Anti-il1RAP antibody and use thereof

Abstract

A novel antibody and antibody fragment specifically binding to IL1RAP, and a composition containing the antibody or the antibody fragment. A nucleic acid encoding the antibody or the antibody fragment thereof, a host cell comprising the nucleic acid, and a related use. A therapeutic and diagnostic use of the antibody and the antibody fragment.

Description

CROSS REFERENCE TO RELATED APPLICATIONS This application is based on and claims priority to Chinese Patent Application No. 202410396541.4, filed on April 2, 2024, the contents of which are incorporated herein by reference in their entirety. The present disclosure relates to a novel antibody and an antibody fragment that specifically bind to IL1RAP and a composition comprising the antibody or the antibody fragment. In addition, the present disclosure relates to a nucleic acid encoding the antibody or the antibody fragment thereof, and a host cell comprising the same, and related use. In addition, the present disclosure relates to therapeutic and diagnostic uses of the antibodies and the antibody fragments. BACKGROUND OF THE INVENTION The suppression of inflammatory cytokine function is the basis of many clinical interventions. Several members of the IL-1 family play important roles in a variety of diseases, such as IL-1B in gout, IL-33 in asthma, and IL-1a and IL-36 in psoriasis. Therefore, blocking the pathways of cytokines and inflammation driven by specific diseases may improve the therapeutic effect on diseases. The IL-1 family consists of 20 members, including 11 ligands and 9 receptors, and plays an important role in innate immunity and acquired immunity. Wherein IL-1R1 binds to IL-1a and IL-1p and recruits IL-1R3 to form a trimeric signal complex; IL-1R4 (ST2) binds to IL-33, and forms a trimeric complex with IL-1R3; and IL-1R6 binds to IL-36a, IL-36P, and IL-36Y and recruits IL-1R3 likewise to form a trimeric complex. In the three different signaling pathways of IL1, IL33, and IL36, IL-1R3, as a co-receptor, forms receptor complexes with receptors specific for the respective pathways, thereby dimerizing cytoplasmic Toll / IL-1R domains and then triggering the activation of downstream signaling pathways to mediate specific immune responses. IL-1R3, also known as interleukin 1 receptor accessory protein (IL1RAP), is an accessory receptor for the type 1 interleukin 1 receptor (IL1R1), and is essential for IL-1 signaling. IL-1R3 mediates the signaling of six different cytokines and plays an important role in a variety of inflammatory and autoimmune diseases, including IL-1R3-dependent cytokine-induced inflammation, type 1 helper T cell (TH1) response, type 2 helper T cell (TH2) response, or a combination of inflammation with TH1 or TH2 response. Therefore, blocking a common co-receptor, rather than a single primary receptor or ligand, may provide a new mode of action for reducing associated disease. An antibody against IL1RAP can specifically bind to IL1RAP, thereby blocking recruitment of IL1RAP by IL1R1, and further inhibiting activation of the NF-kB pathway by cytokines such as IL1. The IL-1 pathway plays an important role in a variety of autoimmune diseases and autoinflammatory diseases, including diseases such as rheumatoid arthritis, gout, Still's disease, and cryopyrin-associated periodic syndrome (CAPS). Blocking the IL-1 pathway can effectively alleviate the symptoms of these diseases. IL-1 inhibitors that have been approved for marketing at present mainly include IL-1R antagonist Anakinra (Kineret), IL-1B monoclonal antibody Canakinumab (Ilaris), and IL-1 cytokine Trap, i.e., IL-1R1 / IL-1RAP extracellular domain fusion protein Rilonacept (Arcalyst). These drugs have shown good therapeutic effects in diseases such as rheumatoid arthritis, CAPS, and familial Mediterranean fever (FMF), and have been approved for marketing. However, all of these drugs have different defects. For example, Anakinra has a molecular weight of only 16.7 Kd and a half-life of only 4-6 hours, so it needs to be taken daily; canakinumab can only block IL-1B but not IL-1a, so it may not show good effect on IL-1a-mediated diseases. Therefore, there is a need in the present disclosure for new antibodies targeting IL1RAP that can overcome the deficiencies of existing drugs. SUMMARY OF THE INVENTION The present disclosure provides a novel antibody that recognizes IL1RAP, which selectively blocks the IL1RAP-related signaling pathway. In some embodiments, the present disclosure provides a novel monoclonal antibody targeting IL-1RAP, which has the characteristic of a long half-life of the monoclonal antibody and can block both IL-1a and IL-1B cytokines, thereby making up for the deficiencies of the drugs known in the prior art. Therefore, the present disclosure relates to an antibody or fragment, e.g., an antigen binding fragment, that specifically binds to IL1RAP, e.g., human IL1RAP. In some embodiments, the antibody or the antigen-binding fragment thereof of the present disclosure binds to human IL1RAP with a KD less than about 2 nM, 1.5 nM, 1.4 nM, 1.35 nM, 1.3 nM, 1.25 nM, 1.2 nM, 1.15 nM, 1.1 nM, 1.05 nM, 1 nM, 0.95 nM, 0.9 nM, 0.85 nM, 0.8 nM, 0.75 nM, 0.7 nM, 0.65 nM, 0.6 nM, 0.55 nM, 0.5 nM, 0.45 nM, or 0.4 nM, or greater than about 0.1 nM or 0.2 nM, or within any numerical range. In some embodiments, said KD is between 0.4 nM and 1.35 nM. In some embodiments, the binding affinity of an antigen to an antibody is determined by ForteBio. The antibody or the antigen-binding fragment thereof of the present disclosure can effectively block the binding of IL1a, ILip, IL33, and IL36 to the IL1RAP receptor complex, thereby relieving the inhibition on the downstream NF-kB signaling pathway. In some embodiments, the antibody or the antigen-binding fragment thereof disclosed herein can effectively block IL1p-mediated activation of downstream signaling pathways. In some embodiments, the antibody or the antigen-binding fragment thereof disclosed herein effectively blocks IL36-mediated activation of downstream signaling pathways. In some embodiments, the antibody or the antigen-binding fragment thereof of the present disclosure effectively blocks IL33-mediated activation of downstream signaling pathways. In some embodiments, the antibody or the antigen-binding fragment thereof of the present disclosure effectively blocks IL36-mediated activation of downstream signaling pathways, e.g., in epithelial cells. In some embodiments, the antibody or the antigen-binding fragment thereof disclosed herein potently inhibits the IL-1, IL-36, and / or IL33 signaling pathway, e.g., in PBMC cells. In some embodiments, the antibody or the antigen-binding fragment thereof of the present disclosure has good pharmacokinetic characteristics in vivo, e.g., good stability, and / or a long half-life. In some embodiments, the antibody or the antigen-binding fragment thereof disclosed herein has a half-life of greater than about 300 h, 305 h, 310 h, or 315 h, e.g., about 316 h, when administered (e.g., by subcutaneous injection). In some embodiments, the antibody or the antigen-binding fragment thereof disclosed herein has a half-life of greater than about 175 h, 180 h, 185 h, or 190 h, e.g., about 192 h, upon administration (e.g., intravenous administration). In some embodiments, the antibody or the antigen-binding fragment thereof of the present disclosure has good pharmacokinetic characteristics, e.g., good colloidal stability, good solubility, and / or good thermal stability. In some embodiments, the antibody or the antigen-binding fragment thereof disclosed herein can effectively prevent or treat inflammation, e.g., abdominal inflammation such as peritonitis (e.g., acute peritonitis), gout (e.g., acute gout), and / or skin inflammation (e.g., dermatitis and psoriasis). In some embodiments, the antibody or the antigen-binding fragment thereof disclosed herein can effectively alleviate abdominal inflammation, e.g., reduce inflammatory cell recruitment in the abdominal cavity, and / or reduce the number of neutrophils and / or monocytes for infiltration. In some embodiments, the antibody or the antigen-binding fragment thereof of the present disclosure can effectively alleviate the gout attack and / or inhibit the paw thickening, and optionally also reduce the production of inflammatory factors in the paw tissue. In some embodiments, the antibody or the antigen-binding fragment thereof disclosed herein can effectively inhibit skin inflammation (e.g., dermatitis), e.g., reduce skin thickness. Accordingly, the present disclosure relates to the following specific aspects. In some aspects, the present disclosure relates to an anti-IL1RAP antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises: three complementarity determining regions HCDR1, HCDR2 and HCDR3 contained in the VH set forth in any one of SEQ ID NOs: 13 to 17, and three complementarity determining regions LCDR1, LCDR2 and LCDR3 contained in the VL set forth in any one of SEQ ID NOs: 23 to 25. In some aspects, the present disclosure relates to an anti-IL1RAP antibody or an antigen-binding fragment thereof, which comprises a first heavy chain complementarity determining region (HCDR1), a second heavy chain complementarity determining region (HCDR2), a third heavy chain complementarity determining region (HCDR3), and a first light chain complementarity determining region (LCDR1), a second light chain complementarity determining region (LCDR2), and a third light chain complementarity determining region (LCDR3), wherein the HCDR1, the HCDR2, the HCDR3, the LCDR1, the LCDR2, and the LCDR3 comprise or consist of amino acid sequences set forth in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. In some embodiments, the anti-IL1RAP antibody or the antigen-binding fragment thereof of the present disclosure comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises or consists of an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence selected from any one of SEQ ID NOs: 13 to 17; or comprises or consists of the amino acid sequence selected from any one of SEQ ID NOs: 13 to 17. In some embodiments, the anti-IL1RAP antibody or the antigen-binding fragment thereof of the present disclosure comprises a light chain variable region (VL), wherein the light chain variable region comprises or consists of an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence selected from any one of SEQ ID NOs: 23 to 25; or comprises or consists of the amino acid sequence selected from any one of SEQ ID NOs: 23 to 25. In some embodiments, the anti-IL1RAP antibody or the antigen-binding fragment thereof comprises (i)      the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO: 13, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto; and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 23, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto; (ii)      the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO: 14 or 15, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto; and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 24, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto; or (iii)     the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO: 16 or 17, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto; and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 25, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto. In some embodiments, the anti-IL1RAP antibody or antigen-binding fragment thereof of the present disclosure comprises a heavy chain variable region and a light chain variable region, wherein (i)      the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 16 or 17 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 25; (ii)      the heavy chain variable region consists of the amino acid sequence set forth in SEQ ID NO: 16 or 17 and the light chain variable region consists of the amino acid sequence set forth in SEQ ID NO: 25; (iii)     the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 13 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 23; (iv)     the heavy chain variable region consists of the amino acid sequence set forth in SEQ ID NO: 13 and the light chain variable region consists of the amino acid sequence set forth in SEQ ID NO: 23; (v)      the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 14 or 15 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 24; or (vi)     the heavy chain variable region consists of the amino acid sequence set forth in SEQ ID NO: 14 or 15 and the light chain variable region consists of the amino acid sequence set forth in SEQ ID NO: 24. In some embodiments, the anti-IL1RAP antibody or the antigen-binding fragment thereof of the present disclosure comprises an Fc region, e.g., the Fc region is derived from an Fc region of IgG1, IgG2, IgG3, or IgG4, e.g., an Fc region of human IgG1, IgG2, IgG3, or IgG4. In some embodiments, the anti-IL1RAP antibody or the antigen-binding fragment thereof of the present disclosure comprises a heavy chain constant region, wherein the heavy chain constant region is derived from a constant region of IgG1, IgG2, IgG3, or IgG4, e.g., a constant region of human IgG1, IgG2, IgG3, or IgG4, for example, the heavy chain constant region of IgG1 (i)       comprises or consists of the amino acid sequence set forth in SEQ ID NO: 50; or (ii)     comprises an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence set forth in SEQ ID NO: 50. In some embodiments, the heavy chain constant region or Fc region of the present disclosure lacks C-terminal lysine. In some embodiments, the heavy chain constant region or the Fc region of the present disclosure comprises a mutation that has reduced binding to an Fcy receptor, e.g., an L234A / L235A mutation and / or a P329G mutation, e.g., an L234A / L235A mutation, or an L234A / L235A mutation and a P329G mutation. In some embodiments, the heavy chain constant region (i) comprises or consists of the amino acid sequence selected from SEQ ID NO: 51 or 52; (ii)     comprises an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence set forth in SEQ ID NO: 51, and comprises a L234A / L235A mutation; or (iii)     comprises an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence set forth in SEQ ID NO: 52, and comprises a L234A / L235A mutation and a P329G mutation. In some embodiments, the anti-IL1RAP antibody or antigen-binding fragment thereof of the present disclosure comprises a light chain constant region, which is a Lambda or Kappa light chain constant region, for example a human Lambda or Kappa light chain constant region. In some embodiments, the light chain constant region (i)      comprises or consists of an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence set forth in SEQ ID NO: 53; or (ii)      comprises or consists of the amino acid sequence set forth in SEQ ID NO: 53. In some embodiments, the anti-IL1RAP antibody or antigen-binding fragment thereof of the present disclosure comprises a heavy chain, wherein the heavy chain (i)      comprises or consists of an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence selected from any one of SEQ ID NO: 32-36; or (ii)      comprises or consists of the amino acid sequence selected from any one of SEQ ID NOs:32-36. In some embodiments, the anti-IL1RAP antibody or antigen-binding fragment thereof of the present disclosure comprises a light chain, wherein the light chain (i)      comprises or consists of an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence selected from any one of SEQ ID NOs: 42-44; or (ii) comprises or consists of the amino acid sequence selected from any one of SEQ ID NOs: 42-44. In some embodiments, provided is the anti-IL1RAP antibody or the antigen-binding fragment thereof of the present disclosure, which comprises a heavy chain and a light chain, wherein (i) the heavy chain comprises or consists of an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence set forth in SEQ ID NO: 32, and the light chain comprises or consists of an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence set forth in SEQ ID NO: 42; (ii) The heavy chain comprises or consists of an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence set forth in SEQ ID NO: 33 or 34, and the light chain comprises or consists of an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence set forth in SEQ ID NO: 43; or (iii)     The heavy chain comprises or consists of an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence set forth in SEQ ID NO: 35 or 36, and the light chain comprises or consists of an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence set forth in SEQ ID NO: 44. In some embodiments, the anti-IL1RAP antibody or antigen-binding fragment thereof of the present disclosure comprises heavy and light chains, wherein (i)      The heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 35 or 36, and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 44; (ii) the heavy chain consists of the amino acid sequence set forth in SEQ ID NO: 35 or 36, and the light chain consists of the amino acid sequence set forth in SEQ ID NO: 44; (iii) The heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 32, and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 42; (iv) the heavy chain consists of the amino acid sequence set forth in SEQ ID NO: 32, and the light chain consists of the amino acid sequence set forth in SEQ ID NO: 42; (v)     The heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 33 or 34, and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 43; or (vi) the heavy chain consists of the amino acid sequence set forth in SEQ ID NO: 33 or 34, and the light chain consists of the amino acid sequence set forth in SEQ ID NO: 43. In some embodiments, the anti-IL1RAP antibody of the present disclosure is a monoclonal antibody. In some embodiments, the anti-IL1RAP antibody of the present disclosure is a humanized antibody or a chimeric antibody. In some embodiments, the antigen-binding fragment of the anti-IL1RAP antibody of the invention is the antibody fragment selected from the group consisting of: Fab, Fab', Fab'-SH, Fv, single-chain antibody (e.g., scFv), (Fab')2, single-domain antibody (e.g., VHH), domain antibody (dAb), bivalent antibody, or linear antibody. In some aspects, the present disclosure relates to an isolated nucleic acid encoding the anti-IL1RAP antibody or the antigen-binding fragment thereof of the present disclosure. In some aspects, the present disclosure relates to a vector comprising the nucleic acid of the present disclosure, preferably the vector is an expression vector. In some aspects, the present disclosure relates to a host cell comprising the nucleic acid or vector of the present disclosure, wherein preferably, the host cell is prokaryotic or eukaryotic, and more preferably, the host cell is selected from the group consisting of yeast cells, mammalian cells (e.g., 293 cells or CHO cells, such as CHO-K cells or HEK293 cells), or other cells suitable for preparing an antibody or an antigen-binding fragment thereof. In some aspects, the present disclosure relates to a method of preparing an anti-IL1RAP antibody or antigen-binding fragment thereof comprising: a) culturing the host cell of the present disclosure under conditions suitable for expression of a nucleic acid encoding the anti-IL1RAP antibody or the antigen-binding fragment thereof of the present disclosure, b) optionally isolating the antibody or antigen-binding fragment thereof, c) optionally the method further comprises recovering the anti-IL1RAP antibody or antigen binding fragment thereof from the host cell, optionally the antibody is purified, e.g., by ProteinA. In some aspects, the present disclosure relates to an immunoconjugate comprising the anti-IL1RAP antibody or the antigen-binding fragment thereof of the present disclosure and an additional substance, e.g., a chemotherapeutic agent, a toxin, a small molecule drug, a cytotoxic agent, an apoptotic agent, a chelating agent, or an immunomodulatory agent, e.g., an immunosuppressive agent. In some aspects, the present disclosure relates to a pharmaceutical composition comprising the anti-IL1RAP antibody or the antigen-binding fragment thereof, or the immunoconjugate of the present disclosure, and optionally a pharmaceutically acceptable auxiliary material. In some aspects, the present disclosure relates to a pharmaceutical combination product comprising the anti-IL1RAP antibody or the antigen-binding fragment thereof or the immunoconjugate of the present disclosure, and one or more additional therapeutic agents. For example, the therapeutic agent is suitable for treating inflammation, e.g., the therapeutic agent is selected from the group consisting of a cytokine, another antibody, a small molecule drug, or an immunomodulatory agent (e.g., an immunosuppressive agent). In some aspects, the present disclosure relates to a method for preventing or treating a disease or disorder related to inappropriate activation of a pathway mediated by IL1RAP receptor complex in an individual, which comprises administering to the subject an effective amount of the antibody or the antigen binding fragment thereof that binds to IL1RAP, or the immunoconjugate, or the pharmaceutical composition, or the pharmaceutical combination product of the present disclosure. In some embodiments, the subject has abnormal activation of an IL1RAP receptor complex-mediated signaling pathway as compared to a healthy individual. In some embodiments, the disease or disorder is selected from a tumor such as a cancer, or an inflammation, e.g., an abdominal inflammation such as peritonitis (e.g., acute peritonitis), gout (e.g., acute gout), and / or a skin inflammation (e.g., dermatitis). In some embodiments, the method further comprises administering one or more additional therapies (e.g., therapeutic modalities and / or additional therapeutic agents). For example, the therapeutic agent is suitable for treating inflammation and is, e.g., selected from the group consisting of cytokines, other antibodies, small molecule drugs, and immunomodulatory agents (e.g., immunosuppressive agents). Description of the Drawings: FIG. 1 shows the binding of the chimeric antibody and the humanized antibody to CHO-hIL1RAP cells. FIG. 2 shows the inhibitory activity of the humanized antibodies in the IL-1 fluorescent reporter cell line. FIG. 3 shows the inhibitory activity of the humanized antibodies in the IL-36 fluorescent reporter cell line. FIG. 4 shows the inhibitory activity of the humanized antibodies in the IL-33 fluorescent reporter cell line. FIG. 5 shows the inhibitory activity of the chimeric antibodies and the humanized antibodies against the IL36 pathway in a human squamous cell carcinoma cell line A431. FIG. 6 shows the inhibitory activity of the chimeric antibodies and the humanized antibodies against the IL1 pathway in PBMCs. FIG. 7 shows the inhibitory activity of the chimeric antibodies and the humanized antibodies against the IL36 pathway in PBMCs. FIG. 8 shows the inhibitory activity of the chimeric antibodies and the humanized antibodies against the IL33 pathway in PBMCs. FIG. 9 shows the results of verifying the biological activity of the antibodies on the IL1 pathway in a mouse acute peritonitis model. FIG. 10 shows the results of verifying the biological activity of the antibodies on IL1 pathway in a mouse acute gout model. FIG. 11 shows the verification of the biological activity of the antibodies on the IL36 pathway in a mouse ear dermatitis model. DETAILED DESCRIPTION OF THE INVENTION Before the present disclosure is described in detail below, it is to be understood that the present disclosure is not limited to the particular methodology, protocols, and reagents described herein, as these may vary. I. Definitions It should be understood that the terminology used herein is only intended to describe specific embodiments rather than limit the scope of the present disclosure, which will be limited only by the appended claims. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which the present disclosure belongs. For the purpose of explaining this specification, the following definitions will be used, and wherever appropriate, terms used in the singular form may also include the plural form, and vice versa. It should be understood that the terms used herein are for the purpose of describing particular embodiments only, and are not limiting. The term "about", when used in combination with a numerical value, is intended to encompass the numerical values in a range from a lower limit less than the specified numerical value by 5% (e.g., 4%, 3%, 2%, or 1%) to an upper limit greater than the specified numerical value by 5% (e.g., 4%, 3%, 2%, or 1%). As used herein, the term "and / or" refers to any one of the options or any two or more or all of the options. As used herein, the term "comprise" or "include" is intended to include the described elements, integers or steps, but not to exclude any other elements, integers or steps. The term "comprise" or "include", unless indicated otherwise, also encompasses the situation where the entirety consists of the described elements, integers or steps. For example, when referring to an antibody variable region "comprising" a particular sequence, it is also intended to encompass an antibody variable region consisting of the particular sequence. An "isolated" antibody or molecule is one that has been isolated from a component of its natural environment. In some embodiments, the antibody or molecule is purified to achieve a purity greater than 95% or 99% as determined, for example, by electrophoresis (e.g., SDS-PAGE, Isoelectric focusing (IEF), capillary electrophoresis) or chromatography (e.g., ion exchange or reverse phase HPLC). As used herein, "IL1RAP" refers to any native IL1RAP polypeptide (e.g., human IL1RAP polypeptide) or variant thereof. The term "IL1RAP" encompasses "full-length" unprocessed IL1RAP polypeptides as well as any form of IL1RAP polypeptide that results from processing in the cell. The term also encompasses naturally occurring variants of IL1RAP, e.g., those encoded by splice variants and allelic variants. The IL1RAP polypeptide described herein can be isolated from a variety of sources, such as from human or from another source, e.g., cynomolgus monkey, or prepared by recombinant or synthetic methods. In one embodiment of the present disclosure, the human IL1RAP protein is as shown in Uniprot, Q9NPH3. In one embodiment, the human IL1RAP gene is as shown in NCBI Gene ID: 3556. In one embodiment of the present disclosure, the cynomolgus monkey IL1RAP protein is as shown in Uniprot, G7NYP7. The terms "whole antibody" and "full-length antibody" are used interchangeably herein to refer to an antibody molecule having the structure of a native immunoglobulin molecule. In the case of a conventional four-chain IgG antibody, the full-length antibody comprises two heavy chains (H) and two light chains (L) interconnected by disulfide bonds. In the case of a heavy chain antibody having only heavy chains and lacking light chains, the full-length antibody comprises two heavy chains (H) interconnected by disulfide bonds. For the conventional four-chain IgG antibody, the full-length antibody heavy chain generally consists of a heavy chain variable region (abbreviated herein as VH) and a heavy chain constant region, wherein the heavy chain constant region comprises at least 3 domains CH1, CH2, and CH3 (optionally also comprising CH4). The full-length antibody light chain consists of a light chain variable region (abbreviated herein as VL) and a light chain constant region, wherein the light chain constant region consists of one domain CL. Each heavy chain variable region VH and each light chain variable region consists of three CDRs and 4 FRs, arranged from amino-terminus to carboxyl-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4. The term "antibody fragment" includes a portion of an intact antibody. In a preferred embodiment, the antibody fragment is an antigen-binding fragment. The term "antigen-binding fragment" of an antibody is a molecule different from a full-length antibody, which comprises a portion of the full-length antibody, but is capable of binding to an antigen of the full-length antibody or competes with the full-length antibody (i.e., a full-length antibody from which the antigen-binding fragment is derived) for binding to an antigen. An antigen-binding fragment can be prepared by recombinant DNA techniques, or by enzymatic or chemical cleavage of an intact antibody. Examples of the antigen-binding fragment include, but are not limited to, Fv, Fab, Fab', Fab'-SH, F(ab')2, dAb (domain antibody), linear antibody, single-chain antibody (e.g., scFv), single-domain antibody such as VHH, bivalent antibody or a fragment thereof, camelid antibody, diabody, single-domain antibody (sdAb), or nanobody. For example, an Fab fragment can be obtained by papain digestion of a full-length antibody. In addition, F(ab')2, a dimer of Fab', is a bivalent antibody fragment produced by pepsin digestion of a portion below disulfide bonds in a hinge region of a complete antibody. F(ab')2 can be reduced by disrupting the disulfide bond in the hinge region under neutral conditions, thereby converting the F(ab')2 dimer into an Fab' monomer. The Fab' monomer is essentially an Fab fragment with a hinge region. The Fv fragment consists of the VL and VH domains of a single arm of an antibody. The two domains VL and VH of the Fv fragment can be encoded by separate genes, but the two domains can also be linked, using recombinant methods, by a synthetic linking peptide so that they are produced as a single protein chain in which the VL and VH regions pair to form a single-chain Fv (scFv). The term "single-chain antibody (scAb)" is used herein in the broadest sense and specifically covers antibodies with monospecificity or multispecificity (e.g., bispecificity) that are initially produced as a single continuous polypeptide chain. Such single chain antibodies include, but are not limited to, those having two linked VL and VH regions. In one embodiment, the single chain antibody is a scFv. A "diabody" is a bivalent small antibody constructed by gene fusion, e.g., a dimer consisting of two polypeptide chains. The VL and VH domains of each polypeptide chain of the diabody are joined by a linker, thereby encoding the VL and VH in the same polypeptide chain to form a dimer having different single-chain variable region fragments. Diabodies generally have two antigen-binding sites. A “complementarity determining region” or "CDR region” or "CDR” is a region of an antibody variable domain that is highly variable in sequence and forms a structurally defined loop ("hypervariable loop") and / or includes an antigencontact residue ("antigencontact point"). The CDRs are primarily responsible for binding to antigenic epitopes. The CDRs of the heavy and light chains are generally referred to as CDR1, CDR2 and CDR3, and are numbered sequentially from the N-terminus. The CDRs located in the heavy chain variable domain of an antibody are referred to as HCDR1, HCDR2 and HCDR3, and the CDRs located in the light chain variable domain of an antibody are referred to as LCDR1, LCDR2 and LCDR3. In a given amino acid sequence of a light chain variable region or a heavy chain variable region, the exact amino acid sequence boundary of each CDR can be determined using any one or a combination of many well-known antibody CDR assignment schemes including, for example, Chothia based on the three-dimensional structure of antibodies and the topology of the CDR loops (Chothia et al. (1989) Nature 342: 877-883, Al-Lazikani et al., "Standard conformations for the canonical structures of immunoglobulins", Journal of Molecular Biology, 273, 927-948 (1997)); Kabat based on antibody sequence variability (Kabat et al., Sequences of Proteins of Immunological Interest, 4th Ed., U.S. Department of Health and Human Services, National Institutes of Health (1987)); AbM (University of Bath), Contact (University College London), International ImMunoGeneTics database (IMGT) (on www.imgt.cines.fr / ), and North CDR definition based on the affinity propagation clustering using a large number of crystal structures. The following is an exemplary scheme for the region ranges of CDRs defined using the Kabat, AbM, Chothia, Contact, and IMGT schemes. CDR Kabat scheme Chothia Protocol Kabat&Chothia LCDR1 L24-L34 L26-L32 LCDR2 L50-L56 L50-L52 LCDR3 L89-L97 L91-L96 HCDR1 H31-H35 H26-H32 H26-H35 HCDR2 H50-H65 H53-H55 HCDR3 H95-H102 H96-H101 Unless otherwise indicated, in the present disclosure, the term "CDR" or "CDR sequence" encompasses CDR sequences determined in any of the ways or their combinations described above. Additionally, the CDR can also be determined based on the same Kabat numbered positions as the reference CDR sequence (e.g., any of the exemplary CDRs of the present disclosure). Unless otherwise stated, in the present disclosure, when referring to residue positions in an antibody variable region (including heavy chain variable region residues and light chain variable region residues), it means numbered positions 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)). In some embodiments, in the heavy chain variable region of the antibody of the present disclosure, CDR1 is determined according to the Kabat & chothia scheme, and CDR2 and CDR3 are determined according to the Kabat scheme, respectively. In some embodiments, the CDRs of the light chain variable region of the antibodies of the present disclosure are respectively determined according to the Kabat scheme. In some embodiments, for the antibody of the present disclosure HCDR1 is determined according to the Kabat & chothia scheme, and HCDR2 and HCDR3 are determined according to the Kabat scheme, respectively; LCDR1, LCDR2, and LCDR3 are determined according to the Kabat scheme, respectively. The "antibody that binds to the same or overlapping epitope" as a reference antibody refers to an antibody that blocks 50%, 60%, 70%, 80%, 90%, or 95% or more of the binding of the reference antibody to its antigen in a competition assay. Conversely, the reference antibody blocks 50%, 60%, 70%, 80%, 90%, or 95% or more of the binding of the antibody to its antigen in a competition assay. An antibody that competes with a reference antibody for binding to an its antigen refers to an antibody that blocks 50%, 60%, 70%, 80%, 90%, or 95% or more of the binding of the reference antibody to the its antigen in a competition assay. Conversely, the reference antibody blocks 50%, 60%, 70%, 80%, 90%, or 95% or more of the binding of the antibody to its antigen in a competition assay. Numerous types of competitive binding assays can be used to determine whether an antibody competes with another, for example: solid-phase direct or indirect radioimmunoassay (RIA), solid-phase direct or indirect enzyme immunoassay (EIA), and sandwich competition assay. An antibody that inhibits (e.g., competitively inhibits) the binding of a reference antibody to its antigen refers to an antibody that inhibits 50%, 60%, 70%, 80%, 90%, or 95% or more of the binding of the reference antibody to its antigen. Conversely, the reference antibody inhibits 50%, 60%, 70%, 80%, 90%, or 95% or more of the binding of the antibody to its antigen. The binding of an antibody to its antigen can be measured by affinity (e.g., equilibrium dissociation constant). Methods to determine affinity are known in the art. An antibody that shows the same or similar binding affinity and / or specificity as a reference antibody refers to an antibody that can have at least 50%, 60%, 70%, 80%, 90%, or 95% or more of the binding affinity and / or specificity of the reference antibody. This can be determined by any method known in the art for determining binding affinity and / or specificity. The term "chimeric antibody" is an antibody molecule in which: (a) a constant region or a portion thereof is modified, replaced, or exchanged such that antigen-binding sites are linked to constant regions of different or modified classes, effector functions, and / or species, or disparate molecules imparting new properties (e.g., enzymes, toxins, hormones, growth factors, and drugs) to chimeric antibodies, etc.; or (b) a variable region or a portion thereof is modified, replaced, or exchanged by variable regions with different or modified antigen-binding specificities. For example, a mouse antibody can be modified by replacing its constant region with a constant region from a human immunoglobulin. Due to the replacement with a human constant region, the chimeric antibody can retain its specificity for recognizing antigens, while having reduced immunogenicity in humans as compared to the original mouse antibody. A "humanized antibody" is an antibody that retains the antigen-specific reactivity of a non-human antibody (e.g., a mouse monoclonal antibody) and is less immunogenic, e.g., when administered to humans as a therapeutic agent. This can be achieved, for example, by retaining non-human antigen-binding sites and substituting the remainder of the antibodies with their human counterparts (i.e., the portions of the constant and variable regions not involved in binding are replaced with the corresponding parts of human antibodies). The term "Fc domain" or "Fc region" is used herein to define a C-terminus region of an immunoglobulin heavy chain, which comprises at least a portion of a constant region. This term includes native sequence Fc regions and variant Fc regions. A native immunoglobulin "Fc domain" comprises two or three constant domains, i.e., a CH2 domain, a CH3 domain, and an optional CH4 domain. For example, in native antibodies, an immunoglobulin Fc domain comprises the second and the third constant domains (CH2 domain and CH3 domain) derived from two heavy chains of antibodies of IgG, IgA, and IgD types; or comprises the second, the third and the fourth constant domains (CH2 domain, CH3 domain, and CH4 domain) derived from two heavy chains of antibodies of IgM and IgE types. Unless otherwise stated herein, amino acid residues in Fc regions or heavy chain constant regions are numbered according to the EU numbering scheme (also known as the EU Index) described in, for example, Kabat et al., Sequences of Proteins of Immunological Interests, 5th Ed., Public Health Service, National Institutes of Health, Bethesda, MD, 1991. "Conservative changes" as described herein include replacements of, deletions of, or additions to a polypeptide sequence that do not substantially change the desired functional activity of the polypeptide sequence. In some embodiments, a conservative change is a conservative replacement. A conservative replacement refers to the replacement of an amino acid by another amino acid of the same class, for example, the replacement of an acidic amino acid by another acidic amino acid, the replacement of a basic amino acid by another basic amino acid, or the replacement of a neutral amino acid by another neutral amino acid. For example, conservative replacements often result in the replacement of an amino acid with a chemically similar amino acid. The table of conservative replacements for functionally similar amino acids is well-known in the art. The following lists 8 groups of amino acids that contain conservative replacements for each other: 1) alanine (A) and glycine (G); 2) aspartic acid (D) and glutamic acid (E); 3) asparagine (N) and glutamine (Q); 4) arginine (R) and lysine (K); 5) isoleucine (I), leucine (L), methionine (M), and valine (V); 6) phenylalanine (F), tyrosine (Y), and tryptophan (W); 7) serine (S) and threonine (T); and 8) cysteine (C) and methionine (M). In some embodiments, the term "conservative change", when applied to the amino acid sequence of an antibody molecule, refers to an amino acid modification that does not significantly affect or change the binding characteristics for an antigen of interest of the antibody molecule of the present disclosure comprising the amino acid sequence. For example, the variant with conservative changes retains at least 80%, 85%, 90%, 95%, 98%, 99% or higher, e.g., 100%-110% or higher, binding affinity for an antigen of interest relative to the parent antibody. The term "vector" used herein refers to a nucleic acid molecule capable of proliferating another nucleic acid to which it is linked. The term includes vectors that serve as self-replicating nucleic acid structures as well as vectors binding to the genome of a host cell into which they have been introduced. Some vectors are capable of directing the expression of a nucleic acid to which they are operably linked. Such vectors are called "expression vectors" herein. An "immunoconjugate" is an antibody conjugated to one or more other substances, including but not limited to labels. In some embodiments, the immunoconjugate encompasses antibody-drug conjugates (ADC). The term "therapeutic agent" described herein encompasses any substance effective in preventing or treating a disease associated with inappropriate activation of pathways mediated by the IL1RAP receptor complex, including cytokines, other antibodies, small molecule drugs, or immunomodulatory agents (e.g., immunosuppressive agents). The term "small molecule drug" refers to an organic compound with low molecular weight capable of modulating biological processes. A "small molecule" is defined as a molecule having a molecular weight of less than 10 kD, typically less than 2 kD, and preferably less than 1 kD. Small molecules include, but are not limited to, inorganic molecules, organic molecules, organic molecules containing inorganic components, molecules containing radioactive atoms, synthetic molecules, peptidomimetics, and antibody mimetics. As therapeutic agents, small molecules may be more permeable to cells, less susceptible to degradation, and less likely to elicit an immune response than large molecules. The term "immunomodulator" as used herein refers to a native or synthetic active agent or drug that inhibits or modulates an immune response. The immune response may be a humoral response or a cellular response. Immunomodulatory agents include immunosuppressive agent. The "immunosuppressive agent", "immunosuppressive drug" or "immunosuppressive substance" used herein is a therapeutic agent used in immunosuppressive therapy to suppress or prevent the activity of the immune system. The term "effective amount" refers to an amount or dose of an antibody or fragment or conjugate or composition or combination of the present disclosure which, upon administration to a patient in a single or multiple doses, produces the desired effect in the patient in need of treatment or prevention. The "therapeutically effective amount" refers to an amount effective to achieve a desired therapeutic result at a necessary dosage for a necessary period of time. A therapeutically effective amount is also one in which any toxic or adverse effect of the antibody or antibody fragment or its conjugate or composition or combination is less than a therapeutically beneficial effect. A "therapeutically effective amount" preferably inhibits a measurable parameter (e.g., IL-1 signaling pathway inhibition) by at least about 20%, more preferably by at least about 40%, and even more preferably by at least about 50%, 60%, or 70%, relative to untreated subjects. The term "therapeutically effective amount" as used herein, in some embodiments, is intended to define the amount of a treatment necessary to treat a condition (e.g., inflammation) or to reduce or eliminate an immune response in a treatment regimen. The "prophylactically effective amount" refers to an amount effective to achieve a desired prophylactic result at a necessary dosage for a necessary period of time. Generally, since a prophylactic dose is administered in a subject before or at an earlier stage of a disease, a prophylactically effective amount will be less than a therapeutically effective amount. The term "prophylactically effective amount" as used herein, in some embodiments, is an amount intended to define the amount of a prophylaxis necessary to prevent the progression and symptoms (e.g., inflammation) of a condition or disease in a treatment regimen, The terms "host cell," "host cell line," and "host cell culture" are used interchangeably and refer to a cell into which an exogenous nucleic acid has been introduced, including progeny of such a cell. The host cells include "transformants" and "transformed cells", which include primary transformed cells and progeny derived therefrom, regardless of the number of passages. Progeny may not be exactly the same as parent cells in terms of nucleic acid content, but may contain mutations. Included herein are screened or selected mutant progeny from the originally transformed cell, which have the same function or biological activity. As used herein, the term "label" refers to a compound or composition that is directly or indirectly conjugated or fused to an agent, such as a polynucleotide probe or antibody, and facilitates the detection of the agent to which it is conjugated or fused. The label itself can be detectable (e.g., a radioisotope label or a fluorescent label) or can catalyze a chemical change of a detectable substrate compound or composition in the case of enzymatic labeling. The term is intended to encompass direct labeling of the probe or antibody by coupling (i.e., physically linking) a detectable substance to the probe or antibody, as well as indirect labeling of the probe or antibody by reaction with another reagent that is directly labeled. The terms "individual," or "subject" are used interchangeably and include mammals. Mammals include, but are not limited to, domestic animals (e.g., cows, sheep, cats, dogs, and horses), primates (e.g., humans and non-human primates such as monkeys), rabbits, and rodents (e.g., mice and rats). In some embodiments, the individual or a subject is a human. The term "subject / patient / individual sample" used in this document refers to a collection of cells or fluids obtained from a patient or subject. The source of tissue or cell samples can be solid tissues, e.g., from fresh, frozen and / or preserved organ or tissue samples or biopsy samples or puncture samples; blood or any blood component; body fluids such as cerebrospinal fluids, amniotic fluids, peritoneal fluids, or interstitial fluids; and cells from a subject at any time during pregnancy or development. Tissue samples may comprise compounds which are naturally not mixed with tissues, such as preservatives, anticoagulants, buffers, fixatives, nutrients, antibiotics, and the like. An " nucleic acid encoding an anti-IL1RAP antibody or a fragment thereof" refers to one or more nucleic acid molecules encoding antibody heavy or light chains (or fragments thereof, such as the heavy chain variable region or the light chain variable region), including such nucleic acid molecules in a single vector or separate vectors, and such nucleic acid molecules present at one or more positions in a host cell. The "percent identity (%)" of an amino acid sequence refers to the percentage of amino acid residues in a candidate sequence that are identical to those of a specific amino acid sequence set forth in this specification when the candidate sequence is aligned with the specific amino acid sequence set forth in this specification, with gaps introduced if necessary to achieve maximum percent sequence identity and without considering any conservative substitution as part of sequence identity. In some embodiments, the present disclosure considers variants of the antibody molecule of the present disclosure, and the variants have a considerable degree of identity to the antibody molecules and sequences thereof specifically disclosed herein, e.g., at least 80%, 85%, 90%, 95%, 97%, 98%, or 99%, or higher identity. The variant may comprise conservative changes. The term "pharmaceutically acceptable auxiliary material" refers to a diluent, adjuvant (e.g., Freund's adjuvant (complete and incomplete)), excipient, carrier or stabilizer, etc., with which the active substance is administered. The term "pharmaceutical composition" refers to such a composition that exists in a form allowing effective biological activity of the active ingredient contained therein, and does not contain additional ingredients having unacceptable toxicity to a subject to which the composition is administered. As used herein, the term "pharmaceutical combination" or "combination product" refers to a non-fixed combination or a fixed combination, including but not limited to a kit, a pharmaceutical composition. The term "non-fixed combination" means that the active ingredients (e.g., (i) the antibody of the present disclosure, and (ii) additional therapeutic agents) are administered, either simultaneously or sequentially (without specific time limitation or at identical or different time intervals), to a patient as separate entities, wherein such administration provides two or more prophylactically or therapeutically effective level of active agents in the patient. The term "fixed combination" means that two or more active agents are administered to a patient simultaneously in the form of a single entity. The dose and / or time intervals of two or more active agents are preferably selected such that the combined use of the components can result in a therapeutic effect on the disease or disorder which is greater than that achieved by the use of either component alone. The ingredients may each take a separate formulation form and such separate formulation forms may be the same or different. The term "combination therapy" refers to the administration of two or more therapeutic agents or modalities (e.g., radiotherapy or surgery) to treat the diseases as described herein. Such administration includes co-administration of these therapeutic agents in a substantially simultaneous manner, for example, in a single capsule with a fixed proportion of active ingredients. Alternatively, such administration includes co-administration of the active ingredients in a variety of or separate containers (such as tablets, capsules, powder and liquid). The powder and / or liquid can be reconstituted or diluted to a desired dosage before administration. In addition, such administration also includes using each type of the therapeutic agents at approximately the same time or in a sequential manner at different times. In any case, the therapeutic regimen will provide the beneficial effect of the pharmaceutical combination in the treatment of disorders or conditions described herein. As used herein, "treatment" (or "treat" or "treating") refers to slowing, interrupting, arresting, alleviating, stopping, lowering, or reversing the onset of symptoms, complications, or biochemical indicators of the disease; alleviating symptoms; or preventing or inhibiting the further progression of a disease, condition, or disorder.. As used herein, "prevention" (or "prevent" or "preventing") includes the inhibition of the onset or progression of a disease or disorder, or symptoms of a specific disease or disorder. II antibody In some embodiments, the anti-IL1RAP antibody or the antigen-binding fragment thereof of the present disclosure comprises 3 complementarity determining regions derived from the heavy chain variable region (HCDRs): HCDR1, HCDR2, and HCDR3. In some embodiments, the anti-IL1RAP antibody or the antigen-binding fragment thereof of the present disclosure comprises 3 complementarity determining regions derived from the light chain variable region (LCDRs): LCDR1, LCDR2, and LCDR3. In some embodiments, the anti-IL1RAP antibody or the antigen-binding fragment thereof of the present disclosure comprises 3 complementarity determining regions derived from the heavy chain variable region (HCDRs) and 3 complementarity determining regions derived from the light chain variable region (LCDRs). In some aspects, the anti-IL1RAP antibody or the antigen-binding fragment thereof of the present disclosure comprises a heavy chain variable region (VH). In some aspects, the anti-IL1RAP antibody or the antigen-binding fragment thereof of the present disclosure comprises a light chain variable region (VH). In some aspects, the anti-IL1RAP antibody or its antigen-binding fragment of the present disclosure comprises a heavy chain variable region and a light chain variable region (VH). In some embodiments, the heavy chain variable region comprises 3 complementarity determining regions (CDRs) derived from the heavy chain variable region: HCDR1, HCDR2, and HCDR3. In some embodiments, the light chain variable region comprises 3 complementarity determining regions (CDRs) derived from the light chain variable region: LCDR1, LCDR2, and LCDR3. In some embodiments, the anti-IL1RAP antibody or antigen-binding fragment thereof of the present disclosure further comprises an antibody heavy chain constant region. In some embodiments, the anti-IL1RAP antibody or antigen-binding fragment thereof of the present disclosure further comprises an antibody light chain constant region. In some embodiments, the anti-IL1RAP antibody or antigen-binding fragment thereof of the present disclosure further comprises a heavy chain constant region and a light chain constant region. In some embodiments, the heavy chain variable region: (i) comprises or consists of an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence selected from any one of SEQ ID NO: 13-17; or (ii)   comprises or consists of the amino acid sequence selected fromany one of SEQ ID NOs: 13-17, or (iii) comprises or consists of an amino acid sequence having 1 or more (preferably not more than 10, more preferably not more than 5, 4, 3, 2, 1) amino acid alterations (preferably amino acid replacements, more preferably amino acid conservative replacements) compared to the amino acid sequence selected from any one of SEQ ID NOs: 13-17, preferably the amino acid alterations do not occur in the CDR region. In some embodiments, the light chain variable region (i) comprises or consists of an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence selected from any one of SEQ ID NOs: 23-25; or (ii)   comprises or consists of the amino acid sequence selected from any one of SEQ ID NOs: 23-25, or (iii) comprises or consists of an amino acid sequence having 1 or more (preferably not more than 10, more preferably not more than 5, 4, 3, 2, 1) amino acid alterations (preferably amino acid replacements, more preferably amino acid conservative replacements) compared to the amino acid sequence selected from any one of SEQ ID NOs: 23-25, preferably the amino acid alterations do not occur in the CDR region. In some embodiments, the three complementarity determining regions (HCDRs) derived from the heavy chain variable region, HCDR1, HCDR2, and HCDR3of the present disclosure are selected from (i)    three complementarity determining regions HCDR1, HCDR2 and HCDR3 contained in a VH set forth in any one of SEQ ID NOs: 13-17; (ii) a sequence comprising a total of at least one and no more than 5, 4, 3, 2, or 1 amino acid alteration (preferably amino acid replacement, and more preferably conservative replacement) in the three HCDRs relative to the sequence of any one of (i). wherein the HCDRs may be determined according to any scheme for determining CDRs, e.g., according to kabat, AbM, Chothia, Contact, or IMGT schemes, or a combination thereof, respectively; For example, the HCDR1 is determined according to the Kabat & chothia scheme, and the HCDR2 and the HCDR3 are respectively determined according to the Kabat scheme. In some embodiments, the 3 complementarity determining regions (LCDRs) derived from the light chain variable region of the present disclosure, LCDR1, LCDR2, and LCDR3, are selected from (i)    three complementarity determining regions LCDR1, LCDR2, and LCDR3 contained in a VL set forth in any one of SEQ ID NOs: 23-25, or (ii) a sequence comprising a total of at least one and no more than 5, 4, 3, 2, or 1 amino acid alteration (preferably amino acid replacement, and more preferably conservative replacement) in the three LCDRs relative to the sequence of any one of (i). wherein the HCDRs may be determined according to any scheme for determining CDRs, e.g., according to kabat, AbM, Chothia, Contact, or IMGT schemes, or a combination thereof, respectively; For example, the LCDR1, LCDR2, and LCDR3 are respectively determined according to the Kabat scheme. In some embodiments, the anti-IL1RAP antibody or the antigen-binding fragment thereof of the present disclosure comprises: (i)    three complementarity determining regions HCDR1, HCDR2 and HCDR3 contained in a VH set forth in any one of SEQ ID NOs: 13 to 17, and three complementarity determining regions LCDR1, LCDR2 and LCDR3 contained in a VL set forth in any one of SEQ ID NOs: 23 to 25; (ii) three complementarity determining regions HCDR1, HCDR2 and HCDR3 contained in a VH set forth in SEQ ID NO: 13, and three complementarity determining regions LCDR1, LCDR2 and LCDR3 contained in a VL set forth in SEQ ID NO: 23; (iii) three complementarity determining regions HCDR1, HCDR2 and HCDR3 contained in a VH set forth in SEQ ID NO: 14 or 15, and three complementarity determining regions LCDR1, LCDR2 and LCDR3 contained in a VL set forth in SEQ ID NO: 24; or (iv) three complementarity determining regions HCDR1, HCDR2 and HCDR3 contained in a VH set forth in SEQ ID NO: 16 or 17, and three complementarity determining regions LCDR1, LCDR2 and LCDR3 contained in a VL set forth in SEQ ID NO: 25; wherein the HCDRs may be determined according to any scheme for determining CDRs, e.g., according to kabat, AbM, Chothia, Contact, or IMGT schemes, or a combination thereof, respectively; For example, the HCDR1 is determined according to the Kabat & chothia scheme, and the HCDR2 and the HCDR3 are respectively determined according to the Kabat scheme. In some embodiments, the HCDR1 comprises or consists of an amino acid sequence set forth in SEQ ID NO: 1, or the HCDR1 comprises an amino acid sequence having one, two, or three alterations (preferably amino acid replacements, and more preferably conservative replacements) compared with the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the HCDR2 comprises or consists of an amino acid sequence set forth in SEQ ID NO: 2, or the HCDR2 comprises an amino acid sequence having one, two, or three alterations (preferably amino acid replacements, and more preferably conservative replacements) compared with the amino acid sequence set forth in SEQ ID NO: 2. In some embodiments, the HCDR3 comprises or consists of an amino acid sequence set forth in SEQ ID NO: 3, or the HCDR3 comprises an amino acid sequence having one, two, or three alterations (preferably amino acid replacements, and more preferably conservative replacements) compared with the amino acid sequence set forth in SEQ ID NO: 3. In some embodiments, the LCDR1 comprises or consists of an amino acid sequence set forth in SEQ ID NO: 4, or the LCDR1 comprises an amino acid sequence having one, two, or three alterations (preferably amino acid replacements, and more preferably conservative replacements) compared with the amino acid sequence set forth in SEQ ID NO: 4. In some embodiments, the LCDR2 comprises or consists of an amino acid sequence set forth in SEQ ID NO: 5, or the LCDR2 comprises an amino acid sequence having one, two, or three alterations (preferably amino acid replacements, and more preferably conservative replacements) compared with the amino acid sequence set forth in SEQ ID NO: 5. In some embodiments, the LCDR3 comprises or consists of an amino acid sequence set forth in SEQ ID NO: 6, or the LCDR3 comprises an amino acid sequence having one, two, or three alterations (preferably amino acid replacements, and more preferably conservative replacements) compared with the amino acid sequence set forth in SEQ ID NO: 6. In some embodiments, the heavy chain constant region of the antibody of the present disclosure is a heavy chain constant region derived from IgG1, IgG2, IgG3 or IgG4, for example, a constant region of human IgG1, IgG2, IgG3 or IgG4, for example, a constant region of human IgG1, IgG2, IgG3 or IgG4. In some embodiments, the constant region has a modification in the Fc region. In one embodiment, the Fc region is modified in properties of the effector function of the Fc region (e.g., complement activation function of the Fc region). In one embodiment, the effector function has been reduced or eliminated relative to a wild-type isotype Fc region. In one embodiment, the effector function is reduced or eliminated by using a method selected from: using an Fc isotype that naturally has a reduced or an eliminated effector function, and performing Fc region modification. The Fc region may further comprise modifications that alter binding affinity for one or more Fc receptors. In one embodiment, the Fc receptor is an Fcy receptor, in particular a human Fcy receptor. In some embodiments, the Fc region comprises a mutation that reduces binding to the Fcy receptor. In some embodiments, the Fc region for use in the present disclosure has an L234A / L235A mutation and / or a P329G mutation that reduces binding to the Fcy receptor. In some embodiments, the heavy chain constant region described herein comprises a mutation that reduces binding to an Fcy receptor, e.g., an L234A / L235A mutation and / or a P329G mutation, e.g., an L234A / L235A mutation, or an L234A / L235A mutation and a P329G mutation. In some embodiments, the heavy chain constant region (i)   comprises or consists of the amino acid sequence selected from SEQ ID NO: 50, 51, or 52; (ii) comprises an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence set forth in SEQ ID NO: 50, 51, or 52 (iii) comprises an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence set forth in SEQ ID NO: 51, and has a L234A / L235A mutation; or (iv) comprises an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence set forth in SEQ ID NO: 52, and has a L234A / L235A mutation and a P329G mutation. In some embodiments, the heavy chain constant region of the present disclosure lacks C terminal lysine. In some embodiments, the antibody light chain constant region of the present disclosure is derived from a Lambda or Kappa light chain constant region, preferably a Kappa light chain constant region, e.g., a human Lambda or Kappa light chain constant region, e.g., a human Lambda or Kappa light chain constant region. In some embodiments, the light chain constant region (i) comprises or consists of an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence set forth in SEQ ID NO: 53; or (ii) comprises or consists of the amino acid sequence set forth in SEQ ID NO: 53. In some specific embodiments, the anti-IL1RAP antibody of the present disclosure comprises a first heavy chain complementarity determining region (HCDR1), a second heavy chain complementarity determining region (HCDR2), a third heavy chain complementarity determining region (HCDR3), a first light chain complementarity determining region (LCDR1), a second light chain complementarity determining region (LCDR2), and a third light chain complementarity determining region (LCDR3), wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise or consist of the amino acid sequence set forth in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, or SEQ ID NO: 6, respectively. In some embodiments, the VH of the present disclosure comprises HCDR1, HCDR2, and HCDR3, and the VL comprises LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprise or consist of the amino acid sequence set forth in SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively, and the LCDR1, LCDR2, and LCDR3 comprise or consist of the amino acid sequence set forth in SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. In some embodiments, the antibody or the antigen-binding fragment thereof of the present disclosure comprises: (i) the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO: 13, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto; and / or the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 23, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto ; (ii) the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO: 14 or 15, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto; and / or the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 24, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto; or (iii) the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO: 16 or 17, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto; and / or the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 25, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto. In some embodiments, the antibody or antigen-binding fragment thereof of the present disclosure comprises a heavy chain variable region and a light chain variable region, wherein (i)    the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 13, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 23; (ii) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 14 or 15, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 24; or (iii) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 16 or 17, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 25. In some embodiments, the anti-IL1RAP antibody or the antigen-binding fragment thereof of the present disclosure comprises an antibody heavy chain. In some embodiments, the anti-IL1RAP antibody or antigen-binding fragment thereof of the present disclosure comprises an antibody light chain. In some embodiments, the anti-IL1RAP antibody or antigen-binding fragment thereof of the present disclosure comprises heavy and light chains. In some embodiments, the antibody heavy chain of the present disclosure comprises or consists of the heavy chain variable region and the heavy chain constant region. In some embodiments, the antibody light chain of the present disclosure comprises or consists of the light chain variable region and the light chain constant region. In some embodiments, the antibody of the present disclosure comprises or consists of two heavy chains and two light chains. In some embodiments, the heavy chain comprises (i) comprises or consists of an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence selected from any one of SEQ ID NOs: 32-36; (ii) comprises or consists of the amino acid sequence selected from any one of SEQ ID NOs:32-36; or (iii) comprises or consists of an amino acid sequence having 1 or more (preferably not more than 20 or 10, more preferably not more than 5, 4, 3, 2, 1) amino acid alterations (preferably amino acid replacements, more preferably amino acid conservative replacements) compared to the amino acid sequence selected from any one of SEQ ID NOs: 32-36. In some embodiments, the light chain comprises (i) comprises or consists of an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence selected from any one of SEQ ID NOs: 42-44; (ii) comprises or consists of the amino acid sequence selected from any one of SEQ ID NOs: 42-44; or (iii) comprises or consists of an amino acid sequence having 1 or more (preferably not more than 20 or 10, more preferably not more than 5, 4, 3, 2, 1) amino acid alterations (preferably amino acid replacements, more preferably amino acid conservative replacements) compared to the amino acid sequence selected from any one of SEQ ID NOs: 42-44. In some embodiments, the antibody or antigen-binding fragment thereof of the present disclosure comprises a heavy chain and a light chain, wherein (i) the heavy chain comprises or consists of an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence set forth in SEQ ID NO: 32, and the light chain comprises or consists of an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence set forth in SEQ ID NO: 42; (ii) The heavy chain comprises or consists of an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence set forth in SEQ ID NO: 33 or 34, and the light chain comprises or consists of an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence set forth in SEQ ID NO: 43; or (iii) The heavy chain comprises or consists of an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence set forth in SEQ ID NO: 35 or 36, and the light chain comprises or consists of an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence set forth in SEQ ID NO: 44. In some embodiments, the antibody or antigen-binding fragment thereof of the present disclosure comprises a heavy chain and a light chain, wherein (i) The heavy chain comprises or consists of the amino acid sequence set forth in SEQ ID NO: 32, and the light chain comprises or consists of the amino acid sequence set forth in SEQ ID NO: 42; (ii) The heavy chain comprises or consists of the amino acid sequence set forth in SEQ ID NO: 33 or 34, and the light chain comprises or consists of the amino acid sequence set forth in SEQ ID NO: 43; or (iii) The heavy chain comprises or consists of the amino acid sequence set forth in SEQ ID NO: 35 or 36, and the light chain comprises or consists of the amino acid sequence set forth in SEQ ID NO: 44. In one embodiment of the present disclosure, the amino acid alteration described herein includes amino acid replacement, insertion, or deletion. Preferably, the amino acid change described herein is an amino acid replacement, preferably a conservative replacement. In a preferred embodiment, the amino acid change described herein occurs in a region outside the CDRs (e.g., in FRs). More preferably, the amino acid alteration described herein occurs in a region outside the heavy chain variable region and / or outside the light chain variable region. In certain embodiments, the antibody provided herein is altered to increase or decrease the extent to which the antibody is glycosylated. Addition or deletion of glycosylation sites of the antibody can be conveniently achieved by altering the amino acid sequence to create or remove one or more glycosylation sites. When the antibody comprises an Fc region, the carbohydrate attached thereto can be altered. In some applications, removing undesired modifications to glycosylation sites may be useful, for example, removing fucose motifs to improve antibody-dependent cellular cytotoxicity (ADCC) function. In other applications, galactosylation modification may be performed to modify complement-dependent cytotoxicity (CDC). In certain embodiments, antibodies modified by cysteine engineering may need to be produced, such as "sulfo-MAb", wherein one or more residues of the antibodies are substituted by cysteine residues. In certain embodiments, the antibody provided herein can be further modified to comprise other non-protein portions known in the art and readily available. Suitable portions for antibody derivatization include, but are not limited to, water-soluble polymers.Non-limiting examples of the water-soluble polymer include, but are not limited to, polyethylene glycol (PEG), ethylene glycol / propylene glycol copolymer, carboxymethylcellulose, dextran, polyvinyl alcohol, polyvinylpyrrolidone, poly-1,3-dioxane, poly-1,3,6-trioxane, ethylene / maleic anhydride copolymer, polyamino acid (homopolymer or random copolymer), and dextran or poly(n-vinylpyrrolidone)polyethylene glycol, propylene glycol homopolymer, polypropylene oxide / ethylene oxide copolymer, polyoxyethylated polyol (e.g., glycerol), polyvinyl alcohol, and mixtures thereof. In some embodiments, the anti-IL1RAP antibody or the antigen-binding fragment thereof of the present disclosure has one or more of the following characteristics: (i) showing the same or similar binding affinity and / or specificity for IL1RAP as the antibody disclosed herein; (ii) inhibiting (e.g., competitively inhibiting) the binding of the antibody of the present disclosure to IL1RAP; (iii) binding to an identical or overlapping epitope as the antibody of the present disclosure; (iv) competing with the antibody of the present disclosure for binding to IL1RAP; (v) having one or more biological properties of the antibody of the present disclosure. In some embodiments, the anti-IL1RAP antibody of the present disclosure is an antibody in the form of IgG1, IgG2, IgG3, or IgG4, preferably an antibody in the form of IgG1. In some embodiments, the anti-IL1RAP antibody is a monoclonal antibody. In some embodiments, the anti-IL1RAP antibody is humanized. In some embodiments, the anti-IL1RAP antibody is a chimeric antibody. In some embodiments, the anti-IL1RAP antibody of the present disclosure is a full-length antibody. In one embodiment, the anti-IL1RAP antibody of the present disclosure also encompasses the antibody fragments (e.g., antigen-binding fragments)thereof, preferably selected from the following antibody fragments: Fab, Fab', Fab'-SH, Fv, single-chain antibodies (e.g., scFv), (Fab')2, single-domain antibodies such as VHH, dAb (domain antibody), bispecific antibodies, or linear antibodies. In one embodiment, the anti-IL1RAP antibody of the present disclosure also encompasses a multispecific antibody, e.g., a bispecific antibody, which specifically binds to anti-IL1RAP and one or more additional antigens. III. Nucleic acid of the present disclosure and host cell comprising same In one aspect, the present disclosure provides a nucleic acid encoding any chain or any monomer or domain of the antibody or antigen-binding fragment thereof of the present disclosure. Polynucleotide sequences encoding each chain can be generated using methods well known in the art. For example, a polypeptide encoded by the nucleic acid is capable of exhibiting human IL1RAP antigen-binding ability when expressed in a suitable expression vector. For example, in some embodiments, the nucleic acid encoding the variable region of a heavy chain and / or a light chain is operably linked to the nucleic acid encoding the constant region of the heavy chain and / or the light chain in a reading frame, thereby producing the nucleic acid encoding the heavy chain and / or the light chain of the antibody when expressed in a suitable expression vector. In one aspect, the present disclosure provides a nucleic acid encoding any of the anti-IL1RAP antibodies or fragments thereof described herein. The nucleic acid may comprise a nucleic acid encoding an amino acid sequence of a light chain variable region and / or a heavy chain variable region of the antibody, or a nucleic acid encoding an amino acid sequence of a light chain and / or a heavy chain of the antibody. For example, the nucleic acid of the present disclosure includes a nucleic acid encoding an amino acid sequence selected from any one of SEQ ID NOs: 13-17, 23-25, 32-36, and 42-44, or a nucleic acid encoding an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence selected from any one of SEQ ID NOs: 13-17, 23-25, 32-36, and 42-44. As will be appreciated by those skilled in the art, each antibody or polypeptide amino acid sequence may be encoded by a variety of nucleic acid sequences because of codon degeneracy. The nucleic acid sequence encoding the molecule of the present disclosure can be generated by methods well known in the art, for example, by de novo solid-phase DNA synthesis or PCR amplification. For ease of production and purification, a secretory signal peptide and / or a tag peptide facilitating purification can be fused to the N-terminus of the heavy chain and / or the light chain of the antibody. The present disclosure also provides a vector comprising the nucleic acid disclosed herein. In one embodiment, the vector is an expression vector, such as a eukaryotic expression vector. The vector includes, but is not limited to, a virus, a plasmid, a cosmid, a X phage, or a yeast artificial chromosome (YAC). In a preferred embodiment, the expression vector of the present disclosure is a pcDNA vector, such as pcDNA3.1 and / or pcDNA3.4 expression vectors. In one embodiment, provided is a host cell comprising the vector.The present disclosure further provides a host cell comprising the nucleic acid or the vector. Host cells suitable for replicating and supporting the expression of the antibody of the present disclosure are well known in the art. Such cells can be transfected or transduced with a particular expression vector, and a large number of vector-containing cells can be cultivated for inoculation in large-scale fermenters, so as to obtain sufficient antibodies for clinical application. Suitable host cells for cloning or expressing an antibody-encoding vector include prokaryotic or eukaryotic cells described herein. For example, the antibody can be produced in bacteria, particularly when glycosylation and Fc effector functions are not required. After expression, the antibody can be isolated from the bacterial cell paste in a soluble fraction and can be further purified. In one embodiment, the host cell is eukaryotic. In another embodiment, the host cell is selected from a yeast cell and a mammalian cell (e.g., a CHO cell (e.g., a CHO-S or a CHO-K) or a 293 cell (e.g., a 293F or an HEK293 cell)) or other cells suitable for the preparation of an antibody or a fragment thereof. In one embodiment, the host cell is prokaryotic, for example, a bacterium, such as *E. coli*. For example, eukaryotic microorganisms such as filamentous fungi or yeast are suitable cloning or expression hosts for vectors encoding antibodies. For example, fungal and yeast strains in which the glycosylation pathway has been "humanized" result in the production of antibodies with a partially or fully human glycosylation pattern. Host cells suitable for expressing glycosylated antibodies are also derived from multicellular organisms (invertebrates and vertebrates). Vertebrate cells may also be used as hosts. For example, a mammalian cell line engineered to be suitable for suspension growth may be used. Other examples of useful mammalian host cell lines are monkey kidney CV1 lines (COS-7) transformed with SV40, human embryonic kidney lines (HEK293, 293F, or 293T cells), and the like. Other useful mammalian host cell lines include Chinese hamster ovary (CHO) cells, including DHFR-CHO cells, CHO-S cells, ExpiCHO; and myeloma cell lines such as Y0, NS0, and Sp2 / 0. Mammalian host cell lines suitable for the production of antibodies are known in the art. IV. Production and purification of the antibody molecule of the present disclosure In one embodiment, the present disclosure provides a method for preparing the antibody molecule or the fragment (preferably an antigen-binding fragment) thereof of the present disclosure, wherein the method comprises culturing the host cell under conditions suitable for expressing the nucleic acid encoding the antibody molecule or the fragment (preferably an antigen-binding fragment) thereof of the present disclosure, and optionally isolating the antibody or the fragment (e.g., an antigen-binding fragment) thereof. In a certain embodiment, the method further comprises recovering the antibody molecule or the fragment (e.g., antigen-binding fragment) of the present disclosure from the host cell. Polynucleotides encoding the polypeptide chain of the antibody of the present disclosure can be inserted into one or more vectors (e.g., pcDNA3.1 and / or pcDNA3.4 expression vectors) for further cloning and / or expression in host cells. Methods known to those skilled in the art can be used to construct expression vectors. Once the expression vector comprising one or more nucleic acid molecules of the present disclosure has been prepared for expression, the expression vector can be transfected or introduced into suitable host cells. Various techniques can be used for this purpose, for example, protoplast fusion, calcium phosphate precipitation, electroporation, retroviral transduction, viral transfection, biolistics, liposome-based transfection, or other conventional techniques. The antibody molecule prepared as described herein can be purified by known prior art such as high performance liquid chromatography, ion exchange chromatography, gel electrophoresis, affinity chromatography, and size exclusion chromatography. The actual conditions used to purify a particular protein also depend on factors such as net charge, hydrophobicity, and hydrophilicity, and these will be apparent to those skilled in the art. The purity of the antibody molecule of the present disclosure can be determined by any one of a variety of well-known analytical methods including size exclusion chromatography, gel electrophoresis, high performance liquid chromatography, and the like. V. Assay The anti-IL1RAP antibody or the fragment thereof provided herein can be identified, screened, or characterized for physical / chemical properties and / or biological activities by a variety of assays known in the art. The present disclosure also provides an assay for identifying anti-IL1RAP antibodies or fragments thereof having biological activity. The biological activity may include, for example, binding to IL1RAP (e.g., binding to human IL1RAP), inhibition of an IL1RAP complex-mediated signaling pathway, prevention or treatment of inflammation, and the like. An antibody having such biological activities in vivo and / or in vitro is also provided. For the determination of the biological activity described above, reference can be made to the exemplary determination methods given in the examples. It can be understood that any of the above assays can be performed by using the immunoconjugate of the present disclosure to replace or supplement the anti-IL1RAP antibody or the fragment thereof. It will be appreciated that any of the above assays can be performed using a combination of the anti-IL1RAP antibody or fragment thereof and an additional therapeutic agent. VI. Immunoconjugate In some embodiments, the present disclosure provides an immunoconjugate comprising any of the anti-IL1RAP antibodies provided herein and other substances, such as any active agent or label suitable for forming an immunoconjugate with the anti-IL1RAP antibody. In some embodiments, the active agent suitable for forming an immunoconjugate with the IL1RAP antibody may be, for example, a chemotherapeutic agent, a toxin, a small molecule drug, a cytotoxic agent, an apoptotic agent, a chelating agent, or an immunomodulatory agent, e.g., an immunosuppressive agent. In some embodiments, the immunoconjugate is antibody-drug conjugates, such as ADC. VII.Pharmaceutical Composition and Pharmaceutical Formulation In some embodiments, the present disclosure provides a composition comprising any anti-IL1RAP antibody or fragment thereof (preferably an antigen-binding fragment) or an immunoconjugate thereof of the present disclosure, preferably the composition is a pharmaceutical composition, e.g., a pharmaceutical formulation. In an embodiment, the composition further comprises a pharmaceutically acceptable auxiliary material. In one embodiment, a composition, e.g., a pharmaceutical composition, comprises an anti-IL1RAP antibody or a fragment or immunconjugate thereof of the present disclosure as well as one or more additional therapeutic agents. The present disclosure also includes a composition (including a pharmaceutical composition or a pharmaceutical formulation) comprising an anti-IL1RAP antibody or an immunoconjugate thereof, or a composition (including a pharmaceutical composition or a pharmaceutical preparation) comprising a polynucleotide encoding the anti-IL1RAP antibody. In certain embodiments, the composition comprises one or more antibodies that bind IL1RAP or fragments thereof, or one or more polynucleotides encoding the one or more anti-IL1RAP antibodies or fragments thereof. These compositions may also contain suitable pharmaceutically acceptable auxiliary material(s) such as pharmaceutical carriers, pharmaceutical excipients, including buffers, as known in the art. As used herein, "pharmaceutically acceptable carrier" includes any and all solvents, dispersion media, isotonic agents and absorption delaying agents, and the like that are physiologically compatible. For the application and uses of pharmaceutically acceptable auxiliary materials, see also "Handbook of Pharmaceutical Excipients", 8th Edition, R.C. Rowe, P.J. Seskey and S.C. Owen, Pharmaceutical Press, London, Chicago. The composition of the present disclosure may be in a variety of forms. Such forms include, for example, liquid, semi-solid, and solid dosage forms, such as liquid solutions (e.g., injectable solutions and infusible solutions), powders or suspensions, liposomal formulations, and suppositories. The preferred form depends on the intended mode of administration and therapeutic use. Pharmaceutical formulations comprising the antibody of the present disclosure described herein can be prepared by mixing the antibody of the present disclosure having the desired purity with one or more optional pharmaceutically acceptable auxiliary materials, preferably in the form of lyophilized formulations or aqueous solutions. The pharmaceutical composition or formulation of the present disclosure may further comprise more than one active ingredient required by a specific indication treated, preferably active ingredients having complementary activities that do not adversely affect one another. For example, it may be desirable to further provide additional therapeutic agents, such as cytokines, small-molecule drugs, immunomodulatory agents (e.g., immunosuppressive agents), or other antibodies. The active ingredients are suitably present in combination in amounts that are effective for the purpose intended. A sustained-release formulation may be prepared. Suitable examples of the sustained-release preparation include a semipermeable matrix of a solid hydrophobic polymer containing an antibody. The matrix is in the form of a shaped article, such as a film or a microcapsule. VIII. Pharmaceutical Combination and Kit In some embodiments, the present disclosure further provides a pharmaceutical combination or a pharmaceutical combination product comprising the anti-IL1RAP antibody or the fragment thereof (preferably the antigen-binding fragment) disclosed herein, or an immunoconjugate thereof, and one or more additional therapeutic agents (e.g., cytokines, chemotherapeutic agents, small molecule drugs, immunomodulatory agents (e.g., immune activators or immunosuppressive agent) or other antibodies). A further object of the present disclosure is to provide a kit of parts comprising the pharmaceutical combination of the present disclosure, preferably in the form of drug dosage units. Dosage units may thus be provided according to a dosing regimen or interval of drug administration. In an embodiment, a kit of parts according to the present disclosure comprises in the same package: - a first container containing a pharmaceutical composition comprising an anti-IL1RAP antibody or a fragment thereof; - a second container containing a pharmaceutical composition comprising additional therapeutic agents. The choice of additional therapeutic agents that can be combined with the molecule of the present disclosure depends on the use of the molecule of the present disclosure. For example, when the molecule of the present disclosure is used to treat autoimmune diseases or autoinflammatory diseases, the additional therapeutic agent is any active agent suitable for treating the autoimmune diseases or autoinflammatory diseases, including but not limited to cytokines, small-molecule drugs, other antibodies, or immunomodulatory agents (e.g., immunosuppressive agents).For example, when the molecule of the present disclosure is used to treat a tumor, the additional therapeutic agent is any active agent suitable for treating the tumor, such as an antineoplastic agent or an anticancer agent, including but not limited to a cytokine, a chemotherapeutic agent, a small molecule drug, an additional antibody, or an immunomodulatory agent (e.g., an immune activator). IX. Uses and Methods In some embodiments, a method for preventing or treating a disease or disorder in an individual with the antibody of the present disclosure as a monotherapy or in a combination comprises administering to the individual the molecule (e.g., the anti-IL1RAP antibody or the antigen-binding fragment thereof, or the immunoconjugate thereof of the present disclosure), the pharmaceutical composition, the pharmaceutical combination, or the kit of the present disclosure. In some embodiments, the present disclosure relates to the molecule (e.g., the anti-IL1RAP antibody or antigen-binding fragment thereof or the immunoconjugate thereof of the present disclosure), pharmaceutical compositions, pharmaceutical combinations, or kits of the present disclosure for therapy, e.g., for preventing or treating the diseases or disorders mentioned herein. In some embodiments, the present disclosure relates to the use of the molecule (e.g., the anti-IL1RAP antibody or antigen-binding fragment thereof or the immunoconjugate thereof of the present disclosure), pharmaceutical compositions, pharmaceutical combinations, or kits of the present disclosure for preparing a drug for therapy, such as for preventing or treating the diseases or conditions mentioned herein. In some embodiments, the present disclosure relates to a method of using the molecule (e.g., the anti-IL1RAP antibody or the antigen-binding fragment thereof, or the immunoconjugate thereof of the present disclosure), the pharmaceutical composition, the pharmaceutical combination, or the kit of the present disclosure, or use thereof in the treatment, or the use thereof in treatment, or the use thereof in the preparation of a medicament for the treatment. In some embodiments, the disease or disorder mentioned herein is a disease or disorder related to abnormal activation of a signaling pathway mediated by the IL1RAP receptor complex, or a disease or disorder related to abnormal activation of a signaling pathway mediated by IL1 (IL1a and / or IL1p), IL33, and / or IL36. In some embodiments, the molecule of the present disclosure (e.g., the anti-IL1RAP antibody or the antigen-binding fragment thereof of the present disclosure or the immunoconjugate thereof) can inhibit the activation of the downstream NF-kB signaling pathway by blocking the binding of IL1 (IL1a and / or IL1P), IL33, and / or IL36 to the IL1RAP receptor complex, thereby preventing and / or treating diseases or conditions associated with one or more of these cytokines. In some embodiments, in the patient with the disease or disorder mentioned herein, the IL1RAP receptor complex-mediated signaling pathway is abnormally activated as compared to healthy individuals. In some embodiments, in patients with the disease or disorder mentioned herein, the signaling pathway mediated by IL1 (IL1a and / or IL10), IL33, and / or IL36 is abnormally activated as compared to healthy individuals. In some embodiments, the disease or disorder suitable for prevention and / or treatment of the present disclosure is an autoimmune disease or an autoinflammatory disease. In some embodiments, the disease or disorder suitable for prevention and / or treatment of the present disclosure is a disease or disorder in the rheumatic, skin and / or vascular field, e.g., inflammation. In some embodiments, the disease or disorder is selected from inflammation, e.g., abdominal inflammation such as peritonitis (e.g., acute peritonitis), gout (e.g., acute gout), and / or skin inflammation (e.g., dermatitis). In some embodiments, the disease or disorder suitable for prevention and / or treatment of the present disclosure is a tumor, e.g., cancer. In some embodiments, the tumor is a solid tumor or a hematological tumor and metastatic lesions. In one embodiment, examples of the solid tumor include a malignant tumor. The cancer may be at an early, intermediate or advanced stage, or may be a metastatic cancer. In some embodiments, the tumor is tumor immune escape. In some embodiments, a signaling pathway mediated by IL1 (IL1a and / or IL10), IL33, and / or IL36 is abnormally activated in the tumor or tumor cell, or IL1RAP-mediated cytokine signaling is abnormally activated, e.g., compared with healthy individuals or healthy cells adjacent to the tumor cell. In some embodiments, the tumor is an IL1RAP-positive tumor or cancer. In some embodiments, the tumor is associated with abnormal expression or abnormal activity of IL1RAP. In some embodiments, the tumor is associated with abnormal expression or abnormal activity of IL1 (IL1 a and / or IL1 0 ), IL33, and / or IL36. In some embodiments, an IL1RAP-positive tumor or cancer refers to a tumor or cancer in a subject that contains tumor cells expressing IL1RAP. In some embodiments, tumor cells of the subject express IL1RAP, e.g., moderately or highly express IL1RAP. In some embodiments, the subject has (e.g., an elevated level of, e.g., nucleic acid or protein level or activity of) IL1RAP (e.g., compared to a healthy subject). In some embodiments, a biological sample (e.g., tumor cells or tumor tissues) of the subject has (e.g., an elevated level of, e.g., nucleic acid or protein level or activity of) IL1RAP (e.g., as compared to a biological sample of a healthy subject (e.g., a corresponding tissue or cell in a healthy subject), or as compared to IL1RAP in an adjacent healthy tissue or cell of the subject). In some embodiments, the antibody or the fragment thereof, the immunoconjugate, the composition, or the pharmaceutical combination or the kit of the present disclosure delays the onset of the disorders and / or symptoms associated with the disorders. In some embodiments, the present disclosure provides use of the anti-IL1RAP antibody or fragment thereof, or the immunoconjugate, the composition, or the drug combination or kit comprising the same of the present disclosure in the manufacture or preparation of a medicament for the use described herein, e.g., for use in preventing or treating the related disease or disorder mentioned herein. In some embodiments, the prevention or treatment method described herein further comprises administering the antibody molecule, the pharmaceutical composition, or the immunoconjugate disclosed herein in combination, as well as one or more additional therapies, e.g., therapeutic modalities and / or additional therapeutic agents to the subject or individual. In some embodiments, the anti-IL1RAP antibody or the fragment thereof (as well as the immunoconjugate, the composition, the pharmaceutical composition, the formulation or the like comprising the same) can also be administered in combination with one or more additional therapies, e.g., therapeutic modalities and / or additional therapeutic agents, for the use described herein, e.g., for use in the prevention and / or treatment of the related diseases or disorders mentioned herein. The choice of additional therapeutic agents for the treatment modality depends on the use of the molecule of the present disclosure. For example, when the molecule of the present disclosure is used to treat autoimmune diseases or autoinflammatory diseases, the additional therapeutic agent is any active agent suitable for treating the autoimmune diseases or autoinflammatory diseases, including but not limited to cytokines, small-molecule drugs, other antibodies, or immunomodulatory agents (e.g., immunosuppressive agents or anti-inflammatory agents). For example, when the molecule of the present disclosure is used to treat a tumor, the additional therapeutic agent is any active agent suitable for treating the tumor, such as an anti-tumor agent or an anti-cancer agent, including but not limited to a cytokine, a chemotherapeutic agent, a small molecule drug, an additional antibody, or an immunomodulatory agent (e.g., an immune activator). The additional therapeutic modality is, for example, selected from surgery or radiotherapy. In some embodiments, the antibodies described herein can be combined with other antibodies for separate administration, e.g., separate administration as separate antibodies, or administration in linkage (e.g., as a bispecific or multispecific antibody molecule). The combination therapy described herein encompasses both combined administration (e.g., two or more therapeutic agents are contained in the same formulation or separate formulations), and separate administration, in which the antibody of the present disclosure can be administered prior to, concurrently with, and / or subsequent to the administration of other therapeutic agents and / or therapies. The antibody or the fragment thereof disclosed herein (as well as the immunoconjugate, the composition, the pharmaceutical composition, the formulation, the combination product or the like comprising the same) can be administered by any suitable method, including parenteral administration and, if required by local treatment, intralesional administration. Parenteral injection or infusion includes intramuscular, intravenous, intraarterial, intraperitoneal, or subcutaneous injection or infusion. X. Methods and Compositions for Diagnosis and Detection In one aspect, the present disclosure further relates to methods for diagnosis and detection using the antibodies or antigen-binding fragments thereof of the disclosure, and to compositions for diagnosis and detection comprising them. In certain embodiments, any of the anti-IL1RAP antibodies or fragments thereof (preferably antigen-binding fragments) provided herein can be used to detect the presence of IL1RAP in a biological sample. The term "detect" as used herein, includes quantitative or qualitative detection, and exemplary detection methods may involve immunohistochemistry, immunocytochemistry, flow cytometry (e.g., FACS), magnetic beads complexed with antibody molecules, ELISA assays, and PCR-techniques (e.g., RT-PCR). In certain embodiments, the biological sample is blood, serum, or other liquid samples of biological origin. In some embodiments, the biological sample comprises cells or tissue. In one embodiment, provided is an anti-IL1RAP antibody or fragment thereof for use in a method of diagnosis or detection. In another aspect, a method of detecting the presence of IL1RAP in a biological sample is provided. In certain embodiments, the method comprises detecting the presence of IL1RAP protein in a biological sample. In certain embodiments, the IL1RAP is human IL1RAP. In certain embodiments, the method comprises contacting the biological sample with the anti-IL1RAP antibody or fragment thereof as described herein under conditions permissive for binding of the anti-IL1RAP antibody or fragment thereof to IL1RAP, and detecting whether a complex is formed between the anti-IL1RAP antibody or fragment thereof and IL1RAP. The formation of a complex indicates the presence of IL1RAP. The method may be an in vitro or in vivo method. In one embodiment, the anti-IL1RAP antibody or fragment thereof is used to select a subject suitable for treatment with the anti-IL1RAP antibody or fragment thereof, e.g., wherein IL1RAP is a biomarker for selecting the subject. In some embodiments, provided is a labeled anti-IL1RAP antibody or a fragment thereof. The label includes, but is not limited to, a label or moiety that is directly detected (such as a fluorescent label, a chromophore label, an electron-dense label, a chemiluminescent label, and a radioactive label), and a moiety that is indirectly detected, such as an enzyme or a ligand, for example, by an enzymatic reaction or molecular interaction. In some embodiments provided herein, the sample is obtained prior to treatment with the anti-IL1RAP antibody or fragment thereof. In some embodiments, the sample is obtained prior to an additional therapy. In some embodiments, the sample is obtained during or after treatment with additional therapies. In some embodiments, IL1RAP is detected prior to treatment, e.g., prior to initial treatment or prior to a treatment after an interval from a certain treatment. In some embodiments, a method of treating a disease of the invention is provided, the method comprising: detecting the presence of IL1RAP in a subject (e.g., a sample) (e.g., a sample of the subject), thereby determining an IL1RAP value; comparing the IL1RAP value to a control value; and if the IL1RAP value is greater than the control value, administering to the subject a therapeutically effective amount of an anti-IL1RAP antibody or fragment thereof (e.g., an anti-IL1RAP antibody or fragment thereof described herein), optionally in combination with one or more additional therapies, thereby treating the disease. These and other aspects and embodiments of the present disclosure are described in the accompanying drawings (a brief description of which follows) and the following detailed description of the invention and illustrated in the following examples. Any or all of the features described above and throughout the present application may be combined in various embodiments of the present disclosure. The following examples further illustrate the present disclosure. However, it is to be understood that the examples are described by way of illustration and not limitation, and that various modifications may occur to those skilled in the art. Examples Example 1. Hybridoma Cell Preparation The research utilized a hybridoma technology platform for antibody discovery. Hybridoma technology is a technology that generates a cell type that can maintain the main characteristics of B lymphocytes and myeloma cells simultaneously by fusing the two. The two types of cells were the antigen-immunized mouse splenic B lymphocytes and the mouse myeloma cells, respectively. The main characteristic of mouse splenic B lymphocytes immunized by a specific antigen is the secretion of antibodies, but they cannot be continuously cultured in vitro; while mouse myeloma cells can divide and proliferate indefinitely under culture conditions, i.e., they are so-called immortalized. Under the action of the selection medium, only when B lymphocytes are fused with myeloma cells to form hybrid cells, can the B lymphocytes have the capacity of continuous culture, and form cell clones with both the antibody secretion function and the retention of cell immortality. In this experiment, the human IL1RAP extracellular domain protein was mixed with Alum or TiterMax adjuvant and mixed well to immunize 5 groups of Balb / c mice, wherein 4 groups were subjected to rapid immunization (4 immunizations within 28 days), and 1 group was subjected to conventional immunization; blood was collected for titer assay after 4 rapid immunizations or 3 conventional immunizations. After the mice with titer up to the standard were sacrificed, splenic B lymphocytes were isolated and subjected to cell fusion plating with myeloma cell line SF (acclimated in-house). Finally, from 640 96-well fusion plates, the binding of the fusion clone supernatants to a GS-CHO cell line stably transfected with human IL1RAP was detected using FACS technique. By combining functional experiments with affinity detection results, 119 clones capable of binding to cells and having inhibitory activity were obtained. Table 1. Experimental Animals and Immunological Information Mouse strain          Balb / c (Beijing Vital River Laboratory Animal Technology Co., Ltd.) Immunization antigen Extracellular domain of human IL1RAP protein (Acro Biosystems, ILP-H5225-1 mg) Immunization method 50 gg / mouse, subcutaneous injection (s.c), 50 pL per spot, 4 spots Number of doses 4 times of rapid immunization, 3 times of conventional immunization Booster               hIL1RAP protein, 50 pg, intraperitoneal injection, performed 3 days immunization         before fusion Electrofusion Dish Preparation: The electrofusion dish was thoroughly soaked in 70% ethanol and blow-dried in an ultra clean bench for later use. Splenocytes were isolated as follows: the mice were sacrificed by cervical dislocation, sterilized with 75% ethanol for body surface for 5 min, and then placed on the mouse dissecting plate in the ultra clean bench in a left lateral decubitus position, with limbs fixed with No. 7 needles. The spleen was taken out following aseptically opening the abdominal cavity, washed with basal medium (prepared as per the following table), and carefully removed the surrounding connective tissue. The spleen was then transferred to another dish containing the basal medium. The spleen was pressed with an elbow forceps and squeezed with a grinding rod to fully release the splenocytes so as to prepare a splenocyte suspension. The cell suspension was filtered through a 40pM cell strainer, washed once with 30 mL of basal medium, and centrifuged at 1200 rpm for 10 min. Table 2. Basic Medium Preparation Method Name            Ingredients                        Preparation method RPMI-1640 (Gibco)                1x Basic medium Penicillin-Streptomycin (Gibco)       1% Lysing red blood cells: The supernatant was removed, the cells were resuspended in 10 mL of RBC lysis buffer (Gibco), and then 20 mL of RBC lysis buffer was added. The suspension was left to stand for 10 min and centrifuged at 1200 rpm for 10 min. After the supernatant was removed, the cells were resuspended in 10 mL of basal medium, and then 20 mL of basal medium was added. The cells were centrifuged at 1200 rpm for 10 min. After the supernatant was removed, the cells were resuspended in 30 mL of basal medium and counted. Electrofusion: SF cells (ATCC, in-house habituated) of mouse myeloma cells were resuspended in 30 mL of basal medium and counted. SF and spleen cells were mixed in a ratio of 1:2 to 1:1, and centrifuged at 1100 rpm for 10 min. After the supernatant was removed, the mixed cells were resuspended in 10 mL of fusion buffer (BTX press). Then 20 mL of fusion buffer was added, and the mixture was centrifuged at 1100 rpm for 10 min, followed by removal of the supernatant. The cells were resuspended in an appropriate amount of fusion buffer, and the mixed cell density was adjusted to 1 x 107 cells / mL. The parameters of the electrofusion instrument were set as follows. 9 mL of cell suspension was added to each dish for electrofusion. Table 3. Parameter Setting of Electrofusion Instrument Condition Mouse (SP2 / 0-ECF-F) Alignment 50V, 30sec Membrane breaking 900V, 30gs, 1X Post-fusion pulse 60V, 3sec Plating after Electrofusion: The cells were left to stand in the dish at room temperature for 15 min. The cells were transferred to a centrifuge tube and diluted to 1-5 x 104 B cells / mL with screening medium (prepared as per the following table). The cell suspension was added to a 96-well plate at 200 pL / well. The screening medium was replaced on day 5 or 7 after the fusion. The screening was performed after day 10 (or longer, depending on the cell growth state) of culture. Hybridoma cells expressing specific anti-hIL1RAP antibodies were screened by FACS (iQue screener). Table 4. Preparation Method of Screening Medium Name Composition Preparation method Hybridoma-SFM (Gibco) 1X OPI media supplement 1X Screening medium Ultra low IgG(BioSUN) 3% HAT medium(Gibco) 100X GlutaMAXTM supplement 100X Positive Hybridoma Cell Subcloning Subcloning step: A 96-well plate was prepared, and 200 pL of the screening medium described above was added to each well in rows 2 to 8. The cells in the positive wells selected from fusion above were made into a cell suspension and added to the first row. 100 pL of the cell suspension of row 1 was added to row 2, and 100 pL was added to the next row after mixing well. repeating the above steps until the volume of the last row becomes 300 pL; leaving the 96-well plate to stand for 15 min, and observing and counting under a microscope. A corresponding volume containing 100 cells was added to 20 mL of subcloning medium AOF (STEMCELL), and the cells were well mixed and plated at 200 pL / well. After one week, the cells were observed under a microscope, and monoclonal wells were identified and marked. Positive wells were picked out for testing. Cell cryopreservation: The cell state was observed. When the cells grew well and the viability was > 90%, the cells were centrifuged at 1000 rpm for 5 min, and the supernatant was removed. The cells were resuspended in cryoprotectant (90% screening medium + 10% DMSO) to 1x107 cells / mL, aliquoted into cryopreservation tubes, placed in programmed cooling boxes, and cryopreserved at -80°C. Example 2. Production and Purification of Chimeric Antibodies In the present disclosure, antibody sequences in anti-hIL1RAP positive hybridoma cells were obtained by using molecular biology techniques, and human-mouse chimeric antibodies were constructed using the antibody sequences. After subcloning the 119 positive fusion cells screened in the above step, the cell binding of the cell line stably transfected with GS-human IL1RAP and the functional assay were performed again, and 55 monoclonal antibodies strains were determined. Subsequently, the 55 strains were subjected to cloning and sequencing by using a molecular cloning technique, and 33 strains of unique sequences were obtained according to sequence diversity to construct chimeric antibodies. The 33 chimeric antibodies were subjected to functional assays and KD affinity assays. The results showed that 63C8H10 had a significant inhibitory effect on the IL-1, IL-33, and IL-36 pathways. Therefore, 63C8H10 was determined as the final lead molecule. Hybridoma Sequencing RNA extraction: RNA was extracted using an RNA extraction kit (Macherey-Nagel): the cells were carefully pipetted and centrifuged at 1000 rpm for 5 min, and the supernatant was discarded; the total number of cells should not exceed 5E6; 350 pL of LBP was added and uniformly mixed until clear, the uniformly mixed liquid was transferred to a DNA Clearance column and centrifuged at 11,000 rpm for 30 s, and 100 pL of BS was added to flow-through and uniformly mixed; the uniformly mixed liquid was transferred to an RNA column and centrifuged at 11,000 rpm for 15 s, and the liquid was discarded; 200 pL of WB1 was added and centrifuged at 11,000 rpm for 15 s, and the liquid was discarded; the RNA column was uncapped and transferred to a new collection tube, and 600 pL of WB2 was added and centrifuged at 11,000 rpm for 15 s, and the liquid was discarded; 250 pL of WB2 was added and centrifuged at 11,000 rpm for 2 min, and the liquid was discarded, and the mixture was centrifuged at 11,000 rpm for 1 min; the RNA column was uncapped and transferred to a new 1.5 mL EP tube, ethanol was volatilized for 2 min, 50 pL of DEPC treated ddH2O was added, the mixture was left to stand for 2 min and centrifuged at 11,000 g for 1 min, and flow-through was collected; the RNA concentration was determined using a Nanodrop instrument, and RNA quality was determined by agarose gel electrophoresis. cDNA obtained by reverse transcription Table 5. The reaction system I was prepared as follows: Name Amount used 5xPrimeScript Buffer * 4 PrimeScript RT Enzyme Mix * 1 Oligo dT Primer * 1 Random Primer * 1 RNA 2ng RNase-Free Water * Up to 20^1 * Available from PrimeScriptTM RT reagent Kit, Purchased from Takara. The mixture was slowly mixed and reverse-transcribed under the following conditions: 15 min at 37 °C^5 min at 85 °C. The mixture was cooled on ice to obtain cDNA. The cDNA was 10-fold diluted as a template and used in the next VH\VL PCR reaction. The PCR reaction system and reaction conditions are shown in Tables 6 and 7. Table 6. The PCR reaction system was prepared as follows: Name Amount used ExTaq (Takara) 0.5 10xExTaq buffer 3 dNTP (2.5 mM each) 4 Forward primer 2 Reverse primer 2 template (cDNA) 1 ddH2O 17.5 Total 30 Table 7: PCR reaction conditions were as follows: 94°C                  5min 94OC                   30s 55°C                   30s 30 cycles 72OC                   40s 72OC 10min Agarose gel electrophoresis 1.5% agarose gel (BIOWEST) was prepared by: boiling the agarose solution and cooling to 50-60 °C; the agarose then added with a nucleic acid dye at a ratio of 1:10000, uniformly mixed and poured into a glue plate; a comb is inserted, then pulled out til the agarose is solidified, and the gel is transferred into an electrophoresis tank for later use; 5 pL of the product after PCR was taken, and 1 pL of 6* loading Buffer was added. The mixture was mixed well, and then added into a gel well, where a marker was DL2000. Electrophoresis was performed for 20 min under the conditions of a voltage of 160 V and a current of 400 mA. After the electrophoresis was completed, the gel was transferred to a fully automatic digital gel image analysis system—Tanon. The software was started, the UV light source was turned on, and the page scaling ratio, exposure value, and focal length were adjusted until a clear gel image could be presented. cDNA was ligated to T vector (Table 8) using Mighty TA-cloning kit (Takara). Table 8: Reaction system Name                 Amount used pMD20-T Vecter          0.5ul Ligation Mighty Mix       5ul Room temperature 4 h PCR product              4.5ul Total                         10ul Transforming cell: The competent DH5a (TIANGEN) was taken from -80°C and thawed on ice. 10 pL of the enzymatic ligation product was added to 50 pL of the competent cells, and the mixture was incubated on ice for 30 min. After heat shock at 42 °C for 90 s, the tube was quickly transferred to ice and left to stand for 3 min. 1 mL of non-resistant LB medium (Sangon Biotech (Shanghai) Co., Ltd.) was added to the tube. The mixture was cultured on a shaker at 37 °C for 60 min at 220 rpm, and then coated on an LBA plate. The plate was cultured in an incubator at 37°C overnight, and clones were picked for sequencing. Construction of chimeric antibody The VH and VL regions, which had been sequenced, of the murine anti-hIL1RAP antibody produced by the hybridoma in Example 1 were amplified by PCR. The PCR amplification product was recovered by gel cutting. Homologous recombination reaction: The homologous recombination system is as follows (Table 9). Table 9: Homologous recombination system Name Amount used 5* Buffer 2 ul Exnase Multis (Vazyme) 1 ul pcDNA3.1-IgG1 LALA (pcDNA3.1 with the constant region of IgG1 LALA (SEQ ID NO: 51)) (20 ng / ul) 1ul pcDNA3.1-kappa (pcDNA3.1 with Kappa constant region (SEQ ID NO: 53)) (20 ng / ul) 1 ul PCR product 3-4 ul H2O Up to 10 The mixture was reacted at 37 °C for 40 min to obtain a recombinant product. The competent DH5a was taken from -80 °C and thawed on ice. 50 pL of the competent DH5a was added to 10 pL of the enzymatic ligation product, and the mixture was incubated on ice for 30 min. After heat shock at 42 °C for 120 s, the tube was quickly transferred to ice and left to stand for 3 min. 1 mL of LB medium was added, and the mixture was cultured on a shaker at 37 °C for 1 h. The mixture was centrifuged at 8000 rpm / min for 30 s, part of the supernatant was discarded, and 100 pL of culture medium was reserved. The bacterial cells were pipetted and mixed well, and coated on an LBA plate. Monoclones were picked for sequencing, and clones containing plasmids with correct insertion direction were selected as positive clones and stored. Expression and Purification of Chimeric Antibodies Plasmid containing anti-hIL1RAP antibody was extracted from the positive clones obtained above. The plasmid was transfected into Expi293F cells, and the target protein was obtained by purification. The specific procedures are as follows: Expi293F cells (purchased from Gibco) were cultured in Expi293F medium (Gibco, REF# A14351-01). The cell density was measured the day before transfection (viability must be greater than 95%) and adjusted to 3x106 cells / mL with fresh Expi293F medium for continued culture, and the cell density was adjusted to 3x106 cells / mL on the day of transfection. 1 / 10 of the final transfection volume of Opti-MEM medium (Gibco, REF# 31985-070) was used as a transfection buffer, and the DNA to be transfected was added according to a ratio of 1 mg / L, wherein the light and heavy chain plasmid ratio was 1:1, and the mixture was mixed uniformly. PEIMax (Polysciences Inc. Cat# 24765-1) was added according to a DNA:PEI mass ratio of 1:3. The mixture was mixed uniformly and incubated at room temperature for 20 min. Then the mixture was gently poured into the Expi293F cell suspension while the suspension was shaken, and the cells were cultured in a shaker under the conditions of 8% CO2, 36.5 °C, and 120 rpm. After culturing for 16-18 h, the cell suspension was supplemented with FEED (100 g / L Phyton peptide + 100g / L Difco Select Phyton) of a concentration of 200 g / L in a volume of 2% (v / v), glucose solution at a final concentration of 5 g / L and Valproic acid sodium salt (Merk, Cat# P4543-100G) at a final concentration of 2.2 mM, followed by blending gently, and the mixture was cultured in 8% CO2, at 36.5°C and 120 rpm for 7 days before sample collection. After centrifugation, the mixture was filtered using a disposable vacuum filtration device of 0.22 pm. Affinity capture of the antibody was performed using a HiTrap MabSelect PrismA (GE Healthcare, Cat# 17549853) affinity chromatography column. Before purification, 10-20 column volumes of 0.1 M NaOH were passed through the pipeline and the affinity chromatography column, and then the pipeline and the column were washed with 10-20 column volumes of distilled water. The packing column was equilibrated with 5 column volumes of 1x PBS (Gibco). The filtered cell broth was passed through the column, and then the packing column was washed with 10 column volumes of 1x PBS to remove non-specific binding proteins. The packing column was washed with 5 column volumes of an elution buffer (100 mM sodium citrate, pH 3.5). The eluate was collected, adjusted to pH 6.0 with 2 M Tris, filtered for sterilization, and sent for SEC analysis. The amino acid sequences of the CDRs, light and heavy chain variable regions, light and heavy chains of 1 chimeric antibody obtained in the present disclosure, as well as the sequence numbers are shown in Table ABCD. The control drugs used in the present disclosure are the IL1 receptor antagonist Anakinra (IL1Ra), and the control antibodies anti-human IL1RAPCAN10, REGN3500, and BI655130, the molecular sequences of which, as well as the amino acid sequences of the CDRs, the light and heavy chain variable regions, and the light and heavy chains of the antibodies, are also shown in Table BCDE. The anti-CAN10 antibody (synthesized in-house), REGN3500 antibody (synthesized in-house), and BI655130 antibody (Biointron) were produced by similar procedures as above. Example 3. Binding Kinetics of Chimeric Antibodies of the Present Disclosure for Antigens Determined by Bio-Layer Interferometry The equilibrium dissociation constant (KD) for binding of the antibodies of the present disclosure to human, cynomolgus monkey, and mouse IL1RAP was determined by Bio-Layer Interferometry (ForteBio). The ForteBio affinity assay was performed according to the existing method (Estep, P, et al., High throughput solution Based measurement of antibody antigen affinity and epitope binning. MAbs, 2013.5(2):2708). Half an hour before the start of the experiment, an appropriate number of AHC (18-5060, Sartorius) sensors were taken and soaked in SD buffer (PBS 1x, BSA 0.1%, Tween 20 0.05%) according to the number of samples. 100 uL of SD buffer, antibodies, and antigens [including human IL1RAP (ILP-H5225, Acro biosystems), mouse IL1RAP (Sino Biological, 52657-M08H), and cynomolgus monkey IL1RAP (Sino Biological, 90934-C08H)] were separately added to 96-well black polystyrene half-area microplates (Greiner, 675076). The sensors are arranged according to the positions of the samples. The instrument settings were as follows: the operation procedures were: Baseline, Loading -1 nm, Baseline, Association, and Dissociation; the run time of each procedure was dependent on the rates of association and dissociation; the rotation speed was 1000 rpm, and the temperature was 30 °C. KD values were analyzed using ForteBio analysis software. In the assay described above, the affinity of antibody 63C8H10 and CAN10 is shown in Table 10: Table 10. Affinity constant (equilibrium dissociation constant) for binding of antigen to antibody by ForteBio assay Antibody name Human KD (M) Monkey KD (M) Mouse KD (M) 63C8H10 4.84E-10 6.47E-10 No binding CAN10 6.32E-10 2.23E-09 No binding In the above assay, the KD values of the chimeric antibody 63C8H10 for human and cynomolgus monkeys were 4.84E-10M and 6.47E-10M, respectively. The antibodies in this study had similar or superior KD values compared to the control antibody CAN10. Example 4. Humanization of chimeric antibodies The chimeric antibodies obtained in Example 1 were humanized. The antibody humanization process was performed using a proprietary software program of Discovery program from Dassault Systemes. Firstly, the sequence was input into software, and the system generated a three-dimensional model of the sequence, which was then humanized through the following steps:: 1. determining the structure of the CDR loop; 2. searching a human germline sequence database for the closest homologous sequences for each V / J region of the heavy and light chains; 3. screening human germlines for the highest match in heavy and light chains and a minimum amount of back mutations; 4. The CDR regions of the chimeric antibody were constructed onto the framework regions of a human antibody. 5. determining the amino acid positions that maintain the CDR functions in the framework regions by using the sequences and structural features; 6. performing back mutation (back to the input amino acids) at important sequence positions determined; 7. Generating a three-dimensional model of the humanized sequence; 8. Manual inspection of sequence and structure to identify risk sites that may lead to misfolding or reduced stability; 9. optimization of amino acids at risk sites. The amino acid sequences of the CDRs, the light and heavy chain variable regions, and the light and heavy chains of the 4 humanized antibodies (HZ63C8.4, HZ63C8.5, HZ63C8.6, and HZ63C8.7) obtained in the present disclosure are shown in Tables A-E below. Example 5. Binding kinetics of humanized antibodies to antigens are determined by ForteBio The equilibrium dissociation constant (KD) for binding of the humanized antibodies of different Fc subtypes of the present disclosure to human IL1RAP was determined by ForteBio assay. The ForteBio affinity assay was the same as that in Example 2. In the assay described above, the affinities of antibodies hz63C8.4, hz63C8.5, hz63C8.6, and hz63C8.7 are shown in Table 11: Table 11. Affinity constants for binding of antigens and antibodies by ForteBio assay Chimeric KD (M,human) antibodies hz63C8.4         4.54E-10 hz63C8.5          5.10E-10 hz63C8.6         3.99E-10 hz63C8.7         4.12E-10 CAN10          6.32E-10 IBI303            No binding In the above assay, the KD values of the humanized antibodies hz63C8.4, hz63C8.5, hz63C8.6, and hz63C8.7 described herein were 4.54E-10M, 5.10E-10M, 3.99E-10M, and 4.12E-10M, respectively. The humanized antibodies in this study had similar or superior KD values compared to the control group CAN10. Example 6. Binding assay of antibodies to cells overexpressing IL1RAP In this study, the binding of the chimeric antibodies and the humanized antibodies of the present disclosure, which were diluted in a gradient, to a CHO stable cell strain overexpressing human IL1RAP on the surface (CHO-hIL1RAP) was assayed by flow cytometry. A CHO cell line (CHO-hIL1RAP) overexpressing human IL1RAP was established by transfecting CHO-GS cells (Lonza) with a full-length plasmid of human IL1RAP (Genewiz). The CHO-hILlRAP cells were counted and diluted to 1 x 10A6 cells / mL, and added to a U-bottom 96-well plate at 100 gL / well. The cell suspension was centrifuged at 400 g for 5 min to remove the cell medium. The chimeric antibody ch63C8 and the humanized antibodies hz63C8.4, hz63C8.5, and hz63C8.6 (the antibodies were serially two-fold diluted from 100 nM or serially three-fold diluted from 300 nM in PBS containing 0.1% bovine serum albumin BSA, and a total of 8 concentrations were tested) were added to the U-plate. The cells were resuspended at 100 gL / well and left to stand on ice for 30 min. The cells were centrifuged at 400 g for 5 min, and then the supernatant was removed. The cells were washed once with PBS. PBS was removed by centrifugation at 400 g for 5 min, and 100 gL of diluted (1:200) PE-labeled secondary antibody anti-human Fc (Biolegend, Cat. No. 410708) was added to each well. The cells were incubated in the dark on ice for 30 min. The cells were centrifuged at 400 g for 5 min, and then the supernatant was removed. The cells were washed once with PBS. The cells were resuspended in 100 gL of 1x PBS and assayed by FACS. The binding of chimeric antibody ch63C8 and humanized antibodies hz63C8.4, hz63C8.5, and hz63C8.6 to CHO-hIL1RAP cells is shown in FIG. 1. In the above assay, the chimeric antibody ch63C8 and the humanized antibodies hz63C8.4, hz63C8.5, and hz63C8.6 can all bind to human IL1RAP overexpressed on CHO cells, with EC50 values being 6.96 nM, 5.94 nM, 9.79 nM, and 4.64 nM, respectively. Example 7. Detection of biological activity of antibody in fluorescent reporter cell strain The anti-IL1RAP antibody can inhibit the activation of the downstream NF-kB signaling pathway by blocking the binding of ILla, ILlp, IL33, and IL36 to the IL1RAP receptor complex. Three fluorescent reporter cell strains provided by Novoprotein Inc. were used in this study: an IL1 pathway activity reporter cell (293-IL1 Res cell strain, XCC10), an IL33 pathway activity reporter cell (293-IL33 Res cell strain, XCC16), and an IL36 pathway activity reporter cell (293-IL36 Res cell strain, XCC15-1). According to the method provided in the instructions, the activation of NF-kB signal was reflected by detecting the expression of fluorescent reporter genes, thereby detecting the inhibitory effect of the binding of the antibodies to IL1RAP. Detection of biological activity of antibodies on IL1 pathway in a fluorescent reporter cell strain Thawing: 1) the cryopreserved cells were thawed by gentle shaking in a water bath at 37 °C, with the sealing ring and the bottle cap kept above the water surface to reduce the risk of bacterial infection, and the thawing should be performed as soon as possible (within 1 min); 2) after the cells were thawed, the cells were immediately disinfected with 75% alcohol and then transferred to an ultra clean bench, and subsequent sterile operations should be performed strictly; 3) the cell suspension was transferred to a centrifuge tube containing 10 mL of preheated subculture medium (FreeStyleTM 293 Expression Medium), and passaged 3 times after thawed, and then Neomycin (100 gg / mL) was added; 4) the cells were centrifuged at 800-1000 rpm (RCF 200-300 g) for 5 min; 5) the supernatant was discarded, and 1 mL of subculture medium was added to resuspend the cells; 6) the cells were transferred to a 125 mL shake flask containing 19 mL of subculture medium; and 7) the cells were cultured with shaking at 120 rpm in a shaker at 37 °C and 7% CO2. Cell culture: The Neomycin pressure (100 gg / mL) is maintained during passaging; passaging is performed every 1-2 days; the density of passaging should be controlled at 0.3-0.5 x 106 cells / mL. Activity assay: 1). Cell plating: the cells were counted, the cell density was adjusted to 3 x 105 cells / mL, and 100 gL of the cells were added to a 96-well plate and cultured overnight in an incubator at 37 °C. 2) Treatment with antibody and cytokine: The test sample hz63C8.6 antibody, HEL (negative control), and CAN10 were diluted to 1.2 gM (with a final concentration of 300 nM) using FreeStyleTM 293 medium, and then serially 3-fold diluted to obtain a total of 11 concentrations. 50 gL of each diluted sample was added to a 96-well plate with cells plated thereon, and the plate was left to stand in an incubator at 37 °C for 1 h. Human IL-1B (Acro Biosystems, ILB-H4110-50 gg) was diluted to 4 ng / mL (with a final concentration of 1 ng / mL) and added at 50 gL / well, with a final volume of 200 uL. The mixture was left to stand for culture for 6 h. 3) Fluorescence detection: A lysis solution of Bio-Lite Luciferase Assay System (Nanjing Vazyme, Cat. No.: DD1201-02) was mixed with the substrate, and then equilibrated at room temperature for 30 min. The 96-well plate was centrifuged at 300 g for 5 min. 100 gL of supernatant was gently pipetted off, and the left 100 gL was remained. Then 100 gL of 1x lysis buffer (1:1 volume) of Bio-Lite Luciferase Assay System was added. The mixture was shaken gently, left to stand for more than 10 min, and tested by the instrument. In the above experiments, the experimental results are shown in FIG. 2. The antibody hz63C8.6 can effectively block the activation of IL1p—mediated downstream signaling pathways, and the inhibitory effect is comparable to that of the benchmark CAN10 (Cantargia). Detection of biological activity of antibodies on IL36 pathway in a fluorescent reporter cell strain Cell culture: The IL36 pathway fluorescent reporter cell strain 293-IL36 Res (Novoprotein, XCC15-1) was cultured in a DMEM medium containing 10% FBS, with no antibiotics added for the first three generations after thawing. The cells were placed in an incubator at 37°C with 5% CO2 for static culture. After three generations of culture, antibiotics are added (25ug / ml-Hygro + 400ug / ml-G418) and the culture is continued. In general, after another 2-3 generations of culture, the cells can be used for experiments. After the cells were digested with TrypLE (GIBCO, 12605028), the cells were counted, and the cell density was adjusted to 3E5 cells / mL with a medium (90% DMEM + 10% FBS + 25 gg / mL-Hygro + 400 gg / mL-G418). 100 gL of the cell suspension was added to each well of a 96-well light-emitting plate (Shanghai Yuhong, WHB-96-03) with a white bottom transparent cover, and the cells were cultured overnight. The next day, each test sample was diluted to 1.2 gM (final concentration: 300 nM) with culture medium, and then serially 3-fold diluted to obtain 11 concentrations. 50 gL of benchmark CAN10 and the anti-IL1RAP antibody hz63C8.6 at corresponding concentrations were added according to the experimental design, and the mixture was incubated in an incubator for 1 h. Then, IL36a (Novoprotein, CR61) was diluted to 400 ng / mL (with a final concentration of 100 ng / mL) with the culture medium and added at 50 afwell, with a final volume of 200 af. The mixture was cultured in an incubator for 6 h. The mixture was centrifuged at 300 g for 5 min, 100 pL of the supernatant was discarded, and 100 Ll of Bio-lite luciferase Assay system was added for lysis for 5-10 min, followed by loading on the machine for assay. In the above experiments, the experimental results are shown in FIG. 3. The antibody hz63C8.6 can effectively block the Il36-mediated activation of downstream signaling pathways, and the inhibitory effect is comparable to that of the benchmark CAN10 (Cantargia). Detection of biological activity of antibodies on IL33 pathway in a fluorescent reporter cell strain Cell culture: The Il33 pathway fluorescent reporter cell strain 293-Il33 Res cell strain (Novoprotein, XCC16) was cultured in a DMEM medium containing 10% FBS, and no antibiotics were added for the first three generations after thawing. The cells were placed in an incubator at 37°C with 5% CO2 for static culture. After three generations of culture, the antibiotics (6.25ug / ml-Hygro + 12.5ug / ml-G418) are added and the culture is continued. Generally, after another 2-3 generations of culture, the cells can be used for experiments. After the cells were digested with TryplE (GIBCO, 12605028), the cells were counted, and the cell density was adjusted to 3E5 cells / ml with a medium (90% DMEM + 10% FBS + 6.25 Lg / ml-Hygro + 12.5 Lg / ml-G418). 100 Ll of the cell suspension was added to each well of a 96-well light-emitting plate (Shanghai Yuhong, WHB-96-03) with a white bottom transparent cover, and the cells were cultured overnight. The next day, each test sample was diluted to 1.2 LM (final concentration: 300 nM) with culture medium, and then serially 3-fold diluted to obtain 11 concentrations. 50 Ll of benchmark CAN10 and the anti-Il1RAP antibody hz63C8.6 at corresponding concentrations were added according to the experimental design, and the mixture was incubated in an incubator for 1 h. Then, human Il33 (PeproTech, 200-33-100UG) was diluted to 80 ng / ml (with a final concentration of 20 ng / ml) with the medium, added to the plate at 50 Ll / well, with a final volume of 200 Ll, and cultured in an incubator for 6 h. The mixture was centrifuged at 300 g for 5 min, 100 Ll of the supernatant was discarded, and 100 gL of Bio-Lite Luciferase Assay system was added for lysis for 5-10 min, followed by loading on the machine for assay. In the above experiments, the experimental results are shown in FIG. 4. The antibody hz63C8.6 can effectively block the activation of IL33-mediated downstream signaling pathways, and the inhibitory effect is better than that of the benchmark CAN10 (Cantargia). Example 8. The activity of the antibodies against the IL36 signaling pathway was verified in squamous cell carcinoma cell line A431 cells Cell culture: A431 squamous cell carcinoma cells (ATCC, CRL-1555) were cultured in a DMEM medium containing 10% FBS. The cells were placed in an incubator at 37°C with 5% CO2 for static culture. In general, after another 2-3 generations of culture, the cells can be used for experiments. After the cells were digested with TrypLE (GIBCO, 12605028), the cells were counted, and the cell density was adjusted to 1E5 cells / mL with a medium (90% DMEM + 10% FBS + 1% Pen / strep). 100 gL of the cell suspension was added to each well of a 96-well light-emitting plate (Shanghai Yuhong, WHB-96-03) with a white bottom transparent cover, and the cells were cultured overnight. The next day, each test sample was diluted to 400 nM (final concentration: 100 nM) with the medium and then serially 10-fold diluted for a total of 6-7 concentrations. 50 gL of benchmark CAN10 (Cantargia), BI655130, and humanized antibodies hz63C8.4, hz63C8.5, hz63C8.6, and hz63C8.7 at corresponding concentrations were added according to the experimental design, and the cells were pretreated in an incubator for 1 h. Then, the cytokine human IL36a (Novoprotein, CR61) was diluted to 400 ng / mL (final concentration: 100 ng / mL) with the medium and added at 50 gL / well, with a final volume of 200 gL. The mixture was incubated in an incubator for another 24 h. The cells were centrifuged at 300 g for 5 min, and the supernatant was collected. After the supernatant was 3-fold diluted, the concentration of IL-8 in the cell supernatant was determined according to the instructions of the Human IL-8 ELISA Ready-SET-Go kit (eBioscience, 88-8086-88). In the above experiment, as shown in FIG. 5, the chimeric antibodies and the humanized antibodies can effectively block the activation of IL36-mediated downstream signaling pathways in epithelial cells. Example 9. The inhibitory activity of the antibodies against the IL-1 pathway was detected in PBMC cells PBMCs were rapidly thawed in a water bath at 37°C and added to an RPMI 1640 complete medium containing DNase I (10% FBS, 1% Pen Strep, 10% Sodium Pyruvate, and 1% 2-Me). The mixture was centrifuged at 250 g for 7 min, and the supernatant was discarded. The cells were washed with the above complete medium and centrifuged again. The procedures were repeated twice. The cells were resuspended in an RPMI 1640 complete medium, and the cell density was adjusted to 2 x 10A6 cells / mL. The cells were seeded into a 96-well round-bottom plate (Corning, 3799) at 100 pLwell. The benchmark proteins anti-IL1RAP antibody CAN10 (Cantargia), Anakinra (IL1R antagonist, IL1Ra, Medchemexpress, HY-108841), the anti-IL1RAP antibody chimeric antibody 63C8H10, and the humanized antibodies hz63C8.4, hz63C8.5, hz63C8.6, and hz63C8.7 were diluted to different concentrations. Each antibody was diluted to 4000 nM (final concentration: 1000 nM) and further 3-fold diluted for 11 points in sequence, or 10-fold diluted from 400 nM (final concentration: 100 nM) for 6 points in sequence, and 50 aL of each dilution was added to the corresponding wells for pretreatment for 1 h. Then, human IL1p (Acro Biosystems, ILB-H4110-50 pg) were diluted to 400 ng / mL (final concentration: 100 ng / mL) and ILla (Novoprotein, C070) were diluted to 400 ng / mL (final concentration: 100 ng / mL) and 50 aL of each of the diluted IL1p and IL1a was added to the corresponding 96-well plate. Final volume per well was 200 ul. After 24 h of co-stimulation, the supernatant was collected and assayed for TNFa secretion by ELISA. The experimental results described above are shown in FIG. 6. Both the chimeric antibodies and the humanized antibodies can strongly inhibit the IL-1 signaling pathway in PBMC cells, and the inhibitory effects are stronger than those of the commercially available drugs Anakinra for the IL-1 pathway and antiIL1RAP benchmark CAN10. Example 10. The inhibitory activity of the antibodies against the IL-36 pathway was detected in PBMC cells PBMCs were rapidly thawed in a water bath at 37°C and added to an RPMI 1640 complete medium containing DNase I (10% FBS, 1% Pen Strep, 10% Sodium Pyruvate, and 1% 2-Me). The mixture was centrifuged at 250 g for 7 min, and the supernatant was discarded. The cells were washed with the above complete medium and centrifuged again. The procedures were repeated twice. The cells were resuspended in an RPMI 1640 complete medium, and the cell density was adjusted to 2 x 10A6 cells / mL. The cells were seeded into a 96-well round-bottom plate (Corning, 3799) at 100 pL / well. The benchmark proteins anti-IL1RAP antibodies CAN10 (Cantargia), BI 655130 (anti-IL36R), and humanized anti-IL1RAP antibodies hz63C8.4, hz63C8.5, hz63C8.6, and hz63C8.7 were diluted to different concentrations. Each antibody was diluted to 400 nM (final concentration: 100 nM), and further 10-fold diluted for 6 different concentrations in sequence. 50 pL of each dilution was added to the corresponding wells, and the mixture was pretreated for 1 h. Then human IL36a (Novoprotein, CR61) was diluted to 400 ng / mL (final concentration: 100 ng / mL), and 50 pL of each diluted IL36a was added to the corresponding 96-well plate. Final volume per well was 200 ul. After 24 h of co-stimulation, the supernatant was collected and assayed for TNFa secretion by ELISA. The experimental results described above are shown in FIG. 7. The humanized anti-IL1RAP antibody can potently inhibit the IL-36 signaling pathway in PBMC cells, and the inhibitory effect is stronger than that of the anti-IL36R benchmark BI 655130. Example 11. The inhibitory activity of the antibodies against the IL-33 pathway was detected in PBMC cells PBMCs were rapidly thawed in a water bath at 37°C and added to an RPMI 1640 complete medium containing DNase I (10% FBS, 1% Pen Strep, 10% Sodium Pyruvate, and 1% 2-Me). The mixture was centrifuged at 250 g for 7 min, and the supernatant was discarded. The cells were washed with the above complete medium and centrifuged again. The procedures were repeated twice. The cells were resuspended in an RPMI 1640 complete medium, and the cell density was adjusted to 2 x 10A6 cells / mL. The cells were seeded into a 96-well round-bottom plate (Corning, 3799) at 100 pL / well. The benchmark proteins anti-IL1RAP antibody CAN10 (Cantargia), REGN3500 (anti-IL33), the anti-IL1RAP antibody chimeric antibody 63C8H10, and the humanized antibodies hz63C8.4, hz63C8.5, hz63C8.6, and hz63C8.7 were diluted to different concentrations. Each antibody was diluted to 400 nM (final concentration: 100 nM), and futher 10-fold diluted in sequence to obtain 6-7 different concentrations. 50 pL of each dilution was added to the corresponding wells, and the mixture was pretreated for 1 h. Then, the cytokines IL33 (PeproTech, 200-33-100UG) were diluted to 80 ng / mL (final concentration: 20 ng / mL) and IL12 (Novoprotein, GMP-CI58) were diluted to 8 ng / mL (final concentration: 2 ng / mL), respectively, and 50 gL of the diluted mixed cytokines of IL33 + IL12 were added to the corresponding 96-well plate. Final volume per well was 200 ul. After 24 h of co-stimulation, the supernatant was collected and assayed for IFNy secretion by ELISA. The experimental results described above are shown in FIG. 8. The chimeric antibodies and the humanized antibodies can all inhibit the IL33 signaling pathway in PBMC cells, and the inhibitory effects were stronger than that of the anti-IL1RAP antibody benchmark CAN10 and weaker than that of the anti-IL33 antibody REGN3500. Example 12. Pharmacokinetic Profile for Subcutaneous Administration in Mice In Balb / c mice, the anti-IL1RAP antibody hz63C8.6 molecule was administered by subcutaneous injection (10 mg / kg). Peripheral blood samples were collected at 0 h, 0.5 h, 2 h, 6 h, 24 h, 48 h, 96 h, 192 h, 336 h, 504 h, 672 h, 840 h and 1008 h post-dose, left to stand at room temperature for 3 h or more, and then subjected to coagulation. The blood samples were centrifuged (at room temperature, 5000 rpm, 5 min) to collect serum. The content of anti-IL1RAP in serum at different time points was determined by ELISA. The results showed that anti-IL1RAP exhibited good pharmacokinetic profile in mice (Table 12). The plasma concentration has not yet dropped below 1 / 10 Cmax for up to 42 days of monitoring. Calculated from the acquired data, the T1 / 2 was 316 h, and the clearance rate CL was 0.23 mL / kg / h (Table 12). Table 12: Pharmacokinetic study parameters of anti-IL1RAP antibody (hz63C8.6) in mice after subcutaneous administration Cmax Tmax AUC0-inf_obs AUC0-t CL / F T1 / 2 Vss / F ug / ml h ug*h / ml ug*h / ml ml / h / kg h ml / kg hz63C8.6   106 24 42620 36689 0.23 316 107 Example 13. Pharmacokinetic Profile for Intravenous Administration in Mice In Balb / c mice, after the anti-IL1RAP antibody hz63C8.6 molecule was administered by tail vein injection (10 mg / kg), peripheral blood was collected 0 h, 0.083 h, 0.5 h, 2 h, 6 h, 24 h, 48 h, 96 h, 168 h, 336 h, and 504 h after the administration, and serum was collected to detect the content of anti-IL1RAP in the peripheral blood by ELISA. The results showed that anti-IL1RAP exhibited good pharmacokinetic characteristics in mice (Table 13). The monitoring lasted for up to 504 h. According to the acquired data, the T1 / 2 was 192 h, and the clearance CL was 0.45 mL / kg / h (Table 13). Table 13: Pharmacokinetic study parameters of anti-IL1RAP antibody (hz63C8.6) in mice after intravenous administration Cmax AUC0-inf_obs AUC0-t CL T1 / 2 Vss ug / ml ug*h / ml ug*h / ml ml / h / kg h ml / kg Hz63C8.6 193 22171 18236 0.45 192 123 Example 14. Analysis of Physicochemical Properties of Antibody IBI303 (adalimumab) and IBI310 (ipililumab) were used as control antibodies in this study. IBI303 has good druggability, and IBI310 has poor druggability. 1) Determination of antibody colloidal stability by SMAC column The colloidal stability of the antibody was determined by recording the retention time of the antibody in the Zenix-HPLC column. 2) Detection of antibody colloid hydrophobicity by HIC column The hydrophobicity of the antibody was detected by recording the retention time of the antibody in the HIC-HPLC column. 3) Detection of non-specificity of antibody by CIC IgG from human serum was coated on an NHS-activated chromatography column, and the retention time of the antibody on the column was investigated by HPLC, which showed a significant negative correlation with its solubility. Therefore, antibodies with better solubility can be screened by this method. 4) Thermal stability of antibodies determined by DLS Dynamic light scattering (DLS) employs laser to irradiate small particles that perform Brownian motion in a solution and detects changes in the intensity of scattered light. DLS can be used to detect the particle size of proteins in solution and its stability at different temperatures or concentrations. 5) Thermal stability of antibody determined by DSC Differential Scanning calorimetry (DSC) is a method of thermal analysis. It is an analysis method for measuring the energy difference between a sample and a reference substance as a function of temperature at a programmed temperature. As the temperature increased, the protein structure changed, and the accompanying heat changes were recorded on a DSC curve by a differential scanning calorimeter. The Tm values of the proteins were obtained by analyzing the DSC curve. Table 14. Detection results of thermal stability of antibodies Colloidal stability Poly-specificity Hydrophobicity Thermostability SMAC (min) CIC (min) HIC (min) Tagg Hz63C8.6 8.35 8.63 16.43 60.88 IBI303 7.89 8.93 11.61 61.3 IBI310 12.76 10.84 15.81 68.6 Example 15. Verification of biological activity of antibodies in a mouse acute peritonitis model IL1RAP humanized mice on male C57BL / 6 background (B-hIL1RACP mice, Biomice, Cat. No: 110072), 6-8 weeks of age, after 1 week of acclimatization, were randomly divided into four groups: an untreated group (i.e., untreated group), an Anakinra treatment group, an hz63C8.6 treatment group, and a PBS treatment group. The latter three groups were injected with Anakinra (10 mg / kg, Medchemexpress, HY-108841), hz63C8.6 (20 mg / kg) and PBS (200 p.L) via the tail vein, and 1 h later intraperitoneally injected with monosodium urate crystals (MSU, InvivoGen, tlrl-msu-25) at 3 mg / animal to induce an acute peritonitis model. After 6 h, the abdominal cavity cells were rinsed with cold PBS (10 mL for each mouse). The collected liquid was placed in a 15-mL centrifuge tube. After all mice were rinsed, the tube was centrifuged at 300 g at 4°C for 5 min. The supernatant was discarded, and the cell pellet was resuspended in PBS containing 0.5% BSA. The cells were counted and stained by flow cytometry to detect the changes in various immune cells. The results showed that after hz63C8.6 treatment, the mice’s abdominal inflammation was significantly alleviated, the inflammatory cell recruitment in the abdominal cavity was significantly reduced (FIG. 9), and the number of neutrophils was significantly reduced (FIG. 9). Moreover, the inhibitory effect of hz63C8.6 tended to be better than that of Anakinra. Example 16. Verification of biological activity of antibodies in a mouse gout model IL1RAP humanized mice on male C57BL / 6 background (B-hIL1RACP mice, Biomice, Cat. No: 110072), 8-10 weeks old, after 1 week of acclimatization, the mice were randomly divided into four groups: untreated group (i.e., untreated group), Anakinra treatment group, hz63C8.6 treatment group, and PBS treatment group. The last three groups were injected with Anakinra (10 mg / kg, Medchemexpress, HY-108841), hz63C8.6 (20 mg / kg) and PBS (200 pL) via the tail vein, and 1 h later injected with monosodium urate crystals (MSU, InvivoGen, tlrl-msu-25) at 1.8 mg / 50 gL per mouse to induce an acute gout model. After 24 hours, the mice were observed for redness and swelling of the paws and the thickness of the paws was measured. The results show that in the hz63C8.6 treatment goup, the onset of gout was significantly alleviated and the paw thickening in mice was inhibited, and the inhibitory effect was better than that of Anakinra (FIG. 10). Example 17. Verification of biological activity of antibodies in mouse dermatitis model IL1RAP and IL36R double humanized mice (B-hIL36R / hIL1RACP mice, Biomice, Cat. No: 112383), 6-8 weeks old, after 1 week of acclimatization, the mice were randomly divided into five groups: an untreated group (i.e., untreated group), an anti-IL36R treatment group (i.e., BI 655130 group), an anti-IL1RAP antibody Bench mark control group (i.e., CAN10 group), an hz63C8.6 treatment group, and a PBS treatment group. The last four groups were administered BI655130 (10 mg / kg), CAN10 (10 mg / kg), hz63C8.6 (10 mg / kg), and PBS (200 gL) via tail vein injection, respectively. Then, human IL-36y cytokine (Novoprotein, CM77-500g) was injected into the ear skin 1 day, 3 days, 5 days and 7 days after administration at 2 gg / 25 gL per mouse to induce an ear dermatitis mouse model, and the change in ear thickness of the mice was measured at the time of each injection of cytokine. The results showed that hz63C8.6 could significantly inhibit the skin inflammation of mice induced by human IL36y, characterized by a decrease in the thickness of the skin of the mice, and its inhibitory effect was comparable to that of BI 655130 and significantly stronger than that of CAN10. (Fig. 11). Sequence Summary Table A. CDR sequences of heavy and light chain variable regions of the exemplary antibodies of the present disclosure and control antibodies described herein Antibody name HCDR1 (Kabat&Chothia) HCDR2 (Kabat) HCDR3 (Kabat) LCDR1 (Kabat) LCDR2 (Kabat) LCDR3 (Kabat) 63C8H10 DYIFITYWMN (SEQ ID NO:1) QIFPASGTTKYNEMFEG (SEQ ID NO:2) NFYYRYEGGYGMDY (SEQ ID NO:3) RASQSVSTSSFSSIH(SEQ ID NON) YASNLES (SEQ     ID NON) QHSWEILST (SEQ ID NON) HZ63C8.4 SEQ ID NON SEQ ID NO:2 SEQ ID NO :3 SEQ ID NON SEQ ID NON SEQ ID NON HZ63C8.5 SEQ ID NON SEQ ID NO:2 SEQ ID NO :3 SEQ ID NON SEQ ID NON SEQ ID NON HZ63C8.6 SEQ ID NON SEQ ID NO:2 SEQ ID NO :3 SEQ ID NON SEQ ID NON SEQ ID NON HZ63C8.7 SEQ ID NON SEQ ID NO:2 SEQ ID NO :3 SEQ ID NON SEQ ID NON SEQ ID NON CAN 10 HFDIT (SEQ ID NO:7) TISPGVSTYYASWAKS (SEQ IDNO:8) GGVGSSWKAFDL (SEQ ID NO: 9) QASESISTALA (SEQ ID NONO) KASTLPS (SEQ     ID NO:11) QQGFSSGNVHN (SEQ ID NO: 12) Table B. Heavy and light chain variable regions of the exemplary antibodies of the present disclosure and control antibodies described herein Antibod y name Heavy chain variable region (VH) Light chain variable region (VL) 63C8H1 0 EVQLQQSGPELVRPGASVKMSCKTSDYIFITYWMNWVKQRPGQGLEWIGQIFPASGTT KYNEMFEGKATLTVDTSSSTAYMQLSSLTSEDSAVYYCARNFYYRYEGGYGMDYWG QGTSLTVSS (SEQ ID NO: 13) DIVLTQSPASLTVSLGQRATISCRASQSVSTSSFSSIHWYQQKPGQPPKLLI KYASNLESGVPARFSGSGSGTDFTLNIHPVEEEDTATYYCQHSWEILSTF GGGTKLDIK (SEQ ID NO:23) HZ63C8 .4 QVQLVQSGAEVKKPGASVKVSCKASDYIFITYWMNWVRQAPGQGLEWMGQIFPASG TTKYNEMFEGRVTMTVDTSTSTVYMELSSLRSEDTAVYYCARNFYYRYEGGYGMDY WGQGTLVTVSS (SEQ ID NO: 14) EIVLTQSPATLSLSPGERATLSCRASQSVSTSSFSSIHWYQQKPGQAPRLLI KYASNLESGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQHSWEILSTFG GGTKVEIK SEQ ID NO:24 HZ63C8 QVQLVQSGAEWKPGASVKVSCKASDYIFITYWMNWVRQAPGQGLEWMGQIFPASG SEQ ID NO:24 .5 TTKYNEMFEGRVTMTVDTSTSTVYMELSSLRSEDTAVYYCARNFYYRYEGGYGMDY WGQGTLVTVSS (SEQ ID NO: 15) HZ63C8 .6 QVQLVQSGAEWKPGASVKVSCKASDYIFITYWMNWVRQAPGQGLEWMGQIFPASG TTKYNEMFEGRVTMTVDTSISTAYMELSRLRSDDTAVYYCARNFYYRYEGGYGMDY WGQGTLVTVSS (SEQ ID NO: 16) EIVLTQSPATLSLSPGERATLSCRASQSVSTSSFSSIHWYQQKPGQAPRLLI KYASNLESGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQHSWEILSTFG GGTKVEIK (SEQ ID NO:25) HZ63C8 .7 QVQLVQSGAEWKPGASVKVSCKASDYIFITYWMNWVRQATGQGLEWMGQIFPASG TTKYNEMFEGRVTMTVNTSISTAYMELSSLRSEDTAVYYCARNFYYRYEGGYGMDY WGQGTLVTVSS (SEQ ID NO: 17) SEQ ID NO:25 CAN10 QEQLEESGGGLVKPGGTLSLTCTVSGPSLSHFDITWIRQPPGKGLEWIGTISPGVSTYYA SWAKSRVTISVDTSLNTVSLKLSSVTAADTATYFCARGGVGSSWKAFDLWGPGTLVTI SS (SEQ ID NO: 18) ELVMTQSPSSVSASVGDRVTITCQASESISTALAWYQQKPGKAPKLLIYK ASTLPSGVPSRFSGSGSGTDFTLTINSLQPEDFATYYCQQGFSSGNVHNAF GGGTKVEIK (SEQ ID NO:27) BI65513 0 QVQLQQSGTELLKPGASVKLSCKASGNTVTSYWMHWVKQRPGQGLEWIGEILPSTGR TNYNENFKGKAMLTVDKSSSTAYMQLSSLASEDSAVYYCTIVYFGNPWFAYWGQGTL VTVAS (SEQ ID NO: 19) QIVLTQSPAIMSASLGERVTMTCTASSSVSSSYLHWYQKKPGSSPKLWV YSTSNLASGVPVRFSGSGSGTSYSLTISSMEAEDAATYYCHQHHRSPVTF GSGTKLEMK (SEQ ID NO: 28) REGN3 500 EVQLVESGGNLEQPGGSLRLSCTASGFTFSRSAMNWVRRAPGKGLEWVSGISGSGGRT YYADSVKGRFTISRDNSKNTLYLQMNSLSAEDTAAYYCAKDSYTTSWYGGMDVWGH GTTVTVSS (SEQ ID NO: 20) DIQMTQSPSSVSASVGDRVTITCRASQGIFSWLAWYQQKPGKAPKLLIYA ASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFAIYYCQQANSVPITFGQGT RLEIK(SEQ ID NO: 29) IBI3O3 ( adali mumab ) EVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSAITWNSG HIDYADSVEGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCAKVSYLSTASSLDYWGQ GTLVTVSS (SEQ ID NO: 21) DIQMTQSPSSLSASVGDRVTITCRASQGIRNYLAWYQQKPGKAPKLLIYA ASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDVATYYCQRYNRAPYTFGQ GTKVEIK (SEQ ID NO: 30) IBI310 ( ipilu mab) QVQLVESGGGWQPGRSLRLSCAASGFTFSSYTMHWVRQAPGKGLEWVTFISYDGNN KYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAIYYCARTGWLGPFDYWGQGTLV TVSS (SEQ ID NO: 22) EIVLTQSPGTLSLSPGERATLSCRASQSVGSSYLAWYQQKPGQAPRLLIY GAFSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQ GTKVEIK (SEQ ID NO: 31) Table C. Heavy and light chains of the exemplary antibodies of the present disclosure and control antibodies described herein Antibody name Heavy chain (HC) Light chain (LC) 63C8H10 EVQLQQSGPELVRPGASVKMSCKTSDYIFITYWMNWVKQRPGQGLEWIGQIFPASGTTKYN EMFEGKATLTVDTSSSTAYMQLSSLTSEDSAVYYCARNFYYRYEGGYGMDYWGQGTSLT VSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS SGLYSLSSWTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGP SVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST YRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:32) DIVLTQSPASLTVSLGQRATISCRASQSVSTSSFSSIHWYQQKPGQPPK LLIKYASNLESGVPARFSGSGSGTDFTLNIHPVEEEDTATYYCQHSWE ILSTFGGGTKLDIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPR EAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK HKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO:42) HZ63C8.4 QVQLVQSGAEVKKPGASVKVSCKASDYIFITYWMNWVRQAPGQGLEWMGQIFPASGTTK YNEMFEGRVTMTVDTSTSTVYMELSSLRSEDTAVYYCARNFYYRYEGGYGMDYWGQGTL VTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL QSSGLYSLSSWTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAG GPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN STYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:33) EIVLTQSPATLSLSPGERATLSCRASQSVSTSSFSSIHWYQQKPGQAPR LLIKYASNLESGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQHSWEI LSTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPR EAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK HKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO:43) HZ63C8.5 QVQLVQSGAEWKPGASVKVSCKASDYIFITYWMNWVRQAPGQGLEWMGQIFPASGTTK YNEMFEGRVTMTVDTSTSTVYMELSSLRSEDTAVYYCARNFYYRYEGGYGMDYWGQGTL VTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL QSSGLYSLSSWTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAG GPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN STYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:34) (SEQ ID NO:43) HZ63C8.6 QVQLVQSGAEWKPGASVKVSCKASDYIFITYWMNWVRQAPGQGLEWMGQIFPASGTTK EIVLTQSPATLSLSPGERATLSCRASQSVSTSSFSSIHWYQQKPGQAPR YNEMFEGRVTMTVDTSISTAYMELSRLRSDDTAVYYCARNFYYRYEGGYGMDYWGQGTL VTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL QSSGLYSLSSWTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAG GPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN STYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:35) LLIKYASNLESGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQHSWEI LSTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPR EAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK HKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO:44) HZ63C8.7 QVQLVQSGAEWKPGASVKVSCKASDYIFITYWMNWVRQATGQGLEWMGQIFPASGTTK YNEMFEGRVTMTVNTSISTAYMELSSLRSEDTAVYYCARNFYYRYEGGYGMDYWGQGTL VTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL QSSGLYSLSSWTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAG GPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN STYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:36) (SEQ ID NO:44) CAN10 QEQLEESGGGLVKPGGTLSLTCTVSGPSLSHFDITWIRQPPGKGLEWIGTISPGVSTYYASWA KSRVTISVDTSLNTVSLKLSSVTAADTATYFCARGGVGSSWKAFDLWGPGTLVTISSASTKG PSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSS WTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPK PKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVL TVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVM HEALHNHYTQKSLSLSPG (SEQ ID NO:37) ELVMTQSPSSVSASVGDRVTITCQASESISTALAWYQQKPGKAPKLLI YKASTLPSGVPSRFSGSGSGTDFTLTINSLQPEDFATYYCQQGFSSGN VHNAFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYP REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE KHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO:45) BI655130 QVQLVQSGAEVKKPGASVKVSCKASGYSFTSSWIHWVKQAPGQGLEWMGEINPGNVRTN YNENFRNKVTMTVDTSISTAYMELSRLRSDDTAVYYCTWFYGEPYFPYWGQGTLVTVSS ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL YSLSSWTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVF LFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR WSVLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQ QIVLTQSPGTLSLSPGERATMTCTASSSVSSSYFHWYQQKPGQAPRL WIYRTSRLASGVPDRFSGSGSGTDFTLTISRLEPEDAATYYCHQFHRS PLTFGAGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPRE AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKH KVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 46) VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF SCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 38) REGN3500 EVQLVESGGNLEQPGGSLRLSCTASGFTFSRSAMNWVRRAPGKGLEWVSGISGSGGRTYYA DSVKGRFTISRDNSKNTLYLQMNSLSAEDTAAYYCAKDSYTTSWYGGMDVWGHGTTVTV SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS GLYSLSSWTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPS VFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY RWSVLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNV FSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 39) DIQMTQSPSSVSASVGDRVTITCRASQGIFSWLAWYQQKPGKAPKLL IYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFAIYYCQQANSVPIT FGQGTRLEIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAK VQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKV YACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO:47) IBI3O3(ad alimumab ) EVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSAITWNSGHIDY ADSVEGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCAKVSYLSTASSLDYWGQGTLVTVS SASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG LYSLSSWTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVF LFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR WSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF SCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 40) DIQMTQSPSSLSASVGDRVTITCRASQGIRNYLAWYQQKPGKAPKLL IYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDVATYYCQRYNRAP YTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPRE AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKH KVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 48) IBI310(ipi lumab) QVQLVESGGGWQPGRSLRLSCAASGFTFSSYTMHWVRQAPGKGLEWVTFISYDGNNKYY ADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAIYYCARTGWLGPFDYWGQGTLVTVSSAST KGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSL SSWTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSV MHEALHNHYTQKSLSLSPGK (SEQ ID NO: 41) EIVLTQSPGTLSLSPGERATLSCRASQSVGSSYLAWYQQKPGQAPRLL IYGAFSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSP WTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPRE AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKH KVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 49) Table D. Heavy and light chain constant regions of the exemplary antibodies IgGl heavy chain constant region ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDK THTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSN KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHE ALHNHYTQKSLSLSPGK (SEQ ID NO:50) IgGl heavy chain constant        region (comprising mutations L234A and L235A at positions 234 and 235) ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDK THTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVS NKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMH EALHNHYTQKSLSLSPGK (SEQ ID NO:51) IgGl heavy chain constant        region (comprising mutations P329G, L234A, and L235A at positions 329, 234, and 235) ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVD KKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV LTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL DSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 52) k light chain constant region RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQG LSSPVTKSFNRGEC (SEQ ID NO:53) Table E. Amino acid sequence of control drug Anakinra used in the present disclosure Anakinra amino acid MRPSGRKSSKMQAFRIWDVNQKTFYLRNNQLVAGYLQGPNVNLEEKIDVVPIEPHALFLGIHGGKMCLSCVKSGDETRLQLEAVNITDLSENR sequence KQDKRFAFIRSDSGPTTSFESAACPGWFLCTAMEADQPVSLTNMPDEGVMVTKFYFQEDE (SEQ ID NO:26)

Claims

1. An anti-IL1RAP antibody or antigen-binding fragment thereof, the antibody or antigen-binding fragment thereof comprises:three complementarity determining regions HCDR1, HCDR2 and HCDR3 contained in the VH set forth in any one of SEQ ID NOs: 13 to 17, and three complementarity determining regions LCDR1, LCDR2 and LCDR3 contained in the VL set forth in any one of SEQ ID NOs: 23 to 25.

2. An anti-IL1RAP antibody or an antigen-binding fragment thereof, comprising a first heavy chain complementarity-determining region (HCDR1), a second heavy chaincomplementarity-determining region (HCDR2), a third heavy chain complementarity-determining region (HCDR3), and a first light chain complementarity-determining region (LCDR1), a second light chain complementarity-determining region (LCDR2), and a third light chaincomplementarity-determining region (LCDR3), wherein the HCDR1, the HCDR2, the HCDR3, the LCDR1, the LCDR2, and the LCDR3 comprise or consist of the amino acid sequences set forth in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, respectively.

3. The anti-IL1RAP antibody or the antigen-binding fragment thereof according to claim 1 or 2, wherein the antibody or the antigen-binding fragment thereof comprises a heavy chain variable region (VH), wherein the heavy chain variable region comprises or consists of an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence selected from any one of SEQ ID NOs: 13-17, or comprises or consists of the amino acid sequence selected from any one of SEQ ID NOs: 13-17; and / or the antibody or the antigen-binding fragment thereof comprises a light chain variable region (VL), wherein the light chain variable region comprises or consists of an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence selected from any one of SEQ ID NOs: 23-25, or comprises or consists of the amino acid sequence selected from any one of SEQ ID NOs: 23-25.

4. An anti-IL1RAP antibody or antigen-binding fragment thereof, the antibody or antigen-binding fragment thereof comprises(i) the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO: 16 or 17, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto; and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 25, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto;(ii) the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO: 13, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto; and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 23, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto; or(iii) the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO: 14 or 15, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto; and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 24, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto.

5. The anti-IL1RAP antibody or the antigen-binding fragment thereof according to claim 1 or 2, comprising a heavy chain variable region and a light chain variable region, wherein(i) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 16 or 17 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 25;(ii) the heavy chain variable region consists of the amino acid sequence set forth in SEQ ID NO: 16 or 17 and the light chain variable region consists of the amino acid sequence set forth in SEQ ID NO: 25;(iii) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 13 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 23;(iv) the heavy chain variable region consists of the amino acid sequence set forth in SEQ ID NO: 13 and the light chain variable region consists of the amino acid sequence set forth in SEQ ID NO: 23;(v) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 14 or 15 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 24; or(vi) the heavy chain variable region consists of the amino acid sequence set forth in SEQ ID NO: 14 or 15 and the light chain variable region consists of the amino acid sequence set forth in SEQ ID NO: 24.

6. The anti-IL1RAP antibody or the antigen-binding fragment thereof according to any one of claims 1-5, comprising an Fc region, e.g.,, the Fc region is derived from an Fc region of IgG1, IgG2, IgG3, or IgG4, e.g., an Fc region of human IgG1, IgG2, IgG3, or IgG4; and / or the antibody or the antigen-binding fragment thereof comprises a heavy chain constant region derived from a constant region of IgG1, IgG2, IgG3, or IgG4, e.g., a constant region of human IgG1, IgG2, IgG3, or IgG4, for example, the heavy chain constant region of IgG1(i)   comprises or consists of the amino acid sequence set forth in SEQ ID NO:50; or(ii) comprises an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence set forth in SEQ ID NO: 50;optionally, the heavy chain constant region or Fc region lacks a C-terminal lysine; and / orthe heavy chain constant region or the Fc region comprises a mutation that has reduced binding to an Fcy receptor, e.g., an L234A / L235A mutation and / or a P329G mutation, e.g., an L234A / L235A mutation or an L234A / L235A mutation and a P329G mutation; for example, the heavy chain constant region(i)   comprises or consists of the amino acid sequence selected from SEQ ID NO:51 or 52;(ii) comprises an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence set forth in SEQ ID NO: 51, and comprises a L234A / L235A mutation; or(iii) comprises an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence set forth in SEQ ID NO: 52, and comprises a L234A / L235A mutation and a P329G mutation.

7. The anti-IL1RAP antibody or the antigen-binding fragment thereof according to any one of claims 1-6, comprising a light chain constant region, wherein the light chain constant region is a Lambda or Kappa light chain constant region, e.g., a human Lambda or Kappa light chain constant region; preferably, the light chain constant region(i) comprises or consists of an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence set forth in SEQ ID NO: 53; or(ii)   comprises or consists of the amino acid sequence set forth in SEQ ID NO:53; or8. The anti-IL1RAP antibody or antigen-binding fragment thereof according to any one of claims 1-7, the antibody or antigen-binding fragment thereof comprising a heavy chain, wherein the heavy chain(i) comprises or consists of an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence selected from any one of SEQ ID NOs: 32-36; or(ii)   comprises or consists of the amino acid sequence selected from any one ofSEQ ID NOs:32-36; and / orthe antibody or the antigen binding fragment thereof comprises a light chain, wherein the light chain(i) comprises or consists of an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence selected from any one of SEQ ID NOs: 42-44; or(ii)   comprises or consists of the amino acid sequence selected from any one ofSEQ ID NOs: 42-44.

9. An anti-IL1RAP antibody or an antigen-binding fragment thereof, comprising a heavy chain and a light chain, wherein(i) the heavy chain comprises or consists of an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence set forth in SEQ ID NO: 35 or 36, and the light chain comprises or consists of an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence set forth in SEQ ID NO: 44;(ii) the heavy chain comprises or consists of an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence set forth in SEQ ID NO: 32, and the light chain comprises or consists of an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence set forth in SEQ ID NO: 42; or(iii) the heavy chain comprises or consists of an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence set forth in SEQ ID NO: 33 or 34, and the light chain comprises or consists of an amino acid sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence set forth in SEQ ID NO: 43.

10. The anti-IL1RAP antibody or antigen-binding fragment thereof according to any one of claims 1-9 comprising a heavy chain and a light chain, wherein(i) the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 35 or 36, and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 44;(ii) the heavy chain consists of the amino acid sequence set forth in SEQ ID NO: 35 or 36, and the light chain consists of the amino acid sequence set forth in SEQ ID NO: 44;(iii) the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:32, and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 42;(iv) the heavy chain consists of the amino acid sequence set forth in SEQ ID NO: 32, and the light chain consists of the amino acid sequence set forth in SEQ ID NO: 42;(v) the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 33 or 34, and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 43; or(vi) the heavy chain consists of the amino acid sequence set forth in SEQ ID NO: 33 or 34, and the light chain consists of the amino acid sequence set forth in SEQ ID NO: 43.

11. The anti-IL1RAP antibody or antigen-binding fragment thereof of any one of claims 1-10, wherein the antibody is a monoclonal antibody; and / or the antibody is a humanized antibody or a chimeric antibody.

12. The anti-IL1RAP antibody or antigen-binding fragment thereof according to any one of claims 1-11, wherein the antigen-binding fragment is the antibody fragment selected from the group consisting of : Fab, Fab', Fab'-SH, Fv, single-chain antibody (e.g., scFv), (Fab')2, dAb (domain antibody), bivalent antibody or linear antibody.

13. The anti-IL1RAP antibody or antigen-binding fragment thereof according to any one of claims 1-12, wherein the antibody or antigen-binding fragment thereof has one or more of the following characteristics:a) binds to IL1RAP (e.g., human IL1RAP) with high affinity;b) effectively blocking the binding of IL1a, ILip, IL33, and IL36 to the IL1RAP receptor complex, thereby eliminating the inhibitory effect on the downstream NF-kB signaling pathway;c) inhibiting IL-1- (e.g., IL10-), IL-36-, and / or IL33-mediated signaling pathways, e.g., in epithelial cells or PBMCs;d) having good pharmacokinetic characteristics, e.g., having good stability (e.g., colloidal stability and / or thermal stability), good solubility, and / or a long half-life;e) effectively preventing or treating inflammation, such as abdominal inflammation (e.g., peritonitis (e.g., acute peritonitis)), gout (e.g., acute gout), and / or skin inflammation (e.g., dermatitis).

14. An isolated nucleic acid encoding the anti-IL1RAP antibody or antigen-binding fragment thereof according to any one of claims 1-13.

15. A vector comprising the nucleic acid according to claim 14, wherein preferably, the vector is an expression vector.

16. A host cell comprising the nucleic acid according to claim 14 or the vector according to claim 15, wherein preferably, the host cell is prokaryotic or eukaryotic, and more preferably, the host cell is selected from yeast cells, mammalian cells (e.g., 293 cells or CHO cells, such as CHO-K cells or HEK293 cells), and other cells suitable for preparing an antibody or an antigen-binding fragment thereof.

17. A method for preparing the anti-IL1RAP antibody or antigen-binding fragment thereof, comprising:a) culturing the host cell of claim 16 under conditions suitable for the expression of the nucleic acid encoding the anti-IL1RAP antibody or the antigen-binding fragment thereof according to any one of claims 1-13,b) optionally isolating the antibody or antigen-binding fragment thereof,c) optionally the method further comprises recovering the anti-IL1RAP antibody or antigen binding fragment thereof from the host cell, optionally the antibody is purified, e.g., by ProteinA.

18. An immunoconjugate comprising the anti-IL1RAP antibody or the antigen-binding fragment thereof according to any one of claims 1-13 and an additional substance, e.g., a chemotherapeutic agent, a toxin, a small molecule drug, a cytotoxic agent, an apoptotic agent, a chelating agent, an immunomodulatory agent, e.g., an immunosuppressive agent.

19. A pharmaceutical composition comprising the anti-IL1RAP antibody or theantigen-binding fragment thereof according to any one of claims 1 to 13 or the immunoconjugate according to claim 18, and optionally a pharmaceutically acceptable auxiliary material.

20. A pharmaceutical combination comprising the anti-IL1RAP antibody or the antigen-binding fragment thereof according to any one of claims 1-13 or the immunoconjugate according to claim 18, and one or more additional therapeutic agents, e.g., the therapeutic agents is selected from the group consisting of cytokines, other antibodies, small molecule drugs, or immunomodulatory agents (e.g., immunosuppressive agents).

21. A method for preventing or treating a disease or disorder related to inappropriate activation of a pathway mediated by IL1RAP receptor complex in an individual, which comprises administering to the subject an effective amount of the anti-IL1RAP antibody or the antigen-binding fragment thereof according to any one of claims 1-13, or the immunoconjugate according to claim 18, or the pharmaceutical composition according to claim 19, or the pharmaceutical combination according to claim 20, wherein for example, the disease or disorder is selected from a tumor such as a cancer, or an inflammation, e.g., an abdominal inflammation such as peritonitis (e.g., acute peritonitis), gout (e.g., acute gout), and / or a skin inflammation (e.g., dermatitis);optionally, the subject has abnormal activation of an IL1RAP receptor complex-mediated signaling pathway as compared to a healthy individual,optionally, the method further comprises administering one or more additional therapies, e.g., therapeutic modalities and / or additional therapeutic agents; for example, the therapeutic agent is selected from the group consisting of a cytokine, another antibody, a small molecule drug, and an immunomodulatory agent (e.g., an immunosuppressive agent).

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