Anti-tl1a fully human antibody and preparation method and application thereof

Abstract

The application belongs to the technical field of antibody preparation, and particularly relates to an anti-TL1A fully human antibody and a preparation method and application thereof. The anti-TL1A antibody comprises a heavy chain variable region and a light chain variable region; the heavy chain variable region comprises three complementarity determining regions, namely CDR-H1, CDR-H2 and CDR-H3, and the light chain variable region comprises three complementarity determining regions, namely CDR-L1, CDR-L2 and CDR-L3. The antibody preparation method is as follows: RNA extraction, reverse transcription, ScFv amplification, enzyme digestion and ligation, electric conversion, construction of a fully human phage library, packaging of phages, three rounds of panning, selection of positive clones for Clone ELISA detection, obtaining of antibodies combined with TL1A proteins, selection of unique sequences after sequencing analysis, high-throughput expression of antibody proteins through a mammalian cell high-throughput expression system, FACS blocking detection through a DR3 high-expression cell line, and finally obtaining of antibodies combined with TL1A and having DR3 blocking activity. The method is simple and rapid in operation, and can obtain human antibodies.

Description

Technical Field

[0001] This invention belongs to the field of antibody preparation technology, specifically relating to an anti-TL1A fully human antibody, its preparation method, and its application. Background Technology

[0002] Fully human antibodies are antibodies produced entirely by the human immune system. Their complementary determination region (CDR) binds to specific antigens, offering several advantages over traditional antibodies: low immunogenicity, high compatibility with the human immune system, and minimal recognition as foreign substances, reducing the production of drug-resistant antibodies; reduced probability of adverse reactions such as allergies caused by immune responses, improving treatment safety and patient tolerability, and reducing long-term risks; high affinity and specificity, enabling precise identification and targeting of specific antigens, reducing damage to healthy tissues and improving treatment efficacy; higher affinity for target antigens, reducing drug dosage and alleviating the economic burden on patients; favorable pharmacokinetic characteristics, reducing dosing frequency and improving patient compliance; and minimal rejection reactions, especially advantageous in areas with high drug safety requirements, such as autoimmune diseases. Adalimumab, the first fully human antibody, is an anti-TNF-α human antibody approved for 10 indications worldwide.

[0003] The main technologies for preparing fully human antibodies include antibody library technology (phage, yeast, bacterial libraries), human single B cell sorting technology, and transgenic mouse technology. The first clinical success of humanized monoclonal antibodies was based on phage display technology, in which different exogenous genes are constructed into phages to form a library. The library proteins are then presented on the surface of the phage as phage coat proteins, allowing selection of specific binding agents and antigen proteins with specific affinity.

[0004] TL1A, also known as TNFSF15 or VEGI, is a member of the tumor necrosis factor ligand superfamily. It is a type II transmembrane protein composed of cytoplasmic, transmembrane, and extracellular domains. It is expressed in various immune cells, such as monocytes, macrophages, dendritic cells, and T cells, as well as non-immune cells, such as synovial fibroblasts and endothelial cells. TL1A plays a crucial role in immune regulation and tissue homeostasis, particularly in inflammatory responses and autoimmune diseases. TL1A competitively binds to death receptor 3 (DR3) or decoy receptor 3 (DcR3). DR3, the functional receptor for TL1A, belongs to the TNFR superfamily and is a type I transmembrane protein. TL1A trimers can bind to DR3 trimers, forming a 3:3 complex that activates two signaling pathways: first, by recruiting TRAF2 and RIP1 via TRADD, it activates the MAPK, NF-κB, and PI3K pathways, promoting the expression of inflammatory factors and participating in immune and inflammatory responses; second, by forming a complex with FADD and RIP3, it activates caspase-8, triggering a caspase cascade reaction and inducing apoptosis. When caspase-8 activity is inhibited, necrosomes can form, leading to MLKL-mediated necrotizing cell death. TL1A stimulates the TH1 and TH17 pathways, which are associated with the instability and severity of intestinal inflammation and fibrosis. TL1A can also activate fibroblasts, which are the main source of fibrosis; therefore, TL1A is an important factor regulating mucosal immunity and fibrosis.

[0005] TL1A plays a crucial role in the occurrence and development of various diseases, particularly those closely related to inflammation and autoimmune diseases. It is highly expressed in the intestinal tissue of patients with inflammatory diseases (IBD) such as ulcerative colitis and Crohn's disease, and is also abnormally activated in autoimmune diseases such as rheumatoid arthritis, psoriasis, systemic lupus erythematosus, and atopic dermatitis. TL1A blockers have emerged as a potential new therapy for treating inflammatory and fibrotic diseases. Targeted therapies against TL1A primarily utilize monoclonal antibodies. Pfizer's fully human TL1A antibody, Afikibart, showed endoscopic and histological improvement in patients with moderate to severe ulcerative colitis (UC) in a phase 2a clinical trial, while Tulisokibart also demonstrated clinical remission in a phase III clinical trial. Watt Pharmaceuticals' Duvakitug is currently undergoing a phase II clinical trial in patients with UC and Crohn's disease, showing anti-inflammatory and anti-fibrotic potential. The clinical application for a TL1A monoclonal antibody developed by 3SBio has been accepted by the National Medical Products Administration, making it the first domestically produced TL1A monoclonal antibody to apply for clinical trials in China.

[0006] Currently, there are no marketed anti-TL1A antibody drugs, therefore, there is an urgent need to develop more and better anti-TL1A antibody products. Phage display technology is an important method for screening high-affinity antibodies. Fully human antibodies have lower immunogenicity and good specificity, which can improve the safety of long-term use. Compared with traditional hybridoma technology, screening of fully human phage libraries avoids the humanization step of mouse antibodies. ScFv antibodies have a low molecular weight, higher affinity than traditional antibodies, are more likely to penetrate and reach the site of inflammation, and are easy to modify, making them a promising method for discovering anti-TL1A antibodies. Summary of the Invention

[0007] The purpose of this invention is to overcome the shortcomings of the prior art and provide an anti-TL1A fully human antibody, its preparation method, and its application.

[0008] The technical solution of this invention to solve the technical problem is as follows: In a first aspect of the present invention, a fully human anti-TL1A antibody is provided, the anti-TL1A fully human antibody comprising a heavy chain variable region and a light chain variable region; the heavy chain variable region comprises three complementarity-determining regions, namely CDR-H1, CDR-H2, and CDR-H3, and the light chain variable region comprises three complementarity-determining regions, namely CDR-L1, CDR-L2, and CDR-L3; the amino acid sequences of each complementarity-determining region are as follows: 1) The amino acid sequence of CDR-H1 is shown in SEQ ID NO:1; the amino acid sequence of CDR-H2 is shown in SEQ ID NO:2; the amino acid sequence of CDR-H3 is shown in SEQ ID NO:3; the amino acid sequence of CDR-L1 is shown in SEQ ID NO:4; the amino acid sequence of CDR-L2 is YDS; and the amino acid sequence of CDR-L3 is shown in SEQ ID NO:5. 2) The amino acid sequences of the complementarity-determining regions CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 have at least 90% sequence identity with the amino acid sequences of the complementarity-determining regions CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 in 1).

[0009] Furthermore, The amino acid sequence of the heavy chain variable region of the antibody is as shown in SEQ ID NO:6, or has at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity with SEQ ID NO:6. The amino acid sequence of the light chain variable region of the antibody is as shown in SEQ ID NO:7, or has at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity with SEQ ID NO:7.

[0010] In one embodiment of the present invention, the anti-TL1A fully human antibody is a ScFv antibody, the amino acid sequence of which is shown in SEQ ID NO:10.

[0011] In a second aspect, the present invention provides an antibody derivative comprising the anti-TL1A fully human antibody described in the first aspect, comprising three complementary determinant regions of the heavy chain variable region, namely CDR-H1, CDR-H2 and CDR-H3, and three complementary determinant regions of the light chain variable region, namely CDR-L1, CDR-L2 and CDR-L3; or comprising only the three complementary determinant regions of the heavy chain variable region, namely CDR-H1, CDR-H2 and CDR-H3.

[0012] Furthermore, the antibody derivative may be selected from any of the following forms: (a) A multivalent nanobody comprising two or more identical or different fully human anti-TL1A antibodies; (b) Bispecific or multispecific antibodies; (c) Antibody conjugates; (d) Heavy chain antibodies or their antigen-binding fragments.

[0013] In a third aspect of the invention, a nucleic acid encoding a fully human antibody against TL1A as described in the first aspect is provided.

[0014] Furthermore, the anti-TL1A fully human antibody comprises a heavy chain variable region and a light chain variable region; the nucleic acid sequence encoding the heavy chain variable region is shown in SEQ ID NO:8, and the nucleic acid sequence encoding the light chain variable region is shown in SEQ ID NO:9.

[0015] In one embodiment of the present invention, the anti-TL1A fully human antibody is a ScFv antibody, and the nucleic acid sequence encoding the ScFv antibody is shown in SEQ ID NO:11.

[0016] In a fourth aspect of the invention, a biomaterial is provided, the biomaterial comprising at least one of the following: (A) A recombinant vector containing nucleic acids as described in the third aspect; (B) A host cell containing the recombinant vector described in (A).

[0017] In a fifth aspect of the present invention, a method for preparing a fully human anti-TL1A antibody as described in the first aspect is provided, comprising the following steps: screening to obtain peripheral blood from healthy individuals, extracting RNA from PBMC cells, reverse transcribing it into cDNA, obtaining an antibody gene fragment by PCR, and constructing it into a phage expression vector; electroporating the obtained vector containing the antibody gene fragment into SS320 electrocompetent cells to obtain a TL1A immune antibody library, performing three rounds of TL1A protein panning, detecting positive clones binding to TL1A protein by Clone ELISA, sequencing analysis, selecting unique sequences, performing high-throughput expression using a mammalian cell high-throughput expression system to obtain antibody protein, performing FACS detection using a TL1A high-expression cell line, and finally obtaining an antibody binding to TL1A.

[0018] In a sixth aspect of the invention, a pharmaceutical composition is provided comprising an anti-TL1A fully human antibody as described in the first aspect, an antibody derivative as described in the second aspect, a nucleic acid as described in the third aspect or a biological material as described in the fourth aspect, and a pharmaceutically acceptable carrier.

[0019] The pharmaceutically acceptable carrier may be selected from excipients, diluents, or adjuvants, such as buffers, stabilizers, preservatives, isotonic modifiers, surfactants, lyophilization protectants, etc.

[0020] In a seventh aspect of the invention, a product or kit is provided comprising an anti-TL1A fully human antibody as described in the first aspect, an antibody derivative as described in the second aspect, a nucleic acid as described in the third aspect, or a biological material as described in the fourth aspect.

[0021] In an eighth aspect of the invention, the use of the anti-TL1A fully human antibody as described in the first aspect, the antibody derivative as described in the second aspect, the nucleic acid as described in the third aspect, or the biomaterial as described in the fourth aspect in the preparation of drugs for treating various inflammatory injuries, autoimmune diseases, tumor immunotherapy, and anti-aging.

[0022] In a ninth aspect of the invention, the use of the anti-TL1A fully human antibody as described in the first aspect, the antibody derivative as described in the second aspect, the nucleic acid as described in the third aspect, or the biological material as described in the fourth aspect in the preparation of products for detecting TL1A is provided.

[0023] In a tenth aspect of the invention, the use of a fully human anti-TL1A antibody as described in the first aspect, an antibody derivative as described in the second aspect, a nucleic acid as described in the third aspect, or a biological material as described in the fourth aspect in the preparation of a product that binds to TL1A is provided.

[0024] The present invention has the following technical effects: 1) The antibodies of the present invention have low immunogenicity, high affinity, and strong specificity, and have the characteristic of highly efficient binding to TL1A.

[0025] 2) The antibody preparation method of the present invention is simple and fast. Attached Figure Description

[0026] Figure 1 Image showing the electrophoresis results of TL1A ScFv; Figure 2 The results show the blocking effect of TL1A antibody on DR3-overexpressing cell lines. Detailed Implementation

[0027] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. Obviously, the described embodiments are only some embodiments of this invention, and not all embodiments.

[0028] The reagents or instruments used, for which the manufacturer is not specified, are all standard products that can be purchased through legitimate channels.

[0029] The operations performed in the embodiments of this invention are all routine procedures in antibody discovery and molecular and cell biology, and those skilled in the art can repeat the experiments.

[0030] Example 1 In this embodiment, the method for preparing the TL1A fully human antibody includes the following steps: 1) Based on the gene and protein sequence information of TL1A (UniProt:Accession 095150), the immunogen TL1A was expressed and a His-tag was linked to its C-terminus to obtain modified amino acids for subsequent purification and detection; 2) Construction of a fully human phage library: Peripheral blood was collected from healthy individuals, PBMCs were isolated, and RNA was extracted using the Trizol method; cDNA was reverse transcribed, and the variable regions VH, VK, and Vλ were amplified separately. Overlap PCR was used to obtain the VH+VK and VH+Vλ fragments. Figure 1 (Electrophoresis image of ScFv fragment). The vector was dephosphorylated after enzyme digestion. The ScFv fragment was digested, and the digested vector was ligated with the ScFv fragment. The ligation product was electroporated and transformed into SS320 electrocompetent cells. The transformed bacteria were serially diluted to calculate the library volume, plated on single-clone plates, and the remaining bacterial culture was plated on 2YT-Amp plates and incubated overnight at 37°C. The next day, the library was scraped off the plate and stored in glycerol. Thirty single clones were selected from each individual plate for sequencing. A qualified library was defined as having an effective insertion rate of 80% and a diversity of over 90%. The phage libraries were then mixed to obtain a mixed library.

[0031] 3) Phage packaging: Take two 50mL centrifuge tubes, each containing 20mL of 2×YT (Amp+ / T+), to achieve an initial OD600 of ~0.1. Incubate at 37℃ and 220 rpm until the logarithmic growth phase. Estimate the amount to be added based on the OD600 of the collected library cells. Incubate until the OD600 reaches 0.3-0.4, then inoculate. Add 5µl of M13KO7 (~5*10^12 pfu / mL) to each tube, incubate at 37℃ and 80 rpm for 0.5 h. Add 20µl of kanamycin (1000×) to each tube, incubate at 37℃ and 220 rpm for 0.5 h. This step is to screen for cells infected by M13KO7. Add 40µl of 0.1M IPTG to each tube and incubate overnight. Centrifuge all overnight cultures at 13000g for 15 min, collect the supernatant, and add PEG NaCl6000. Incubate on ice for 1 hour; centrifuge at 12000g for 10 minutes, remove the supernatant, add 0.5ml of 1×PBS, resuspend, and store in sterile glycerol to a final concentration of 20%.

[0032] 4) Document screening: A three-round screening method using solid-phase screening is adopted. The specific scheme is shown in Table 1.

[0033] Take two 96-well microplates. For the positive sieve plate, coat four wells with hTL1A-his at 1ug / well and 100µL / well. For the negative sieve plate, coat with 3% BSA at 100µL / well and incubate overnight at 4°C. Wash both plates three times with 0.1% PBST (1×PBS containing 0.1% Tween 20). Block both plates with 3% BSA at 200µL / well, add 5E 10pfu pH, and incubate at RT. 1h incubation; Negative sieve incubation: Remove the blocking solution from the negative sieve plate, wash 3 times with 0.1% PBST, add the blocked phage to the negative sieve plate, and incubate at RT for 1h; Positive sieve incubation: Remove the blocking solution from the positive sieve plate, wash 3 times with 0.1% PBST, transfer the supernatant from the negative sieve plate to the positive sieve wells, and incubate at RT for 1h; Elution: After positive sieve incubation, wash 10 times with 0.1% PBST, add 12ug of cation exchanger for competitive elution, and aspirate the supernatant at RT for 1h; 200uL is added to the shaken SS320, and the cells are incubated at 37°C for 30 min; centrifuge at 3000g for 5 min, discard the excess supernatant, resuspend the cells in the remaining 200uL of liquid, and plate.

[0034] Table 1 Specific selection schemes for the first to third rounds

[0035] 5) Phage Titer Assay: Use pre-prepared SS320 (OD600 approximately 0.5) as the solution for serial dilution of the sample. Use a 96-well dilution plate, starting with a 10-fold dilution, and then successively using the next higher-order 10-fold dilution. Generally, dilute to a gradient of 10-12. Incubate at 37°C for 30 min. Spotting: Use a multi-channel pipette to spot 2 μL of diluted sample onto the plate at intervals according to the sample's resistance. Incubate overnight at 37°C. Count the phages the following day.

[0036] 6) Initial screening of single clones: Select single clones for initial screening and incubate overnight at 37°C with shaking at 220 rpm using 700 μL / well 2YT medium (containing A+, T+, K+, M13K07). Coat 96-well microplates with 1 μg / ml hTL1A-His (100 μL / well) and negative screening plates with 1% BSA overnight at 4°C. Remove the supernatant from the coated plates, wash three times with 0.05% PBST (using a plate washer), spin dry, and block the coated 96-well microplates at room temperature for 1 hour with 200 μL / well 1% BSA. Remove the blocking solution, wash three times with 0.05% PBST (using a plate washer), add 50 μL of phage supernatant and 50 μL of 1% BSA to each well, add 100 μL of positivor (1 μg / mL) to E12 / F12 and 100 μL of antagonist (1 μg / mL) to G12 / H12 of each plate, and incubate at room temperature for 1 h. Remove the phage supernatant, wash three times with 0.05% PBST (using a plate washer), dry, and add secondary antibody. For wells containing phage supernatant, add 100 μL of Anti-M13-HRP (1:10000) per well; for wells containing positive and negative controls, add 100 μL of Anti-human-Fc-HRP (1:5000) per well. Incubate at room temperature for 45 min. Remove the secondary antibody, wash six times with 0.05% PBST (using a plate washer), dry, add 100 μL of TMB chromogenic buffer per well, and incubate for 5-10 min. Add 100 μL of stop solution per well. Analyze the OD450 values ​​using a microplate reader and examine the experimental data (Table 2 shows the results of the three rounds of panning for single-clone ELISA). The third round of panning yielded 11 positive clones. These positive clones were sequenced, and after removing repetitive sequences, antibody sequences from 5 positive clones were obtained. The positive clone antibodies were expressed for subsequent functional validation experiments.

[0037] Table 2 Results of the three rounds of single-clone ELISA screening

[0038] 7) FACS blocking assay: A DR3 overexpression vector plasmid was constructed, lentivirus was packaged in 293T cells, and the viral supernatant was collected by filtration. HEK-293-NFκB cells were then infected, and puromycin was added to select positive cells. HEK293-DR3-NFκB-luc cells were cultured, and cells were collected and prepared to a concentration of 2E+06 cells / ml using ice-cold MACS buffer. 50 μL of cell suspension was added to each well of a 96-well plate. A 4-fold concentration antibody solution (200 nM) and a 4-fold concentration TL1A solution (2 μg / ml) were prepared using MACS buffer. 25 μL of TL1A diluent and antibody diluent were added to the designated wells of the 96-well plate, mixed thoroughly, and a positive control PC (Anti-Human TL1A, Afimkibart) and an isotype control were added. The plate was incubated at 4°C in the dark for 60 min. Wash three times with MACS buffer, resuspend the cells in 100 μL of fluorescent secondary antibody (1:500), and incubate at 4°C in the dark for 30 min. Wash three times with MACS buffer, resuspend the cells in 200 μL of MACS buffer, and perform flow cytometry for measurement and data analysis.

[0039] Table 3 shows the data on the blocking effect of TL1A antibody on DR3 overexpressing cell lines. The results are as follows: Figure 2 As shown, antibody 08 (TL1A) exhibited significant blocking activity in DR3-overexpressing cells, demonstrating its excellent blocking function.

[0040] Table 3 IC50 values ​​for FACS blocking detection

[0041] The anti-TL1A fully human antibody, designated TL1A-08, comprises a heavy chain variable region and a light chain variable region. The heavy chain variable region contains three complementarity-determining regions (CDRs): CDR-H1, CDR-H2, and CDR-H3. The light chain variable region contains three complementarity-determining regions (CDRs): CDR-L1, CDR-L2, and CDR-L3. The sequence of complementarity-determining region CDR-H1 is shown in SEQ ID NO: 1; the sequence of complementarity-determining region CDR-H2 is shown in SEQ ID NO: 2; the sequence of complementarity-determining region CDR-H3 is shown in SEQ ID NO: 3; the sequence of complementarity-determining region CDR-L1 is shown in SEQ ID NO: 4; the amino acid sequence of complementarity-determining region CDR-L2 is YDS; and the sequence of complementarity-determining region CDR-L3 is shown in SEQ ID NO: 5.

[0042] The amino acid sequence of the heavy chain variable region of the anti-TL1A fully human antibody (TL1A-08) is shown in SEQ ID NO:6, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO:7. The nucleic acid sequence encoding the heavy chain variable region is shown in SEQ ID NO:8, and the nucleic acid sequence encoding the light chain variable region is shown in SEQ ID NO:9.

[0043] The above are merely embodiments of the present invention and do not limit the patent scope of the present invention. Any equivalent modifications made based on the content of the present invention specification, or direct or indirect applications in other related technical fields, are similarly included within the patent protection scope of the present invention.

Claims

1. A fully human antibody against TL1A, characterized in that, The anti-TL1A fully human antibody includes a heavy chain variable region and a light chain variable region; the heavy chain variable region includes three complementarity-determining regions, namely CDR-H1, CDR-H2 and CDR-H3, and the light chain variable region includes three complementarity-determining regions, namely CDR-L1, CDR-L2 and CDR-L3. The amino acid sequence of CDR-H1 is shown in SEQ ID NO:1; The amino acid sequence of the CDR-H2 is shown in SEQ ID NO:2; The amino acid sequence of CDR-H3 is shown in SEQ ID NO:3; The amino acid sequence of CDR-L1 is shown in SEQ ID NO:4; The amino acid sequence of CDR-L2 is YDS; The amino acid sequence of CDR-L3 is shown in SEQ ID NO:

5.

2. The anti-TL1A fully human antibody according to claim 1, characterized in that, The amino acid sequence of the heavy chain variable region of the antibody is as shown in SEQ ID NO:6, or has at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity with SEQ ID NO:

6. The amino acid sequence of the light chain variable region of the antibody is as shown in SEQ ID NO:7, or has at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity with SEQ ID NO:

7.

3. An antibody derivative, characterized in that, The antibody derivative comprises the anti-TL1A fully human antibody of claim 1, comprising three complementary determinant regions of the heavy chain variable region, namely CDR-H1, CDR-H2 and CDR-H3, and three complementary determinant regions of the light chain variable region, namely CDR-L1, CDR-L2 and CDR-L3; or comprises only the three complementary determinant regions of the heavy chain variable region, namely CDR-H1, CDR-H2 and CDR-H3.

4. The antibody derivative according to claim 3, characterized in that, Choose from any of the following forms: (a) A multivalent nanobody comprising two or more identical or different fully human anti-TL1A antibodies; (b) Bispecific or multispecific antibodies; (c) Antibody conjugates; (d) Heavy chain antibodies or their antigen-binding fragments.

5. The nucleic acid encoding the anti-TL1A fully human antibody as described in claim 1 or 2.

6. A biomaterial, characterized in that, The biomaterial includes at least one of the following: (A) A recombinant vector containing the nucleic acid as described in claim 5; (B) A host cell containing the recombinant vector described in (A).

7. The method for preparing the anti-TL1A fully human antibody as described in claim 2, characterized in that, The procedure includes the following steps: RNA is extracted from healthy human PBMCs and reverse transcribed into cDNA. Antibody gene fragments are obtained by PCR and ScFv fragments are constructed. The ScFv fragments, after enzyme digestion, are ligated into a phage expression vector using T4 DNA ligase. The vector containing the antibody gene fragment is electroporated into SS320 competent cells to obtain a fully human antibody library. After three rounds of TL1A solid-phase panning and Clone ELISA detection, positive clones binding to TL1A protein are obtained. Unique sequences are selected after sequencing analysis. Antibody protein is obtained through high-throughput expression using a mammalian cell high-throughput expression system. The antibody binding to TL1A is finally obtained by FACS detection using a TL1A high-expression cell line.

8. A pharmaceutical composition, characterized in that, It contains the anti-TL1A fully human antibody as described in claim 1 or 2, the antibody derivative as described in claim 3, the nucleic acid as described in claim 5, or the biological material as described in claim 6, and a pharmaceutically acceptable carrier.

9. Products or kits containing the anti-TL1A fully human antibody as described in claim 1 or 2, the antibody derivative as described in claim 3, the nucleic acid as described in claim 5, or the biological material as described in claim 6.

10. The use of the anti-TL1A fully human antibody as described in claim 1 or 2, the antibody derivative as described in claim 3, the nucleic acid as described in claim 5, or the biomaterial as described in claim 6 in the preparation of drugs for treating various inflammatory injuries, autoimmune diseases, tumor immunotherapy, and anti-aging.

11. The application of the anti-TL1A fully human antibody as described in claim 1 or 2, the antibody derivative as described in claim 3, the nucleic acid as described in claim 5, or the biomaterial as described in claim 6 in the preparation of products for detecting TL1A.

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