ANTI-CLDN18.2 ANTIBODY AND ITS USES

Abstract

The present invention relates to the field of immunology and the treatment of diseases. In particular, the present invention relates to an anti-CLDN18.2 antibody or antigen-binding fragment thereof, a nucleic acid molecule encoding it, an immunoconjugate, a bispecific molecule, a chimeric antigen receptor, and a pharmaceutical composition comprising it, and its uses for the prevention and / or treatment of a tumor.

Description

ANTI-CLDN18.2 ANTIBODY AND ITS USES DESCRIPTION Technical field The present invention relates to the field of immunology and the treatment of diseases. In particular, the present invention relates to an anti-CLDN18.2 antibody or an antigen-binding fragment thereof, a nucleic acid molecule encoding it, an immunoconjugate, a bispecific molecule, a chimeric antigen receptor and a composition pharmaceutical that contains them, and their use for the prevention and / or treatment of a tumor. Background Stomach cancer is one of the most common malignant tumors in the world, its 5-year survival rate is low and is at the level of 20% to 40% in most countries, and about 700,000 people die at cause of this disease every year. The survival rate of stomach cancer in China is 35.9%. According to statistics, the number of new cases of stomach cancer reached 679.1 per 100,000 and the number of deaths reached 498.0 per 100,000 in China in 2015, and therefore, stomach cancer became the second most common tumor with high morbidity and mortality after lung cancer. Stomach cancer has a high degree of malignancy, and because stomach cancer screening has not been widely carried out, patients are generally diagnosed at an advanced stage, thus missing the opportunity for surgery. radical and only chemotherapy remains the main treatment method. With the development of tumor molecular biology, it is confirmed that immunotherapy and targeted drugs are effective in the treatment of hematoma, breast cancer, and colorectal cancer, but their application in the treatment of stomach cancer has been relatively stopped. Currently, internationally approved targets for targeted therapy of stomach cancer include human epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor (VEGF), and approved stomach cancer immunotherapy target It is programmed cell death protein 1 (PD-1). In September 2017, based on the large-scale phase III clinical trial of ATTRACTION-2, the Ministry of Health, Labor and Welfare of Japan approved the PD-1 antibody Opdivo for the treatment of patients with refractory advanced stomach cancer. to chemotherapy: Compared with placebo, Opdivo could reduce the mortality rate by 37% and showed an effectiveness rate of 11.2%. Based on the Phase II clinical trial of Keynote 059, the US FDA has accelerated approval of the use of PD-1 Keytruda antibodies in the treatment of patients with chemotherapy-resistant PD-L1 positive advanced stomach cancer, which shows an effectiveness rate of 15.5 ΜΛ / t / ZUZ I / υοοζου %. In terms of targeted therapy, vascular endothelial growth factor (VEGF) not only promotes tumor angiogenesis, but also binds to receptors on the surface of tumor cells to activate downstream signaling pathways and directly participates in the formation , appearance and migration of tumor stem cells. The VEGFR2 inhibitors apatinib and ramucirumab have been clinically confirmed to be safe and effective for VEGFR-targeted therapy of second-line and higher advanced stomach cancer. HER2 gene amplification or protein overexpression occurs in about 6% to 35% of new stomach cancer cases each year, therefore, HER2 is one of the important targets in cancer treatment. The TOGA phase III clinical trial demonstrated for the first time the advantages of trastuzumab in the first-line treatment of HER2(+) advanced stomach cancer, and the OS of the group treated with trastuzumab combined with chemotherapy was significantly longer than that of the group treated with chemotherapy alone (13.8 months vs. 11 months), and secondary endpoints including PFS (progression-free survival), ORR (objective response rate), and TTP (time to progression) were also significantly improved. However, the proportion of HER2-positive patients in China is only about 10%, therefore, it is imperative to explore new therapeutic targets for stomach cancer. Claudin is a transmembrane protein complex within the tight junctions of epithelia and endothelia and is located on the upper side of the space between adjacent cells. Its distribution is specific to tissues and organs, and its functions mainly include cell adhesion, maintaining cell polarity, regulating paracellular permeability and participating in the regulation of cell proliferation and differentiation. The molecule Claudin18 is a tetraspanin with four hydrophobic transmembrane regions and two extracellular loops, and occurs as two different splice variants: CLDN18.1 and CLDN18.2. CLDN18.1 and CLDN18.2 differ in sequence at the N terminus of the intracellular region and the first extracellular loop, but share the same primary protein sequence in the other parts. The tissue distribution of CLDN18 shows that CLDN18.1 is only selectively expressed in lung cells, while CLDN18.2 is only expressed in gastric cells, and the expression of CLDN18.2 in the normal stomach is limited to differentiated cells of short-lived gastric epithelium. CLDN18.2 is frequently retained during malignant transformation of gastric cells and is therefore frequently displayed on the surface of human stomach cancer cells, and 60% to 80% of gastrointestinal adenomas are positive. for CLDN18.2 (Clinical Cancer Research 2008,14 (23): 7624-34). Furthermore, CLDN18.2 is highly expressed in pancreatic duct cancer and metastatic pancreatic cancer, with a positive rate between 60% and 70%, and therefore, can be used as a diagnostic marker and therapeutic target for MA / t / ZUZ I / υοοζου pancreatic / pancreatic duct cancer (Journal of Clinical Pathology 2012, 65: 431- 436; World Journal of Gastroenterology 2014, 20 (31): 10813-10824; International Journal of Cancer 2014,134 :731-739). There is no comprehensive research on ectopic activation of CLDN18.2 in other tumors, and currently available papers show that, in addition to the above-mentioned ectopic activation in pancreatic cancer, this protein is also expressed in pancreatic cancer. esophagus, in bronchial cancer, non-small cell lung cancer (NSCLC), breast cancer, ENT tumor (ear, nose and throat), ovarian cancer, colon cancer, liver cancer and metastases thereof, in especially in gastric cancer metastases such as Krukenberg tumor, peritoneal metastases and lymph node metastases (Clinical Cancer Research 2008, 14 (23): 7624-34; International Journal of Cancer 2014, 134: 731-739; Cancer Letters 2017, 403: 66-73; International Journal of Cancer 2014, 135 (9): 2206-2214). CLDN18.2 is a tumor target with preventive and therapeutic value, and its differential expression between cancer cells and normal cells, its localization in the membrane, its absence in most normal tissues relevant for toxicity, and the restriction of its expression in the stomach with respect to differentiated gastric cells that can be replenished with target-negative stem cells (or stem cells inaccessible due to their position) from the stomach, make CLDN18.2 an attractive target for cancer immunotherapy . Therefore, it is urgent and necessary to develop anti-CLDN18.2 antibodies with higher specificity, lower toxic or side effects, and better clinical efficacy, which will provide more medication options for cancer patients. Content of the present invention The antibody of the present invention can specifically recognize / bind to human CLDN18.2, and can induce the destruction of a cell (for example, a tumor cell) that expresses CLDN18.2 through ADCC and / or CDC, and shows better functional characteristics compared to the known anti-CLDN18.2 antibody. Therefore, the antibody of the present invention has the potential to prevent and / or treat a tumor, and has great clinical value. Antibodies of the present invention Therefore, in one aspect, the present invention provides an antibody or antigen-binding fragment thereof that is capable of specifically binding to CLDN18.2, comprising: (a) a heavy chain variable region (VH) comprising the following three complementary determining regions (CDRs): (i) VH CDR1, consisting of the following sequence: SEQ ID NO: 75, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to SEQ ID NO: 75, MA / t / ZUZ I / υοοζου (i) VH CDR2, consisting of the following sequence: SEQ ID NO: 76, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution , deletion or addition of 1,2 or 3 amino acids) compared to SEQ ID NO: 76, and (iii) VH CDR3, which consists of the following sequence: SEQ ID NO: 77, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to SEQ ID NO: 77; and / or (b) a light chain variable region (VL) comprising the following three complementary determining regions (CDR): (iv) VL CDR1, which consists of the following sequence: SEQ ID NO: 78, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to SEQ ID NO: 78, (v) VL CDR2, which consists of the following sequence: SEQ ID NO: 79, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to SEQ ID NO: 79, and (vi) VL CDR3, which consists of the following sequence: SEQ ID NO: 80, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to SEQ ID NO: 80. In certain preferred embodiments, the substitution as mentioned in any one of points (i) to (vi) is a conservative substitution; In certain preferred embodiments, the VH of the antibody or antigen binding fragment thereof comprises: VH CDR1 as shown in SEQ ID NO: 75, VH CDR2 as shown in SEQ ID NO: 76, VH CDR3 as shown in SEQ ID NO: 77; and the VL of the antibody or antigen binding fragment thereof comprises: VL CDR1 as shown in SEQ ID NO: 78 or 96, VL CDR2 as shown in SEQ ID NO: 79 and VL CDR3 as shown sample in SEQ ID NO: 80. The present invention also provides an antibody or antigen-binding fragment thereof that is capable of specifically binding to CLDN18.2, comprising a heavy chain variable region and a light chain variable region, wherein, (a) the region heavy chain variable comprises the 3 CDRs of the heavy chain variable region as shown in SEQ ID NO: 73; and the light chain variable region comprises the 3 CDRs of the light chain variable region as shown in SEQ ID NO: 74; or (b) the heavy chain variable region comprises the 3 CDRs of the heavy chain variable region M A / t / ZUZ I / υοοζου heavy chain as shown in SEQ ID NO: 91; and the light chain variable region comprises the 3 CDRs of the light chain variable region as shown in SEQ ID NO: 92. In certain preferred embodiments, the 3 CDRs of the heavy chain variable region, and / or the 3 CDRs of the light chain variable region, are determined using the Kabat, Chothia or IMGT numbering system. In certain preferred embodiments, the antibody or antigen-binding fragment thereof is 44F7 or an antigen-binding fragment thereof, a chimeric antibody thereof, or a humanized antibody thereof, or a variant thereof, wherein The variant substantially retains the biological function of the antibody or antigen-binding fragment from which it is derived. In certain preferred embodiments, the antibody or antigen-binding fragment thereof has one or more of the following biological functions: (a) binding to human CLDN18.2 with an EC50 of 0.1 pg / ml or less (e.g., 0.05 pg / ml or less); (b) binding to mouse CLDN18.2 with an EC50 of 0.1 pg / ml or less; (c) no binding to human CLDN18.1; (d) induction of killing of a human CLDN18.2-expressing cell (e.g., a tumor cell, such as a CLDN18.2-expressing tumor cell) via antibody-dependent cellular cytotoxicity (ADCC). English); (e) induction of killing of a human CLDN18.2-expressing cell (e.g., a tumor cell, such as a CLDN18.2-expressing tumor cell) via complement-dependent cytotoxicity (CDC). ); (f) prevention and / or treatment of a tumor (for example, a tumor that expresses CLDN18.2) in a subject. In certain preferred embodiments, the antibody or antigen-binding fragment thereof comprises: (1) VH CDR1 as shown in SEQ ID NO: 75, VH CDR2 as shown in SEQ ID NO: 76, VH CDR3 as shown in SEQ ID NO: 77; VL CDR1 as shown in SEQ ID NO: 78 or 96, VL CDR2 as shown in SEQ ID NO: 79, VL CDR3 as shown in SEQ ID NO: 80; or (2) (a) the 3 CDRs of the heavy chain variable region as shown in SEQ ID NO: 73; and the 3 CDRs of the light chain variable region as shown in SEQ ID NO: 74; or (b) the 3 CDRs of the heavy chain variable region as shown in SEQ MA / t / ZUZ I / UODZDO ID NO: 91; and the 3 CDRs of the light chain variable region as shown in SEQ ID NO: 92. In an illustrative embodiment, the antibody or antigen-binding fragment thereof comprises: (a) a heavy chain variable region (VH) comprising an amino acid sequence selected from the group consisting of: (i) the sequence as shown in SEQ ID NO: 73; (i) a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2, 3, 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 73; or (iii) a sequence that has a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 73; and / or (b) a variable light chain (VL) region comprising an amino acid sequence selected from the group consisting of: (iv) the sequence as shown in SEQ ID NO: 74; (v) a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2, 3, 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 74; or (vi) a sequence that has a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 74. In certain preferred embodiments, the substitution as mentioned in (i) or (v) is a conservative substitution. In certain preferred embodiments, the antibody or antigen-binding fragment thereof comprises: a VH having a sequence as shown in SEQ ID NO: 73 and a VL having a sequence as shown in SEQ ID NO: 74. In certain preferred embodiments, the antibody or antigen-binding fragment thereof is humanized. In certain preferred embodiments, the VH of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) framework region (FR). M A / I / UODZDO derived from a human immunoglobulin, and / or the VL of the antibody or antigen binding fragment thereof comprises a framework region (FR) of the variable region of the light chain (VL) derived from a human immunoglobulin. In such embodiments, the FR of the heavy chain variable region and / or the FR of the light chain variable region of the antibody or antigen-binding fragment thereof may comprise one or more non-human amino acid residues (e.g. , murine), for example, the heavy chain FR framework region and / or the light chain FR framework region may comprise one or more amino acid retromutations, and the corresponding murine amino acid residues are contained in these retromutations. In certain preferred embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a heavy chain framework region of a human immunoglobulin or a variant thereof, wherein the variant has a conservative substitution of up to 20 amino acids (for example, a conservative substitution of up to 15, up to 10 or up to 5 amino acids ; for example, a conservative substitution of 1,2, 3, 4 or 5 amino acids) compared to the sequence from which it is derived; and / or (b) a framework region of the light chain of a human immunoglobulin or a variant thereof, wherein the variant has a conservative substitution of up to 20 amino acids (for example, a conservative substitution of up to 15, up to 10 , or up to 5 amino acids; for example, a conservative substitution of 1,2, 3, 4 or 5 amino acids) compared to the sequence from which it is derived. In certain preferred embodiments, the antibody or antigen-binding fragment thereof comprises a framework region of a human immunoglobulin, such as a framework region contained in an amino acid sequence encoded by a human germline antibody gene. In certain preferred embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain framework region contained in an amino acid sequence encoded by a human heavy chain germline gene, and / or a framework region of light chain contained in an amino acid sequence encoded by a human light chain germ chain gene. In such embodiments, the framework region (heavy chain framework region and / or light chain framework region) of the antibody or antigen-binding fragment thereof may comprise one or more non-human (e.g., murine) amino acid residues. . In certain preferred embodiments, the framework region (heavy chain framework region and / or light chain framework region) comprises one or more amino acid residues that backmutate to the corresponding murine residues or a conservative amino acid substitution of the residues. corresponding murine MA / / UOOZOO (such a mutation is called a retromutation). Therefore, in certain preferred embodiments, the antibody or antigen-binding fragment thereof comprises a framework region of a human immunoglobulin (for example, a framework region contained in an amino acid sequence encoded by a line antibody gene. human germline), the framework region optionally comprises one or more backmutations of human residues to murine residues. In an illustrative embodiment, the antibody or antigen-binding fragment thereof comprises: (a) a heavy chain variable region (VH) comprising an amino acid sequence selected from the group consisting of: (i) the sequence as shown in SEQ ID NO: 91; (i) a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2, 3, 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 91; or (i¡) a sequence that has a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%. at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 91; and / or (b) a variable light chain (VL) region comprising an amino acid sequence selected from the group consisting of: (iv) the sequence as shown in SEQ ID NO: 92; (v) a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2, 3, 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 92; or (vi) a sequence that has a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 92. In certain preferred embodiments, the substitution as mentioned in (i) or (v) is a conservative substitution. In certain preferred embodiments, the antibody or antigen-binding fragment thereof comprises: a VH having a sequence as shown in SEQ ID NO: 91, and a VL having a sequence as shown in SEQ ID NO: 92. MA / t / ZUZ I / υοοζου In an illustrative embodiment, the antibody or antigen-binding fragment thereof comprises: (a) a heavy chain variable region (VH) comprising an amino acid sequence selected from the group consisting of: (i) the sequence as shown in SEQ ID NO: 99; (i) a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2, 3, 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 99; or (iii) a sequence that has a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 99; and / or (b) a variable light chain (VL) region comprising an amino acid sequence selected from the group consisting of: (iv) the sequence as shown in SEQ ID NO: 100; (v) a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2, 3, 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 100; or (vi) a sequence that has a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 100. In certain preferred embodiments, the substitution as mentioned in (i) or (v) is a conservative substitution. In certain preferred embodiments, the antibody or antigen-binding fragment thereof comprises: a VH having a sequence as shown in SEQ ID NO: 99 and a VL having a sequence as shown in SEQ ID NO: 100. In an illustrative embodiment, the antibody or antigen-binding fragment thereof comprises: (a) a heavy chain variable region (VH) comprising an amino acid sequence selected from the group consisting of: (i) the sequence as shown in SEQ ID NO: 101; (i) a sequence that has a substitution, deletion or addition of one or more amino acids M A / t / ZUZ I / υοοζου (e.g., a substitution, deletion or addition of 1,2, 3, 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 101; or (iii) a sequence that has a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 101; and / or (b) a variable light chain (VL) region comprising an amino acid sequence selected from the group consisting of: (iv) the sequence as shown in SEQ ID NO: 102; (v) a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2, 3, 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 102; or (vi) a sequence that has a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 102. In certain preferred embodiments, the substitution as mentioned in (i) or (v) is a conservative substitution. In certain preferred embodiments, the antibody or antigen-binding fragment thereof comprises: a VH having a sequence as shown in SEQ ID NO: 101 and a VL having a sequence as shown in SEQ ID NO: 102. In one aspect, the present invention provides an antibody or antigen-binding fragment thereof that is capable of specifically binding to CLDN18.2, comprising: (a) a heavy chain variable region (VH) comprising the following three complementary determining regions (CDR): (i) VH CDR1, consisting of the following sequence: SEQ ID NO: 3, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to them; (i) VH CDR2, consisting of the following sequence: SEQ ID NO: 4, or a sequence having a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared thereto; and (iii) VH CDR3, which consists of the following sequence: SEQ ID NO: 5, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, MA / I / UOOZOO deletion or addition of 1,2 or 3 amino acids) compared to them; and / or (b) a light chain variable region (VL) comprising the following three complementary determining regions (CDR): (iv) VL CDR1, which consists of the following sequence: SEQ ID NO: 6, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to them; (v) VL CDR2, which consists of the following sequence: SEQ ID NO: 7, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to them; and (vi) VL CDR3, which consists of the following sequence: SEQ ID NO: 8, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to them. In certain preferred embodiments, the substitution, as mentioned in any one of points (i) to (vi), is a conservative substitution. In certain preferred embodiments, the VH of the antibody or antigen binding fragment thereof comprises: VH CDR1 as shown in SEQ ID NO: 3, VH CDR2 as shown in SEQ ID NO: 4, and VH CDR3 as shown in SEQ ID NO: 5; and the VL of the antibody or antigen binding fragment thereof comprises: VL CDR1 as shown in SEQ ID NO: 6, VL CDR2 as shown in SEQ ID NO: 7 and VL CDR3 as shown in SEQ ID NO: 8. The present invention also provides an antibody or antigen-binding fragment thereof that is capable of specifically binding to CLDN18.2, comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the 3 CDRs of the heavy chain variable region as shown in SEQ ID NO: 1; and the light chain variable region comprises the 3 CDRs of the light chain variable region as shown in SEQ ID NO: 2. In certain preferred embodiments, the 3 CDRs of the heavy chain variable region, and / or the 3 CDRs of the light chain variable region, are determined using the Kabat, Chothia or IMGT numbering system. In certain preferred embodiments, the antibody or antigen-binding fragment thereof is 1D10 or an antigen-binding fragment thereof, a chimeric antibody thereof, or a humanized antibody thereof, or a variant thereof, wherein that the variant substantially retains a biological function of the antibody or antigen-binding fragment of the ΜΛ / t / ZUZ I / υοοζου which derives. In certain preferred embodiments, the antibody or antigen-binding fragment thereof has one or more of the following biological functions: (a) binding to human CLDN18.2 with an EC50 of 0.1 pg / ml or less (e.g., 0.05 pg / ml, 0.02 pg / ml or less); (b) binding to mouse CLDN18.2 with an EC50 of 1 pg / ml or less; (c) induction of killing of a human CLDN18.2-expressing cell (e.g., a tumor cell, such as a CLDN18.2-expressing tumor cell) via antibody-dependent cellular cytotoxicity (ADCC); (d) induction of destruction of a human CLDN18.2-expressing cell (e.g., a tumor cell, such as a CLDN18.2-expressing tumor cell) through complement-dependent cytotoxicity (CDC); (e) mediating internalization of CLDN18.2 into a cell (e.g., a tumor cell), e.g. with an internalization level of at least 10% (e.g., at least 15%, at least 20% or plus) as measured by FACS or flow cytometry; the cell has CLDN18.2 expressed on its surface; (f) prevention and / or treatment of a tumor (for example, a tumor that expresses CLDN18.2) in a subject. In certain preferred embodiments, the antibody or antigen-binding fragment thereof comprises: (1) VH CDR1 as shown in SEQ ID NO: 3, VH CDR2 as shown in SEQ ID NO: 4 and VH CDR3 as shown in SEQ ID NO: 5; VL CDR1 as shown in SEQ ID NO: 6; VL CDR2 as shown in SEQ ID NO: 7; VL CDR3 as shown in SEQ ID NO: 8; or (2) the 3 CDRs of the heavy chain variable region as shown in SEQ ID NO: 1; and the 3 CDRs of the light chain variable region as shown in SEQ ID NO: 2. In an illustrative embodiment, the antibody or antigen-binding fragment thereof comprises: (a) a heavy chain variable region (VH) comprising an amino acid sequence selected from the group consisting of: (i) the sequence as shown in SEQ ID NO: 1; (i) a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2, 3, 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 1; either M A / t / ZUZ I / υοοζου (ii) a sequence that has a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93% , at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 1; and / or (b) a variable light chain (VL) region comprising an amino acid sequence selected from the group consisting of: (iv) the sequence as shown in SEQ ID NO: 2; (v) a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2, 3, 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 2; or (vi) a sequence that has a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 2. In certain preferred embodiments, the substitution as mentioned in (i) or (v) is a conservative substitution. In certain preferred embodiments, the antibody or antigen-binding fragment thereof comprises: a VH having a sequence as shown in SEQ ID NO: 1, and a VL having a sequence as shown in SEQ ID NO: 2. In certain preferred embodiments, the antibody or antigen-binding fragment thereof is humanized. In certain preferred embodiments, the VH of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) framework region (FR) derived from a human immunoglobulin, and / or the VL of the antibody or fragment Antigen binding thereof comprises a framework region (FR) of the variable region of the light chain (VL) derived from a human immunoglobulin. In such embodiments, the FR of the heavy chain variable region and / or the FR of the light chain variable region of the antibody or antigen-binding fragment thereof may comprise one or more non-human amino acid residues (e.g. , murine), for example, the heavy chain FR framework region and / or the light chain FR framework region may comprise one or more amino acid retromutations, and the corresponding murine amino acid residues are contained in these retromutations. In one aspect, the present invention provides an antibody or antigen-binding fragment thereof that is capable of specifically binding to CLDN18.2, comprising: MA / t / ZUZ I / υοοζου (a) a heavy chain variable region (VH) comprising the following three complementary determining regions (CDR): (i) VH CDR1, consisting of the following sequence: SEQ ID NO: 11, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to them; (i) VH CDR2, consisting of the following sequence: SEQ ID NO: 12, or a sequence having a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared thereto; and (ü) VH CDR3, which consists of the following sequence: SEQ ID NO: 13, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1, 2 or 3 amino acids) compared to them; and / or (b) a light chain variable region (VL) comprising the following three complementary determining regions (CDR): (iv) VL CDR1, which consists of the following sequence: SEQ ID NO: 14, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to them; (v) VL CDR2, which consists of the following sequence: SEQ ID NO: 15, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to them; and (vi) VL CDR3, which consists of the following sequence: SEQ ID NO: 16, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to them. In certain preferred embodiments, the substitution, as mentioned in any one of points (i) to (vi), is a conservative substitution. In certain preferred embodiments, the VH of the antibody or antigen binding fragment thereof comprises: VH CDR1 as shown in SEQ ID NO: 11, VH CDR2 as shown in SEQ ID NO: 12, and VH CDR3 as shown in SEQ ID NO: 13; and the VL of the antibody or antigen binding fragment thereof comprises: VL CDR1 as shown in SEQ ID NO: 14, VL CDR2 as shown in SEQ ID NO: 15 and VL CDR3 as shown in SEQ ID NO: 16. The present invention also provides an antibody or antigen-binding fragment thereof that is capable of specifically binding to CLDN18.2, comprising a heavy chain variable region and a light chain variable region, wherein the chain variable region M A / t / ZUZ I / υοοζου heavy comprises the 3 CDRs of the chain variable region as shown in SEQ ID NO: 9; and the light chain variable region contains the 3 CDRs of the light chain variable region as shown in SEQ ID NO: 10. In certain preferred embodiments, the 3 CDRs of the heavy chain variable region, and / or the 3 CDRs of the light chain variable region, are determined using the Kabat, Chothia or IMGT numbering system. In certain preferred embodiments, the antibody or antigen-binding fragment thereof is 2F12 or an antigen-binding fragment thereof, a chimeric antibody thereof, or a humanized antibody thereof, or a variant thereof, wherein that the variant substantially retains a biological function of the antibody or antigen-binding fragment from which it is derived. In certain preferred embodiments, the antibody or antigen-binding fragment thereof has one or more of the following biological functions: (a) binding to human CLDN18.2 with an EC50 of 0.1 pg / ml or less (e.g., 0.05 pg / ml or less); (b) binding to mouse CLDN18.2 with an EC50 of 0.1 pg / ml or less; (c) no binding to human CLDN18.1; (d) induction of killing of a human CLDN18.2-expressing cell (e.g., a tumor cell, such as a CLDN18.2-expressing tumor cell) via antibody-dependent cellular cytotoxicity (ADCC); (e) induction of destruction of a human CLDN18.2-expressing cell (e.g., a tumor cell, such as a CLDN18.2-expressing tumor cell) through complement-dependent cytotoxicity (CDC). refers to an anti-CLDN18.2 antibody or antigen-binding fragment thereof, a nucleic acid molecule that encodes it, an immunoconjugate, a bispecific molecule, a chimeric antigen receptor and a pharmaceutical composition comprising it, and the uses of the same for prevention and / or treatment of a tumor. (f) prevention and / or treatment of a tumor (for example, a tumor that expresses CLDN18.2) in a subject. In certain preferred embodiments, the antibody or antigen-binding fragment thereof comprises: (1) VH CDR1 as shown in SEQ ID NO: 11, VH CDR2 as shown in SEQ ID NO: 12, VH CDR3 as shown in SEQ ID NO: 13; VL CDR1 as shown in SEQ ID NO: 14; VL CDR2 as shown in SEQ ID NO: 15; VL CDR3 such MA / t / ZUZ I / UODZDO as shown in SEQ ID NO: 16; or (2) the 3 CDRs of the heavy chain variable region as shown in SEQ ID NO: 9; and the 3 CDRs of the light chain variable region as shown in SEQ ID NO: 10. In an illustrative embodiment, the antibody or antigen-binding fragment thereof comprises: (a) a heavy chain variable region (VH) comprising an amino acid sequence selected from the group consisting of: (i) the sequence as shown in SEQ ID NO: 9; (i) a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2, 3, 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 9; or (iii) a sequence that has a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 9; and / or (b) a variable light chain (VL) region comprising an amino acid sequence selected from the group consisting of: (iv) the sequence as shown in SEQ ID NO: 10; (v) a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2, 3, 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 10; or (vi) a sequence that has a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 10. In certain preferred embodiments, the substitution as mentioned in (i) or (v) is a conservative substitution. In certain preferred embodiments, the antibody or antigen-binding fragment thereof comprises: a VH having a sequence as shown in SEQ ID NO: 9, and a VL having a sequence as shown in SEQ ID NO: 10. In certain preferred embodiments, the antibody or antigen-binding fragment thereof is humanized. In certain preferred embodiments, the VH of the antibody or binding fragment MA / t / ZUZ I / υοοζου antigen thereof comprises a heavy chain variable region (VH) framework region (FR) derived from a human immunoglobulin, and / or the VL of the antibody or antigen binding fragment thereof comprises a framework region (FR) of the light chain variable region (VL) derived from a human immunoglobulin. In such embodiments, the FR of the heavy chain variable region and / or the FR of the light chain variable region of the antibody or antigen-binding fragment thereof may comprise one or more non-human amino acid residues (e.g. , murine), for example, the heavy chain FR framework region and / or the light chain FR framework region may comprise one or more amino acid retromutations, and the corresponding murine amino acid residues are contained in these retromutations. In another aspect, the present invention provides an antibody or antigen-binding fragment thereof that is capable of specifically binding to CLDN18.2, comprising: (a) a heavy chain variable region (VH) comprising the following three complementary determining regions (CDR): (i) VH CDR1, consisting of the following sequence: SEQ ID NO: 19, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to them; (i) VH CDR2, consisting of the following sequence: SEQ ID NO: 20, or a sequence having a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared thereto; and (i¡) VH CDR3, which consists of the following sequence: SEQ ID NO: 21, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1 ,2 or 3 amino acids) compared to them; and / or (b) a light chain variable region (VL) comprising the following three complementary determining regions (CDR): (iv) VL CDR1, which consists of the following sequence: SEQ ID NO: 22, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to them; (v) VL CDR2, which consists of the following sequence: SEQ ID NO: 23, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to them; and (vi) VL CDR3, which consists of the following sequence: SEQ ID NO: 24, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to them. ΜΛ / t / ZUZ I / υοοζου In certain preferred embodiments, the substitution, as mentioned in any one of points (i) to (vi), is a conservative substitution. In certain preferred embodiments, the VH of the antibody or antigen binding fragment thereof comprises: VH CDR1 as shown in SEQ ID NO: 19, VH CDR2 as shown in SEQ ID NO: 20, VH CDR3 as shown in SEQ ID NO: 21; and the VL of the antibody or antigen binding fragment thereof comprises: VL CDR1 as shown in SEQ ID NO: 22, VL CDR2 as shown in SEQ ID NO: 23 and VL CDR3 as shown in SEQ ID NO: 24. The present invention also provides an antibody or antigen-binding fragment thereof that is capable of specifically binding to CLDN18.2, comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the 3 CDRs of the heavy chain variable region as shown in SEQ ID NO: 17; and the light chain variable region comprises the 3 CDRs of the light chain variable region as shown in SEQ ID NO: 18. In certain preferred embodiments, the 3 CDRs of the heavy chain variable region, and / or the 3 CDRs of the light chain variable region, are determined using the Kabat, Chothia or IMGT numbering system. In certain preferred embodiments, the antibody or antigen-binding fragment thereof is 3F2 or an antigen-binding fragment thereof, a chimeric antibody thereof, or a humanized antibody thereof, or a variant thereof, wherein that the variant substantially retains a biological function of the antibody or antigen-binding fragment from which it is derived. In certain preferred embodiments, the antibody or antigen-binding fragment thereof has one or more of the following biological functions: (a) binding to human CLDN18.2 with an EC50 of 0.1 pg / ml or less (e.g., 0.05 pg / ml or less); (b) binding to mouse CLDN18.2 with an EC50 of 0.1 pg / ml or less; (c) no binding to human CLDN18.1; (d) induction of killing of a human CLDN18.2-expressing cell (e.g., a tumor cell, such as a CLDN18.2-expressing tumor cell) via antibody-dependent cellular cytotoxicity (ADCC); (e) induction of destruction of a human CLDN18.2-expressing cell (e.g., a tumor cell, such as a CLDN18.2-expressing tumor cell) through complement-dependent cytotoxicity (CDC); M A / t / ZUZ I / υοοζου (f) prevention and / or treatment of a tumor (for example, a tumor that expresses CLDN18.2) in a subject. In certain preferred embodiments, the antibody or antigen-binding fragment thereof comprises: (1) VH CDR1 as shown in SEQ ID NO: 19, VH CDR2 as shown in SEQ ID NO: 20, VH CDR3 as shown in SEQ ID NO: 21; VL CDR1 as shown in SEQ ID NO: 22; VL CDR2 as shown in SEQ ID NO: 23; VL CDR3 as shown in SEQ ID NO: 24; or (2) the 3 CDRs of the heavy chain variable region as shown in SEQ ID NO: 17; and the 3 CDRs of the light chain variable region as shown in SEQ ID NO: 18. In an illustrative embodiment, the antibody or antigen-binding fragment thereof comprises: (a) a heavy chain variable region (VH) comprising an amino acid sequence selected from the group consisting of: (i) the sequence as shown in SEQ ID NO: 17; (i) a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2, 3, 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 17; or (i¡) a sequence that has a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%. at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 17; and / or (b) a variable light chain (VL) region comprising an amino acid sequence selected from the group consisting of: (iv) the sequence as shown in SEQ ID NO: 18; (v) a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2, 3, 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 18; or (vi) a sequence that has a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 18. In certain preferred embodiments, the substitution as mentioned in (i) or (v) M A / / UOOZOO is a conservative substitution. In certain preferred embodiments, the antibody or antigen-binding fragment thereof comprises: a VH having a sequence as shown in SEQ ID NO: 17, and a VL having a sequence as shown in SEQ ID NO: 18. In certain preferred embodiments, the antibody or antigen-binding fragment thereof is humanized. In certain preferred embodiments, the VH of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) framework region (FR) derived from a human immunoglobulin, and / or the VL of the antibody or fragment Antigen binding thereof comprises a framework region (FR) of the variable region of the light chain (VL) derived from a human immunoglobulin. In such embodiments, the FR of the heavy chain variable region and / or the FR of the light chain variable region of the antibody or antigen-binding fragment thereof may comprise one or more non-human amino acid residues (e.g. , murine), for example, the heavy chain FR framework region and / or the light chain FR framework region may comprise one or more amino acid retromutations, and the corresponding murine amino acid residues are contained in these retromutations. In another aspect, the present invention provides an antibody or antigen-binding fragment thereof that is capable of specifically binding to CLDN18.2, comprising: (a) a heavy chain variable region (VH) comprising the following three complementary determining regions (CDR): (i) VH CDR1, consisting of the following sequence: SEQ ID NO: 27, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to them; (i) VH CDR2, consisting of the following sequence: SEQ ID NO: 28, or a sequence having a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared thereto; and (iii) VH CDR3, which consists of the following sequence: SEQ ID NO: 29, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared thereto; and / or (b) a light chain variable region (VL) comprising the following three complementary determining regions (CDR): (iv) VL CDR1, which consists of the following sequence: SEQ ID NO: 30, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, M A / t / ZUZ I / UOOZOO deletion or addition of 1,2 or 3 amino acids) compared thereto; (v) VL CDR2, which consists of the following sequence: SEQ ID NO: 31, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to them; and (vi) VL CDR3, which consists of the following sequence: SEQ ID NO: 32, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to them. In certain preferred embodiments, the substitution, as mentioned in any one of points (i) to (vi), is a conservative substitution. In certain preferred embodiments, the VH of the antibody or antigen binding fragment thereof comprises: VH CDR1 as shown in SEQ ID NO: 27, VH CDR2 as shown in SEQ ID NO: 28, VH CDR3 as shown in SEQ ID NO: 29; and, the VL of the antibody or antigen binding fragment thereof comprises: VL CDR1 as shown in SEQ ID NO: 30, VL CDR2 as shown in SEQ ID NO: 31, and VL CDR3 as shown sample in SEQ ID NO: 32. The present invention also provides an antibody or antigen-binding fragment thereof that is capable of specifically binding to CLDN18.2, comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the 3 CDRs of the heavy chain variable region as shown in SEQ ID NO: 25; and the light chain variable region comprises the 3 CDRs of the light chain variable region as shown in SEQ ID NO: 26. In certain preferred embodiments, the 3 CDRs of the heavy chain variable region, and / or the 3 CDRs of the light chain variable region, are determined using the Kabat, Chothia or IMGT numbering system. In certain preferred embodiments, the antibody or antigen-binding fragment thereof is 5F9 or an antigen-binding fragment thereof, a chimeric antibody thereof, or a humanized antibody thereof, or a variant thereof, wherein that the variant substantially retains a biological function of the antibody or antigen-binding fragment from which it is derived. In certain preferred embodiments, the antibody or antigen-binding fragment thereof has one or more of the following biological functions: (a) binding to human CLDN18.2 with an EC50 of 0.5 pg / ml or less; (b) binding to mouse CLDN18.2 with an EC50 of 0.2 pg / ml or less; (c) induction of destruction of a cell expressing human CLDN18.2 (e.g. M A / t / ZUZ I / UODZDO a tumor cell, such as a tumor cell that expresses CLDN18.2) through antibody-dependent cellular cytotoxicity (ADCC); (d) induction of destruction of a human CLDN18.2-expressing cell (e.g., a tumor cell, such as a CLDN18.2-expressing tumor cell) through complement-dependent cytotoxicity (CDC); (e) mediating internalization of CLDN18.2 into a cell (e.g., a tumor cell), e.g. with an internalization level of at least 10% (e.g., at least 15%, at least 20% or plus) as measured by FACS or flow cytometry; the cell has CLDN18.2 expressed on its surface; (f) prevention and / or treatment of a tumor (for example, a tumor that expresses CLDN18.2) in a subject. In certain preferred embodiments, the antibody or antigen-binding fragment thereof comprises: (1) VH CDR1 as shown in SEQ ID NO: 27, VH CDR2 as shown in SEQ ID NO: 28, VH CDR3 as shown in SEQ ID NO: 29; VL CDR1 as shown in SEQ ID NO: 30, VL CDR2 as shown in SEQ ID NO: 31, VL CDR3 as shown in SEQ ID NO: 32; or (2) the 3 CDRs of the heavy chain variable region as shown in SEQ ID NO: 25; and the 3 CDRs of the light chain variable region shown in SEQ ID Nos: 26. In an illustrative embodiment, the antibody or antigen-binding fragment thereof comprises: (a) a heavy chain variable region (VH) comprising an amino acid sequence selected from the group consisting of: (i) the sequence as shown in SEQ ID NO: 25; (i) a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2, 3, 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 25; or (iii) a sequence that has a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 25; and / or (b) a variable light chain (VL) region comprising an amino acid sequence selected from the group consisting of: ΜΛ / t / ZUZ I / υοοζου (iv) the sequence as shown in SEQ ID NO: 26; (v) a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2, 3, 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 26; or (vi) a sequence that has a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 26. In certain preferred embodiments, the substitution as mentioned in (i) or (v) is a conservative substitution. In certain preferred embodiments, the antibody or antigen-binding fragment thereof comprises: a VH having a sequence as shown in SEQ ID NO: 25, and a VL having a sequence as shown in SEQ ID NO: 26. In certain preferred embodiments, the antibody or antigen-binding fragment thereof is humanized. In certain preferred embodiments, the VH of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) framework region (FR) derived from a human immunoglobulin, and / or the VL of the antibody or fragment Antigen binding thereof comprises a framework region (FR) of the variable region of the light chain (VL) derived from a human immunoglobulin. In such embodiments, the FR of the heavy chain variable region and / or the FR of the light chain variable region of the antibody or antigen-binding fragment thereof may comprise one or more non-human amino acid residues (e.g. , murine), for example, the heavy chain FR framework region and / or the light chain FR framework region may comprise one or more amino acid retromutations, and the corresponding murine amino acid residues are contained in these retromutations. In another aspect, the present invention provides an antibody or antigen-binding fragment thereof that is capable of specifically binding to CLDN18.2, comprising: (a) a heavy chain variable region (VH) comprising the following three complementary determining regions (CDR): (i) VH CDR1, consisting of the following sequence: SEQ ID NO: 35, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to them; (i) VH CDR2, consisting of the following sequence: SEQ ID NO: 36, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, ΜΛ / I / UOOZOO deletion or addition of 1,2 or 3 amino acids) compared thereto; and (ü) VH CDR3, which consists of the following sequence: SEQ ID NO: 37, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1, 2 or 3 amino acids) compared to them; and / or (b) a light chain variable region (VL) comprising the following three complementary determining regions (CDR): (iv) VL CDR1, which consists of the following sequence: SEQ ID NO: 38, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to them; (v) VL CDR2, which consists of the following sequence: SEQ ID NO: 39, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to them; and (vi) VL CDR3, which consists of the following sequence: SEQ ID NO: 40, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to them. In certain preferred embodiments, the substitution, as mentioned in any one of points (i) to (vi), is a conservative substitution. In certain preferred embodiments, the VH of the antibody or antigen binding fragment thereof comprises: VH CDR1 as shown in SEQ ID NO: 35, VH CDR2 as shown in SEQ ID NO: 36, VH CDR3 as shown in SEQ ID NO: 37; and the VL of the antibody or antigen binding fragment thereof comprises: VL CDR1 as shown in SEQ ID NO: 38, VL CDR2 as shown in SEQ ID NO: 39 and VL CDR3 as shown in SEQ ID NO: 40. The present invention also provides an antibody or antigen-binding fragment thereof that is capable of specifically binding to CLDN18.2, comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the 3 CDRs of the heavy chain variable region as shown in SEQ ID NO: 33; and the light chain variable region comprises the 3 CDRs of the light chain variable region as shown in SEQ ID NO: 34. In certain preferred embodiments, the 3 CDRs of the heavy chain variable region, and / or the 3 CDRs of the light chain variable region, are determined using the Kabat, Chothia or IMGT numbering system. In certain preferred embodiments, the antibody or antigen binding fragment M A / t / ZUZ I / υοοζου thereof is 9F3 or an antigen-binding fragment thereof, a chimeric antibody thereof, or a humanized antibody thereof, or a variant thereof, wherein the variant substantially retains a function biology of the antibody or antigen-binding fragment from which it is derived. In certain preferred embodiments, the antibody or antigen-binding fragment thereof has one or more of the following biological functions: (a) binding to human CLDN18.2 with an EC50 of 0.2 pg / ml or less; (b) binding to mouse CLDN18.2 with an EC50 of 0.1 pg / ml or less; (c) no binding to human CLDN18.1; (d) induction of killing of a human CLDN18.2-expressing cell (e.g., a tumor cell, such as a CLDN18.2-expressing tumor cell) via antibody-dependent cellular cytotoxicity (ADCC); (e) induction of destruction of a human CLDN18.2-expressing cell (e.g., a tumor cell, such as a CLDN18.2-expressing tumor cell) through complement-dependent cytotoxicity (CDC); (f) prevention and / or treatment of a tumor (for example, a tumor that expresses CLDN18.2) in a subject. In certain preferred embodiments, the antibody or antigen-binding fragment thereof comprises: (1) VH CDR1 as shown in SEQ ID NO: 35, VH CDR2 as shown in SEQ ID NO: 36, VH CDR3 as shown in SEQ ID NO: 37; VL CDR1 as shown in SEQ ID NO: 38, VL CDR2 as shown in SEQ ID NO: 39, VL CDR3 as shown in SEQ ID NO: 40; or (2) the 3 CDRs of the heavy chain variable region as shown in SEQ ID NO: 33; and the 3 CDRs of the light chain variable region as shown in SEQ ID NO: 34. In an illustrative embodiment, the antibody or antigen-binding fragment thereof comprises: (a) a heavy chain variable region (VH) comprising an amino acid sequence selected from the group consisting of: (i) the sequence as shown in SEQ ID NO: 33; (i) a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2, 3, 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 33; or (iii) a sequence that has a sequence identity of at least 80%, at least 85%, M A / t / ZUZ I / UO3Z00 at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 33; and / or (b) a variable light chain (VL) region comprising an amino acid sequence selected from the group consisting of: (iv) the sequence as shown in SEQ ID NO: 34; (v) a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2, 3, 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 34; or (vi) a sequence that has a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 34. In certain preferred embodiments, the substitution as mentioned in (i) or (v) is a conservative substitution. In certain preferred embodiments, the antibody or antigen-binding fragment thereof comprises: a VH having a sequence as shown in SEQ ID NO: 33, and a VL having a sequence as shown in SEQ ID NO: 34. In certain preferred embodiments, the antibody or antigen-binding fragment thereof is humanized. In certain preferred embodiments, the VH of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) framework region (FR) derived from a human immunoglobulin, and / or the VL of the antibody or fragment Antigen binding thereof comprises a framework region (FR) of the variable region of the light chain (VL) derived from a human immunoglobulin. In such embodiments, the FR of the heavy chain variable region and / or the FR of the light chain variable region of the antibody or antigen-binding fragment thereof may comprise one or more non-human amino acid residues (e.g. , murine), for example, the heavy chain FR framework region and / or the light chain FR framework region may comprise one or more amino acid retromutations, and the corresponding murine amino acid residues are contained in these retromutations. In another aspect, the present invention provides an antibody or antigen-binding fragment thereof that is capable of specifically binding to CLDN18.2, comprising: (a) a heavy chain variable region (VH) comprising the following three regions M A / t / ZUZ I / υοοζου complementary determinants (CDR): (i) VH CDR1, consisting of the following sequence: SEQ ID NO: 43, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to them; (i) VH CDR2, consisting of the following sequence: SEQ ID NO: 44, or a sequence having a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared thereto; and (iii) VH CDR3, which consists of the following sequence: SEQ ID NO: 45, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared thereto; and / or (b) a light chain variable region (VL) comprising the following three complementary determining regions (CDR): (iv) VL CDR1, which consists of the following sequence: SEQ ID NO: 46, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to them; (v) VL CDR2, which consists of the following sequence: SEQ ID NO: 47, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to them; and (vi) VL CDR3, which consists of the following sequence: SEQ ID NO: 48, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to them. In certain preferred embodiments, the substitution, as mentioned in any one of points (i) to (vi), is a conservative substitution. In certain preferred embodiments, the VH of the antibody or antigen binding fragment thereof comprises: VH CDR1 as shown in SEQ ID NO: 43, VH CDR2 as shown in SEQ ID NO: 44, VH CDR3 as shown in SEQ ID NO: 45; and the VL of the antibody or antigen binding fragment thereof comprises: VL CDR1 as shown in SEQ ID NO: 46, VL CDR2 as shown in SEQ ID NO: 47 and VL CDR3 as shown in SEQ ID NO: 48. The present invention also provides an antibody or antigen-binding fragment thereof that is capable of specifically binding to CLDN18.2, comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the 3 CDRs of the heavy chain variable region as shown in the ΜΛ / I / UODZDO SEQ ID NO: 41; and the light chain variable region comprises the 3 CDRs of the light chain variable region as shown in SEQ ID NO: 42. In certain preferred embodiments, the 3 CDRs of the heavy chain variable region, and / or the 3 CDRs of the light chain variable region, are determined using the Kabat, Chothia or IMGT numbering system. In certain preferred embodiments, the antibody or antigen-binding fragment thereof is 10B11 or an antigen-binding fragment thereof, a chimeric antibody thereof, or a humanized antibody thereof, or a variant thereof, wherein that the variant substantially retains a biological function of the antibody or antigen-binding fragment from which it is derived. In certain preferred embodiments, the antibody or antigen-binding fragment thereof has one or more of the following biological functions: (a) binding to human CLDN18.2 with an EC50 of 0.1 pg / ml or less (e.g., 0.05 pg / ml or less); (b) binding to mouse CLDN18.2 with an EC50 of 0.1 pg / ml or less; (c) no binding to human CLDN18.1; (d) induction of killing of a human CLDN18.2-expressing cell (e.g., a tumor cell, such as a CLDN18.2-expressing tumor cell) via antibody-dependent cellular cytotoxicity (ADCC); (e) induction of destruction of a human CLDN18.2-expressing cell (e.g., a tumor cell, such as a CLDN18.2-expressing tumor cell) through complement-dependent cytotoxicity (CDC); (f) prevention and / or treatment of a tumor (for example, a tumor that expresses CLDN18.2) in a subject. In certain preferred embodiments, the antibody or antigen-binding fragment thereof comprises: (1) VH CDR1 as shown in SEQ ID NO: 43, VH CDR2 as shown in SEQ ID NO: 44, VH CDR3 as shown in SEQ ID NO: 45; VL CDR1 as shown in SEQ ID NO: 46, VL CDR2 as shown in SEQ ID NO: 47, VL CDR3 as shown in SEQ ID NO: 48; or (2) the 3 CDRs of the heavy chain variable region as shown in SEQ ID NO: 41; and the 3 CDRs of the light chain variable region as shown in SEQ ID NO: 42. In an illustrative embodiment, the antibody or antigen-binding fragment thereof comprises: M A / t / ZUZ I / υοοζου (a) a heavy chain variable region (VH) comprising an amino acid sequence selected from the group consisting of: (i) the sequence as shown in SEQ ID NO: 41; (i) a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2, 3, 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 41; or (i¡) a sequence that has a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%. at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 41; and / or (b) a variable light chain (VL) region comprising an amino acid sequence selected from the group consisting of: (iv) the sequence as shown in SEQ ID NO: 42; (v) a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2, 3, 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 42; or (vi) a sequence that has a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 42. In certain preferred embodiments, the substitution as mentioned in (i) or (v) is a conservative substitution. In certain preferred embodiments, the antibody or antigen-binding fragment thereof comprises: a VH having a sequence as shown in SEQ ID NO: 41, and a VL having a sequence as shown in SEQ ID NO: 42. In certain preferred embodiments, the antibody or antigen-binding fragment thereof is humanized. In certain preferred embodiments, the VH of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) framework region (FR) derived from a human immunoglobulin, and / or the VL of the antibody or fragment Antigen binding thereof comprises a framework region (FR) of the variable region of the light chain (VL) derived from a human immunoglobulin. In such embodiments, the FR of the heavy chain variable region and / or the FR of the light chain variable region of the antibody or binding fragment M A / t / ZUZ I / υοοζου the antigen thereof may comprise one or more non-human (e.g., murine) amino acid residues, for example, the heavy chain FR framework region and / or the light chain FR framework region may contain one or more amino acid retromutations, and the corresponding murine amino acid residues are contained in these retromutations. In another aspect, the present invention provides an antibody or antigen-binding fragment thereof that is capable of specifically binding to CLDN18.2, comprising: (a) a heavy chain variable region (VH) comprising the following three complementary determining regions (CDR): (i) VH CDR1, consisting of the following sequence: SEQ ID NO: 51, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to them; (i) VH CDR2, consisting of the following sequence: SEQ ID NO: 52, or a sequence having a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared thereto; and (i¡) VH CDR3, which consists of the following sequence: SEQ ID NO: 53, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1 ,2 or 3 amino acids) compared to them; and / or (b) a light chain variable region (VL) comprising the following three complementary determining regions (CDR): (v) VL CDR1, consisting of the following sequence: SEQ ID NO: 54, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared thereto; (v) VL CDR2, which consists of the following sequence: SEQ ID NO: 55, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to them; and (vi) VL CDR3, which consists of the following sequence: SEQ ID NO: 56, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to them. In certain preferred embodiments, the substitution, as mentioned in any one of points (i) to (vi), is a conservative substitution. In certain preferred embodiments, the VH of the antibody or antigen binding fragment thereof comprises: VH CDR1 as shown in SEQ ID NO: 51, VH CDR2 as shown in SEQ ID NO: 52, VH CDR3 as shown in SEQ ID NO: 53; and the M A / t / ZUZ I / υοοζου VL of the antibody or antigen binding fragment thereof comprises: VL CDR1 as shown in SEQ ID NO: 54, VL CDR2 as shown in SEQ ID NO: 55 and VL CDR3 as shown in SEQ ID NO: 56. The present invention also provides an antibody or antigen-binding fragment thereof that is capable of specifically binding to CLDN18.2, comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the 3 CDRs of the heavy chain variable region as shown in SEQ ID NO: 49; and the light chain variable region comprises the 3 CDRs of the light chain variable region as shown in SEQ ID NO: 50. In certain preferred embodiments, the 3 CDRs of the heavy chain variable region, and / or the 3 CDRs of the light chain variable region, are determined using the Kabat, Chothia or IMGT numbering system. In certain preferred embodiments, the antibody or antigen-binding fragment thereof is 27B5 or an antigen-binding fragment thereof, a chimeric antibody thereof, or a humanized antibody thereof, or a variant thereof, wherein that the variant substantially retains a biological function of the antibody or antigen-binding fragment from which it is derived. In certain preferred embodiments, the antibody or antigen-binding fragment thereof has one or more of the following biological functions: (a) binding to human CLDN18.2 with an EC50 of 0.2 pg / ml or less; (b) binding to mouse CLDN18.2 with an EC50 of 0.1 pg / ml or less; (c) no binding to human CLDN18.1; (d) induction of killing of a human CLDN18.2-expressing cell (e.g., a tumor cell, such as a CLDN18.2-expressing tumor cell) via antibody-dependent cellular cytotoxicity (ADCC); (e) induction of destruction of a human CLDN18.2-expressing cell (e.g., a tumor cell, such as a CLDN18.2-expressing tumor cell) through complement-dependent cytotoxicity (CDC); (f) prevention and / or treatment of a tumor (for example, a tumor that expresses CLDN18.2) in a subject. In certain preferred embodiments, the antibody or antigen-binding fragment thereof comprises: (1) VH CDR1 as shown in SEQ ID NO: 51, VH CDR2 as shown in SEQ ID NO: 52, VH CDR3 as shown in SEQ ID NO: 53; VL CDR1 as shown MA / I / UOOZOO shows in SEQ ID NO: 54, VL CDR2 as shown in SEQ ID NO: 55, VL CDR3 as shown in SEQ ID NO: 56; or (2) the 3 CDRs of the heavy chain variable region as shown in SEQ ID NO: 49; and the 3 CDRs of the light chain variable region as shown in SEQ ID NO: 50. In an illustrative embodiment, the antibody or antigen-binding fragment thereof comprises: (a) a heavy chain variable region (VH) comprising an amino acid sequence selected from the group consisting of: (i) the sequence as shown in SEQ ID NO: 49; (i) a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2, 3, 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 49; or (iii) a sequence that has a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 49; and / or (b) a variable light chain (VL) region comprising an amino acid sequence selected from the group consisting of: (iv) the sequence as shown in SEQ ID NO: 50; (v) a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2, 3, 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 50; or (vi) a sequence that has a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 50. In certain preferred embodiments, the substitution as mentioned in (i) or (v) is a conservative substitution. In certain preferred embodiments, the antibody or antigen-binding fragment thereof comprises: a VH having a sequence as shown in SEQ ID NO: 49, and a VL having a sequence as shown in SEQ ID NO: 50. In certain preferred embodiments, the antibody or antigen-binding fragment thereof is humanized. M A / t / ZUZ I / υοοζου In certain preferred embodiments, the VH of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) framework region (FR) derived from a human immunoglobulin, and / or the VL of the antibody or fragment Antigen binding thereof comprises a framework region (FR) of the variable region of the light chain (VL) derived from a human immunoglobulin. In such embodiments, the FR of the heavy chain variable region and / or the FR of the light chain variable region of the antibody or antigen-binding fragment thereof may comprise one or more non-human amino acid residues (e.g. , murine), for example, the heavy chain FR framework region and / or the light chain FR framework region may comprise one or more amino acid retromutations, and the corresponding murine amino acid residues are contained in these retromutations. In another aspect, the present invention provides an antibody or antigen-binding fragment thereof that is capable of specifically binding to CLDN18.2, comprising: (a) a heavy chain variable region (VH) comprising the following three complementary determining regions (CDR): (i) VH CDR1, consisting of the following sequence: SEQ ID NO: 59, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to them; (i) VH CDR2, consisting of the following sequence: SEQ ID NO: 60, or a sequence having a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared thereto; and (iii) VH CDR3, which consists of the following sequence: SEQ ID NO: 61, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared thereto; and / or (b) a light chain variable region (VL) comprising the following three complementary determining regions (CDR): (iv) VL CDR1, which consists of the following sequence: SEQ ID NO: 62, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to them; (v) VL CDR2, which consists of the following sequence: SEQ ID NO: 63, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to them; and (vi) VL CDR3, which consists of the following sequence: SEQ ID NO: 64, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, M A / t / ZUZ I / UODZDO deletion or addition of 1,2 or 3 amino acids) compared to them. In certain preferred embodiments, the substitution, as mentioned in any one of points (i) to (vi), is a conservative substitution. In certain preferred embodiments, the VH of the antibody or antigen binding fragment thereof comprises: VH CDR1 as shown in SEQ ID NO: 59, VH CDR2 as shown in SEQ ID NO: 60, VH CDR3 as shown in SEQ ID NO: 61; and, the VL of the antibody or antigen binding fragment thereof comprises: VL CDR1 as shown in SEQ ID NO: 62, VL CDR2 as shown in SEQ ID NO: 63, and VL CDR3 as shown sample in SEQ ID NO: 64. The present invention also provides an antibody or antigen-binding fragment thereof that is capable of specifically binding to CLDN18.2, comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the 3 CDRs of the heavy chain variable region as shown in SEQ ID NO: 57; and the light chain variable region comprises the 3 CDRs of the light chain variable region as shown in SEQ ID NO: 58. In certain preferred embodiments, the 3 CDRs of the heavy chain variable region, and / or the 3 CDRs of the light chain variable region, are determined using the Kabat, Chothia or IMGT numbering system. In certain preferred embodiments, the antibody or antigen-binding fragment thereof is 37B1 or an antigen-binding fragment thereof, a chimeric antibody thereof, or a humanized antibody thereof, or a variant thereof, wherein that the variant substantially retains a biological function of the antibody or antigen-binding fragment from which it is derived. In certain preferred embodiments, the antibody or antigen-binding fragment thereof has one or more of the following biological functions: (a) binding to human CLDN18.2 with an EC50 of 0.1 pg / ml or less (e.g., 0.05 pg / ml or less); (b) binding to mouse CLDN18.2 with an EC50 of 0.1 pg / ml or less; (c) no binding to human CLDN18.1; (d) induction of killing of a human CLDN18.2-expressing cell (e.g., a tumor cell, such as a CLDN18.2-expressing tumor cell) via antibody-dependent cellular cytotoxicity (ADCC); (e) induction of destruction of a human CLDN18.2-expressing cell (e.g., a tumor cell, such as a CLDN18.2-expressing tumor cell) through cytotoxicity M A / t / ZUZ I / υοοζου complement dependent (CDC); (f) prevention and / or treatment of a tumor (for example, a tumor that expresses CLDN18.2) in a subject. In certain preferred embodiments, the antibody or antigen-binding fragment thereof comprises: (1) VH CDR1 as shown in SEQ ID NO: 59, VH CDR2 as shown in SEQ ID NO: 60, VH CDR3 as shown in SEQ ID NO: 61; VL CDR1 as shown in SEQ ID NO: 62, VL CDR2 as shown in SEQ ID NO: 63, VL CDR3 as shown in SEQ ID NO: 64; or (2) the 3 CDRs of the heavy chain variable region as shown in SEQ ID NO: 57; and the 3 CDRs of the light chain variable region as shown in SEQ ID NO: 58. In an illustrative embodiment, the antibody or antigen-binding fragment thereof comprises: (a) a heavy chain variable region (VH) comprising an amino acid sequence selected from the group consisting of: (i) the sequence as shown in SEQ ID NO: 57; (i) a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2, 3, 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 57; or (i¡) a sequence that has a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%. at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 57; and / or (b) a variable light chain (VL) region comprising an amino acid sequence selected from the group consisting of: (iv) the sequence as shown in SEQ ID NO: 58; (v) a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2, 3, 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 58; or (vi) a sequence that has a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 58. ΜΛ / t / ZUZ I / υοοζου In certain preferred embodiments, the substitution as mentioned in (i) or (v) is a conservative substitution. In certain preferred embodiments, the antibody or antigen-binding fragment thereof comprises: a VH having a sequence as shown in SEQ ID NO: 57, and a VL having a sequence as shown in SEQ ID NO: 58. In certain preferred embodiments, the antibody or antigen-binding fragment thereof is humanized. In certain preferred embodiments, the VH of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) framework region (FR) derived from a human immunoglobulin, and / or the VL of the antibody or fragment Antigen binding thereof comprises a framework region (FR) of the variable region of the light chain (VL) derived from a human immunoglobulin. In such embodiments, the FR of the heavy chain variable region and / or the FR of the light chain variable region of the antibody or antigen-binding fragment thereof may comprise one or more non-human amino acid residues (e.g. , murine), for example, the heavy chain FR framework region and / or the light chain FR framework region may comprise one or more amino acid retromutations, and the corresponding murine amino acid residues are contained in these retromutations. In another aspect, the present invention provides an antibody or antigen-binding fragment thereof that is capable of specifically binding to CLDN18.2, comprising: (a) a heavy chain variable region (VH) comprising the following three complementary determining regions (CDR): (i) VH CDR1, consisting of the following sequence: SEQ ID NO: 67, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to them; (i) VH CDR2, consisting of the following sequence: SEQ ID NO: 68, or a sequence having a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared thereto; and (iii) VH CDR3, which consists of the following sequence: SEQ ID NO: 69, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared thereto; and / or (b) a light chain variable region (VL) comprising the following three complementary determining regions (CDR): (iv) VL CDR1, which consists of the following sequence: SEQ ID NO: 70, or a sequence that M A / t / ZUZ I / υοοζου has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared thereto; (v) VL CDR2, which consists of the following sequence: SEQ ID NO: 71, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to them; and (vi) VL CDR3, which consists of the following sequence: SEQ ID NO: 72, or a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to them. In certain preferred embodiments, the substitution, as mentioned in any one of points (i) to (vi), is a conservative substitution. In certain preferred embodiments, the VH of the antibody or antigen binding fragment thereof comprises: VH CDR1 as shown in SEQ ID NO: 67, VH CDR2 as shown in SEQ ID NO: 68, VH CDR3 as shown in SEQ ID NO: 69; and, the VL of the antibody or antigen binding fragment thereof comprises: VL CDR1 as shown in SEQ ID NO: 70, VL CDR2 as shown in SEQ ID NO: 71, and VL CDR3 as shown sample in SEQ ID NO: 72. The present invention also provides an antibody or antigen-binding fragment thereof that is capable of specifically binding to CLDN18.2, comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the 3 CDRs of the heavy chain variable region as shown in SEQ ID NO: 65; and the light chain variable region comprises the 3 CDRs of the light chain variable region as shown in SEQ ID NO: 66. In certain preferred embodiments, the 3 CDRs of the heavy chain variable region, and / or the 3 CDRs of the light chain variable region, are determined using the Kabat, Chothia or IMGT numbering system. In certain preferred embodiments, the antibody or antigen-binding fragment thereof is 44A8 or an antigen-binding fragment thereof, a chimeric antibody thereof, or a humanized antibody thereof, or a variant thereof, wherein that the variant substantially retains a biological function of the antibody or antigen-binding fragment from which it is derived. In certain preferred embodiments, the antibody or antigen-binding fragment thereof has one or more of the following biological functions: (a) binding to human CLDN18.2 with an EC50 of 0.1 pg / ml or less; (b) binding to mouse CLDN18.2 with an EC50 of 0.1 pg / ml or less; M A / t / ZUZ I / υοοζου (c) no binding to human CLDN18.1; (d) induction of killing of a human CLDN18.2-expressing cell (e.g., a tumor cell, such as a CLDN18.2-expressing tumor cell) via antibody-dependent cellular cytotoxicity (ADCC); (e) induction of destruction of a human CLDN18.2-expressing cell (e.g., a tumor cell, such as a CLDN18.2-expressing tumor cell) through complement-dependent cytotoxicity (CDC); (f) mediating the internalization of CLDN18.2 into a cell (e.g., a tumor cell), for example with an internalization level of at least 10% (e.g., at least 15%, at least 20% or plus) as measured by FACS or flow cytometry; the cell has CLDN18.2 expressed on its surface; (g) prevention and / or treatment of a tumor (for example, a tumor that expresses CLDN18.2) in a subject. In certain preferred embodiments, the antibody or antigen-binding fragment thereof comprises: (1) VH CDR1 as shown in SEQ ID NO: 67, VH CDR2 as shown in SEQ ID NO: 68, VH CDR3 as shown in SEQ ID NO: 69; VL CDR1 as shown in SEQ ID NO: 70, VL CDR2 as shown in SEQ ID NO: 71, VL CDR3 as shown in SEQ ID NO: 72; or (2) the 3 CDRs of the heavy chain variable region as shown in SEQ ID NO: 65; and the 3 CDRs of the light chain variable region as shown in SEQ ID NO: 66. In an illustrative embodiment, the antibody or antigen-binding fragment thereof comprises: (a) a heavy chain variable region (VH) comprising an amino acid sequence selected from the group consisting of: (i) the sequence as shown in SEQ ID NO: 65; (i) a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2, 3, 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 65; or (iii) a sequence that has a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 65; I M A / t / ZUZ I / UOOZOO (b) a light chain variable region (VL) comprising an amino acid sequence selected from the group consisting of: (v) the sequence as shown in SEQ ID NO: 66; (v) a sequence that has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2, 3, 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 66; or (vi) a sequence that has a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 66. In certain preferred embodiments, the substitution as mentioned in (i) or (v) is a conservative substitution. In certain preferred embodiments, the antibody or antigen-binding fragment thereof comprises: a VH having a sequence as shown in SEQ ID NO: 65, and a VL having a sequence as shown in SEQ ID NO: 66. In certain preferred embodiments, the antibody or antigen-binding fragment thereof is humanized. In certain preferred embodiments, the VH of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) framework region (FR) derived from a human immunoglobulin, and / or the VL of the antibody or fragment Antigen binding thereof comprises a framework region (FR) of the variable region of the light chain (VL) derived from a human immunoglobulin. In such embodiments, the FR of the heavy chain variable region and / or the FR of the light chain variable region of the antibody or antigen-binding fragment thereof may comprise one or more non-human amino acid residues (e.g. , murine), for example, the heavy chain FR framework region and / or the light chain FR framework region may comprise one or more amino acid retromutations, and the corresponding murine amino acid residues are contained in these retromutations. In certain preferred embodiments, the antibody or antigen-binding fragment thereof of the present invention may further comprise a constant region sequence or a variant thereof derived from a mammalian (e.g., murine or human) immunoglobulin. , in which the variant has a substitution, deletion or addition of one or more amino acids compared to the sequence from which it is derived. In certain preferred embodiments, the variant has a conservative substitution of one or more amino acids compared to the sequence from which it is derived. M A / t / ZUZ I / UODZDD In certain preferred embodiments, the heavy chain of the antibody or antigen-binding fragment thereof of the present invention comprises a heavy chain constant (CH) region of a human immunoglobulin or a variant thereof, wherein the variant has a substitution, deletion, or addition of one or more amino acids (e.g., a substitution, deletion, or addition of up to 20, up to 15, up to 10, or up to 5 amino acids; e.g., a substitution, deletion, or addition of 1.2 , 3,4 or 5 amino acids); I The light chain of the antibody or antigen-binding fragment thereof of the present invention comprises a light chain constant region (CL) of a human immunoglobulin or a variant thereof, wherein the variant has a substitution, deletion or addition of up to 20 amino acids (for example, a substitution, deletion or addition of up to 15, up to 10, or up to 5 amino acids; for example, a substitution, deletion or addition of 1,2, 3, 4 or 5 amino acids). In certain preferred embodiments, the heavy chain constant region is an IgG heavy chain constant region, such as an lgG1, lgG2, lgG3 or lgG4 heavy chain constant region. In certain preferred embodiments, the heavy chain constant region is a murine lgG1, lgG2, lgG3 or lgG4 heavy chain constant region. In certain preferred embodiments, the heavy chain constant region is a human lgG1, lgG2, lgG3 or lgG4 heavy chain constant region. In certain embodiments, the heavy chain constant region is preferably a human lgG1 or lgG4 heavy chain constant region. In certain preferred embodiments, the light chain constant region is a light chain constant region k. In certain preferred embodiments, the light chain constant region is a murine κ light chain constant region. In certain preferred embodiments, the light chain constant region is a human κ light chain constant region. In certain illustrative embodiments, the antibody or antigen-binding fragment thereof of the present invention comprises a heavy chain constant (CH) region as shown in SEQ ID NO: 81; and / or, a light chain constant region (LC) as shown in SEQ ID NO: 82. In certain preferred embodiments, the antibody of the present invention is a murine antibody, a chimeric antibody, a humanized antibody, a bispecific antibody, or a multispecific antibody. In certain preferred embodiments, the antigen binding fragment of the present invention is selected from the group consisting of Fab, Fab', (Fabjg, Fv, disulfide-linked Fv, scFv, diabody and single domain antibody (sdAb). . In the present invention, the antibody or antigen-binding fragment thereof of the M A / t / ZUZ I / UO3Z00 The present invention may include a variant that differs from the antibody or antigen-binding fragment thereof from which it is derived only by a conservative substitution of one or more amino acid residues (for example, a conservative substitution of up to 20, up to 15, up to 10 or up to 5 amino acids), or has a sequence identity of at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98% , at least 99% or 100% of the antibody or antigen-binding fragment thereof from which it is derived, and substantially retains the biological function of the antibody or antigen-binding fragment thereof from which it is derived. Preparation of antibodies The antibody of the present invention can be prepared by a variety of methods known in the art, for example, by recombinant genetic engineering techniques. For example, a DNA molecule encoding the heavy chain and light chain genes of the antibody of the present invention is obtained by chemical synthesis or PCR amplification. The resulting DNA molecule is inserted into an expression vector and then transfected into a host cell. The transfected host cell is then cultured under specific conditions to express the antibody of the present invention. The antigen-binding fragment of the present invention can be obtained by hydrolyzing an intact antibody molecule (see: Morimoto at. al., J. Biochem. Biophys. Methods 24: 107-117 (1992); and Brennan at. al., Science 229: 81 (1985)). Alternatively, these antigen-binding fragments can also be produced directly by recombinant host cells (reviewed in Hudson, Curr. Opin. Immunol. 11: 548-557 (1999); Little et al., Immunol. Today, 21: 364 -370 (2000)). For example, Fab' fragments can be obtained directly from host cells; Fab' fragments can be chemically coupled to form F(ab'>2) fragments (Carter et al., Bio / Technology, 10: 163-167 (1992)). Furthermore, Fv, Fab or F(ab') fragments 2 can also be isolated directly from the culture medium of the recombinant host cells. Other techniques for preparing these antigen-binding fragments are well known to those skilled in the art. Therefore, in another aspect, the present invention provides an isolated nucleic acid molecule comprising a nucleotide sequence encoding the antibody or antigen-binding fragment thereof of the present invention, or a heavy chain variable region and / or or light chain variable region thereof. In certain preferred embodiments, the isolated nucleic acid molecule encodes the antibody or antigen-binding fragment thereof of the present invention, or a heavy chain variable region and / or light chain variable region thereof. In another aspect, the present invention provides a vector (for example, a vector of M A / t / ZUZ I / UO3Z00 cloning or an expression vector) comprising an isolated nucleic acid molecule of the present invention. In certain preferred embodiments, the vector of the present invention is, for example, a plasmid, a cosmid, a phage and the like. In certain preferred embodiments, the vector is capable of expressing the antibody or antigen-binding fragment thereof of the present invention in a subject (e.g., a mammal, such as a human). In another aspect, the present invention provides a host cell comprising an isolated nucleic acid molecule of the present invention or a vector of the present invention. Said host cell includes, but is not limited to, prokaryotic cells such as E. coli cells, and eukaryotic cells such as yeast cells, insect cells, plant cells and animal cells (for example, mammalian cells, such as mouse, human cells, etc.). In certain preferred embodiments, the host cell of the present invention is a mammalian cell, such as a CHO (e.g., CHO-K1, CHO-S, CHO DG44). In another aspect, there is provided a method for preparing the antibody or antigen-binding fragment thereof of the present invention, comprising culturing a host cell of the present invention in a condition that allows expression of the antibody or antigen-binding fragment thereof. thereof, and recovering the antibody or antigen-binding fragment thereof from the cultured host cell culture. Derived antibodies The antibody or antigen-binding fragment thereof of the present invention can be derivatized, for example, linked to another molecule (for example, another polypeptide or protein). In general, derivatization (e.g., labeling) of the antibody or antigen-binding fragment thereof does not adversely affect its binding to CLDN18.2 (especially human CLDN18.2). Therefore, the antibody or antigen-binding fragment thereof of the present invention is also intended to include such forms of derivatization. For example, the antibody or antigen-binding fragment thereof of the present invention may be functionally linked (by chemical coupling, gene fusion, non-covalent bonding, or other means) to one or more other molecular groups, such as another antibody (e.g. , to form a bispecific antibody), a detection reagent, a pharmaceutical reagent and / or a protein or polypeptide (for example, avidin or polyhistidine tag) capable of mediating the binding of the antibody or antigen-binding fragment thereof to another molecule. Furthermore, the antibody or antigen-binding fragment thereof of the present invention may also be derivatized with a chemical group, such as polyethylene glycol (PEG), methyl or ethyl, or glycosyl. These groups can be used to improve the biological properties of the antibody, such as increasing the serum half-life. Therefore, in certain preferred embodiments, the antibody or binding fragment M A / / UOOZOO the antigen thereof of the present invention is labeled. In certain preferred embodiments, the antibody or antigen-binding fragment thereof of the present invention carries a detectable label, such as an enzyme, a radionuclide, a fluorescent dye, a luminescent substance (e.g., a chemiluminescent substance), or a biotin. The detectable marker according to the present invention may be any substance that can be detected by fluorescent, spectroscopic, photochemical, biochemical, immunological, electrical, optical or chemical means. Such labels are well known in the art, and examples thereof include, among others, enzymes (e.g., horseradish peroxidase, alkaline phosphatase, β-galactosidase, urease, glucose oxidase, etc.), radionuclides (e.g., 3H,125l, 35S,14C, o32P), fluorescent dyes (e.g. fluorescein isothiocyanate (FITC), fluorescein, tetramethylrhodamine isothiocyanate (TRITC), phycoerythrin (PE), Texas red, rhodamine, quantum dots or derivatives of cyanine dyes (e.g. , Cy7, Alexa 750), luminescent materials (e.g., chemiluminescent materials such as acridine asters), magnetic beads (e.g., Dynabeads®), calorimetric labels such as colloidal gold or glass or colored plastic beads (e.g. example, polystyrene, polypropylene, latex, etc.), and biotins to bind an avidin (e.g., streptavidin) modified by the labels above. Patents dealing with the use of these labels include, but are not limited to, US patents N.s3,817,837; 3,850,752; 3,939,350; 3,996,345; 4,277,437; 4,275,149; and 4,366,241 (all incorporated herein by reference). Markers detectable as described above can be detected by methods known in the art. For example, radioactive tracers can be detected using photographic film or a scintillation counter, and fluorescent tracers can be detected using a photodetector to detect emitted light. The enzyme label is usually detected by providing a substrate to the enzyme and detecting a reaction product produced by the enzyme's effect on the substrate. And calorimetric markers are detected simply by viewing the colored markers. In certain embodiments, such markers may be suitable for immunological detection (e.g., enzyme-linked immunoassay, radioimmunoassay, fluorescent immunoassay, chemiluminescence immunoassay, etc.). In certain embodiments, the detectable marker as described above may be attached to the antibody or antigen-binding fragment thereof of the present invention through linkers of different lengths to reduce potential spherical hindrance. Bispecific or multispecific molecules The antibody or antigen-binding fragment thereof of the present invention can be used to form bispecific or multispecific molecules. The antibody or binding fragment ΜΛ / I / UODZDO the antigen thereof of the present invention may be part of a bispecific or multispecific molecule, and the bispecific or multispecific molecule comprises a second functional module (for example, a second antibody) that has a binding specificity different from that of the antibody or antigen-binding fragment thereof of the present invention, so that it is capable of binding to at least two different binding sites and / or target molecules. For example, the antibody or antigen-binding fragment thereof of the present invention may bind to a second antibody or antigen-binding fragment thereof that is capable of specifically binding to any protein that may be used as a potential target for therapy. of combination. To generate the bispecific or multispecific molecule, the antibody or antigen-binding fragment thereof of the present invention may be linked (e.g., by chemical coupling, gene fusion, non-covalent association, or other means) to one or more binding molecules ( for example, additional antibodies, antibody fragments, peptides or binding mimics). Therefore, in another aspect, the present invention provides a bispecific or multispecific molecule comprising the antibody or antigen-binding fragment thereof of the present invention. In certain preferred embodiments, the bispecific or multispecific molecule specifically binds to CLDN18.2 and furthermore, specifically binds to one or more different targets. In certain preferred embodiments, the bispecific or multispecific molecule further comprises at least one molecule (e.g., a second antibody) that has a second binding specificity for a second target. Immunoconjugated The antibody or antigen-binding fragment thereof of the present invention can be linked to a therapeutic agent to form an immunoconjugate. Because these immunoconjugates have the ability to selectively deliver one or more therapeutic agents to target tissues (e.g., tumor-associated antigens, such as tumors expressing CLDN18.2), the immunoconjugates can improve the therapeutic efficacy of the antibody or fragment. antigen binding thereof of the present invention in the treatment of diseases (for example, cancers). Therefore, in another aspect, the present invention provides an immunoconjugate comprising the antibody or antigen-binding fragment thereof of the present invention and a therapeutic agent linked to the antibody or antigen-binding fragment thereof. In certain preferred embodiments, the immunoconjugate is an antibody-drug conjugate (ADC). M A / t / ZUZ I / υοοζου In certain preferred embodiments, the therapeutic agent is a cytotoxic agent. In the present invention, the cytotoxic agent includes any agent that is harmful to a cell (for example, that kills cells). In certain preferred embodiments, the therapeutic agent is selected from the group consisting of alkylating agents, antimitotic agents, antitumor antibiotics, antimetabolites, topoisomerase inhibitors, tyrosine kinase inhibitors, radionuclide agents and any combination thereof. Examples of alkylating agents that can be used in the immunoconjugates of the present invention include, but are not limited to, nitrogen mustards (e.g., dichloroethylmethylamine, phenylbutyric acid mustard, melphalan, cyclophosphamide, etc.), ethyleneimines (e.g., thiotepa , etc.), sulfonates and polyols (for example, busulfan, dibromomannitol), nitrosoureas (for example, carmustine, lomustine, etc.), platinum-based antitumor agents (for example, rdscisplatin, oxaliplatin, carboplatin, etc.). Examples of antimitotic agents that can be used in the immunoconjugates of the present invention include, but are not limited to, maytansinoids (e.g., maytansin, maytansinol, maytansinol C-3 esters, etc.), taxanes (e.g., docetaxel , paclitaxel or paclitaxel nanoparticles, etc.), pink vinca alkaloids (for example, vinblastine sulfate, vincristine, vinblastine or vinorelbine, etc.) Examples of antitumor antibiotics that can be used in the immunoconjugates of the present invention include, but are not limited to, actinomycin, anthracycline antibiotics (e.g., daunorubicin, doxorubicin, epirubicin, idarubicin, etc.), calicheamicin, duocarmycin , etc. Examples of antimetabolites that can be used in the immunoconjugates of the present invention include, but are not limited to, folate antagonists (e.g., methotrexate, etc.), pyrimidine antagonists (e.g., 5-fluorouracil, fluorouridine, cytarabine , capecitabine, gemcitabine, etc.), purine antagonists (e.g., 6-mercaptopurine, 6-thioguanine, etc.), adenosine deaminase inhibitors (e.g., cladribine, fludarabine, nelarabine, pentostatin, etc.). Examples of topoisomerase inhibitors that can be used in the immunoconjugates of the present invention include, but are not limited to, camptothecins and their derivatives (e.g., irinotecan, topotecan, etc.), amsacrine, daunomycin, adriamycin, epipodophyllotoxin, ellipticin, epirubicin, etoposide, razoxane, teniposide, etc. Examples of tyrosine kinase inhibitors that can be used in the immunoconjugates of the present invention include, but are not limited to, axitinib, bosutinib, ΜΛ / t / ZUZ I / υοοζου sildenib, dasatinib, erlotinib, gefitinib, imatinib, lapatinib, lestaurtinib, nilotinib, semaxanib, sunitinib, vandetanib, etc. Examples of radionuclide agents that can be used in the immunoconjugate of the present invention include, but are not limited to, I131, In111, Y90, Lu177, and the like. In certain illustrative embodiments, the therapeutic agent is selected from the group consisting of platinum-based antitumor agents, anthracycline antibiotics, taxanes, nucleoside analogs, camptothecin compounds and analogs or homologs thereof, as well as any combination of the same. In certain preferred embodiments, the antibody or antigen-binding fragment thereof of the present invention is optionally conjugated to the therapeutic agent through a linker. In the present invention, the cytotoxic agent can be coupled to the antibody or antigen-binding fragment thereof of the present invention using a linker technology available in the art. Examples of types of linkers that have been used to couple a cytotoxic agent to an antibody include, but are not limited to, hydrazones, thioethers, esters, disulfides, and peptide-containing linkers. A linker may be selected, for example, that is susceptible to cleavage by low pH within the lysosomal compartment or susceptible to cleavage by proteases, such as proteases expressed, preferably, in tumor tissue such as cathepsins (e.g., cathepsins B, C , D). For additional commentary on the types of cytotoxic agents, linkers and methods of coupling therapeutic agents to antibodies, see also Salto, G. et al. (2003) Adv. Drug Deliv. Rev. 55: 199-215; Trail, PA at. to the. (2003) Cancer Immunol. Immunother. 52: 328-337; Payne, G. (2003) Cancer Cell 3: 207-212; Alien, TM (2002) Nat. Rev. Cancer 2: 750-763; Pastan, I. and Kreitman, RJ (2002) Curr. Opinion. Drug Researcher 3:1089-1091; Senter, PD and Springer, CJ (2001) Adv. Drug Deliv. Rev 53: 247-264. chimeric antigen receptor The antibody or antigen-binding fragment thereof of the present invention can be used to construct a chimeric antigen receptor (CAR), the chimeric antigen receptor comprising an extracellular antigen-binding domain (e.g., scFv) that specifically binds to CLDN18.2, and binds to a transmembrane domain and one or more intracellular T cell signaling domains. Intracellular T cell signaling domains may include, for example, T cell receptor signaling domains, T cell costimulatory signaling domains, or combinations thereof. The T cell receptor signaling domain refers to a part of CAR that contains the domain ΜΛ / t / ZUZ I / υοοζου intracellular T cell receptor (e.g., an intracellular part of the CD3ζ protein). The costimulatory signaling domain refers to a part of CAR that contains the intracellular domain of a costimulatory molecule, and the costimulatory molecule is a cell surface molecule other than the antigen receptors or ligands thereof that are required for a response. efficiency of lymphocytes against the antigen. Features of the CAR of the present invention include its ability to redirect T cell specificity and reactivity toward a cell expressing CLDN18.2 (e.g., a tumor cell) in a non-MHC-restricted manner. Non-MHC-restricted recognition of CLDN18.2 gives T cells expressing the CAR of the present invention the ability to recognize an antigen independent of antigen processing. Therefore, in another aspect, the present invention provides a chimeric antigen receptor (CAR) comprising an antigen-binding domain of the antibody or antigen-binding fragment thereof of the present invention. In certain preferred embodiments, the antigen binding domain comprises a heavy chain variable region and a light chain variable region of the antibody or antigen binding fragment thereof of the present invention. In certain preferred embodiments, the antigen binding domain is an scFv. In certain preferred embodiments, the antigen-binding receptor comprises an antigen-binding fragment (e.g., a scFv) of the antibody of the present invention. In certain preferred embodiments, the antigen-binding receptor is expressed by an immune effector cell (e.g., a T cell). In certain preferred embodiments, there may be a spacer domain comprising a polypeptide sequence between the antigen binding domain and the transmembrane domain of the CAR. The spacer domain may comprise up to 300 amino acids, preferably 10 to 100 amino acids, and most preferably 25 to 50 amino acids. In some embodiments, the spacer domain may comprise an immunoglobulin domain, such as a human immunoglobulin sequence. In certain illustrative embodiments, the immunoglobulin domain comprises CH2 and CH3 immunoglobulin domain sequences. In such embodiments, without being limited by a particular theory, it is believed that the CH2 and CH3 domains move the antigen-binding domain of CAR away from the membrane of the CAR-expressing cell, and may more accurately mimic the size and the domain structure of a natural TCR. In certain preferred embodiments, the transmembrane domain may be derived from a natural or synthetic source. In such embodiments, the domain may be derived from any M A / t / ZUZ I / uoozoo membrane-bound or transmembrane protein. Illustrative transmembrane domains that can be used in the CAR of the present invention can comprise at least the transmembrane region of the α, β or ζ chain of the T cell receptor, and the T cell receptor can be selected from the group consisting of CD28, CD3e, CD45, CD4, CD5, CDS, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137, CD154. Alternatively, the transmembrane domain may be synthetic, in which case it will contain primarily hydrophobic residues such as leucine and valine. In certain illustrative embodiments, the transmembrane domain comprises a T cell receptor transmembrane domain, such as a CD8 transmembrane domain. In certain illustrative embodiments, the transmembrane domain comprises a T cell costimulatory molecule transmembrane domain (e.g., CD137 or CD28). In certain preferred embodiments, examples of intracellular T cell domain that can be used in the CAR include cytoplasmic T cell receptor (TCR) sequences and costimulatory molecules that act in concert to initiate transduction. of signals after engagement of the antigen receptor, and any derivative or variant of these sequences and any synthetic sequence with the same functional capacity. In certain preferred embodiments, the intracellular region of the CAR may comprise a primary cytoplasmic signaling sequence that acts in a stimulatory manner, which may comprise a signaling motif known as an immunotyrosine-based immunoreceptor activation motif or ITAM. acronym in English. Examples of ITAMs containing primary cytoplasmic signaling sequences that may be comprised in the CAR include those derived from the proteins CD3ζ, FcRy, FcRp, CD3y, CD3ó, CD3¿, CDS, CD22, CD79a, CD79b and CD66d. In certain preferred embodiments, the intracellular region of the CAR may comprise an ITAM that contains a primary cytoplasmic signaling domain (e.g., CD3ζ) alone or in combination with any other desired cytoplasmic domain that can be used in the CAR. For example, the cytoplasmic domain of CAR comprises a portion of the CD3ζ chain and an intracellular costimulatory signaling domain. The costimulatory signaling domain refers to the portion of the CAR that contains the intracellular domain of a costimulatory molecule. The costimulatory molecule is a cell surface molecule other than the antigen receptors or ligands thereof necessary for an efficient lymphocyte response against the antigen. Examples of such a molecule include CD27, CD28, 4-1BB (CD137), 0X40 (CD134), CD30, CD40, PD-1, ICOS, lymphocyte function-associated antigen 1 (LFA-1), CD2, CD7, LIGHT, MA / I / UOOZOO NKG2C and B7-H3. In certain preferred embodiments, the CAR may comprise a Οϋ3ζ signaling domain, a CD8 signaling domain, a CD28 signaling domain, a CD137 signaling domain, or any combination thereof. Those skilled in the art can change the order of one or more T cell signaling domains in the CAR as necessary. Methods for generating the chimeric antigen receptor and T cells containing said receptor, and their uses (for example, uses for the treatment of cancer) are known in the art, and detailed descriptions thereof can be found in , for example, Brentjens et al., 2010, Molecular Therapy, 18: 4,666-668; Morgan et al., 2010, Molecular Therapy, published online February 23, 2010, pages 1-9; Till et al, 2008, Blood, 112: 2261-2271; Park et al, Trends Biotechnol., 29: 550-557, 2011; Grupp et al., NEngIJMed., 368:1509-1518, 2013; Han at. aL, J. Hematol Oncol., 6:47, 2013; PCT Patent Publication WO2012 / 079000, WO2013 / 126726; and US Patent Publication 2012 / 0213783, which documents are incorporated herein in their entirety by reference. For example, a nucleic acid molecule encoding the chimeric antigen-binding receptor of the present invention may be contained in an expression vector (e.g., a lentiviral vector) for expression in a host cell, such as a T cell, in order to produce the CAR. In certain illustrative embodiments, a method of using the chimeric antigen receptor comprises isolating a T cell from a subject, transforming the T cell with an expression vector (e.g., a lentiviral vector) encoding the chimeric antigen receptor, and administering the engineered T cell expressing the chimeric antigen receptor to the subject to perform treatment, for example, treating a tumor in the subject. Therefore, in another aspect, the present invention provides an isolated nucleic acid molecule comprising a nucleotide sequence encoding the chimeric antigen receptor of the present invention. In certain preferred embodiments, the isolated nucleic acid molecule encodes the chimeric antigen receptor of the present invention. In another aspect, the present invention provides a vector (e.g., a cloning vector or an expression vector) comprising the isolated nucleic acid molecule as described above. In certain preferred embodiments, the vector of the present invention is, for example, a plasmid. In another aspect, the present invention provides a host cell comprising the isolated nucleic acid molecule or vector as described above. In certain embodiments, the host cell is a T cell. In certain preferred embodiments, the host cell is a chimeric antigen receptor T cell (CAR-T). M A / t / ZUZ I / UODZDD Treatment method and pharmaceutical composition The antibody or antigen-binding fragment thereof of the present invention can induce ADCC and / or CDC by binding to CLDN18.2, and therefore, can be used to prevent and / or treat a tumor. Therefore, in another aspect, the present invention provides a pharmaceutical composition comprising the antibody or antigen-binding fragment thereof, bispecific or multispecific molecule, or immunoconjugate of the present invention, and a pharmaceutically acceptable carrier and / or excipient. In certain preferred embodiments, the pharmaceutical composition may further comprise an additional pharmaceutically active agent. In certain preferred embodiments, the additional pharmaceutically active agent is an antitumor agent, such as an alkylating agent, an antimitotic agent, an antitumor antibiotic, an antimetabolite, a topoisomerase inhibitor, a tyrosine kinase inhibitor, a radionuclide, a radiosensitizer. (e.g., gemcitabine, 5-fluorouracil, taxane, cisplatin, etc.), an antiangiogenesis agent, a cytokine (e.g., GM-CSF, IL-7, IL-12, IL-15, IL-18, IL21, etc.), a molecular targeting agent (e.g., CD20 antibody such as rituximab, Her2 antibody such as trastuzumab, VEGF antibody such as bevacizumab, EGFR antibody such as cetuximab, etc.), an immune checkpoint inhibitor (e.g., PD-antibody 1, PD-L1 antibody, CTLA-4 antibody, LAG-3 antibody, etc.), an eneolithic virus and the like. In certain preferred embodiments, in the pharmaceutical composition, the antibody or antigen-binding fragment thereof, bispecific or multispecific molecule, or immunoconjugate of the present invention and the additional pharmaceutically active agent are provided as separate components or as components of a unique composition. Therefore, the antibody or antigen-binding fragment thereof, bispecific or multispecific molecule, or immunoconjugate of the present invention and the additional pharmaceutically active agent can be administered simultaneously, separately or sequentially. In certain illustrative embodiments, the pharmaceutical composition comprises a sterile injectable liquid (e.g., an aqueous or non-aqueous suspension or solution). In certain illustrative embodiments, said sterile injectable liquid is selected from the group consisting of water for injection (WFI), bacteriostatic water for injection (BWFI), sodium chloride solution (e.g., 0.9% (wt / vol) NaCl), glucose solution (e.g., 5% glucose), a solution containing surfactant (e.g., 0.01% polysorbate 20), a pH buffer solution (for example, a phosphate buffer solution), a Ringer's solution and any combination thereof. M A / t / ZUZ I / UO3Z00 In another aspect, the present invention provides a method for reducing the level of expression of CLDN18.2 on the surface of a cell, comprising contacting the cell with the antibody or antigen-binding fragment thereof, bispecific or multispecific molecule. , immunoconjugate or pharmaceutical composition of the present invention to reduce the expression level of CLDN18.2 on the cell surface; where the cell has CLDN18.2 expressed on its surface. In certain preferred embodiments, the cell is a tumor cell that expresses CLDN18.2. In certain preferred embodiments, the method is used to reduce the expression level of CLDN18.2 on a cell surface in vitro not for a diagnostic purpose. In another aspect, there is provided the use of the antibody or antigen-binding fragment thereof, bispecific or multispecific molecule, immunoconjugate or pharmaceutical composition of the present invention in the manufacture of a medicament to reduce the level of expression of CLDN18.2 in a cell surface. In another aspect, the antibody or antigen binding fragment, bispecific or multispecific molecule, immunoconjugate or pharmaceutical composition of the present invention is provided to reduce the expression level of CLDN18.2 on a cell surface. In another aspect, the present invention provides a method of inhibiting the growth and / or destroying a tumor cell expressing CLDN 18.2, comprising contacting the tumor cell with an effective amount of the antibody or antigen-binding fragment thereof, molecule bispecific or multispecific, immunoconjugate, pharmaceutical composition, chimeric antigen receptor or host cell that expresses the chimeric antigen receptor (for example, chimeric antigen receptor T cell (CAR-T)) of the present invention. The method can be used for a therapeutic purpose or for a non-therapeutic purpose. In certain preferred embodiments, the method may be used for a non-therapeutic purpose, and the method is used to inhibit the growth and / or kill a tumor cell expressing CLDN 18.2 in vitro. In another aspect, the use of the antibody or antigen-binding fragment thereof, bispecific or multispecific molecule, immunoconjugate, pharmaceutical composition, chimeric antigen receptor or host cell that expresses the chimeric antigen receptor (for example, T cell) is provided. chimeric antigen receptor (CAR-T)) of the present invention in the manufacture of a medicament to inhibit the growth and / or destroy a tumor cell that expresses CLDN 18.2. In another aspect, the antibody or antigen-binding fragment thereof is provided, M A / t / ZUZ I / UO3Z00 bispecific or multispecific molecule, immunoconjugate, pharmaceutical composition, chimeric antigen receptor or host cell expressing the chimeric antigen receptor (for example, chimeric antigen receptor T cell (CAR-T)) for inhibit the growth and / or destroy a tumor cell that expresses CLDN 18.2. In another aspect, the present invention provides a method of preventing and / or treating a tumor in a subject (for example, a human), comprising administering to the subject in need thereof an effective amount of the antibody or antigen-binding fragment of the same, bispecific or multispecific molecule, immunoconjugate, pharmaceutical composition, chimeric antigen receptor or host cell that expresses the chimeric antigen receptor (for example, chimeric antigen receptor T cell (CAR-T)). In certain preferred embodiments, the tumor contains a tumor cell that expresses CLDN18.2. In certain preferred embodiments, CLDN18.2 is expressed on the surface of the tumor cell. In certain preferred embodiments, the tumor expresses CLDN18.2. In certain preferred embodiments, the tumor is selected from the group consisting of gastric cancer, esophageal cancer, pancreatic cancer, bronchial cancer, non-small cell lung cancer, breast cancer, ear-nose-throat cancer, ovarian cancer, colon cancer, liver cancer, head and neck cancer, gallbladder cancer and their metastatic cancers (for example, gastric cancer metastases, such as Krukenberg tumor, peritoneal metastasis or lymph node metastasis). In certain preferred embodiments, the antibody or antigen-binding fragment thereof, bispecific or multispecific molecule, immunoconjugate, pharmaceutical composition, chimeric antigen receptor or host cell that expresses the chimeric antigen receptor (e.g., chimeric antigen receptor T cell chimeric antigen (CAR-T)) of the present invention is used in combination with an additional antitumor agent. Said additional antitumor agent may be administered before, at the same time or after the antibody or antigen-binding fragment thereof, bispecific or multispecific molecule, immunoconjugate, pharmaceutical composition, chimeric antigen receptor or host cell expressing the receptor is administered. chimeric antigen (e.g., CAR-T) of the present invention. In certain preferred embodiments, the antibody or antigen-binding fragment thereof, bispecific or multispecific molecule, immunoconjugate, pharmaceutical composition, chimeric antigen receptor or host cell expressing the chimeric antigen receptor (e.g., CAR-T) of the present invention is administered in combination with additional therapy. Said additional therapy may be any known therapy for tumors, such as surgery, M A / t / ZUZ I / υοοζου chemotherapy, radiotherapy, targeted therapy, immunotherapy, hormone therapy, gene therapy or palliative care. Such additional therapy may be performed before, at the same time or after the antibody or antigen-binding fragment thereof, bispecific or multispecific molecule, immunoconjugate, pharmaceutical composition, chimeric antigen receptor or host cell expressing the antigen receptor is administered. chimeric (e.g., CAR-T) of the present invention. The antibody or antigen-binding fragment thereof, bispecific or multispecific molecule, immunoconjugate, pharmaceutical composition, chimeric antigen receptor or host cell expressing the chimeric antigen receptor (e.g., CAR-T) of the present invention can be formulated in any dosage form known in the medical field, for example, in tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injectable liquids, sterile powders for injection and solutions concentrates for injection), inhalants, aerosols, etc. The preferred dosage form depends on the intended route of administration and therapeutic use. The pharmaceutical composition of the present invention must be sterile and stable under manufacturing and storage conditions. A preferred dosage form is an injection. Said injection may be a sterile injectable solution. For example, the sterile injectable solution can be prepared by the following method: incorporating a necessary amount of the antibody of the present invention in an appropriate solvent, and optionally, at the same time incorporating other desired ingredients (including, but not limited to, pH adjustment agent, surfactant, adjuvant, ionic strength enhancer, isotonic agent, preservative, diluent or any combination thereof), and then, performing a filtered sterilization. Additionally, the sterile injectable solution can be prepared as a sterile lyophilized powder (e.g., by vacuum drying or lyophilization) for convenience of storage and use. Such sterile lyophilized powder can be dispersed before use in a suitable vehicle, such as water for injection (WFI), bacteriostatic water for injection (BWFI), sodium chloride solution (for example, 0.9% NaCl (w / vol)), glucose solution (e.g., 5% glucose), surfactant-containing solution (e.g., 0.01% polysorbate 20), pH buffered solution (e.g., phosphate buffered solution), solution Ringer's and any combination thereof. Furthermore, the antibody or antigen-binding fragment thereof, bispecific or multispecific molecule, immunoconjugate, pharmaceutical composition, chimeric antigen receptor or host cell expressing the chimeric antigen receptor (e.g., T cell) of the present invention may be present in unit dose form in a composition M A / t / ZUZ I / υοοζου pharmaceutical for greater convenience of administration. The antibody or antigen-binding fragment thereof, bispecific or multispecific molecule, immunoconjugate, pharmaceutical composition, chimeric antigen receptor or host cell expressing the chimeric antigen receptor (e.g., T cell) of the present invention can be administered by any suitable method known in the art, including, but not limited to, oral, buccal, sublingual, eyeball, topical, parenteral, rectal, intrathecal, intracytoplasmic, groin, intravesical, local (e.g., powder, ointment or drops) or nasally. However, for many therapeutic uses, the preferred route / mode of administration is parenteral administration (e.g., intravenous injection or rapid intravenous injection, subcutaneous injection, intraperitoneal injection, intramuscular injection). One skilled in the art will understand that the route and / or mode of administration will vary depending on the intended purpose. In a preferred embodiment, the antibody or antigen-binding fragment thereof, bispecific or multispecific molecule, immunoconjugate, pharmaceutical composition, chimeric antigen receptor or host cell that expresses the chimeric antigen receptor (for example, T cell) The present invention is administered by intravenous injection or rapid intravenous injection. The pharmaceutical composition of the present invention may comprise a therapeutically effective amount or a prophylactically effective amount of the antibody or antigen-binding fragment thereof, bispecific or multispecific molecule, immunoconjugate, pharmaceutical composition, chimeric antigen receptor or host cell expressing the receptor. chimeric antigen (for example, T cell) of the present invention. The term "prophylactically effective amount" refers to an amount sufficient to prevent, arrest or delay the onset of a disease. The term therapeutically effective amount refers to an amount sufficient to cure or at least partially block a disease and its complications in a patient already suffering from the disease. The therapeutically effective amount of the antibody or antigen-binding fragment thereof of the present invention may vary depending on factors such as the severity of the disease to be treated, the general state of the patient's immune system, the general condition of the patient, such as age, weight and sex, route of administration and other therapies applied simultaneously. In the present invention, the dosage regimen can be adjusted to obtain an optimal response (for example, a therapeutic or preventive response). For example, a single dose may be administered, or multiple doses may be administered over a period of time, or the dose may be reduced or increased proportionally as indicated by the demands of the therapeutic situation. M A / t / ZUZ I / υοοζου In the present invention, the subject may be a mammal, such as a human. Detection method and kit The antibody or antigen-binding fragment thereof of the present invention can specifically bind to CLDN18.2 and therefore can be used to detect the presence or level of CLDN18.2 in a sample. Accordingly, in another aspect, the present invention provides a kit comprising the antibody or antigen-binding fragment thereof of the present invention. In certain embodiments, the antibody or antigen-binding fragment thereof of the present invention is labeled with a detectable marker. In a preferred embodiment, the kit further comprises a secondary antibody that specifically recognizes the antibody or antigen-binding fragment thereof of the present invention. Preferably, the second antibody further comprises a detectable label. In the present invention, the detectable marker can be any substance that can be detected by fluorescent, spectroscopic, photochemical, biochemical, immunological, electrical, optical or chemical means. It is particularly preferable that said marker may be suitable for immunological detection (for example, enzyme-linked immunoassay, radioimmunoassay, fluorescent immunoassay, chemiluminescence immunoassay, etc.). Such labels are well known in the art, and include, among others, enzymes (e.g., horseradish peroxidase, alkaline phosphatase, β-galactosidase, urease, glucose oxidase, etc.), radionuclides (e.g., 3H,125l, 35S,14C, o32P), fluorescent dyes (e.g. fluorescein isothiocyanate (FITC), fluorescein, tetramethylrhodamine isothiocyanate (TRITC), phycoerythrin (PE), Texas red, rhodamine, quantum dots or derivatives of cyanine dyes (e.g. , Cy7, Alexa 750), luminescent materials (e.g. chemiluminescent materials such as acridine esters), magnetic beads (e.g. Dynabeads®), calorimetric labels such as colloidal gold or glass or colored plastic beads (e.g. example, polystyrene, polypropylene, latex, etc.), and biotins to bind an avidin (e.g., streptavidin) modified by the labels above. Patents dealing with the use of these labels include, but are not limited to, US patents N.s3,817,837; 3,850,752; 3,939,350; 3,996,345; 4,277,437; 4,275,149; and 4,366,241 (all incorporated herein by reference). Markers detectable as described above can be detected by methods known in the art. For example, radioactive tracers can be detected using photographic film or a scintillation counter, and fluorescent tracers can be detected using a photodetector to detect emitted light. The enzyme label is usually detected by providing a substrate to the enzyme and detecting a product ΜΛ / t / ZUZ I / υοοζου reaction produced by the effect of the enzyme on the substrate. And calorimetric labels are detected simply by viewing the colored labels. In certain embodiments, the detectable label as described above may be linked to the antibody or antigen-binding fragment thereof of the present invention through linkers of different lengths to reduce potential steric hindrance. In another aspect, the present invention provides a method for detecting the presence or amount of CLDN18.2 in a sample, comprising the steps of: (1) contacting the sample with the antibody or antigen-binding fragment thereof of the present invention; (2) detect the formation or amount of a complex between the antibody or antigen-binding fragment thereof and CLDN18.2. Formation of the complex indicates the presence of CLDN18.2 or a cell expressing CLDN18.2. In certain preferred embodiments, the sample is a cell sample, that is, a sample comprising a cell (e.g., a tumor cell). In such embodiments, preferably, the complex is formed between the antibody, the antigen-binding fragment or the conjugate and CLDN18.2 expressed by a cell in the sample. In a preferred embodiment, the antibody or antigen-binding fragment thereof of the present invention is additionally labeled with a detectable marker. In another preferred embodiment, in step (2), a reagent with a detectable label is used to detect the antibody or antigen-binding fragment thereof of the present invention. The method may be used for a diagnostic purpose or for a purpose other than a diagnosis (for example, the sample is a cell sample, rather than a patient sample). In certain preferred embodiments, CLDN18.2 is human CLDN18.2. In another aspect, there is provided the use of the antibody or antigen-binding fragment thereof of the present invention in the manufacture of a kit for detecting the presence or amount of CLDN18.2 in a sample. In certain preferred embodiments, CLDN18.2 is human CLDN18.2. In another aspect, the present invention provides a method for determining whether a tumor is treatable by antitumor therapy targeting CLDN18.2, comprising the following steps: (1) contacting a sample containing the tumor cell with the antibody or antigen-binding fragment thereof of the present invention; (2) detect the formation of a complex between the antibody or antigen-binding fragment M A / t / ZUZ I / UO3Z00 of the same and CLDN18.2. In certain preferred embodiments, the complex is formed between the antibody or antigen-binding fragment thereof and CLDN18.2 expressed by the tumor cell in the sample. In certain preferred embodiments, the sample comes from a subject who has a tumor, is suspected of having a tumor, or is at risk of having a tumor. In certain preferred embodiments, the sample is from a tissue or organ in which the cells do not substantially express CLDN18.2 when the tissue or organ is free of cancer. In certain preferred embodiments, the tissue is selected from the group consisting of gastric tissue, lung tissue, esophageal tissue, pancreatic tissue or breast tissue, and the tissue has optionally been diagnosed as affected by cancer, for example, by visual inspection or culture test of tissue or organ cells. In certain preferred embodiments, the tissue is a tissue other than gastric tissue. In certain preferred embodiments, the tissue is lung tissue, esophageal tissue, pancreatic tissue or breast tissue. In such embodiments, the subject is indicated as suitable for an antitumor therapy targeting CLDN18.2 when CLDN18.2 or a cell expressing CLDN18.2 is present, and / or when the number of CLDN18.2 cells or that express CLDN18.2 increases compared to a reference level (for example, compared to a patient without a tumor disease). In a preferred embodiment, the antibody or antigen-binding fragment thereof of the present invention is additionally labeled with a detectable marker. In another preferred embodiment, in step (2), a reagent with a detectable label is used to detect the antibody or antigen-binding fragment thereof of the present invention. In certain preferred embodiments, CLDN18.2 is human CLDN18.2. In certain preferred embodiments, the tumor is selected from the group consisting of gastric cancer, esophageal cancer, pancreatic cancer, bronchial cancer, non-small cell lung cancer, breast cancer, ear-nose-throat cancer, ovarian cancer, colon cancer, liver cancer, head and neck cancer, gallbladder cancer and their metastatic cancers (for example, gastric cancer metastases, such as Krukenberg tumor, peritoneal metastasis or lymph node metastasis). In certain preferred embodiments, the tumor is selected from the group consisting of esophageal cancer, pancreatic cancer, bronchial cancer, non-small cell lung cancer, breast cancer, ear-nose-throat cancer, ovarian cancer. , colon cancer, liver cancer, head and neck cancer, gallbladder cancer and their metastatic cancers (for example, gastric cancer metastases, such as Krukenberg tumor, peritoneal metastasis or lymph node metastasis). M A / t / ZUZ I / UODZDD In another aspect, there is provided the use of the antibody or antigen-binding fragment thereof of the present invention in the manufacture of a kit for determining whether a tumor is treatable by an antitumor therapy targeting CLDN18.2. In certain preferred embodiments, the antibody or antigen-binding fragment thereof is labeled with a detectable label. In certain preferred embodiments, CLDN18.2 is human CLDN18.2. In certain preferred embodiments, the tumor is selected from the group consisting of gastric cancer, esophageal cancer, pancreatic cancer, bronchial cancer, non-small cell lung cancer, breast cancer, ear-nose-throat cancer, ovarian cancer, colon cancer, liver cancer, head and neck cancer, gallbladder cancer and their metastatic cancers (for example, gastric cancer metastases, such as Krukenberg tumor, peritoneal metastasis or lymph node metastasis). In certain preferred embodiments, the tumor is selected from the group consisting of esophageal cancer, pancreatic cancer, bronchial cancer, non-small cell lung cancer, breast cancer, ear-nose-throat cancer, ovarian cancer. , colon cancer, liver cancer, head and neck cancer, gallbladder cancer and their metastatic cancers (for example, gastric cancer metastases, such as Krukenberg tumor, peritoneal metastasis or lymph node metastasis). Definition of terms In the present invention, unless otherwise indicated, the scientific and technical terms used herein have meanings commonly understood by those skilled in the art. Furthermore, the cell culture, biochemistry, nucleic acid chemistry, and immunology laboratory procedures used herein are routine procedures that are widely used in the corresponding fields. Meanwhile, to better understand the present invention, definitions and explanations of related terms are provided below. As used herein, the term CLDN18 (Claudin 18) has the meaning commonly understood by those skilled in the art, that it belongs to the Claudin family and is a transmembrane protein within the tight junction of the epithelium and endothelium, and exists in the form of two splice variants, CLDN18.1 and CLDN18.2. The sequences of CLDN18.1 and CLDN18.2 are well known in the art. For more information, see NCBI database accession numbers NP 057453.1 and NP 001002026.1. As used herein, the term antibody refers to an immunoglobulin molecule that typically consists of two pairs of polypeptide chains, and each pair M A / t / ZUZ I / UO3Z00 has a light chain (LC) and a heavy chain (HC). Antibody light chains can be classified as κ (kappa) and λ (lambda) light chains. Heavy chains can be classified as μ, δ, γ, αοε, and antibody isotypes are defined as IgM, IgD, IgG, IgA and IgE, respectively. Within the light and heavy chains, the variable and constant regions are linked by a J region of about 12 or more amino acids, and the heavy chains additionally contain a D region of about 3 or more amino acids. Each heavy chain is composed of a heavy chain variable (VH) region and a heavy chain constant (CH) region. The heavy chain constant region consists of three domains (CH1, CH2, and CH3). Each light chain consists of a variable light chain (VL) region and a constant light chain (CL) region. The constant region of the light chain consists of a CL domain. The constant domains do not directly participate in the binding of the antibody to the antigen, but exhibit a variety of selective functions, such as mediating the binding of the immunoglobulin to a tissue or host factor, including various cells of the immune system (e.g., cells effectors) and the first component (C1q) of the classical complement system. The VH and VL regions can also be subdivided into regions with high denaturation (termed complementary determining regions (CDR)), which are interspersed with interspaced conservative regions called framework regions (FR). Vh and Vl are each composed of 3 CDRs and 4 FRs arranged in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4 from the amino terminus to the carboxy terminus. The variable regions (VH and VL) of each heavy / light chain pair form an antigen binding site, respectively. The assignment of amino acids to various regions or domains can be according to the definitions of Kabat, Sequences of Proteins of Immunological Interest (National Institutes of Health, Bethesda, Md. (1987 and 1991)), Chothia et al. J. Mol. BioL 196:901-917 (1987), or Chothia et al., Nature 342:878-883 (1989). As used herein, the term complementary determining region or CDR refers to the amino acid residues in the variable region of the antibody that are responsible for binding to the antigen. The variable regions of the heavy and light chains each contain 3 CDRs, called CDR1, CDR2 and CDR3. The precise boundaries of these CDRs can be defined according to various numbering systems known in the art, for example, according to the Kabat numbering system (Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md., 1991), Chothia numbering system (Chothia & Lesk (1987) J. Mol. Biol. 196: 901-917; Chothia et al. (1989) Nature 342: 878 -883) or IMGT numbering system (Lefranc et al., Dev. Comparat. Immunol. 27: 55-77, 2003). For a given antibody, those skilled in the art will readily identify the CDRs defined by each numbering system. And the M A / t / ZUZ I / UOOZOO correspondence between different numbering systems is well known to those skilled in the art (for example, see Lefranc et al., Dev. Comparat. Immunol. 27: 55-77, 2003). In the present invention, the CDRs contained in the antibody or antigen-binding fragment thereof of the present invention can be determined according to various numbering systems known in the art. In certain embodiments, the CDRs contained in the antibody or antigen-binding fragment thereof of the present invention are preferably determined by the Kabat, Chothia or IMGT numbering system. In certain embodiments, the CDRs contained in the antibody or antigen-binding fragment thereof of the present invention are preferably determined by the Kabat numbering system. As used herein, the term "framework region or FR residue" refers to those amino acid residues other than CDR residues as defined above in antibody variable regions. The term antibody is not limited to any particular method of producing antibodies. For example, it includes recombinant antibody, monoclonal antibody and polyclonal antibody. The antibody may be an antibody of different isotypes, for example, IgG (for example, subtypes lgG1, lgG2, lgG3 or lgG4), lgA1, lgA2, IgD, IgE or IgM antibodies. As used herein, the term "antibody antigen-binding fragment" refers to a polypeptide comprising a fragment of a full-length antibody that retains the ability to bind specifically to the same antigen to which the antibody binds. full length and / or competes with the full length antibody to specifically bind to the antigen, which is also called the antigen binding portion. See generally Fundamental Immunology, Chapter 7 (Paul, W., ed., 2nd edition, Raven Press, NY (1989)), which is incorporated herein by reference in its entirety for all purposes. The antigen-binding antibody fragment can be produced by recombinant DNA technology or by enzymatic or chemical cleavage of the complete antibody. Non-limiting examples of antigen-binding fragments include Fab, Fab', F(ab')2, Fd, Fv, complementary determining region (CDR) fragments, scFv, diabody, single domain antibody, chimeric antibody, linear antibody , nanobody (Domantis technology), probody and said polypeptides, comprising at least a portion of antibody that is sufficient to confer specific antigen binding capacity to the polypeptide. Holliger et al, 2005; Nat Biotechnol, 23: 1126-1136 conducts a review of engineered antibody variants. As used herein, the term "full-length antibody" refers to an antibody consisting of two full-length heavy chains and two M A / t / ZUZ I / υοοζου full-length light chains. Full-length heavy chain refers to a polypeptide chain consisting of a heavy chain variable region (VH), a heavy chain constant region CH1 domain, a hinge region (HR), a chain constant region CH2 domain heavy and a heavy chain constant region CH3 domain in a direction from the N-terminus to the C-terminus; and, when the full-length antibody is an IgE isotype, the CH4 domain of the heavy chain constant region is optionally further included. Preferably, the full-length heavy chain is a polypeptide chain consisting of VH, CH1, HR, CH2 and CH3 in a direction from the N-terminus to the C-terminus. The term "full-length light chain" refers to a polypeptide chain. consisting of a variable light chain (VL) region and a constant light chain (CL) region in a direction from the N-terminus to the C-terminus. Two pairs of full-length antibody chains are linked to each other by a disulfide bond between CL and CH1 and a disulfide bond between HR of two full-length heavy chains. The full-length antibody of the present invention may be from a single species, such as a human; or it may be a chimeric or humanized antibody. The full-length antibody of the present invention comprises two antigen binding sites formed by VH and VL pairs, respectively, and these two antigen binding sites specifically recognize / bind to the same antigen. As used herein, the term Fd refers to an antibody fragment consisting of VH and CH1 domains; The term dAb fragment refers to an antibody fragment consisting of the VH domain (Ward et al., Nature 341: 544-546 (1989)); The term Fab fragment refers to an antibody fragment consisting of VL, VH, CL and CH1 domains; the term F(ab') / fragment refers to an antibody fragment comprising two Fab fragments connected by a disulfide bridge in the hinge region; The term Fab'fragment refers to a fragment obtained by reducing the disulfide bond connecting the two heavy chain fragments in the F(ab')2 fragment, which consists of a complete light chain and an Fd Fragment (composed of domains VH and CH1) of heavy chain. As used herein, the term Fv refers to an antibody fragment consisting of VL and VH domains of an antibody arm. The Fv fragment is generally considered the smallest antibody fragment that can form a complete antigen binding site. It is generally believed that 6 CDRs confer antigen binding specificity to an antibody. However, even a variable region (e.g., an Fd fragment containing only 3 antigen-specific CDRs) can recognize and bind to an antigen, although its affinity may be lower than that of the entire binding site. As used herein, the term Fe refers to a fragment of M A / t / ZUZ I / υοοζου antibody that is formed by joining the second and third constant regions of the first heavy chain of an antibody to the second and third constant regions of the second heavy chain through a disulfide bond. The Fe fragment of the antibody has many different functions, but is not involved in antigen binding. As used herein, the term scFv refers to a single polypeptide chain comprising VL and VH domains, where VL and VH are linked by a linker (see, for example, Bird et al., Science 242: 423-426 (1988); Huston et al., Proc. Nati. Acad. Sci. USA 85: 5879-5883 (1988); and Pluckthun, The Pharmacology of Monoclonal Antibodies, Vol. 113, eds. Roseburg and Moore, Springer-Verlag, New York, 269-315 (1994). Said scFv molecule can have a general structure of: NH2-VL-linker-VH-COOH or NH2-VH-linker-VL-COOH. A suitable prior art linker consists of a repetitive GGGGS amino acid sequence or a variant thereof. For example, a linker having an amino acid sequence (GGGGS)4 may be used, but a variant thereof may also be used (Holliger et al. (1993), Proc. Nati. Acad. Sci. USA 90 : 6444-6448). Other connectors useful in the present invention are described in Alfthan et al. (1995), Protein Eng. 8: 725-731, Choi at. to the. (2001), Eur. J. Immunol. 31:94-106, Huat. to the. (1996), Cancer Res. 56: 3055-3061, Kipriyanov et al. (1999), J. Mol. Biol. 293: 41-56 and Roovers et al. (2001), Cancer Immunol. In some cases, a disulfide bond may also exist between the VH and VL of scFv. As used herein, the term diabody refers to a fragment in which the VH and VL domains thereof are expressed on a single polypeptide chain, but the linker used is too short to allow pairing between the two. domains of the same chain, thus forcing the domain to pair with the complementary domain of another chain and generate two antigen binding sites (see, for example, Holliger P. at. al., Proc. Nati. Acad. Sci. USA 90: 6444-6448 (1993), and Poljak RJ et al., Structure 2: 1121-1123 (1994)). As used herein, the term single domain antibody (sdAb) has the meaning commonly understood by those skilled in the art, and refers to an antibody fragment consisting of a single monomer variable antibody domain ( for example, a single heavy chain variable region), which retains the ability to bind specifically to the same antigen to which the full-length antibody binds. Single domain antibody is also known as nanobody. As used herein, the term "probody" has the meaning commonly understood by those skilled in the art, and refers to a masked antibody that remains inert in healthy tissue but can be specifically activated in a disease setting (e.g. example, proteolytic cleavage by a protease that is enriched or M A / t / ZU¿ 1 / UOOZOO specifically present in the disease environment). For a detailed report, see, for example, Desnoyers et al., Sci. Transí. Med., 5: 207ra144, 2013. Similar masking techniques can be used on any of the antibodies or antigen-binding portions thereof described herein. Each of the above antibody fragments retains the ability to bind specifically to the same antigen to which the full-length antibody binds, and / or competes with the full-length antibody to specifically bind to the antigen. The antigen-binding antibody fragment (e.g., the above-mentioned antibody fragment) can be obtained from a given antibody (e.g., the antibody provided by the present invention) using a conventional technique known to those skilled in the art. technique (for example, recombinant DNA technology or enzymatic or chemical fragmentation methods), and its specificity can be analyzed in the same way that intact antibodies are selected. In context, unless expressly specified, when reference is made to the term antibody, it includes not only the intact antibody but also an antigen-binding fragment of the antibody. As used herein, the terms monoclonal antibody, mAb have the same meaning and are used interchangeably, which refer to an antibody or an antibody fragment derived from a population of highly homologous antibody molecules, i.e. a population of identical antibody molecules, except for natural mutations that can occur spontaneously. A monoclonal antibody is highly specific for a single epitope on an antigen. The polyclonal antibody, relative to the monoclonal antibody, typically contains at least two or more different antibodies that generally recognize different epitopes on the antigen. Furthermore, the monoclonal modifier simply indicates the character of the antibody obtained from a highly homogeneous population of antibodies, and should not be interpreted as requiring production of the antibody by any particular method. The monoclonal antibody of the present invention can be prepared by a variety of techniques, such as hybridoma technology (see, for example, Kohler et al. Nature, 256: 495, 1975), recombinant DNA technology (see, for example, the United States Patent Application η.θ4,816,567), or phage antibody library technology (see, for example, Clackson et al. Nature 352: 624-628, 1991, or Marks et al. J. Mol. Biol. 222: 581-597, 1991). Antibodies can be purified by well-known techniques, such as affinity chromatography, using protein A or protein G. Subsequently or as M A / t / ZUZ I / UO3Z00 alternatively, a specific antigen (a target molecule recognized by the antibody) or its epitope can be immobilized on a column and the immunospecific antibody can be purified by immunoaffinity chromatography. Purification of immunoglobulin may refer, for example, to D. Wilkinson (The Scientist, published by The Scientist, Inc., Philadelphia Pa., Vol. 14, No. 8 (April 17, 2000), pp. 25 -28). As used herein, the term "chimeric antibody" refers to an antibody, wherein a portion of the light and / or heavy chain thereof is derived from an antibody (which may be derived from a specific species or belong to a specific antibody class or subclass), and another part of the light or heavy chain thereof is derived from another antibody (which may be derived from the same or different species or belong to the same or different class or subclass of antibodies), but In any case, it still retains the binding activity to the target antigen (USP 4,816,567 of Cabilly et al.; Morrison et al., Proc. Nati. Acad. Sci. USA, 81: 6851 6855 (1984)). For example, the term chimeric antibody may comprise such an antibody (e.g., human-mouse chimeric antibody) in which the variable regions of the heavy and light chain of the antibody are derived from a first antibody (e.g., murine antibody), while The heavy and light chain constant region of the antibody is derived from a secondary antibody (e.g., a human antibody). As used herein, the term "humanized antibody" refers to a genetically modified non-human antibody whose amino acid sequence is modified to increase homology with the human antibody sequence. In general, all or part of the CDR regions of humanized antibodies are derived from a non-human antibody (donor antibody), and all or part of the non-CDR regions (e.g., FR variable region and / or constant region) are derived from an immunoglobulin. human (receptor antibody). The humanized antibody generally retains the expected properties of the donor antibody, including, but not limited to, antigen specificity, affinity, reactivity, and the like. The donor antibody may be a mouse, rat, rabbit or non-human primate (e.g., cynomolgus monkey) antibody with the expected properties (e.g., antigen specificity, affinity, reactivity, etc.). In the present application, the expected properties of the antibody of the present invention include the abilities to: (1) specifically recognize / bind CLDN18.2 (especially human CLDN18.2); (2) mediate internalization of CLDN18.2; (3) inducing the destruction of a human CLDN18.2-expressing cell through antibody-dependent cellular cytotoxicity (ADCC); (4) inducing the destruction of a human CLDN18.2-expressing cell through complement-dependent cytotoxicity (CDC); (5) prevent and / or treat a tumor. The antibody of the present invention has one or more of the expected properties mentioned above. M A / t / ZUZ I / UODZDD The chimeric antibody or humanized antibody of the present invention can be prepared based on the sequence of murine monoclonal antibody prepared as described above. DNA encoding heavy and light chains can be obtained from a target murine hybridoma, and can be engineered to contain a non-murine (e.g., human) immunoglobulin sequence using a standard molecular biology technique. To prepare a chimeric antibody, a murine immunoglobulin variable region can be linked to a human immunoglobulin constant region using a method known in the art (see, for example, US Patent No. 4,816,567 to Cabilly et al.). For example, a DNA encoding VH is operably linked to another DNA molecule encoding the heavy chain constant region to obtain a full-length heavy chain gene. The sequence of the human heavy chain constant region gene is known in the art (see, for example, Kabat, EA et al. (1991) Sequences of Proteins of Immunological Interest, fifth edition, Department of Health and Human Services of USA, NIH Publication No 91 -3242). A DNA fragment containing these regions can be obtained by standard POR amplification. The heavy chain constant region may be an lgG1, lgG2, lgG3, lgG4, IgA, IgE, IgM or IgD constant region, but in general, it is preferably an lgG1 or lgG4 constant region. For example, a DNA encoding VL is operably linked to another DNA molecule encoding the CL constant region of the light chain to obtain a full-length light chain gene (as well as a Fab light chain gene). The sequence of the human light chain constant region gene is known in the art (see, for example, Kabat, EA et al. (1991) Sequences of Proteins of Immunological Interest, Fifth Edition, Department of Health and Human Services of USA, NIH Publication No. 91-3242). A DNA fragment containing these regions can be obtained by standard PCR amplification. The light chain constant region may be a κ or λ constant region, but in general, it is preferably a κ constant region. To prepare a humanized antibody, murine CDR regions can be grafted onto a human framework sequence using any method known in the art (see US Pat. No. 5,225,539 to Winter; US Pat. Nos. 5,530,101, 5,585,089, 5,693). .762 and 6,180,370 by Queen et al.; and Lo, Benny, KC, editor, in Antibody Engineering: Methods and Protocols, volume 248, Humana Press, New Jersey, 2004). Alternatively, a transgenic animal can also be used, which is capable of producing a complete library of human antibodies without producing an endogenous immunoglobulin after immunization. For example, homozygous deletion of the antibody heavy chain binding (JH) region gene in chimeric and germline mutant mice has been reported to result in a M A / t / ZUZ I / UO3Z00 Complete inhibition of endogenous antibody production and transfer of the human germline immunoglobulin gene cluster in such germline mutant mice will result in the production of human antibodies upon challenge with the antigen (see, for example, Jakobovits et al., 1993, Proc. Nati. Acad. Sel. USA 90: 2551; Jakobovits et al., 1993, Nature 362: 255-258; Bruggermann et al., 1993, Year in Immunology 7:33; and Duchosal et al., 1992, Nature 355: 258). Non-limiting examples of the above-mentioned transgenic animal include HuMAb mice (Medarex, Inc.) comprising human immunoglobulin gene miniloci encoding unrearranged human heavy chains (μ and γ) and κ and κ light chain immunoglobulin sequences. and a targeted mutation that inactivates the endogenous μ and κ chain loci (see, for example, Lonberg et al. (1994) Nature 368 (6474): 856-859); or KM mouse™ carrying a human heavy chain transgene and a human light chain transchromosome (see: patent application WO02 / 43478). Other methods of antibody humanization include phage display technology (Hoogenboom et al., 1991, J. Mol. Biol. 227: 381; Marks et al., J. Mol. Biol. 1991, 222: 581-597; Vaughan et al., 1996, Nature Biotech 14: 309). As used herein, the term "germline antibody gene" or "germline antibody gene segment" refers to a sequence present in the genome of an organism that encodes immunoglobulin, which has not undergone a maturation process. which can lead to genetic rearrangements and mutations for the expression of a particular immunoglobulin. In the present invention, the term germline heavy chain gene refers to a germline antibody gene or gene fragment encoding an immunoglobulin heavy chain, comprising a V gene (variable), a D gene (diversity ), a J gene (union) and a C gene (constant); Similarly, the term germline light chain gene refers to a germline antibody gene or gene fragment encoding an immunoglobulin light chain, comprising a V gene (variable), a J gene (junction) and a C gene (constant). In the present invention, the amino acid sequence encoded by the germline antibody gene or the germline antibody gene fragment is also called the germline sequence. The germline antibody gene or germline antibody gene fragment, as well as the corresponding germline sequence thereof, are well known to those skilled in the art and can be obtained or queried in databases. professionals (e.g. IMGT, UNSWIg, NCBI or VBASE2). As used herein, the term specific binding or specifically binding refers to a non-random binding reaction between two molecules, such as a reaction between an antibody and a targeted antigen. The strength or affinity of a specific binding interaction can be expressed in terms of the equilibrium dissociation constant (KD). MA / I / UOOZOO of interaction. In the present invention, the term Kd refers to the dissociation equilibrium constant of the specific antigen-antibody interaction, which is used to describe the binding affinity between the antibody and the antigen. The lower the equilibrium dissociation constant, the tighter the antibody-antigen binding and the greater the affinity between the antibody and the antigen. In some embodiments, an antibody that specifically binds to an antigen (or an antibody that is specific to an antigen) means that the antibody binds to the antigen with an affinity (Kd) of less than about 10.9M, e.g. For example, less than about 10.9M, 10-10Μ, 10-11Μ or 1012M or less. The specific binding property between two molecules can be determined using a method known in the art, for example, determined by surface plasmon resonance (SPR) on a BIACORE instrument. As used herein, the term cytotoxic agent comprises any agent that is harmful to a cell (e.g., destroying a cell), such as a chemotherapeutic drug, a bacterial toxin, a phytotoxin or a radioisotope, and the like. As used herein, the term "vector" refers to a nucleic acid carrier into which a polynucleotide can be inserted. When a vector allows the expression of a protein encoded by the inserted polynucleotide, the vector is called an expression vector. A vector can be introduced into a host cell by transformation, transduction or transfection, so that elements of the genetic material carried by the vector can be expressed in the host cell. Vectors are well known to those skilled in the art and include, but are not limited to, the following: plasmids; phagemids; cosmids; artificial chromosomes, such as yeast artificial chromosomes (YAC), bacterial artificial chromosomes (BAC) or P1-derived artificial chromosomes (PAC); phages such as phage λ or phage M13 and animal viruses. Animal viruses that can be used as vectors include, but are not limited to, retroviruses (including lentiviruses), adenoviruses, adeno-associated viruses, herpes viruses (e.g., herpes simplex virus), poxviruses, baculoviruses, papillomaviruses, papova viruses ( for example, SV40) A vector may comprise a variety of elements that control expression, including, but not limited to, the following: promoter sequence, transcription initiation sequence, enhancer sequence, selection element and reporter gene. Additionally, the vector may comprise a replication initiation site. As used herein, the term "host cell" refers to a cell into which a vector can be introduced, including, but not limited to, prokaryotic cells such as E. coli or Bacillus subtilis, fungal cells such as such as yeast or aspergillus cells, insect cells such as S2 drosophila or Sf9 cells, or animal cells such as M A / t / ZUZ I / υοοζου fibroblasts, CHO cells, COS cells, NSO cells, HeLa cells, BHK cells, HEK 293 cells or human cells. As used herein, the term identity refers to the degree of match between two polypeptides or between two nucleic acids. When two sequences for comparison have the same base or amino acid monomeric subunit at a given site (for example, each of two DNA molecules has an adenine at a given site, or each of two polypeptides has a lysine at a given site). given site), the two molecules are identical at the site. The percentage of identity between two sequences is a function of the number of identical sites shared by the two sequences over the total number of sites for comparison x 100. For example, if 6 of 10 sites of two sequences match, these two sequences have an identity of 60%. For example, the DNA sequences: CTGACT and CAGGTT share 50% identity (3 of 6 sites match). In general, the comparison of two sequences is performed in a way to produce maximum identity. Said alignment can be carried out using a computer program such as the Align program (DNAstar, Inc.) which is based on the method of Needleman, et al. (J. Mol. Biol. 48: 443-453, 1970). The percentage of identity between two amino acid sequences can also be determined using the algorithm of E. Meyers and W. Miller (Comput. Appl. Biosci., 4: 11-17 (1988)) which has been incorporated into the ALIGN program (version 2.0), using a PAM120 residual weight table, a gap length penalty of 12, and a gap penalty of 4. Additionally, the percent identity between two amino acid sequences can be determined using the Needleman and Wunsch algorithm (J . Mol. Biol. 48: 444-453 (1970)) which has been incorporated into the GAP program in the GCG program package (available at http: / / www.gcg.com), using a Blossum 62 matrix or a PAM250 matrix , and a gap weight of 16, 14, 12, 10, 8, 6 or 4 and a length weight of 1.2, 3, 4, 5 or 6. As used herein, the terms conservative substitution and conservative amino acid substitution refer to amino acid substitutions that would not disadvantageously affect or change the expected properties of a protein / polypeptide comprising the amino acid sequence. For example, a conservative substitution can be introduced by standard techniques known in the art, such as site-directed mutagenesis and POR-mediated mutagenesis. Conservative amino acid substitutions include substitutions in which one amino acid residue is substituted with another amino acid residue that has a similar side chain, for example, a physically or functionally similar residue (such as, having a size, shape, charge, similar chemical property including the ability to form a covalent bond or hydrogen bond, etc.) to the corresponding amino acid residue. Families of amino acid residues that have side chains Similar M A / t / ZUZ I / υοοζου have been defined in the art. These families include amino acids that have basic side chains (e.g., lysine, arginine, and histidine), amino acids that have acidic side chains (e.g., aspartic acid and glutamic acid), amino acids that have uncharged polar side chains (e.g., glycine , asparagine, glutamine, serine, threonine, tyrosine, cysteine, tryptophan), amino acids that have non-polar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine), amino acids that have β-branched side chains ( such as threonine, valine, isoleucine) and amino acids that have aromatic side chains (for example, tyrosine, phenylalanine, tryptophan, histidine). Therefore, a corresponding amino acid residue is preferably replaced with another amino acid residue of the same side chain family. Methods for identifying conservative amino acid substitutions are well known in the art (see, for example, Brummell et al., Biochem. 32:11 BOUS? (1993); Kobayashi et al., Protein Eng. 12(10): 879 - 884 (1999) and Burks et al, Proc. Nati Acad. Set USA 94: 412-417 (1997), which are incorporated herein by reference). The 20 conventional amino acids involved herein are expressed according to routine methods. See, for example, Immunology-A Synthesis (2nd Edition, E. S. Golub and D. R. Gren, Eds., Sinauer Associates, Sunderland, Mass. (1991)), which is incorporated herein by reference. In the present invention, the terms polypeptide and protein have the same meaning and can be used interchangeably. Furthermore, in the invention, amino acids are generally expressed as one-letter codes and three-letter codes. For example, alanine can be expressed as A or Ala. As used herein, the term chimeric antigen receptor (CAR) refers to an engineered T cell receptor that has an extracellular targeting domain derived from an antibody (e.g., scFv) that is conjugated to one or plus intracellular signaling domains of a T cell receptor. In the present invention, the term chimeric antigen receptor T cell refers to a T cell that expresses a CAR and has antigen specificity determined by the targeting domain of the CAR. Methods for preparing CAR (e.g., for use in cancer treatments) are known in the art. See, for example, Park et al., Trends Biotechnol., 29: 550-557, 2011; Grupp et al., NEngIJMed., 368: 1509-1518, 2013; Han at. al., J. Hematol Oncol., 6:47, 2013; PCT Patent Publications WO2012 / 079000, WO2013 / 059593; and US Patent Publication 2012 / 0213783, all of which are incorporated herein by reference in their entirety. As used herein, the term pharmaceutically acceptable vehicle and / or excipient refers to a vehicle and / or excipient that is pharmacological and / or M A / t / ZUZ I / υοοζου physiologically compatible with a subject and an active ingredient, which is well known in the art (see, for example, Remington's Pharmaceutical Sciences, edited by Gennaro AR, 19th ed. Pa.: Mack Publishing Company, 1995 ) and includes, but is not limited to: pH adjusting agents, surfactants, adjuvants, ionic strength enhancers, diluents, agents to maintain osmotic pressure, agents to delay absorption, preservatives. For example, pH adjusting agents include, but are not limited to, phosphate buffered saline. Surfactants include, but are not limited to, cationic, anionic or nonionic surfactants, such as Tween-80. Ionic strength enhancers include, but are not limited to, sodium chloride. Preservatives include, but are not limited to, various antibacterial and antifungal agents, such as parabens, trichloro-t-butanol, phenol, sorbic acid and the like. Agents for maintaining osmotic pressure include, but are not limited to, sugar, NaCl and the like. Agents to delay absorption include, but are not limited to, monostearate and gelatin. Diluents include, but are not limited to, water, aqueous buffers (e.g., buffered saline), alcohols and polyols (e.g., glycerol), and the like. Preservatives include, but are not limited to, various antibacterial and antifungal agents, such as thimerosal, 2-phenoxyethanol, parabens, trichloro-t-butanol, phenol, sorbic acid and the like. Stabilizers have the meaning commonly understood by those skilled in the art, which can stabilize the desired activity of the active ingredient in the drug, including, but not limited to, sodium glutamate, gelatin, SPGA, saccharides (for example, sorbitol, mannitol, starch , sucrose, lactose, dextran or glucose), amino acids (for example, glutamic acid, glycine), proteins (for example, dried whey, albumin or casein) or degradation products thereof (for example, lactalbumin hydrolyzate), etc. . In certain illustrative embodiments, the pharmaceutically acceptable carrier or excipient includes a sterile injectable liquid (e.g., an aqueous or non-aqueous suspension or solution). In certain illustrative embodiments, said sterile injectable liquid is selected from the group consisting of water for injection (WFI), bacteriostatic water for injection (BWFI), sodium chloride solution (e.g., 0.9% (wt / vol) NaCl), glucose solution (e.g., 5% glucose), a solution containing surfactant (e.g., 0.01% polysorbate 20), a pH buffer solution (for example, a phosphate buffer solution), a Ringer's solution and any combination thereof. As used herein, the term prevention refers to a method performed to prevent or delay the onset of a disease or disorder or symptom (e.g., a tumor) in a subject. As used herein, the term treatment refers to a method performed to obtain a beneficial or desired clinical result. For the purposes of the present invention, the beneficial or desired clinical result includes, but is not limited to alleviating ΜΛ / I / UODZDO the symptoms, reduce the extent of the disease, stabilize (i.e., not exacerbate) the disease state, delay or retard the development of disease, improve or alleviate the disease state, and alleviate a symptom (whether in part or in whole), whether detectable or undetectable. Additionally, the term treatment can also refer to prolonging the survival period compared to the expected survival period (if not receiving treatment). As used herein, the term subject refers to a mammal, such as a primate mammal, such as a human. In certain embodiments, the subject (e.g., a human) has a tumor (e.g., a tumor that expresses CLDN18.2), or is at risk for having the aforementioned diseases. As used herein, the term "effective amount" refers to an amount sufficient to obtain or at least partially obtain a desired effect. For example, an amount effective to prevent a disease (e.g., tumor) is an amount sufficient to prevent, arrest or delay the onset of a disease (e.g., tumor); An effective amount to treat a disease is an amount sufficient to cure or at least partially block a disease and its complications in a patient with the disease. Determining such an effective amount is within the capabilities of those skilled in the art. For example, the effective amount for therapeutic use will depend on the severity of the disease to be treated, the general state of the patient's immune system, the general condition of the patient, such as age, weight and sex, the route of administration of additional medications and therapies used simultaneously, etc. As used herein, the term immune effector cell includes cells that have a hematopoietic origin and play a role in the immune response, for example, lymphocytes such as B lymphocytes and T lymphocytes; natural killer lymphocytes; myeloid cells such as monocytic cells, macrophages, eosinophils, mast cells, basophils and granulocytes. In certain preferred embodiments, the immune effector cell is a T cell. As used herein, the term metastasis refers to the spread of cancer cells from their original site to other parts of the body. Metastasis formation is a very complex process and depends on the detachment of malignant cells from the primary tumor, invasion of the extracellular matrix, penetration of the endothelial basement membrane to enter body cavities and blood vessels, and subsequent infiltration of target organs by blood transport. Finally, the growth of new tumors (i.e., secondary tumors or metastatic tumors) at the target site depends on angiogenesis. Tumor metastasis often occurs even after removal of the primary tumor, because tumor cells or components may remain and develop metastatic potential. In In one embodiment, the term metastasis according to the present invention refers to distant metastasis, which refers to a metastasis that is distant from the primary tumor and the regional lymph node system. The cells of a secondary or metastatic tumor are similar to those of the original tumor. This means, for example, that if ovarian cancer metastasizes to the liver, the secondary tumor is made up of abnormal ovarian cells (rather than abnormal liver cells). And that is why tumors in the liver are called metastatic ovarian cancer (not liver cancer). The beneficial effects of the present invention Compared with the prior art, the technical solution of the present invention has the following beneficial effects: The antibody of the invention is capable of specifically recognizing / binding to CLDN18.2, and is capable of inducing the destruction of a cell (e.g., a tumor cell) that expresses CLDN18.2 through ADCC and / or CDC. Therefore, the antibody of the present invention has the potential to be used for the prevention and / or treatment of a tumor, especially a tumor that expresses CLDN18.2. The humanized antibody of the present invention not only retains the function and properties of the original antibody, but also has a high degree of humanization, so that it can be safely administered to a human subject without triggering an immunogenic response. It is particularly surprising that the antibody of the present invention has significantly improved affinity and tumor killing activity compared to known anti-CLDN18.2 antibodies. Therefore, the antibody (especially the humanized antibody) of the present invention has great clinical value. Embodiments of the present invention will be described in detail below with reference to the drawings and examples, but those skilled in the art will understand that the following drawings and examples are only used to illustrate the present invention, rather than limit the scope. scope of this invention. Various objects and advantageous aspects of the present invention will be possible to those skilled in the art from the following detailed description of the drawings and preferred embodiments. Description of the drawings Figures 1A to 1D show the results of measuring the binding activity of murine anti-CLDN18.2 antibody to CLDN18.2 or CLDN18.1 on different cell surfaces, respectively. Figure 1A: HEK293T-hCLDN18.2; Figure 1B: HEK293T-mCLDN18.2; Figure 1C: HEK293T-hCLDN18.1; Figure 1D: HEK293T. Figure 2 shows the results of measuring the binding activity of the chimeric anti-CLDN18.2 antibody to the CLDN18.2 cell surface. M A / t / ZUZ I / UO3Z00 Figures 3A to 3C show the results of measuring the ADCC activity of the chimeric anti-CLDN18.2 antibody with respect to HEK293T-hCLDN18.2, KATO-lll and NUGC4, respectively. Figure 3A: HEK293T-hCLDN18.2; Figure 3B: KATO-lll; Figure 3C: NUGC4. Figures 4A to 4B show the results of measuring the CDC activity of the chimeric anti-CLDN18.2 antibody in relation to HEK293T-hCLDN18.2 and KATO-lll, respectively. Figure 4A: HEK293T-hCLDN18.2; Figure 4B: KATO-lll. Figure 5 shows the results of measuring the binding activity of the humanized anti-CLDN18.2 antibody to the CLDN18.2 cell surface. Figure 6 shows the results of measuring the ADCC activity of the humanized anti-CLDN18.2 antibody in relation to KATO-lll. Figure 7 shows the results of measuring the CDC activity of the humanized anti-CLDN18.2 antibody in relation to KATO-lll. Figures 8A to 8B show the effects of anti-CLDN18.2 antibody on tumor volume (A) and survival time (B) in mouse tumor models, respectively. Sequence information Information on some sequences involved in the present invention is provided in Table 1 below. Table 1: Sequence description ΜΛ / t / ZUZ I / υοοζου SEQ ID NC Description Sequence information 1 Heavy chain variable region 1D10 QVQLQQP GAE LVKPG AS VKLS CHAS G YTF~S YWMH WV KQ R PG QGLEWIGMIYPNSGSINYNEKFKNKATL'VDKSSSTAYMQLSSLT SEDSAWFCSVYFDY'A'GQGT-L_VSS 2 Light chain variable region 1D*C DIQGTQSPSSLSASLGERYSLTCRASQDIGSSLNWLQQEPDGTI KRLIYA'SSLDSGVPKRFSVSRSGSDYSLTISSLESEDFVDYYCL QYASSPPTFGGGTKLE1K 3 1D10 HCDR- GY'FTSY 4 1D10 HCDR2 YPNSGS 5 1D10 HCDR3 YFDY 3 1D10 LCDR1 QDIGSSL N 1D10 LCDR2 A'SSLDS s 1D10 LCDR3 LQYASSPPT 9 String variable region EVQLVESGGG-VKFGGSLKLSCAASGFTFSDYGHWVRQAFEK GLEWYAYISSGSSTIYYADTVKGRFTISRDNAKNTLFLQMTSLRS SEQ ID NC Description Weight sequence information 2F12 E D T AIY YC A KWD RG N C=D Y WG QGT'L'VS S 10 Light chain variable region 2F12 DIVLTQSPSSL'VTAGEKYTMSCKSSQSLLNSGNQKKYL'WYQQ KV3QPPK_UW¿4SIRECGYPDRF'GSGSGTDFLT:SSVQAED_ AVYYCCNAYS YPLTFGAG'KLELK 11 2F12 HCDR' GFTFSDY 12 2 = 12 HCDR2 SS3SST 13 2 = 12 HCDR3 WDRGMCFDY 14 2 = 12 LCDR1 KSSQS-LNSGHQKKYL' 15 2 = 12 LCDR2 WASIREO 16 2 = 12 LCDR3 QNAYS YFL~ 17 Weight chain variable region 3=2 E V V LVES Light chain variable region 3F2 E V V LVES AM S WVRQ'P E K RLE '.VIA'INDGGTYTYYPDNVKGRFTISRDNAKKNLYLHVSHLK SDD'AIHYC'RLARGNSMDYWGQGTSV'VSS 19 3=2 HCDR' ω -1 η ω l 20 3=2 HCDR2 ND3GTY 21 3=2 HCDR3 LARGNSMDY 22 3=2 ^CDR1 KSSQS-LNSGNQK NY-T 23 3= 2 -CDR2 WASTREY 24 3=2 ^CDR3 QNNYIYP-T 25 Weight chain variable region 5=9 QVQLQQSSAELVKPGASVKLSCKASGYTF'SvWVMH'AVKQRFG QGLEW GMIHPNSVS'NYNEKFKSKATLTVDKSSSTAWQLcSL 'SEDSAVYYCAVvFDYWGQGT'L'V SS 26 Light chain variable region 5FG DIQVTQS=SSLSASL3ERVSL' CRASQDIGSSLNV.'-QQEPD3TI KR Ll YA S S S_N S GV P K R FSVS R S 3 S D YS L~l S S L E S=D FVDYYCL QYA'SPPTFG33~KLEIK 5=9 HCDR' GY'FTSY 23 5=9 HCDR2 HPNSVS MA / t / ZUZ I / UOOZOO SEQ ID NO. Description Sequence information 29 5=9 HCDR3 AVYFDY 30 5=9 -CDR1 RA3QDIGSS-N 31 5=9 -CDR2 ASSS-NS 32 5=9 -CDR3 LQYATSPP' 33 Dumbbell chain variable region 9=3 EVRLQQSGFELVK^GASVKIPCKWSGYKF' DYNMD'AVKQSHGK SLEWIGEINPNNGG'IYKQKFKGKATL'VDKSSSTAYMELRSLTS E CTAVYYCARIYYG NSFAYWGQ3~L V '7S S 34 Light chain variable region 9F3 DIVM~Q3FSSL~VTAGEKVTM3CKS3QSLLNSGNLKNYL~'.WQ QKPGQPPKLLIYWAS'RESG VPDRF'GSGSGTDFTLTISSVQAE DLAVYYOQNDYFYP-TFGAGTKLEIK 35 9=3 HCDR- GYKFTDY 35 9 =3 HCDR2 KFNNGG 3? 9F3 HCDR3 IYYGNSFAY 33 9=3 -CDR1 KSSQS-LNSGNLKNYLT 39 9=3 -CDR2 WASTRES 40 9=3 -CDR3 QNDYFYFL 41 Weight chain variable region 10B11 QVQMKESGAELVKPGASVKISCKASGYAFSTYWMCWVKQRPG K3LEWIGQ YFGN3 DTNYNGK=KGKA'LTADKSSSTADMQLSS_ '3EDSAVYFCAR_GYGNSFTVWGQGTL''.'FVSA 42 Region light chain variable 13B' 1 DIQVTQSPSSLTVTAGEKVTMSCKSSQSL^NSGKQKNYLrA'YQ QKPGQPPKLLIYWAS'RESGVPDRF'GSGFGTDF'LTISSVQAE D LA ΥΎ Y 3 Q N A Y FY F F T F G 3 G T K L EIK 43 10B11 HCDR1 GYAFSTY 44 1 0B11 HCDR2 YP3KGD 45 10B1 1 HCDR3 LGYGN3FTY 46 10B11 LCDR1 KSSQS^LNSGNCKNY ^T 47 10B11 LCDR2 WASTRES 48 10B11 LCDR3 QNAYFYPF* 49 Chain variable region QVQLQQPG'ELVKPSASVKLSCKASGYTFTSYWMFWVKQRPG QGLEW GNIHPSNGGSNHNEKF-KSKAT-TVDKSSS'AYMQLSSL SEQ ID NO. Description Weight sequence information 27B5 'S E DSAVYYCAPIYYGN S LAYWG H 3TL VTYS A 50 Light chain variable region 27B5 DWM'QSFSSL'v^AGEKVTMSCKSSQSLLNSGNQKNYLT'vVYQ QKPGQPPKLLLYWAS'RESG'.',PDRF'GSGSGTDFT_TISS'.''QAE DLAVYYDQ NSYFy'FFTFGSGTKLEIK 51 27B5 HCDR1 GY~FTSY 52 27B5 HCDR2 HPSN3G 53 27B5 HCDR3 IYYGNSLAY 54 27B5 LCDR1 KSSQS^LNSGNQKNY^T 55 27B5 LCDR2 WASTRES 55 27B5 LCDR2 QNSYFYPF "7 CSGFELVKOGASVKMSCKASGYSFTDYNMHWVKQSHG KS PEWVG YIN PN KGGTGV N Q KF KG KAT _TV N KS S S TAN ME L R S L T S E D Ξ A YYY' 0 A RI WV G N S F A y' W G Q G T _ VTV S A 58 Light chain variable region 37B DWM'QEFSSL'VTAGEKVTMSCKSSQSLLNSGNQKNYLTV.VQ QKPGQFPKLLlYWAS'RESGVPDRF'GSGSGTDFTLTISSvQAE D LAWFCQKDYFy'FFTFGSGTKLEIK 59 37B1 HCDR1 GYSFTDY 60 37B1 HCDR2 KPNK33 61 37B1 HCDR3 IWYGMSFAY 62 37B1 LCDR1 KSSQS-LNSGNQKNY-T 63 37B1 LCDR2 WASTRES 64 37B1 LCDR3 QNDYFYFFT 65 Weight chain variable region 44A8 EVRLQQSGFELVK^GASvKMSG^SGYT- TDYNMHWvKQSHG KSLEWIGYINPKNGGIRYNQKFTGKATLT'v'NKSSSTAYMELRSLSED SAVYY DAR G G YY GKTLD NWGQGTSWS S 65 Light chain variable region Q4A3 KPKNGG SEQ ID NC Description Sequence information 68 44A8 HCDR3 GGYYGNTL3N 70 44A8LCDR1 KSSQS-LNSGNQKNY-T 71 44A8LCDR2 WASTSES 72 44A8 LCDR3 QNAYFYPWT 73 Heavy chain variable region 44F? 74 Light chain variable region F7 WYQ QKPGQPPKLLIY'A'AS'RESGVPDRF'GSGSGTDFTLTISSVQAE DLAVYYCQNAYYYPFTFGSG'KLEIK 75 44R7 HCDR' GY'FTSY 76 44F7 HCDR2 YPGNGD 7 and 44F7 HCDR3 GGYYGNSLDY 78 44F~ LCDR1 KSSQSLLNSGNQKNYLT 78 44F~ LCDR2 WASTRES 80 44F~ LCDR3 QNAYYYPFT 81 Human IgG' heavy chain constant region AS'KGFSVFFLAPSS¿STSGGTAAL3GL7KDV=PEPVTVSWNS G A L T S G V H T F F A V L Q S S G L ' F G L S S 'V'V ~ V F S S S L G ~ Q T YIC N V N H NGCFENNYK'TPPVLDSCGSFFLVSKLTVDKSRWCQGNV FSCSYMHEALHNHY'QKSLSLSPGK 82 Human κ light chain constant region RTVAAPSVFIFPPSDEQLKSG'ASVVCLLNNFYPREAKVQWKVD KALQSGNSQESVTEQDGKDSTYSLSSTLTLSKADYEKHKVYACE V'HQ 3 L S3 PVT KSPKR3EC 83 CLDM18 DNA 2-ECL1 3A3AT3 GGAGCACCCAGGACCT3TA0GACAACCCC3 GAC CAGCGTGT'CCAGTACGAGGGCCTGTGGAGGAGCTGCG_GA GGCAGAGCAGCGGCTTDACGGAGT 3GAGGCCCTAC Γ CAGC A~CCTGGGCC~GCCCGCCA~GCTGCAGGCCG~GAGG SEQ ID NC. Description Sequence information 84 DNA of OLDN18 2- EOL1-C3d G A OC A 3'GG AGC A DC CAAGAC Γ GTAOAACAAC CC CGTAACA GCT3”TT~CAACTAC0AGGGGCTGTGGCGCTC0TGTGT0C3A GAGAGOTOTGGOTTOACOGAGTGCCGGGGC'ACTTCAOCCT GCTGGGGCTGOCAGCCATGC'GCAGGOAGTGOGAGGCAGC GG0AGCGGCGGOGGCGGCAGCGGCGGCGGCGGCAGOGGC A G OCA OC~G ATC GTG AC CC CC G C G G AGCACCTGGCTGACCGCCTACGTGG ”GAAGGT G Γ CAGCCTGGCCGCCAACCT 3A”CGCCAT CGACA GCCAOGT GOT 3~GC3 GOGCOGT GAAGTGGCT GATCCT GGAG AA30AGAAGCOC3 A OGGCGTG1 CCAGGAGGAC3G0C0CGT GA~COACCAGGAGAT GAT OGGCGGC”TCAGGAAOGCOAAGG AGGCCGACGTGAGCCTGACOGCOT'CG'GCTGATCGCCCTS OAGGAGGCCAGGGACATCTGCGAGGGCCAGGT GAACAGCCT G CC CGGCAG CATO AACAAG 30 C 3 G CG AGTA 0 ATC G AGGCO A G0TA0ATGAACCT30AGAGGCCCTACA0C3'GGCCATCGCC G G OT A OGC OC~G GC 0 C~ G ATG AACAAG OT GGAGGAGCCCTA OC ~GGGCAAG~TCCT GAA0AC0GC0AAGGACA3GAA0AGGT G GGAG G AGC CC3A0 CAGO AGC~G TACAAOGT 3 3A33CCA0C A3CTACGCCC”GCTGGCCC”GCTGCT3CT3AA33A0T”CGA CAGCGTGCCCCCOGTGGTGAGGTGGOTGAAOGAGCAGAGGT A0TACGGC3G0GGCTACGG OAGCACCCA GGCCACCT CAT G GTGT'CCAGGCCCTGGCOCAG'AOCAGAOCGACGTGCCCGA CCACAAGGACOT GAACAT GGACGT GAGCTTCCACCTGCOCA GCAGGGG0AGC3A3GAG ΓC 85 ADN debCLDN'8.2 A~GGCOGT3ACC30C-GC0AGGGC0TGGG0T ~C3~GGTGAG OC~GATCGGCATOGCCG 30ATCATCGOCGOCAOCTGCA”GG ACCA3~GGAGCA0CCAGGAC0T G” ACAACAAOCCCS” GACC SEQ ID NC. Description Sequence information GCCGTGT~CAACTACCAGGGCOTG~GGAGGAGCTGCGTGAG GGAGAGCAGCGGC ΓCAOCGAGTGCAGGGGCTAO1 CACCC 'GC'GGGCCTGCCCGCCATGCTGCAGGCCGTGAGGGCCCTG A'GATCGTGGGCATCGTGCTGGGCGCCATCGGCCTGCTGGT GAGCATCTT CGCCCT GAAGT GOAT CAGGATCGGCAGCATGG AGGAOAGCGCCAAGG OCAAOAT GACCCT GACOAGCGGCAT 0 A'GTTCATCGTGAGCGGCCTG'GCGCCA'CGCCGGCGTGAG OGTG TCGCCAACAT 30TGG~GACCAACTTC~GGATGAGCAC OGCOAACA~GT ACAOCGGOATGGGCGGCAT GGT GCAGACCG 'GCA3ACCAG3 'ACACCT'C3GCGCCGCCCTGT'C3'GGGC 'GGGTGGCCGGCGGCC'GACCCTGATCGGCGGCGTGATGAT GTGCA'CGCC'GCAGGGGCC'GGCCCCCGAGGAGACCAACT ACAAGGCCGT 3A33TACCACGCCAGC330CA0AGC3~GGC0 'ACAAGCCCGGCGGCI CAAGGCCAGCACCGGC TCGGCAG 0AACACCAAGAACAAGAA 3A-CTAOGACGGCGGCGCOAGGA OC G AGGA 3GAGGTG CAGAGCTAC OC 0AGCAAG 0AC3ACT AC GTG 86 Human CLDN182 ar-incaciccs sequence MAVTACQGLGFVVSLIGIAGIIAATCMDQV .'STQDLYNNPV'AVFN YQGLWR S CVR E SS GFTEC RG YF~LLG LPAM LQAV R ALMIVG: VL GAIGL_VSIFALKCIR1GSVEDSAKANM~LTSGIMFIVSGLOAIAGV S V FAN M LV~N FWM STAN M Y'G M G G M VQ'VQTR Y'FG AALFVG 'yC'.'MGoLTLIG ^vMM^IACRGLAPEE N ' Y HrtokjHSVAY K PGGFKASTGFGSNTKNKKIYDGGAR~EDEVQSVPSKHCYV 8? Mouse CLDN18 2 ar-incaciccs sequence M S VT AC QG L G F VVS L1G F AG 11AATC Γ D Q WS'CD L VN N P VT A V F KYQGLWRSCVRESSGFTECRGYFT.LGLPAh'LQAVRALMIVGIV LGVIGILVSIFALKCRIGSVDDSAKAKM'L'SGILFIISGISAIIGVSV F ANMLVTNFWMSTAKMYSGMGGVGG'.IVQTYQTRYTFGAALF VGWVAGGLTLIGGVMMCIACRGLTPDDSNFKAVSYHASGQNVA YRFGGFKASTGFGSN'RNKKIYDGGARTEDDEQSHPTKYDYV 88 Sequence of ar'incáciccs of MST'TCQVVAFLLSIJGLAGClAATGrDMWSTQDLYDNFVTSVF Q YE G LWR S CVRQ S S G FTEC RP YF~I L 3 L P AM LQAV R ALM IVG: V SEQ ID NO. Description Human OLDN18' sequence information LGAIG_LVSIFALKOlRIGSVEDSAKANMTL~SGIMFIVSGLCAIAG VSVFANMLV'NFWVSTANMY'GMGGMVQTVQTRY'FGAALFv G Ά'ν' A G G L T LIG G 'ν' Μ M 0 A C R G LA F E E ~ N Y / .A '·.· S Y H A S G H S VA Y K PGGFKASTGFGSNTKNKKIYDGGAR'EDEVQSYPSKHDYV 89 Heavy duty chain amine sequence 175D10 KDVFPEPVTVSV.'NSGAL'SGVHTFF AVLQSSGLYSLSSVVTVPSSS-GTQTYICNVNHKPShTKVDKRV EPKSCDKTHTCFFCPAPELLGGPSVFLFFFKFKDTLMISRTPEVT CVWDVSHEDPE' / KFN'ZvYVCGVEVHNAK~KFREEQVNS~YRV VSVLTVLHGDWLNGKEVKC KVSNKALPAPIEKTISKAKGQPREP QVY~LPPSREEM~KNQVSLTCLVKGFYFSD AVEWESNGQPEN KYKTTPPVLDSDGSFFLYSKLTVCKSR 'vVQQGNVFSCSSWHEAL FNHYTQKS-SLSPGK 90 Light Chain An-¡ncaciccs Sequence 175D10 DIVM-QSFSSL'VTAGEKVTMSCKSSQSLLNSGNQKNYLTWYQ QKPGQPPKLLlYWAS'RESGvPDRF'GSGSGTOFTLTISSVQAE DLAVYYOQNDY3YFFTFG3 GTK_EIKRTVAAPSvFIFFPSDEQLK SG'ASVVCLLNNFYFREAKYQWKVDNALQSGNSQESYTEQOSK DSTYSLSSTLT-SKADYEKHKVYACEVTHQGLSSP'v'TKSFNRGE 91 Weight chain variable region T0C¿09bu15 Q VQ 92 Light chain variable region 70C¿- 09bu15 DIW I'QSFDS-AV^LGERATINCKSSQSVLNSGNCKNYLAWYQ QKPGQPPKLLIY' / vAS_RESGvPDRFSGSGS3_DFTLTSSLQAE 0VA Wy oqNΑΥΎΥpFTFgq gtkleik 93 7004-ü9hj'5 RCDR1 GY~FTSY ΜΛ / t / ZUZ I / UOOZOO SEQ ID NO Description Sequence information 94 7004-09hu'5 RCDR2 YPGKGD 95 7004-09hu*5 HCDR3 GGYYGNSLDY 93 7004-09hu'5 LCDR1 KSSQSV-NS G KQKNY LA 97 7004-09hj*5 LCDR2 WASTREc 98 7004-09hj'5 LCDR3 QNAYYYFFT 99 Heavy chain variable region 70C4- •39b u 39 MGWSCILFLVATATGVHSQVQLVQSGAEVKKPGASVKYSCKAS GY~FTSYNMHWVRQAPGQGLEWMGT YFGNGDTSVNQKFQG RVTMTRDKSTSP / YME-SSLRSED^AWFCARGGYYGNSLDYW GQGTLV TVS 130 Light chain variable region 70C4- •39b u 39 M G WS CI hF LVATATGVHS DIV V TQ S P D S 131 Variable region of the weighing chain 7QQ4. Light chain variable region 7QC4. •39bu10 M GWS CILF LVATATGVHS DIV V TQ S P D S LAV S LGERA'INCKS S QSL-NSGNQKNYLPAVQQKPGQPPKLUYWAS'RESGVPDRFS GSGSGTDFTLTISSLQAEDVAVYYCQKAYYYPFTPGQGTKLEIK 133 Arurin nucleic sequence that cocodes the variable region of the heavy chain CAGGTO CAACTGCAGCAGCCTGGGGC'GAGC'GGTAAAGCC ~GGGGCTTCAGTGAAGTTGTCC-GCAAGGCTTOTGGOTACAC ~TTOACOAGC~ACTGGATGCACTGGGTGAAGCAGAGGCCTG GACAAGGCO1 GAGTGGATT GGAAT GA ΓΤΑΤ OCTAA.TAGT G GTAGCA~T AAC~ACAAT GA GAA G~T CAA GAACAAGGC CACAO MA / t / ZUZ I / UOOZOO SEQ ID NO. Description Sequence information 1313 'GAC'GTAGACAAA'CCTCCAGCACAGCCTACATGCAACTCA SCAGCCTGACATCTGAGGACTC'GCGGTC'ATT'CTGTTCTG AGI FGACT AC~GGGGCGAAGGCACCACTCT CAGAGT OT 3C'CA 134 Anurin nucleic sequence that links the light hip variable region 1D13 GACATCCAGGGGA3ACAG~CT GCA ~CCTCCTTATCTGCGT ST 0T33GAGAAA3A3~CAG~0TCAC~TGTCGGGCAAGTCAGGA SATTGGTAGTA33T'AAA3TG33T'GAGCAGGAACCAGATGG AACTAT~AAACGCCT3A~C~AGGCCACATC3AGT~TAGAT~CT GGTGTCCCCAAAAGG'TCAG'GTCAGTAGGTCTGGGTCAGA' ATT3TCTCACCA CAGCAGCCTTGAGTC GAAG ATT TGTAG AOTAT-AC'GTCTACAATA'GC'AGTTCTOC'CCGACGTTCGG ~GG AGGCA0CAAACTG3AAAT OAAA 135 Sequence of anurin nucleic that encodes the variable region of the heavy chain 2-12 GAGGTGCAGCTGGTGGAGTCT33GGGAGGC~TAGT3AA3CC _GGAGGGTGCGTGAAACTCTCGTG~GCTGCCTCTGGAT_CAC 'TTOAGTGACTATGGGATCOAC'GGGT'CG'CAGGCTCCAGA GAAGGGGCTGGAGTGGG'TGCATACATTAGTAG'GGCAG'A GTACCATCTAC ATGCAGA3ACA3 GAAGGGCOGAT CACCA ~C~CCAGAGACAAT 3CCAAGAACACCGT 3TTCCTGCAAAT 3A 0CA3~C ~GAG3TCT GAG3ACAGG3CCATA~ATTACT 3T3CAA A3~GGGAC0GG33~AA0T3d Γ GAC~AC~GGGGCOAAGGC ACCACTCTCAOAGTCTCCTOA 136 Sequence of snurin nucleic that cocodes the variable region of the light chain 2-12 3A0ATTGTGT'GAC0CAG'CT0CA'C0TCCCTGAC'GT3A 0A 3GAGGAGAGAAGGT OAC—AT GAGCT GCAA3TCCAGT CAGAG C GTTAAA^AGTG3AAATCAAAAGAAA ACI TGAC0T33 AT 0AGCA3AAA3~AGGGCA3CC~CCTAAAC~GTT3A~TTA0T33 G0ATCCATTAGGGAAT3~GGGGTCCCTGA~0GCTTCACAG3C AS'GGATCTGGAACAGATTTOAT'CTOACCATCAGCAG'GTG CAGGCT GAAGACCTG3CAGTTTATTACT G~CAGAAT GCT—ATA GTTATGCGCTCACG'TCGGTGCTGGGACCAAGCTGGAGCTG 137 Sequence of GAGGT GAT G OT G G^GGAGTCTGG G GGAGGCT^AGT GAAGCC SEQ ID NO Description Information on the sequence .qrjHn nucleic that encodes the variable region of the heavy scene 3=2 'GGAGGGTOCCTSAAACTCTCOTG'GCAGCC'CTGGATTCAC 'TTOAGTAOC'ATGC 0 AT G'CTTGGGT'C 3 OCA 3 ACT C3 3A AAA3A330T33A3~GGATCGCAACCAl AATGAT33~ GGTAC ~TACAOC~AC~ATCOAGACAAT 3TAAAGGGCCGA1 CACCAT 0 COA3AGACAATG OC.AA GAACAACCTGTAOC ACACATGAGC OATCTGAAGTOT3ACGACACAGCCATC0A1 ACTGTACAAGA 0TA30GAGGGG3AA1 C~AT GGAC~AC~GGGGTCAAGGAAC OTCAGTCACCGTCTCCTCA 13S Plowing sequence in nucleic that encodes the variable region of the light hip 3=2 GAGGT GAT GOT G3~ GGAGTCTGG33GAGGC1 AGT GAAGCC 'GGAGGGTOCCTGAAACTCTCOTG'GCAGOC'CTGGATTCAC 'TTOAGTAOC'ATGC 0 AT 3'CTTGGGT'C G OCA 3 ACT C3 3A AAA3A330T33A3~GGATCGCAACCA1 AATGAT 3G~GGTA0 FACAOC” AC~ ATCOAG ACAAT GTAAAGGGC0GA1 CACC ATO ~ CCAGAGACAATGOCAAGAAOAA.CCTGTAOC~ACACAT GAGC OAT CT GAAGT OT GA0GACACAGCCATCCA1 ACT GTACAAGA 0TAG0GAGGGGGAA1 C~ AT GGAC~AC~GGGGTOAAGGAAC OTCAGTCACCGTCTCCTCA 139 Sequence of Aourin nucleic acid that cocodes the variable region of the heavy chain 5=9 OAGGTOCAACTGCAGCAGTOTGGGGCTGAGCTGGTAAAGCO 'GGGGCTTCAGTGAAGTTGTOC' GCAAGGOTTOTSGOTACAC ~TT0AC0AGC~ACTGGATGCA0T33GTGAAGCAGAG30CTG GAOAAGGCOT GAGTGGATT GGAAT 3A Γ CA~CCT AATAG -G TAGTAOTAACT ACAA~GAGAAGTTCAAGAGCAAGGOCACACT GAOTS'AGACAAATOC'CCAGCACAGOCTACA'GCAACTCAG OAGCOTSAOATCTGAGGACTC'GCGG'C'ATTACTGTGCTGT OTACT1 GAC~ACT GGGGCCAAGGCACCACT C~ CACAGT CTC OTOA 110 Sequence of nucleic srudn that cocifies the variable region of the light hip GAOATCCAGG'GACACAGTC'COATCOTOC' TATOTGOC'CT OT GGGAGAAA3AG~CA3~0T OAC~T GT OGGGOAAGTCAGGA 0 ATT G GT AGTA 3 3ΓΑΑΑ OT 3 3 OTO AGC AG GAAOC AGATGG AAOTAT'AAACGCCTGA'C'ACGCCTCATOCAS'TTAAATTC' GGTGTCCOCAAAAGG'TCAG'GTCAGTAGGTOTGGGTCAGA' ΜΛ / t / ZUZ I / UOOZOD SEQ ID NC Description Sequence information 5=9 ~ATT CTCTCACCA” CAGCAGCCTT GAGTC-GAAGAT1 Γ GTAG AOTAT-AC'GTCTACAATA'GC'ACTTC'CCTCCGACGTTCGG ~GGAGGCA0CAA30T3GAAAT CAAA 1 11 Nucleic srudn sequence that encodes the variable region of the heavy chain 9 =3 3A33TTCGGC~GC.AACAGTCT GGACCT GAGOT GGT GAAGCC ”GGGGCTTCAGTGAAGATACCCTGCAAGGC~TCTGGATACAA A'TCA0T3ACTACAA0AT33ACTGG3'GAAGCAGA3CCA'GG AAAGAGCC Γ GAGT GGATT G3A3AAATT AATCCTAACAAT GGT GGTAC-ATCTACAACCAGAAG1 CAAGGGOAA GGCOACA TG ACT G~AGACAAGTCC''CCAGCACAGCCTACA~GGAGC~CCGC AGOC'GACAT CT GAGGAOAC ~GCAG~C~ ATT ACT GT GCAAGA A'TTACTATGGTAAC'CCTT'GC'TAC'GGGGCOAAGGGACTC 'GGTCACTGTCTC'TCA 1 12 Sequence of anurin nucleic encoding the variable region of the light chain 9=3 GAOATTGTGATGACACAG'CTCCA'CCTCCCTGACTGTGACA G CAGGAGAGAAGGT0AC~ ATGAGCTGCAAGTCCAGTCAGAG ~C~GTTAAACAGTGGAAATCTAAAGAAC~ACTTGACOTGG~ AC OAGCAGAAACCAGGGOAGCOTCC-AAA01 TTGA-CTAOTGG GCATOCACTAGGGAATOTGGGGTCOC~GATCGC ΓCAOAGGC AG'GGATCTGGAACAGATTTCACTC'CACCATCAGCAG'GTG OAGGCTGAAGACCT GGCAGTTT ATTAOT G~CAGAAT GA Γ Al TTA~CCGC—CACGTTOGGT GOT GGGAOCAAGOT GGAAAT CA 113 Cocoding nucleic arurin sequence the heavy chain variable region 10B11 OAGGTGCAAAT GAAGGAGT OTGGGGCT GAGCTGGTGAAGCC GGGGCOT OAGT GAAGA rTCC-GCAAAGCTTCT GGCT ACGC A~T CAGT ACCTACTGGAT GGACTGGGTGAAGCAGAGGOCT G GAAAGGGTC'TGAGTGGATTGGACAGATTTATCCTGGAAA'G GTGATACTAAC ACAACGGAAAGTTCA AGGGCAAG3CCACAC ~ GAC~ GCAGACAAA” CCTCCAGCACAGCCGACAT GCAGOTCA GCAGCCTGAOC'CTGAGGACTOTGOGGTOTATTCTGTGCAA GA'TGGGG'ATGGTAAOTCGTTTAC' TAC'GGGGCCAAGGGA OTCTGG'CACTGTCTCTGCA 114 Sequence of GAOATCCAGG~GACACAGTC~CCATCOT OCOT GACTGT GAGA MA / / UOOZOO SEQ ID MC Description Information on the nucleic acid sequence that codes for the light hip variable region 10B11 GOAGGAGAGAAGGT OAC~AT GAGCTGC.AAGT CCAGTCAGAG — C~ GTTAAACAGT GGAAATCAAAGAAOTAOTT GAOC-GGTAC CAGCAGAAACCAGGGCAGCCTCC-AAACT G Γ GAT OTACT GG GOATCCACTAGGGAATCTGGGGTCCC”GATCGC~ TCACAGGC AG~ GGATTTGGA ACAGA ΓΤ CAC~CTCACCATCAGCAG~GTG CAGGCTGAAGACCTGGCAGTTTATTACTG”CAGAATGCT~ATT 'TTA'COATTOACG'TCGGC'CGGGGAOAAAGCTGGAAATCA 115 Nucleic athyroid sequence that cocifies the variable region of the heavy scene 27B5 CAGGTCCAACTGCAGCAGCCTGGGACCGAGC'GGTGA AGCC 'GGGGCTTCAGTGAAGCTGTOC'GCAAGGCT'CTGGCTACAC CT'CACCAGCTAC'GGATGCACTGGGTGAAGCAGAGGCCTG GAOAAGGCOT GAGTGGATTGGAAATAT CATCCTAGCAA G GT GGTAG~AACCACAAT GAGAAG~T CAA GAGCAAGGC CACAO GAC GTAGACAAA CCTCCAGCACAGCOTACATGCAGOTCA GOAGCCTGACATCTGAGGACTC'GCGGTC'ATTA'TGTGOGC OTATCTAOTATGGTAAC'CGOTTGCT'ATTGGGGCCACGGGA CTCTGG'CACTGTCTCTGCA 11 6 Nucleic acid sequence that coacifies the variable region of the light chain 27B5 GA'GTTGTGATGAOCOAGTCTCCATOC 'CCCTGACTG'GACA GOAGGAGAGAAGGT CAC~AT GAGCTGC.AAGT CCAGTCAGAG 'C'GTTAAACAGTGGAAATCAAAAGAACTACTTGAOC'GGTAC CAGCAGAAACCAGGGOAGCCTCC”AAAOTATTGC”C”AOTGG GOATCCACTAGGGAATOTGGGGTCOC~GATCGC ΓCAOAGGC AG GGATCTGGAACAGATTTCACTC CACCATOAGCA G GTG OAGGCT GAAGACCTGGCAGTTTATT AOT G~CAGAATAG TAI 'TTA'COATTCACG'TCGGC'OGGGGAOAAAGCTGGAAATCA 117 Sequence of nucleic athyrio that encodes the variable region of the pessda scene GAGGTTCGGC~GCAACAGTCTGGACOT GAGOT GGTGAAGCC GGGGCTTCAGTGAAGATGTCCTGCAAGGC'TCTGGATACTC A Γ CACT GACTACAAOAT GCAC~GGGT GAAGCAGAGCCAT GG AAAGAGCCCTGAG'GGGTTGGATATATTAACCCTAAOAAGGG ~GGTACT GGCTACAACCAGA AG Γ CAAGGGCAAGGCCACAT MA / t / ZUZ I / UOOZOO SEQ ID NO Description Sequence information 3~B1 GACTG AAADAAGTCC CCAGCACAGGCAACATGGAGGTCCG CAGCCTGACATCGGAGGATTCCGCAGTCTATTAC'GTGCACG GA'ATGGTATGGTAATTCG'TTGCT'ACTGGGGCCAAGGGAC 'C'GGTCACTGTC'CAGCA 1 1S Anurin nucleic sequence that cocodes the light hip variable region 37B1 GA'G TTGTGATGACACAG'CTCCA 'CCTCCCTGAC'GTGACA GOAGGAGAGAAGGT OAC~AT GAGCTGCAAGTCCAGTCAGAG 'C'GTTAAACAGTGGAAATCAAAAGAAGTACTTGAGC'GGTAC CAGCAGAAACCAGGGCAGCCTOC'AAACTG'TGATCTACTGG GGATCCACTAGGGAAT OTGGGGTCCC-GATCGC Γ CAOAGGC AG~GGATCTGGAACAGATTT CACT C~CACCAT CAGCAG~GT G CAGGCTGAAGACOTGGCAGTTTATTTC'GTCAGAATGATTA'T TTA~CCATTCACG Γ CGGC~GGGGGACAAAGTT GGAAA ~AAA 1 19 Sequence of Afurin nucleic encoding the variable region of the heavy chain 44A8 GAGGTTCGGC~GCAACAGTCTGGACCTGAGOT GGTGAAGCC 'GGGGCTTCAGTGAAGATGTCDTGCAAGGC'TCTGGATACAC A'TCACTGACTACAACATGCAC'GGGTGAAACAGAGCCATGG AAAGAGCC Γ GAGT GGATTGGA~ATATT AACCCTAAGA AT GGT GGTATTAGATACAACCAGAAG1 CACGGGCAAGG OCAS ATT G ACTG~AAACAAGTCCTCCAGCACAGCCTACATGGAGC~CCGC AGOC ~GACAT CGGAGGA Γ C~GCAG~C~ATTACTGT GCAAGA GGGGGTTAOTACGGTAATACTTTGGACAACTGGGGTCAAGGA ACC'CAGTCACCGTCTCC'CA 120 Sequence of arurin nucleic encoding the variable region of the light chain 44A8 GACATTGTGATGACACAG*CTCCA~CCTCCCTGACTC~GACA GOAGGAGAGAAGGTCAC'ATGAGCTGCA AGTCCAGTCAGAG 'C'GTTAAACAGTGGAAATCAAAAGAACTACTTGAOC'GGTAC CAGCAGAAACCAGGGOAGCOTCC -AAAOT G Γ GAT OTACT GG GCATCCACTAGTGAA~CTGGGGTCCCTGATOGCTTCACAGGC AG~GGATCTGGAACAGATTTOACTC-CACCATOAGCAG—GTG OAGGCT GAAGACCTGGOAAT1 ATTACT GT OAGAAT GCTTA Γ -TTA'CCGTGGACGTTCGGTGGAGGCACCAAACTGGAGATCA MA / I / UOOZOO SEQ 1D NC. Description Sequence information 121 Arurin nucleic sequence that codes for the variable region of the heavy stage 44F7 0AGGT0CAACTGCAGCAGTCT33GGCTGAGCTGGTGAGGCC ~GGGGCCT0AGT3AA3A~GTCCT30AAGGC~TCTGGCTACA0 A TTACCA3 TACAA ATGCA0T333TAAAGCA33CACCTAG A0AGGGCCT33AA~GG ATTGGAACTA~TTA~CCAGGAAATGG ~ GATACTTOC~ACAATOAGAAGTT 0AAGGGC.AA33CCA0AC~ 3A0T3~AGACAAATCC~CCAGCACAGCCTACA ~GCAGCTCAG OAGCOT 3ACATCT GAGGACT C~ GC3G~ C~ ATI CTGT GC.AA3 A3GGGGC'A0TA~GGTAACTC'CTTGAC'ACTGGGGC0AAGG OACOAC CT0ACA3 C CCTCA 122 Sequence of arurin nucleic that cocodes the light hip variable region 44F7 GAOATCCAGATGACACAG~C~CCATCOTOCOTGACTGT 3ADA GOAGGAGAGAAGGTOAC~AT GAGCTGCAAGT COAGT CAGAG ~CGTTAAACAGTGGAAATCAAAAGAACTAOTTGAOC”GGTAC 0AGCAGAAACCAG3A0AGC0TCCTAAA0TGTTGATCTACTGG GCATCCACTAGGGAAT OT 3GGGTC0C~GATCGC PCAOAGGC A3~GGATCTGGAACAGATTTCACTC~CACCAT0AGCA3~G TG OAGGCT GAAGACCTG30AGTTTATTA0T 3~CAGAATG0T~ATT A Γ ATOCA Γ CA0G1 CG30TCGGGGACAAAG0T GGAGA~CA 123 Arurin nucleic sequence that codes for the variable region of the heavy box 7004-OGhu* 5 0AGGTG0AGC~GGT30AGT0TGGGG0T3A3G~GAAGAAGCC ~GGGGC0T0AGT3AAGG~TT0C~GCA.AGG0ATCTGGATA0AC 01 CACCAGCTAC-AT AT 30AC~GGGT GCGACAG30C0C-GG ACAAGGGC'TGAG'GGATGGGAACTATOTATOC 'GGTAATGG GAT AC AAG OTAO AACC AG AA GTTO C AG 3 g 0 Ag AGT 0 AC OAT GACCAGGGGAAAGCACGAGCACAGTCT AC ~ GGAGC ~ GA GCAGCOTG.AG.A ~ C ~ GAGGACACGGCOGGTG ~ att ~ ot gtgcga gagg0gg3 ~ atta ~ gggaacagt0t ~ gac ~ a0tgggggggccagccagccagccagcca Cc 124 sequence of nucleic arurin that cook the GACATCGTGATGACCCAGT0T0CAGACTCCCTGGCTGT3~CT 0T33GCGAGAGGG0CACCAT CAAC~GCAAGT OCAGCCAGAG ~GTTTT AAACAG CGGC AACCA GAA GAA OT ACTTA GOTT G GT AC 0AGCAGAAACCAG3A0AGCCTCCTAA3~TGCTCA~TTA0T3G variable region ΜΛ / t / ZUZ! / UdOZOO SEQ ID NO Description Sequence information for the light hip '004-06hu'5 GCGTOTACCCGGGAATCCGGGGTCCC'GACCGATTOAGTGG CAGCGGTCTGGGACAGATTTCAC~C~CACCAT~AGCAGCC_ GCAGGCTGAAGATG'GGCAG'TTA'TAC'GTCAGAATGCA'A 'TACTACOCOTTCAC'TTTGGCCAGGGGACCAAGCTGGAGAT 125 Sequence of anurln nucleic cocoding region heavy scene variable '004-0Ghu0& A'GGGC'GGAGC'GCA'CATOC'GTTOCTCGTGGCOACAGOT AOAGGAGTGOATAGCCAGG'GCAGCTGGTGCAGTOTGGGGC 'GAGGT GAAGAAGOC'GGGGCOTCAGTGAAGGTTTOC'GCA AG GOATCTGGATAOACOT-CACOAGCTACAACATGCAOTGGG 'GCGAOAGGCOCOTG GAOAAGGGCTT GAG'GGATGGGAACT A” CTA'CCTGG'AATGGT GA'ACAAGCTACAAOCAGAAGTTCO AG GGCAGAGTCACCATGACCAGGGACAAGTCCACGAGOACA GTC~ACATGGAGOTGAGOAGCOT GAGA'C'GAGGACACGGC CGTG'ATT'C'GTGCGAGAGGCGGGTATTA'GGGAACAG'C' 'GAC'ACTGGGGCCAGGGAACCC'GGTCACCGTCTCC 126 Nucleic link sequence that codes for the variable region of the light chain '0C'4-0Ghu 0G A'GGGC 'GGAGC'GCA'CATOC'GTTOCTCGTGGCOACAGOT AOAGGAGTGOATAGCGACATOGT GA~GACCCAG—CTOCAGAS ' COC' GGC'GT GT OTOT GGGOGAGAGGGCCACCAT OAAC'G OAAGTCCAGCCAGAGO1 TTAAACAGTGGCAACCAGAAG.AA OTATTTAGOTT GGTACOAGCAGAAACCAGGACAGCOTCOTAA GTTGCTCATT AC TGGGCATOTACCCGGGAATCCGGGG-COC 'GACCGATTCAGTGGCAGCGGGTCAGGAACAGACTTCACTOT 0ACOATCAGCAGC CTG 0AGGCTGAAGATG'GGCAG'TTA'TA OT G” CAGAAT GOATATT AC~ ACCOGTT CAOTTTTGGOCAGGG GAOCAAGOT GGAGA'CAAA 12' Nucleic .anudn sequence that codes the variable region of the heavy chain '0C'4-0Ghu'C' A'GGGC'GGAGC'GCA'CATOC'GTTCCTCGTGGCCACAGOT ACAGGAGTGOATAGCCAGG'GCAGOTGGTGCAGTOTGGGGC ~ GAGGT GAAGAAGOC'GGGGCOTCAGT GAAGGTTTCC-GCA AG GOATCT GGATACACOT CACCAGCT AC'AT AT GCAC'GGG 'GCGAOAGGCOCOTG GAOAAGGGCTTGAG'GGATGGGAACT A-CTA~CCTG3~AATGGT GA'ACAAGCTACAAOCAGAAGTTCO MA / t / ZUZ I / UOOZOO SEQ ID NO Description Sequence information A3GG0AGAGT0AC0ATGACCAGG3ACAAGTCCACGAG0ACA GTO”ACATGGAGOTGAGCAGCOT GAGA~C—GAGGACACGGC OGTG'ATT'C'GTGCGAGAGGCGGGTATTA'GGGAACAG'C' 'GAC'ACTGGGGCCAGGGAACOC'GGTCAOCGTCTCC 12S Nucleic acid sequence that contains the variable region 70C4- light hip 06hu'0 A'GGGC'GGAGC'GCA'CATOC'GTTOCTCGTGGCOACAGOT ACAGGAGT30ATAGCGACAT0GT GA~GACOCAG-CTOCAGAO ~COC~GGCCGT G~CT 0T3GG0GAGAGG 3CCACCAT OAAC~G OAAGTCCAGCCAGAG CT TTAAA0AGC3G0AACCAGAAGAA CTACTTAA0TTGGTAC0AGCA3AA ACCAGGACAGCCTCCTAA GTTGCTCATT~ACTGGGCGTCTACCCGGGAATCC3GGGTC0C ~ GACOGATT OAGT 3G0T0C3GGT C~ GGG ACAGA ΓΤ OAC” CT 0ACCATCAGCAGCCTGCAGGCTGAAGAT3'GGCA3'TTA'TA OT 3~CAAAAT GOATACTAC'AOCCGTT CACTTTTG30CA3GG GA0CAA30TG3A3A”CAA A ΜΛ / I / UODZDO Specific ways to put the invention into practice The invention will now be described with reference to the following examples which are intended to illustrate the invention without limiting it. Unless otherwise specified, the experimental molecular biology methods and immunoassays used in the present invention can basically be referred to J. Sambrook et al, Molecular Cloning: Laboratory Manual, 2nd Edition, Coid Spring Harbor Laboratory Press, 1989, and F.M. Ausubel at. al., Short Protocols in Molecular Biology, 3rd edition, John Wiley & Sons, Inc., 1995. The use of restriction enzymes was in accordance with the conditions recommended by the product manufacturer. Those skilled in the art know that the embodiments describe the present invention by way of example and are not intended to limit the scope of the invention according to its claims. Example 1 Production of murine anti-CLDN18.2 antibodies To obtain the human anti-CLDN18.2 antibody, mice (Beijing Weitong Lihua Experimental Animal Technology Co., Ltd., strain 216) were vaccinated using different immunization strategies (Table 2) to activate the generation of murine monoclonal antibodies. The antigens included: an expression plasmid expressing the nucleic acid sequence encoding the extracellular domain 1 of human CLDN18.2 (CLDN18.2-ECL1 DNA; SEQ ID NO: 83, the vector was pcDNA3.1), a expression plasmid that expresses the nucleic acid sequence encoding the C3 complement of the extracellular domain 1 of human CLDN18.2 (CLDN18.2ECL1-C3d DNA; SEQ ID NO: 84, the vector was pcDNA3.1), a plasmid of expression expressing the nucleic acid sequence encoding full-length human CLDN18.2 (hCLDN18.2 DNA; SEQ ID NO: 85, the vector was pcDNA3.1), the transfected Chinese hamster ovary cell expressing CLDN18. 2 (CHO-hCLDN18.2), the transfected embryonic kidney cell that highly expresses human CLDN18.2 (HEK293-hCLDN18.2). Adjuvants included: in vivo-jetPEI (Polyplus Transfection Company, Catalog No. 201-50G), ODN 1826 VacciGrade (InvivoGen Company, Catalog No. vac-1826-1), Freund's Complete CFA Adjuvant (InvivoGen Company, catalog no. vac-cfa-60). And the routes of administration include: intramuscular (im), intraperitoneal (ip) and subcutaneous (se) injections. Three days after the booster immunization, spleen cells from the immunized mice were fused with SP2 / 0 murine myeloma cells using the polyethylene glycol method, thus obtaining fusion cells that could express antibodies and proliferate indefinitely in vitro, and Fusion cells were cultured in HAT selective medium. The fused hybridoma cells were placed in a 96-well cell culture plate, and positive clones were selected by primary screening and subjected to 2 to 3 rounds of subcloning. Table 2: Immunization protocols used to generate monoclonal antibodies M A / t / ZUZ I / υοοζου Antigen 3csis Adjuvant Durac in immune Route of administration ACN of CLDN18 2- ECL1 100 pg for the first time. 50 -g each time from entorces In vi vc-i&£& once poop 2 weeks, for a total ce 3 times IP ACN of CLDN18 .2- ECL1 100 pg for the first time. 50 -g each time starting from 3 weeks, for a total of 3 times IP CHOhCLDN132 5E6 CFA cells for the first time. PBS starting once every 2 weeks, for a total of 4 times So HEK293- hCLDN13 2 5E5 CFA cells for the first time. PBS starting □once poop 2 weeks, for a So Antigen 3c=is Adjuvant Durac in immune Administration route of then total oe 4 times ACM of CLDN18 2- ECL1-C3c 100 pg once Η νίνο-ίί»^ and ODN 1326 once poop 2 weeks, for a total ce 4 times IV ACN of hCLDN132 100 pg each time in vivo-j^&l and 3DM 132« once poop 2 weeks, for a total of 4 times IV Primary screening: In the primary screening, the supernatant of growing clones was tested for their ability to bind CLDN18.2 on the cell surface by using cells expressing human CLDN18.2. The presence of reactive antibodies in the supernatant was detected using a goat anti-mouse IgG secondary antibody Dyl_ight488 (Abcam, Nede catalog ab97015), and the binding capacity was evaluated on a full-field scanning cytometer (see Example 3 ). Secondary screening: The supernatant of the fused clone that bound human CLDN18.2 was tested for its ability to bind CLDN18.1 on the cell surface using the cells expressing human CLDN18. The presence of reactive antibodies in the supernatant was detected by using a goat anti-mouse IgG DyLight488 secondary antibody (Abcam, catalog number ab97015), and the binding capacity was assessed on a full-field scanning cytometer ( For detailed experimental steps, see Example 3). Finally, 10 positive monoclonal hybridoma cell strains were obtained, and the following antibodies were isolated and purified from the culture supernatant: 1D10, 2F12, 3F2, 5F9, 9F3, 10B11,27B5, 37B1,44A8, 44F7. Example 2: Evaluation of the antigen binding activity of murine anti-CLDN18.2 antibodies 2.1 Construction of cell lines expressing CLDN18.2 Human CLDN18.2 (SEQ ID NO: 86) or CLDN18.1 (SEQ ID NO: 88), or murine CLDN18.2 (SEQ ID NO: 87) was overexpressed in HEK293T cells (ATCC), CHOS cells (Invitrogen), OCUM-1 gastric cancer tumor cells (Nanjing Kebai Biotechnology Co., Ltd.), using the lentivirus infection detection and antibiotic resistance detection method (MOI = 3 to 10.5 pg / ml polybrene). Shanghai Genechem Co., Ltd. provided the lentivirus. After 72 hours of cell infection, the corresponding antibiotic was applied and culture was continued for 2 to 4 weeks, followed by expansion and cryopreservation for subsequent experiments. 2.2 Detection of mouse antibody binding to CLDN18.2 and CLDN18.1 on the cell surface by cell scanning cytometer HEK293T-hCLDN18.2 and OCUM-1-hCLDN18.2 expressing human CLDN18.2 (hCLDN18.2), or HEK293T-mCLDN18.2 expressing mouse CLDN18.2 (mCLDN18.2) and the cell line were used. corresponding negative control HEK293T; or HEK293T-hCLDN18.1 and CHOS-hCLDN18.1 expressing human CLDN18.1 (hCLDN18.1). Goat anti-mouse IgG DyLight488 (Abcam, catalog number ab97015) or goat anti-human IgG DyLight488 (Abcam, catalog number ab97003) was used as secondary antibody. Binding curves were generated using the following method. 10,000 cells were plated in 100 μl of DMEM containing 10% FBS per well in a flat-bottom 96-well plate. After the cells adhered or settled to the bottom of the well overnight, the supernatant was removed the next day. A 3-fold gradient dilution of antibody was performed by diluting 1 / 3 of the total volume (i.e., 100 μΙ) in 200 μΙ DMEM. 100 μΙ of the diluted antibody (supernatants from clones or fused subclones were used in the selection) was added to each well of the cell plate, 100 μΙ of DMEM was added to the corresponding negative control well, and incubation was carried out for 1 hour at room temperature. After removing the supernatant, 100 μΙ of secondary antibody (5 pg / ml, diluted in DMEM) was added to each well, and incubated at room temperature for half an hour. The supernatant was removed after staining, followed by washing with PBS once. 100 μl of PBS was added to each well, and then the reading was performed on the cytometer. A full-field scanning cytometer (Nexcelom, Celigo® imaging cytometer) was used to measure the experimental plate readings. During measurement, high-speed scanning images of the cells on the plate were produced simultaneously in the green fluorescent channel corresponding to the secondary antibody and in the bright-field channel. The cells that bound the antibody were counted in the image obtained from the green fluorescent channel under the set of parameters according to the morphology and fluorescence intensity of the fluorescently labeled cells, and the cells were counted. adhered cells in the image obtained from the bright field channel under the set of parameters according to the morphology of the cells. And the percentage of cells that bound to the antibodies with green fluorescence in the total number of adhered cells (percentage of fluorescent cells) was obtained by dividing the count result obtained from the green fluorescent channel by the count result obtained from the bright field channel. . The binding activity of the anti-CLDN18.2 antibody to CLDN18.2-expressing cells was determined according to this percentage, that is, the lower the percentage, the lower the ability of the anti-CLDN18.2 antibody to M A / t / ZUZ I / υοοζου bind to CLDN18.2 on cell surface; conversely, the higher the percentage, the better the ability of the anti-CLDN18.2 antibody to bind to CLDN18.2 on the cell surface. Data analysis was performed with GraphPad. The results of measuring the binding activities of anti-CLDN18.2 antibody with respect to HEK293T expressing human CLDN18.2, HEK293T expressing murine CLDN18.2, HEK293T expressing human CLDN18.1 and control HEK293T are shown in Figures 1A to 1D, in which the abscissa indicates the logarithm of the antibody concentration, and the ordinate indicates the percentage of cells that bind to the CLDN18.2 antibody with green fluorescence in the total number of adhered cells. The EC50 of the antigen binding activity of the anti-CLDN18.2 antibody was also obtained from the fitted curves, and the results are shown in Table 3, in which the reference antibody was 175D10 (Ganymed Pharmaceuticals AG). , which was described, for example, in documents CN101312989B and CN103509114B. Table 3: Results of measuring the binding activity of anti-CLDN18.2 antibody to CLDN18.2 M A / t / ZUZ I / υοοζου Antibody EC50 i ug.'ml; ΗΞΚ293hCLDNA'8.2 HEK293- mCLDN18 2 OCUVhCLDM182 HEK293 •DIO C.0'8 089' 0028 N B 2F12 C.041 ocse 0183 N B 3F2 C.034 0C59 0121 N B 5F9 C.091 0179 00 68 N B 9F3 C.053 0C43 0150 N B 10B1 1 C.038 0C35 0135 N B 27B5 C.041 0C33 0142 N B 37B1 C.040 0C32 0148 N B 44A8 C.034 0C26 0097 N B 44-7 C.028 0C26 0092 N B -75D-C 1.22 0 31 8.54 N B Note: N.B Indians that there was no union within the range of the measured concentration. The above results showed that 1D10, 2F12, 3F2, 5F9, 9F3, 10B11, 27B5, 37B1, 44A8 and 44F7 could all bind to cells expressing human CLDN18.2, and were significantly better than the reference antibody 175D10 , and these antibodies do not bind to negative control cells (HEK293T) that did not express CLDN18.2. The EC50 values ​​of the binding activity of anti-CLDN18.2 antibody with respect to CLDN18.1 are shown in Table 4. The results indicated that none of 2F12, 3F2, 9F3, 10B11,27B5, 37B1,44A8 and 44F7 bound to CLDN18.1, showing good binding specificity to CLDN18.2. Table 4: Results of measuring the binding activity of anti-CLDN18.2 antibody to CLDN18.1 MA / t / ZUZ I / υοοζου Antibody CE50 Mg r'l: CHOS-hCLDN18 ' HEK2&3-hCLDN'8.1 1D'0 0.C92 0.C41 2-12 N.B N.B 3F2 N.B 5F9 0.714 9F3 N.B N.B 10B11 N.B N.B 27B5 N.B N.B 37B 1 N. B N.B 44A8 N.B N.B 44F~ N.B N.B •75D1C N.B N.B Net: K E. indicates that there was no difference within the range of the measured concentration and the blank indicates that the antibody was not measured for these these Example 3: Determination of Murine Anti-CLDN18.2 Antibody Sequence and Preparation of Chimeric Antibody 3.1 Determination of the variable region sequence of the murine anti-human CLDN18.2 antibody Hybridoma cells were collected by centrifugation and 5-10 x 106 cells were added with 1 ml of TRIzol and 0.2 ml of chloroform, shaken vigorously for 15 seconds, followed by incubation at room temperature for 3 minutes. After centrifugation, the aqueous phase was collected and added with 0.5 ml of isopropanol, followed by incubation for 10 minutes at room temperature. The precipitate was collected, washed with ethanol, and dried to obtain RNA. Template RNA and primers were added to the centrifuge tube in an ice bath; Reverse transcription was carried out when the primers and template were correctly matched, followed by PCR amplification. Once amplification was completed, 4 microcentrifuge tubes with 2.5 μl of dNTP / ddNTP mixture were added and incubated at 37°C for 5 minutes for later use. In an empty microcentrifuge tube, 1 pmol of PCR amplification product, 10 pmol of sequencing primer, 2 μΙ of 5x sequencing buffer were added, and double distilled water was added to a total volume of 10 μΙ, then subjected heating at 96SC for 8 minutes, ice bath for 1 minute and centrifugation at 4 °C and 10,000 g for 10 seconds. 2 μΙ of pre-chilled marker mixture (0.75 pmol / l each for dCTP, dGTP and dTTP), 5 pCi a-32P-dATP, 1 μΙ of 0.1 mol / l DDT, 2U of enzyme were added sequencing, then water was added to reach 15 μΙ, mixed well and placed on ice for 2 minutes. 3.5 μΙ of the labeling reaction mixture was added to the 4 prepared microcentrifuge tubes and incubated at 37 °C for 5 minutes. 4 μΙ of stop solution was added to each tube. Samples were thermally denatured in a water bath at 80°C for 5 minutes, loaded onto each lane of sequencing gel in an amount of 2 μΙ, and these fragments were separated by electrophoresis to collect sequence information. The VH and VL sequences of the 10 mouse antibodies are shown in Table 5 below. And in addition, the CDR sequences of the 10 murine monoclonal antibodies were determined (Table 6) using the method described by Kabat et al. (Kabat et al., Protein Sequences of Immunological Interest, Fifth Edition, Public Health Service, National Institutes of Health, Bethesda, Maryland (1991), pp. 647-669). Table 5: Amino acid sequences of light and heavy chain variable regions of murine antibodies M A / t / ZUZ I / UO3Z00 Antibody VH VL SEQ IC NO SEQ ID NO ID 1C 1 2 2F12 9 10 3F2 17 18 5F8 25 26 9F3 33 34 10B1 1 41 42 27B5 49 50 37B1 57 58 44A8 65 66 44=7 73 74 Table 6: CDR sequences of murine antibodies Antic jerpo VH (SEC ID NO.i VL (EEQ ID MC.i CDR1 CDR2 CDR3 CDR1 CDR2 CDR3 Ό10 O 4 5 6 7 O 2F12 1 · 12 13 14 15 16 3F2 19 20 2' 22 23 24 5F9 27 23 29 30 o 32 9F3 35 36 o; 33 39 40 - CB11 43 44 45 46 47 43 27B5 5· 52 53 54 55 56 37B1 59 60 6· 62 63 64 4 AS 67 Oj Cú 69 70 7 · «2 44F7 7 5 76 γγ 7Ό 79 so 3.2 Preparation of mouse-human chimeric antibodies and evaluation of antigen-binding activity The gene sequences (see SEQ ID NO: 103-122) encoding the variable regions of the heavy chain and the light chain of the mouse antibodies mentioned above were linked to the sequences encoding the constant region of the chain. heavy (SEQ ID NO: 81) and the light chain constant region (SEQ ID NO: 82) of the human antibody, respectively, and were expressed recombinantly in HEK293 (ATOO) cells, thus obtaining the corresponding chimeric antibodies 1 D10 -chlgG1, 2F12-chlgG1, 3F2-chlgG1, 5F9chlgGI, 9F3 -chlgGI, 10B11-chlgG1, 27B5-chlgG1,37B1-chlgG1, 44A8-chlgG1, 44F7-chlgG1. The method described in Example 2 detected the binding activity of chimeric antibodies of different concentrations to HEK293T cells expressing human CLDN18.2 (HEK293ThCLDN18.2). The results are shown in Figure 2, in which the abscissa indicates the logarithm of the antibody concentration, and the ordinate indicates the percentage of CLDN18.2 cells that bind to the antibody with green fluorescence in the total number of adhered cells ( percentage of fluorescent cells). Furthermore, the EC50 values ​​of the antigen binding activity of the chimeric antibodies were obtained from the fitted curves, and are shown in Table 7. The results demonstrated that the chimeric antibodies 3F2-chlgG1, 5F9-chlgG1, 9F3 -chlgG1, 10Β11-chlgG1, 27B5-chlgG1, 37B1-chlgG1, 44A8-chlgG1 and 44F7-chlgG1 could all recognize / bind human CLDN18.2. Table 7: Results of measuring the binding activity of chimeric antibodies to CLDN18.2 ΜΛ / t / zuz 1 / υοοζου Artibody CE 50:μg.r·.l? HEK293-hCLDNA1S 2 3F2-cHgG1 0.363 5F8-cNgG1 0.283 9F3-cNgG1 0.104 10B11 -chlgG 1 0.330 27B5-chgG1 0.103 37B1 -chgG 1 0.33 44A8-chgG 1 0.369 ¿4 = 7-cNgG 1 0.327 175D 10 0.536 Example 4: Evaluation of the activity of chimeric anti-CLDN18.2 antibody to induce ADCC HEK293T-hCLDN18.2 or human gastric cancer tumor cell lines were used KATO-lll and NUGC4 naturally expressing hCLDNI 8.2, as target cells; and Ficoll-isolated human peripheral blood mononuclear cells (PBMCs) were used as effector cells. Target cells were harvested and washed twice with PBS. The live cell dye Calcein AM (50 pg Calcein AM dry powder (Life Technologies, Cat No. C3100MP) dissolved in 50 μl DMSO) was diluted to 3 μΜ, and the target cells were stained with 5% CO2 at 37 °C for 30 minutes. After staining, cells were washed twice with PBS, and 5,000 target cells were plated in 100 μΙ DMEM per well in a 96-well flat-bottom plate. A 3-fold gradient dilution of the tested antibody was carried out by diluting 1 / 3 of the total volume (i.e., 100 μΙ) in 200 μΙ DMEM. 50 μΙ of the diluted antibody was added to the corresponding wells of the cell plate (50 μΙ of DMEM medium was added to the control wells for non-specific killing), and incubated with the target cells under CO2 at a temperature of 37 ° C for 30 minutes. Then, 50,000 isolated PBMCs in 50 μΙ were added to each well as effector cells, followed by centrifugation at 1,000 rpm for 3 minutes to allow the cells to settle to the bottom of the plate. The experimental plate was measured for readings on a full-field scanning cytometer (Nexcelom, Celigo® imaging cytometer) at multiple time points (0 hour, 2 hours, 3 hours, 4 hours, and 6 hours). During the measurement, high-speed scanning images of the cells on the plate were produced simultaneously in the green fluorescent channel corresponding to Calcein AM and in the bright field channel. A count of live cells in each well was carried out from the image obtained from the green fluorescent channel under the established parameters according to the morphology and fluorescence intensity of the fluorescently labeled cells, and a count of the total cells in each well in the image obtained from the bright field channel under the parameters established according to the morphology of the cells. And the percentage of live cells with green fluorescence in the total number of cells was obtained by dividing the counting result obtained from the green fluorescent channel by the counting result obtained from the bright field channel. The percentage of cells that had undergone specific cell lysis in the presence of the antibody in the total number of cells was obtained by subtracting the corresponding percentage obtained in the presence of the antibody from the percentage of the non-specific control well. The activity of the anti-CLDN18.2 antibody to induce ADCC was determined based on this percentage value; that is, the lower the percentage, the lower the ability of the anti-CLDN18.2 antibody to induce ADCC; conversely, the higher the percentage, the better the ability of the anti-CLDN18.2 antibody to induce ADCC. Data analysis was performed with GraphPad. The results of measuring the activity of the anti-CLDN18.2 antibody to induce ADCC are shown in Figures 3A to 3C, in which the abscissa indicates the logarithm of the antibody concentration and the ordinate indicates the corrected percentage of specific lysis. . The EC50 of the activity of the anti-CLDN18.2 chimeric antibody to induce ADCC was also obtained from the fitted curves, and the results are shown in Table 8. The results showed that the tested antibodies could induce the killing effect of PBMC on cells expressing human CLDN18.2, which were significantly better than the reference antibody 175D10. M A / t / ZUZ! / UOOZOO measurement, high-speed scanning images of the cells on the plate were obtained simultaneously in the green fluorescent channel corresponding to Calcein AM and in the bright field channel. A count of live cells in each well was carried out from the image obtained from the green fluorescent channel under the established parameters according to the morphology and fluorescence intensity of the fluorescently labeled cells, and a count of the total cells in each well in the image obtained from the bright field channel under the parameters established according to the morphology of the cells. And the percentage of live cells with green fluorescence in the total number of cells was obtained by dividing the counting result obtained from the green fluorescent channel by the counting result obtained from the bright field channel. The percentage of cells that had been destroyed in the presence of the antibody in the total number of cells was obtained by subtracting the corresponding percentage obtained in the presence of the antibody from the percentage of the non-specific control well. The activity of the anti-CLDN18.2 antibody to induce CDC was determined based on this percentage value; that is, the lower the percentage, the lower the ability of the antiCLDN18.2 antibody to induce CDC; conversely, the higher the percentage, the better the ability of the anti-CLDN18.2 antibody to induce CDC. Data analysis was performed with GraphPad. The results of measuring the activity of the anti-CLDN18.2 antibody to induce CDC are shown in Figures 4A and 4B, in which the abscissa indicates the logarithm of the antibody concentration and the ordinate indicates the corrected percentage of cell destruction. specific. The EC50 of anti-CLDN18.2 antibody to induce CDC was also obtained from the fitted curves, and the results are shown in Table 9. The results showed that the tested antibodies could induce the complement-destroying effect. in human serum in cells expressing human CLDN18.2, which were significantly better than the reference antibody 175D10. Table 9: Measurement results of the activity of the chimeric antibody to induce CDC ΜΛ / t / ZUZ I / υοοζου CDC EC50 antibody (pg / ml) HEK293~-hCLDN 8 2 KATO-lll 3F2-ohlgG1 1.1 5F9-chlgG1 5.25 9F3-chlgG1 1.86 10B1'-chlgG' 1.35 27B5-chlgG ‘ 5.17 37B'-ohlg G 1.93 100 ¿AS-ohlgG' 2.40 44F7-chlgG1 0.90 0.18 •75D1C - 8.1S 73.05 Net: _cs blank spaces indicate that these data were not used for this previous body M A / t / ZUZ I / UO3Z00 Example 6: Evaluation of the activity of the anti-CLDN18.2 antibody to induce the internalization of CLDN18.2 In this example, the level of internalization of CLDN18.2 on the cell surface (HEK293T-hCLDN 18.2) mediated by anti-CLDN18.2 antibody was detected by flow cytometry. Two cell samples were incubated with 10 pg / ml of chimeric antibody at 37°C for 1 hour and 4 hours, respectively. After washing several times with PBS containing 2% FBS, 10 pg / ml secondary antibody was added and stained at 4°C for 30 minutes. Then, the expression level of CLDN18.2 on the cell surface was analyzed by flow cytometry. MFknwas the MFI of the sample after 4 hours of incubation, MFIiHwas the MFI of the sample after 1 hour of incubation, where it was assumed that antibody binding had been completed and endocytosis had not yet occurred. Background MFI was the MFI of the secondary antibody only. The percentage of antibody-mediated internalization of CLDN18.2 cell surface was calculated using the following formula: Percentage of CLDN18.2 internalized (%) = 100-100 χ (MFl4H-MFIiH) / (MFIiH-MFIbackground) The results are shown in Table 10. These antibodies mediated the internalization of CLDN18.2 on the surface of HEK293T-hCLDN18.2 cells to varying degrees. Table 10: Measurement results of CLDN18.2 internalization induced by chimeric antibodies Antibody Percentage of internalization ;%] 'D1O-ohlgG' 28.7 5F8-chlgG 1 S.3 27B5-chgG1 -2.2 37B1-cn:gG1 -3.2 44F7-cHgG1 -1.5 101 44A8-cn gG1 2.5 MA / t / ZUZ I / υοοζου Example 7: Humanization of the anti-CLDN18.2 antibody and evaluation of its activity In order to improve the sequence homology of the candidate antibodies and human antibodies and reduce the immunogenicity of the antibodies with respect to humans, the murine antibodies provided in the above examples could be subjected to design and preparation for humanization, in the that murine CDR regions were grafted onto human scaffold sequences (see US Patent Ne5,225,539 to Winter; US Patents Ne5,530,101, 5,585,089, 5,693,762 and 6,180,370 to Queen et al; and Lo, Benny, KC, editor, in Antibody Engineering: Methods and Protocols, volume 248, Humana Press, New Jersey, 2004). Typically, all or part of the CDR regions of humanized antibodies were derived from non-human antibodies (donor antibodies), and all or part of the non-CDR regions (e.g., FR variable regions and / or constant regions) were derived from human immunoglobulin ( receptor antibody). Based on this, the inventors herein prepared and obtained 3 humanized antibodies of the murine antibody 44F7, designated 7004-09hu09, 7004-09hu10 and 700409hu15, respectively. Their amino acid sequences are shown in the table below. Table 11: Amino acid sequences of light and heavy chain variable regions of humanized antibodies Antibody 7C34-38huC8 7C34-38hu13 7CO4-3Qhu15 SEQ D NO VH G8 1 C1 81 HC3R- 75 75 83 HC3R2 73 73 84 HC3R3 vy Ty 85 VL ICO 102 82 LCCR1 78 78 83 LCDR2 78 78 87 LCCR3 83 83 98 102 The gene sequences (see SEQ ID NO: 123-128) encoding the heavy chain and light chain variable regions of the above-mentioned humanized antibodies were ligated to the sequences encoding the heavy chain constant region. (SEQ ID NO: 81) and the constant light chain region (SEQ ID NO: 82) of human antibody respectively, followed by recombinant expression. The binding capacity of humanized antibodies to CLDN18.2 expressed on the surface of HEK293T-hCLDN18.2 was determined by a cell scanning cytometer and using the method described in Example 2.2. The results are shown in Figure 5, in which the abscissa indicates the logarithm of the antibody concentration, and the ordinate indicates the percentage of CLDN18.2 antibody-binding cells with green fluorescence in the total number of adhered cells (percentage of fluorescent cells). The EC50 of the antigen binding activity of the humanized antiCLDN18.2 antibody was also obtained from the fitted curves, and the results are shown in Table 12. The results showed that all the humanized antibodies tested could bind to cells expressing hCLDN18.2, and its affinity was of the same order of magnitude as that of the parental chimeric antibody. Table 12: Measurement results of the binding activity of humanized antibodies to CLDN18.2 M A / t / ZUZ I / υοοζου Antibody CE50 ¿pg.r-.l· HEK293-hCLDNA1S 2 7004-09hu09 0.35* 7004-09hu W 0.347 7004-09hu15 0.003 4¿F7-chgG1 0.012 •75D1C 0.035 Furthermore, the inventors herein investigated the ability of humanized antibodies to induce ADCC, and the evaluation method refers to that described in Example 4. Human gastric cancer tumor cells KATO-lll were used as target cells, and human peripheral blood mononuclear cells isolated by Ficoll as effector cells. The measurement results are shown in Figure 6, in which the abscissa indicates the logarithm of the antibody concentration and the ordinate indicates the corrected percentage of specific cell lysis. The EC50 of the activity of the anti-CLDN18.2 chimeric antibody to induce ADCC was also obtained from the fitted curves, and the results are shown in Table 13. The results 103 showed that all antibodies tested could induce the killing effect of PBMC in cells expressing human CLDN18.2, and their ability to induce ADCC was of the same order of magnitude as that of the parental chimeric antibody, and was significantly better than that of the reference antibody 175D10. Table 13: Measurement results of the activity of humanized antibodies to induce ADCC ΜΛ / t / ZUZ I / UODZDO Antibody CE50 <pg.r-.l;> ΚΑΤΟ-ΙΙΙ 7004-0&hu0& 0.C02S 7004-09hu10 0.C033 7004-09hu15 0.C05* 4¿F7-chgG1 0.C 117 '75D1C 0.73S4 The inventors herein also investigated the ability of humanized antibodies to induce CDC, and the evaluation method refers to that of Example 5. Human gastric cancer tumor cells ΚΑΤΟ-ΙΙΙ were used as target cells, and fresh human serum was used as effector cells. The measurement results are shown in Figure 7, in which the abscissa indicates the logarithm of the antibody concentration and the ordinate indicates the corrected percentage of specific cell death. The EC50 of the activity of the chimeric anti-CLDN18.2 antibody to induce CDC was also obtained from the fitted curves, and the results are shown in Table 14. The results showed that all antibodies tested were able to induce the complement-destroying effect of human serum on cells expressing human CLDN18.2, and its ability to induce CDC was of the same order of magnitude as that of the original chimeric antibody, and was significantly better than that of the reference antibody 175D10. Table 14: Measurement results of the activity of humanized antibodies to induce CDC Antibody EC 50 ipg.r-l; KATO-lll 7004-09hu09 C.33 7004-09hu 10 C.2~ 7004-09hu15 C.27 104 Antibody CE50 / pg.r'l:· KATO-lll 44F7-chgG 1 C.52 •75C1C 2-4.33 M A / t / ZUZ I / υοοζου The above results indicated that the humanized antibodies of the present invention not only had a high degree of humanization and therefore reduced the possibility of immune rejection, but also exhibited antitumor activity that was comparable to that of its original chimeric antibody. and better than that of known antibodies. Example 8: Evaluation of In Vivo Antitumor Activity of Chimeric Anti-CLDN18.2 Antibody To investigate the antitumor effect of anti-CLDN18.2 antibody in animals, nude mice (SCID, Beijing Weitonglihua Experimental Animal Technology Co.) were inoculated subcutaneously. ., Ltd.) with 1 x 107 HEK293T-hCLDN18.2 cells. Intravenous administration and intraperitoneal administration were alternated from the day of inoculation, twice a week for 4 weeks, 10 mg / kg at a time. Detection of tumor size in the mice continued after administration was completed. Figure 8A shows the change in tumor volume in mice after treatment. The results showed that treatment with 44F7-chlgG1 antibody not only significantly inhibited tumor growth, but also completely eliminated the tumors in the mice in the administration group, and its antitumor effect was significantly better than that of the reference antibody 175D10 . Furthermore, Figure 8B shows that 44F7-chlgG1 significantly prolonged the overall survival time of tumor-bearing mice, demonstrating excellent antitumor activity. It could be seen that compared with the reference antibody 175D10, 44F7-chlgG1 also showed a significant advantage in prolonging survival time. Such technical effects were significant and unexpected. Although specific embodiments of the present invention have been described in detail, those skilled in the art will understand that, in accordance with all published teachings, various modifications and changes in details may be made, and these changes are They are all within the scope of protection of the present invention. The entirety of the present invention is given by the attached claims and any equivalent thereof.

Claims

1. An antibody or antigen-binding fragment thereof that is capable of specifically binding to CLDN18.2, comprising: (a) a heavy chain variable region (VH) comprising the following three complementary determinant regions (CDRs): (i) VH CDR1, consisting of the following sequence: SEQ ID NO: 75, or a sequence having a substitution, deletion, or addition of one or more amino acids (e.g., a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; (ii) VH CDR2, consisting of the following sequence: SEQ ID NO: 76, or a sequence having a substitution, deletion, or addition of one or more amino acids (e.g., a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; and (i¡¡) VH CDR3, which consists of the following sequence: SEQ ID NO: 77, or a sequence having a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to the same; and / or (b) a variable light chain region (VL) comprising the following three complementary determining regions (CDRs): (iv) VL CDR1, consisting of the following sequence: SEQ ID NO: 78, or a sequence having a substitution, deletion, or addition of one or more amino acids (e.g., a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; (v) VL CDR2, consisting of the following sequence: SEQ ID NO: 79, or a sequence having a substitution, deletion, or addition of one or more amino acids (e.g., a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; and (vi) VL CDR3, consisting of the following sequence: SEQ ID NO: 80, or a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; preferably,The substitution as mentioned in any one of points (i) to (vi) is a conservative substitution; preferably, the VH of the antibody or antigen-binding fragment thereof comprises: VH CDR1 as shown in SEQ ID NO: 75, VH CDR2 as shown in SEQ ID NO: 76, VH CDR3 as shown in SEQ ID NO: 77; and the VL of the antibody or antigen-binding fragment thereof comprises: VL CDR1 as shown in SEQ ID NO: 78 or 96, VL CDR2 as shown in SEQ ID NO: 79, and VL CDR3 as shown in SEQ ID 106 NO:

80.

2. An antibody or antigen-binding fragment thereof that is capable of specifically binding to CLDN18.2, comprising a heavy-chain variable region and a light-chain variable region, wherein,(a) the heavy chain variable region comprises the 3 CDRs of the heavy chain variable region as shown in SEQ ID NO: 73; and the light chain variable region comprises the 3 CDRs of the light chain variable region as shown in SEQ ID NO: 74; or (b) the heavy chain variable region comprises the 3 CDRs of the heavy chain variable region as shown in SEQ ID NO: 91; and the light chain variable region comprises the 3 CDRs of the light chain variable region as shown in SEQ ID NO: 92; preferably, the 3 CDRs of the heavy chain variable region, and / or the 3 CDRs of the light chain variable region, are determined using the Kabat, Chothia, or IMGT numbering system.

3. An antibody or antigen-binding fragment thereof that is capable of specifically binding to CLDN18.2,comprising: (a) a heavy chain variable region (HV) comprising the following three complementary determining regions (CDRs): (i) HV CDR1, consisting of the following sequence: SEQ ID NO: 3, or a sequence having a substitution, deletion, or addition of one or more amino acids (e.g., a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; (ii) HV CDR2, consisting of the following sequence: SEQ ID NO: 4, or a sequence having a substitution, deletion, or addition of one or more amino acids (e.g., a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; and (ii) HV CDR3, consisting of the following sequence: SEQ ID NO: 5, or a sequence having a substitution, deletion, or addition of one or more amino acids (e.g., a substitution, deletion, or addition of 1,2 or 3 amino acids) compared to the same; and / or (b) a variable light chain region (VL) comprising the following three complementary determining regions (CDRs): (iv) VL CDR1, consisting of the following sequence: SEQ ID NO: 6, or a sequence having a substitution, deletion, or addition of one or more amino acids (e.g., a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; 107 (v) VL CDR2, consisting of the following sequence: SEQ ID NO: 7, or a sequence having a substitution, deletion, or addition of one or more amino acids (e.g., a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; and (vi) VL CDR3, consisting of the following sequence: SEQ ID NO: 8, or a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; preferably,The substitution as mentioned in any one of points (i) to (vi) is a conservative substitution; preferably, the VH of the antibody or antigen-binding fragment thereof comprises: VH CDR1 as shown in SEQ ID NO: 3, VH CDR2 as shown in SEQ ID NO: 4, VH CDR3 as shown in SEQ ID NO: 5; and, the VL of the antibody or antigen-binding fragment thereof comprises: VL CDR1 as shown in SEQ ID NO: 6, VL CDR2 as shown in SEQ ID NO: 7, and VL CDR3 as shown in SEQ ID NO:

8.

4. An antibody or antigen-binding fragment thereof that is capable of specifically binding to CLDN18.2, comprising: (a) a heavy-chain variable region (VH) comprising the following three complementary determinant regions (CDRs): (i) VH CDR1, consisting of the following sequence: SEQ ID NO: 11, or a sequence having a substitution, deletion, or addition of one or more amino acids (e.g.,(i) VH CDR2, consisting of the following sequence: SEQ ID NO: 12, or a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; and (iii) VH CDR3, consisting of the following sequence: SEQ ID NO: 13, or a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; and / or (b) a variable light chain (VL) region comprising the following three complementary determining regions (CDRs): (iv) VL CDR1, consisting of the following sequence: SEQ ID NO: 14, or a sequence having a substitution, deletion, or addition of one or more amino acids (e.g., a substitution, deletion, or addition of 1,(v) VL CDR2, consisting of the following sequence: SEQ ID NO: 15, or a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; and (vi) VL CDR3, consisting of the following sequence: SEQ ID NO: 16, or a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; preferably, the substitution as mentioned in any one of points (i) to (vi) is a conservative substitution; Preferably, the VH of the antibody or antigen-binding fragment thereof comprises: VH CDR1 as shown in SEQ ID NO: 11, VH CDR2 as shown in SEQ ID NO: 12, VH CDR3 as shown in SEQ ID NO: 13; and,The VL of the antibody or antigen-binding fragment thereof comprises: VL CDR1 as shown in SEQ ID NO: 14, VL CDR2 as shown in SEQ ID NO: 15, and VL CDR3 as shown in SEQ ID NO:

16.

5. An antibody or antigen-binding fragment thereof that is capable of specifically binding to CLDN18.2, comprising: (a) a heavy chain variable region (VH) comprising the following three complementary determinant regions (CDRs): (i) VH CDR1, consisting of the following sequence: SEQ ID NO: 19, or a sequence having a substitution, deletion, or addition of one or more amino acids (e.g., a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; (i) VH CDR2, consisting of the following sequence: SEQ ID NO: 20, or a sequence having a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,(iii) VH CDR3, consisting of the following sequence: SEQ ID NO: 21, or a sequence having a substitution, deletion, or addition of one or more amino acids (e.g., a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; and / or (b) a light chain variable region (VL) comprising the following three complementary determinant regions (CDRs): (iv) VL CDR1, consisting of the following sequence: SEQ ID NO: 22, or a sequence having a substitution, deletion, or addition of one or more amino acids (e.g., a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; (v) VL CDR2, consisting of the following sequence: SEQ ID NO: 23, or a sequence having a substitution, deletion or addition of one or more amino acids (for example, a substitution, ML / I / UODZDO 109 deletion or addition of 1,2 or 3 amino acids) compared to the same; and (vi) VL CDR3, consisting of the following sequence: SEQ ID NO: 24, or a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; preferably, the substitution as mentioned in any one of points (i) to (vi) is a conservative substitution; preferably, the VH of the antibody or antigen-binding fragment thereof comprises: VH CDR1 as shown in SEQ ID NO: 11, VH CDR2 as shown in SEQ ID NO: 12, VH CDR3 as shown in SEQ ID NO: 13; and, the VL of the antibody or antigen-binding fragment thereof comprises: VL CDR1 as shown in SEQ ID NO: 14, VL CDR2 as shown in SEQ ID NO: 15,and VL CDR3 as shown in SEQ ID NO:

16.

6. An antibody or antigen-binding fragment thereof that is capable of specifically binding to CLDN18.2, comprising: (a) a heavy chain variable region (VH) comprising the following three complementary determinant regions (CDRs): (i) VH CDR1, consisting of the following sequence: SEQ ID NO: 27, or a sequence having a substitution, deletion, or addition of one or more amino acids (e.g., a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; (ii) VH CDR2, consisting of the following sequence: SEQ ID NO: 28, or a sequence having a substitution, deletion, or addition of one or more amino acids (e.g., a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; and (iii) VH CDR3, consisting of the following sequence: SEQ ID NO: 29, or a sequence having a substitution,deletion or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; and / or (b) a light chain variable region (VL) comprising the following three complementary determining regions (CDRs): (iv) VL CDR1, consisting of the following sequence: SEQ ID NO: 30, or a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; (v) VL CDR2, consisting of the following sequence: SEQ ID NO: 31, or a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; and 110 ML / I / UOOZOO (vi) VL CDR3, which consists of the following sequence: SEQ ID NO: 32, or a sequence having a substitution,deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1, 2 or 3 amino acids) compared to the same; preferably, the substitution as mentioned in any one of points (i) to (vi) is a conservative substitution; preferably, the VH of the antibody or antigen-binding fragment thereof comprises: VH CDR1 as shown in SEQ ID NO: 27, VH CDR2 as shown in SEQ ID NO: 28, VH CDR3 as shown in SEQ ID NO: 29; and, the VL of the antibody or antigen-binding fragment thereof comprises: VL CDR1 as shown in SEQ ID NO: 30, VL CDR2 as shown in SEQ ID NO: 31, and VL CDR3 as shown in SEQ ID NO:

32.

7. An antibody or antigen-binding fragment thereof that is capable of specifically binding to CLDN18.2,comprising: (a) a heavy chain variable region (HV) comprising the following three complementary determining regions (CDRs): (i) HV CDR1, consisting of the following sequence: SEQ ID NO: 35, or a sequence having a substitution, deletion, or addition of one or more amino acids (e.g., a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; (ii) HV CDR2, consisting of the following sequence: SEQ ID NO: 36, or a sequence having a substitution, deletion, or addition of one or more amino acids (e.g., a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; and (iii) HV CDR3, consisting of the following sequence: SEQ ID NO: 37, or a sequence having a substitution, deletion, or addition of one or more amino acids (e.g., a substitution, deletion, or addition of 1,2 or 3 amino acids) compared to the same; and / or (b) a variable light chain region (VL) comprising the following three complementary determining regions (CDRs): (iv) VL CDR1, consisting of the following sequence: SEQ ID NO: 38, or a sequence having a substitution, deletion, or addition of one or more amino acids (e.g., a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; (v) VL CDR2, consisting of the following sequence: SEQ ID NO: 39, or a sequence having a substitution, deletion, or addition of one or more amino acids (e.g., a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; and (vi) VL CDR3, consisting of the following sequence: SEQ ID NO: 40, or a sequence that ML / t / ZUZ I / υοοζου 111 has a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2 or 3 amino acids) compared to the same; preferably, the substitution as mentioned in any one of points (i) to (vi) is a conservative substitution; preferably, the VH of the antibody or antigen-binding fragment thereof comprises: VH CDR1 as shown in SEQ ID NO: 35, VH CDR2 as shown in SEQ ID NO: 36, VH CDR3 as shown in SEQ ID NO: 37; and, the VL of the antibody or antigen-binding fragment thereof comprises: VL CDR1 as shown in SEQ ID NO: 38, VL CDR2 as shown in SEQ ID NO: 39, and VL CDR3 as shown in SEQ ID NO:

40.

8. An antibody or antigen-binding fragment thereof that is capable of specifically binding to CLDN18.2, comprising: (a) a heavy chain variable region (VH) comprising the following three complementary determinant regions (CDRs): (i) VH CDR1, consisting of the following sequence: SEQ ID NO: 43,or a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; (i) VH CDR2, consisting of the following sequence: SEQ ID NO: 44, or a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; and (iii) VH CDR3, consisting of the following sequence: SEQ ID NO: 45, or a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; and / or (b) a variable light chain (VL) region comprising the following three complementary determining regions (CDRs): (iv) VL CDR1, consisting of the following sequence: SEQ ID NO: 46, or a sequence having a substitution,deletion or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; (v) VL CDR2, consisting of the following sequence: SEQ ID NO: 47, or a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; and (vi) VL CDR3, consisting of the following sequence: SEQ ID NO: 48, or a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; preferably, the substitution as mentioned in any one of points (i) to (vi) is a conservative substitution; Preferably, the VH of the antibody or antigen-binding fragment thereof comprises: VH CDR1 as shown in SEQ ID NO: 43,VH CDR2 as shown in SEQ ID NO: 44, VH CDR3 as shown in SEQ ID NO: 45; and, the VL of the antibody or antigen-binding fragment thereof comprises: VL CDR1 as shown in SEQ ID NO: 46, VL CDR2 as shown in SEQ ID NO: 47, and VL CDR3 as shown in SEQ ID NO:

48.

9. An antibody or antigen-binding fragment thereof that is capable of specifically binding to CLDN18.2, comprising: (a) a heavy chain variable region (VH) comprising the following three complementary determinant regions (CDRs): (i) VH CDR1, consisting of the following sequence: SEQ ID NO: 51, or a sequence having a substitution, deletion, or addition of one or more amino acids (e.g., a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; (i) VH CDR2, consisting of the following sequence: SEQ ID NO: 52, or a sequence having a substitution,deletion or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; and (iii) VH CDR3, consisting of the following sequence: SEQ ID NO: 53, or a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; and / or (b) a light chain variable region (VL) comprising the following three complementary determinant regions (CDRs): (iv) VL CDR1, consisting of the following sequence: SEQ ID NO: 54, or a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; (v) VL CDR2, consisting of the following sequence: SEQ ID NO: 55, or a sequence having a substitution, deletion or addition of one or more amino acids (for example,a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; and (vi) VL CDR3, consisting of the following sequence: SEQ ID NO: 56, or a sequence having a substitution, deletion, or addition of one or more amino acids (e.g., a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; preferably, the substitution as mentioned in any one of points (i) to (vi) is a conservative substitution; preferably, the VH of the antibody or antigen-binding fragment thereof comprises: VH CDR1 as shown in SEQ ID NO: 51, VH CDR2 as shown in SEQ ID NO: 52, VH CDR3 as shown in SEQ ID NO: 53; and, the VL of the antibody or antigen-binding fragment thereof comprises: VL CDR1 as shown in SEQ ID NO: 54, VL CDR2 as shown in SEQ ID NO: 55,and VL CDR3 as shown in SEQ ID NO:

56.

10. An antibody or antigen-binding fragment thereof that is capable of specifically binding to CLDN18.2, comprising: (a) a heavy chain variable region (VH) comprising the following three complementary determinant regions (CDRs): (i) VH CDR1, consisting of the following sequence: SEQ ID NO: 59, or a sequence having a substitution, deletion, or addition of one or more amino acids (e.g., a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; (ii) VH CDR2, consisting of the following sequence: SEQ ID NO: 60, or a sequence having a substitution, deletion, or addition of one or more amino acids (e.g., a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; and (ii) VH CDR3, consisting of the following sequence: SEQ ID NO: 61, or a sequence having a substitution,deletion or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; and / or (b) a light chain variable region (VL) comprising the following three complementary determining regions (CDRs): (iv) VL CDR1, consisting of the following sequence: SEQ ID NO: 62, or a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; (v) VL CDR2, consisting of the following sequence: SEQ ID NO: 63, or a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; and (vi) VL CDR3, consisting of the following sequence: SEQ ID NO: 64, or a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution,deletion or addition of 1, 2 or 3 amino acids) compared to the same; preferably, the substitution as mentioned in any one of points (i) to (vi) MA / E / ZυZΊ / UOOZOO 114 is a conservative substitution; preferably, the VH of the antibody or antigen-binding fragment thereof comprises: VH CDR1 as shown in SEQ ID NO: 59, VH CDR2 as shown in SEQ ID NO: 60, VH CDR3 as shown in SEQ ID NO: 61; and, the VL of the antibody or antigen-binding fragment thereof comprises: VL CDR1 as shown in SEQ ID NO: 62, VL CDR2 as shown in SEQ ID NO: 63, and VL CDR3 as shown in SEQ ID NO:

64.

11. An antibody or antigen-binding fragment thereof that is capable of specifically binding to CLDN18.2, comprising: (a) a heavy chain variable region (VH) comprising the following three complementary determinant regions (CDRs): (i) VH CDR1,consisting of the following sequence: SEQ ID NO: 67, or a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; (i) VH CDR2, consisting of the following sequence: SEQ ID NO: 68, or a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; and (iii) VH CDR3, consisting of the following sequence: SEQ ID NO: 69, or a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; and / or (b) a variable light chain region (VL) comprising the following three complementary determinant regions (CDRs): (iv) VL CDR1, consisting of the following sequence: SEQ ID NO: 70,or a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; (v) VL CDR2, consisting of the following sequence: SEQ ID NO: 71, or a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; and (vi) VL CDR3, consisting of the following sequence: SEQ ID NO: 72, or a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, or 3 amino acids) compared to the same; preferably, the substitution as mentioned in any one of points (i) to (vi) is a conservative substitution; 115 Preferably, the VH of the antibody or antigen-binding fragment thereof comprises: VH CDR1 as shown in SEQ ID NO: 67,VH CDR2 as shown in SEQ ID NO: 68, VH CDR3 as shown in SEQ ID NO: 69; and, the VL of the antibody or antigen-binding fragment thereof comprises: VL CDR1 as shown in SEQ ID NO: 70, VL CDR2 as shown in SEQ ID NO: 71, and VL CDR3 as shown in SEQ ID NO:

72.

12. The antibody or antigen-binding fragment thereof according to claim 1 or 2, wherein the antibody or antigen-binding fragment thereof comprises: (a) a heavy-chain variable region (VH) comprising an amino acid sequence selected from the group consisting of: (i) the sequence as shown in SEQ ID NO: 73; (ii) a sequence having a substitution, deletion, or addition of one or more amino acids (e.g., a substitution, deletion, or addition of 1, 2, 3,(a) 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 73; or (ii) a sequence having a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% to the sequence as shown in SEQ ID NO: 73; and / or (b) a variable light chain (VL) region comprising an amino acid sequence selected from the group consisting of: (iv) the sequence as shown in SEQ ID NO: 74; (v) a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, 3, 4, or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 74; or (vi) a sequence having a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%,at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% to the sequence as shown in SEQ ID NO: 74; preferably, the substitution as mentioned in (i) or (v) is a conservative substitution. Preferably, the antibody or antigen-binding fragment thereof comprises: a VH having a sequence as shown in SEQ ID NO: 73, and a VL having a sequence as shown in SEQ ID NO:

74. MA / t / ZUZ I / UO3Z00 116 13. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 11, wherein the antibody or antigen-binding fragment thereof is humanized.

14. The antibody or antigen-binding fragment thereof according to claim 1, 2, or 13,wherein the antibody or antigen-binding fragment thereof comprises: (a) a heavy chain variable (HV) region comprising an amino acid sequence selected from the group consisting of: (i) the sequence as shown in SEQ ID NO: 91; (ii) a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, 3, 4, or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 91; or (iii) a sequence having a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%,at least 99% or 100% to the sequence as shown in SEQ ID NO: 91; and / or (b) a variable light chain (VL) region comprising an amino acid sequence selected from the group consisting of: (iv) the sequence as shown in SEQ ID NO: 92; (v) a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, 3, 4, or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 92; or (vi) a sequence having a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% to the sequence as shown in SEQ ID NO: 92; preferably, the substitution as mentioned in (i) or (v) is a conservative substitution.The antibody or antigen-binding fragment thereof comprises: a VH having a sequence as shown in SEQ ID NO: 91, and a VL having a sequence as shown in SEQ ID NO:

92.

15. The antibody or antigen-binding fragment thereof according to claim 1, 2 or 13, wherein the antibody or antigen-binding fragment thereof comprises: (a) a heavy-chain variable region (VH) comprising a sequence of 117 amino acids selected from the group consisting of: (i) the sequence as shown in SEQ ID NO: 99; (ii) a sequence having a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1, 2, 3, 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 99; or (iii) a sequence having a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%,at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 99; and / or (b) a variable light chain (VL) region comprising an amino acid sequence selected from the group consisting of: (iv) the sequence as shown in SEQ ID NO: 100; (v) a sequence having a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1, 2, 3, 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 100; or (vi) a sequence having a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% to the sequence as shown in SEQ ID NO: 100; preferably,The substitution as mentioned in (i) or (v) is a conservative substitution. Preferably, the antibody or antigen-binding fragment thereof comprises: a VH having a sequence as shown in SEQ ID NO: 99, and a VL having a sequence as shown in SEQ ID NO:

100.

16. The antibody or antigen-binding fragment thereof according to claim 1, 2, or 13, wherein the antibody or antigen-binding fragment thereof comprises: (a) a heavy-chain variable region (VH) comprising an amino acid sequence selected from the group consisting of: (i) the sequence as shown in SEQ ID NO: 101; (ii) a sequence having a substitution, deletion, or addition of one or more amino acids (e.g., a substitution, deletion, or addition of 1, 2, 3,4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 101; or (iii) a sequence having a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% to the sequence as shown in SEQ ID NO: 101; and / or (b) a variable light chain (VL) region comprising an amino acid sequence selected from the group consisting of: (v) the sequence as shown in SEQ ID NO: 102; (v) a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, 3, 4, or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 102; or (vi) a sequence having a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%,at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% to the sequence as shown in SEQ ID NO: 102; preferably, the substitution as mentioned in (i) or (v) is a conservative substitution. Preferably, the antibody or antigen-binding fragment thereof comprises: a VH having a sequence as shown in SEQ ID NO: 101, and a VL having a sequence as shown in SEQ ID NO:

102.

17. The antibody or antigen-binding fragment thereof according to claim 3, wherein the antibody or antigen-binding fragment thereof comprises: (a) a heavy-chain variable region (VH) comprising an amino acid sequence selected from the group consisting of: (i) the sequence as shown in SEQ ID NO: 1; (i) a sequence having a substitution, deletion or addition of one or more amino acids (e.g., a substitution,deletion or addition of 1, 2, 3, 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 1; or (iii) a sequence having a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 1; and / or (b) a variable light chain (VL) region comprising an amino acid sequence selected from the group consisting of: MA / t / ZUZ I / υοοζο΅ 119 (iv) the sequence as shown in SEQ ID NO: 2; (v) a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, 3, 4, or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 2; or (vi) a sequence having a sequence identity of at least 80%, at least 85%, at least 90%,at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% to the sequence as shown in SEQ ID NO: 2; preferably, the substitution as mentioned in (i) or (v) is a conservative substitution. Preferably, the antibody or antigen-binding fragment thereof comprises: a VH having a sequence as shown in SEQ ID NO: 1, and a VL having a sequence as shown in SEQ ID NO:

2.

18. The antibody or antigen-binding fragment thereof according to claim 4, wherein the antibody or antigen-binding fragment thereof comprises: (a) a heavy-chain variable region (VH) comprising an amino acid sequence selected from the group consisting of: (i) the sequence as shown in SEQ ID NO: 9; (i) a sequence having a substitution, deletion or addition of one or more amino acids (for example,a substitution, deletion, or addition of 1, 2, 3, 4, or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 9; or (iii) a sequence having a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% to the sequence as shown in SEQ ID NO: 9; and / or (b) a variable light chain (VL) region comprising an amino acid sequence selected from the group consisting of: (iv) the sequence as shown in SEQ ID NO: 10; (v) a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, 3, 4, or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 10; or (vi) a sequence having a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%,at least 92%, at least 93%, at least 94%, at least 95%, to ML / t / ZUZ I / UOOZOO 120 less 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 10; preferably, the substitution as mentioned in (i) or (v) is a conservative substitution. Preferably, the antibody or antigen-binding fragment thereof comprises: a VH having a sequence as shown in SEQ ID NO: 9, and a VL having a sequence as shown in SEQ ID NO:

10.

19. The antibody or antigen-binding fragment thereof according to claim 5, wherein the antibody or antigen-binding fragment thereof comprises: (a) a heavy-chain variable region (VH) comprising an amino acid sequence selected from the group consisting of: (i) the sequence as shown in SEQ ID NO: 17; (ii) a sequence having a substitution, deletion, or addition of one or more amino acids (e.g.,a substitution, deletion, or addition of 1, 2, 3, 4, or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 17; or (ii) a sequence having a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% to the sequence as shown in SEQ ID NO: 17; and / or (b) a variable light chain (VL) region comprising an amino acid sequence selected from the group consisting of: (iv) the sequence as shown in SEQ ID NO: 18; (v) a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, 3, 4, or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 18; or (vi) a sequence having a sequence identity of at least 80%, at least 85%, at least 90%,at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 18; preferably, the substitution as mentioned in (i) or (v) is a conservative substitution. Preferably, the antibody or antigen-binding fragment thereof comprises: a VH having a sequence as shown in SEQ ID NO: 17, and a VL having a MA / t / ZUZ I / UO3Z00 121 sequence as shown in SEQ ID NO:

18.

20. The antibody or antigen-binding fragment thereof according to claim 6, wherein the antibody or antigen-binding fragment thereof comprises: (a) a heavy-chain variable region (VH) comprising an amino acid sequence selected from the group consisting of: (i) the sequence as shown in SEQ ID NO: 25; (ii) a sequence having a substitution,deletion or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, 3, 4, or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 25; or (iii) a sequence having a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% to the sequence as shown in SEQ ID NO: 25; and / or (b) a variable light chain (VL) region comprising an amino acid sequence selected from the group consisting of: (iv) the sequence as shown in SEQ ID NO: 26; (v) a sequence having a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1,2,3,4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 26; or (vi) a sequence having a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% to the sequence as shown in SEQ ID NO: 26; preferably, the substitution as mentioned in (i) or (v) is a conservative substitution. Preferably, the antibody or antigen-binding fragment thereof comprises: a VH having a sequence as shown in SEQ ID NO: 25, and a VL having a sequence as shown in SEQ ID NO:

26.

21. The antibody or antigen-binding fragment thereof according to claim 7,wherein the antibody or antigen-binding fragment thereof comprises: (a) a heavy chain variable (HV) region comprising an amino acid sequence selected from the group consisting of: (i) the sequence as shown in SEQ ID NO: 33; ML / t / ZUZ I / υοοζο΅ 122 (ii) a sequence having a substitution, deletion, or addition of one or more amino acids (e.g., a substitution, deletion, or addition of 1, 2, 3, 4, or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 33; or (iii) a sequence having a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%,at least 99% or 100% to the sequence as shown in SEQ ID NO: 33; and / or (b) a variable light chain (VL) region comprising an amino acid sequence selected from the group consisting of: (iv) the sequence as shown in SEQ ID NO: 34; (v) a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, 3, 4, or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 34; or (vi) a sequence having a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% to the sequence as shown in SEQ ID NO: 34; preferably, the substitution as mentioned in (i) or (v) is a conservative substitution.The antibody or antigen-binding fragment thereof comprises: a VH having a sequence as shown in SEQ ID NO: 33, and a VL having a sequence as shown in SEQ ID NO:

34.

22. The antibody or antigen-binding fragment thereof according to claim 8, wherein the antibody or antigen-binding fragment thereof comprises: (a) a heavy-chain variable region (VH) comprising an amino acid sequence selected from the group consisting of: (i) the sequence as shown in SEQ ID NO: 41; (ii) a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, 3, 4, or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 41; or (iii) a sequence having a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%,at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 41; and / or (b) a variable light chain (VL) region comprising an amino acid sequence selected from the group consisting of: (iv) the sequence as shown in SEQ ID NO: 42; (v) a sequence having a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1, 2, 3, 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 42; or (vi) a sequence having a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% to the sequence as shown in SEQ ID NO: 42; preferably, the substitution as mentioned in (i) or (v) is a conservative substitution.The antibody or antigen-binding fragment thereof comprises: a VH having a sequence as shown in SEQ ID NO: 41, and a VL having a sequence as shown in SEQ ID NO:

42.

23. The antibody or antigen-binding fragment thereof according to claim 9, wherein the antibody or antigen-binding fragment thereof comprises: (a) a heavy-chain variable region (VH) comprising an amino acid sequence selected from the group consisting of: (i) the sequence as shown in SEQ ID NO: 49; (ii) a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, 3, 4, or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 49; or (iii) a sequence having a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%,at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 49; and / or (b) a variable light chain (VL) region comprising an amino acid sequence selected from the group consisting of: (iv) the sequence as shown in SEQ ID NO: 50; (v) a sequence having a substitution, deletion or addition of one or more amino acids (e.g., a substitution, deletion or addition of 1, 2, 3, 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 50; or (vi) a sequence having a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% to the sequence as shown in SEQ ID NO: 50; preferably,The substitution as mentioned in (i) or (v) is a conservative substitution. Preferably, the antibody or antigen-binding fragment thereof comprises: a VH having a sequence as shown in SEQ ID NO: 49, and a VL having a sequence as shown in SEQ ID NO:

50.

24. The antibody or antigen-binding fragment thereof according to claim 10, wherein the antibody or antigen-binding fragment thereof comprises: (a) a heavy-chain variable region (VH) comprising an amino acid sequence selected from the group consisting of: (i) the sequence as shown in SEQ ID NO: 57; (ii) a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, 3, 4, or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 57; or (iii) a sequence having a sequence identity of at least 80%,at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 57; and / or (b) a variable light chain (VL) region comprising an amino acid sequence selected from the group consisting of: (iv) the sequence as shown in SEQ ID NO: 58; (v) a sequence having a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1, 2, 3, 4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 58; or (vi) a sequence having a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%,at least 99% or 100% to the sequence as shown in SEQ ID NO: 58; ML / I / UOOZOO 125. Preferably, the substitution as mentioned in (i) or (v) is a conservative substitution. Preferably, the antibody or antigen-binding fragment thereof comprises: a VH having a sequence as shown in SEQ ID NO: 57, and a VL having a sequence as shown in SEQ ID NO:

58.

25. The antibody or antigen-binding fragment thereof according to claim 11, wherein the antibody or antigen-binding fragment thereof comprises: (a) a heavy-chain variable region (VH) comprising an amino acid sequence selected from the group consisting of: (i) the sequence as shown in SEQ ID NO: 65; (i) a sequence having a substitution, deletion or addition of one or more amino acids (e.g., a substitution, deletion or addition of 1,2,3,4 or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 65; or (iii) a sequence having a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% to the sequence as shown in SEQ ID NO: 65; and / or (b) a variable light chain (VL) region comprising an amino acid sequence selected from the group consisting of: (iv) the sequence as shown in SEQ ID NO: 66; (v) a sequence having a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, 3, 4, or 5 amino acids) compared to the sequence as shown in SEQ ID NO: 66; or (vi) a sequence having a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%,at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% to the sequence as shown in SEQ ID NO: 66; preferably, the substitution as mentioned in (i) or (v) is a conservative substitution. Preferably, the antibody or antigen-binding fragment thereof comprises: a VH having a sequence as shown in SEQ ID NO: 65, and a VL having a sequence as shown in SEQ ID NO:

66.

26. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 25, wherein the antibody or antigen-binding fragment thereof further comprises: (a) a heavy chain (CH) constant region of a human immunoglobulin or a variant thereof, wherein the variant has a substitution, deletion, or addition of one or more amino acids (e.g., a substitution, deletion, or addition of up to 20, up to 15,up to 10 or up to 5 amino acids (for example, a substitution, deletion or addition of 1, 2, 3, 4 or 5 amino acids) compared to the sequence from which the variant is derived; and (b) a light chain (LC) constant region of a human immunoglobulin or a variant thereof, wherein the variant has a substitution, deletion or addition of up to 20 amino acids (for example, a substitution, deletion or addition of up to 15, up to 10 or up to 5 amino acids; for example, a substitution, deletion or addition of 1, 2, 3, 4 or 5 amino acids) compared to the sequence from which the variant is derived; preferably, the heavy chain constant region is an IgG heavy chain constant region, such as an IgG 1, lgG2, lgG3 or lgG4 heavy chain constant region; Preferably, the antibody or antigen-binding fragment thereof comprises a heavy chain (CH) constant region as shown in SEQ ID NO: 81; preferably,The light chain constant region is a kκ light chain constant region; preferably, the antibody or antigen-binding fragment thereof comprises a light chain constant (LC) region as shown in SEQ ID NO: 82; 27. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 26, wherein the antigen-binding fragment is selected from the group consisting of Fab, Fab', (Fabj2, Fv, disulfide-linked Fv, scFv, diabody, and single-domain antibody (sdAb); and / or, the antibody is a murine antibody, a chimeric antibody, a humanized antibody, a bispecific antibody, or a multispecific antibody.

28. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 27, wherein the antibody or antigen-binding fragment thereof is labeled; preferably,The antibody or antigen-binding fragment thereof is labeled with a detectable tag, such as an enzyme (e.g., horseradish peroxidase), a radionuclide, a fluorescent dye, a luminescent substance (e.g., a chemiluminescent substance), or biotin.

29. An isolated nucleic acid molecule encoding the antibody or antigen-binding fragment thereof according to any one of claims 1 to 28, or a variable heavy-chain and / or variable light-chain region thereof.

30. A vector comprising the isolated nucleic acid molecule according to claim 29; preferably, the vector is a cloning vector or an expression vector.

31. A host cell,comprising the isolated nucleic acid molecule according to claim 29 or the vector according to claim 30.

32. A method for preparing the antibody or antigen-binding fragment thereof according to any one of claims 1 to 28, comprising culturing the host cell according to claim 31 in a condition permitting expression of the antibody or antigen-binding fragment thereof, and recovering the antibody or antigen-binding fragment thereof from a culture of the cultured host cell.

33. A bispecific or multispecific molecule, comprising the antibody or antigen-binding fragment thereof according to any one of claims 1 to 28; preferably, the bispecific or multispecific molecule binds specifically to CLDN18.2 and further binds specifically to one or more different targets; preferably, the bispecific or multispecific molecule further comprisesat least one molecule (for example, a second antibody) having a second binding specificity for a second target.

34. An immunoconjugate, comprising the antibody or antigen-binding fragment thereof according to any one of claims 1 to 28, and a therapeutic agent conjugated to the antibody or antigen-binding fragment thereof; preferably, the therapeutic agent is a cytotoxic agent; preferably, the therapeutic agent is selected from an alkylating agent, an antimitotic agent, an antitumor antibiotic, an antimetabolite, a topoisomerase inhibitor, a tyrosine kinase inhibitor, a radionuclide, and any combination thereof; preferably, the immunoconjugate is an antibody-drug conjugate (ADC).

35. A pharmaceutical composition, comprising the antibody or antigen-binding fragment thereof according to any one of claims 1 to 28,the bispecific or multispecific molecule according to claim 33, or the immunoconjugate according to claim 34, and a pharmaceutically acceptable vehicle and / or excipient; preferably, the pharmaceutical composition further comprises an additional pharmaceutically active agent; preferably, the additional pharmaceutically active agent is an antitumor agent, such as an alkylating agent, an antimitotic agent, an antitumor antibiotic, an antimetabolite, a topoisomerase inhibitor, a tyrosine kinase inhibitor, a radionuclide, a radiosensitizer, an antiangiogenesis agent, a cytokine, a molecularly targeted agent, an immune checkpoint inhibitor, or an oncolytic virus; preferably, the antibody or antigen-binding fragment thereof,A bispecific or multispecific molecule or immunoconjugate and the additional pharmaceutically active agent are provided as separate components or as components of a single composition.

36. A kit comprising the antibody or antigen-binding fragment thereof according to any one of claims 1 to 28; preferably, the antibody or antigen-binding fragment thereof is labeled with a detectable marker, such as an enzyme (e.g., horseradish peroxidase), a radionuclide, a fluorescent dye, a luminescent substance (e.g., a chemiluminescent substance), or biotin; preferably, the kit further comprises a second antibody that specifically recognizes the antibody or antigen-binding fragment thereof according to any one of claims 1 to 28; preferably, the second antibody further comprises a detectable marker, such as an enzyme (e.g.,horseradish peroxidase), a radionuclide, a fluorescent dye, a luminescent substance (e.g., a chemiluminescent substance), or a diotin.

37. A chimeric antigen receptor, comprising an antibody antigen-binding domain or antigen-binding fragment thereof according to any one of claims 1 to 28; preferably, the antigen-binding domain comprises a variable heavy-chain region and a variable light-chain region of the antibody or antigen-binding fragment thereof according to any one of claims 1 to 28; preferably, the antigen-binding domain is scFv; preferably, the antigen-binding receptor comprises an antibody antigen-binding fragment according to any one of claims 1 to 28; preferably, the antigen-binding receptor is expressed by an immune effector cell (e.g.,a T lymphocyte).

38. An isolated nucleic acid molecule encoding the chimeric antigen receptor according to claim 37.

39. A vector comprising the isolated nucleic acid molecule according to claim 38; preferably, the vector is used to prepare a chimeric antigen receptor T cell.

40. A host cell comprising the isolated nucleic acid molecule according to MA / t / ZUZ I / UO3Z00 129 with claim 38 or the vector according to claim 39; preferably, the host cell is an immune effector cell (e.g., a T cell or an NK cell); preferably, the host cell is a chimeric antigen receptor (CART) T lymphocyte.

41. A method for reducing the expression level of CLDN18.2 on the surface of a cell, comprising contacting the cell with the antibody or antigen-binding fragment thereof according to any one of claims 1 to 28.or the bispecific or multispecific molecule according to claim 33, or the immunoconjugate according to claim 34, or the pharmaceutical composition according to claim 35, or the chimeric antigen receptor according to claim 37, or the host cell according to claim 40, such that the level of CLDN18.2 expression on the cell surface is reduced; wherein the cells have CLDN18.2 expressed on their surface; preferably, the cell is a tumor cell expressing CLDN18.

2.

42. A method for inhibiting the growth of a tumor cell expressing CLDN18.2 and / or destroying the tumor cell expressing CLDN18.2, comprising contacting the tumor cell with an effective amount of the antibody or antigen-binding fragment thereof according to any one of claims 1 to 28, or the bispecific or multispecific molecule according to claim 33,or the immunoconjugate according to claim 34, or the pharmaceutical composition according to claim 35, or the chimeric antigen receptor according to claim 37, or the host cell according to claim 40.

43. A method for preventing and / or treating a tumor in a subject (e.g., a human), comprising administering to the subject in need an effective quantity of the antibody or antigen-binding fragment thereof according to any one of claims 1 to 28, or the bispecific or multispecific molecule according to claim 33, or the immunoconjugate according to claim 34, or the pharmaceutical composition according to claim 35, or the chimeric antigen receptor according to claim 37, or the host cell according to claim 40; preferably, the tumor expresses CLDN18.2; preferably,The tumor involves a tumor cell expressing CLDN18.2; preferably, CLDN18.2 is expressed on the surface of the tumor cell; preferably, the tumor is selected from the group consisting of gastric cancer, esophageal cancer, pancreatic cancer, bronchial cancer, non-small cell lung cancer, breast cancer, ear-nose-throat cancer, ovarian cancer, colon cancer, liver cancer, head and neck cancer, gallbladder cancer and its metastatic cancer (e.g., gastric cancer metastasis, such as Krukenberg tumor, peritoneal metastasis, or lymph node metastasis); preferably, the subject is a mammal, such as a human; Preferably, the method further comprises administering an additional antitumor agent, such as an alkylating agent, an antimitotic agent, an antitumor antibiotic, an antimetabolite, a topoisomerase inhibitor, a tyrosine kinase inhibitor, or a radionuclide.a radiosensitizer, an antiangiogenesis agent, a cytokine, a molecularly targeted agent, an immune checkpoint inhibitor, or an oncolytic virus; preferably, the method further comprises administering additional antitumor therapy, such as surgery, chemotherapy, radiotherapy, targeted therapy, immunotherapy, hormone therapy, gene therapy, or palliative care.

44. Use of the antibody or antigen-binding fragment thereof according to any one of claims 1 to 28, or the bispecific or multispecific molecule according to claim 33, or the immunoconjugate according to claim 34, or the pharmaceutical composition according to claim 35, or the chimeric antigen receptor according to claim 37, or the host cell according to claim 40 in the manufacture of a medicament for preventing and / or treating a tumor in a subject (e.g., a human); preferably,The drug further comprises an additional pharmaceutically active agent; preferably, the additional pharmaceutically active agent is an antitumor agent, such as an alkylating agent, an antimitotic agent, an antitumor antibiotic, an antimetabolite, a topoisomerase inhibitor, a tyrosine kinase inhibitor, a radionuclide, a radiosensitizer, an antiangiogenesis agent, a cytokine, a molecularly targeted agent, an immune checkpoint inhibitor, or an oncolytic virus; preferably, the tumor expresses CLDN18.2; preferably, the tumor involves a tumor cell expressing CLDN18.2; preferably, CLDN18.2 is expressed on the surface of the tumor cell; preferably, the tumor is selected from the group consisting of gastric cancer, esophageal cancer, pancreatic cancer, bronchial cancer, non-small cell lung cancer, breast cancer, ear-nose-throat cancer, ovarian cancer, colon cancer, liver cancer,head and neck cancer, gallbladder cancer and its metastatic cancer (e.g., gastric cancer metastasis, such as Krukenberg tumor, peritoneal metastasis, or lymph node metastasis); preferably, the subject is a mammal, such as a human.

45. A method for detecting the presence or amount of CLDN18.2 (e.g., human CLDN18.2) in a sample, comprising the following steps: (1) contacting the sample with the antibody or antigen-binding fragment thereof according to any one of claims 1 to 28; (2) detecting the formation or amount of a complex between the antibody or antigen-binding fragment thereof and CLDN18.2; preferably, the antibody or antigen-binding fragment thereof is labeled with a detectable marker; preferably,CLDN18.2 is a human CLDN18.

2.

46. A method for determining whether a tumor is treatable by an antitumor therapy directed at CLDN18.2, comprising the following steps: (1) contacting a sample containing the tumor cell with the antibody or antigen-binding fragment thereof according to any one of claims 1 to 28; (2) detecting the formation of a complex between the antibody or antigen-binding fragment thereof and CLDN18.2; preferably, the antibody or antigen-binding fragment thereof is labeled with a detectable marker; preferably, the CLDN18.2 is human CLDN18.2; preferably, the tumor is selected from gastric cancer, esophageal cancer, pancreatic cancer, bronchial cancer, non-small cell lung cancer, breast cancer, ear-nose-throat cancer, ovarian cancer, colon cancer, liver cancer, head and neck cancer, gallbladder cancer and its metastatic cancer (e.g., gastric cancer metastasis, such as Krukenberg tumor, peritoneal metastasis or lymph node metastasis).

47. The use of the antibody or antigen-binding fragment thereof according to any one of claims 1 to 28 in the manufacture of a kit for determining whether a tumor is treatable by an antitumor therapy directed at CLDN18.2; preferably, the antibody or antigen-binding fragment thereof is labeled with a detectable marker; preferably, CLDN18.2 is a human CLDN18.2; preferably, the tumor is selected from gastric cancer, esophageal cancer, pancreatic cancer, bronchial cancer, non-small cell lung cancer, breast cancer, ear-nose-throat cancer, ovarian cancer, colon cancer, liver cancer, head and neck cancer, gallbladder cancer and its metastatic cancer (e.g., gastric cancer metastasis, such as Krukenberg tumor, peritoneal metastasis, or lymph node metastasis).