Antibody specifically binding to LRRC15 and use thereof

Abstract

The present invention relates to a novel LRRC15 antibody and a use thereof. According to one aspect, an antibody specifically binding to LRRC15 can be used as a biomarker for diagnosing or predicting cancer and a cancer-targeting therapeutic agent.

Description

Antibodies specifically binding to LRRC15 and uses thereof

[0001] The present invention relates to a novel antibody specifically binding to LRRC15 and its use.

[0002] The complex and dynamic interactions between cancer cells and the surrounding tumor microenvironment play a critical role in determining the malignant potential and aggressiveness of cancer. Multiple autocrine and paracrine signaling exchanges between cancer cells and their surrounding stroma allow cancer cells to modify their microenvironment in ways that support their proliferation, growth, survival, and metastatic properties. Several studies have shown that these interactions are associated with cancers with a rich fibrous stroma, such as pancreatic cancer, triple-negative breast cancer (TNBC), sarcomas, ovarian cancer, and colorectal cancer. These interactions have revealed that the activated stroma impedes the active uptake of traditional chemotherapeutic drugs and creates an immunosuppressive environment favorable for tumor growth. Therefore, there is growing interest in developing therapeutic approaches that target tumor-stroma interactions to improve drug delivery.

[0003] The leucine-rich repeat (LRR) domain is a short (19-29 residue) sequence motif present in many proteins with diverse structures, functions, and locations across bacteria, fungi, plants, and animals. LRR domains typically have a horseshoe structure, with a concave face composed of parallel β-strands and a convex face containing a variable region of helix-like secondary structure. The structural arrangement of LRR motifs within repeats of varying lengths forms an adaptable framework for various protein-protein interactions. Proteins containing LRRs are known to be involved in various functions, including adhesion, receptor-ligand binding, and target recognition.

[0004] Meanwhile, Leucine-rich repeat-containing protein 15 (LRRC15) is located on chromosome 3q29 and belongs to the LRR superfamily involved in cell-cell and cell-matrix (ECM) interactions. In particular, LRRC15 is highly expressed in cancer-associated fibroblasts (CAFs) in the stroma of numerous solid tumors, is directly expressed in mesenchymal-derived tumors such as glioblastoma, sarcoma, and melanoma, and is known to be overexpressed in the microenvironment of breast, head and neck, lung, pancreas, and colon cancer. Furthermore, LRRC15 is known to show higher expression levels in solid tumors than in normal tissues and to bind to ECM components such as fibronectin and collagen.

[0005] Therefore, targeting LRRC15, which is highly expressed in most solid tumors with rich fibrotic stroma, as a cancer therapeutic target may be an effective strategy, and targeting LRRC15 using a specific antibody-drug conjugate (ADC) in patients with LRRC15-positive (LRRC15+) cancer may significantly improve the treatment outcomes of the cancer.

[0006] Therefore, there is a need to develop an LRRC15 antibody that can be used as a cancer targeting treatment.

[0007] One aspect is to provide an antibody or antigen-binding fragment thereof that specifically binds to LRRC15.

[0008] Another aspect is to provide a nucleic acid encoding the antibody or antigen-binding fragment thereof.

[0009] Another aspect is to provide a host cell expressing the nucleic acid.

[0010] Another aspect is to provide a bispecific antibody comprising the antibody or an antigen-binding fragment thereof.

[0011] Another aspect is to provide a chimeric antigen receptor comprising the antibody or antigen-binding fragment thereof.

[0012] Another aspect is to provide an antibody-drug conjugate (ADC) comprising the antibody or an antigen-binding fragment thereof.

[0013] Another aspect is to provide a pharmaceutical composition for preventing or treating cancer, comprising the antibody or an antigen-binding fragment thereof; the bispecific antibody; the chimeric antigen receptor; or the antibody drug conjugate.

[0014] Another aspect provides a method for preventing or treating cancer, comprising administering to a subject in need thereof an effective amount of an antibody or an antigen-binding fragment thereof that specifically binds to the Leucine-rich repeat-containing protein 15 (LRRC15); the bispecific antibody; the chimeric antigen receptor; or the antibody drug conjugate.

[0015] Another aspect provides a use of an antibody or an antigen-binding fragment thereof that specifically binds to the LRRC15 (Leucine-rich repeat-containing protein 15); the bispecific antibody; the chimeric antigen receptor; or the antibody drug conjugate; for use in the manufacture of a pharmaceutical preparation for preventing or treating cancer.

[0016] One aspect provides an antibody or antigen-binding fragment thereof that specifically binds to LRRC15.

[0017] As used herein, the term "antibody", "antigen-binding region or site" or "antigen-binding polypeptide" may refer to a polypeptide or polypeptide complex that specifically recognizes and binds to an antigen. The antibody may be a whole antibody, any antigen-binding fragment thereof, or a single chain. The whole antibody has a structure having two full-length light chains and two full-length heavy chains, each light chain being linked to a heavy chain by a disulfide bond. The whole antibody includes IgA, IgD, IgE, IgM and IgG, and IgG is a subtype, including IgG1, IgG2, IgG3 and IgG4.

[0018] Additionally, the antibody may comprise any protein or peptide-containing molecule comprising at least a portion of an immunoglobulin molecule having biological activity that binds to an antigen. Examples thereof include, but are not limited to, a complementarity determining region (CDR) of a heavy or light chain or a ligand-binding portion thereof, a heavy or light chain variable region, a heavy or light chain constant region, a framework (FR) region, or any portion thereof, or at least a portion of a binding protein.

[0019] The heavy chain refers to both a full-length heavy chain and fragments thereof, comprising a variable domain VH comprising an amino acid sequence having sufficient variable region sequence to confer specificity to an antigen, and three constant region domains CH1, CH2, and CH3. In addition, the light chain refers to both a full-length light chain and fragments thereof, comprising a variable domain VL comprising an amino acid sequence having sufficient variable region sequence to confer specificity to an antigen, and a constant region domain CL.

[0020] In one embodiment, the antibody may include, but is not limited to, a monoclonal antibody, a monospecific antibody, a bispecific antibody, a trispecific antibody, a bispecific antibody, a multispecific antibody, a multivalent antibody, a minibody, a domain antibody, an antibody mimetic (or synthetic antibody), a chimeric antibody, a humanized antibody, or an antibody fusion (or antibody conjugate) and fragments thereof, and may include various forms of antibodies disclosed herein. The antibody may be derived from any mammal, including but not limited to, a human, a chicken, a mouse, a rat, a camelid, or a rabbit.

[0021] As used herein, the term "antigen" or "immunogen" may mean a molecule or portion of a molecule, for example, to which an antigen-binding protein (e.g., an antibody or an immunologically functional antigen-binding fragment thereof) can bind, and which can be used to produce antibodies capable of binding to an antigen in an animal. An antigen may comprise one or more epitopes capable of interacting with different antibodies or fragments thereof.

[0022] As used herein, the term "antibody fragment" or "antigen-binding fragment" may comprise a portion of an antibody that lacks some amino acids compared to the full-length chain, but is still capable of specifically binding to an antigen. Such fragments may be considered biologically active in that they can specifically bind to a target antigen or compete with other antibodies or antigen-binding fragments for binding to a specific epitope. In one aspect, the "antibody fragment" or "antigen-binding fragment" comprises at least one CDR present in a full-length light or heavy chain, and in some embodiments, may comprise a shorter heavy and / or light chain, or a portion thereof.

[0023] The above "antibody fragment" or "antigen-binding fragment" may be produced by recombinant DNA technology, or may be produced by enzymatic or chemical cleavage of an intact antibody, for example. Immunologically, the "antibody fragment" or "antigen-binding fragment" includes, but is not limited to, Fab, Fab', F(ab')2, scFab, dsFv, Fv, scFv-Fc, scFab-Fc, aptamers, spiegelmers, diabodies, minibodies, scAb, dAb, half-IgG, or combinations thereof. Furthermore, the "antibody fragment" or "antigen-binding fragment" may include any synthetic or genetically engineered protein that acts like an antibody by binding to a specific antigen to form a complex. Functional portions of antibodies, such as one or more of the CDRs described herein, can be covalently linked to a second protein or small molecule compound, thereby enabling use as a targeted therapeutic agent for a specific target.

[0024] The above "Fc" region may comprise two heavy chain fragments comprising the CH2 and CH3 domains of an antibody. These two heavy chain fragments may be joined to each other by two or more disulfide bonds and hydrophobic interactions of the CH3 domains.

[0025] The above "Fab fragment" may be composed of one heavy chain and one light chain, each containing only CH1 and variable regions. The heavy chain of a Fab molecule may not form a disulfide bond with another heavy chain molecule.

[0026] The above "Fab' fragment" includes, in addition to the Fab fragment, a region between the CH1 and CH2 domains of the heavy chain, which can form a disulfide bond between two heavy chains of two molecules of the Fab' fragment to form an F(ab')2 molecule.

[0027] The above "F(ab')2 fragment" comprises two heavy chains and two light chains, each including a variable region, CH1, and a portion of a constant region between the CH1 and CH2 domains, as described above, thereby forming an intrachain disulfide bond between the two heavy chains. Therefore, the F(ab')2 fragment is composed of two Fab' fragments, and the two Fab' fragments can bind to each other by the disulfide bond between them.

[0028] The above "Fv region" may be an antibody comprising the variable regions of each heavy and light chain, but not the constant region. An scFv may be an Fv linked by a flexible linker. An scFv-Fc may be an Fc linked to an scFv. A minibody may be a CH3 linked to an scFv. A diabody may comprise two molecules of scFv.

[0029] The term "single-chain variable fragment" or "scFv" may refer to a fusion protein of the variable regions of the heavy (VH) and light (VL) chains of an immunoglobulin. In one embodiment, the regions may be linked to a short linker peptide of 10 to about 25 amino acids. The linker may be enriched in glycine for flexibility and in serine or threonine for solubility, and may link the N-terminus of the VH to the C-terminus of the VL, or vice versa. Such a protein may retain the specificity of the original immunoglobulin despite the removal of the constant region and the introduction of the linker. ScFv molecules are known in the art and are described, for example, in U.S. Patent No. 5,892,019.

[0030] The above "scAb (short-chain antibody)" may be a single polypeptide chain comprising one variable region of a heavy or light chain constant region, with the heavy and light chain variable regions connected by a flexible linker. For short-chain antibodies, see, for example, U.S. Patent No. 5,260,203.

[0031] The above "dAb (domain antibody)" may be an immunologically functional immunoglobulin fragment comprising only the variable region of the heavy chain or the variable region of the light chain. In one embodiment, two or more VH regions may be covalently linked by a peptide linker to form a bivalent domain antibody. The two VH regions of such a bivalent domain antibody may target the same or different antigens.

[0032] The term "antibody or antigen-binding fragment thereof that specifically binds to LRRC15" in this specification is used interchangeably with "ED2 antibody" or "ED2".

[0033] Additionally, the antibody or antigen-binding fragment thereof that specifically binds to LRRC15 may comprise "variants." The variants may refer to polypeptides in which one or more amino acid residues are inserted, deleted, added, and / or substituted from the polypeptide sequence. Accordingly, as long as the desired biological activity and / or structure of the antibody and / or antigen-binding fragment is maintained, the variants may be linked to another polypeptide to form a fusion polypeptide. The variant may have at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the sequence of the antibody or antigen-binding fragment thereof, for example, may have about 99%, 98%, 97%, 96%, 95%, 94%, 93%, 92%, 91%, 90%, 89%, 88%, 87%, 86%, 85%, 84%, 83%, 82%, 81%, or 80% sequence identity.

[0034] As used herein, the terms "homology" or "identity" may refer to the overall relatedness between nucleic acid molecules and / or between polypeptides. In one embodiment, nucleic acids or polypeptides may be considered "substantially identical" to each other if their sequences are at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical. Calculating the percent identity of two nucleic acid or polypeptide sequences may be performed, for example, by aligning the two sequences for optimal comparison purposes. In certain embodiments, the length of the aligned sequence for comparison purposes can be at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or substantially 100% of the length of the reference sequence.

[0035] The term "anti-LRRC15 optimized antibody" as used herein refers to an antibody that specifically recognizes and binds to human LRRC15 (Leucine-Rich Repeat Containing 15) protein, and is selected through a sequence modification or screening process to improve characteristics such as binding affinity, binding stability, or antigen specificity compared to the parent antibody. For example, the optimized antibody can be obtained through a technical process such as a change in the CDR sequence, systematic mutagenesis, or in vitro affinity maturation of an antibody in the form of Fab, scFv, or IgG derived from the parent antibody, and in the present invention, antibodies obtained through such processes are collectively defined as "anti-LRRC15 optimized antibody."

[0036] In one specific example, the antibody or antigen-binding fragment thereof that specifically binds to LRRC15 is not naturally occurring and may be chemically or recombinantly synthesized.

[0037] In one embodiment, the antibody or antigen-binding fragment thereof that specifically binds to LRRC15 comprises (i) heavy chain complementarity determining regions (CDRs) of CDRH1, CDRH2, and CDRH3, and (ii) light chain complementarity determining regions of CDRL1, CDRL2, and CDRL3, wherein CDRH1 is an amino acid sequence having at least 85, 90, 95, 99, or 100% homology or identity to any one of the amino acid sequences represented by SEQ ID NOs: 1 to 30 and 316 to 325; and wherein CDRH2 is an amino acid sequence having at least 85, 90, 95, 99, or 100% homology or identity to any one of the amino acid sequences represented by SEQ ID NOs: 31 to 67 and 326 to 336; The CDRH3 is an amino acid sequence having at least 85, 90, 95, 99 or 100% homology or identity to any one of the amino acid sequences represented by SEQ ID NOs: 68 to 115, 337 and 338; the CDRL1 is an amino acid sequence having at least 85, 90, 95, 99 or 100% homology or identity to any one of the amino acid sequences represented by SEQ ID NOs: 116 to 150, 339 and 340; the CDRL2 is an amino acid sequence having at least 85, 90, 95, 99 or 100% homology or identity to any one of the amino acid sequences represented by SEQ ID NOs: 151 to 169, 341 and 342; And the CDRL3 may be an amino acid sequence having at least 85, 90, 95, 99 or 100% homology or identity with any one of the amino acid sequences represented by SEQ ID NOs: 170 to 211 and 343.

[0038] The term "complementarity determining region (CDR)" as used herein refers to the amino acid sequence of the hypervariable region of the immunoglobulin heavy and light chains (Kabat et al. Sequences of Proteins of Immunological Interest, 4th Ed., US Department of Health and Human Services, National Institutes of Health (1987)). The heavy chains (CDRH1, CDRH2, and CDRH3) and the light chains (CDRL1, CDRL2, and CDRL3) each contain three CDRs, which provide key contact residues for antibody binding to an antigen or epitope. For example, the variable regions of the light and heavy chains include three hypervariable regions called complementarity-determining regions (hereinafter referred to as "CDRs") and four framework regions (FRs). The above CDRs primarily play a role in binding to epitopes of antigens. The CDRs of each chain are typically sequentially referred to as CDR1, CDR2, and CDR3 starting from the N-terminus, and are also identified by the chain on which the specific CDR is located. In this specification, the CDR contained in the heavy chain variable region is referred to as "CDRH", and the CDR contained in the light chain variable region is referred to as "CDRL".

[0039] In one specific example, the CDRs (CDRL) of each variable region of the light chain and the CDRs (CDRH) of each variable region of the heavy chain can be freely combined.

[0040] In one specific example, the antibody or antigen-binding fragment thereof that specifically binds to LRRC15 may comprise CDRH1, CDRH2 and CDRH3 in any one of the following combinations:

[0041] (1) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 1, 31, and 68, respectively; (2) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 1, 32, and 69, respectively; (3) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 2, 33, and 70, respectively; (4) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 2, 33, and 71, respectively; (5) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 2, 34, and 72, respectively; (6) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 3, 35, and 73, respectively; (7) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 1, 36, and 74, respectively; (8) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 4, 37, and 75, respectively; (9) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 2, 38, and 76, respectively; (10) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 2, 36, and 77, respectively; (11) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 5, 39, and 78, respectively; (12) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 2, 40, and 79, respectively; (13) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 5, 41, and 80, respectively; (14) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 6, 42, and 81, respectively; (15) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 7, 43, and 82, respectively;(16) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 7, 43, and 83, respectively; (17) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 8, 44, and 84, respectively; (18) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 9, 45, and 85, respectively; (19) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 10, 34, and 86, respectively; (20) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 11, 46, and 87, respectively; (21) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 12, 47, and 88, respectively; (22) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 13, 48, and 89, respectively; (23) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 14, 49, and 90, respectively; (24) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 15, 50, and 91, respectively; (25) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 16, 51, and 92, respectively; (26) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 8, 52, and 93, respectively; (27) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 2, 53, and 94, respectively; (28) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 17, 54, and 95, respectively; (29) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 18, 55, and 96, respectively; (30) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 19, 56, and 97, respectively;(31) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 20, 52, and 98, respectively; (32) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 6, 57, and 99, respectively; (33) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 21, 58, and 100, respectively; (34) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 6, 42, and 101, respectively; (35) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 22, 59, and 102, respectively; (36) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 23, 33, and 103, respectively; (37) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 9, 52, and 104, respectively; (38) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 24, 60, and 105, respectively; (39) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 10, 61, and 106, respectively; (40) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 10, 61, and 107, respectively; (41) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 25, 62, and 108, respectively; (42) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 26, 43, and 109, respectively; (43) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 21, 63, and 110, respectively; (44) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 27, 64, and 111, respectively;(45) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 28, 61, and 112, respectively; (46) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 29, 65, and 113, respectively; (47) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 10, 66, and 114, respectively; (48) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 30, 67, and 115, respectively; (49) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 326, and 337, respectively; (50) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 317, 327, and 337, respectively; (51) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 328, and 337, respectively; (52) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 318, 328, and 337, respectively; (53) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 319, 328, and 337, respectively; (54) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 320, 327, and 337, respectively; (55) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 318, 327, and 337, respectively; (56) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 318, 329, and 337, respectively; (57) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 317, 328, and 337, respectively; (58) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 321, 327, and 337, respectively;(59) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 320, 328, and 337, respectively; (60) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 321, 328, and 337, respectively; (61) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 318, 326, and 337, respectively; (62) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 320, 329, and 337, respectively; (63) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 320, 326, and 337, respectively; (64) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 319, 327, and 337, respectively; (65) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 327, and 337, respectively; (66) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 322, 326, and 337, respectively; (67) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 330, and 337, respectively; (68) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 323, 326, and 337, respectively; (69) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 324, 326, and 337, respectively; (70) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 331, and 337, respectively; (71) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 325, 326, and 337, respectively; (72) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 332, and 337, respectively;(73) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 326, and 338, respectively; (74) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 333, and 337, respectively; (75) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 334, and 337, respectively; (76) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 335, and 337, respectively; and (77) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 336, and 337, respectively.

[0042] In one specific example, the CDRH1, CDRH2 and CDRH3 of the antibody or antigen-binding fragment thereof that specifically binds to LRRC15 may comprise an amino acid sequence having at least 85, 90, 95, 99 or 100% homology or identity with any one of the combinations (1) to (77) of the CDRH1, CDRH2 and CDRH3.

[0043] In one specific example, the antibody or antigen-binding fragment thereof that specifically binds to LRRC15 may comprise any one of the following combinations of CDRL1, CDRL2, and CDRL3: (1) the CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 116, 151, and 170, respectively; (2) the CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 117, 152, and 171, respectively; (3) the CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 118, 152, and 172, respectively; (4) the CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 119, 152, and 173, respectively; (5) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 118, 153, and 174, respectively; (6) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 116, 152, and 170, respectively; (7) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 120, 153, and 174, respectively; (8) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 116, 152, and 175, respectively; (9) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 116, 153, and 176, respectively; (10) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 121, 153, and 171, respectively; (11) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 118, 153, and 177, respectively; (12) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 118, 153, and 178, respectively;(13) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 116, 152, and 179, respectively; (14) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 122, 154, and 180, respectively; (15) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 123, 155, and 181, respectively; (16) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 124, 156, and 182, respectively; (17) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 125, 153, and 183, respectively; (18) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 126, 157, and 184, respectively; (19) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 127, 158, and 185, respectively; (20) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 121, 157, and 186, respectively; (21) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 128, 159, and 187, respectively; (22) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 129, 160, and 188, respectively; (23) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 130, 153, and 189, respectively; (24) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 131, 154, and 190, respectively; (25) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 131, 154, and 180, respectively; (26) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 132, 153, and 191, respectively;(27) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 133, 153, and 189, respectively; (28) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 134, 161, and 192, respectively; (29) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 135, 157, and 193, respectively; (30) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 118, 153, and 194, respectively; (31) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 136, 162, and 195, respectively; (32) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 137, 157, and 196, respectively; (33) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 138, 163, and 197, respectively; (34) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 139, 164, and 198, respectively; (35) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 140, 154, and 180, respectively; (36) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 141, 153, and 191, respectively; (37) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 122, 154, and 199, respectively; (38) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 142, 154, and 199, respectively; (39) The CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 143, 153, and 200, respectively; (40) The CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 144, 165, and 201, respectively;(41) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 145, 161, and 202, respectively; (42) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 146, 161, and 203, respectively; (43) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 132, 153, and 204, respectively; (44) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 144, 161, and 205, respectively; (45) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 147, 155, and 206, respectively; (46) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 144, 166, and 207, respectively; (47) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 144, 161, and 208, respectively; (48) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 148, 167, and 209, respectively; (49) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 149, 168, and 210, respectively; (50) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 150, 169, and 211, respectively; (51) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively; (52) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 340, 341, and 343, respectively; And (53) the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 342, and 343, respectively.;

[0044] In one specific example, CDRL1, CDRL2, and CDRL3 of the antibody or antigen-binding fragment thereof that specifically binds to LRRC15 may comprise an amino acid sequence having at least 85, 90, 95, 99, or 100% homology or identity with any one of the combinations (1) to (53) of CDRL1, CDRL2, and CDRL3.

[0045] In one specific example, the antibody or antigen-binding fragment thereof that specifically binds to LRRC15 may comprise any one of CDRH1, CDRH2 and CDRH3; and CDRL1, CDRL2 and CDRL3; in combination:

[0046] The CDRH1, CDRH2, and CDRH3 are any one of the following combinations: (1) the CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 1, 31, and 68, respectively; (2) the CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 1, 32, and 69, respectively; (3) the CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 2, 33, and 70, respectively; (4) the CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 2, 33, and 71, respectively; (5) the CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 2, 34, and 72, respectively; (6) the CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 3, 35, and 73, respectively; (7) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 1, 36, and 74, respectively; (8) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 4, 37, and 75, respectively; (9) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 2, 38, and 76, respectively; (10) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 2, 36, and 77, respectively; (11) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 5, 39, and 78, respectively; (12) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 2, 40, and 79, respectively; (13) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 5, 41, and 80, respectively; (14) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 6, 42, and 81, respectively;(15) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 7, 43, and 82, respectively; (16) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 7, 43, and 83, respectively; (17) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 8, 44, and 84, respectively; (18) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 9, 45, and 85, respectively; (19) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 10, 34, and 86, respectively; (20) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 11, 46, and 87, respectively; (21) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 12, 47, and 88, respectively; (22) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 13, 48, and 89, respectively; (23) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 14, 49, and 90, respectively; (24) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 15, 50, and 91, respectively; (25) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 16, 51, and 92, respectively; (26) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 8, 52, and 93, respectively; (27) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 2, 53, and 94, respectively; (28) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 17, 54, and 95, respectively; (29) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 18, 55, and 96, respectively;(30) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 19, 56, and 97, respectively; (31) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 20, 52, and 98, respectively; (32) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 6, 57, and 99, respectively; (33) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 21, 58, and 100, respectively; (34) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 6, 42, and 101, respectively; (35) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 22, 59, and 102, respectively; (36) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 23, 33, and 103, respectively; (37) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 9, 52, and 104, respectively; (38) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 24, 60, and 105, respectively; (39) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 10, 61, and 106, respectively; (40) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 10, 61, and 107, respectively; (41) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 25, 62, and 108, respectively; (42) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 26, 43, and 109, respectively; (43) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 21, 63, and 110, respectively;(44) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 27, 64, and 111, respectively; (45) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 28, 61, and 112, respectively; (46) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 29, 65, and 113, respectively; (47) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 10, 66, and 114, respectively; (48) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 30, 67, and 115, respectively; (49) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 326, and 337, respectively; (50) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 317, 327, and 337, respectively; (51) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 328, and 337, respectively; (52) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 318, 328, and 337, respectively; (53) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 319, 328, and 337, respectively; (54) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 320, 327, and 337, respectively; (55) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 318, 327, and 337, respectively; (56) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 318, 329, and 337, respectively; (57) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 317, 328, and 337, respectively;(58) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 321, 327, and 337, respectively; (59) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 320, 328, and 337, respectively; (60) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 321, 328, and 337, respectively; (61) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 318, 326, and 337, respectively; (62) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 320, 329, and 337, respectively; (63) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 320, 326, and 337, respectively; (64) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 319, 327, and 337, respectively; (65) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 327, and 337, respectively; (66) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 322, 326, and 337, respectively; (67) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 330, and 337, respectively; (68) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 323, 326, and 337, respectively; (69) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 324, 326, and 337, respectively; (70) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 331, and 337, respectively; (71) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 325, 326, and 337, respectively;(72) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 332, and 337, respectively; (73) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 326, and 338, respectively; (74) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 333, and 337, respectively; (75) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 334, and 337, respectively; (76) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 335, and 337, respectively; and (77) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 336, and 337, respectively; and;

[0047] The CDRL1, CDRL2 and CDRL3 are any one of the following combinations: (1) the CDRL1, CDRL2 and CDRL3 are amino acid sequences represented by SEQ ID NOs: 116, 151 and 170, respectively; (2) the CDRL1, CDRL2 and CDRL3 are amino acid sequences represented by SEQ ID NOs: 117, 152 and 171, respectively; (3) the CDRL1, CDRL2 and CDRL3 are amino acid sequences represented by SEQ ID NOs: 118, 152 and 172, respectively; (4) the CDRL1, CDRL2 and CDRL3 are amino acid sequences represented by SEQ ID NOs: 119, 152 and 173, respectively; (5) the CDRL1, CDRL2 and CDRL3 are amino acid sequences represented by SEQ ID NOs: 118, 153 and 174, respectively; (6) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 116, 152, and 170, respectively; (7) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 120, 153, and 174, respectively; (8) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 116, 152, and 175, respectively; (9) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 116, 153, and 176, respectively; (10) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 121, 153, and 171, respectively; (11) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 118, 153, and 177, respectively; (12) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 118, 153, and 178, respectively; (13) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 116, 152, and 179, respectively;(14) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 122, 154, and 180, respectively; (15) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 123, 155, and 181, respectively; (16) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 124, 156, and 182, respectively; (17) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 125, 153, and 183, respectively; (18) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 126, 157, and 184, respectively; (19) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 127, 158, and 185, respectively; (20) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 121, 157, and 186, respectively; (21) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 128, 159, and 187, respectively; (22) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 129, 160, and 188, respectively; (23) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 130, 153, and 189, respectively; (24) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 131, 154, and 190, respectively; (25) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 131, 154, and 180, respectively; (26) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 132, 153, and 191, respectively; (27) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 133, 153, and 189, respectively;(28) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 134, 161, and 192, respectively; (29) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 135, 157, and 193, respectively; (30) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 118, 153, and 194, respectively; (31) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 136, 162, and 195, respectively; (32) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 137, 157, and 196, respectively; (33) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 138, 163, and 197, respectively; (34) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 139, 164, and 198, respectively; (35) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 140, 154, and 180, respectively; (36) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 141, 153, and 191, respectively; (37) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 122, 154, and 199, respectively; (38) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 142, 154, and 199, respectively; (39) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 143, 153, and 200, respectively; (40) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 144, 165, and 201, respectively; (41) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 145, 161, and 202, respectively;(42) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 146, 161, and 203, respectively; (43) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 132, 153, and 204, respectively; (44) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 144, 161, and 205, respectively; (45) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 147, 155, and 206, respectively; (46) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 144, 166, and 207, respectively; (47) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 144, 161, and 208, respectively; (48) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 148, 167, and 209, respectively; (49) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 149, 168, and 210, respectively; (50) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 150, 169, and 211, respectively; (51) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively; (52) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 340, 341, and 343, respectively; and (53) The CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 340, 342, and 343, respectively.

[0048] In one specific example, the antibody or antigen-binding fragment thereof that specifically binds to LRRC15 may include CDRH1, CDRH2 and CDRH3; and CDRL1, CDRL2 and CDRL3; having an amino acid sequence that is at least 85, 90, 95, 99 or 100% homologous or identical to any one of the combinations (1) to (77) of CDRH1, CDRH2 and CDRH3; and an amino acid sequence that is at least 85, 90, 95, 99 or 100% homologous or identical to any one of the combinations (1) to (53) of CDRL1, CDRL2 and CDRL3.

[0049] In one specific example, the antibody or antigen-binding fragment thereof that specifically binds to LRRC15 may comprise any one of CDRH1, CDRH2 and CDRH3; and a combination of CDRL1, CDRL2 and CDRL3: (1) wherein CDRH1, CDRH2 and CDRH3 have amino acid sequences represented by SEQ ID NOs: 1, 31 and 68, respectively, and wherein CDRL1, CDRL2 and CDRL3 have amino acid sequences represented by SEQ ID NOs: 116, 151 and 170, respectively; (2) wherein CDRH1, CDRH2 and CDRH3 have amino acid sequences represented by SEQ ID NOs: 1, 32 and 69, respectively, and wherein CDRL1, CDRL2 and CDRL3 have amino acid sequences represented by SEQ ID NOs: 117, 152 and 171, respectively; (3) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 2, 33, and 70, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 118, 152, and 172, respectively; (4) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 2, 33, and 71, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 119, 152, and 173, respectively; (5) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 2, 34, and 72, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 118, 153, and 174, respectively; (6) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 3, 35, and 73, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 116, 152, and 170, respectively;(7) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 1, 36, and 74, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 120, 153, and 174, respectively; (8) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 4, 37, and 75, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 116, 152, and 175, respectively; (9) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 2, 38, and 76, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 116, 153, and 176, respectively; (10) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 2, 36, and 77, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 121, 153, and 171, respectively; (11) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 5, 39, and 78, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 118, 153, and 177, respectively; (12) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 2, 40, and 79, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 118, 153, and 178, respectively; (13) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 5, 41, and 80, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 116, 152, and 179, respectively;(14) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 6, 42, and 81, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 122, 154, and 180, respectively; (15) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 7, 43, and 82, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 123, 155, and 181, respectively; (16) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 7, 43, and 83, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 124, 156, and 182, respectively; (17) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 8, 44, and 84, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 125, 153, and 183, respectively; (18) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 9, 45, and 85, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 126, 157, and 184, respectively; (19) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 10, 34, and 86, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 127, 158, and 185, respectively; (20) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 11, 46, and 87, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 121, 157, and 186, respectively;(21) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 12, 47, and 88, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 128, 159, and 187, respectively; (22) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 13, 48, and 89, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 129, 160, and 188, respectively; (23) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 14, 49, and 90, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 122, 154, and 180, respectively; (24) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 15, 50, and 91, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 130, 153, and 189, respectively; (25) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 6, 42, and 81, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 131, 154, and 190, respectively; (26) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 6, 42, and 81, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 131, 154, and 180, respectively; (27) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 16, 51, and 92, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 132, 153, and 191, respectively;(28) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 8, 52, and 93, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 133, 153, and 189, respectively; (29) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 2, 53, and 94, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 134, 161, and 192, respectively; (30) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 17, 54, and 95, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 135, 157, and 193, respectively; (31) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 18, 55, and 96, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 118, 153, and 194, respectively; (32) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 19, 56, and 97, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 136, 162, and 195, respectively; (33) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 20, 52, and 98, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 137, 157, and 196, respectively; (34) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 6, 57, and 99, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 138, 163, and 197, respectively;(35) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 21, 58, and 100, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 139, 164, and 198, respectively; (36) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 6, 42, and 101, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 140, 154, and 180, respectively; (37) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 22, 59, and 102, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 141, 153, and 191, respectively; (38) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 6, 42, and 81, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 122, 154, and 199, respectively; (39) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 23, 33, and 103, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 142, 154, and 199, respectively; (40) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 9, 52, and 104, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 143, 153, and 200, respectively; (41) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 24, 60, and 105, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 144, 165, and 201, respectively;(42) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 10, 61, and 106, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 145, 161, and 202, respectively; (43) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 10, 61, and 107, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 146, 161, and 203, respectively; (44) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 25, 62, and 108, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 132, 153, and 204, respectively; (45) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 26, 43, and 109, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 144, 161, and 205, respectively; (46) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 21, 63, and 110, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 147, 155, and 206, respectively; (47) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 27, 64, and 111, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 144, 166, and 207, respectively; (48) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 28, 61, and 112, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 144, 161, and 208, respectively;(49) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 29, 65, and 113, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 148, 167, and 209, respectively; (50) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 10, 66, and 114, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 149, 168, and 210, respectively; (51) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 30, 67, and 115, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 150, 169, and 211, respectively; (52) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 316, 326, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively; (53) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 317, 327, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 341, and 343, respectively; (54) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 316, 328, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 341, and 343, respectively; (55) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 318, 328, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 341, and 343, respectively;(56) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 319, 328, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 341, and 343, respectively; (57) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 320, 327, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 342, and 343, respectively; (58) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 318, 327, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 341, and 343, respectively; (59) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 318, 329, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 341, and 343, respectively; (60) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 317, 328, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 342, and 343, respectively; (61) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 321, 327, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 341, and 343, respectively; (62) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 320, 328, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 341, and 343, respectively;(63) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 318, 327, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 342, and 343, respectively; (64) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 318, 328, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 342, and 343, respectively; (65) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 321, 328, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 341, and 343, respectively; (66) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 320, 327, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 341, and 343, respectively; (67) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 320, 327, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively; (68) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 318, 326, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 342, and 343, respectively; (69) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 321, 328, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively;(70) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 320, 329, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 341, and 343, respectively; (71) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 320, 326, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 341, and 343, respectively; (72) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 320, 328, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively; (73) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 319, 327, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 341, and 343, respectively; (74) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 316, 327, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 341, and 343, respectively; (75) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 322, 326, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively; (76) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 316, 330, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively;(77) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 323, 326, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively; (78) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 324, 326, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively; (79) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 316, 331, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively; (80) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 325, 326, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively; (81) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 316, 332, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively; (82) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 316, 326, and 338, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively; (83) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 316, 333, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively;(84) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 316, 334, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively; (85) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 316, 335, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively; and (86) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 316, 336, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively.

[0050] In one specific example, the antibody or antigen-binding fragment thereof that specifically binds to LRRC15 may comprise an amino acid sequence having at least 85, 90, 95, 99 or 100% homology or identity with any one of the combinations (1) to (86) of CDRH1, CDRH2 and CDRH3; and CDRL1, CDRL2 and CDRL.

[0051] In one embodiment, the antibody or antigen-binding fragment thereof that specifically binds to LRRC15 may comprise a heavy chain variable region (VH) comprising an amino acid sequence having at least 85, 90, 95, 99, or 100% homology or identity to any one amino acid sequence selected from the group consisting of SEQ ID NOs: 212 to 263 and 344 to 382; and a light chain variable region (VL) comprising an amino acid sequence having at least 85, 90, 95, 99, or 100% homology or identity to any one amino acid sequence selected from the group consisting of SEQ ID NOs: 264 to 315 and 383 to 421.

[0052] In one specific example, the heavy chain variable region (VH) and the light chain variable region (VL) disclosed in Tables 5 and 9 below can be freely combined.

[0053] In one specific example, the antibody or antigen-binding fragment thereof that specifically binds to LRRC15 may comprise a combination of a heavy chain variable region (VH) and a light chain variable region (VL).

[0054] In one embodiment, the heavy chain variable region and light chain variable region of the antibody or antigen-binding fragment thereof that specifically binds to LRRC15 may be linked to at least a portion of a human constant region. The choice of the constant region may be determined in part by whether antibody-dependent cell-mediated cytotoxicity, antibody-dependent cell phagocytosis, and / or complement-dependent cytotoxicity is desired.

[0055] In one specific example, the antibody or antigen-binding fragment thereof that specifically binds to LRRC15 may further comprise a human immunoglobulin heavy chain region and a light chain region. For example, the human immunoglobulin may be IgG.

[0056] In one specific embodiment, the antibody or antigen-binding fragment thereof that specifically binds to LRRC15 may be a human antibody, and the heavy chain constant region may be of the IgG1-, IgG2-, IgG3-, or IgG4-type.

[0057]

[0058] Another aspect provides a nucleic acid encoding an antibody or antigen-binding fragment thereof that specifically binds to the above LRRC15.

[0059] As used herein, the terms "nucleic acid" or "polynucleotide" may include single-stranded and double-stranded nucleotide polymers. The terms "nucleic acid" and "polynucleotide" may be used interchangeably. The nucleotides constituting the polynucleotide may be ribonucleotides or deoxyribonucleotides, or modified forms of both types of nucleotides. Such modifications may include base modifications such as bromouridine and inosine derivatives, ribose modifications such as 2',3'-dideoxyribose, and internucleotide linkage modifications such as phosphorothioate, phosphorodithioate, phosphoroselenoate, phosphorodiselenoate, phosphoroanilothioate, phosphoranilate, and phosphoramidate.

[0060] The nucleic acid sequence encoding the antibody or antigen-binding fragment thereof that specifically binds to the above LRRC15 can be cloned into a number of types of vectors. For example, the nucleic acid can be cloned into a plasmid, a phagemid, a phage derivative, an animal virus, and a cosmid. Other vectors can include expression vectors, replication vectors, probe production vectors, sequencing vectors, and viral vectors. In another example, the vector can be a foamy viral (FV) vector, a type of retroviral vector prepared from spumavirus. Viral vector design and techniques are well known in the art, such as those described in Sambrook et al., (Molecular Cloning: A Laboratory Manual, 2001), and in other virology and molecular biology manuals.

[0061] As used herein, the term "vector" may refer to a nucleic acid molecule that is introduced into a host cell to produce a transformed host cell. The vector may include a nucleic acid sequence that allows replication in the host cell, such as an origin of replication. The vector may also include one or more therapeutic genes and / or selectable marker genes, as well as other genetic elements known in the art. The vector may transduce, transform, or infect a cell, thereby causing the cell to express nucleic acids and / or proteins other than those native to the cell. The vector may optionally include materials that aid in the entry of the nucleic acid into the cell, such as viral particles, liposomes, protein coatings, etc.

[0062]

[0063] Another aspect provides a host cell transformed with a vector comprising a nucleic acid encoding an antibody or an antigen-binding fragment thereof that specifically binds to the above LRRC15.

[0064] As used herein, the term "host cell" may refer to a cell that has been or can be transformed with a nucleic acid sequence and thus expresses a gene of interest. A host cell may include progeny of a parent cell, regardless of whether the progeny are morphologically or genetically identical to the original parent cell, as long as the gene of interest is present. For example, the host cell may refer to a cell expressing a nucleic acid encoding an antibody or antigen-binding fragment thereof that specifically binds to LRRC15.

[0065]

[0066] Another aspect provides a bispecific antibody comprising an antibody or an antigen-binding fragment thereof that specifically binds to LRRC15.

[0067] As used herein, the term "bispecific" or "dual-specific" antigen-binding protein or antibody may be a hybrid antigen-binding protein or antibody having two different antigen-binding sites. Such bispecific antibodies are a type of multispecific antigen-binding protein or multispecific antibody, which can be produced by various known methods, such as linking of Fab' fragments or fusion of hybridomas. See, e.g., Songsivilai and Lachmann, 1990, Clin. Exp. Immunol. 79:315-321; Kostelny et al., 1992, J. Immunol. 148:1547-1553, etc. The two different epitopes bound by the two antigen-binding sites of the bispecific antigen-binding protein or antibody may be located on the same or different protein targets.

[0068] Another aspect provides a nucleic acid encoding the bispecific antibody, a vector comprising the nucleic acid, and a cell transformed with the vector. The terms "nucleic acid," "vector," and "cell" are as described above.

[0069]

[0070] Another aspect provides a chimeric antigen receptor (CAR) comprising an antibody or antigen-binding fragment thereof that specifically binds to LRRC15.

[0071] In one specific example, the chimeric antigen receptor (CAR) is a chimeric antigen receptor (CAR) comprising an antigen binding domain; a transmembrane domain; a hinge domain; an intracellular co-stimulatory domain; and an intracellular signal transduction domain, wherein the antigen binding domain may be an antibody or an antigen-binding fragment thereof that specifically binds to the LRRC15.

[0072] The term "antigen binding domain" as used herein refers to a portion of a chimeric antigen receptor that recognizes and binds to a specific antigen. The term "binding domain" may be used interchangeably with "antigen-specific binding domain" and may refer to a chimeric antigen receptor (CAR) domain or fragment that has the ability to specifically bind to a target antigen (e.g., LRRC15).

[0073] In one specific example, the "antigen binding domain" is an antibody or an antigen-binding fragment thereof that specifically binds to Leucine-rich repeat-containing protein 15 (LRRC15), wherein the antibody or antigen-binding fragment comprises (i) heavy chain complementarity determining regions (CDRs) of CDRH1, CDRH2 and CDRH3 and (ii) light chain complementarity determining regions of CDRL1, CDRL2 and CDRL3, wherein the CDRH1 is an amino acid sequence having at least 85, 90, 95, 99 or 100% homology or identity with any one of the amino acid sequences represented by SEQ ID NOs: 1 to 30 and 316 to 325; The CDRH2 is an amino acid sequence having at least 85, 90, 95, 99 or 100% homology or identity to any one of the amino acid sequences represented by SEQ ID NOs: 31 to 67 and 326 to 336; the CDRH3 is an amino acid sequence having at least 85, 90, 95, 99 or 100% homology or identity to any one of the amino acid sequences represented by SEQ ID NOs: 68 to 115, 337 and 338; the CDRL1 is an amino acid sequence having at least 85, 90, 95, 99 or 100% homology or identity to any one of the amino acid sequences represented by SEQ ID NOs: 116 to 150, 339 and 340; The CDRL2 may be an amino acid sequence having at least 85, 90, 95, 99 or 100% homology or identity to any one of the amino acid sequences represented by SEQ ID NOs: 151 to 169, 341 and 342; and the CDRL3 may be an amino acid sequence having at least 85, 90, 95, 99 or 100% homology or identity to any one of the amino acid sequences represented by SEQ ID NOs: 170 to 211 and 343, but is not limited thereto.

[0074] The term "transmembrane domain" as used herein generally refers to a portion that passes through the cell membrane and connects to an intracellular signaling domain, thereby playing a role in signal transduction. The transmembrane domain may be derived from a protein selected from the group consisting of, but not limited to, CD8α, CD4, CD28, CD137, CD80, CD86, CD152, and PD1.

[0075] The term "hinge domain" as used herein refers to any oligopeptide or polypeptide, which may comprise 1 to 100 amino acid residues, preferably 10 to 70 amino acid residues, and may comprise all or part of a CD8-derived hinge domain, but is not limited thereto.

[0076] In one specific example, the antigen binding domain of the chimeric antigen receptor may be linked to the transmembrane domain by a hinge domain.

[0077] The term "intracellular co-stimulatory domain" as used herein generally refers to an intracellular domain capable of providing an immunostimulatory molecule, which is a cell surface molecule necessary for an effective response of a lymphocyte to an antigen. The intracellular co-stimulatory domain may include, but is not limited to, the intracellular co-stimulatory domain of CD28, and the intracellular co-stimulatory domains of the TNF receptor family, such as OX40 and 4-1BB.

[0078] The term "intracellular signal transduction domain" as used herein generally refers to a domain located inside a cell and capable of transducing a signal. For example, the intracellular signal transduction domain may be selected from an intracellular signal transduction domain selected from the group consisting of CD3 zeta (ζ), CD3 gamma (γ), CD3 delta (δ), CD3 epsilon (ε), FcR gamma, FcR beta, CD5, CD22, CD79a, CD79b, and CD66d, but is not limited thereto.

[0079] Another aspect provides a bispecific chimeric antigen receptor comprising an antibody or antigen-binding fragment thereof that specifically binds to LRRC15.

[0080] As used herein, the term "bispecific chimeric antigen receptor" means a chimeric antigen receptor capable of simultaneously recognizing and targeting two or more different antigens, comprising two or more different antigen binding domains, which antigen binding domains are capable of specifically binding to different antigens.

[0081] Specifically, the bispecific chimeric antigen receptor may include an antigen binding domain; a transmembrane domain; a hinge domain; an intracellular co-stimulatory domain; and an intracellular signal transduction domain. The bispecific chimeric antigen receptor may include two or more antigen binding domains that recognize different antigens, and the antigen binding domains that recognize different antigens may be connected by a linker.

[0082] In one embodiment, the bispecific chimeric antigen receptor may comprise a bispecific antibody comprising an antibody or an antigen-binding fragment thereof that specifically binds to LRRC15 (Leucine-rich repeat-containing protein 15).

[0083] Another aspect provides a nucleic acid encoding the chimeric antigen receptor or bispecific chimeric antigen receptor, a vector comprising the nucleic acid, and a cell expressing the nucleic acid.

[0084] In one specific example, the cell expressing the nucleic acid encoding the chimeric antigen receptor or bispecific chimeric antigen receptor may be an immune cell. More specifically, the immune cell may refer to a cell that regulates immunity by resisting pathogens or toxins that have invaded the body, and may include a natural killer cell, a T cell, a T lymphocyte, a B cell, a dendritic cell, or a macrophage. Furthermore, the immune cell may be an autologous or allogeneic immune cell.

[0085] Another aspect provides an antibody-drug conjugate (ADC) comprising an antibody or an antigen-binding fragment thereof that specifically binds to the Leucine-rich repeat-containing protein 15 (LRRC15), or a bispecific antibody or an antigen-binding fragment thereof comprising the same; a drug moiety; and a linker connecting the drug moiety and the antibody or an antigen-binding fragment thereof.

[0086] Another aspect provides a composition for diagnosing cancer comprising an antibody or an antigen-binding fragment thereof that specifically binds to the above LRRC15.

[0087] As used herein, the term "cancer" or tumor may collectively refer to a disease caused by cells that have an aggressive characteristic in which cells divide and proliferate while ignoring normal growth limits, an invasive characteristic in which cells invade surrounding tissues, and a metastatic characteristic in which cells spread to other parts of the body. The cancer may be any type of cancer that expresses LRRC15, and for example, the cancer may be a solid cancer. The solid cancer may be selected from the group consisting of, but is not limited to, colorectal cancer, pancreatic cancer, biliary tract cancer, breast cancer, ovarian cancer, sarcoma, melanoma, skin cancer, peritoneal cancer, bone cancer, brain cancer, head and neck cancer, lung cancer, stomach cancer, colon cancer, rectal cancer, esophageal cancer, prostate cancer, bladder cancer, kidney cancer, urethral cancer, thyroid cancer, liver cancer, cervical cancer, and anal cancer.

[0088] As used herein, the term “diagnosis” means determining the presence, extent (symptoms), and / or characteristics of a pathological condition.

[0089] In one specific example, the antibody or antigen-binding fragment thereof that specifically binds to the LRRC15 can be used in combination with various labels.

[0090] In one specific example, when the antibody or antigen-binding fragment thereof that specifically binds to LRRC15 does not have a detection label, the antibody or antigen-binding fragment thereof can be captured and identified by treating it with another antibody that has a detection label.

[0091] Another aspect provides a cancer diagnostic kit comprising the above cancer diagnostic composition. The cancer diagnostic kit may further comprise a composition, solution, or device containing one or more other components suitable for an analytical method.

[0092] The composition and cancer are as described above.

[0093] Another aspect provides a method for providing information for diagnosing cancer, comprising detecting LRRC15 protein in a separate biological sample from a subject suspected of having cancer using an antibody or an antigen-binding fragment thereof that specifically binds to LRRC15. Specifically, the step of detecting LRRC15 protein in a separate biological sample from a subject suspected of having cancer may utilize an antigen-antibody reaction.

[0094] The term "antigen-antibody complex" as used herein refers to a combination of the LRRC15 protein antigen in a sample and the antibody or antigen-binding fragment thereof according to the present invention that recognizes the same, and the formation of such an antigen-antibody complex can be detected by any method selected from the group consisting of a colorimetric method, an electrochemical method, a fluorimetric method, a luminometry method, a particle counting method, a visual assessment method, and a scintillation counting method. However, it is not necessarily limited to these and various applications and applications are possible.

[0095] Various markers can be used to detect the above antigen-antibody complex. For example, they can be selected from the group consisting of enzymes, fluorescent substances, ligands, luminescent substances, microparticles, and radioactive isotopes, but are not limited thereto. Specifically, enzymes used as detection markers include acetylcholinesterase, alkaline phosphatase, β-galactosidase, horseradish peroxidase, β-ratamase, etc., and fluorescent substances include fluorescein, Eu 3+ , Eu 3+It includes chelates or cryptates, etc., and as ligands, it includes biotin derivatives, etc., as luminescent materials, it includes acridinium esters, isoluminol derivatives, etc., as microparticles, it includes colloidal gold, colored latex, etc., and as radioactive isotopes, it includes 57 Co, 3 H, 125 I, 125 Includes I-Bonton Hunter reagent, etc. More specifically, antigen-antibody complexes can be detected using enzyme-linked immunosorbent assay (ELISA). ELISA includes various ELISA methods, such as direct ELISA using a labeled antibody that recognizes an antigen attached to a solid support, indirect ELISA using a labeled secondary antibody that recognizes a capture antibody in a complex of antibodies that recognize the antigen attached to the solid support, direct sandwich ELISA using another labeled antibody that recognizes an antigen in a complex of antibodies and antigens attached to a solid support, and indirect sandwich ELISA using a labeled secondary antibody that recognizes an antibody after reacting with another antibody that recognizes an antigen in a complex of antibodies and antigens attached to a solid support.

[0096]

[0097] Another aspect provides a pharmaceutical composition for treating cancer comprising the antibody, antigen-binding fragment, bispecific antibody or antibody drug conjugate.

[0098] In one specific example, the cancer may be at least one selected from the group consisting of colorectal cancer, pancreatic cancer, biliary tract cancer, breast cancer, ovarian cancer, sarcoma, melanoma, skin cancer, peritoneal cancer, bone cancer, brain cancer, head and neck cancer, lung cancer, stomach cancer, colon cancer, rectal cancer, esophageal cancer, prostate cancer, bladder cancer, kidney cancer, urethral cancer, thyroid cancer, liver cancer, cervical cancer, and anal cancer, but is not limited thereto.

[0099] The pharmaceutical composition may contain the antibody or antigen-binding fragment thereof as an active ingredient in an amount of about 0.1 wt% to about 90 wt%, specifically about 0.5 wt% to about 75 wt%, and more specifically about 1 wt% to about 50 wt%, based on the total weight of the composition.

[0100] The pharmaceutical composition may include conventional, non-toxic, pharmaceutically acceptable additives formulated into a formulation according to conventional methods. For example, the pharmaceutical composition may additionally include a pharmaceutically acceptable carrier, diluent, or excipient.

[0101] Examples of additives used in the above pharmaceutical composition may include sweeteners, binders, solvents, solubilizers, wetting agents, emulsifiers, isotonic agents, absorbents, disintegrants, antioxidants, preservatives, lubricants, glidants, fillers, flavoring agents, and the like. For example, the additives may include lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, glycine, silica, talc, stearic acid, stearin, magnesium stearate, magnesium aluminosilicate, starch, gelatin, gum tragacanth, alginic acid, sodium alginate, methylcellulose, sodium carboxymethylcellulose, agar, water, ethanol, polyethylene glycol, polyvinylpyrrolidone, sodium chloride, calcium chloride, orange essence, strawberry essence, vanilla flavoring, and the like.

[0102] The pharmaceutical composition may be formulated in various formulations for oral administration (e.g., tablets, pills, powders, capsules, syrups or emulsions) or parenteral administration (e.g., intramuscular, intravenous or subcutaneous injection).

[0103] Specifically, when the pharmaceutical composition is formulated as a preparation for oral administration, additives used may include cellulose, calcium silicate, corn starch, lactose, sucrose, dextrose, calcium phosphate, stearic acid, magnesium stearate, calcium stearate, gelatin, talc, surfactants, suspending agents, emulsifiers, diluents, etc. In addition, examples of glidants include colloidal silicon dioxide, magnesium silicate, etc.; Examples of diluents include microcrystalline cellulose, lactose anhydrous, lactose monohydrate, and silicified MCC HD 90; examples of disintegrants include croscarmellose sodium and crospovidone; and examples of lubricants include magnesium stearate, sodium lauryl sulfate, and stearic acid.

[0104] In addition, liquid preparations for oral administration may include suspensions, emulsions, syrups, etc., and may include various excipients such as wetting agents, sweeteners, fragrances, and preservatives in addition to commonly used simple diluents such as water and liquid paraffin.

[0105] Additionally, preparations for parenteral administration may include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solvents and suspending agents may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Suppository bases may include withepsol, macrogol, Tween 61, cacao butter, laurin, and glycerogelatin. Meanwhile, injections may include conventional additives such as solubilizers, isotonic agents, suspending agents, emulsifiers, stabilizers, and preservatives.

[0106] The pharmaceutical composition may be administered to a patient in a therapeutically effective amount or a pharmaceutically effective amount.

[0107] The term "therapeutically effective amount" or "pharmaceutically effective amount" as used herein refers to an amount of a compound or composition that is effective in preventing or treating a target disease, and is sufficient to treat the disease at a reasonable benefit / risk ratio applicable to medical treatment, and does not cause side effects. The level of the effective amount may be determined based on factors including the patient's health condition, type and severity of the disease, activity of the drug, sensitivity to the drug, method of administration, time of administration, route of administration and excretion rate, duration of treatment, drugs used in combination or concurrently, and other factors well known in the medical field.

[0108] The above pharmaceutical composition may be administered as an individual treatment or in combination with other treatments, sequentially or simultaneously with conventional treatments, or in single or multiple doses. Taking all of the above factors into account, it is important to administer the amount that achieves maximum effect with the minimum amount possible without causing side effects, a determination readily available to those skilled in the art.

[0109] Specifically, the effective amount of the antibody or antigen-binding fragment thereof in the pharmaceutical composition may vary depending on the patient's age, sex, and weight, and is generally about 0.1 mg to about 1,000 mg, or about 5 mg to about 200 mg per kg of body weight, administered daily or every other day, or divided into one to three times a day. However, the range is not limited thereto, as it may increase or decrease depending on the route of administration, severity of the disease, sex, weight, age, etc.

[0110] Additionally, the pharmaceutical composition may be administered for oncology therapy in combination with chemotherapy, radiation therapy, immunotherapy, hormonal therapy, bone marrow transplantation, stem cell replacement therapy, other biological therapies, surgical intervention, or a combination thereof. For example, it may be used as adjuvant therapy alongside other long-term treatment strategies, or to maintain the patient's condition after tumor regression or chemoprevention in critically ill patients.

[0111] Another aspect provides a method for preventing or treating cancer, comprising administering to a subject in need thereof an effective amount of an antibody or an antigen-binding fragment thereof that specifically binds to the Leucine-rich repeat-containing protein 15 (LRRC15); the bispecific antibody; the chimeric antigen receptor; or the antibody drug conjugate.

[0112] Another aspect provides the use of an antibody or an antigen-binding fragment thereof that specifically binds to Leucine-rich repeat-containing protein 15 (LRRC15); the bispecific antibody; the chimeric antigen receptor; or the antibody drug conjugate; for use in the manufacture of a pharmaceutical preparation for preventing or treating cancer.

[0113] Duplicate contents are omitted in consideration of the complexity of this specification, and terms not otherwise defined in this specification have meanings commonly used in the technical field to which the present invention belongs.

[0114] According to one aspect, antibodies that specifically bind to LRRC15 can be used as cancer diagnostic or predictive biomarkers and cancer targeted therapeutics.

[0115] Figure 1 is a photograph confirming the ED2 antigen using a PAGE gel.

[0116] Figures 2a and 2b show the results of measuring the Viable Cell Density and Viability of Expi293F cells transfected with a vector containing the sequence of an antibody converted into the full IgG form of anti-LRRC15 Fab.

[0117] Figures 3a to 3c show the results of measuring the Viable Cell Density and Viability of ExpiCHO-S cells transfected with a vector containing the sequence of an antibody converted into the full IgG form of anti-LRRC15 scFv.

[0118] Figures 4a and 4b show the results of separating and purifying antibodies converted into whole IgG form using protein A chromatogram of anti-LRRC15 Fab (13 types).

[0119] Figures 5a to 5c show the results of separating and purifying LRRC15 scFv (39 types) using protein A chromatogram of antibodies converted into whole IgG form.

[0120] Figures 6a and 6b are photographs confirming the purity of anti-LRRC15 antibodies (Fab (13 types) and scFv (39 types), 52 types).

[0121] Figure 7 is a graph showing the results of analyzing the degree to which anti-LRRC15 Fabs (13 types) bind to LRRC15 expressed on the cell surface using a FACS system: Figure 7a is a graph showing the results of FACS analysis of anti-LRRC15 Fabs (13 types) in HEK293F-ED2, Figure 7b is a graph showing the results of FACS analysis of anti-LRRC15 Fabs (13 types) in HCT116-ED2, and Figure 7c is a graph showing the results of FACS analysis of anti-LRRC15 Fabs (13 types) in CCD-18Co-ED2.

[0122] Figure 8 is a graph showing the results of analyzing the degree to which anti-LRRC15 scFv (39 types) binds to LRRC15 expressed on the cell surface using a FACS system: Figures 8a to 8c are graphs showing the results of FACS analysis of anti-LRRC15 scFv (39 types) in HEK293F-ED2, Figures 8d to 8f are graphs showing the results of FACS analysis of anti-LRRC15 scFv (39 types) in HCT116-ED2, and Figures 8g to 8i are graphs showing the results of FACS analysis of anti-LRRC15 scFv (39 types) in CCD-18Co-ED2.

[0123] Figure 9 is a graph showing the results of measuring the binding affinity between 15 types of anti-LRRC15 antibodies selected from Example 2.5 and the LRRC15 antigen using a biomolecular reaction analyzer (Octet QK384).

[0124] Figure 10 is a graph showing the internalization results of anti-LRRC15 Fab antibodies (13 types): Figure 10a is a graph showing the internalization results of anti-LRRC15 Fab antibodies (13 types) in HEK293F, Figure 10b is a graph showing the internalization results of anti-LRRC15 Fab antibodies (13 types) in HCT116, and Figure 10c is a graph showing the internalization results of anti-LRRC15 Fab antibodies (13 types) in CCD-18Co.

[0125] Figure 11 is a graph showing the internalization results of anti-LRRC15 scFv antibodies (13 types): Figure 11a is a graph showing the internalization results of anti-LRRC15 scFv antibodies (13 types) in HEK293F, Figure 11b is a graph showing the internalization results of anti-LRRC15 scFv antibodies (13 types) in HCT116, and Figure 11c is a graph showing the internalization results of anti-LRRC15 scFv antibodies (13 types) in CCD-18Co.

[0126] Figure 12 is a graph showing the internalization results of anti-LRRC15 scFv antibodies (26 types): Figure 12a is a graph showing the internalization results of anti-LRRC15 scFv antibodies (26 types) in HEK293F, Figure 12b is a graph showing the internalization results of anti-LRRC15 scFv antibodies (26 types) in HCT116, and Figure 12c is a graph showing the internalization results of anti-LRRC15 scFv antibodies (26 types) in CCD-18Co.

[0127] Figures 13a to 13c are graphs showing the results of SPR analysis for 24 types of optimized antibodies and 3 types of comparative samples according to one specific example of the present invention.

[0128] Figure 14 shows SPR sensorgrams (left) measuring binding reactions with antigen (LRRC15) at various concentrations for the parent antibody (WT) and seven types of optimized antibodies in FASEBA format according to one specific example of the present invention, and the results of deriving binding curves and KD values ​​calculated based on a 1:1 binding model for some antibodies (right).

[0129] Figures 15a and 15b are graphs showing SPR analysis data for each of 12 optimized antibodies in Fab format and the parent antibody (WT) according to one specific example of the present invention.

[0130] Figures 16a and 16b illustrate the SPR sensorgram results evaluating the binding and dissociation characteristics of eight types of anti-LRRC15 optimized antibodies and the parent antibody (WT) according to one specific example of the present invention after recombining them into an IgG1 format with the recombined LRRC15 antigen.

[0131] Figures 17a and 17 are graphs showing the results of ELISA analyzing the binding ability of anti-LRRC15 optimized antibody clones according to one embodiment of the present invention selected through affinity maturation to recombinant human LRRC15-ECD antigen.

[0132] Figures 18a to 18c are graphs showing the results of ELISA analysis of antibody binding to recombinant LRRC15 antigens derived from human, monkey, and mouse to evaluate the cross-species reactivity of anti-LRRC15 antibodies according to one specific example of the present invention.

[0133] FIG. 19 is a graph showing the results of quantitatively evaluating the degree to which anti-LRRC15 optimized antibodies according to one specific example of the present invention exhibit cell surface binding ability to human LRRC15 antigen expressed in various cancer-derived cell lines through flow cytometry (FACS): FIG. 19a is a graph showing the results of analyzing the binding ability of anti-LRRC15 antibodies according to the present invention to cell surface antigens using HEK293F-ED2 and HEK293F-ED2-C-His cell lines expressing human LRRC15 in HEK293F-derived cells, FIG. 19b is a graph showing the results of evaluating the cell binding ability of anti-LRRC15 antibodies according to the present invention using KHOS / NP-ED2 cells expressing human LRRC15 in KHOS / NP, an osteosarcoma-derived cell line, and FIG. 19c is a graph showing the results of evaluating the cell binding ability of anti-LRRC15 antibodies according to the present invention to RPMI-7951, a melanoma-derived cell line. This graph shows the results of analyzing the degree of binding to antigens expressed on the cell surface.

[0134] FIG. 20 is a graph showing the internalization results of anti-LRRC15 optimized antibodies according to one specific example of the present invention: FIG. 20a is a graph showing the internalization results of anti-LRRC15 optimized antibodies (AHF45168, AHF45171, AHF45176, AHF45184, AHF45199, AHF45202) in Saos-2 and Huo9 cell lines, FIG. 20b is a graph showing the internalization results of anti-LRRC15 optimized antibodies in KHOS / NP ED2 and colon fibroblast cell lines (CCD-18Co-ED2), and FIG. 20c is a graph showing the internalization results of anti-LRRC15 optimized antibodies in Saos-2 and SK-MEL-28 ED2 overexpressing clones.

[0135] The following examples are provided for more detailed explanation. However, these examples are provided for illustrative purposes only and the scope of the present invention is not limited to these examples.

[0136]

[0137] Example 1. Preparation of antibodies

[0138] Example 1.1. Preparation of antigen

[0139] Antigens used in phage display library screening for anti-LRRC15 antibody production were purchased and used. For human LRRC15, a recombinant LRRC15 protein (15786-H08H, Sino Biological) containing amino acid sequences 1 to 538 of NP_570843.2 and a histidine-tag at the C-terminus was used. The same antigen was also used in the ELISA and Octet assays described below. The antigens used were analyzed by PAGE, and the results are shown in Figure 1.

[0140] Figure 1 is a photograph confirming the ED2 antigen using a PAGE gel.

[0141]

[0142] Example 1.2: Antibody selection and production through phage library screening

[0143] Preparation of library phage

[0144] Escherichia coli (E. coli) containing the human synthetic antibody library (KFab-I, KFab-II) provided by the New Drug Development Support Center of the Oseong Advanced Medical Industry Promotion Foundation and the human unprimed antibody library (scFv, single-chain variable fragment) provided by Y-Biologics were inoculated into 2X YT-GMC (Glucose, MgCl2, Chloramphenicol) medium and cultured in a shaking incubator at 37°C. OD 600 When the value reached 0.5, M13 helper phage was added at an MOI (Multiplicity Of Infection) = 10 and cultured in a 37℃ shaking incubator to induce M13 helper phage infection. After centrifugation of the culture, the pellet was resuspended in 2X YT-IPTG-MKC (IPTG, MgCl2, Kanamycin, Chloramphenicol) medium. The suspension was cultured in a 30℃ shaking incubator to induce scFv and Fab-phage production. After centrifugation of the culture, 4% PEG6000, 3% NaCl were added to the supernatant and the reaction was performed on ice. After centrifugation of the reaction solution, the pellet was suspended in DPBS. The suspension was centrifuged to obtain phage.

[0145] panning

[0146] To select antibodies that bind to human LRRC15 protein, panning was performed three times in total using the recombinant LRRC15 protein to which the histidine-tag (His-tag) of Example 1.1 was linked, as follows.

[0147] Specifically, a positive antigen was coated (or bound) to an immunotube (or magnetic bead). The supernatant was removed and blocked by adding a blocking solution (4% skim milk). The supernatant was removed, and the purified library phage was added to the antigen-coated immunotube (or bead) for reaction. After removing the phage, it was washed several times with PBST. The bound phage was eluted by adding 100 mM TAE, and then neutralized by adding 1 M Tris-HCl (pH 7.5). The eluted phage was added to XL1-Blue (with instructions for E. coli added) and infection was induced in a 37℃ incubator. E. coli was plated on a SOBCG (Trypton, Yeast, NaCl, Agers, Glucose, MgCl2, Chloramphenicol) plate and cultured in a 37℃ incubator.

[0148] Polyclonal Phage Preparation

[0149] The library and the output colonies obtained after 1, 2, and 3 rounds of panning, and the negative control group AB#38 were inoculated into 2x YT-GMC medium and cultured. OD 600 When the concentration of phage reached 0.5, M13 helper phage was added at a multiplicity of infection (MOI) of 10. M13 helper phage infection was induced by culturing in an incubator, the culture solution was centrifuged, and the pellet was resuspended in 2X YT-IPTG-MKC medium. The suspension was cultured in a shaking incubator at 30°C to induce scFv and Fab-phage production.

[0150] Preparation of Monoclonal Phage

[0151] A single clone obtained from the output of rounds 2 and 3 was inoculated into a deep well plate (or conical tube) containing 2X YT-GMC medium and cultured in a 37℃ shaking incubator. When the OD600 reached 0.5, M13 helper phage was added at an MOI (Multiplicity Of Infection) = 10. Incubation in an incubator induced M13 helper phage infection, and the culture solution was centrifuged. The pellet was resuspended in 2X YT-IPTG-MKC medium. The suspension was cultured in a 30℃ shaking incubator to induce scFv and Fab-phage production.

[0152] Selection of phages with binding specificity for LRRC15

[0153] ELISA

[0154] To detect phages binding to LRRC15, an Enzyme-Linked Immunosorbent Assay (ELISA) was performed. Specifically, LRRC15 (positive) and negative antigens were suspended in DPBS at 1 μg / mL and added to an immunoplate (Immuno-plate) at 100 μL / well to coat the antigens. The supernatant was removed, and blocking solution (4% skim milk) was added to block. The supernatant was removed, and 100 μL of poly-phage (or mono-phage) was added to the antigen-coated immunoplate to induce binding. The supernatant was removed, and 200 μL / well of PBST was added three times to wash. The immunoplate was reacted with 100 μL / well of Anti-M13-HRP. The supernatant was removed, and 200 μL / well of PBST was added three times to wash. 100 μL / well of TMB peroxidase substrate (or o-Phenylenediamine dihydrochloride) was added to the immunoplate to initiate the reaction, and 50 μL / well of Stop solution (with added sulfuric acid) was added to stop the reaction after 10 minutes. The absorbance was measured at a wavelength of 450 nm (or 490 nm) using an ELISA device (plate reader).

[0155] Non-specific Phage ELISA

[0156] To evaluate non-specific binding, phage was prepared in the same manner as the mono-phage preparation and the experiment was performed using the same process as the ELISA above.

[0157] As a result, the sequences of 13 Fab formats, 13 scFv formats, and 26 additionally selected scFv formats were obtained. The CDR sequences of the Fabs and scFvs selected as a result of ELISA are shown in Tables 1 and 2, and the VH VL sequences of the selected Fabs and scFvs are shown in Tables 3 and 4. In addition, the entire sequence information of the selected Fabs and scFvs is described in Table 5.

[0158] 명칭서열서열번호VH CDR1(CDRH1)GFTFSNYA1GFTFSSYA2GFTFSSYG3GGTFSAYG4GGTFSSYG5GYSFTSYW6GYTFSSYW7GFTFGDYA8GYVFSTFD9GFTFDDYA10GFTFSSSW11GFPFSSYA12GFTFNNYA13GFTFSRYW14GFTFNDYA15GYTFSNFY16GFNFDDYA17GFTFSTYG18GFTFSDNY19GFSFGDYA20GFTFDDYG21GDTLISNY22GFTVSSNY23GYTFSNYG24GDSVSSNSAA25GYTFGSYV26GFTFSTYA27GFTFDEYA28GFNFDDYG29GASISSYH30VH CDR2(CDRH2)ISSSGSYT31ISGTGGST32ISGSGGST33ISGDGGST34IKSSGGNK35ISGSGGET36ISPYSGGT37ISGSGSST38IIPILGIA39ISGSGGDI40IIASGGIT41IYPGNSDT42INPGNGHT43LSATGGRT44MNPKTGST45INQAGSVK46ISWRNDST47VTGYRDST48ISSGSRFI49IHWRSDYI50INPIDGYT51IRSKAYGGTT52ISYDGSNK53ISWNSDDI54ISDGGHST55IATSGTTT56IYPGDSDT57INWNGERT58INPSGDYT59VSPYNGNT60ISWNSGSI61TYYRSKWYN62INWNGGST63ISNDGSRE64ISWISSSE65ISGDGENT66IDYSGSA67VHCDR3(CDRH3)AKEGIGGTEEAMDV68AKRIRRYFDF69AKRRFLFFDY70AKRAWRGFDI71AKRKQRGFDY72AKHGSYRFDY73AKRGQRRFDN74ARGSSWWETGGFDY75AKRRHQTFDF76AKREHRSYLFDY77ARQGYTRGTFTLDY78AKSIWREFDY79ARERWTYSYYFDI80VAAGAGGLDY81AREGASSGHYDS82ASDKRGWTLNGMDV83ARSSGWGAFDI84ARQGEWELRGAFDI85ARGHAYGDYIGTY86ARDSIGGTLDV87GRHAGGSSFDY88ARRASGRGFDI89VKGGWFYPFDF90ARDKYGLDV91ARPISTSYYYAMDV92ARLEFPDSSGYYSNYYFYYGMDV93ATDRAGIIDFDD94AREGEWGLRAAFDI95ARDPGGVYPSYLDY96AKGEG97AKDLMIYANSPRGIDY98ARHAGSRGGYYYEPSDF99AKNRGLGVVPFDF100ARGGGLTGFDP101AKDARGNPFYFDF102PRVGRLLGAFDI103TRGGWFYPFDS104ATNTAMGYFDY105AKDRELGFGELSWFDP106VRDSYAGYSTH107VRDGSLQINNVWYDLLDS108ASGIRGVRSPDY109ARTSHFHYYGMDV110AKDDVYNSSWYAPDY111ARSDRYGDYLGRAFDI112VRDPGYSGHGPKIDY113ARVDEISVASFDY114AASTDILRHFPYYYHGMDV115

[0159] 명칭서열서열번호VL CDR1(CDRL1)QSISNY116QSIGNW117QSISSY118QTISNW119QTISNY120QSISSW121QSLVHSNGNTY122HDISTY123QSLLDSHDGNTY124QDVSKW125QSISNW126QSLLQRNGYNY127RSNFGAGHD128QHISTW129QSISRW130QSLVHSSGNTY131QGISSY132QAISSW133NSDIGGYNY134QNISNW135SSNIRSNT136QNINSW137QSVLLRSNNKNY138SSDVGAYNY139QSLVRSDGTTY140QSISTW141QSLVHSDGNTY142QSVGSY143SSDVGGYNY144SNDVGGYTY145TSDVGGYYY146QYIGTY147SSDIGDYNY148KLETKY149KLGDKF150VL CDR2(CDRL2)DAS151ATS152AAS153KIS154GAS155TLS156KAS157LGS158GNN159SAS160DVS161NDD162WAS163EVT164DVT165DVD166DVH167QDY168QDD169VLCDR3(CDRL3)QQSYSFPWT170QQSYSYPWT171QQSSSTPWT172QQTYSTPWT173QQSYSTPWT174QQSYSFPFT175QQSYSSPWT176QQSYSFPYT177QQSYSFPLT178QQSYTFPWT179VQAKQFPLT180QQYDAYPLT181MQRVEFPFT182LQATSFPYT183QQLNSYPFT184MQAVQFPRT185QQYASFSPYT186QSFDSRLGVV187QQANSFPPT188QQANSFPLT189VQAKEFPLT190QQGYGTPYT191CSYAGNSTYV192QQSHGYAT193QQLNSYPLT194AAWDDSLNWVV195HQTSTAPQT196QQYYSTPYT197GSYTSSSTFEV198LQAKQFPLT199QQYGTTPYT200HSYIGGSTFGV201SSYAGSYTWV202GSYTSSSSLV203QQSYSTPG204SSYTSNTTPR205QHLNSYPVT206SSFTNNRTVV207ASYAGSYTYV208ASYTASTALVI209QAWDSNTAI210QAWDSSTHVV211

[0160]

[0161]

[0162]

[0163] Example 2. Conversion of anti-LRRC15 Fab and scFv into full IgG form and production thereof

[0164] Example 2.1. Cloning of anti-LRRC15 Fab into full IgG form

[0165] In Example 1, polynucleotides having nucleotide sequences encoding the selected Fab antibodies were synthesized. The prepared polynucleotides were cloned into animal cell expression vectors (heavy chain expression vector: pCEP4-HC, and light chain expression vector: pCEP4-LC). A total of 26 vectors containing polynucleotides encoding the heavy and light chains for each of the 13 antibody clones were prepared. Each of the vectors prepared for pCEP4-HC and pCEP4-LC contained an IgG1-type sequence.

[0166] Example 2.2. Cloning of anti-LRRC15 scFv into full IgG form

[0167] In Example 1, polynucleotides having nucleotide sequences encoding the scFv antibodies selected were synthesized. The prepared polynucleotides were cloned into animal cell expression vectors (heavy chain expression vector: pcDNA3.4-HC and light chain expression vector: pcDNA3.4-LC). A total of 78 vectors containing polynucleotides encoding the heavy and light chains for each of the 39 antibody clones were prepared. Each of the vectors prepared for pcDNA3.4-HC and pcDNA3.4-HC contained an IgG1-type sequence.

[0168] Example 2.3. Expression of anti-LRRC15 antibodies

[0169] Expression of anti-LRRC15 antibodies converted into whole IgG forms of Fab and scFv of Examples 2.1 and 2.2 was performed using Expi293F™ (ThermoFishier, A14527) and ExpiCHO-S™ (Thermo Fisher, A29127) cells developed by Thermo, and in compliance with the protocols of Expi293™Expression System Kit (Thermo Fisher, A14635) and ExpiCHO™Expression System Kit (Thermo Fisher, A29133).

[0170] Specifically, Expi293F cells were cultured under conditions of 37℃≥80% humidity, 8% CO2, 120 rpm, and on the day of transfection, Expi293F cells were seeded at 3X10 6 The cells were diluted and prepared by adding Expi293™ expression medium (Thermo Fisher, A1435101) at a cell concentration of 10 cells / mL.

[0171] The heavy chain vector of Example 2.1 was diluted in Opti-MEM™I Reduced Serum medium (ThermoFisher, 31985070) at 0.33 μg per mL of medium, and the light chain vector of Example 2.1 was diluted in Opti-MEM™I Reduced Serum medium at 0.67 μg per mL, and ExpiFectamine™ 293 Reagent was diluted in Opti-MEM™I Reduced Serum medium. The vector and ExpiFectamine™293 mixture were mixed, reacted at room temperature for 10 to 20 minutes, and cultured for 20 hours under the conditions of 37°C, ≥80% humidity, 8% CO2, and 120 rpm. After 20 hours, ExpiFectamine™ 293 Transfection Enhancer 1 and ExpiFectamine™ 293 Transfection Enhancer 2 included in the ExpiFectamine™ expression system were added, and cultured for 5 days. After culturing, the culture medium of the cells was centrifuged at 3600 rpm at 4°C for 30 minutes, and the supernatant was separated and stored in a refrigerator.

[0172] ExpiCHO-S cells were cultured at 37°C, ≥80% humidity, 8% CO2, and 120 rpm. On the day of transfection, ExpiCHO-S cells were seeded at 6X10 6 Dilution was performed by adding ExpiCHO-S™ expression medium (Thermo Fisher, A29100-01) to a cell concentration of 10 cells / mL.

[0173] The heavy chain vector of Example 2.2 was diluted in OptiPRO™ SFM medium (Thermo Fisher, 12309050) at 0.5 μg per mL of medium, and the light chain vector of Example 2.2 was diluted in OptiPRO™ SFM medium at 0.5 μg per mL, and ExpiFectamine™ CHO Reagent was diluted in OptiPRO™ SFM medium. The vector and ExpiFectamine™ CHO mixture were mixed and reacted at room temperature for 1 to 5 minutes, and then cultured for 20 hours under conditions of 37°C≥80% humidity, 8% CO2, and 120 rpm. After 20 hours, ExpiCHO™ Enhancer and ExpiCHO™ Feed in the ExpiCHO™ expression system kit (Thermo Fisher, A29133) were added and cultured for 10 days. After culture, the cell culture medium was centrifuged at 4°C and 3600 rpm for 30 minutes, and the supernatant was separated and stored in the refrigerator.

[0174] Example 2.4. Measurement of culture of cells introduced with anti-LRRC15 antibodies

[0175] The culture status of cells expressing antibodies converted into whole IgG forms of anti-LRRC15 Fab and scFv of Example 2.3 was confirmed by measuring Viable Cell Density and Viability.

[0176] Specifically, the trypan blue dye exclusion method and automated Vi-CELL BLU equipment were used. Viable cell density and viability were measured based on captured images after mixing 200 μL of a sample solution containing cells and trypan blue dye in a 1:1 ratio.

[0177] The results are shown in Figures 2 and 3.

[0178] Figures 2a and 2b show the results of measuring the Viable Cell Density and Viability of Expi293F cells transfected with a vector containing the sequence of an antibody converted into the full IgG form of anti-LRRC15 Fab.

[0179] Figures 3a to 3c show the results of measuring the Viable Cell Density and Viability of ExpiCHO-S cells transfected with a vector containing the sequence of an antibody converted into the full IgG form of anti-LRRC15 scFv.

[0180] As shown in FIGS. 2a to 3c, it was confirmed that each cell (Expi293F cell, ExpiCHO-S cell) transformed with a vector containing the antibody sequence of Example 2.3 had high Viability in the early stage of culture, and Viable Cell Density increased as culture time passed.

[0181] Example 2.5. Isolation and purification of anti-LRRC15 antibodies

[0182] To isolate and purify the anti-LRRC15 antibodies (Fab and scFv, 52 types) of Example 2.3, the culture medium stored in Example 2.3 was filtered through a 0.22 μm PES Bottle Top Filter. 5 mL of Amsphere A3 resin was packed into a Hiscale 16 / 20 column, washed with 100 mL of triple-distilled water at a flow rate of 5 mL / min, and the column was equilibrated with 25 mL of equilibration buffer (20 mM sodium phosphate, pH 7.5). The filtered sample was bound to the Amsphere A3 column at a flow rate of 1.5 mL / min, and then 10 mL of equilibration buffer was flowed to stabilize the UV280 nm value to the Base Line. Impurities were removed by flowing 15 mL of wash buffer I (20 mM sodium phosphate, 1 M NaCl, pH 6.0) at a flow rate of 5 mL / min, and the UV280 nm value was stabilized to the baseline by flowing 15 mL of wash buffer II (20 mM sodium phosphate, pH 6.0). The antibody was eluted by flowing 25 mL of elution buffer (100 mM sodium acetate, pH 3.3) at a flow rate of 1.5 mL / min, and the fraction volume was set to 4 mL, and 600 μL of saturated Tris solution was added to each fraction tube. The eluted antibody was placed in a Dialysis Tube and exchanged with 3 L of PBS, 10% Glycerol, pH 7.4 buffer for 4 hours in a low temperature room (4°C), then replaced with 3 L of new PBS, 10% Glycerol, pH 7.4 and exchanged for 16 hours. After filtration with a 0.22 μm PES Syringe Filter, the A280 absorbance was measured, and the results are shown in Figs. 4 and 5.

[0183] Figures 4a and 4b show the results of separating and purifying antibodies converted into whole IgG form using protein A chromatogram of anti-LRRC15 Fab (13 types).

[0184] Figures 5a to 5c show the results of separating and purifying LRRC15 scFv (39 types) using protein A chromatogram of antibodies converted into whole IgG form.

[0185] As shown in Figures 4a to 5c, it was confirmed that the antibodies converted into the full IgG form of LRRC15 Fab and scFv were well separated and purified from the cell culture medium.

[0186] Example 2.6. Confirmation of the purity of the isolated and purified anti-LRRC15 antibody.

[0187] To confirm the purity of the anti-LRRC15 antibodies (Fab and scFv, 52 types) of Example 2.5, SDS-PAGE was performed.

[0188] Specifically, the anti-LRRC15 antibody (Fab and scFv, 52 types) of Example 2.5 was prepared as a Reducing Sample and a Non-reducing Sample, respectively. 7.5 μL of 4X Reducing Sample Buffer was added to 2 μg / 22.5 μL, vortexed at 3,300 rpm for 10 seconds, heated in a heating block at 70℃ for 10 minutes, and centrifuged for 1 minute to prepare a Reducing Sample. 7.5 μL of 4X Non-reducing Sample Buffer was added to 2 μg / 22.5 μL, vortexed at 3,300 rpm for 10 seconds, heated in a heating block at 70℃ for 10 minutes, and centrifuged for 1 minute to prepare a Non-reducing Sample. Each sample was loaded with 5 μL of Protein Marker and 30 μL of test solution onto a 4-20% Mini-PROTEAN TGX Precast Protein Gel and electrophoresis was performed at 140 V for 60 minutes. After electrophoresis, 20 mL of EZ-Gel Staining Solution was added, stained for 1 hour, and destained with triple-distilled water to observe the bands. The results are shown in Figure 6.

[0189] Figures 6a and 6b are photographs confirming the purity of anti-LRRC15 antibodies (Fab (13 types) and scFv (39 types), 52 types).

[0190] As shown in Figures 6a and 6b, the purity of the anti-LRRC15 antibodies (52 types) was confirmed to be high.

[0191] Example 3. Analysis of binding specificity of anti-LRRC15 antibodies to LRRC15

[0192] Example 3.1. Analysis of binding specificity of anti-LRRC15 antibodies to recombinant antigens

[0193] In Example 2.5, the specific binding ability of the purified anti-LRRC15 antibody to the recombinant LRRC15 antigen protein was analyzed using the Sandwich ELISA method.

[0194] Specifically, Anti-His antibody was used as a coating antibody, LRRC15-ECD (Extracellular Domain)-His corresponding to the extracellular region of human LRRC15 was used as an antigen protein, and HRP-conjugated anti-human polyclonal antibody reagent (Sigma, cat# A8667-2ML) was used as a secondary antibody to perform the test as follows. Anti-His antibody at 13.3 nM per well was coated on the ELISA plate, the plate was washed with PBST, and then incubated with SuperBlock (Thermo, cat# 37515) to prevent non-specific binding, and then the plate was washed with PBST. Human recombinant LRRC15-ECD-His protein was added to each well at 20 nM and incubated at room temperature for 1 hour, washed with PBST, and treated with the prepared anti-LRRC15 antibody to each well, reacted for 1 hour at room temperature, and washed five times with PBST. Afterwards, color was developed using HRP-conjugated anti-human polyclonal antibody and TMB (Sigma, cat# T4319-4X100ML), and the results were analyzed by measuring the absorbance at 450 nm.

[0195] Example 3.2. Cross-species reactivity analysis of anti-LRRC15 antibodies against human, monkey, and mouse antigens

[0196] To analyze the cross-species reactivity of the purified anti-LRRC15 antibody in Example 2.5, the binding affinity to recombinant LRRC15 antigen proteins of human, monkey, and mouse was compared using the Sandwich ELISA method.

[0197] Anti-His antibody was used as a coating antibody, LRRC15-ECD (Extracellular Domain)-His corresponding to the extracellular region of LRRC15 of human, monkey, and mouse was used as an antigen protein, and HRP-conjugated anti-human polyclonal antibody reagent (Sigma, cat# A8667-2ML) was used as a secondary antibody and the test was performed as follows. Anti-His antibody at 13.3 nM per well was coated on the ELISA plate, the plate was washed with PBST, and then incubated with SuperBlock (Thermo, cat# 37515) to prevent non-specific binding, and the plate was washed with PBST. Recombinant LRRC15-ECD-His protein was added to each well at 20 nM and incubated at room temperature for 1 hour, washed with PBST, and treated with the prepared anti-LRRC15 antibody to each well, reacted for 1 hour at room temperature, and washed the plate 5 times with PBST. Afterwards, color was developed using HRP-conjugated anti-human polyclonal antibody and TMB (Sigma, cat# T4319-4X100ML), and the results were analyzed by measuring the absorbance at 450 nm.

[0198] Example 3.3. Analysis of binding specificity of anti-LRRC15 antibodies to LRRC15

[0199] The extent to which the selected anti-LRRC15 antibodies bound to LRRC15 expressed on the cell surface was analyzed using a FACS system. Specifically, HEK293F-LRRC15, HCT116-LRRC15, and CCD-18Co-LRRC15 cell lines (manufactured by Edisbiotech) overexpressing human LRRC15 were prepared, and HEK293F-pCMV3, HCT116-pCMV3, and CCD-18Co-pCMV3 cell lines that do not express LRRC15 were prepared as a control group.

[0200] The purified anti-LRRC15 antibody from Example 2.5 was added at 300 nM to the prepared cells, incubated at 4°C for 1 hour, and then washed twice with PBS. Anti-human IgG antibody-PE was diluted to 10 nM and incubated at 4°C for 30 minutes, washed three times with PBS, and the fluorescence intensity of the cells was measured using a BD Accuri™C6 Plus device, and the results are shown in Figs. 7 and 8. (HEK-ED2 is HEK293F-LRRC15 or HEK293F-pCMV3 cell line with anti-LRRC15 antibody, HCT-ED2 is HCT116-LRRC15 or HCT116-pCMV3 cell line with anti-LRRC15 antibody, and CCD-ED2 is CCD-18Co-LRRC15 or CCD-18Co-pCMV3 cell line with anti-LRRC15 antibody.)

[0201] Figure 7 is a graph showing the results of analyzing the degree to which anti-LRRC15 Fabs (13 types) bind to LRRC15 expressed on the cell surface using a FACS system: Figure 7a is a graph showing the results of FACS analysis of anti-LRRC15 Fabs (13 types) in HEK-ED2, Figure 7b is a graph showing the results of FACS analysis of anti-LRRC15 Fabs (13 types) in HCT-ED2, and Figure 7c is a graph showing the results of FACS analysis of anti-LRRC15 Fabs (13 types) in CCD-ED2.

[0202] Figure 8 is a graph showing the results of analyzing the degree to which anti-LRRC15 scFv (39 types) binds to LRRC15 expressed on the cell surface using a FACS system: Figures 8a to 8c are graphs showing the results of FACS analysis of anti-LRRC15 scFv (39 types) in HEK-ED2, Figures 8d to 8f are graphs showing the results of FACS analysis of anti-LRRC15 scFv (39 types) in HCT-ED2, and Figures 8g to 8i are graphs showing the results of FACS analysis of anti-LRRC15 scFv (39 types) in CCD-ED2.

[0203] In Figures 7 and 8, the blue peak represents the non-specific binding signal between antibodies and cells bound to the hIgG1 isotype control, and the orange peak (indicated by hatching) represents the specific binding signal between antibodies and cells bound to each anti-LRRC15 antibody.

[0204] As shown in FIGS. 7 and 8, the specific binding of the purified anti-LRRC15 antibodies (52 types) to LRRC15 in Example 2.5 was confirmed based on the degree of increase in the fluorescence intensity (X-axis) and the number of reacting cells (Y-axis) of the corresponding peak.

[0205] Example 3.4. Measurement of binding ability of anti-LRRC15 antibodies to cell surface-expressed LRRC15 antigen in various cancer types.

[0206] The extent to which the selected anti-LRRC15 antibodies bind to LRRC15 expressed on the surface of various cancer cell lines was analyzed using a FACS system.

[0207] Specifically, two osteosarcoma cell lines (Saos-2, U-2 OS) and two glioblastoma cell lines (A172, U-138 MG) that express human LRRC15 were prepared, and KHOS / NP (osteosarcoma) and T98G (glioblastoma) cell lines that do not express LRRC15 were prepared as control groups. 300 nM of the purified anti-LRRC15 antibody in Example 2.5 was added to the prepared cells, incubated at 4°C for 1 hour, and washed twice with PBS. Anti-human IgG antibody-PE was diluted to 10 nM, incubated at 4°C for 30 minutes, washed three times with PBS, and the results were analyzed by measuring the fluorescence intensity of the cells using a BD Accuri™C6 Plus instrument.

[0208]

[0209] Example 4. Affinity measurement of anti-LRRC15 antibodies to LRRC15

[0210] Using a biomolecular reaction analyzer (Octet QK384), 15 types of anti-LRRC15 antibodies of Example 2.5 were selected and their antigen-antibody binding affinity to LRRC15 was measured.

[0211] Specifically, 15 types of antibodies were each fixed to the sensor at 5 μg / mL, and then the antigen protein LRRC15-His was bound at a concentration of 100 nM to 2000 nM to obtain a sensorgram. The curve fit model for analyzing the binding strength was a 1:1 binding model to calculate the KD value, and the analysis result was X 2 Value less than or equal to 3, R 2 The value was confirmed to be 0.95 or higher within the confidence interval range.

[0212] The results are shown in Table 6 and Fig. 9.

[0213] ProteinK D (M)Kon (1 / Ms)Kdis (1 / s)X 2 R 2 ED2-K-4G115.858 x 10-8 4.042 x 10 5 2.368 x 10 -2 0.0760.98ED2-Y-1H096.234 x 10 -8 2.451 x 10 5 1.528 x 10 -2 0.1130.97ED2-Y-4C041.692 x 10 -8 2.087 x 10 4 3.532 x 10 -4 0.0280.99ED2-Y-1E106.839 x 10 -7 7.317 x 10 4 5.004 x 10 -2 0.0550.96ED2-Y-2E072.597 x 10 -9 9.357 x 10 4 2.430 x 10 -4 0.0110.99ED2-Y-1F113.023 x 10 -8 3.443 x 10 4 1.041 x 10 -3 0.0790.97ED2-Y-3F072.215 x 10 -7 7.026 x 10 4 1.556 x 10 -2 0.1950.95ED2-K-E31.315 x 10 -8 3.544 x 10 4 4.662 x 10 -4 0.1060.98ED2-K-2C111.699 x 10 -7 2.708 x 10 4 4.600 x 10 -3 0.0780.99ED2-Y-7B125.895 x 10 -8 6.543 x 10 4 3.857 x 10 -3 0.0760.97ED2-Y-0B12N.DN.DN.DN.DN.DED2-Y-9H111.806 x 10 -7 1.383 x 10 4 2.498 x 10 -3 0.0450.96ED2-K-3C21.492 x 10 -71.459 x 10 4 2.176 x 10 -3 0.0730.98ED2-K-2H7< 1.0 x 10 -12 2.239 x 10 4 < 1.0 x 10 -7 0.0830.99ED2-K-3G37.142 x 10 -7 1.236 x 10 4 8.830 x 10 -3 0.0360.98

[0214] Table 6 shows the results of calculating the KD value by applying the 1:1 binding model to the graph of Fig. 9.

[0215] Figure 9 is a graph showing the results of measuring the binding affinity between 15 types of anti-LRRC15 antibodies selected from Example 2.5 and the LRRC15 antigen using a biomolecular reaction analyzer (Octet QK384).

[0216] As shown in Figure 9, the binding affinity of the 15 selected LRRC15 antibodies and the LRRC15 antigen was 1.0 x 10, except for the ED2-Y-0B12 antibody for which binding was not measured. -12 7.1 x 10 in -7 It was confirmed that they were in a relationship.

[0217] Example 5. Internalization analysis of anti-LRRC15 antibodies

[0218] The extent to which the selected anti-LRRC15 antibodies bind to LRRC15 expressed on the cell surface and are internalized into cells was analyzed using an Incucyte device.

[0219] Specifically, HEK293F-LRRC15, HCT116-LRRC15, CCD-18Co-LRRC15 cell lines (manufactured by Edisbiotech) that overexpress human LRRC15, two osteosarcoma cell lines (Saos-2, U-2 OS) that express human LRRC15, and two glioblastoma cell lines (A172, U-138 MG) that express human LRRC15 were prepared, and as a control group, HEK293F-pCMV3, HCT116-pCMV3, CCD-18Co-pCMV3 cell lines (manufactured by Edisbiotech), KHOS / NP (osteosarcoma), and T98G (glioblastoma) cell lines that do not express LRRC15 were prepared. In Example 2.5, 0.1 ug of the purified anti-LRRC15 antibody and 0.1 ug of Incucyte®Fabfluor-pH Antibody Labeling Reagents were treated with the prepared cells after dark reaction at 37°C for 15 minutes, and internalization was measured using an Incucyte device for 24 hours, and the results are shown in Figures 10 to 12.

[0220] Figure 10 is a graph showing the internalization results of anti-LRRC15 Fab antibodies (13 types): Figure 10a is a graph showing the internalization results of anti-LRRC15 Fab antibodies (13 types) in HEK293F, Figure 10b is a graph showing the internalization results of anti-LRRC15 Fab antibodies (13 types) in HCT116, and Figure 10c is a graph showing the internalization results of anti-LRRC15 Fab antibodies (13 types) in CCD-18Co.

[0221] Figure 11 is a graph showing the internalization results of anti-LRRC15 scFv antibodies (13 types): Figure 11a is a graph showing the internalization results of anti-LRRC15 scFv antibodies (13 types) in HEK293F, Figure 11b is a graph showing the internalization results of anti-LRRC15 scFv antibodies (13 types) in HCT116, and Figure 11c is a graph showing the internalization results of anti-LRRC15 scFv antibodies (13 types) in CCD-18Co.

[0222] Figure 12 is a graph showing the internalization results of anti-LRRC15 scFv antibodies (26 types): Figure 12a is a graph showing the internalization results of anti-LRRC15 scFv antibodies (26 types) in HEK293F, Figure 12b is a graph showing the internalization results of anti-LRRC15 scFv antibodies (26 types) in HCT116, and Figure 12c is a graph showing the internalization results of anti-LRRC15 scFv antibodies (26 types) in CCD-18Co.

[0223] As shown in Figures 10 to 12, internalization was not observed in the comparative cell line that does not express LRRC15, whereas internalization occurred in the cell line that expresses LRRC15. This means that the anti-LRRC15 antibodies (52 types) purified in Example 2.5 specifically bind to LRRC15 expressed on the cell surface and are internalized into the cells.

[0224]

[0225] Example 6: Production of optimized antibodies

[0226] Among the anti-LRRC15 antibodies obtained in Example 1, the 4G11 antibody was used as a parent, and an optimized antibody with improved antigen-binding properties was generated by introducing targeted mutations into the CDR region. The optimized antibody was obtained through the FASEBA format or Fab format antibody expression and screening system constructed by GenScript and K-BIO.

[0227] Specifically, mutations were induced focusing on CDR1, CDR2, CDR3 and adjacent framework regions included in the variable regions (VH and VL) of the 4G11 antibody, thereby constructing a variant library composed of various sequence combinations. As a result of screening for an antigen (LRRC15) using the antibody library, a total of 37 antibody variants with structural diversity composed of FASEBA format or Fab format were obtained. The heavy chain variable region CDR sequences (CDRH) of each obtained antibody are shown in Table 7, the light chain variable region CDRs (CDRL) are shown in Table 8, and the entire VH and VL sequences are shown in Table 9.

[0228] Name Sequence Sequence Number VH CDR1(CDRH1)SYAMS316YYAMA317WYAMS318YYAMS319WYAMA320SYAMA321NYGMS322YYGMS323IYGMS324SYGMA325VH CDR2(CDRH2)RISGSGGDIYYYADSVKG326RISGSGWDIYYAESVKG327RISGSGWDIYYADSVKG328RISGSGGDIYYAESVKG329RISGPGSDIYYYADSVKG330RISGP GVDVYYADSVKG331RISGSGHDLYYADSVKG332RISAPGGDVYVADSVKG333RISPPGADFYYADSVKG334RISPPGSDVYNADSVKG335RISGPGGDLYYADSVKG336VH CDR3(CDRH3)SIWREFDY337EIWRDFDY338

[0229] Name Sequence Sequence Number VL CDR1(CDRL1)RASQSISSYLN339RASQSISPYLN340VL CDR2(CDRL2)AASSLES341ATSSLES342VL CDR3(CDRL3)QQSYSFPLT343

[0230]

[0231] Example 7: Analysis of antigen binding properties of anti-LRRC15 optimized antibodies

[0232] Example 7.1 SPR analysis results of FASEBA format anti-LRRC15 optimized antibody

[0233] To quantitatively evaluate the binding properties of the anti-LRRC15 optimized antibody obtained in Example 6, SPR (Surface Plasmon Resonance)-based sensorgram analysis was performed using a recombinant LRRC15 antigen.

[0234] Specifically, among the anti-LRRC15 optimized antibodies obtained in Example 6, 24 types of FASEBA format were selected, and the binding characteristics to the recombinant LRRC15 antigen were quantitatively analyzed based on SPR for a total of 27 antibody samples, including the parent antibody (WT-FASEBA), negative control (NC), and blank sample (Blank), and the results are shown in Fig. 13. The 24 antibodies of FASEBA format are optimized antibodies produced by GenScript in FASEBA antibody format, and all have mutations introduced into the CDR sequence, which is the antigen-binding portion. The FASEBA (FAst Screening for Expression, Biophysical-properties and Affinity) format refers to a form in which a BSA (Bovine Serum Albumin) binding domain is additionally fused to a Fab fragment, and is a format designed to rapidly evaluate the expression efficiency, biophysical properties, and antigen-binding affinity of antibody candidates.

[0235] Figures 13a to 13c are graphs showing the results of SPR analysis for 24 types of optimized antibodies and 3 types of comparative samples according to one specific example of the present invention.

[0236] As shown in Fig. 13, most of the optimized antibodies according to one embodiment of the present invention exhibited lower equilibrium dissociation constants (KD) compared to the parent antibody (WT-FASEBA), indicating improved binding affinity to the antigen (LRRC15). Some antibodies showed significantly reduced dissociation rates (kD), thereby maintaining excellent binding persistence to the antigen, and thus, it was confirmed that the overall antigen binding ability was improved.

[0237] Among the 24 optimized antibodies in the FASEBA format, 7 representative antibodies (AHF45172, AHF45177, AHF45178, AHF45175, AHF45169-M112L, AHF45168, and AHF45169) with excellent antigen binding ability were selected, and their antigen binding characteristics are shown in Table 10 and Figure 12.

[0238] Table 10 numerically summarizes the binding characteristics, such as the association rate constant (ka), dissociation rate constant (kd), and equilibrium dissociation constant (KD), for the seven antibodies with excellent antigen binding affinity for the recombinant antigen.

[0239] LigandChi² (RU²)ka (1 / Ms)kd (1 / s)KD (M)Rmax (RU)Ratio (WT / Clone) kdWT (parent antibody)5.42E+002.39E+051.14E-024.78E-0887.21.0AHF451722.90E-019.58E+044.85E-045.06E-09107.823.51AH F451772.89E-017.00E+041.42E-042.03E-09127.280.28AHF451782.06E-018.15E+042.09E-042.56E-09114.954.55AHF 451751.96E-018.05E+043.56E-044.42E-09103.832.02AHF45169-M112L1.19E-017.15E+041.55E-042.17E-0994.873.5 5AHF451681.48E+009.40E+043.33E-043.54E-09110.134.23AHF451691.17E-017.43E+041.70E-042.29E-09152.767.06

[0240] FIG. 14 shows SPR sensorgrams (left) measuring binding reactions with antigen (LRRC15) at various concentrations for the parent antibody (WT) and seven types of optimized antibodies in FASEBA format according to one specific example of the present invention, and the results of deriving binding curves and KD values ​​(right) calculated based on a 1:1 binding model for some antibodies. As shown in Table 10 and FIG. 14, it was confirmed that the optimized antibodies in FASEBA format according to the present example had improved binding affinity for the antigen (LRRC15) compared to the parent antibody (WT), and for some antibodies, the binding stability was increased through a significant decrease in the dissociation rate (kd).

[0241] These results indicate that the anti-LRRC15 optimized antibody according to one specific example of the present invention has improved binding affinity and binding persistence to the anti-LRRC15 antigen, thereby enabling more stable antigen recognition.

[0242] Example 7.2 SPR analysis results of Fab format anti-LRRC15 optimized antibody

[0243] In order to confirm the binding characteristics of the 12 Fab format anti-LRRC15 optimized antibodies obtained in Example 6 and the parent antibody (WT) to the recombinant LRRC15 antigen, SPR (Surface Plasmon Resonance)-based sensorgram analysis was performed.

[0244] Specifically, 12 Fab format antibodies were selected from the anti-LRRC15 optimized antibodies obtained in Example 6, injected at various concentrations, and their binding reactions to the recombinant antigen were measured in real time using SPR sensorgrams. The binding propensity of each antibody to the antigen was qualitatively compared, and the results are shown in Table 11 and Figures 15a and 15b.

[0245] Sampleka (1 / Ms)kd (1 / s)KD (M)Rmax (RU)Chi² (RU²)U-valueFoldh-sb2-E76.03E+053.25E-035.40E-09179.19.69.65.9h-sb2-H55.71E+ 052.85E-034.99E-09208.211.21.46.4h-sb2-1C126.64E+055.63E-038.48E-0971.81.61.1 3.7h-sb2-1D55.53E+054.04E-037.30E-0977.32.11.14.3h-sb2-1D115.57E+052.27E-034.07E-09128.85.31.97.8h-sb2-D106.78E+059.68E-031.43E-08214.43.20.72.2h-sb2-C76 .60E+058.71E-031.32E-08166.62.20.72.4h-sb2-E18.48E+051.24E-021.46E-08147.31.80.72.2h-sb2-1B16.67E+059.66E-031.45E-0891.10.70.72.2h-sb2-1C16.17E+054.41E-0 47.15E-1044.71.19.044.3h-sb2-1C76.54E+055.93E-049.07E-1048.81.36.935.0h-sb2-1E66.69E+056.20E-039.26E-0982.51.00.83.4WT4.36E+051.38E-023.17E-0838.93.35.3-

[0246] Figures 15a and 15b are graphs showing SPR analysis data for each of 12 optimized antibodies in Fab format and the parent antibody (WT) according to one specific example of the present invention. Each graph for the 12 antibodies in Fab format (h-sb2-E7, h-sb2-H5, h-sb2-1C12, h-sb2-1D5, h-sb2-1D11, h-sb2-D10, h-sb2-C7, h-sb2-E1, h-sb2-1B1, h-sb2-1C1, h-sb2-1C7, and h-sb2-1E6) includes binding reactions at various concentrations, and indicates whether there is a relative affinity improvement through an increase in binding signal (Response Unit, RU) proportional to the concentration and a difference in dissociation rate. As shown in Figures 15a and 15b, many of the optimized antibodies in Fab format exhibited high binding signals and gentle dissociation curves compared to the parent antibody.

[0247] These results indicate that the anti-LRRC15 optimized antibody according to one specific example of the present invention has improved binding affinity and binding persistence to the anti-LRRC15 antigen, thereby enabling more stable antigen recognition.

[0248]

[0249] Example 8. Evaluation of antigen binding properties of optimized anti-LRRC15 antibodies converted to IgG1 format.

[0250] To confirm the binding characteristics derived from the Fab format in the IgG structure and verify whether binding characteristics suitable for a therapeutic antibody format are maintained, some of the anti-LRRC15 optimized antibodies in the Fab format of Example 8 were recombined into the IgG1 format, and the binding characteristics of these antibodies to the anti-LRRC15 antigen were analyzed based on SPR. The analysis was performed at K-BIO, and real-time binding reactions were measured for a total of 13 antibody samples (12 candidate antibodies and parent antibodies).

[0251] Specifically, after injecting recombinant IgG1 antibodies at various concentrations, the association rate constant (ka), dissociation rate constant (kd), and equilibrium dissociation constant (KD) of each antibody were calculated through SPR sensorgram analysis, and the results are shown in Table 12, Figures 16a and 16b.

[0252] Sampleka (1 / Ms)kd (1 / s)KD (M)Rmax (RU)Chi² (RU²)U-valueFoldh-sb2-E7 IgG13.70E+054.65E-031.26E-08225.15.450.74.5h-sb2-H5 IgG13.69E+055.37E-031.45E-08206.93.550.73.9h-sb2-1C12 IgG13.94E+055.33E-031.35E-08224.76.040.84.2h-sb2-1D5 IgG14.24E+057.29E-031.72E-08228.24.560.73.3h-sb2-1D11 IgG13.40E+053.33E-039.77E-09218.25.340.85.8h-sb2-1C1 IgG12.53E+057.69E-043.04E-092203.22.418.7h-sb2-1C7 IgG12.52E+059.82E-043.50E-09243.83.81.916.2h-sb2-1E6 IgG13.37E+059.30E-032.76E-08219.51.580.52.1WT IgG12.25E+051.27E-025.67E-0841.45.075.3-

[0253] Table 12 shows the data such as the association rate constant (ka), dissociation rate constant (kd), equilibrium dissociation constant (KD), maximum response value (Rmax), and confidence indices Chi² and U-value, which were measured by performing SPR sensorgram analysis at various concentrations for the recombinant IgG1 antibodies. In addition, the Fold value, which indicates the degree of relative antigen affinity improvement of each antibody, is also shown. The confidence level was evaluated based on the case where Chi² is 10% or less of the Rmax value and the U-value is 25 or less. As shown in Table 12, most of the optimized antibodies according to this example had significantly lower equilibrium dissociation constant (KD) values ​​than the parent antibody (4G11 IgG1, KD = 5.67E-08 M), indicating that the binding affinity for the antigen was improved. In particular, 4G11-29 IgG1 (KD = 3.04E-09 M) and 4G11-30 IgG1 (KD = 3.50E-09 M) showed approximately 18.7-fold and 16.2-fold improved binding affinity (Fold standard), respectively, compared to the parent antibody, confirming that the affinity for the antigen was significantly improved.

[0254] Figures 16a and 16b illustrate the SPR sensorgram results evaluating the binding and dissociation characteristics of eight types of anti-LRRC15 optimized antibodies and the parent antibody (WT) according to one specific example of the present invention after recombining them into an IgG1 format with the recombined LRRC15 antigen.

[0255] As shown in Figures 16a and 16b, antibodies such as h-sb2-1C1 IgG1, h-sb2-1C7 IgG1, and h-sb2-1D11 IgG1 showed a faster rate of increase in binding signal (RU) in the association phase compared to the parent antibody (WT IgG1), and the response curve was maintained gently even in the dissociation phase. These results suggest that the antibodies not only have strong binding affinity to the antigen, but also exhibit high binding persistence.

[0256]

[0257] Example 9. Cross-species reactivity analysis of anti-LRRC15 optimized antibodies against human, monkey, and mouse antigens.

[0258] Among the anti-LRRC15 optimized antibodies obtained in Example 6, antibodies with excellent antigen binding characteristics were selected, and their binding characteristics to recombinant LRRC15 antigen proteins derived from humans, monkeys, and mice were compared and analyzed by ELISA to analyze their cross-species reactivity.

[0259] Specifically, ELISA plates were coated with 13.3 nM of anti-His antibody as a coating antibody in each well, washed with PBST, and nonspecific binding was blocked with SuperBlock (Thermo, cat# 37515) solution. Then, recombinant LRRC15 extracellular domain (ECD)-His antigen proteins derived from each species (human, monkey, mouse) were treated at a concentration of 20 nM, incubated at room temperature for 1 hour, and washed.

[0260] Next, anti-LRRC15 optimized antibody clones and control antibodies (such as ED2-CTL) were diluted in a concentration gradient and treated in each well, and then reacted at room temperature for 1 hour and washed five times with PBST. After treating with HRP-conjugated anti-human polyclonal antibodies as a secondary antibody, color development was performed using TMB as a substrate, and after stopping the reaction, the absorbance was measured at 450 nm, and the results are shown in Figures 17a and 17b, and Figures 18a to 18c.

[0261] FIG. 17 a and FIG. 17 b are graphs showing the results of ELISA analyzing the binding ability of anti-LRRC15 optimized antibody clones according to one embodiment of the present invention selected through affinity maturation to recombinant human LRRC15-ECD antigen.

[0262] As shown in FIG. 17 a and FIG. 17 b, the optimized antibodies (AHF45168, AHF45169, AHF45169-M112L, AHF45172, AHF45175, AHF45177, AHF45178, AHF45166, AHF45171, AHF45176, AHF45184, AHF45199, AHF45202) and secondary screening clones (h-sb2-E7, h-sb2-H5, h-sb2-1C12, h-sb2-1D5, h-sb2-1D11, h-sb2-1C1, h-sb2-1C7, h-sb2-1E6) according to one specific example of the present invention are compared with the control antibodies (ED2-CTL and Compared to ED2-001), the antibody concentration increased rapidly, and most clones showed a strong binding reaction even at concentrations below 1 nM. These results suggest that the antigen binding affinity of the anti-LRRC15 optimized antibody was improved through the affinity maturation process, and in particular, some clones stably maintained high OD values, indicating excellent antigen recognition ability and binding persistence.

[0263] Meanwhile, FIGS. 18a to 18c are graphs showing the results of analyzing antibody binding to recombinant LRRC15 antigens derived from human, monkey, and mouse using ELISA to evaluate the cross-species reactivity of anti-LRRC15 antibodies according to one specific example of the present invention.

[0264] As shown in Figures 18a to 18c, the optimized antibody clones of the present invention (AHF45166, AHF45171, AHF45172, AHF45175, AHF45177, h-sb2-E7, h-sb2-H5, h-sb2-1C12, etc.) showed high absorbance (OD450) not only for human antigens but also for monkey and mouse antigens, confirming that they have cross-reactivity between species. In particular, some antibodies showed similar levels of binding affinity for all three species of antigens, suggesting that the antibodies are capable of recognizing antigens in species other than human.

[0265] These results imply that these antibodies are directly applicable to efficacy or toxicity assessments using nonclinical test models (e.g., mice or primates), and further imply that they can be utilized as therapeutic or diagnostic platform antibodies applicable to various species.

[0266]

[0267] Example 10. Measurement of binding ability of anti-LRRC15 optimized antibodies to cell surface-expressed LRRC15 antigen in various cancer types.

[0268] Among the anti-LRRC15 optimized antibodies obtained in Example 6, 15 antibodies with the best antigen binding characteristics were selected, and the extent to which they bind to LRRC15 expressed on the surface of various cancer cell lines was analyzed using a FACS system.

[0269] Specifically, the cell surface binding affinity of the antibody was analyzed for HEK293F-ED2, osteosarcoma-derived KHOS / NP-ED2 cell line, and melanoma-derived RPMI-7951 cell line, which were engineered to express the human LRRC15 gene. The anti-LRRC15-optimized antibody of Example 8 was treated to a final concentration of 300 nM for the above cells, reacted at 4°C for 1 hour, and washed twice with PBS. Subsequently, anti-human IgG antibody-PE was diluted to a concentration of 10 nM, and a second incubation was performed at 4°C for 30 minutes, and washed three times with PBS. Finally, the fluorescence intensity of the cells was measured using a BD Accuri™ C6 Plus flow cytometer, and the results are shown in Figures 19a to 19c, respectively.

[0270] FIG. 19 is a graph showing the results of quantitatively evaluating the degree to which anti-LRRC15 optimized antibodies according to one specific example of the present invention exhibit cell surface binding ability to human LRRC15 antigen expressed in various cancer-derived cell lines through flow cytometry (FACS): FIG. 19a is a graph showing the results of analyzing the binding ability of anti-LRRC15 antibodies according to the present invention to cell surface antigens using HEK293F-ED2 and HEK293F-ED2-C-His cell lines expressing human LRRC15 in HEK293F-derived cells, FIG. 19b is a graph showing the results of evaluating the cell binding ability of anti-LRRC15 antibodies according to the present invention using KHOS / NP-ED2 cells expressing human LRRC15 in KHOS / NP, an osteosarcoma-derived cell line, and FIG. 19c is a graph showing the results of evaluating the cell binding ability of anti-LRRC15 antibodies according to the present invention to RPMI-7951, a melanoma-derived cell line. This graph shows the results of analyzing the degree of binding to antigens expressed on the cell surface.

[0271] As shown in FIGS. 19a to 19c, the anti-LRRC15 optimized antibodies according to one embodiment of the present invention showed an increase in binding signal in an antibody concentration-dependent manner for human LRRC15 expressed on the cell surface, and in particular, some optimized antibodies showed a significantly higher fluorescence intensity (Geometric mean PE-A) than the control antibody (ED2-CTL or ED2-001).

[0272] These results indicate that the antibodies of the present invention have excellent specific binding ability to the LRRC15 antigen expressed in various cancer-derived cell lines and can be effectively utilized for cancer cell surface target recognition.

[0273]

[0274] Example 11. Internalization analysis of anti-LRRC15 optimized antibodies

[0275] The extent to which the anti-LRRC15 optimized antibodies obtained in Example 6 bind to LRRC15 expressed on the cell surface and are internalized into cells was analyzed.

[0276] Specifically, two osteosarcoma cell lines expressing human LRRC15 (Saos-2, Huo9), an osteosarcoma cell line overexpressing human LRRC15 (KHOS / NP ED2 OE), a colon cancer stromal cell line (CCD-18Co ED2 OE), and a melanoma cell line (SK-MEL-28 ED2 OE) were prepared. 0.1 µg of anti-LRRC15 antibody and 0.1 µg of Incucyte® Fabfluor-pH Antibody Labeling Reagents were incubated at 37°C for 15 minutes, and then treated to the prepared cells, and internalization was measured using an Incucyte device for 24 to 48 hours.

[0277] The results are shown in Figures 20a to 20c.

[0278] FIG. 20 is a graph showing the internalization results of anti-LRRC15 optimized antibodies according to one specific example of the present invention: FIG. 20a is a graph showing the internalization results of anti-LRRC15 optimized antibodies (AHF45168, AHF45171, AHF45176, AHF45184, AHF45199, AHF45202) in Saos-2 and Huo9 cell lines, FIG. 20b is a graph showing the internalization results of anti-LRRC15 optimized antibodies in KHOS / NP ED2 overexpressing cell line and normal colon fibroblast cell line (CCD-18Co ED2 OE), and FIG. 20c is a graph showing the internalization results of anti-LRRC15 optimized antibodies in Saos-2 and SK-MEL-28 ED2 overexpressing clones.

[0279] As shown in FIGS. 20A to 20C, the anti-LRRC15 optimized antibody clones of the present invention showed a time-dependent increase in internalization in various LRRC15-expressing cell lines, such as KHOS / NP ED2 OE, SK-MEL-28 ED2 OE, Huo9, and CCD-18Co ED2 OE, and in particular, it was confirmed that some optimized antibodies showed significantly higher internalization efficiency than the control antibody (ED2-CTL).

[0280] These results indicate that the anti-LRRC15 optimized antibody of the present invention recognizes the LRRC15 antigen expressed in various cancer types and stromal cell lines and is internalized into cells with excellent efficiency.

Claims

1. An antibody or antigen-binding fragment thereof that specifically binds to LRRC15 (Leucine-rich repeat-containing protein 15), The antibody or antigen-binding fragment comprises (i) the heavy chain complementarity determining regions (CDRs) of CDRH1, CDRH2 and CDRH3 and (ii) the light chain complementarity determining regions (CDRs) of CDRL1, CDRL2 and CDRL3, The CDRH1 is an amino acid sequence having at least 85, 90, 95, 99 or 100% homology or identity with any one of the amino acid sequences represented by SEQ ID NOs: 1 to 30 and 316 to 325; The CDRH2 is an amino acid sequence having at least 85, 90, 95, 99 or 100% homology or identity to any one of the amino acid sequences represented by SEQ ID NOs: 31 to 67 and 326 to 336; The CDRH3 is an amino acid sequence having at least 85, 90, 95, 99 or 100% homology or identity to any one of the amino acid sequences represented by SEQ ID NOs: 68 to 115, 337 and 338; The above CDRL1 is an amino acid sequence having at least 85, 90, 95, 99 or 100% homology or identity with any one of the amino acid sequences represented by SEQ ID NOs: 116 to 150, 339 and 340; The above CDRL2 is an amino acid sequence having at least 85, 90, 95, 99 or 100% homology or identity with any one of the amino acid sequences represented by SEQ ID NOs: 151 to 169, 341 and 342; and An antibody or antigen-binding fragment thereof that specifically binds to LRRC15, wherein the CDRL3 is an amino acid sequence having at least 85, 90, 95, 99 or 100% homology or identity with any one of the amino acid sequences represented by SEQ ID NOs: 170 to 211 and 343.

2. In paragraph 1, An isolated antibody or antigen-binding fragment thereof that specifically binds to LRRC15, wherein the above CDRH1, CDRH2 and CDRH3 are any one of the following combinations: (1) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 1, 31, and 68, respectively; (2) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 1, 32, and 69, respectively; (3) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 2, 33, and 70, respectively; (4) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 2, 33, and 71, respectively; (5) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 2, 34, and 72, respectively; (6) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 3, 35, and 73, respectively; (7) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 1, 36, and 74, respectively; (8) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 4, 37, and 75, respectively; (9) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 2, 38, and 76, respectively; (10) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 2, 36, and 77, respectively; (11) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 5, 39, and 78, respectively; (12) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 2, 40, and 79, respectively; (13) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 5, 41, and 80, respectively; (14) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 6, 42, and 81, respectively; (15) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 7, 43, and 82, respectively; (16) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 7, 43, and 83, respectively; (17) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 8, 44, and 84, respectively; (18) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 9, 45, and 85, respectively; (19) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 10, 34, and 86, respectively; (20) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 11, 46, and 87, respectively; (21) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 12, 47, and 88, respectively; (22) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 13, 48, and 89, respectively; (23) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 14, 49, and 90, respectively; (24) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 15, 50, and 91, respectively; (25) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 16, 51, and 92, respectively; (26) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 8, 52, and 93, respectively; (27) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 2, 53, and 94, respectively; (28) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 17, 54, and 95, respectively; (29) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 18, 55, and 96, respectively; (30) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 19, 56, and 97, respectively; (31) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 20, 52, and 98, respectively; (32) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 6, 57, and 99, respectively; (33) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 21, 58, and 100, respectively; (34) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 6, 42, and 101, respectively; (35) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 22, 59, and 102, respectively; (36) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 23, 33, and 103, respectively; (37) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 9, 52, and 104, respectively; (38) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 24, 60, and 105, respectively; (39) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 10, 61, and 106, respectively; (40) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 10, 61, and 107, respectively; (41) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 25, 62, and 108, respectively; (42) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 26, 43, and 109, respectively; (43) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 21, 63, and 110, respectively; (44) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 27, 64, and 111, respectively; (45) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 28, 61, and 112, respectively; (46) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 29, 65, and 113, respectively; (47) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 10, 66, and 114, respectively; (48) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 30, 67, and 115, respectively; (49) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 326, and 337, respectively; (50) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 317, 327, and 337, respectively; (51) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 328, and 337, respectively; (52) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 318, 328, and 337, respectively; (53) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 319, 328, and 337, respectively; (54) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 320, 327, and 337, respectively; (55) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 318, 327, and 337, respectively; (56) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 318, 329, and 337, respectively; (57) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 317, 328, and 337, respectively; (58) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 321, 327, and 337, respectively; (59) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 320, 328, and 337, respectively; (60) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 321, 328, and 337, respectively; (61) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 318, 326, and 337, respectively; (62) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 320, 329, and 337, respectively; (63) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 320, 326, and 337, respectively; (64) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 319, 327, and 337, respectively; (65) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 327, and 337, respectively; (66) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 322, 326, and 337, respectively; (67) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 330, and 337, respectively; (68) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 323, 326, and 337, respectively; (69) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 324, 326, and 337, respectively; (70) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 331, and 337, respectively; (71) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 325, 326, and 337, respectively; (72) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 332, and 337, respectively; (73) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 326, and 338, respectively; (74) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 333, and 337, respectively; (75) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 334, and 337, respectively; (76) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 335, and 337, respectively; and (77) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 336, and 337, respectively.

3. An antibody or antigen-binding fragment thereof that specifically binds to LRRC15, wherein the CDRH1, CDRH2 and CDRH3 have an amino acid sequence having at least 85, 90, 95, 99 or 100% homology or identity with any one of the combinations (1) to (77) of the second paragraph.

4. In paragraph 1, An isolated antibody or antigen-binding fragment thereof that specifically binds to LRRC15, wherein the above CDRL1, CDRL2 and CDRL3 are any one of the following combinations: (1) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 116, 151, and 170, respectively; (2) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 117, 152, and 171, respectively; (3) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 118, 152, and 172, respectively; (4) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 119, 152, and 173, respectively; (5) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 118, 153, and 174, respectively; (6) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 116, 152, and 170, respectively; (7) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 120, 153, and 174, respectively; (8) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 116, 152, and 175, respectively; (9) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 116, 153, and 176, respectively; (10) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 121, 153, and 171, respectively; (11) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 118, 153, and 177, respectively; (12) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 118, 153, and 178, respectively; (13) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 116, 152, and 179, respectively; (14) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 122, 154, and 180, respectively; (15) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 123, 155, and 181, respectively; (16) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 124, 156, and 182, respectively; (17) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 125, 153, and 183, respectively; (18) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 126, 157, and 184, respectively; (19) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 127, 158, and 185, respectively; (20) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 121, 157, and 186, respectively; (21) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 128, 159, and 187, respectively; (22) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 129, 160, and 188, respectively; (23) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 130, 153, and 189, respectively; (24) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 131, 154, and 190, respectively; (25) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 131, 154, and 180, respectively; (26) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 132, 153, and 191, respectively; (27) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 133, 153, and 189, respectively; (28) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 134, 161, and 192, respectively; (29) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 135, 157, and 193, respectively; (30) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 118, 153, and 194, respectively; (31) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 136, 162, and 195, respectively; (32) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 137, 157, and 196, respectively; (33) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 138, 163, and 197, respectively; (34) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 139, 164, and 198, respectively; (35) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 140, 154, and 180, respectively; (36) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 141, 153, and 191, respectively; (37) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 122, 154, and 199, respectively; (38) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 142, 154, and 199, respectively; (39) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 143, 153, and 200, respectively; (40) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 144, 165, and 201, respectively; (41) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 145, 161, and 202, respectively; (42) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 146, 161, and 203, respectively; (43) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 132, 153, and 204, respectively; (44) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 144, 161, and 205, respectively; (45) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 147, 155, and 206, respectively; (46) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 144, 166, and 207, respectively; (47) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 144, 161, and 208, respectively; (48) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 148, 167, and 209, respectively; (49) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 149, 168, and 210, respectively; (50) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 150, 169, and 211, respectively; (51) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively; (52) The above CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 341, and 343, respectively; and (53) The above CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 342, and 343, respectively.

5. An antibody or antigen-binding fragment thereof that specifically binds to LRRC15, wherein CDRL1, CDRL2, and CDRL3 are amino acid sequences having at least 85, 90, 95, 99, or 100% homology or identity with any one of the combinations (1) to (53) of paragraph 4.

6. In paragraph 1, An antibody or antigen-binding fragment thereof that specifically binds to LRRC15, wherein the CDRH1, CDRH2 and CDRH3; and the CDRL1, CDRL2 and CDRL3; are any one of the following combinations: The above CDRH1, CDRH2 and CDRH3 are any one of the following combinations: (1) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 1, 31, and 68, respectively; (2) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 1, 32, and 69, respectively; (3) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 2, 33, and 70, respectively; (4) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 2, 33, and 71, respectively; (5) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 2, 34, and 72, respectively; (6) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 3, 35, and 73, respectively; (7) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 1, 36, and 74, respectively; (8) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 4, 37, and 75, respectively; (9) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 2, 38, and 76, respectively; (10) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 2, 36, and 77, respectively; (11) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 5, 39, and 78, respectively; (12) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 2, 40, and 79, respectively; (13) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 5, 41, and 80, respectively; (14) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 6, 42, and 81, respectively; (15) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 7, 43, and 82, respectively; (16) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 7, 43, and 83, respectively; (17) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 8, 44, and 84, respectively; (18) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 9, 45, and 85, respectively; (19) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 10, 34, and 86, respectively; (20) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 11, 46, and 87, respectively; (21) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 12, 47, and 88, respectively; (22) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 13, 48, and 89, respectively; (23) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 14, 49, and 90, respectively; (24) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 15, 50, and 91, respectively; (25) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 16, 51, and 92, respectively; (26) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 8, 52, and 93, respectively; (27) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 2, 53, and 94, respectively; (28) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 17, 54, and 95, respectively; (29) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 18, 55, and 96, respectively; (30) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 19, 56, and 97, respectively; (31) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 20, 52, and 98, respectively; (32) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 6, 57, and 99, respectively; (33) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 21, 58, and 100, respectively; (34) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 6, 42, and 101, respectively; (35) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 22, 59, and 102, respectively; (36) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 23, 33, and 103, respectively; (37) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 9, 52, and 104, respectively; (38) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 24, 60, and 105, respectively; (39) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 10, 61, and 106, respectively; (40) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 10, 61, and 107, respectively; (41) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 25, 62, and 108, respectively; (42) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 26, 43, and 109, respectively; (43) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 21, 63, and 110, respectively; (44) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 27, 64, and 111, respectively; (45) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 28, 61, and 112, respectively; (46) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 29, 65, and 113, respectively; (47) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 10, 66, and 114, respectively; (48) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 30, 67, and 115, respectively; (49) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 326, and 337, respectively; (50) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 317, 327, and 337, respectively; (51) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 328, and 337, respectively; (52) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 318, 328, and 337, respectively; (53) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 319, 328, and 337, respectively; (54) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 320, 327, and 337, respectively; (55) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 318, 327, and 337, respectively; (56) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 318, 329, and 337, respectively; (57) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 317, 328, and 337, respectively; (58) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 321, 327, and 337, respectively; (59) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 320, 328, and 337, respectively; (60) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 321, 328, and 337, respectively; (61) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 318, 326, and 337, respectively; (62) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 320, 329, and 337, respectively; (63) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 320, 326, and 337, respectively; (64) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 319, 327, and 337, respectively; (65) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 327, and 337, respectively; (66) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 322, 326, and 337, respectively; (67) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 330, and 337, respectively; (68) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 323, 326, and 337, respectively; (69) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 324, 326, and 337, respectively; (70) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 331, and 337, respectively; (71) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 325, 326, and 337, respectively; (72) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 332, and 337, respectively; (73) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 326, and 338, respectively; (74) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 333, and 337, respectively; (75) The above CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 334, and 337, respectively; (76) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 335, and 337, respectively; and (77) The CDRH1, CDRH2, and CDRH3 have amino acid sequences represented by SEQ ID NOs: 316, 336, and 337, respectively; and The above CDRL1, CDRL2 and CDRL3 are any one of the following combinations: (1) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 116, 151, and 170, respectively; (2) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 117, 152, and 171, respectively; (3) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 118, 152, and 172, respectively; (4) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 119, 152, and 173, respectively; (5) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 118, 153, and 174, respectively; (6) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 116, 152, and 170, respectively; (7) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 120, 153, and 174, respectively; (8) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 116, 152, and 175, respectively; (9) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 116, 153, and 176, respectively; (10) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 121, 153, and 171, respectively; (11) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 118, 153, and 177, respectively; (12) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 118, 153, and 178, respectively; (13) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 116, 152, and 179, respectively; (14) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 122, 154, and 180, respectively; (15) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 123, 155, and 181, respectively; (16) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 124, 156, and 182, respectively; (17) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 125, 153, and 183, respectively; (18) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 126, 157, and 184, respectively; (19) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 127, 158, and 185, respectively; (20) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 121, 157, and 186, respectively; (21) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 128, 159, and 187, respectively; (22) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 129, 160, and 188, respectively; (23) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 130, 153, and 189, respectively; (24) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 131, 154, and 190, respectively; (25) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 131, 154, and 180, respectively; (26) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 132, 153, and 191, respectively; (27) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 133, 153, and 189, respectively; (28) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 134, 161, and 192, respectively; (29) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 135, 157, and 193, respectively; (30) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 118, 153, and 194, respectively; (31) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 136, 162, and 195, respectively; (32) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 137, 157, and 196, respectively; (33) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 138, 163, and 197, respectively; (34) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 139, 164, and 198, respectively; (35) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 140, 154, and 180, respectively; (36) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 141, 153, and 191, respectively; (37) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 122, 154, and 199, respectively; (38) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 142, 154, and 199, respectively; (39) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 143, 153, and 200, respectively; (40) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 144, 165, and 201, respectively; (41) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 145, 161, and 202, respectively; (42) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 146, 161, and 203, respectively; (43) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 132, 153, and 204, respectively; (44) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 144, 161, and 205, respectively; (45) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 147, 155, and 206, respectively; (46) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 144, 166, and 207, respectively; (47) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 144, 161, and 208, respectively; (48) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 148, 167, and 209, respectively; (49) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 149, 168, and 210, respectively; (50) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 150, 169, and 211, respectively; (51) The above CDRL1, CDRL2, and CDRL3 have amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively; (52) The above CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 341, and 343, respectively; and (53) The above CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 342, and 343, respectively.

7. An antibody or antigen-binding fragment thereof that specifically binds to LRRC15, wherein the CDRH1, CDRH2 and CDRH3; and the CDRL1, CDRL2 and CDRL3 have an amino acid sequence that is at least 85, 90, 95, 99 or 100% homologous or identical to any one of the combinations of CDRH1, CDRH2 and CDRH3 of (1) to (77) of the above paragraph 6; and an amino acid sequence that is at least 85, 90, 95, 99 or 100% homologous or identical to any one of the combinations of CDRL1, CDRL2 and CDRL3 of (1) to (53) of the above paragraph 5.

8. In paragraph 1, An antibody or antigen-binding fragment thereof that specifically binds to LRRC15, wherein the CDRH1, CDRH2 and CDRH3; and the CDRL1, CDRL2 and CDRL3 are any one of the following combinations: (1) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 1, 31, and 68, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 116, 151, and 170, respectively; (2) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 1, 32, and 69, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 117, 152, and 171, respectively; (3) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 2, 33, and 70, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 118, 152, and 172, respectively; (4) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 2, 33, and 71, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 119, 152, and 173, respectively; (5) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 2, 34, and 72, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 118, 153, and 174, respectively; (6) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 3, 35, and 73, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 116, 152, and 170, respectively; (7) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 1, 36, and 74, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 120, 153, and 174, respectively; (8) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 4, 37, and 75, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 116, 152, and 175, respectively; (9) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 2, 38, and 76, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 116, 153, and 176, respectively; (10) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 2, 36, and 77, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 121, 153, and 171, respectively; (11) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 5, 39, and 78, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 118, 153, and 177, respectively; (12) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 2, 40, and 79, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 118, 153, and 178, respectively; (13) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 5, 41, and 80, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 116, 152, and 179, respectively; (14) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 6, 42, and 81, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 122, 154, and 180, respectively; (15) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 7, 43, and 82, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 123, 155, and 181, respectively; (16) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 7, 43, and 83, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 124, 156, and 182, respectively; (17) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 8, 44, and 84, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 125, 153, and 183, respectively; (18) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 9, 45, and 85, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 126, 157, and 184, respectively; (19) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 10, 34, and 86, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 127, 158, and 185, respectively; (20) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 11, 46, and 87, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 121, 157, and 186, respectively; (21) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 12, 47, and 88, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 128, 159, and 187, respectively; (22) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 13, 48, and 89, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 129, 160, and 188, respectively; (23) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 14, 49, and 90, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 122, 154, and 180, respectively; (24) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 15, 50, and 91, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 130, 153, and 189, respectively; (25) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 6, 42, and 81, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 131, 154, and 190, respectively; (26) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 6, 42, and 81, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 131, 154, and 180, respectively; (27) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 16, 51, and 92, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 132, 153, and 191, respectively; (28) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 8, 52, and 93, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 133, 153, and 189, respectively; (29) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 2, 53, and 94, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 134, 161, and 192, respectively; (30) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 17, 54, and 95, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 135, 157, and 193, respectively; (31) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 18, 55, and 96, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 118, 153, and 194, respectively; (32) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 19, 56, and 97, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 136, 162, and 195, respectively; (33) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 20, 52, and 98, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 137, 157, and 196, respectively; (34) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 6, 57, and 99, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 138, 163, and 197, respectively; (35) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 21, 58, and 100, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 139, 164, and 198, respectively; (36) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 6, 42, and 101, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 140, 154, and 180, respectively; (37) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 22, 59, and 102, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 141, 153, and 191, respectively; (38) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 6, 42, and 81, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 122, 154, and 199, respectively; (39) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 23, 33, and 103, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 142, 154, and 199, respectively; (40) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 9, 52, and 104, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 143, 153, and 200, respectively; (41) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 24, 60, and 105, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 144, 165, and 201, respectively; (42) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 10, 61, and 106, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 145, 161, and 202, respectively; (43) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 10, 61, and 107, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 146, 161, and 203, respectively; (44) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 25, 62, and 108, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 132, 153, and 204, respectively; (45) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 26, 43, and 109, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 144, 161, and 205, respectively; (46) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 21, 63, and 110, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 147, 155, and 206, respectively; (47) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 27, 64, and 111, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 144, 166, and 207, respectively; (48) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 28, 61, and 112, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 144, 161, and 208, respectively; (49) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 29, 65, and 113, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 148, 167, and 209, respectively; (50) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 10, 66, and 114, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 149, 168, and 210, respectively; (51) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 30, 67, and 115, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 150, 169, and 211, respectively; (52) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 316, 326, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively; (53) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 317, 327, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 341, and 343, respectively; (54) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 316, 328, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 341, and 343, respectively; (55) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 318, 328, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 341, and 343, respectively; (56) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 319, 328, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 341, and 343, respectively; (57) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 320, 327, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 342, and 343, respectively; (58) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 318, 327, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 341, and 343, respectively; (59) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 318, 329, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 341, and 343, respectively; (60) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 317, 328, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 342, and 343, respectively; (61) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 321, 327, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 341, and 343, respectively; (62) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 320, 328, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 341, and 343, respectively; (63) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 318, 327, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 342, and 343, respectively; (64) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 318, 328, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 342, and 343, respectively; (65) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 321, 328, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 341, and 343, respectively; (66) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 320, 327, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 341, and 343, respectively; (67) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 320, 327, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively; (68) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 318, 326, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 342, and 343, respectively; (69) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 321, 328, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively; (70) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 320, 329, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 341, and 343, respectively; (71) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 320, 326, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 341, and 343, respectively; (72) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 320, 328, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively; (73) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 319, 327, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 341, and 343, respectively; (74) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 316, 327, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 340, 341, and 343, respectively; (75) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 322, 326, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively; (76) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 316, 330, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively; (77) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 323, 326, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively; (78) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 324, 326, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively; (79) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 316, 331, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively; (80) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 325, 326, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively; (81) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 316, 332, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively; (82) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 316, 326, and 338, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively; (83) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 316, 333, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively; (84) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 316, 334, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively; (85) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 316, 335, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively; and (86) The CDRH1, CDRH2, and CDRH3 are amino acid sequences represented by SEQ ID NOs: 316, 336, and 337, respectively, and the CDRL1, CDRL2, and CDRL3 are amino acid sequences represented by SEQ ID NOs: 339, 341, and 343, respectively.

9. An antibody or antigen-binding fragment thereof that specifically binds to LRRC15, wherein the CDRH1, CDRH2 and CDRH3; and the CDRL1, CDRL2 and CDRL3; are amino acid sequences having at least 85, 90, 95, 99 or 100% homology or identity with any one of the combinations of CDRH1, CDRH2 and CDRH3; and CDRL1, CDRL2 and CDRL3; of (1) to (86) of the above paragraph 8.

10. In the first paragraph, the antibody or antigen-binding fragment comprises a heavy chain variable region (VH) comprising an amino acid sequence having at least 85, 90, 95, 99 or 100% homology or identity with any one amino acid sequence selected from the group consisting of SEQ ID NOs: 212 to 263 and 344 to 382; and An antibody or antigen-binding fragment thereof that specifically binds to LRRC15, comprising a light chain variable region (VL) comprising an amino acid sequence having at least 85, 90, 95, 99 or 100% homology or identity to any one amino acid sequence selected from the group consisting of SEQ ID NOs: 264 to 315 and 383 to 421.

11. An antibody or antigen-binding fragment thereof that specifically binds to LRRC15, wherein the antibody or antigen-binding fragment thereof further comprises a human immunoglobulin heavy chain region and a light chain region in the first paragraph.

12. A nucleic acid encoding an antibody or an antigen-binding fragment thereof according to any one of claims 1 to 11.

13. A vector comprising a nucleic acid encoding an antibody or an antigen-binding fragment thereof according to any one of claims 1 to 11.

14. A host cell transformed with a vector containing a nucleic acid encoding an antibody or an antigen-binding fragment thereof according to any one of claims 1 to 11.

15. A bispecific antibody comprising any one of the antibodies or antigen-binding fragments thereof according to claims 1 to 11.

16. Antigen binding domain; transmembrane domain; hinge domain; an intracellular co-stimulatory domain; and A chimeric antigen receptor (CAR) comprising an intracellular signal transduction domain, A chimeric antigen receptor, wherein the antigen binding domain is an antibody or an antigen binding fragment thereof according to any one of claims 1 to 11.

17. An antibody-drug conjugate (ADC) comprising an antibody or an antigen-binding fragment thereof that specifically binds to LRRC15 (Leucine-rich repeat-containing protein 15) of paragraph 1, or a bispecific antibody or an antigen-binding fragment thereof; a drug moiety; and a linker connecting the drug moiety and the antibody or an antigen-binding fragment thereof.

18. A pharmaceutical composition for preventing or treating cancer, comprising an antibody or antigen-binding fragment thereof that specifically binds to LRRC15 (Leucine-rich repeat-containing protein 15) of claim 1; a bispecific antibody of claim 15; a chimeric antigen receptor of claim 16; or an antibody-drug conjugate of claim 17.

19. In paragraph 18, A composition for preventing or treating cancer, wherein the cancer is at least one selected from the group consisting of colon cancer, pancreatic cancer, biliary tract cancer, breast cancer, ovarian cancer, sarcoma, melanoma, skin cancer, peritoneal cancer, bone cancer, brain cancer, head and neck cancer, lung cancer, stomach cancer, colon cancer, rectal cancer, esophageal cancer, prostate cancer, bladder cancer, kidney cancer, urethral cancer, thyroid cancer, liver cancer, cervical cancer, and anal cancer.

20. A method for preventing or treating cancer, comprising administering to a subject in need thereof an effective amount of an antibody or antigen-binding fragment thereof that specifically binds to LRRC15 (Leucine-rich repeat-containing protein 15) of claim 1; a bispecific antibody of claim 15; a chimeric antigen receptor of claim 16; or an antibody-drug conjugate of claim 17.

21. Use of an antibody or antigen-binding fragment thereof that specifically binds to LRRC15 (Leucine-rich repeat-containing protein 15) of claim 1 for use in the manufacture of a pharmaceutical preparation for the prevention or treatment of cancer; a bispecific antibody of claim 15; a chimeric antigen receptor of claim 16; or an antibody-drug conjugate of claim 17.

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