the entire length of the compared sequences.

[0080] In the present disclosure, the term "specific binding" or "specifically binds" refers to a non-random binding reaction between two molecules, for example, a reaction between an antibody and an antigen. In some specific embodiments, for example, the binding is determined by flow cytometry fluorescence sorting technology.

[0081] In the present disclosure, the term "anti-CDH17 antibody" refers to an antibody that can specifically bind to CDH17. In some specific embodiments, the "anti-CDH17 antibody" specifically binds to human and / or monkey CDH17.

[0082] In the present disclosure, the term "affinity" or "avidity" refers to the strength of the non-covalent interaction between an immunoglobulin molecule (i.e., an antibody) or a fragment thereof and an antigen. The strength or affinity of an immunological binding interaction can be expressed as the equilibrium dissociation constant (KD) of the interaction, where a smaller KD value indicates a higher affinity. KD can be determined using any conventional method known in the art, including but not limited to Biacore assays, Octet methods, microthermophoresis, HPLC-MS methods, and flow cytometry fluorescence sorting techniques.

[0083] The binding of the antibodies or antigen-binding fragments thereof provided herein to CDH17 can also be measured using a "half-maximal effective concentration (EC50)," which refers to the concentration of the drug or antibody that achieves 50% of the maximum biological effect after a specific exposure time. Generally, the lower the EC50, the better the affinity, indicating that binding to the target protein can be achieved at a lower concentration. The EC50 value can be determined by binding assays known in the art, such as direct or indirect binding assays (e.g., enzyme-linked immunosorbent assay (ELISA), flow cytometry fluorescence sorting technology, and other binding assays).

[0084] In the present disclosure, the term "epitope" refers to any antigenic determinant on an antigen that is bound by the paratope of an antibody. Antigenic determinants are typically special chemical groups with a certain composition and structure. An epitope can be linear (i.e., continuous) or conformational (i.e., comprising spaced-apart amino acid residues, non-continuous). An epitope defines the minimum binding site for an antibody and is therefore the specific target of an antibody or its antigen-binding fragment. An epitope can be determined by any method well known in the art, such as conventional immunoassays, antibody competitive binding assays, or X-ray crystallography or related structural determination methods (e.g., nuclear magnetic resonance spectroscopy).

[0085] In the present disclosure, the term "multispecific antibody" refers to an antibody molecule that can bind to multiple (two or more) different antigenic epitopes of the same antigen or multiple (two or more) different antigens.

[0086] The “chimeric antigen receptor” in the present disclosure, CAR is an artificial receptor that simulates the function of TCR, which is composed of an extracellular domain, a transmembrane domain and an intracellular signaling domain connected in sequence. When the antigen (receptor) on the surface of the tumor cell binds to the antibody (ligand) of the chimeric antigen receptor, the signal can be transmitted to the cell through the hinge region and the transmembrane region. The intracellular signaling domain then converts the signal into an activation signal to activate effector cells. The effector cells kill tumor cells by secreting perforin or producing cytokines. At the same time, the effector cells themselves also amplify, further expanding the immune killing effect. The extracellular domain is generally composed of a single-chain variable fragment (scFv) of a monoclonal antibody responsible for recognizing and binding to the antigen and a hinge region (Hinge) that acts as a connection. The single-chain variable fragment is the antigen binding domain of CAR, which determines the specificity and function of CAR-immune cells. The hinge region is the extracellular domain of the CAR that connects the single-chain variable fragment and the transmembrane domain. It generally maintains the stability required for robust CAR expression and activity in effector cells. The hinge region of most CARs is derived from the hinge of IgG or the extracellular region of CD8α / CD28. The type and length of the hinge region have a significant impact on the functional activity of the CAR. The transmembrane domain connects the extracellular domain of the CAR to the intracellular signaling domain. Commonly used transmembrane domains are derived from CD4, CD8, CD28, and CD3ζ or their derivatives. The choice of transmembrane domain influences the degree of activation of the CAR structure in cellular function. The intracellular domain consists of a costimulatory domain and a signaling domain. The costimulatory domain is typically derived from the CD28 receptor family (CD28, ICOS) or the tumor necrosis factor receptor family (4-1BB, OX40, CD27). The signaling domain is typically the T cell receptor TCR / CD3ζ chain or the immunoglobulin Fc receptor FcεRIγ chain.

[0087] The CAR of the present disclosure (including functional parts and functional variants thereof) can be obtained by methods known in the art, for example, can be prepared by any suitable method for preparing a polypeptide or protein.

[0088] In the present disclosure, the term "engineered immune cell" refers to an immune cell expressing CAR or an immune cell modified by CAR, wherein the immune cell includes but is not limited to T cells (e.g., α / β T cells and γ / δ T cells), natural killer cells (NK cells), monocytes, macrophages, NKT cells (Natural killer T cell), dendritic cells, granulocytes, B cells, lymphocytes, leukocytes and / or peripheral blood mononuclear cells.

[0089] In this disclosure, the term "nucleic acid molecule" refers to a polymeric form of nucleotides of any length, including ribonucleotides and / or deoxyribonucleotides. Examples of nucleic acid molecules include, but are not limited to, single-stranded, double-stranded, or multi-stranded DNA or RNA, genomic DNA, cDNA, DNA-RNA hybrids, or polymers comprising purine and pyrimidine bases or other natural, chemically or biochemically modified, non-natural, or derived nucleotide bases. When a nucleic acid molecule encodes a protein or polypeptide, the encoding may optionally encode a sense strand or an antisense strand. Nucleic acid molecules may be naturally occurring, synthetic, recombinant, or any combination thereof. "Nucleic acid molecule," "nucleic acid," and "polynucleotide" may be used interchangeably.

[0090] In alternative embodiments, the nucleic acid molecule is RNA or DNA. The nucleic acid molecule can be single-stranded or double-stranded, preferably double-stranded DNA. A nucleic acid molecule is "operably linked" when it is placed in a functional relationship with another nucleic acid sequence. For example, if a promoter or enhancer affects the transcription of a coding sequence, then the promoter or enhancer is operably linked to the coding sequence. When it is incorporated into a vector, DNA is preferably used.

[0091] In the present disclosure, the term "vector" refers to a vehicle into which a genetic element (e.g., the aforementioned nucleic acid molecule) can be operatively inserted and the genetic element can be expressed, for example, to produce a protein, RNA, or DNA encoded by the genetic element, or to replicate the genetic element. A vector can be used to transform, transduce, or transfect a host cell so that the genetic element it carries is expressed in the host cell. For example, vectors include: plasmids, phagemids, cosmids, artificial chromosomes such as yeast artificial chromosomes (YACs), bacterial artificial chromosomes (BACs), or P1-derived artificial chromosomes (PACs), bacteriophages such as lambda phage or M13 phage, and animal viruses. A vector can contain a variety of elements that control expression, including promoter sequences, transcription initiation sequences, enhancer sequences, selection elements, and reporter genes. In addition, a vector can also contain a replication initiation site. A vector can also include components that assist its entry into cells, including, but not limited to, viral particles, liposomes, or protein coats. A vector can be an expression vector or a cloning vector. In some embodiments, the vectors provided by the present disclosure (e.g., expression vectors) contain a nucleic acid sequence encoding an antibody or antigen-binding fragment thereof as described in the present disclosure, at least one promoter (e.g., SV40, CMV, EF-1α) operably linked to the nucleic acid sequence, and at least one selection marker.

[0092] In this disclosure, the term "purified" or "isolated" in connection with a polypeptide or nucleic acid means that the polypeptide or nucleic acid is not in its natural medium or natural form. Thus, the term "isolated" includes a polypeptide or nucleic acid removed from its original environment, e.g., if it is naturally occurring, from its natural environment. In connection with a nucleic acid, the term isolated or purified indicates, for example, that the nucleic acid is not in its natural genomic context (e.g., in a vector, as an expression cassette, linked to a promoter, or artificially introduced into a heterologous host cell).

[0093] In this disclosure, the term "recombinant cell" refers to a cell into which an exogenous polynucleotide and / or vector can be or has been introduced. The exogenous polynucleotide may or may not be integrated into the genome of the "recombinant cell." When the recombinant cell contains a vector, the vector can be introduced into a mammalian cell to construct a recombinant cell, which can then be used to express the antibodies or antigen-binding fragments provided herein. Culturing the recombinant cells can yield the corresponding antibodies. Examples of mammalian cells that can be used include CHO cells.

[0094] In the present disclosure, the term "pharmaceutical composition" refers to a composition that is in a form that allows the biological activity of the active ingredient to be effective and does not contain additional ingredients that are unacceptably toxic to the subject to which the composition is administered. In some specific embodiments, the antibody contained in the pharmaceutical composition or the expressed antibody can specifically target and bind to CDH17.

[0095] In the present disclosure, the term "binding to CDH17" includes binding to isolated CDH17 molecules and / or cells expressing CDH17.

[0096] In this disclosure, "pharmaceutically acceptable carrier" can include any solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like that are physiologically compatible.

[0097] In this disclosure, the term "subject" or "patient" refers to a mammalian subject or patient. Exemplary subjects include, but are not limited to, humans, monkeys, dogs, cats, mice, rats, cattle, horses, camels, birds, goats, and sheep. In certain embodiments, the subject is a human. In some embodiments, the subject is a human suspected of having cancer, an autoimmune disease or condition, and / or an infection.

[0098] In this disclosure, the term "diagnosis" refers to the identification of a pathological state, disease, or condition, such as the identification of a CDH17-related disease, or the identification of a subject with a CDH17-related disease who may benefit from a specific treatment regimen. In some embodiments, diagnosis comprises the identification of abnormal levels or activity of CDH17. In some embodiments, diagnosis refers to the identification of cancer or an autoimmune disease in a subject.

[0099] In this disclosure, a "CDH17-associated" disease, disorder, or condition refers to any disease or condition caused by, exacerbated by, or associated with an increase or decrease in the expression or activity of CDH17. In some embodiments, a CDH17-associated disease, disorder, or condition is a condition associated with excessive cell proliferation, such as cancer. In some embodiments, a CDH17-associated disease or condition is characterized by expression or overexpression of CDH17 and / or a CDH17-related gene.

[0100] In the present disclosure, the term "CDH17-expressing" cancer refers to cancers that express CDH17 in cancer cells or tumor-infiltrating immune cells or immunosuppressive cells, and the level of CDH17 expressed in cancer cells or tumor-infiltrating immune cells or immunosuppressive cells is significantly higher than the expected level in normal cells.

[0101] In the present disclosure, the term "effective amount" refers to a therapeutic amount, which is sufficient to reduce or improve the severity and / or duration of a condition or one or more symptoms thereof; prevent the progression of the disease; cause the disease to regress; prevent the recurrence, development or progression of one or more symptoms associated with the disease; detect the disease; or enhance or improve the prophylactic or therapeutic effect of another therapy (e.g., a prophylactic or therapeutic agent). The therapeutically effective dose of the antibody or antigen-binding fragment thereof described in the present disclosure depends on a variety of factors well known in the art, such as body weight, age, past medical history, current treatment, the health status of the subject and the potential for cross-infection, allergies, hypersensitivity and side effects, as well as the route of administration and the degree of tumor development. A person skilled in the art (e.g., a doctor or veterinarian) may proportionally reduce or increase the dose according to these or other conditions or requirements.

[0102] In a first aspect, an anti-CDH17 antibody or an antigen-binding fragment thereof is provided. The anti-CDH17 antibody or antigen-binding fragment thereof specifically binds to one or more of CDH17 extracellular domain 1 (D1), CDH17 extracellular domain 2 (D2), CDH17 extracellular domain 3 (D3), CDH17 extracellular domain 4 (D4), CDH17 extracellular domain 5 (D5), CDH17 extracellular domain 6 (D6), and CDH17 extracellular domain 7 (D7).

[0103] In an optional embodiment, the amino acid sequence of the extracellular region of CDH17 is shown in SEQ ID NO.597;

[0104] In an optional embodiment, the amino acid sequence of the extracellular domain 1 (D1) is as shown in amino acids 30 to 128 from the N-terminus to the C-terminus of CDH17.

[0105] In an optional embodiment, the amino acid sequence of the extracellular domain 2 (D2) is as shown in amino acids 129 to 244 from the N-terminus to the C-terminus of CDH17.

[0106] In an optional embodiment, the amino acid sequence of the extracellular domain 3 (D3) is as shown in amino acids 245 to 340 from the N-terminus to the C-terminus of CDH17.

[0107] In an optional embodiment, the amino acid sequence of the extracellular domain 4 (D4) is as shown in amino acids 341 to 449 from the N-terminus to the C-terminus of CDH17.

[0108] In an optional embodiment, the amino acid sequence of the extracellular domain 5 (D5) is as shown in amino acids 450 to 566 from the N-terminus to the C-terminus of CDH17.

[0109] In an optional embodiment, the amino acid sequence of the extracellular domain 6 (D6) is as shown in amino acids 567 to 667 from the N-terminus to the C-terminus of CDH17.

[0110] In an optional embodiment, the amino acid sequence of the extracellular domain 7 (D7) is as shown in amino acids 668 to 777 from the N-terminus to the C-terminus of CDH17.

[0111] In an optional embodiment, the anti-CDH17 antibody or its antigen-binding fragment specifically binds to one or more of CDH17 extracellular domain 1 (D1), CDH17 extracellular domain 2 (D2), CDH17 extracellular domain 3 (D3), CDH17 extracellular domain 4 (D4), CDH17 extracellular domain 5 (D5), CDH17 extracellular domain 6 (D6) or CDH17 extracellular domain 7 (D7).

[0112] In an optional embodiment, the anti-CDH17 antibody or its antigen-binding fragment specifically binds to one or more of CDH17 extracellular domain 1 (D1), CDH17 extracellular domain 2 (D2), CDH17 extracellular domain 3 (D3) and CDH17 extracellular domain 4 (D4).

[0113] In an optional embodiment, the anti-CDH17 antibody or antigen-binding fragment thereof specifically binds to one or more of CDH17 extracellular domain 5 (D5), CDH17 extracellular domain 6 (D6) and CDH17 extracellular domain 7 (D7).

[0114] In an optional embodiment, the antibody or antigen-binding fragment thereof contains the complementarity determining regions of the heavy chain variable region and / or the complementarity determining regions of the light chain variable region;

[0115] The complementarity determining regions of the heavy chain variable region include HCDR1, HCDR2 and HCDR3, and the complementarity determining regions of the light chain variable region include LCDR1, LCDR2 and LCDR3;

[0116] The HCDR1 comprises amino acid residue DY, amino acid residue EY, amino acid residue GY, amino acid residue NY, amino acid residue SG, amino acid residue SH, amino acid residue SY, amino acid residue TS or amino acid residue TY.

[0117] In an optional embodiment, according to the IMGT definition, the HCDR1 includes an amino acid sequence as shown in any one of SEQ ID NO. 45, 50, 54, 58, 63, 67, 72, 77, 81, 85, 90, 95, 100, 104, 107 and 113.

[0118] The HCDR2 comprises an amino acid sequence as shown in any one of SEQ ID NOs. 184-186, 188, 191-199, 202-205 and 208.

[0119] In an optional embodiment, according to the IMGT definition, the HCDR2 includes an amino acid sequence as shown in any one of SEQ ID NO. 121, 125, 129, 133, 137, 141, 145, 149, 153, 157, 162, 167, 171, 175, 179, 183, 189 and 190.

[0120] The HCDR3 comprises an amino acid sequence as shown in any one of SEQ ID NO. 209, 212, 215, 218, 221, 224, 227, 230, 233, 236, 239, 242, 245, 248, 251, 254, 257, 260 and 278.

[0121] In an optional embodiment, according to the IMGT definition, the HCDR3 includes an amino acid sequence as shown in any one of SEQ ID NO. 211, 214, 217, 220, 223, 226, 229, 232, 235, 238, 241, 244, 247, 250, 253, 256, 259, 262 and 266.

[0122] The LCDR1 includes amino acid residue NID, amino acid residue NNF, amino acid residue NNW, amino acid residue NY, amino acid residue SDF, amino acid residue SGY, amino acid residue SND, amino acid residue SSA or amino acid residue SY, or an amino acid sequence as shown in any one of SEQ ID NO. 290, 294, 299, 308, 319 and 332.

[0123] In an optional embodiment, according to the IMGT definition, the LCDR1 includes an amino acid sequence as shown in any one of SEQ ID NO. 286, 288, 292, 293, 296, 298, 301, 303, 305, 307, 310, 312, 321, 322 and 333.

[0124] The LCDR2 includes amino acid residue AA, amino acid residue DT, amino acid residue FA, amino acid residue GA, amino acid residue KV, amino acid residue RA, amino acid residue RT, amino acid residue SA, amino acid residue ST, amino acid residue WA, amino acid residue YA or amino acid residue YT.

[0125] In an optional embodiment, according to the IMGT definition, the LCDR2 includes amino acid residue AA, amino acid residue DT, amino acid residue FA, amino acid residue GA, amino acid residue KV, amino acid residue RA, amino acid residue RT, amino acid residue SA, amino acid residue ST, amino acid residue WA, amino acid residue YA or amino acid residue YT.

[0126] The LCDR3 comprises an amino acid sequence as shown in any one of SEQ ID NOs. 368, 370, 372, 374, 376, 378, 380, 382, ​​384, 386, 388, 390, 392, 394 and 396.

[0127] In an optional embodiment, according to the IMGT definition, the LCDR3 includes an amino acid sequence as shown in any one of SEQ ID NO. 369, 371, 373, 375, 377, 379, 381, 383, 385, 387, 389, 391, 393, 395 and 397.

[0128] In an optional embodiment, the complementarity determining region of the anti-CDH17 antibody or antigen-binding fragment thereof comprises any one of the following (a) to (t):

[0129] (a) HCDR1 comprises amino acid residues SY, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO. 185, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO. 209, LCDR1 comprises amino acid residues SND, LCDR2 comprises amino acid residues YA, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO. 386; or,

[0130] (b) HCDR1 comprises amino acid residues EY, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO. 192, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO. 278, LCDR1 comprises the amino acid sequence set forth in SEQ ID NO. 319, LCDR2 comprises amino acid residues WA, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO. 376; or,

[0131] (c) HCDR1 comprises amino acid residues SY, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO. 203, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO. 212, LCDR1 comprises amino acid residues NNF, LCDR2 comprises amino acid residues RT, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO. 378; or,

[0132] (d) HCDR1 comprises amino acid residue SY, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO. 196, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO. 215, LCDR1 comprises amino acid residue SY, LCDR2 comprises amino acid residue DT, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO. 372; or,

[0133] (e) HCDR1 comprises amino acid residues GY, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO.197, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO.218, LCDR1 comprises the amino acid sequence set forth in SEQ ID NO.332, LCDR2 comprises amino acid residues ST, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO.374; or,

[0134] (f) HCDR1 comprises the amino acid residue SH, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO. 208, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO. 221, LCDR1 comprises the amino acid sequence set forth in SEQ ID NO. 290, LCDR2 comprises the amino acid residue RA, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO. 394; or

[0135] (g) HCDR1 comprises amino acid residue TY, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO.191, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO.224, LCDR1 comprises the amino acid sequence set forth in SEQ ID NO.332, LCDR2 comprises amino acid residue ST, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO.374; or,

[0136] (h) HCDR1 comprises amino acid residues GY, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO.195, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO.227, LCDR1 comprises the amino acid sequence set forth in SEQ ID NO.294, LCDR2 comprises amino acid residues YA, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO.382; or,

[0137] (i) HCDR1 comprises amino acid residues SG, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO. 205, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO. 230, LCDR1 comprises amino acid residues SSA, LCDR2 comprises amino acid residues SA, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO. 392; or,

[0138] (j) HCDR1 comprises the amino acid residue TS, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO.186, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO.233, LCDR1 comprises the amino acid sequence set forth in SEQ ID NO.299, LCDR2 comprises the amino acid residue KV, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO.370; or,

[0139] (k) HCDR1 comprises amino acid residues EY, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO. 194, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO. 278, LCDR1 comprises the amino acid sequence set forth in SEQ ID NO. 319, LCDR2 comprises amino acid residues WA, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO. 376; or,

[0140] (1) HCDR1 comprises amino acid residue SY, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO. 199, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO. 236, LCDR1 comprises amino acid residue SY, LCDR2 comprises amino acid residue DT, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO. 368; or,

[0141] (m) HCDR1 comprises amino acid residues EY, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO. 194, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO. 239, LCDR1 comprises the amino acid sequence set forth in SEQ ID NO. 319, LCDR2 comprises amino acid residues WA, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO. 376; or,

[0142] (n) HCDR1 comprises amino acid residues DY, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO. 193, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO. 242, LCDR1 comprises amino acid residues NNW, LCDR2 comprises amino acid residues GA, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO. 396; or,

[0143] (o) HCDR1 comprises amino acid residue TY, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO. 202, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO. 245, LCDR1 comprises amino acid residue NY, LCDR2 comprises amino acid residue YT, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO. 388; or,

[0144] (p) HCDR1 comprises amino acid residues NY, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO. 198, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO. 248, LCDR1 comprises amino acid residues SDF, LCDR2 comprises amino acid residues YA, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO. 384; or,

[0145] (q) HCDR1 comprises amino acid residues TY, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO. 204, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO. 251, LCDR1 comprises amino acid residues SGY, LCDR2 comprises amino acid residues AA, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO. 380; or,

[0146] (r) HCDR1 comprises amino acid residues TY, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO. 204, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO. 254, LCDR1 comprises amino acid residues SGY, LCDR2 comprises amino acid residues AA, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO. 380; or,

[0147] (s) HCDR1 comprises amino acid residue NY, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO. 184, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO. 257, LCDR1 comprises the amino acid sequence set forth in SEQ ID NO. 308, LCDR2 comprises amino acid residue FA, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO. 382; or,

[0148] (t) HCDR1 comprises amino acid residues DY, HCDR2 comprises the amino acid sequence shown in SEQ ID NO.188, HCDR3 comprises the amino acid sequence shown in SEQ ID NO.260, LCDR1 comprises amino acid residues NID, LCDR2 comprises amino acid residues SA, and LCDR3 comprises the amino acid sequence shown in SEQ ID NO.390.

[0149] In an optional embodiment, according to the IMGT definition, the complementarity determining region of the anti-CDH17 antibody or antigen-binding fragment thereof includes any one of the following (a')-(t'):

[0150] (a') HCDR1 comprises the amino acid sequence set forth in SEQ ID NO.45, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO.121, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO.211, LCDR1 comprises the amino acid sequence set forth in SEQ ID NO.286, LCDR2 comprises amino acid residues YA, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO.387; or,

[0151] (b') HCDR1 comprises the amino acid sequence set forth in SEQ ID NO.113, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO.125, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO.266, LCDR1 comprises the amino acid sequence set forth in SEQ ID NO.322, LCDR2 comprises amino acid residue WA, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO.377; or,

[0152] (c') HCDR1 comprises the amino acid sequence set forth in SEQ ID NO.50, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO.129, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO.214, LCDR1 comprises the amino acid sequence set forth in SEQ ID NO.288, LCDR2 comprises amino acid residue RT, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO.379; or,

[0153] (d') HCDR1 comprises the amino acid sequence set forth in SEQ ID NO.54, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO.133, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO.217, LCDR1 comprises the amino acid sequence set forth in SEQ ID NO.333, LCDR2 comprises amino acid residue DT, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO.373; or,

[0154] (e') HCDR1 comprises the amino acid sequence set forth in SEQ ID NO.58, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO.137, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO.220, LCDR1 comprises the amino acid sequence set forth in SEQ ID NO.293, LCDR2 comprises amino acid residue ST, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO.375; or,

[0155] (f') HCDR1 comprises the amino acid sequence set forth in SEQ ID NO.63, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO.141, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO.223, LCDR1 comprises the amino acid sequence set forth in SEQ ID NO.292, LCDR2 comprises amino acid residue RA, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO.395; or,

[0156] (g') HCDR1 comprises the amino acid sequence set forth in SEQ ID NO.107, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO.145, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO.226, LCDR1 comprises the amino acid sequence set forth in SEQ ID NO.293, LCDR2 comprises amino acid residue ST, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO.375; or,

[0157] (h') HCDR1 comprises the amino acid sequence set forth in SEQ ID NO.67, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO.149, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO.229, LCDR1 comprises the amino acid sequence set forth in SEQ ID NO.296, LCDR2 comprises amino acid residues YA, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO.383; or,

[0158] (i') HCDR1 comprises the amino acid sequence set forth in SEQ ID NO.72, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO.153, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO.232, LCDR1 comprises the amino acid sequence set forth in SEQ ID NO.298, LCDR2 comprises amino acid residue SA, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO.393; or,

[0159] (j') HCDR1 comprises the amino acid sequence set forth in SEQ ID NO.77, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO.157, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO.235, LCDR1 comprises the amino acid sequence set forth in SEQ ID NO.301, LCDR2 comprises amino acid residues KV, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO.371; or,

[0160] (k') HCDR1 comprises the amino acid sequence set forth in SEQ ID NO.113, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO.189, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO.266, LCDR1 comprises the amino acid sequence set forth in SEQ ID NO.322, LCDR2 comprises amino acid residue WA, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO.377; or,

[0161] (1') HCDR1 comprises the amino acid sequence set forth in SEQ ID NO.81, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO.162, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO.238, LCDR1 comprises the amino acid sequence set forth in SEQ ID NO.333, LCDR2 comprises amino acid residue DT, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO.369; or,

[0162] (m') HCDR1 comprises the amino acid sequence set forth in SEQ ID NO.113, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO.189, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO.241, LCDR1 comprises the amino acid sequence set forth in SEQ ID NO.322, LCDR2 comprises amino acid residue WA, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO.377; or,

[0163] (n') HCDR1 comprises the amino acid sequence set forth in SEQ ID NO.85, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO.167, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO.244, LCDR1 comprises the amino acid sequence set forth in SEQ ID NO.303, LCDR2 comprises amino acid residue GA, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO.397; or,

[0164] (o') HCDR1 comprises the amino acid sequence set forth in SEQ ID NO.90, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO.171, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO.247, LCDR1 comprises the amino acid sequence set forth in SEQ ID NO.305, LCDR2 comprises amino acid residue YT, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO.389; or,

[0165] (p') HCDR1 comprises the amino acid sequence set forth in SEQ ID NO.95, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO.175, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO.250, LCDR1 comprises the amino acid sequence set forth in SEQ ID NO.307, LCDR2 comprises amino acid residues YA, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO.385; or,

[0166] (q') HCDR1 comprises the amino acid sequence set forth in SEQ ID NO.107, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO.190, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO.253, LCDR1 comprises the amino acid sequence set forth in SEQ ID NO.321, LCDR2 comprises amino acid residue AA, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO.381; or,

[0167] (r') HCDR1 comprises the amino acid sequence set forth in SEQ ID NO.107, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO.190, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO.256, LCDR1 comprises the amino acid sequence set forth in SEQ ID NO.321, LCDR2 comprises amino acid residue AA, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO.381; or,

[0168] (s') HCDR1 comprises the amino acid sequence set forth in SEQ ID NO.100, HCDR2 comprises the amino acid sequence set forth in SEQ ID NO.179, HCDR3 comprises the amino acid sequence set forth in SEQ ID NO.259, LCDR1 comprises the amino acid sequence set forth in SEQ ID NO.310, LCDR2 comprises amino acid residue FA, and LCDR3 comprises the amino acid sequence set forth in SEQ ID NO.383; or,

[0169] (t') HCDR1 includes the amino acid sequence shown in SEQ ID NO.104, HCDR2 includes the amino acid sequence shown in SEQ ID NO.183, HCDR3 includes the amino acid sequence shown in SEQ ID NO.262, LCDR1 includes the amino acid sequence shown in SEQ ID NO.312, LCDR2 includes amino acid residue SA, and LCDR3 includes the amino acid sequence shown in SEQ ID NO.391.

[0170] In an optional embodiment, the anti-CDH17 antibody or antigen-binding fragment thereof contains the complementarity determining regions HCDR1, HCDR2 and HCDR3 of the heavy chain variable region, and / or the complementarity determining regions LCDR1, LCDR2 and LCDR3 of the light chain variable region.

[0171] The HCDR1, HCDR2 and HCDR3 include amino acid sequences consistent with the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region shown in any one of SEQ ID NO.1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37 or 39.

[0172] The LCDR1, LCDR2 and LCDR3 include amino acid sequences consistent with the LCDR1, LCDR2 and LCDR3 of the light chain variable region shown in any one of SEQ ID NO. 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38 or 40.

[0173] The above-mentioned HCDR1, HCDR2 and HCDR3, and LCDR1, LCDR2 and LCDR3 are determined according to the Kabat definition, the Chothia definition, the AbM definition, the Contact definition or the IMGT definition.

[0174] In an optional embodiment, the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 of the anti-CDH17 antibody or antigen-binding fragment thereof can be independently selected from Tables 1 to 20.

[0175] Table 1 shows an exemplary antibody F1-41.16 (the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO. 1, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO. 2).

[0176] Table 1

[0177] Table 2 shows an exemplary antibody F1-87.15 (the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO. 3, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO. 4).

[0178] Table 2

[0179] Table 3 shows an exemplary antibody F1-111.5 (the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO. 5, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO. 6).

[0180] Table 3

[0181] Table 4 shows an exemplary antibody F1-143.7 (the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO. 7, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO. 8).

[0182] Table 4

[0183] Table 5 shows an exemplary antibody F2-55.10 (the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO. 9, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO. 10).

[0184] Table 5

[0185] Table 6 shows an exemplary antibody F2-155.7 (the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO. 11, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO. 12).

[0186] Table 6

[0187] Table 7 shows an exemplary antibody F2-186.1 (the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO. 13, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO. 14).

[0188] Table 7

[0189] Table 8 shows an exemplary antibody F2-238.14 (the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO. 15, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO. 16).

[0190] Table 8

[0191] Table 9 shows an exemplary antibody F2-324.7 (the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO. 17, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO. 18).

[0192] Table 9

[0193] Table 10 shows an exemplary antibody F3-1.5 (the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO. 19, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO. 20).

[0194] Table 10

[0195] Table 11 shows an exemplary antibody F1-76.12 (the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO. 21, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO. 22).

[0196] Table 11

[0197] Table 12 shows an exemplary antibody F1-86.9 (the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO. 23, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO. 24).

[0198] Table 12

[0199] Table 13 shows an exemplary antibody F1-99.29 (the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO. 25, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO. 26).

[0200] Table 13

[0201] Table 14 shows an exemplary antibody F1-124.38 (the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO. 27, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO. 28).

[0202] Table 14

[0203] Table 15 shows an exemplary antibody F1-127.8 (the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO. 29, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO. 30).

[0204] Table 15

[0205] Table 16 shows an exemplary antibody F2-71.18 (the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO. 31, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO. 32).

[0206] Table 16

[0207] Table 17 shows an exemplary antibody F2-89.7 (the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO. 33, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO. 34).

[0208] Table 17

[0209] Table 18 shows an exemplary antibody F2-291.2 (the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO. 35, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO. 36).

[0210] Table 18

[0211] Table 19 shows an exemplary antibody F3-6.18 (the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO. 37, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO. 38).

[0212] Table 19

[0213] Table 20 shows an exemplary antibody F3-36.14 (the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO. 39, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO. 40).

[0214] Table 20

[0215] In an optional embodiment, the above-mentioned anti-CDH17 antibody or its antigen-binding fragment contains a heavy chain framework region and / or a light chain framework region, and the above-mentioned heavy chain framework region and / or light chain framework region are derived from at least one of a murine antibody, a human antibody, a primate antibody or a mutant thereof.

[0216] In an optional embodiment, the three CDRs of the above-mentioned anti-CDH17 antibody or its antigen-binding fragment are separated by flanking portions called framework regions (FR, light chain FR includes LFR1, LFR2, LFR3 and LFR4, heavy chain FR includes HFR1, HFR2, HFR3 and HFR4).

[0217] In an optional embodiment, the HFR1 comprises an amino acid sequence as shown in any one of SEQ ID NOs. 398 to 415, or comprises a sequence having at least 78% (e.g., 78%, 80%, 82%, 85%, 87%, 89%, 90%, 91%, 92%, 93%, 95%, 97%, 98% or 99%) sequence identity to the amino acid sequence shown in any one of SEQ ID NOs. 398 to 415.

[0218] In an optional embodiment, the HFR2 comprises an amino acid sequence as shown in any one of SEQ ID NO. 416, 418, 422, 426, 428, 431, 433, 436, 439, 442 and 445-448, or comprises a sequence having at least 70% (e.g., 70%, 72%, 75%, 78%, 80%, 82%, 85%, 87%, 89%, 90%, 91%, 92%, 93%, 95%, 97%, 98% or 99%) sequence identity to the amino acid sequence shown in any one of SEQ ID NO. 416, 418, 422, 426, 428, 431, 433, 436, 439, 442 and 445-448.

[0219] In an optional embodiment, the HFR3 comprises an amino acid sequence as shown in any one of SEQ ID NO. 449, 451, 453, 455, 457, 459, 461, 463, 465, 467, 469, 472, 474, 477, 479, 481, 483, 485 and 487, or comprises an amino acid sequence as shown in any one of SEQ ID NO. Nos. 449, 451, 453, 455, 457, 459, 461, 463, 465, 467, 469, 472, 474, 477, 479, 481, 483, 485 and 487 have an amino acid sequence having at least 72% (e.g., 72%, 75%, 78%, 80%, 82%, 85%, 87%, 89%, 90%, 91%, 92%, 93%, 95%, 97%, 98% or 99%) sequence identity.

[0220] In an optional embodiment, the HFR4 comprises an amino acid sequence as shown in any one of SEQ ID NOs. 488 to 493, or comprises a sequence having at least 86% (e.g., 86%, 87%, 89%, 90%, 91%, 92%, 93%, 95%, 97%, 98% or 99%) sequence identity to the amino acid sequence shown in any one of SEQ ID NOs. 488 to 493.

[0221] In an optional embodiment, the LFR1 comprises an amino acid sequence as shown in any one of SEQ ID NO. 494, 496, 498, 500, 502, 504, 506, 508, 510, 512, 514, 516, 518, 520, 522, 524 and 526, or comprises an amino acid sequence as shown in any one of SEQ ID NO. The amino acid sequence shown in any one of NOs. 494, 496, 498, 500, 502, 504, 506, 508, 510, 512, 514, 516, 518, 520, 522, 524 and 526 has a sequence having at least 70% (e.g., 70%, 72%, 75%, 78%, 80%, 82%, 85%, 87%, 89%, 90%, 91%, 92%, 93%, 95%, 97%, 98% or 99%) sequence identity.

[0222] In an optional embodiment, the LFR2 includes an amino acid sequence as shown in any one of SEQ ID NO.528, 533, 535, 537, 539, 541, 543 and 549-552, or includes a sequence having at least 80% (e.g., 80%, 82%, 85%, 87%, 89%, 90%, 91%, 92%, 93%, 95%, 97%, 98% or 99%) sequence identity with the amino acid sequence shown in any one of SEQ ID NO.528, 533, 535, 537, 539, 541, 543 and 549-552.

[0223] In an optional embodiment, the LFR3 comprises an amino acid sequence as shown in any one of SEQ ID NO. 554, 556, 558, 560, 562, 564, 566, 568, 570, 572, 574, 576, 578, 580, 581 and 582, or comprises a sequence having at least 79% (e.g., 79%, 80%, 82%, 85%, 87%, 89%, 90%, 91%, 92%, 93%, 95%, 97%, 98% or 99%) sequence identity to the amino acid sequence shown in any one of SEQ ID NO. 554, 556, 558, 560, 562, 564, 566, 568, 570, 572, 574, 576, 578, 580, 581 and 582.

[0224] In an optional embodiment, the LFR4 includes an amino acid sequence as shown in any one of SEQ ID NOs. 586 to 590, or includes a sequence having at least 95% (e.g., 95%, 97%, 98% or 99%) sequence identity with the amino acid sequence shown in any one of SEQ ID NOs. 586 to 590.

[0225] In an optional embodiment, the HFR1 comprises the HFR1 of the heavy chain variable region shown in any one of SEQ ID NO. 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37 and 39.

[0226] In an optional embodiment, the HFR2 comprises the HFR2 of the heavy chain variable region shown in any one of SEQ ID NO. 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37 and 39.

[0227] In an optional embodiment, the HFR3 comprises the HFR3 of the heavy chain variable region shown in any one of SEQ ID NO. 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37 and 39.

[0228] In an optional embodiment, the HFR4 comprises the HFR4 of the heavy chain variable region shown in any one of SEQ ID NO. 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37 and 39.

[0229] In an optional embodiment, the LFR1 comprises the LFR1 of the light chain variable region shown in any one of SEQ ID NO. 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38 and 40.

[0230] In an optional embodiment, the LFR2 comprises the LFR2 of the light chain variable region shown in any one of SEQ ID NO. 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38 and 40.

[0231] In an optional embodiment, the LFR3 comprises the LFR3 of the light chain variable region shown in any one of SEQ ID NO. 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38 and 40.

[0232] In an optional embodiment, the LFR4 comprises the LFR4 of the light chain variable region shown in any one of SEQ ID NO. 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38 and 40.

[0233] In an optional embodiment, the HFR1, HFR2, HFR3 and HFR4 comprise the HFR1, HFR2, HFR3 and HFR4 of the heavy chain variable region shown in any one of SEQ ID NOs. 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37 and 39. The CDR regions are determined according to the Kabat definition, Chothia definition, AbM definition, Contact definition or IMGT definition in Tables 1 to 20, and the FR regions of the corresponding definition are obtained according to the structure of the heavy chain variable region.

[0234] Taking the IMGT definition as an example, the heavy chain framework region of the anti-CDH17 antibody or antigen-binding fragment thereof includes any one of the following (A)-(T):

[0235] (A) HFR1 comprises the amino acid sequence of SEQ ID NO. 414, HFR2 comprises the amino acid sequence of SEQ ID NO. 417, HFR3 comprises the amino acid sequence of SEQ ID NO. 450, and HFR4 comprises the amino acid sequence of SEQ ID NO. 490;

[0236] (B) HFR1 comprises the amino acid sequence of SEQ ID NO. 405, HFR2 comprises the amino acid sequence of SEQ ID NO. 444, HFR3 comprises the amino acid sequence of SEQ ID NO. 452, and HFR4 comprises the amino acid sequence of SEQ ID NO. 491;

[0237] (C) HFR1 comprises the amino acid sequence of SEQ ID NO. 399, HFR2 comprises the amino acid sequence of SEQ ID NO. 419, HFR3 comprises the amino acid sequence of SEQ ID NO. 454, and HFR4 comprises the amino acid sequence of SEQ ID NO. 491;

[0238] (D) HFR1 comprises the amino acid sequence of SEQ ID NO. 414, HFR2 comprises the amino acid sequence of SEQ ID NO. 420, HFR3 comprises the amino acid sequence of SEQ ID NO. 456, and HFR4 comprises the amino acid sequence of SEQ ID NO. 493;

[0239] (E) HFR1 comprises the amino acid sequence of SEQ ID NO. 404, HFR2 comprises the amino acid sequence of SEQ ID NO. 421, HFR3 comprises the amino acid sequence of SEQ ID NO. 458, and HFR4 comprises the amino acid sequence of SEQ ID NO. 492;

[0240] (F) HFR1 comprises the amino acid sequence of SEQ ID NO. 411, HFR2 comprises the amino acid sequence of SEQ ID NO. 423, HFR3 comprises the amino acid sequence of SEQ ID NO. 460, and HFR4 comprises the amino acid sequence of SEQ ID NO. 493;

[0241] (G) HFR1 comprises the amino acid sequence of SEQ ID NO. 407, HFR2 comprises the amino acid sequence of SEQ ID NO. 424, HFR3 comprises the amino acid sequence of SEQ ID NO. 462, and HFR4 comprises the amino acid sequence of SEQ ID NO. 493;

[0242] (H) HFR1 comprises the amino acid sequence of SEQ ID NO. 401, HFR2 comprises the amino acid sequence of SEQ ID NO. 425, HFR3 comprises the amino acid sequence of SEQ ID NO. 464, and HFR4 comprises the amino acid sequence of SEQ ID NO. 488;

[0243] (I) HFR1 comprises the amino acid sequence of SEQ ID NO. 409, HFR2 comprises the amino acid sequence of SEQ ID NO. 427, HFR3 comprises the amino acid sequence of SEQ ID NO. 466, and HFR4 comprises the amino acid sequence of SEQ ID NO. 491;

[0244] (J) HFR1 comprises the amino acid sequence of SEQ ID NO.415, HFR2 comprises the amino acid sequence of SEQ ID NO.429, HFR3 comprises the amino acid sequence of SEQ ID NO.468, and HFR4 comprises the amino acid sequence of SEQ ID NO.493;

[0245] (K) HFR1 comprises the amino acid sequence of SEQ ID NO. 403, HFR2 comprises the amino acid sequence of SEQ ID NO. 444, HFR3 comprises the amino acid sequence of SEQ ID NO. 470, and HFR4 comprises the amino acid sequence of SEQ ID NO. 491;

[0246] (L) HFR1 comprises the amino acid sequence of SEQ ID NO. 410, HFR2 comprises the amino acid sequence of SEQ ID NO. 430, HFR3 comprises the amino acid sequence of SEQ ID NO. 471, and HFR4 comprises the amino acid sequence of SEQ ID NO. 491;

[0247] (M) HFR1 comprises the amino acid sequence of SEQ ID NO. 406, HFR2 comprises the amino acid sequence of SEQ ID NO. 432, HFR3 comprises the amino acid sequence of SEQ ID NO. 473, and HFR4 comprises the amino acid sequence of SEQ ID NO. 491;

[0248] (N) HFR1 comprises the amino acid sequence of SEQ ID NO. 400, HFR2 comprises the amino acid sequence of SEQ ID NO. 434, HFR3 comprises the amino acid sequence of SEQ ID NO. 475, and HFR4 comprises the amino acid sequence of SEQ ID NO. 492;

[0249] (O) HFR1 comprises the amino acid sequence of SEQ ID NO. 412, HFR2 comprises the amino acid sequence of SEQ ID NO. 435, HFR3 comprises the amino acid sequence of SEQ ID NO. 476, and HFR4 comprises the amino acid sequence of SEQ ID NO. 492;

[0250] (P) HFR1 comprises the amino acid sequence of SEQ ID NO. 408, HFR2 comprises the amino acid sequence of SEQ ID NO. 437, HFR3 comprises the amino acid sequence of SEQ ID NO. 478, and HFR4 comprises the amino acid sequence of SEQ ID NO. 491;

[0251] (Q) HFR1 comprises the amino acid sequence of SEQ ID NO. 398, HFR2 comprises the amino acid sequence of SEQ ID NO. 438, HFR3 comprises the amino acid sequence of SEQ ID NO. 480, and HFR4 comprises the amino acid sequence of SEQ ID NO. 489;

[0252] (R) HFR1 comprises the amino acid sequence of SEQ ID NO. 398, HFR2 comprises the amino acid sequence of SEQ ID NO. 440, HFR3 comprises the amino acid sequence of SEQ ID NO. 482, and HFR4 comprises the amino acid sequence of SEQ ID NO. 493;

[0253] (S) HFR1 comprises the amino acid sequence of SEQ ID NO. 413, HFR2 comprises the amino acid sequence of SEQ ID NO. 441, HFR3 comprises the amino acid sequence of SEQ ID NO. 484, and HFR4 comprises the amino acid sequence of SEQ ID NO. 492;

[0254] (T) The HFR1 comprises the amino acid sequence shown in SEQ ID NO.402, HFR2 comprises the amino acid sequence shown in SEQ ID NO.443, HFR3 comprises the amino acid sequence shown in SEQ ID NO.486, and HFR4 comprises the amino acid sequence shown in SEQ ID NO.493.

[0255] In an optional embodiment, the LFR1, LFR2, LFR3 and LFR4 comprise the LFR1, LFR2, LFR3 and LFR4 of the light chain variable region shown in any one of SEQ ID NOs. 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38 and 40. The CDR regions are determined according to the Kabat definition, Chothia definition, AbM definition, Contact definition or IMGT definition in Tables 1 to 20, and the FR regions of the corresponding definition are obtained according to the structure of the light chain variable region.

[0256] Taking the IMGT definition as an example, the light chain framework region of an anti-CDH17 antibody or antigen-binding fragment thereof includes any one of the following (A')-(T'):

[0257] (A') the LFR1 comprises the amino acid sequence of SEQ ID NO.495, the LFR2 comprises the amino acid sequence of SEQ ID NO.553, the LFR3 comprises the amino acid sequence of SEQ ID NO.555, and the LFR4 comprises the amino acid sequence of SEQ ID NO.587;

[0258] (B') the LFR1 comprises the amino acid sequence of SEQ ID NO.527, the LFR2 comprises the amino acid sequence of SEQ ID NO.546, the LFR3 comprises the amino acid sequence of SEQ ID NO.585, and the LFR4 comprises the amino acid sequence of SEQ ID NO.587;

[0259] (C') the LFR1 comprises the amino acid sequence of SEQ ID NO.497, the LFR2 comprises the amino acid sequence of SEQ ID NO.529, the LFR3 comprises the amino acid sequence of SEQ ID NO.557, and the LFR4 comprises the amino acid sequence of SEQ ID NO.586;

[0260] (D') the LFR1 comprises the amino acid sequence of SEQ ID NO.499, the LFR2 comprises the amino acid sequence of SEQ ID NO.530, the LFR3 comprises the amino acid sequence of SEQ ID NO.559, and the LFR4 comprises the amino acid sequence of SEQ ID NO.587;

[0261] (E') the LFR1 comprises the amino acid sequence of SEQ ID NO. 501, the LFR2 comprises the amino acid sequence of SEQ ID NO. 547, the LFR3 comprises the amino acid sequence of SEQ ID NO. 583, and the LFR4 comprises the amino acid sequence of SEQ ID NO. 587;

[0262] (F') the LFR1 comprises the amino acid sequence of SEQ ID NO.525, the LFR2 comprises the amino acid sequence of SEQ ID NO.531, the LFR3 comprises the amino acid sequence of SEQ ID NO.561, and the LFR4 comprises the amino acid sequence of SEQ ID NO.588;

[0263] (G') the LFR1 comprises the amino acid sequence of SEQ ID NO. 503, the LFR2 comprises the amino acid sequence of SEQ ID NO. 547, the LFR3 comprises the amino acid sequence of SEQ ID NO. 583, and the LFR4 comprises the amino acid sequence of SEQ ID NO. 587;

[0264] (H') the LFR1 comprises the amino acid sequence of SEQ ID NO.505, the LFR2 comprises the amino acid sequence of SEQ ID NO.532, the LFR3 comprises the amino acid sequence of SEQ ID NO.563, and the LFR4 comprises the amino acid sequence of SEQ ID NO.587;

[0265] (I') the LFR1 comprises the amino acid sequence of SEQ ID NO.507, the LFR2 comprises the amino acid sequence of SEQ ID NO.534, the LFR3 comprises the amino acid sequence of SEQ ID NO.565, and the LFR4 comprises the amino acid sequence of SEQ ID NO.589;

[0266] (J') the LFR1 comprises the amino acid sequence of SEQ ID NO.509, the LFR2 comprises the amino acid sequence of SEQ ID NO.536, the LFR3 comprises the amino acid sequence of SEQ ID NO.567, and the LFR4 comprises the amino acid sequence of SEQ ID NO.587;

[0267] (K') the LFR1 comprises the amino acid sequence of SEQ ID NO.527, the LFR2 comprises the amino acid sequence of SEQ ID NO.546, the LFR3 comprises the amino acid sequence of SEQ ID NO.585, and the LFR4 comprises the amino acid sequence of SEQ ID NO.587;

[0268] (L') the LFR1 comprises the amino acid sequence of SEQ ID NO.511, the LFR2 comprises the amino acid sequence of SEQ ID NO.538, the LFR3 comprises the amino acid sequence of SEQ ID NO.569, and the LFR4 comprises the amino acid sequence of SEQ ID NO.589;

[0269] (M') the LFR1 comprises the amino acid sequence of SEQ ID NO.513, the LFR2 comprises the amino acid sequence of SEQ ID NO.546, the LFR3 comprises the amino acid sequence of SEQ ID NO.585, and the LFR4 comprises the amino acid sequence of SEQ ID NO.587;

[0270] (N') the LFR1 comprises the amino acid sequence of SEQ ID NO.515, the LFR2 comprises the amino acid sequence of SEQ ID NO.540, the LFR3 comprises the amino acid sequence of SEQ ID NO.571, and the LFR4 comprises the amino acid sequence of SEQ ID NO.590;

[0271] (O') the LFR1 comprises the amino acid sequence of SEQ ID NO.517, the LFR2 comprises the amino acid sequence of SEQ ID NO.542, the LFR3 comprises the amino acid sequence of SEQ ID NO.573, and the LFR4 comprises the amino acid sequence of SEQ ID NO.589;

[0272] (P') the LFR1 comprises the amino acid sequence shown in SEQ ID NO.519, the LFR2 comprises the amino acid sequence shown in SEQ ID NO.544, the LFR3 comprises the amino acid sequence shown in SEQ ID NO.575, and the LFR4 comprises the amino acid sequence shown in SEQ ID NO.587,

[0273] (Q') the LFR1 comprises the amino acid sequence of SEQ ID NO.523, the LFR2 comprises the amino acid sequence of SEQ ID NO.548, the LFR3 comprises the amino acid sequence of SEQ ID NO.584, and the LFR4 comprises the amino acid sequence of SEQ ID NO.587;

[0274] (R') the LFR1 comprises the amino acid sequence of SEQ ID NO.523, the LFR2 comprises the amino acid sequence of SEQ ID NO.548, the LFR3 comprises the amino acid sequence of SEQ ID NO.584, and the LFR4 comprises the amino acid sequence of SEQ ID NO.587;

[0275] (S') the LFR1 comprises the amino acid sequence of SEQ ID NO.525, the LFR2 comprises the amino acid sequence of SEQ ID NO.545, the LFR3 comprises the amino acid sequence of SEQ ID NO.577, and the LFR4 comprises the amino acid sequence of SEQ ID NO.587;

[0276] (T') The LFR1 comprises the amino acid sequence shown in SEQ ID NO.521, the LFR2 comprises the amino acid sequence shown in SEQ ID NO.553, the LFR3 comprises the amino acid sequence shown in SEQ ID NO.579, and the LFR4 comprises the amino acid sequence shown in SEQ ID NO.587.

[0277] In an optional embodiment, the above-mentioned anti-CDH17 antibody or its antigen-binding fragment has an amino acid sequence as shown in any one of SEQ ID NO.1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37 and 39, or a heavy chain variable region having at least 64% (e.g., 64%, 65%, 68%, 70%, 72%, 75%, 77%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity to the amino acid sequence shown in any one of SEQ ID NO.1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37 and 39.

[0278] In an optional embodiment, the above-mentioned anti-CDH17 antibody or its antigen-binding fragment has an amino acid sequence as shown in any one of SEQ ID NO. 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38 and 40, or a light chain variable region having at least 70% (e.g., 70%, 72%, 75%, 77%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity to the amino acid sequence shown in any one of SEQ ID NO. 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38 and 40.

[0279] In an optional embodiment, the anti-CDH17 antibody or antigen-binding fragment thereof comprises the heavy chain variable region and light chain variable region of any one of the following:

[0280] (a″) a heavy chain variable region having the amino acid sequence shown in SEQ ID NO.1; and a light chain variable region having the amino acid sequence shown in SEQ ID NO.2;

[0281] (b″) a heavy chain variable region having the amino acid sequence shown in SEQ ID NO. 3; and a light chain variable region having the amino acid sequence shown in SEQ ID NO. 4;

[0282] (c″) a heavy chain variable region having the amino acid sequence shown in SEQ ID NO. 5; and a light chain variable region having the amino acid sequence shown in SEQ ID NO. 6;

[0283] (d″) a heavy chain variable region having the amino acid sequence shown in SEQ ID NO. 7; and a light chain variable region having the amino acid sequence shown in SEQ ID NO. 8;

[0284] (e″) a heavy chain variable region having the amino acid sequence shown in SEQ ID NO.9; and a light chain variable region having the amino acid sequence shown in SEQ ID NO.10;

[0285] (f″) a heavy chain variable region having the amino acid sequence shown in SEQ ID NO.11; and a light chain variable region having the amino acid sequence shown in SEQ ID NO.12;

[0286] (g″) a heavy chain variable region having the amino acid sequence shown in SEQ ID NO. 13; and a light chain variable region having the amino acid sequence shown in SEQ ID NO. 14;

[0287] (h″) a heavy chain variable region having the amino acid sequence shown in SEQ ID NO. 15; and a light chain variable region having the amino acid sequence shown in SEQ ID NO. 16;

[0288] (i″) a heavy chain variable region having the amino acid sequence shown in SEQ ID NO. 17; and a light chain variable region having the amino acid sequence shown in SEQ ID NO. 18;

[0289] (j″) a heavy chain variable region having the amino acid sequence shown in SEQ ID NO. 19; and a light chain variable region having the amino acid sequence shown in SEQ ID NO. 20;

[0290] (k″) a heavy chain variable region having the amino acid sequence shown in SEQ ID NO. 21; and a light chain variable region having the amino acid sequence shown in SEQ ID NO. 22;

[0291] (1″) a heavy chain variable region having the amino acid sequence shown in SEQ ID NO. 23; and a light chain variable region having the amino acid sequence shown in SEQ ID NO. 24;

[0292] (m″) a heavy chain variable region having the amino acid sequence shown in SEQ ID NO. 25; and a light chain variable region having the amino acid sequence shown in SEQ ID NO. 26;

[0293] (n″) a heavy chain variable region having the amino acid sequence shown in SEQ ID NO. 27; and a light chain variable region having the amino acid sequence shown in SEQ ID NO. 28;

[0294] (o″) the heavy chain variable region of the amino acid sequence shown in SEQ ID NO.29; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.30;

[0295] (p″) the heavy chain variable region of the amino acid sequence shown in SEQ ID NO.31; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.32;

[0296] (q″) the heavy chain variable region of the amino acid sequence shown in SEQ ID NO. 33; and the light chain variable region of the amino acid sequence shown in SEQ ID NO. 34;

[0297] (r″) the heavy chain variable region of the amino acid sequence shown in SEQ ID NO. 35; and the light chain variable region of the amino acid sequence shown in SEQ ID NO. 36;

[0298] (s″) a heavy chain variable region having the amino acid sequence shown in SEQ ID NO. 37; and a light chain variable region having the amino acid sequence shown in SEQ ID NO. 38;

[0299] (t″) the heavy chain variable region of the amino acid sequence shown in SEQ ID NO. 39; and the light chain variable region of the amino acid sequence shown in SEQ ID NO. 40.

[0300] In an optional embodiment, the antigen-binding fragment includes one or more of F(ab')2, Fab', Fab, Fv, scFv, dsFv and the minimum recognition unit of an antibody.

[0301] In an optional embodiment, the anti-CDH17 antibody or antigen-binding fragment thereof comprises a partial or complete sequence of a constant region, wherein the constant region is derived from at least one of a murine antibody, a human antibody, a primate antibody, or a mutant thereof;

[0302] In an optional embodiment, the heavy chain constant region contains a sequence of part or all of the constant region of any one of IgG1, IgG2a, IgG2b, IgG3, IgG4, IgA, IgM, IgE or IgD.

[0303] In an optional embodiment, the heavy chain constant region contains a sequence of part or all of the constant region of IgG1, and the anti-CDH17 antibody or antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region of any one of the following:

[0304] (a″) a heavy chain variable region having the amino acid sequence shown in SEQ ID NO.1; and a light chain variable region having the amino acid sequence shown in SEQ ID NO.2;

[0305] (c″) a heavy chain variable region having the amino acid sequence shown in SEQ ID NO. 5; and a light chain variable region having the amino acid sequence shown in SEQ ID NO. 6;

[0306] (t″) the heavy chain variable region of the amino acid sequence shown in SEQ ID NO. 39; and the light chain variable region of the amino acid sequence shown in SEQ ID NO. 40.

[0307] In an optional embodiment, the heavy chain constant region contains a sequence of part or all of the constant region of IgG2a, and the anti-CDH17 antibody or antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region of any one of the following:

[0308] (d″) a heavy chain variable region having the amino acid sequence shown in SEQ ID NO. 7; and a light chain variable region having the amino acid sequence shown in SEQ ID NO. 8;

[0309] (f″) a heavy chain variable region having the amino acid sequence shown in SEQ ID NO.11; and a light chain variable region having the amino acid sequence shown in SEQ ID NO.12;

[0310] (g″) a heavy chain variable region having the amino acid sequence shown in SEQ ID NO. 13; and a light chain variable region having the amino acid sequence shown in SEQ ID NO. 14;

[0311] (i″) a heavy chain variable region having the amino acid sequence shown in SEQ ID NO. 17; and a light chain variable region having the amino acid sequence shown in SEQ ID NO. 18;

[0312] (j″) a heavy chain variable region having the amino acid sequence shown in SEQ ID NO. 19; and a light chain variable region having the amino acid sequence shown in SEQ ID NO. 20;

[0313] (n″) a heavy chain variable region having the amino acid sequence shown in SEQ ID NO. 27; and a light chain variable region having the amino acid sequence shown in SEQ ID NO. 28;

[0314] (o″) the heavy chain variable region of the amino acid sequence shown in SEQ ID NO.29; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.30;

[0315] (p″) the heavy chain variable region of the amino acid sequence shown in SEQ ID NO.31; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.32;

[0316] (q″) the heavy chain variable region of the amino acid sequence shown in SEQ ID NO. 33; and the light chain variable region of the amino acid sequence shown in SEQ ID NO. 34;

[0317] (r″) the heavy chain variable region of the amino acid sequence shown in SEQ ID NO. 35; and the light chain variable region of the amino acid sequence shown in SEQ ID NO. 36;

[0318] (s″) the heavy chain variable region of the amino acid sequence shown in SEQ ID NO. 37; and the light chain variable region of the amino acid sequence shown in SEQ ID NO. 38.

[0319] In an optional embodiment, the heavy chain constant region contains a sequence of part or all of the constant region of IgG2b, and the anti-CDH17 antibody or antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region of any one of the following:

[0320] (b″) a heavy chain variable region having the amino acid sequence shown in SEQ ID NO. 3; and a light chain variable region having the amino acid sequence shown in SEQ ID NO. 4;

[0321] (e″) a heavy chain variable region having the amino acid sequence shown in SEQ ID NO.9; and a light chain variable region having the amino acid sequence shown in SEQ ID NO.10;

[0322] (h″) a heavy chain variable region having the amino acid sequence shown in SEQ ID NO. 15; and a light chain variable region having the amino acid sequence shown in SEQ ID NO. 16;

[0323] (k″) a heavy chain variable region having the amino acid sequence shown in SEQ ID NO. 21; and a light chain variable region having the amino acid sequence shown in SEQ ID NO. 22;

[0324] (1″) a heavy chain variable region having the amino acid sequence shown in SEQ ID NO. 23; and a light chain variable region having the amino acid sequence shown in SEQ ID NO. 24;

[0325] (m″) the heavy chain variable region of the amino acid sequence shown in SEQ ID NO. 25; and the light chain variable region of the amino acid sequence shown in SEQ ID NO. 26.

[0326] In an alternative embodiment, the light chain constant region is a kappa or lambda chain.

[0327] In an optional embodiment, the constant region is derived from species comprising one or more of mice, rats, guinea pigs, hamsters, rabbits, ferrets, cats, dogs, goats, sheep, cows, pigs, horses, monkeys and humans.

[0328] In an optional embodiment, the anti-CDH17 antibody or antigen-binding fragment thereof has one or more of the following properties (i) to (iv):

[0329] (i) binds to human CDH17 with an EC50 of no more than 1 μg / mL (e.g., no more than 0.01 μg / mL, 0.02 μg / mL, 0.03 μg / mL, 0.04 μg / mL, 0.05 μg / mL, 0.06 μg / mL 0.07 μg / mL, 0.08 μg / mL, 0.09 μg / mL, 0.1 μg / mL, 0.2 μg / mL, 0.3 μg / mL, 0.4 μg / mL, 0.5 μg / mL, 0.6 μg / mL, 0.7 μg / mL, 0.8 μg / mL, 0.9 μg / mL or 1 μg / mL), as determined by flow cytometry fluorescence sorting. The determination method can be referred to in Example 2.

[0330] (ii) binds to monkey CDH17 with an EC50 of no more than 1 μg / mL (e.g., no more than 0.01 μg / mL, 0.02 μg / mL, 0.03 μg / mL, 0.04 μg / mL, 0.05 μg / mL, 0.06 μg / mL 0.07 μg / mL, 0.08 μg / mL, 0.09 μg / mL, 0.1 μg / mL, 0.2 μg / mL, 0.3 μg / mL, 0.4 μg / mL, 0.5 μg / mL, 0.6 μg / mL, 0.7 μg / mL, 0.8 μg / mL, 0.9 μg / mL or 1 μg / mL), as determined by ELISA. The assay method can be referred to in Example 3.

[0331] (iii) having ADCC activity (antibody-dependent cell-mediated cytotoxicity), which is detected by flow cytometry fluorescence sorting technology or lactate dehydrogenase cytotoxicity assay. The assay method can be referred to Example 5.

[0332] (iv) It has the activity of mediating cell endocytosis, and the activity of mediating cell endocytosis is detected by ELISA technology. The determination method can refer to Example 6.

[0333] In alternative embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof binds to or does not bind to murine CDH17.

[0334] In an optional embodiment, the CDH17 in (i) to (iii) above is an isolated CDH17 molecule or a cell expressing CDH17, and the cell includes but is not limited to a mammalian cell, such as a tumor cell.

[0335] The anti-CDH17 antibodies or antigen-binding fragments thereof provided in the first aspect can specifically bind to CDH17 protein, and in some embodiments can bind to CDH17 protein expressed by mammalian cells (e.g., CHO cells), or CDH17 endogenously expressed by tumor cells (e.g., AsPC-1 cells that endogenously express CDH17). The anti-CDH17 antibodies or antigen-binding fragments thereof provided in the first aspect have ADCC activity and can mediate cellular endocytosis, providing new possibilities for the treatment and / or prevention of cancer.

[0336] In a second aspect, the present disclosure provides an anti-CDH17 antibody or an antigen-binding fragment thereof, which competitively binds to CDH17 with the anti-CDH17 antibody described in the first or second aspect, or the epitope thereof that binds to the CDH17 antigen is the same as the epitope of the anti-CDH17 antibody described in the first or second aspect that binds to the CDH17 antigen.

[0337] In a third aspect, the present disclosure provides a multispecific antibody comprising any of the aforementioned anti-CDH17 antibodies or antigen-binding fragments thereof.

[0338] In an optional embodiment, the multispecific antibody further comprises an antibody or antigen-binding fragment thereof that specifically binds to other target molecules. Exemplary other target molecules include, but are not limited to, tumor surface antigens or immune checkpoints.

[0339] Exemplary tumor surface antigens include, but are not limited to, MUC16, VEGFR-2 (KDR / FIK-1), K-RAS, , CD2, CD3, CD19, CD19, CD20, CD21, CD22, CD30, CD32B, CD33, CD38, CD39, CD40, CD45, CD52, CD70, CD80, CD60, CD62, CD72, CD79a, CD79B, CD123, EGFR, HER2, HER3, HER4, GPC3, CLL1, TGF-beta, TGF-beta RII, VEGF, GD3, CCR4, CCR5, BCMA, CTLA4, mesothelin, and OX40.

[0340] Exemplary immune checkpoints include, but are not limited to, PD-1, PD-L1, PD-L2, TIGIT, CD47, CD27, CD28, CD40, CD122, CD137, CD94 / NKG2A, OX40, GITR, ICOS, A2AR, B7-H3, B7-H4, BTLA, LAG3, TIM-3, VISTA, GARP, PS, CSF1R, TDO, CTLA-4, IDO, KIR, GITR, TNFR, FasR / DcR, and CEACAM1.

[0341] In a fourth aspect, the present disclosure provides a chimeric antigen receptor (CAR), which includes an extracellular region, wherein the extracellular region includes an antigen binding domain; and the antigen binding domain contains the anti-CDH17 antibody or antigen binding fragment thereof shown in any of the aforementioned items.

[0342] In an optional embodiment, the anti-CDH17 antibody or antigen-binding fragment thereof in the chimeric antigen receptor is a single-chain antibody scFv.

[0343] In a fifth aspect, a nucleic acid molecule is provided, which encodes the anti-CDH17 antibody or antigen-binding fragment thereof of the first or second aspect, or the multispecific antibody of the third aspect, or the chimeric antigen receptor of the fourth aspect.

[0344] In an alternative embodiment, the nucleic acid molecule is an isolated nucleic acid molecule.

[0345] In a sixth aspect, a vector is provided, wherein the vector carries the nucleic acid molecule of the fifth aspect.

[0346] In a seventh aspect, the present disclosure provides a recombinant cell, which expresses the anti-CDH17 antibody or antigen-binding fragment thereof of the first or second aspect, or expresses the multispecific antibody of the third aspect, or expresses the chimeric antigen receptor of the fourth aspect, or contains the nucleic acid molecule of the fifth aspect, or contains the vector of the sixth aspect.

[0347] In an eighth aspect, the present disclosure provides an engineered immune cell, which expresses the chimeric antigen receptor of the fourth aspect or contains a nucleic acid molecule encoding the chimeric antigen receptor of the fourth aspect.

[0348] In the ninth aspect, the present disclosure provides a pharmaceutical composition containing the anti-CDH17 antibody or antigen-binding fragment thereof of the first or second aspect, or the multispecific antibody of the third aspect, or the chimeric antigen receptor of the fourth aspect, or the nucleic acid molecule of the fifth aspect, or the vector of the sixth aspect, or the recombinant cell of the seventh aspect, or the engineered immune cell of the eighth aspect.

[0349] In an optional embodiment, the pharmaceutical composition further comprises a pharmaceutically acceptable carrier and / or excipient. The acceptable carrier and pharmaceutically acceptable excipient may be any conventional carrier and / or excipient known in the art. Examples of carriers include, but are not limited to, any physiologically compatible solvent, dispersion medium, coating, antibacterial and antifungal agents, isotonic and absorption-delaying agents, and the like; examples of excipients include, but are not limited to, fillers, disintegrants, preservatives, solubilizers, and emulsifiers.

[0350] In an optional embodiment, the pharmaceutical composition further comprises one or more active pharmaceutical ingredients having other therapeutic effects, including but not limited to one or more combinations of chemotherapeutic agents, anticancer drugs, radiotherapeutic agents, immunotherapeutic agents, anti-angiogenic agents, targeted therapeutic agents, cell therapeutic agents, gene therapeutic agents, hormone therapeutic agents, antiviral agents, antibiotics, analgesics, antioxidants, metal chelators and cytokines.

[0351] In an optional embodiment, the pharmaceutical composition is used as a drug for treating, preventing or alleviating a disease, disorder or condition associated with CDH17.

[0352] In a tenth aspect, the present disclosure provides use of the anti-CDH17 antibody or antigen-binding fragment thereof of the first or second aspect, or the multispecific antibody of the third aspect, or the chimeric antigen receptor of the fourth aspect, or the nucleic acid molecule of the fifth aspect, or the vector of the sixth aspect, or the recombinant cell of the seventh aspect, or the engineered immune cell of the eighth aspect, or the pharmaceutical composition of the ninth aspect in any of the following:

[0353] (I) Detection of CDH17 or cells expressing CDH17;

[0354] (II) preparing products for detecting CDH17 or cells expressing CDH17;

[0355] (III) for treating, preventing or alleviating diseases, disorders or conditions associated with CDH17

[0356] (IV) Preparing a pharmaceutical composition for treating, preventing or alleviating a disease, disorder or condition associated with CDH17.

[0357] In an optional embodiment, the application of aspect (I) above can utilize anti-CDH17 antibodies or their antigen-binding fragments to specifically target and bind to CDH17, and detect CDH17 or cells expressing CDH17 based on immunoassay technology. For example, when the antibody or its antigen-binding fragment chain is an immunoconjugate, for example, it is connected to a fluorescent group, and a fluorescence detection device can be used to achieve the positioning or real-time detection of CDH17. For example, it can be used for immunoblotting, immunoprecipitation or flow cytometry, etc., which involve the use of the specific binding properties of CDH17 antigen and antibody to detect CDH17 or cells expressing CDH17. Accordingly, in aspect (II) above, those skilled in the art can select the reagent composition in the kit according to the actual detection method, including but not limited to antagonists, anti-CDH17 antibodies or drug reference materials; protein purification columns; immunoglobulin affinity purification buffers; cell assay diluents; instructions or literature, etc. The kit can also be used to detect diseases, diseases or conditions related to CDH17.

[0358] In an optional embodiment, the application of aspect (I) above is for non-diagnostic and non-therapeutic purposes.

[0359] In an alternative embodiment, the method for treating, preventing or alleviating a disease, disorder or condition associated with CDH17 comprises administering to a subject a therapeutically effective amount of the aforementioned anti-CDH17 antibody or antigen-binding fragment thereof and / or the aforementioned pharmaceutical composition.

[0360] In an eleventh aspect, the present disclosure provides a method for producing the aforementioned anti-CDH17 antibody or an antigen-binding fragment thereof, comprising the following steps:

[0361] (a) culturing the aforementioned recombinant cell under conditions for expressing an anti-CDH17 antibody or an antigen-binding fragment thereof;

[0362] (b) isolating and purifying the anti-CDH17 antibody or antigen-binding fragment thereof obtained in step (a).

[0363] In an alternative embodiment, the "CDH17-related" disease, disorder or condition in any of the above aspects comprises: a solid tumor or a hematological tumor.

[0364] In alternative embodiments, a "CDH17-associated" disease, disorder or condition is characterized by overexpression of CDH17.

[0365] In an optional embodiment, the solid tumor involved in any of the above-mentioned diseases, disorders or conditions includes one or more of the following groups: gastric cancer, colorectal cancer, pancreatic cancer, liver cancer, breast cancer, lung cancer, colon cancer, bladder cancer, thyroid cancer, skin cancer, esophageal cancer and cervical cancer.

[0366] In an optional embodiment, the blood tumor involved in any of the above-mentioned diseases, disorders or conditions includes one or more of the following groups: chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), multiple myeloma and T or B cell lymphoma.

[0367] In alternative embodiments, the antibodies, antigen-binding fragments, or pharmaceutical compositions described herein can be administered at a therapeutically effective dose of between about 0.001 mg / kg and about 1000 mg / kg. In some embodiments, the dosage can vary over the course of treatment. For example, in some embodiments, the initial dosage can be higher than subsequent dosages. In some embodiments, the dosage is adjusted over the course of treatment based on the subject's response.

[0368] In an optional embodiment, the antibodies or antigen-binding fragments thereof or pharmaceutical compositions disclosed in the present disclosure can be administered alone or in combination with a therapeutically effective amount of a second therapeutic agent. For example, the antibodies or antigen-binding fragments thereof or pharmaceutical compositions disclosed in the present disclosure can be administered in combination with a second therapeutic agent (e.g., a chemotherapeutic agent, an anticancer agent, a radiotherapeutic agent, an immunotherapeutic agent, an anti-angiogenic agent, a targeted therapy agent, a cell therapy agent, a gene therapy agent, a hormone therapy agent, an antiviral agent, an antibiotic, an analgesic, an antioxidant, a metal chelator or a cytokine).

[0369] In an optional embodiment, the antibodies or antigen-binding fragments thereof or pharmaceutical compositions disclosed herein, when used in combination with one or more additional therapeutic agents, may be administered simultaneously with the one or more additional therapeutic agents. In certain such embodiments, the antibodies or antigen-binding fragments thereof and the additional therapeutic agents may be administered simultaneously as part of the same composition. However, antibodies or antigen-binding fragments thereof or pharmaceutical compositions "used in combination" with other therapeutic agents do not need to be administered simultaneously or in the same composition as the therapeutic agents. The meaning of "used in combination" in the present disclosure also includes that antibodies or antigen-binding fragments thereof or pharmaceutical compositions administered before or after another therapeutic agent are also considered to be "used in combination" with the therapeutic agent, that is, the antibodies or antigen-binding fragments thereof or pharmaceutical compositions and the second substance are administered by different administration methods.

[0370] In a twelfth aspect, the present disclosure provides a kit for detecting CDH17, comprising the aforementioned anti-CDH17 antibody or an antigen-binding fragment thereof.

[0371] In an optional embodiment, the product of any of the above aspects, such as but not limited to the anti-CDH17 antibody or antigen-binding fragment thereof in the reagent, kit, blocking agent and pharmaceutical composition is conjugated with at least one diagnostic agent and / or therapeutic agent to form an immunoconjugate.

[0372] The diagnostic agent includes one or more of a radioactive contrast agent, a paramagnetic ion, a metal, a fluorescent marker, a chemiluminescent marker, an ultrasound contrast agent, and a photosensitizer;

[0373] The therapeutic agent includes one or more of a cytotoxic agent, a drug, a radionuclide, a boron atom, an immunomodulator, an anti-apoptotic agent, a photosensitizing therapeutic agent, an immunoconjugate, and an oligonucleotide.

[0374] Radionuclides include but are not limited to 110 In, 111 In, 177 Lu, 18 F. 52 Fe, 62 Cu, 64 Cu, 67 Cu, 67 Ga, 68 Ga, 86 Y. 90 Y. 89 Zr, 94 mTc, 94 Tc, 99 mTc, 120 I. 123 I. 124 I. 125 I. 131 I.154-158 Gd, 32 P. 11 C. 13 N. 15 O. 186 Re、 188 Re、 51 Mn, 52 mMn, 55 Co、 72 As、 75 Br, 76 Br, 82 mRb and 83 One or more of Sr.

[0375] Paramagnetic ions include, but are not limited to, one or more of chromium (III), manganese (II), iron (III), iron (II), cobalt (II), nickel (II), copper (II), neodymium (III), samarium (III), ytterbium (III), gadolinium (III), vanadium (II), terbium (III), dysprosium (III), holmium (III), and erbium (III).

[0376] Fluorescent labels include, but are not limited to, Alexa 350, Alexa 405, Alexa 430, Alexa 488, Alexa 555, Alexa 647, AMCA, aminoacridine, BODIPY630 / 650, BODIPY650 / 665, BODIPY-FL, BODIPY-R6G, BODIPY-TMR, BODIPY-TRX, 5-carboxy-4′,5′-dichloro-2′,7′-dimethoxyfluorescein, 5-carboxy-2′,4′,5′,7′-tetrachlorofluorescein, 5-carboxyfluorescein, 5-carboxyrhodamine, 6-carboxyrhodamine, 6-carboxytetramethylrhodamine, Cascade Blue, Cy2, Cy3, Cy5, Cy7, 6-FAM, dansyl chloride, fluorescein, HEX, 6-JOE, NBD (7-nitrobenz-2-oxa-1,3-diazole), Oregon Green 488, Oregon Green 500, Oregon Green 514, Pacific Blue, phthalic acid, terephthalic acid, isophthalic acid, cresol fast violet, cresol blue violet, brilliant cresol blue, p-aminobenzoic acid, erythrosine, phthalocyanine, azomethine, cyanine, xanthine, succinylfluorescein, rare earth metal cryptates, europium trisbipyridyldiamine, europium cryptates or chelates, diamines, bis-anthocyanin, La Jolla blue dye, allophycocyanin, allococyanin B, one or more of phycocyanin C, phycocyanin R, thiamine, phycoerythrin, phycoerythrin R, REG, rhodamine green, rhodamine isothiocyanate, rhodamine red, ROX, TAMRA, TET, TRIT (tetramethylrhodamine isothiol), tetramethylrhodamine, and Texas Red.

[0377] Oligonucleotides include, but are not limited to, one or more of shRNA, miRNA, and siRNA.

[0378] Drugs include, but are not limited to, methotrexate, fluorouracil, mercaptopurine, hydroxyurea, cytarabine, nitrogen mustard, cyclophosphamide, thiotepa, cisplatin, mitomycin, bleomycin, camptothecin, podophyllotoxin, actinomycin D, doxorubicin, daunorubicin, vinblastine, paclitaxel, cephalotaxel alkaloids, and L-asparaginase.

[0379] Immunomodulators include, but are not limited to, one or more of cytokines, chemokines, stem cell growth factors, lymphotoxins, hematopoietic factors, colony stimulating factors (CSFs), interferons, erythropoietins, thrombopoietins, tumor necrosis factors (TNFs), interleukins (ILs), granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), and stem cell growth factors.

[0380] Radionuclides include but are not limited to 111 In, 111 At 177 Lu, 211 Bi, 212 Bi, 213 Bi, 211 At 62 Cu, 67 Cu, 90 Y. 125 I. 131 I. 133 I. 32 P. 33 P. 47 Sc, 111 Ag, 67 Ga, 153 Sm, 161 Tb, 152 Dy, 166 Dy, 161 Ho, 166 Ho, 186 Re、 188 Re、 189 Re、 211 Pb, 212 Pb, 223 Ra, 225 Ac, 77 As、 89 Sr. 99 Mo, 105 Rh, 149 Pm, 169 Second, 194 Ir, 58 Co、 80 mBr, 99 mTc, 103 mRh, 109 Pt, 119 Sb, 189 mOs, 192 Ir, 219 Rn, 215 Po, 221 Fr, 255 Fm, 11 C. 13 N. 15 O. 75 Br, 198 Au, 199 Au, 224 Ac, 77 Br, 113 mIn、 95 Such as 97 Such as103 Such as 105 Such as 107 Hg, 203 Hg, 121 mTe, 122 mTe, 125 mTe, 165 Tm, 167 Tm, 168 Tm, 197 Pt, 109 Pd, 142 Pr, 143 Pr, 161 Tb, 57 Co、 58 Co、 51 Cr, 59 Fe, 75 Se, 201 Tl, 76 Br and 169 One or more of Yb.

[0381] The present disclosure is further illustrated below through specific examples. However, it should be understood that these examples are only used for more detailed description and should not be understood as limiting the present disclosure in any form.

[0382] Example 1. Generation of mouse antibodies against CDH17

[0383] 1. Material Preparation

[0384] To generate cells stably expressing human CDH17, CHO cells were transfected with a vector encoding human CDH17 (SEQ ID NO. 591). The CDH17-targeting antibody (Boehringer-Ingelheim) R2800 (sequence from patent CN110582513A, heavy chain variable region amino acid sequence shown as SEQ ID NO. 592, light chain variable region amino acid sequence shown as SEQ ID NO. 593) was then used as a positive control. Stable cell lines were screened using flow cytometry using CHO cells as a negative control. A eukaryotic expression vector encoding a fragment of the human CDH17 extracellular domain (SEQ ID NO. 594, SEQ ID NO. 595, SEQ ID NO. 596) was constructed and used to transiently transfect HEK293 cells to express the purified immunogen and screening proteins. A schematic diagram of the structural relationship between human CDH17 and the extracellular region fragment of human CDH17 (i.e., human CDH17 ECD) is shown in Figure 2 , wherein human CDH17 ECD includes a total of 7 domains, D1-D7 (also referred to as EC1-EC7), and the structure of CDH17 ECD is shown in Figure 1 .

[0385] The amino acid sequence of human CDH17 is shown in SEQ ID NO. 591 (only the underlined portion is the AAL sequence, only the bold portion is the D1-D4 domain of human CDH17, the bold and underlined portion is the D5-D7 domain of human CDH17, the italicized portion is the transmembrane region of human CDH17, and the italicized and underlined portion is the intracellular region of human CDH17):

[0386] mFc-tagged human CDH17 ECD, the amino acid sequence is shown in SEQ ID NO. 594 (only the underlined portion is the AAL sequence, only the bold portion is the human CDH17 ECD, and only the underlined portion is the mFc tag):

[0387] His-tagged human CDH17 ECD, the amino acid sequence is shown in SEQ ID NO. 595 (only the underlined portion is the AAL sequence, only the bold portion is the human CDH17 ECD, and only the underlined portion is the His tag):

[0388] His-tagged human CDH17 (D5-D7), the amino acid sequence is shown in SEQ ID NO. 596 (only the bold portion is the human CDH17 D5-D7 domain, and only the underlined portion is the His tag):

[0389] 2. Immunity

[0390] Mice immunization was performed according to the following immunization schedule (Table 21).

[0391] Female BALB / c mice, 5 to 8 weeks old, were immunized weekly, with the first immunization administered subcutaneously and the subsequent immunizations administered intraperitoneally. The immunogen was R2426 (amino acid sequence shown in SEQ ID NO. 594). The immunization strategy is shown in Table 21.

[0392] Table 21: Immunization scheme for generating monoclonal antibodies

[0393] 3. Generation of hybridomas producing mouse monoclonal antibodies against CDH17

[0394] The target mice were given an immune booster to recover and expand sufficient sp2 / mIL6 myeloma cells in advance to ensure cell number and viability. Twelve feeding mice were sacrificed 3 days in advance, and the peritoneal suspension was removed and spread over 96-well plates as feeding fusion plates, with 150 μL per well. Mouse spleen cells were isolated according to standard protocols and 5×10 6 / plate, 3.1×106 / plate, 4.4×10 6 The cells were mixed with mouse myeloma cells at a 1:1 ratio. The cells were fused using an electrofusion instrument and added to feeder fusion plates in a 50 μL volume. The cells were then placed in an incubator (Panasonic MCO-18AIC) at 37°C with 5% CO2. Six days after electrofusion, the old medium in the fusion plates was aspirated and 200 μL of fresh medium was added to each well. On day 7, the supernatant was collected for hCDH17-his (SEQ ID NO. 595) ELISA binding assay. Positive wells were identified based on the results and sterilely replaced with 200 μL of medium. On day 8 after electrofusion, 100 μL of the culture supernatant was collected for hCDH17(D5-D7)-his (SEQ ID NO. 596) ELISA binding screening. On day 9 after electrofusion, the culture supernatant was collected for AsPC-1 flow cytometry binding assay, and on day 12 after electrofusion, the culture supernatant was collected for CHO-hCDH17 flow cytometry binding screening. The positive pool was selected for subcloning based on the comprehensive screening results. Then, at least one clone that retained the reactivity of the parental mother cell (determined by FACS) was selected from the hybridomas cultured in vitro. 9-20 tubes were generated for each clone and stored in liquid nitrogen.

[0395] 4. Selection of monoclonal antibodies that bind to CDH17

[0396] We performed isotype ELISA assays to determine the antibody isotype. The Ig subclass of the identified CDH17-reactive monoclonal antibodies was determined using a Mouse Monoclonal Antibody Ig Class / Subclass Identification ELISA Kit (IgG1, IgG2a, IgG2b, IgG3, IgM, IgA) (Biolon, Cat# BF06001). The isotypes of the antibodies generated are shown in Table 22, the amino acid sequences of the variable regions are shown in Table 23, and the CDR regions of each antibody are shown in Tables 1 to 20.

[0397] Table 22. Mouse monoclonal antibody subtypes

[0398] The amino acid sequences of the variable regions are shown in the following table:

[0399] Table 23 Variable region amino acid sequence

[0400] 5. Production of Monoclonal Antibodies

[0401] 2×10 6Hybridoma cells were inoculated into a dialysis-based bioreactor at a concentration of 10 cells / ml and the antibody-containing supernatant was harvested weekly. Mouse monoclonal antibodies were purified using Protein A (GE-MabSelectSuRe LX, Cat# 17-5438-03) using FPLC. Antibody concentration was determined by BCA kit or A280 absorbance, and antibody purity was determined by SEC (size exclusion chromatography) and checked by SDS (sodium dodecyl sulfate) gel electrophoresis and Coomassie brilliant blue staining.

[0402] Example 2. Binding characteristics of monoclonal antibodies against CDH17

[0403] We used flow cytometry to assay the binding activity of monoclonal antibodies to CHO-CDH17 and AsPC-1 cells, which express human CDH17 and are overexpressed in CHO-CDH17 cells and endogenously express CDH17 in AsPC-1 cells.

[0404] 1. CHO-CDH17 cell binding

[0405] Cultivate enough CHO-CDH17 cells and collect them by centrifugation. Dilute the monoclonal antibody and the corresponding positive antibody with PBS + 3% FBS, starting from 10 μg / mL, and dilute them 3-fold or 4-fold to obtain 8 concentration gradients for later use. Wash the collected cells with PBS + 3% FBS and resuspend them in PBS + 3% FBS to 2 × 10 6 Cells were plated in 96-well plates, with 100 μL (2×10 5 Cells were collected and 100 μL of diluted antibody was added. The cells were incubated at 4°C for 30 minutes. The supernatant was removed by centrifugation, and the cells were washed twice with PBS. The cells were then resuspended with diluted PE-labeled anti-mouse IgG FC antibody (Biolegend, 405307). The cells were incubated at 4°C in the dark for 30 minutes. The cells were washed twice with PBS and resuspended with 100 μL of PBS. The cells were detected on a microscope. The mean fluorescence intensity was used to analyze the EC50 value of the binding affinity between the antibody and CHO-CDH17 using GraphPad Prism 7.0 software. The results are shown in Figures 3, 4, and 5. Most monoclonal antibodies have excellent binding to CHO-hCDH17. R2800 is a positive control antibody, the heavy chain amino acid sequence is shown in SEQ ID NO.592, and the light chain amino acid sequence is shown in SEQ ID NO.593 (as shown in Table 23). mIgG2a is a negative control antibody.

[0406] 2. AsPC-1 cell binding

[0407] Flow cytometry was used to detect the binding activity of monoclonal antibodies to AsPC-1 cells. After digesting the cells with Versene solution (Gibco, 15040066), the cells were collected by centrifugation and set aside. The antibody was incubated with cells in 8 concentration gradients, starting from 10 μg / mL or 20 μg / mL, with 3-fold or 4-fold serial dilutions. The subsequent experimental process was the same as the CHO-CDH17 cell binding experiment. The cells were resuspended in 100 μL PBS and detected on the flow cytometer. The EC50 value of the binding affinity of the antibody to AsPC-1 cells was calculated by analyzing the mean fluorescence intensity using GraphPad Prism 7.0 software.

[0408] The results are shown in Figures 6, 7 and 8. All 20 mouse monoclonal antibodies bind well to AsPC-1.

[0409] Example 3. Detection of binding activity of monoclonal antibodies to monkey CDH17

[0410] This example detects the binding activity of a monoclonal antibody to monkey CDH17 (Acrobiosystem). Dilute the Cyno.CDH17 recombinant protein (monkey CDH17) to 0.5 μg / mL in advance with 50 mmol Coating Buffer, add 100 μL per well, and incubate at 4°C overnight. Discard the supernatant, wash the plate three times with 1×PBST buffer, then add 100 μL / well of PBS + 1% FBS and block at 37°C for 1 hour. Simultaneously, dilute the monoclonal antibody to the corresponding positive control R2800 with PBS + 1% FBS, starting at 10 μg / mL and diluting 4-fold to obtain 8 concentration gradients for later use. After blocking, the supernatant was discarded, 100 μL of diluted antibody was added, and the plate was incubated at 37°C for 1 hour. After the incubation, the plate was washed four times with 1×PBST buffer, and 100 μL / well of diluted HRP-conjugated anti-mouse IgG c antibody (Sigma, A0168) was added and incubated at 37°C for 30 minutes. After the incubation, the plate was washed five times with 1×PBST buffer. The color development solution was added and the color development was stopped after appropriate color development. The value was read by a microplate reader, and the EC50 value of the antibody binding to the Cyno.CDH17 recombinant protein was calculated by analyzing the software GraphPadPrism 7.0 at OD450nm.

[0411] The results are shown in Figures 9 and 10. The control antibody R2800 did not bind to monkey CDH17. Except for a few with slightly poor binding activity, all the mouse monoclonal antibodies had good binding to monkey CDH17.

[0412] Example 4. Detection of binding activity of monoclonal antibodies to mouse CDH17

[0413] We tested the binding activity of monoclonal antibodies to mouse CDH17. mCDH17 recombinant protein (mouse CDH17) was diluted to 0.5 μg / mL in 50 mmol Coating Buffer in advance, with 100 μL per well incubated at 4°C overnight. The supernatant was discarded, and the plate was washed three times with 1× PBST buffer. Then, 100 μL / well of PBS + 1% FBS was added and the plate was blocked at 37°C for 1 hour. Simultaneously, the monoclonal antibody and the corresponding positive control R2800 were diluted in PBS + 1% FBS, starting at 10 μg / mL and serially diluted 4-fold to obtain eight concentration gradients for later use. After blocking, the supernatant was discarded, 100 μL of diluted antibody was added, and the plate was incubated at 37°C for 1 hour. After the incubation, the plate was washed four times with 1×PBST buffer, and 100 μL / well of diluted HRP-conjugated anti-mouse IgG c antibody (Sigma, A0168) was added and incubated at 37°C for 30 minutes. After the incubation, the plate was washed five times with 1×PBST buffer, and the color development solution was added to develop the color appropriately, and the color development was stopped. The value was read by a microplate reader, and the EC50 value of the antibody binding to the mCDH17 recombinant protein was calculated by analyzing the OD450nm using the software GraphPadPrism 7.0.

[0414] The results are shown in Figures 11 and 12. The positive control R2800 did not bind to mCDH17. Among the other monoclonal antibodies, F1-127.8 and F1-41.16 had good binding to mCDH17, while the other monoclonal antibodies did not bind to it.

[0415] Example 5 Detection of binding activity of monoclonal antibodies to hCDH17

[0416] This example tested the binding activity of a monoclonal antibody to hCDH17 (ACRO, CA7-H52H3). hCDH17 recombinant protein (human CDH17) was diluted to 0.5 μg / mL in 50 mmol Coating Buffer in advance. 100 μL was added to each well and incubated overnight at 4°C. The antibody was then diluted to 10 μg / mL in a five-fold gradient over six concentrations. All other procedures were the same as in Example 4. The EC50 value for antibody binding to hCDH17 recombinant protein was calculated using GraphPad Prism 7.0 software, using OD450 nm.

[0417] The results are shown in Figures 13 and 14. Except for F2-238.14, F2-55.10, F1-139.6, F2-71.18, F2-324.17, F2-324.7, F2-186.1, and F3-6.18, the binding activity of the remaining antibodies to the full-length CDH17 was better than that of the positive antibody R2800 (higher platform or smaller EC50).

[0418] Example 6 Identification of Monoclonal Antibody Bound Epitopes

[0419] This example examined the binding epitopes of monoclonal antibodies. Proteins R2795 (hCDH17 D1-D4.his) and R2796 (hCDH17 D5-D7.his) were constructed. The amino acid sequence of R2795 is shown in SEQ ID NO. 615, and the amino acid sequence of R2796 is shown in SEQ ID NO. 616.

[0420] Amino acid sequence of A2795 huCDH17(D1-D4)-his:

[0421] Amino acid sequence of R2796 huCDH17(D5-D7)-his:

[0422] Dilute R2795 and R2796 to 0.5 μg / mL in 50 mmol Coating Buffer in advance, add 100 μL per well, and incubate at 4°C overnight. Discard the supernatant and wash the plate three times with 1× PBST buffer. Then, add 100 μL / well of PBS + 1% FBS and block at 37°C for 1 hour. Simultaneously, dilute the monoclonal antibody and the corresponding positive control R2800 in PBS + 1% FBS, starting at 10 μg / mL, in a 5-fold gradient to obtain six concentrations for later use. After blocking, the supernatant was discarded, 100 μL of diluted antibody was added, and the plates were incubated at 37°C for 1 hour. After incubation, the plates were washed four times with 1×PBST buffer, and 100 μL / well of diluted HRP-conjugated anti-mouse IgG c antibody (Sigma, A0168) was added. The plates were incubated at 37°C for 30 minutes. After incubation, the plates were washed five times with 1×PBST buffer. The color development solution was added to develop the color appropriately, and the color development was stopped. The values ​​were read using a microplate reader, and the antibody binding epitope and its binding EC50 value were calculated using OD450 nm using GraphPadPrism 7.0 software.

[0423] The results are shown in Figures 15 to 18. The positive control R2800 did not bind to mCDH17. Among the other monoclonal antibodies, F1-127.8 and F1-41.16 had good binding to mCDH17, while the other monoclonal antibodies did not bind to it.

[0424] Example 7 Detection of Monoclonal Antibody-Mediated Cell Killing Activity

[0425] Flow cytometry was used to detect the cytotoxic activity of monoclonal antibodies against CHO-hCDH17 cells overexpressing the gene.

[0426] Cultivate enough CHO-hCDH17 cells, collect the cells by centrifugation, label them with fluorescent dye CFSE (BD Bioscience, 565082), and resuspend the cells to adjust the cell density to 4×10 5 Cells / mL were collected and used as standby. The cultured NK92 cells were collected, centrifuged and resuspended in target cell (AsPC-1 cell) culture medium to adjust the cell density to 1.2×10 6 cells / mL, and at the same time, the monoclonal antibody and the corresponding positive control antibodies R2800 and R2803 (R2803 is a nanobody with an amino acid sequence as shown in SEQ ID NO.598) were diluted with target cell culture medium. R0860 is an mIgG2a isotype control antibody (Isotype Control). The concentration started from 20 μg / mL and was diluted 40-fold to obtain 3 concentration gradients for standby use. The collected target cells were resuspended and the cells were diluted in 50 μL (2×10 4 The collected effector cells (NK92 cells) were plated and 100 μL (1.2×10 5 cells), then add 50 μL of diluted antibody and incubate at 37°C for 6 hours; then centrifuge to remove the supernatant, resuspend the cells with diluted Propidium Iodide Solution (Biolegend, 421301), 100 μL per well, incubate at room temperature in the dark for 20 minutes, and then detect on the microscope. + PE + The percentage of antibody-mediated cell killing was calculated by analysis using GraphPadPrism 7.0 software.

[0427] As shown in Figure 19, no killing activity was detected in the positive antibodies, and among the monoclonal antibodies, F1-87.15, F1-127.8, F1-86.9, F1-41.16, F1-127.13, F2-71.18, F2-71.19, F2-155.7, F2-186.1, F2-324.7, F2-84.3 and F2-291.2 had ADCC (antibody-dependent cell-mediated cytotoxicity) activity.

[0428] At the same time, the monoclonal antibody-mediated killing activity against AsPC-1 cells endogenously expressing human CDH17 was detected using the LDH method (lactate dehydrogenase cytotoxicity assay). Sufficient AsPC-1 cells were cultured, collected by centrifugation, and the cell density was adjusted to 4×10 5 Cells / ml were collected and used as standby. The cultured NK92 cells were collected, centrifuged and resuspended in target cell culture medium to adjust the cell density to 1.2×10 6At the same time, the monoclonal antibody and the corresponding positive control antibodies R2800 and R2803 were diluted with the target cell (AsPC-1 cell) culture medium, starting from 20 μg / mL, and 40-fold gradient dilution was performed to obtain 3 concentration gradients for standby use. The collected target cells were resuspended and the cells were diluted in 50 μL (2×10 4 The collected effector cells (NK92 cells) were plated and 100 μL (1.2×10 5 cells), then add 50 μL of diluted antibody and incubate at 37°C for 6 hours; 45 minutes in advance, add 20 μL of lysis buffer to the target cell maximum release well, then centrifuge and take 40 μL of supernatant to a new 96-well transparent flat-bottom plate, and add CytoTox 40 μL of the reagent (Promega, G1780) was added to each well and mixed at room temperature for 30 min. Then, 40 μL / well of the stop solution was added and mixed at room temperature for 5-10 min. OD490 nm was read on a microplate reader and the antibody-mediated cell killing was calculated by analysis using GraphPad Prism 7.0 software.

[0429] As shown in Figure 20 , ADCC activity was detected in most of the mouse monoclonal antibodies, among which F1-87.15, F1-76.12, F2-155.7, F2-186.1, F2-238.14, F2-324.7, F2-55.10, F2-84.3 and F3-1.5 were more effective.

[0430] Example 8 Monoclonal Antibody-Mediated Endocytosis Activity Detection

[0431] Based on the above test results, the endocytic activity of AsPC-1 cells towards F1-87.15, F1-99.29, F1-76.12, F1-86.9, F1-143.7, F2-238.14, F2-55.10, F3-1.5, F3-6.18, F3-36.14 and positive antibodies was detected.

[0432] Culture enough AsPC-1 cells, collect the cells by centrifugation after digestion, and adjust the cell density to 1×10 5 Cells / mL, 50μL / well plate, overnight. Dilute the antibody with the corresponding culture medium of AsPC-1 cells to 10μg / mL, dilute 3 times to obtain 8 concentration points, and dilute the secondary antibody anti-mIgG FC-MMAF (MORADEC, AM-102-AF) to 2μg / mL. Add the antibody and secondary antibody at 25μL / well and mix well. Then place in a 37℃ incubator and incubate for 3 days. Add 100μL / well Luminescent Cell Viability Assay (Promega, G7571) was mixed on a plate shaker, and luminescence was read on a microplate reader. The endocytic activity of the antibody was calculated using GraphPad Prism 7.0 software. The results are shown in FIG21 .

[0433] Example 9 Preparation of humanized CDH-17 mouse-derived conventional antibody

[0434] The hIgG1 subtype chimeric antibodies R4723 and R4850 were prepared using the murine antibody sequences of F2-155.7 and F2-89.7, respectively.

[0435] Humanized antibodies were prepared using the murine antibody sequences of R4723 and R4850. Three-dimensional homology modeling of the selected sequences was performed, and acceptable structures were determined using methods such as Pull-Draw. The antibody sequences were compared with the GermLine database to obtain human germline templates with high homology. The CDRs were then transplanted into the corresponding human templates. The transplanted antibodies were subjected to three-dimensional structural simulation and analysis again. Embedded residues, residues directly interacting with the CDR region, and residues that have a significant impact on the conformation of the variable region were reversely mutated. Chemically unstable amino acid residues in the CDR region were optimized. A series of humanized antibody molecules R4709-R4718 were generated for R4723. The amino acid sequences of the heavy chain variable regions of the antibodies are shown in Table 24, the amino acid sequences of the light chain variable regions are shown in Table 25, and the combinations of the heavy chain variable regions and the light chain variable regions are shown in Table 26. A series of humanized antibody molecules R4832-R4843 were generated for R4850. The amino acid sequences of the heavy chain variable regions of the antibodies are shown in Table 27, the amino acid sequences of the light chain variable regions are shown in Table 28, and the combinations of the heavy chain variable regions and the light chain variable regions are shown in Table 29.

[0436] Table 24 Humanized antibody heavy chain variable region sequences of R4723

[0437] Table 25 Humanized antibody light chain variable region sequences of R4723

[0438] Table 26 Combinations of heavy chain variable regions and light chain variable regions of the humanized antibody R4723

[0439] Table 27 Humanized antibody heavy chain variable region sequences of R4850

[0440] Table 28 Humanized antibody light chain variable region sequences of R4850

[0441] Table 29 Combinations of heavy chain variable regions and light chain variable regions of the humanized antibody R4850

[0442] Example 10 Detection of humanized antibody binding activity

[0443] We used CHO-CDH17 cells, which are constructed to express human CDH17, as overexpression cells, and AsPC-1 (human metastatic pancreatic adenocarcinoma cells) and OCUM-1 cells, which endogenously express CDH17. We used flow cytometry to assay the binding activity of the monoclonal antibody against CHO-CDH17 cells, AsPC-1 cells, and OCUM-1 cells.

[0444] 1. CHO-CDH17 cell binding

[0445] Cultivate enough CHO-CDH17 cells and collect them by centrifugation. Dilute the monoclonal antibody and the corresponding positive antibody with PBS + 3% FBS, starting from 10 μg / mL or 5 μg / mL, and dilute them 3-fold or 4-fold to obtain 10 or 8 concentration gradients for later use. Wash the collected cells with PBS + 3% FBS and resuspend them in PBS + 3% FBS to 2 × 10 6 Cells were plated in 96-well plates, with 100 μL (2×10 5 Cells were centrifuged and the supernatant was removed. The cells were washed twice with PBS and resuspended with diluted APC-labeled anti-human IgG FC antibody (Biolegend, 409306) or PE-labeled anti-human IgG FC antibody (Biolegend, 409304). The cells were incubated at 4°C in the dark for 30 minutes. The cells were washed twice with PBS and resuspended in 100 μL of PBS. The cells were detected on a microscope and the mean fluorescence intensity was used to calculate the EC50 value of the binding affinity of the antibody to CHO-CDH17 using GraphPad Prism 7.0 software. The results are shown in Figures 22-25. Compared with the parent antibody R4723, the binding activity of the humanized antibody was basically the same as that of the parent antibody; compared with the parent antibody R4850, the binding activity of some antibodies in the humanized antibody was basically the same as that of the parent antibody. R0861 is a negative control antibody for hIgG1.

[0446] 2. AsPC-1 cell binding

[0447] Flow cytometry was used to detect the binding activity of monoclonal antibodies to AsPC-1 cells. After digesting the cells with Versene solution, all cells were collected by centrifugation and set aside. The concentration started from 10 μg / mL or 5 μg / mL, and 10 or 8 concentration gradients were obtained by 3-fold or 4-fold gradient dilution. After the antibody and cells were co-incubated, the subsequent experimental process was the same as the CHO-CDH17 cell binding experiment. The cells were resuspended in 100 μL PBS and detected on the flow cytometer. The mean fluorescence intensity was then used to analyze and calculate the EC50 value of the binding affinity of the antibody to AsPC-1 cells using GraphPadPrism 7.0 software.

[0448] The results are shown in Figures 26-29. Compared with the parent antibody R4723, the binding activity of the humanized antibody was basically the same as that of the parent antibody; compared with the parent antibody R4850, the binding activity of some antibodies in the humanized antibody was basically the same as that of the parent antibody. R0861 is a negative control antibody for hIgG1.

[0449] 3.OCUM-1 cell binding

[0450] Flow cytometry was used to detect the binding activity of the monoclonal antibody to OCUM-1 cells. The cells were collected and centrifuged, digested with Versene, and centrifuged again for later use. The concentration started at 10 μg / mL or 5 μg / mL, and was diluted 3-fold or 4-fold to obtain 10 or 8 concentration gradients. After the antibody and cells were co-incubated, the subsequent experimental process was the same as the CHO-CDH17 cell binding experiment. The cells were resuspended in 100 μL PBS and detected on the flow cytometer. The mean fluorescence intensity was then used to analyze the binding affinity of the antibody to AsPC-1 cells and the EC50 value was calculated using GraphPadPrism 7.0 software.

[0451] The results are shown in Figures 30-33. Compared with the parent antibody R4723, the binding activity of the humanized antibody was basically the same as that of the parent antibody; compared with the parent antibody R4850, the binding activity of some antibodies in the humanized antibody was basically the same as that of the parent antibody. R0861 is a negative control antibody for hIgG1.

[0452] Example 11. Detection of binding activity of humanized antibodies to monkey CDH17

[0453] This example detects the binding activity of a monoclonal antibody to monkey CDH17 (Acrobiosystem). Dilute the Cyno.CDH17 recombinant protein (monkey CDH17) to 0.5 μg / mL in advance with 50 mmol Coating Buffer, add 100 μL per well, and incubate at 4°C overnight. Discard the supernatant, wash the plate three times with 1×PBST buffer, then add 100 μL / well of PBS + 1% FBS, block at 37°C for 1 hour, and dilute the antibody with PBS + 1% FBS starting at 10 μg / mL. Dilute the antibody in a 5-fold or 3-fold gradient starting at 10 μg / mL to obtain 8 or 10 concentration gradients for later use. After blocking, discard the supernatant, add 100 μL of diluted antibody, incubate at 37°C for 1 hour, wash the plate four times with 1×PBST buffer after the incubation, and then add 100 μL / well of diluted HRP-conjugated anti-human IgG antibody (Sigma, A0170), incubate at 37°C for 30 minutes, wash the plate five times with 1×PBST buffer after the incubation, add color development solution and stop color development after appropriate color development, read the value with a microplate reader, and then use OD450nm to analyze and calculate the EC50 value of the binding of the antibody to the Cyno.CDH17 recombinant protein using the software GraphPadPrism 7.0.

[0454] The results are shown in Figures 34-37. Compared with the parent antibody R4723, the binding activity of the humanized antibodies was basically the same as that of the parent antibody. Compared with the parent antibody R4850, the binding activity of some antibodies in the humanized antibodies was closer to that of the parent antibody. R0861 is a negative control antibody for hIgG1.

[0455] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present disclosure, rather than to limit them. Although the present disclosure has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present disclosure.

Claims

1. An anti-CDH17 antibody or an antigen-binding fragment thereof, characterized in that, The anti-CDH17 antibody or antigen-binding fragment thereof specifically binds to one or more of CDH17 extracellular domain 1, CDH17 extracellular domain 2, CDH17 extracellular domain 3, CDH17 extracellular domain 4, CDH17 extracellular domain 5, CDH17 extracellular domain 6, and CDH17 extracellular domain 7.

2. The anti-CDH17 antibody or antigen-binding fragment thereof according to claim 1, wherein The antibody or antigen-binding fragment thereof comprises complementarity-determining regions HCDR1, HCDR2, and HCDR3 of the heavy-chain variable region, and / or complementarity-determining regions LCDR1, LCDR2, and LCDR3 of the light-chain variable region; the HCDR1 comprises amino acid residues DY, EY, GY, NY, SG, SH, SY, TS, or TY; The HCDR2 comprises an amino acid sequence as shown in any one of SEQ ID NOs: 184-186, 188, 191-199, 202-205, and 208; The HCDR3 comprises an amino acid sequence as shown in any one of SEQ ID NOs: 209, 212, 215, 218, 221, 224, 227, 230, 233, 236, 239, 242, 245, 248, 251, 254, 257, 260, and 278; The LCDR1 comprises amino acid residues NID, NNF, NNW, NY, SDF, SGY, SND, SSA, or SY, or an amino acid sequence as shown in any one of SEQ ID NOs: 290, 294, 299, 308, 319, and 332; The LCDR2 comprises amino acid residues AA, DT, FA, GA, KV, RA, RT, SA, ST, WA, YA, or YT; The LCDR3 comprises an amino acid sequence as shown in any one of SEQ ID NOs: 368, 370, 372, 374, 376, 378, 380, 382, 384, 386, 388, 390, 392, 394, and 396; Optionally, the HCDR1, HCDR2, and HCDR3 comprise amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region shown in any one of SEQ ID NO.1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, or 39, and the LCDR1, LCDR2, and LCDR3 comprise amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region shown in any one of SEQ ID NO.2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, or 40; Optionally, the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, or LCDR3 of the variable region is defined by any one system of Kabat, Chothia, IMGT, ABM, or Contact or a combination of multiple definition systems; Optionally, according to the IMGT definition method: The HCDR1 comprises an amino acid sequence shown in any one of SEQ ID NO.45, 50, 54, 58, 63, 67, 72, 77, 81, 85, 90, 95, 100, 104, 107, and 113; The HCDR2 comprises an amino acid sequence shown in any one of SEQ ID NO.121, 125, 129, 133, 137, 141, 145, 149, 153, 157, 162, 167, 171, 175, 179, 183, 189, and 190; The HCDR3 comprises an amino acid sequence shown in any one of SEQ ID NO.211, 214, 217, 220, 223, 226, 229, 232, 235, 238, 241, 244, 247, 250, 253, 256, 259, 262, and 266; The LCDR1 comprises an amino acid sequence shown in any one of SEQ ID NO.286, 288, 292, 293, 296, 298, 301, 303, 305, 307, 310, 312, 321, 322, and 333; The LCDR2 comprises amino acid residue AA, amino acid residue DT, amino acid residue FA, amino acid residue GA, amino acid residue KV, amino acid residue RA, amino acid residue RT, amino acid residue SA, amino acid residue ST, amino acid residue WA, amino acid residue YA, or amino acid residue YT; The LCDR3 comprises an amino acid sequence shown in any one of SEQ ID NO.369, 371, 373, 375, 377, 379, 381, 383, 385, 387, 389, 391, 393, 395, and 397.

3. The anti-CDH17 antibody or antigen-binding fragment thereof according to claim 1 or 2, characterized in that, The complementarity determining regions of the anti-CDH17 antibody or its antigen-binding fragment include any one of the following (a) to (t): (a) HCDR1 comprises the amino acid residues SY, HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 185, HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 209, LCDR1 comprises the amino acid residues SND, LCDR2 comprises the amino acid residues YA, and LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 386; or, (b) HCDR1 comprises the amino acid residues EY, HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 192, HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 278, LCDR1 comprises the amino acid sequence shown in SEQ ID NO. 319, LCDR2 comprises the amino acid residues WA, and LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 376; or, (c) HCDR1 comprises the amino acid residues SY, HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 203, HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 212, LCDR1 comprises the amino acid residues NNF, LCDR2 comprises the amino acid residues RT, and LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 378; or, (d) HCDR1 comprises the amino acid residues SY, HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 196, HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 215, LCDR1 comprises the amino acid residues SY, LCDR2 comprises the amino acid residues DT, and LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 372; or, (e) HCDR1 comprises the amino acid residues GY, HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 197, HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 218, LCDR1 comprises the amino acid sequence shown in SEQ ID NO. 332, LCDR2 comprises the amino acid residues ST, and LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 374; or, (f) HCDR1 comprises the amino acid residues SH, HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 208, HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 221, LCDR1 comprises the amino acid sequence shown in SEQ ID NO. 290, LCDR2 comprises the amino acid residues RA, and LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 394; or, (g) The HCDR1 comprises the amino acid residue TY, the HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 191, the HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 224, the LCDR1 comprises the amino acid sequence shown in SEQ ID NO. 332, the LCDR2 comprises the amino acid residue ST, and the LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 374; or, (h) The HCDR1 comprises the amino acid residue GY, the HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 195, the HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 227, the LCDR1 comprises the amino acid sequence shown in SEQ ID NO. 294, the LCDR2 comprises the amino acid residue YA, and the LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 382; or, (i) The HCDR1 comprises the amino acid residue SG, the HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 205, the HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 230, the LCDR1 comprises the amino acid residue SSA, the LCDR2 comprises the amino acid residue SA, and the LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 392; or, (j) The HCDR1 comprises the amino acid residue TS, the HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 186, the HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 233, the LCDR1 comprises the amino acid sequence shown in SEQ ID NO. 299, the LCDR2 comprises the amino acid residue KV, and the LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 370; or, (k) The HCDR1 comprises the amino acid residue EY, the HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 194, the HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 278, the LCDR1 comprises the amino acid sequence shown in SEQ ID NO. 319, the LCDR2 comprises the amino acid residue WA, and the LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 376; or, (l) The HCDR1 comprises the amino acid residue SY, the HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 199, the HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 236, the LCDR1 comprises the amino acid residue SY, the LCDR2 comprises the amino acid residue DT, and the LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 368; or, (m) The HCDR1 comprises the amino acid residues EY, the HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 194, the HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 239, the LCDR1 comprises the amino acid sequence shown in SEQ ID NO. 319, the LCDR2 comprises the amino acid residues WA, and the LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 376; or, (n) The HCDR1 comprises the amino acid residues DY, the HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 193, the HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 242, the LCDR1 comprises the amino acid residues NNW, the LCDR2 comprises the amino acid residues GA, and the LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 396; or, (o) The HCDR1 comprises the amino acid residues TY, the HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 202, the HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 245, the LCDR1 comprises the amino acid residues NY, the LCDR2 comprises the amino acid residues YT, and the LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 388; or, (p) The HCDR1 comprises the amino acid residues NY, the HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 198, the HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 248, the LCDR1 comprises the amino acid residues SDF, the LCDR2 comprises the amino acid residues YA, and the LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 384; or, (q) The HCDR1 comprises the amino acid residues TY, the HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 204, the HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 251, the LCDR1 comprises the amino acid residues SGY, the LCDR2 comprises the amino acid residues AA, and the LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 380; or, (r) The HCDR1 comprises the amino acid residues TY, the HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 204, the HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 254, the LCDR1 comprises the amino acid residues SGY, the LCDR2 comprises the amino acid residues AA, and the LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 380; or, (s) The HCDR1 comprises the amino acid residues NY, the HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 184, the HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 257, the LCDR1 comprises the amino acid sequence shown in SEQ ID NO. 308, the LCDR2 comprises the amino acid residues FA, and the LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 382; or, (t)HCDR1 comprises the amino acid residues DY, HCDR2 comprises the amino acid sequence shown in SEQ ID NO.188, HCDR3 comprises the amino acid sequence shown in SEQ ID NO.260, LCDR1 comprises the amino acid residues NID, LCDR2 comprises the amino acid residues SA, and LCDR3 comprises the amino acid sequence shown in SEQ ID NO.390; Optionally, according to the IMGT definition, the complementarity determining regions of the anti-CDH17 antibody or its antigen-binding fragment include any one of the following (a') to (t'): (a')HCDR1 comprises the amino acid sequence shown in SEQ ID NO.63, HCDR2 comprises the amino acid sequence shown in SEQ ID NO.141, HCDR3 comprises the amino acid sequence shown in SEQ ID NO.223, LCDR1 comprises the amino acid sequence shown in SEQ ID NO.292, LCDR2 comprises the amino acid residues RA, and LCDR3 comprises the amino acid sequence shown in SEQ ID NO.395; or, (b')HCDR1 comprises the amino acid sequence shown in SEQ ID NO.113, HCDR2 comprises the amino acid sequence shown in SEQ ID NO.125, HCDR3 comprises the amino acid sequence shown in SEQ ID NO.266, LCDR1 comprises the amino acid sequence shown in SEQ ID NO.322, LCDR2 comprises the amino acid residues WA, and LCDR3 comprises the amino acid sequence shown in SEQ ID NO.377; or, (c')HCDR1 comprises the amino acid sequence shown in SEQ ID NO.50, HCDR2 comprises the amino acid sequence shown in SEQ ID NO.129, HCDR3 comprises the amino acid sequence shown in SEQ ID NO.214, LCDR1 comprises the amino acid sequence shown in SEQ ID NO.288, LCDR2 comprises the amino acid residues RT, and LCDR3 comprises the amino acid sequence shown in SEQ ID NO.379; or, (d')HCDR1 comprises the amino acid sequence shown in SEQ ID NO.54, HCDR2 comprises the amino acid sequence shown in SEQ ID NO.133, HCDR3 comprises the amino acid sequence shown in SEQ ID NO.217, LCDR1 comprises the amino acid sequence shown in SEQ ID NO.333, LCDR2 comprises the amino acid residues DT, and LCDR3 comprises the amino acid sequence shown in SEQ ID NO.373; or, (e') The HCDR1 comprises the amino acid sequence shown in SEQ ID NO. 58, the HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 137, the HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 220, the LCDR1 comprises the amino acid sequence shown in SEQ ID NO. 293, the LCDR2 comprises the amino acid residues ST, and the LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 375; or, (f') The HCDR1 comprises the amino acid sequence shown in SEQ ID NO. 45, the HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 121, the HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 211, the LCDR1 comprises the amino acid sequence shown in SEQ ID NO. 286, the LCDR2 comprises the amino acid residues YA, and the LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 387; or, (g') The HCDR1 comprises the amino acid sequence shown in SEQ ID NO. 107, the HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 145, the HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 226, the LCDR1 comprises the amino acid sequence shown in SEQ ID NO. 293, the LCDR2 comprises the amino acid residues ST, and the LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 375; or, (h') The HCDR1 comprises the amino acid sequence shown in SEQ ID NO. 67, the HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 149, the HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 229, the LCDR1 comprises the amino acid sequence shown in SEQ ID NO. 296, the LCDR2 comprises the amino acid residues YA, and the LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 383; or, (i') The HCDR1 comprises the amino acid sequence shown in SEQ ID NO. 72, the HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 153, the HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 232, the LCDR1 comprises the amino acid sequence shown in SEQ ID NO. 298, the LCDR2 comprises the amino acid residues SA, and the LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 393; or, (j') The HCDR1 comprises the amino acid sequence shown in SEQ ID NO. 77, the HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 157, the HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 235, the LCDR1 comprises the amino acid sequence shown in SEQ ID NO. 301, the LCDR2 comprises the amino acid residues KV, and the LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 371; or, (k') The HCDR1 comprises the amino acid sequence shown in SEQ ID NO. 113, the HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 189, the HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 266, the LCDR1 comprises the amino acid sequence shown in SEQ ID NO. 322, the LCDR2 comprises the amino acid residue WA, and the LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 377; or, (l') The HCDR1 comprises the amino acid sequence shown in SEQ ID NO. 81, the HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 162, the HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 238, the LCDR1 comprises the amino acid sequence shown in SEQ ID NO. 333, the LCDR2 comprises the amino acid residue DT, and the LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 369; or, (m') The HCDR1 comprises the amino acid sequence shown in SEQ ID NO. 113, the HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 189, the HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 241, the LCDR1 comprises the amino acid sequence shown in SEQ ID NO. 322, the LCDR2 comprises the amino acid residue WA, and the LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 377; or, (n') The HCDR1 comprises the amino acid sequence shown in SEQ ID NO. 85, the HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 167, the HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 244, the LCDR1 comprises the amino acid sequence shown in SEQ ID NO. 303, the LCDR2 comprises the amino acid residue GA, and the LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 397; or, (o') The HCDR1 comprises the amino acid sequence shown in SEQ ID NO. 90, the HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 171, the HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 247, the LCDR1 comprises the amino acid sequence shown in SEQ ID NO. 305, the LCDR2 comprises the amino acid residue YT, and the LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 389; or, (p') The HCDR1 comprises the amino acid sequence shown in SEQ ID NO. 95, the HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 175, the HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 250, the LCDR1 comprises the amino acid sequence shown in SEQ ID NO. 307, the LCDR2 comprises the amino acid residue YA, and the LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 385; or, (q') The HCDR1 comprises the amino acid sequence shown in SEQ ID NO. 107, the HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 190, the HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 253, the LCDR1 comprises the amino acid sequence shown in SEQ ID NO. 321, the LCDR2 comprises the amino acid residue AA, and the LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 381; or, (r') The HCDR1 comprises the amino acid sequence shown in SEQ ID NO. 107, the HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 190, the HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 256, the LCDR1 comprises the amino acid sequence shown in SEQ ID NO. 321, the LCDR2 comprises the amino acid residue AA, and the LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 381; or, (s') The HCDR1 comprises the amino acid sequence shown in SEQ ID NO. 100, the HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 179, the HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 259, the LCDR1 comprises the amino acid sequence shown in SEQ ID NO. 310, the LCDR2 comprises the amino acid residue FA, and the LCDR3 comprises the amino acid sequence shown in SEQ ID NO. 383; or, (t') The HCDR1 comprises the amino acid sequence shown in SEQ ID NO. 104, the HCDR2 comprises the amino acid sequence shown in SEQ ID NO. 183, the HCDR3 comprises the amino acid sequence shown in SEQ ID NO. 262, the LCDR1 comprises the amino acid sequence shown in SEQ ID NO. 312, the LCDR2 comprises the amino acid residue SA, and the LCDR3 comprises the amino acid sequence shown in SEQ ID NO.

391.

4. The anti-CDH17 antibody or antigen-binding fragment thereof according to any one of claims 1 to 3, characterized in that, The antibody contains a heavy chain framework region and / or a light chain framework region, and the heavy chain framework region and / or the light chain framework region is derived from at least one of a murine antibody, a human antibody, a primate antibody or a mutant thereof.

5. The anti-CDH17 antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, characterized in that The framework region of the heavy chain variable region comprises HFR1, HFR2, HFR3 and HFR4, and the framework region of the light chain variable region comprises LFR1, LFR2, LFR3 and LFR4, wherein, The HFR1 comprises the amino acid sequence shown in any one of SEQ ID NOs. 398 to 415, or comprises a sequence having at least 78% sequence identity with the amino acid sequence shown in any one of SEQ ID NOs. 398 to 415; and / or, the HFR2 comprises an amino acid sequence as shown in any one of SEQ ID NO.416, 418, 422, 426, 428, 431, 433, 436, 439, 442 and 445-448, or comprises a sequence having at least 70% sequence identity with the amino acid sequence as shown in any one of SEQ ID NO.416, 418, 422, 426, 428, 431, 433, 436, 439, 442 and 445-448; and / or, the HFR3 comprises an amino acid sequence as shown in any one of SEQ ID NO.449, 451, 453, 455, 457, 459, 461, 463, 465, 467, 469, 472, 474, 477, 479, 481, 483, 485 and 487, or comprises a sequence having at least 72% sequence identity with the amino acid sequence as shown in any one of SEQ ID NO.449, 451, 453, 455, 457, 459, 461, 463, 465, 467, 469, 472, 474, 477, 479, 481, 483, 485 and 487; and / or, the HFR4 comprises an amino acid sequence as shown in any one of SEQ ID NO.488-493, or comprises a sequence having at least 86% sequence identity with the amino acid sequence as shown in any one of SEQ ID NO.488-493; and / or, the LFR1 comprises an amino acid sequence as shown in any one of SEQ ID NO.494, 496, 498, 500, 502, 504, 506, 508, 510, 512, 514, 516, 518, 520, 522, 524 and 526, or comprises a sequence having at least 70% sequence identity with the amino acid sequence as shown in any one of SEQ ID NO.494, 496, 498, 500, 502, 504, 506, 508, 510, 512, 514, 516, 518, 520, 522, 524 and 526; and / or, the LFR2 comprises an amino acid sequence as shown in any one of SEQ ID NO.528, 533, 535, 537, 539, 541, 543 and 549-552, or comprises a sequence having at least 80% sequence identity with the amino acid sequence as shown in any one of SEQ ID NO.528, 533, 535, 537, 539, 541, 543 and 549-552; And / or, the LFR3 comprises an amino acid sequence as shown in any one of SEQ ID NOs. 554, 556, 558, 560, 562, 564, 566, 568, 570, 572, 574, 576, 578, 580, 581 and 582, or comprises a sequence having at least 79% sequence identity with the amino acid sequence as shown in any one of SEQ ID NOs. 554, 556, 558, 560, 562, 564, 566, 568, 570, 572, 574, 576, 578, 580, 581 and 582; And / or, the LFR4 comprises an amino acid sequence as shown in any one of SEQ ID NOs. 586 to 590, or comprises a sequence having at least 95% sequence identity with the amino acid sequence as shown in any one of SEQ ID NOs. 586 to 590; Optionally, according to the IMGT definition: the heavy chain framework region of the anti-CDH17 antibody or its antigen-binding fragment comprises any one of the following (A) to (T): (A) The HFR1 comprises the amino acid sequence shown in SEQ ID NO. 414, the HFR2 comprises the amino acid sequence shown in SEQ ID NO. 417, the HFR3 comprises the amino acid sequence shown in SEQ ID NO. 450, and the HFR4 comprises the amino acid sequence shown in SEQ ID NO. 490; (B) The HFR1 comprises the amino acid sequence shown in SEQ ID NO. 405, the HFR2 comprises the amino acid sequence shown in SEQ ID NO. 444, the HFR3 comprises the amino acid sequence shown in SEQ ID NO. 452, and the HFR4 comprises the amino acid sequence shown in SEQ ID NO. 491; (C) The HFR1 comprises the amino acid sequence shown in SEQ ID NO. 399, the HFR2 comprises the amino acid sequence shown in SEQ ID NO. 419, the HFR3 comprises the amino acid sequence shown in SEQ ID NO. 454, and the HFR4 comprises the amino acid sequence shown in SEQ ID NO. 491; (D) The HFR1 comprises the amino acid sequence shown in SEQ ID NO. 414, the HFR2 comprises the amino acid sequence shown in SEQ ID NO. 420, the HFR3 comprises the amino acid sequence shown in SEQ ID NO. 456, and the HFR4 comprises the amino acid sequence shown in SEQ ID NO. 493; (E) The HFR1 comprises the amino acid sequence shown in SEQ ID NO. 404, the HFR2 comprises the amino acid sequence shown in SEQ ID NO. 421, the HFR3 comprises the amino acid sequence shown in SEQ ID NO. 458, and the HFR4 comprises the amino acid sequence shown in SEQ ID NO. 492; (F) The HFR1 contains the amino acid sequence shown in SEQ ID NO. 411, the HFR2 contains the amino acid sequence shown in SEQ ID NO. 423, the HFR3 contains the amino acid sequence shown in SEQ ID NO. 460, and the HFR4 contains the amino acid sequence shown in SEQ ID NO. 493; (G) The HFR1 contains the amino acid sequence shown in SEQ ID NO. 407, the HFR2 contains the amino acid sequence shown in SEQ ID NO. 424, the HFR3 contains the amino acid sequence shown in SEQ ID NO. 462, and the HFR4 contains the amino acid sequence shown in SEQ ID NO. 493; (H) The HFR1 contains the amino acid sequence shown in SEQ ID NO. 401, the HFR2 contains the amino acid sequence shown in SEQ ID NO. 425, the HFR3 contains the amino acid sequence shown in SEQ ID NO. 464, and the HFR4 contains the amino acid sequence shown in SEQ ID NO. 488; (I) The HFR1 contains the amino acid sequence shown in SEQ ID NO. 409, the HFR2 contains the amino acid sequence shown in SEQ ID NO. 427, the HFR3 contains the amino acid sequence shown in SEQ ID NO. 466, and the HFR4 contains the amino acid sequence shown in SEQ ID NO. 491; (J) The HFR1 contains the amino acid sequence shown in SEQ ID NO. 415, the HFR2 contains the amino acid sequence shown in SEQ ID NO. 429, the HFR3 contains the amino acid sequence shown in SEQ ID NO. 468, and the HFR4 contains the amino acid sequence shown in SEQ ID NO. 493; (K) The HFR1 contains the amino acid sequence shown in SEQ ID NO. 403, the HFR2 contains the amino acid sequence shown in SEQ ID NO. 444, the HFR3 contains the amino acid sequence shown in SEQ ID NO. 470, and the HFR4 contains the amino acid sequence shown in SEQ ID NO. 491; (L) The HFR1 contains the amino acid sequence shown in SEQ ID NO. 410, the HFR2 contains the amino acid sequence shown in SEQ ID NO. 430, the HFR3 contains the amino acid sequence shown in SEQ ID NO. 471, and the HFR4 contains the amino acid sequence shown in SEQ ID NO. 491; (M) The HFR1 contains the amino acid sequence shown in SEQ ID NO. 406, the HFR2 contains the amino acid sequence shown in SEQ ID NO. 432, the HFR3 contains the amino acid sequence shown in SEQ ID NO. 473, and the HFR4 contains the amino acid sequence shown in SEQ ID NO. 491; (N) The HFR1 comprises the amino acid sequence shown in SEQ ID NO.400, the HFR2 comprises the amino acid sequence shown in SEQ ID NO.434, the HFR3 comprises the amino acid sequence shown in SEQ ID NO.475, and the HFR4 comprises the amino acid sequence shown in SEQ ID NO.492; (O) The HFR1 comprises the amino acid sequence shown in SEQ ID NO.412, the HFR2 comprises the amino acid sequence shown in SEQ ID NO.435, the HFR3 comprises the amino acid sequence shown in SEQ ID NO.476, and the HFR4 comprises the amino acid sequence shown in SEQ ID NO.492; (P) The HFR1 comprises the amino acid sequence shown in SEQ ID NO.408, the HFR2 comprises the amino acid sequence shown in SEQ ID NO.437, the HFR3 comprises the amino acid sequence shown in SEQ ID NO.478, and the HFR4 comprises the amino acid sequence shown in SEQ ID NO.491; (Q) The HFR1 comprises the amino acid sequence shown in SEQ ID NO.398, the HFR2 comprises the amino acid sequence shown in SEQ ID NO.438, the HFR3 comprises the amino acid sequence shown in SEQ ID NO.480, and the HFR4 comprises the amino acid sequence shown in SEQ ID NO.489; (R) The HFR1 comprises the amino acid sequence shown in SEQ ID NO.398, the HFR2 comprises the amino acid sequence shown in SEQ ID NO.440, the HFR3 comprises the amino acid sequence shown in SEQ ID NO.482, and the HFR4 comprises the amino acid sequence shown in SEQ ID NO.493; (S) The HFR1 comprises the amino acid sequence shown in SEQ ID NO.413, the HFR2 comprises the amino acid sequence shown in SEQ ID NO.441, the HFR3 comprises the amino acid sequence shown in SEQ ID NO.484, and the HFR4 comprises the amino acid sequence shown in SEQ ID NO.492; (T) The HFR1 comprises the amino acid sequence shown in SEQ ID NO.402, the HFR2 comprises the amino acid sequence shown in SEQ ID NO.443, the HFR3 comprises the amino acid sequence shown in SEQ ID NO.486, and the HFR4 comprises the amino acid sequence shown in SEQ ID NO.493; Optionally, according to the IMGT definition, the light chain framework region of the anti-CDH17 antibody or its antigen-binding fragment comprises any one of the following (A') to (T'): (A') The LFR1 comprises the amino acid sequence shown in SEQ ID NO.495, the LFR2 comprises the amino acid sequence shown in SEQ ID NO.553, the LFR3 comprises the amino acid sequence shown in SEQ ID NO.555, and the LFR4 comprises the amino acid sequence shown in SEQ ID NO.587; (B') The LFR1 contains the amino acid sequence shown in SEQ ID NO. 527, the LFR2 contains the amino acid sequence shown in SEQ ID NO. 546, the LFR3 contains the amino acid sequence shown in SEQ ID NO. 585, and the LFR4 contains the amino acid sequence shown in SEQ ID NO. 587; (C') The LFR1 contains the amino acid sequence shown in SEQ ID NO. 497, the LFR2 contains the amino acid sequence shown in SEQ ID NO. 529, the LFR3 contains the amino acid sequence shown in SEQ ID NO. 557, and the LFR4 contains the amino acid sequence shown in SEQ ID NO. 586; (D') The LFR1 contains the amino acid sequence shown in SEQ ID NO. 499, the LFR2 contains the amino acid sequence shown in SEQ ID NO. 530, the LFR3 contains the amino acid sequence shown in SEQ ID NO. 559, and the LFR4 contains the amino acid sequence shown in SEQ ID NO. 587; (E') The LFR1 contains the amino acid sequence shown in SEQ ID NO. 501, the LFR2 contains the amino acid sequence shown in SEQ ID NO. 547, the LFR3 contains the amino acid sequence shown in SEQ ID NO. 583, and the LFR4 contains the amino acid sequence shown in SEQ ID NO. 587; (F') The LFR1 contains the amino acid sequence shown in SEQ ID NO. 525, the LFR2 contains the amino acid sequence shown in SEQ ID NO. 531, the LFR3 contains the amino acid sequence shown in SEQ ID NO. 561, and the LFR4 contains the amino acid sequence shown in SEQ ID NO. 588; (G') The LFR1 contains the amino acid sequence shown in SEQ ID NO. 503, the LFR2 contains the amino acid sequence shown in SEQ ID NO. 547, the LFR3 contains the amino acid sequence shown in SEQ ID NO. 583, and the LFR4 contains the amino acid sequence shown in SEQ ID NO. 587; (H') The LFR1 contains the amino acid sequence shown in SEQ ID NO. 505, the LFR2 contains the amino acid sequence shown in SEQ ID NO. 532, the LFR3 contains the amino acid sequence shown in SEQ ID NO. 563, and the LFR4 contains the amino acid sequence shown in SEQ ID NO. 587; (I') The LFR1 contains the amino acid sequence shown in SEQ ID NO. 507, the LFR2 contains the amino acid sequence shown in SEQ ID NO. 534, the LFR3 contains the amino acid sequence shown in SEQ ID NO. 565, and the LFR4 contains the amino acid sequence shown in SEQ ID NO. 589; (J') The LFR1 comprises the amino acid sequence shown in SEQ ID NO. 509, the LFR2 comprises the amino acid sequence shown in SEQ ID NO. 536, the LFR3 comprises the amino acid sequence shown in SEQ ID NO. 567, and the LFR4 comprises the amino acid sequence shown in SEQ ID NO. 587; (K') The LFR1 comprises the amino acid sequence shown in SEQ ID NO. 527, the LFR2 comprises the amino acid sequence shown in SEQ ID NO. 546, the LFR3 comprises the amino acid sequence shown in SEQ ID NO. 585, and the LFR4 comprises the amino acid sequence shown in SEQ ID NO. 587; (L') The LFR1 comprises the amino acid sequence shown in SEQ ID NO. 511, the LFR2 comprises the amino acid sequence shown in SEQ ID NO. 538, the LFR3 comprises the amino acid sequence shown in SEQ ID NO. 569, and the LFR4 comprises the amino acid sequence shown in SEQ ID NO. 589; (M') The LFR1 comprises the amino acid sequence shown in SEQ ID NO. 513, the LFR2 comprises the amino acid sequence shown in SEQ ID NO. 546, the LFR3 comprises the amino acid sequence shown in SEQ ID NO. 585, and the LFR4 comprises the amino acid sequence shown in SEQ ID NO. 587; (N') The LFR1 comprises the amino acid sequence shown in SEQ ID NO. 515, the LFR2 comprises the amino acid sequence shown in SEQ ID NO. 540, the LFR3 comprises the amino acid sequence shown in SEQ ID NO. 571, and the LFR4 comprises the amino acid sequence shown in SEQ ID NO. 590; (O') The LFR1 comprises the amino acid sequence shown in SEQ ID NO. 517, the LFR2 comprises the amino acid sequence shown in SEQ ID NO. 542, the LFR3 comprises the amino acid sequence shown in SEQ ID NO. 573, and the LFR4 comprises the amino acid sequence shown in SEQ ID NO. 589; (P') The LFR1 comprises the amino acid sequence shown in SEQ ID NO. 519, the LFR2 comprises the amino acid sequence shown in SEQ ID NO. 544, the LFR3 comprises the amino acid sequence shown in SEQ ID NO. 575, and the LFR4 comprises the amino acid sequence shown in SEQ ID NO. 587, (Q') The LFR1 comprises the amino acid sequence shown in SEQ ID NO. 523, the LFR2 comprises the amino acid sequence shown in SEQ ID NO. 548, the LFR3 comprises the amino acid sequence shown in SEQ ID NO. 584, and the LFR4 comprises the amino acid sequence shown in SEQ ID NO. 587; (R') The LFR1 comprises the amino acid sequence shown in SEQ ID NO.523, the LFR2 comprises the amino acid sequence shown in SEQ ID NO.548, the LFR3 comprises the amino acid sequence shown in SEQ ID NO.584, and the LFR4 comprises the amino acid sequence shown in SEQ ID NO.587; (S') The LFR1 comprises the amino acid sequence shown in SEQ ID NO.525, the LFR2 comprises the amino acid sequence shown in SEQ ID NO.545, the LFR3 comprises the amino acid sequence shown in SEQ ID NO.577, and the LFR4 comprises the amino acid sequence shown in SEQ ID NO.587; (T') The LFR1 comprises the amino acid sequence shown in SEQ ID NO.521, the LFR2 comprises the amino acid sequence shown in SEQ ID NO.553, the LFR3 comprises the amino acid sequence shown in SEQ ID NO.579, and the LFR4 comprises the amino acid sequence shown in SEQ ID NO.

587.

6. The anti-CDH17 antibody or antigen-binding fragment thereof according to any one of claims 1 to 5, characterized in that The anti-CDH17 antibody or its antigen-binding fragment has a heavy chain variable region having an amino acid sequence shown in any one of SEQ ID NO.1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 599-603, 606-609 or having at least 64% sequence identity with the amino acid sequence shown in any one of SEQ ID NO.1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 599-603, 606-609; and / or, the anti-CDH17 antibody or its antigen-binding fragment has a light chain variable region having an amino acid sequence shown in any one of SEQ ID NO.2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 604, 605, 610-614 or having at least 70% sequence identity with the amino acid sequence shown in any one of SEQ ID NO.2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 604, 605, 610-614.

7. The anti-CDH17 antibody or antigen-binding fragment thereof according to any one of claims 1 to 6, characterized in that, The anti-CDH17 antibody or its antigen-binding fragment comprises a heavy chain variable region and a light chain variable region selected from any of the following: (a”) a heavy chain variable region having the amino acid sequence shown in SEQ ID NO.11; and a light chain variable region having the amino acid sequence shown in SEQ ID NO.12; (b”) a heavy chain variable region having the amino acid sequence shown in SEQ ID NO.599; and a light chain variable region having the amino acid sequence shown in SEQ ID NO.604; (c”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.5; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.6; (d”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.7; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.8; (e”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.9; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.10; (f”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.1; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.2; (g”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.13; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.14; (h”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.15; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.16; (i”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.17; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.18; (j”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.19; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.20; (k”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.21; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.22; (l”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.23; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.24; (m”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.25; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.26; (n”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.27; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.28; (o”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.29; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.30; (p”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.31; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.32; (q”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.33; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.34; (r”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.35; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.36; (s”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO. 37; and the light chain variable region of the amino acid sequence shown in SEQ ID NO. 38; (t”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO. 39; and the light chain variable region of the amino acid sequence shown in SEQ ID NO. 40; (u”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO. 3; and the light chain variable region of the amino acid sequence shown in SEQ ID NO. 4; (v”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO. 599; and the light chain variable region of the amino acid sequence shown in SEQ ID NO. 605; (w”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO. 600; and the light chain variable region of the amino acid sequence shown in SEQ ID NO. 604; (x”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO. 600; and the light chain variable region of the amino acid sequence shown in SEQ ID NO. 605; (y”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO. 601; and the light chain variable region of the amino acid sequence shown in SEQ ID NO. 604; (z”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO. 601; and the light chain variable region of the amino acid sequence shown in SEQ ID NO. 605; (a”') The heavy chain variable region of the amino acid sequence shown in SEQ ID NO. 602; and the light chain variable region of the amino acid sequence shown in SEQ ID NO. 604; (b”') The heavy chain variable region of the amino acid sequence shown in SEQ ID NO. 602; and the light chain variable region of the amino acid sequence shown in SEQ ID NO. 605; (c”') The heavy chain variable region of the amino acid sequence shown in SEQ ID NO. 603; and the light chain variable region of the amino acid sequence shown in SEQ ID NO. 604; (d”') The heavy chain variable region of the amino acid sequence shown in SEQ ID NO. 603; and the light chain variable region of the amino acid sequence shown in SEQ ID NO. 605; (e”') The heavy chain variable region of the amino acid sequence shown in SEQ ID NO. 606; and the light chain variable region of the amino acid sequence shown in SEQ ID NO. 613; (f”') The heavy chain variable region of the amino acid sequence shown in SEQ ID NO. 607; and the light chain variable region of the amino acid sequence shown in SEQ ID NO. 610; (g”') The heavy chain variable region of the amino acid sequence shown in SEQ ID NO. 607; and the light chain variable region of the amino acid sequence shown in SEQ ID NO. 611; (h”')The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.607; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.612; (i”')The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.607; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.613; (j”')The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.608; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.611; (k”')The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.608; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.612; (l”')The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.608; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.613; (m”')The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.609; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.611; (n”')The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.609; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.612; (o”')The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.609; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.613; (p”')The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.610; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.

614.

8. The anti-CDH17 antibody or antigen-binding fragment thereof according to any one of claims 1 to 7, wherein The anti-CDH17 antibody or its antigen-binding fragment comprises a partial or full sequence of a constant region, which is derived from at least one of murine antibodies, human antibodies, primate antibodies or their mutants; Optionally, the heavy chain constant region contains a partial or full sequence of the constant region of any one of IgG1, IgG2a, IgG2b, IgG3, IgG4, IgA, IgM, IgE or IgD; the light chain constant region of the antibody is a κ or λ chain; Optionally, the heavy chain constant region contains the constant region sequence of IgG1, IgG2a or IgG2b; Optionally, the heavy chain constant region contains a partial or full sequence of the constant region of IgG1, and the anti-CDH17 antibody or its antigen-binding fragment comprises the heavy chain variable region and the light chain variable region of any one of the following: (a”)The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.599; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.604; (c”)The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.5; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.6; (t”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.39; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.40; (u”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.1; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.2; (v”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.599; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.605; (w”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.600; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.604; (x”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.600; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.605; (y”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.601; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.604; (z”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.601; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.605; (a”') The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.602; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.604; (b”') The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.602; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.605; (c”') The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.603; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.604; (d”') The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.603; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.605; (e”') The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.606; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.613; (f”') The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.607; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.610; (g”') The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.607; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.611; (h”') The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.607; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.612; (i”') The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.607; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.613; (j”') The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.608; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.611; (k”') The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.608; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.612; (l”') The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.608; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.613; (m”') The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.609; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.611; (n”') The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.609; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.612; (o”') The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.609; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.613; (p”') The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.610; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.614; Optionally, the heavy chain constant region contains the sequence of part or all of the constant region of IgG2a, and the anti-CDH17 antibody or its antigen-binding fragment comprises the heavy chain variable region and the light chain variable region of any of the following: (d”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.7; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.8; (f”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.11; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.12; (g”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.13; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.14; (i”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.17; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.18; (j”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.19; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.20; (n”) The heavy chain variable region of the amino acid sequence shown in SEQ ID NO.27; and the light chain variable region of the amino acid sequence shown in SEQ ID NO.28; (o”) The heavy chain variable region of the amino acid sequence as shown in SEQ ID NO.29; and the light chain variable region of the amino acid sequence as shown in SEQ ID NO.30; (p”) The heavy chain variable region of the amino acid sequence as shown in SEQ ID NO.31; and the light chain variable region of the amino acid sequence as shown in SEQ ID NO.32; (q”) The heavy chain variable region of the amino acid sequence as shown in SEQ ID NO.33; and the light chain variable region of the amino acid sequence as shown in SEQ ID NO.34; (r”) The heavy chain variable region of the amino acid sequence as shown in SEQ ID NO.35; and the light chain variable region of the amino acid sequence as shown in SEQ ID NO.36; (s”) The heavy chain variable region of the amino acid sequence as shown in SEQ ID NO.37; and the light chain variable region of the amino acid sequence as shown in SEQ ID NO.38; Optionally, the heavy chain constant region contains the sequence of part or all of the constant region of IgG2b, and the anti-CDH17 antibody or its antigen-binding fragment comprises the heavy chain variable region and the light chain variable region of any one of the following: (b”) The heavy chain variable region of the amino acid sequence as shown in SEQ ID NO.3; and the light chain variable region of the amino acid sequence as shown in SEQ ID NO.4; (e”) The heavy chain variable region of the amino acid sequence as shown in SEQ ID NO.9; and the light chain variable region of the amino acid sequence as shown in SEQ ID NO.10; (h”) The heavy chain variable region of the amino acid sequence as shown in SEQ ID NO.15; and the light chain variable region of the amino acid sequence as shown in SEQ ID NO.16; (k”) The heavy chain variable region of the amino acid sequence as shown in SEQ ID NO.21; and the light chain variable region of the amino acid sequence as shown in SEQ ID NO.22; (l”) The heavy chain variable region of the amino acid sequence as shown in SEQ ID NO.23; and the light chain variable region of the amino acid sequence as shown in SEQ ID NO.24; (m”) The heavy chain variable region of the amino acid sequence as shown in SEQ ID NO.25; and the light chain variable region of the amino acid sequence as shown in SEQ ID NO.

26.

9. The anti-CDH17 antibody or antigen-binding fragment thereof according to any one of claims 1 to 8, characterized in that, The antigen-binding fragment comprises one or more of F(ab’)2, Fab’, Fab, Fv, scFv, dsFv and the minimum antibody recognition unit.

10. The anti-CDH17 antibody or antigen-binding fragment thereof according to any one of claims 1 to 9, characterized in that The anti-CDH17 antibody or its antigen-binding fragment has one or more of the following properties (i) to (iv): (i) Binds to human CDH17 with an EC50 of no more than 1 μg / mL, and the binding is determined by flow cytometry fluorescence-activated cell sorting technology; (ii) Binds to cynomolgus monkey CDH17 with an EC50 of no more than 1 μg / mL, and the binding is determined by ELISA technology; (iii) Has ADCC activity; (iv) Has the activity of mediating endocytosis.

11. An anti-CDH17 antibody or an antigen-binding fragment thereof, characterized in that, It competitively binds to CDH17 with the anti-CDH17 antibody described in any one of claims 1 to 10, or the epitope of the CDH17 antigen it binds to is the same as the epitope of the CDH17 antigen bound by the anti-CDH17 antibody described in any one of claims 1 to 10.

12. A biological material, characterized in that, The biological material includes any one of the following (i) to (vi): (i) A multispecific antibody that includes the anti-CDH17 antibody shown in any one of claims 1 to 11; (ii) A chimeric antigen receptor that includes an extracellular region, and the extracellular region includes an antigen-binding domain; and the antigen-binding domain contains the anti-CDH17 antibody described in any one of claims 1 to 11 or an antigen-binding fragment thereof; (iii) A nucleic acid molecule that encodes the anti-CDH17 antibody described in any one of claims 1 to 11 or an antigen-binding fragment thereof, or the multispecific antibody described in (i), or the chimeric antigen receptor described in (ii); (iv) A vector that carries the nucleic acid molecule described in (iii); (v) A recombinant cell, characterized in that the recombinant cell expresses the anti-CDH17 antibody described in any one of claims 1 to 11 or an antigen-binding fragment thereof, or expresses the multispecific antibody described in (i), or expresses the chimeric antigen receptor described in (ii), or contains the nucleic acid molecule described in (iii), or contains the vector described in (iv); (vi) An engineered immune cell, characterized in that the immune cell expresses the chimeric antigen receptor described in (ii) or contains a nucleic acid molecule encoding the chimeric antigen receptor described in (ii).

13. A pharmaceutical composition, characterized in that, The pharmaceutical composition contains the anti-CDH17 antibody described in any one of claims 1 to 11 or an antigen-binding fragment thereof, or the biological material described in claim 12; Optionally, the pharmaceutical composition further includes a pharmaceutically acceptable carrier and / or excipient.

14. Use of the anti-CDH17 antibody described in any one of claims 1 to 11 or an antigen-binding fragment thereof, or the biological material described in claim 12, or the pharmaceutical composition described in claim 13 in any one of the following: (Ⅰ) Detecting CDH17 or cells expressing CDH17; (Ⅱ) Preparing a product for detecting CDH17 or cells expressing CDH17; (Ⅲ) For treating, preventing or alleviating diseases, disorders or conditions related to CDH17; (Ⅳ) Preparing a pharmaceutical composition for treating, preventing or alleviating diseases, disorders or conditions related to CDH17.

15. A method for generating an anti-CDH17 antibody or an antigen-binding fragment thereof as described in any one of claims 1 to 11, characterized in that, The method includes the following steps: (a) Culturing the recombinant cell described in claim 12 under conditions for expressing the anti-CDH17 antibody or an antigen-binding fragment thereof; (b) Separating and purifying the anti-CDH17 antibody or an antigen-binding fragment thereof obtained in step (a).

16. A method for treating a disease, the method comprising administering to a subject in need thereof a therapeutically effective amount of the anti-CDH17 antibody or antigen-binding fragment thereof according to any one of claims 1 to 11, the biological material according to claim 12, or the pharmaceutical composition according to claim 13; optionally, the disease is a human CDH17 high-expression related disease; Optionally, the disease is a tumor; Optionally, the tumor is selected from lung cancer, prostate cancer, breast cancer, head and neck cancer, esophageal cancer, gastric cancer, colon cancer, rectal cancer, bladder cancer, cervical cancer, uterine cancer, ovarian cancer, liver cancer, melanoma, kidney cancer, squamous cell carcinoma, and hematological cancer.

17. A kit for detecting CDH17, characterized in that, Comprising the anti-CDH17 antibody or antigen-binding fragment thereof according to any one of claims 1 to 11, or the multispecific antibody according to claim 12.

Images