B7-H3 conjugated antibody and its use

Abstract

This application provides anti-B7-H3 monoclonal antibodies, particularly high-affinity B7-H3 humanized monoclonal antibodies that have cross-activity with humans, cynomolgus monkeys, and mice, as well as nucleic acids encoding the antibody, vectors containing the nucleic acid, and host cells containing the nucleic acid or vector. This application further discloses pharmaceutical compositions and conjugates containing the antibody, and therapeutic methods using the antibody.

Description

[Technical Field]

[0001] This disclosure relates to the field of biomedicine, and more particularly to antibodies that bind to B7-H3 and their use in cancer therapy. [Background technology]

[0002] B7-H3 (CD276) is a member of the B7 family of proteins and plays a crucial role in cancer development. As one of the immune checkpoint targets, B7-H3 is selectively expressed in tumor cells and immune cells within the tumor microenvironment, participating in tumor cell proliferation and metastasis, and is also associated with drug resistance. The protein expression level of B7-H3 differs significantly between normal tissue and tumor tissue. B7-H3 is highly expressed in various tumor tissues, such as prostate cancer, pancreatic cancer, and hepatocellular carcinoma, while it is hardly expressed in normal tissue (Zhou WT, Jin WL. B7-H3 / CD276: An Emerging Cancer Immunotherapy. Front Immunol. 2021;12:701006.). By utilizing this characteristic and targeting B7-H3 with drugs, cancer tissue can be specifically killed while minimizing damage to healthy cells. Due to these properties, B7-H3 is a promising target for cancer treatment. [Overview of the project] [Means for solving the problem]

[0003] This disclosure provides a novel antibody or antigen-binding fragment that targets B7-H3.

[0004] In a first embodiment, the disclosure provides an antibody or antigen-binding fragment that specifically binds to B7-H3, comprising a heavy chain variable region (VH) and a light chain variable region (VL).

[0005] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 3, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 13.

[0006] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 26, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 27.

[0007] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 28, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 29.

[0008] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 30, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 29.

[0009] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 22, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 23.

[0010] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 33, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 42.

[0011] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 34, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 42.

[0012] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 33, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 41.

[0013] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 34, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 39.

[0014] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 34, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 40.

[0015] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 34, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 41.

[0016] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 1, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 2.

[0017] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 3, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 4.

[0018] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 5, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 6.

[0019] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 7, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 8.

[0020] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 9, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 10.

[0021] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed in the present specification, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein said VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence set forth in SEQ ID NO: 11, and said VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence set forth in SEQ ID NO: 12.

[0022] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed in the present specification, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein said VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence set forth in SEQ ID NO: 14, and said VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence set forth in SEQ ID NO: 15.

[0023] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed in the present specification, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein said VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence set forth in SEQ ID NO: 16, and said VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence set forth in SEQ ID NO: 17.

[0024] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed in the present specification, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein said VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence set forth in SEQ ID NO: 18, and said VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence set forth in SEQ ID NO: 19.

[0025] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 20, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 21.

[0026] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 24, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 25.

[0027] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1 as described in SEQ ID NO: 84, HCDR2 as described in SEQ ID NO: 86, and HCDR3 as described in SEQ ID NO: 88, and the VL comprises LCDR1 as described in SEQ ID NO: 173, LCDR2 as described in SEQ ID NO: 175, and LCDR3 as described in SEQ ID NO: 177.

[0028] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1 as described in SEQ ID NO: 84, HCDR2 as described in SEQ ID NO: 86, and HCDR3 as described in SEQ ID NO: 126, and the VL comprises LCDR1 as described in SEQ ID NO: 213, LCDR2 as described in SEQ ID NO: 175, and LCDR3 as described in SEQ ID NO: 177.

[0029] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1 as described in SEQ ID NO: 111, HCDR2 as described in SEQ ID NO: 113, and HCDR3 as described in SEQ ID NO: 115, and the VL comprises LCDR1 as described in SEQ ID NO: 201, LCDR2 as described in amino acid sequence NAK, and LCDR3 as described in SEQ ID NO: 205.

[0030] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1 as described in SEQ ID NO: 111, HCDR2 as described in SEQ ID NO: 113, and HCDR3 as described in SEQ ID NO: 115, and the VL comprises LCDR1 as described in SEQ ID NO: 201, LCDR2 as described in amino acid sequence NAK, and LCDR3 as described in SEQ ID NO: 203.

[0031] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1 as described in SEQ ID NO: 44, HCDR2 as described in SEQ ID NO: 46, and HCDR3 as described in SEQ ID NO: 48, and the VL comprises LCDR1 as described in SEQ ID NO: 135, LCDR2 as described in amino acid sequence YAS, and LCDR3 as described in SEQ ID NO: 139.

[0032] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1 as described in SEQ ID NO: 51, HCDR2 as described in SEQ ID NO: 53, and HCDR3 as described in SEQ ID NO: 55, and the VL comprises LCDR1 as described in SEQ ID NO: 142, LCDR2 as described in amino acid sequence YAS, and LCDR3 as described in SEQ ID NO: 145.

[0033] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1 as described in SEQ ID NO: 58, HCDR2 as described in SEQ ID NO: 60, and HCDR3 as described in SEQ ID NO: 62, and the VL comprises LCDR1 as described in SEQ ID NO: 148, LCDR2 as described in amino acid sequence KVS, and LCDR3 as described in SEQ ID NO: 152.

[0034] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1 as described in SEQ ID NO: 65, HCDR2 as described in SEQ ID NO: 67, and HCDR3 as described in SEQ ID NO: 69, and the VL comprises LCDR1 as described in SEQ ID NO: 154, LCDR2 as described in amino acid sequence RMS, and LCDR3 as described in SEQ ID NO: 158.

[0035] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1 as described in SEQ ID NO: 72, HCDR2 as described in SEQ ID NO: 74, and HCDR3 as described in SEQ ID NO: 76, and the VL comprises LCDR1 as described in SEQ ID NO: 160, LCDR2 as described in amino acid sequence GAS, and LCDR3 as described in SEQ ID NO: 164.

[0036] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1 as described in SEQ ID NO: 79, HCDR2 as described in SEQ ID NO: 81, and HCDR3 as described in SEQ ID NO: 83, and the VL comprises LCDR1 as described in SEQ ID NO: 166, LCDR2 as described in amino acid sequence SGS, and LCDR3 as described in SEQ ID NO: 170.

[0037] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1 as described in SEQ ID NO: 90, HCDR2 as described in SEQ ID NO: 92, and HCDR3 as described in SEQ ID NO: 94, and the VL comprises LCDR1 as described in SEQ ID NO: 179, LCDR2 as described in amino acid sequence FAS, and LCDR3 as described in SEQ ID NO: 183.

[0038] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1 as described in SEQ ID NO: 96, HCDR2 as described in SEQ ID NO: 98, and HCDR3 as described in SEQ ID NO: 100, and the VL comprises LCDR1 as described in SEQ ID NO: 185, LCDR2 as described in amino acid sequence KVS, and LCDR3 as described in SEQ ID NO: 186.

[0039] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1 as described in SEQ ID NO: 101, HCDR2 as described in SEQ ID NO: 102, and HCDR3 as described in SEQ ID NO: 104, and the VL comprises LCDR1 as described in SEQ ID NO: 188, LCDR2 as described in amino acid sequence DTS, and LCDR3 as described in SEQ ID NO: 192.

[0040] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1 as described in SEQ ID NO: 79, HCDR2 as described in SEQ ID NO: 107, and HCDR3 as described in SEQ ID NO: 109, and the VL comprises LCDR1 as described in SEQ ID NO: 195, LCDR2 as described in amino acid sequence WAS, and LCDR3 as described in SEQ ID NO: 199.

[0041] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1 as described in SEQ ID NO: 117, HCDR2 as described in SEQ ID NO: 119, and HCDR3 as described in SEQ ID NO: 121, and the VL comprises LCDR1 as described in SEQ ID NO: 208, LCDR2 as described in amino acid sequence DTS, and LCDR3 as described in SEQ ID NO: 211.

[0042] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 3, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 13.

[0043] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 26, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 27.

[0044] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 28, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 29.

[0045] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 30, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 29.

[0046] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 22, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 23.

[0047] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 33, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 42.

[0048] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 34, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 42.

[0049] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 33, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 41.

[0050] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 34, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 39.

[0051] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 34, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 40.

[0052] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 34, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 41.

[0053] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 1, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 2.

[0054] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 3, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 4.

[0055] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 5, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 6.

[0056] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 7, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 8.

[0057] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 9, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 10.

[0058] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 11, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 12.

[0059] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 14, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 15.

[0060] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 16, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 17.

[0061] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 18, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 19.

[0062] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 20, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 21.

[0063] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 24, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 25.

[0064] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 3, and the VL comprises the amino acid sequence described in SEQ ID NO: 13.

[0065] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 26, and the VL comprises the amino acid sequence described in SEQ ID NO: 27.

[0066] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 28, and the VL comprises the amino acid sequence described in SEQ ID NO: 29.

[0067] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 30, and the VL comprises the amino acid sequence described in SEQ ID NO: 29.

[0068] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 22 and the VL comprises the amino acid sequence described in SEQ ID NO: 23.

[0069] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 33 and the VL comprises the amino acid sequence described in SEQ ID NO: 42.

[0070] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 34, and the VL comprises the amino acid sequence described in SEQ ID NO: 42.

[0071] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 33 and the VL comprises the amino acid sequence described in SEQ ID NO: 41.

[0072] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 34, and the VL comprises the amino acid sequence described in SEQ ID NO: 39.

[0073] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 34 and the VL comprises the amino acid sequence described in SEQ ID NO: 40.

[0074] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 34 and the VL comprises the amino acid sequence described in SEQ ID NO: 41.

[0075] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 1, and the VL comprises the amino acid sequence described in SEQ ID NO: 2.

[0076] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 3, and the VL comprises the amino acid sequence described in SEQ ID NO: 4.

[0077] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 5, and the VL comprises the amino acid sequence described in SEQ ID NO: 6.

[0078] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 7, and the VL comprises the amino acid sequence described in SEQ ID NO: 8.

[0079] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 9, and the VL comprises the amino acid sequence described in SEQ ID NO: 10.

[0080] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 11, and the VL comprises the amino acid sequence described in SEQ ID NO: 12.

[0081] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 14, and the VL comprises the amino acid sequence described in SEQ ID NO: 15.

[0082] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 16, and the VL comprises the amino acid sequence described in SEQ ID NO: 17.

[0083] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 18, and the VL comprises the amino acid sequence described in SEQ ID NO: 19.

[0084] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 20, and the VL comprises the amino acid sequence described in SEQ ID NO: 21.

[0085] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 24, and the VL comprises the amino acid sequence described in SEQ ID NO: 25.

[0086] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the antibody is a mouse antibody, a chimeric antibody, a humanized antibody, or a human antibody.

[0087] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the antibodies are isotypes selected from the group consisting of IgG, IgA, IgM, IgE, and IgD.

[0088] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the antibodies are subtypes selected from the group consisting of IgG1, IgG2, IgG3, and IgG4.

[0089] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the antigen-binding fragment is selected from the group consisting of Fab, Fab', F(ab')2, Fv, scFv, and ds-scFv.

[0090] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the antibodies are monoclonal antibodies.

[0091] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 230, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 231.

[0092] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 248, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 249.

[0093] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 250, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 251.

[0094] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 252, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 251.

[0095] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 240, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 241.

[0096] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 255, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 264.

[0097] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 256, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 264.

[0098] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 255, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 263.

[0099] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 256, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 261.

[0100] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 256, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 262.

[0101] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the antibodies comprise a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 256, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 263.

[0102] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 218, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 219.

[0103] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 220, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 221.

[0104] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 222, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 223.

[0105] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 224, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 225.

[0106] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 226, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 227.

[0107] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 228, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 229.

[0108] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 232, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 233.

[0109] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 234, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 235.

[0110] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 236, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 237.

[0111] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 238, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 239.

[0112] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 242, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 243.

[0113] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the antibodies are bispecific or multispecific antibodies.

[0114] In a second aspect, the Disclosure provides nucleic acids encoding an antibody or an antigen-binding fragment thereof according to a first aspect of the Disclosure.

[0115] In a third embodiment, the Disclosure provides a vector comprising nucleic acid according to a second embodiment of the Disclosure.

[0116] In a fourth embodiment, the Disclosure provides a host cell comprising a nucleic acid according to a second embodiment of the Disclosure or a vector according to a third embodiment of the Disclosure.

[0117] In a fifth aspect, the Disclosure provides a pharmaceutical composition comprising (i) an antibody or antigen-binding fragment relating to a first aspect of the Disclosure, a nucleic acid relating to a second aspect of the Disclosure, a vector relating to a third aspect of the Disclosure, or a host cell relating to a fourth aspect of the Disclosure, and (ii) a pharmaceutically acceptable carrier or excipient. In some embodiments of the pharmaceutical compositions disclosed herein, the composition further comprises a second therapeutic agent. In some embodiments of the pharmaceutical compositions disclosed herein, the composition further comprises a second therapeutic agent selected from the group consisting of cytokines, antibodies, chemotherapeutic agents, and small molecule drugs.

[0118] In a sixth aspect, the disclosure provides a complex comprising an antibody or antigen-binding fragment according to a first aspect of the disclosure and a chemical moiety bound thereto. In some embodiments of the complexes disclosed herein, the chemical moiety bound to the antibody or antigen-binding fragment is selected from the group consisting of therapeutic agents, detectable moieties, and immunostimulatory molecules.

[0119] In a seventh aspect, the Disclosure provides the use of an antibody or antigen-binding fragment according to a first aspect of the Disclosure, a nucleic acid according to a second aspect of the Disclosure, a vector according to a third aspect of the Disclosure, or a host cell according to a fourth aspect of the Disclosure, a pharmaceutical composition according to a fifth aspect of the Disclosure, or a conjugate according to a sixth aspect of the Disclosure in the manufacture of a drug for treating a target cancer. In some embodiments, the cancer is a B7-H3 positive cancer. In some embodiments of the use disclosed herein, the cancers include adrenal tumors, AIDS-related cancers, hydatidiform soft part sarcomas, astrocytomas, adrenal cancers, bladder cancers, bone cancers, brain and spinal cord cancers, metastatic brain tumors, B-cell cancers, breast cancers, carotid bulb tumors, cervical cancers, chondrosarcomas, chordomas, chromophobe renal cell carcinomas, clear cell carcinomas, colon cancers, colorectal cancers, benign fibrous histiocytomas, fibrinogenic round cell tumors, ependymomas, Ewing's tumors, extraskeletal myxoid chondrosarcomas, fibrous dysplasia, fibrous dysplasia, gallbladder or bile duct cancers, gastric cancers, gestational trophoblastic disease, germ cell tumors, head and neck cancers, hepatocellular carcinomas, and pancreatic islet cell tumors. The following are selected from the group consisting of cystic tumors, Kaposi's sarcoma, renal cancer, leukemia, liposarcoma / malignant lipomatous tumor, liver cancer, lymphoma, lung cancer, medulloblastoma, melanoma, meningioma, multiple endocrine neoplasia, multiple myeloma, myelodysplastic syndrome, neuroblastoma, neuroendocrine tumor, ovarian cancer, pancreatic cancer, papillary thyroid cancer, parathyroid tumor, childhood cancer, peripheral nerve sheath tumor, pheochromocytoma, pituitary tumor, prostate cancer, posterior uveal melanoma, renal metastasis, rhabdoid tumor, rhabdomyosarcoma, sarcoma, skin cancer, soft tissue sarcoma, squamous cell carcinoma, gastric cancer, synovial sarcoma, testicular cancer, thymic cancer, thymoma, metastatic thyroid cancer, and uterine cancer. In some embodiments of the use disclosed herein, the above-mentioned drug is used in combination with a second therapeutic agent. In some embodiments of the use disclosed herein, the above-mentioned second therapeutic agent is selected from the group consisting of cytokines, antibodies, chemotherapeutic agents, and small molecule drugs.

[0120] In an eighth aspect, the Disclosure provides a method for treating a target cancer, comprising administering to the target an effective amount of an antibody or antigen-binding fragment according to a first aspect of the Disclosure, a nucleic acid according to a second aspect of the Disclosure, a vector according to a third aspect of the Disclosure, or a host cell according to a fourth aspect of the Disclosure, a pharmaceutical composition according to a fifth aspect of the Disclosure, or a conjugate according to a sixth aspect of the Disclosure. In some embodiments, the cancer is a B7-H3 positive cancer. In some embodiments of the use disclosed herein, the cancers include adrenal tumors, AIDS-related cancers, hydatidiform soft part sarcomas, astrocytomas, adrenal cancers, bladder cancers, bone cancers, brain and spinal cord cancers, metastatic brain tumors, B-cell cancers, breast cancers, carotid bulb tumors, cervical cancers, chondrosarcomas, chordomas, chromophobe renal cell carcinomas, clear cell carcinomas, colon cancers, colorectal cancers, benign fibrous histiocytomas, fibrinogenic round cell tumors, ependymomas, Ewing's tumors, extraskeletal myxoid chondrosarcomas, fibrous dysplasia, fibrous dysplasia, gallbladder or bile duct cancers, gastric cancers, gestational trophoblastic disease, germ cell tumors, head and neck cancers, hepatocellular carcinomas, and pancreatic islet cell tumors. The following are selected from the group consisting of cystic tumors, Kaposi's sarcoma, renal cancer, leukemia, liposarcoma / malignant lipomatous tumor, liver cancer, lymphoma, lung cancer, medulloblastoma, melanoma, meningioma, multiple endocrine neoplasia, multiple myeloma, myelodysplastic syndrome, neuroblastoma, neuroendocrine tumor, ovarian cancer, pancreatic cancer, papillary thyroid cancer, parathyroid tumor, childhood cancer, peripheral nerve sheath tumor, pheochromocytoma, pituitary tumor, prostate cancer, posterior uveal melanoma, renal metastasis, rhabdoid tumor, rhabdomyosarcoma, sarcoma, skin cancer, soft tissue sarcoma, squamous cell carcinoma, gastric cancer, synovial sarcoma, testicular cancer, thymic cancer, thymoma, metastatic thyroid cancer, and uterine cancer. In some embodiments of the use disclosed herein, the above-mentioned drug is used in combination with a second therapeutic agent. In some embodiments of the use disclosed herein, the above-mentioned second therapeutic agent is selected from the group consisting of cytokines, antibodies, chemotherapeutic agents, and small molecule drugs.

[0121] In a ninth aspect, the Disclosure provides an antibody or antigen-binding fragment according to a first aspect of the Disclosure, a nucleic acid according to a second aspect of the Disclosure, a vector according to a third aspect of the Disclosure, or a host cell according to a fourth aspect of the Disclosure, a pharmaceutical composition according to a fifth aspect of the Disclosure, or a conjugate according to a sixth aspect of the Disclosure, for use in the treatment of a cancer of interest. In some embodiments, the cancer is a B7-H3 positive cancer. In some embodiments of the use disclosed herein, the cancers include adrenal tumors, AIDS-related cancers, hydatidiform soft part sarcomas, astrocytomas, adrenal cancers, bladder cancers, bone cancers, brain and spinal cord cancers, metastatic brain tumors, B-cell cancers, breast cancers, carotid bulb tumors, cervical cancers, chondrosarcomas, chordomas, chromophobe renal cell carcinomas, clear cell carcinomas, colon cancers, colorectal cancers, benign fibrous histiocytomas, fibrinogenic round cell tumors, ependymomas, Ewing's tumors, extraskeletal myxoid chondrosarcomas, fibrous dysplasia, fibrous dysplasia, gallbladder or bile duct cancers, gastric cancers, gestational trophoblastic disease, germ cell tumors, head and neck cancers, hepatocellular carcinomas, and pancreatic islet cell tumors. The following are selected from the group consisting of cystic tumors, Kaposi's sarcoma, renal cancer, leukemia, liposarcoma / malignant lipomatous tumor, liver cancer, lymphoma, lung cancer, medulloblastoma, melanoma, meningioma, multiple endocrine neoplasia, multiple myeloma, myelodysplastic syndrome, neuroblastoma, neuroendocrine tumor, ovarian cancer, pancreatic cancer, papillary thyroid cancer, parathyroid tumor, childhood cancer, peripheral nerve sheath tumor, pheochromocytoma, pituitary tumor, prostate cancer, posterior uveal melanoma, renal metastasis, rhabdoid tumor, rhabdomyosarcoma, sarcoma, skin cancer, soft tissue sarcoma, squamous cell carcinoma, gastric cancer, synovial sarcoma, testicular cancer, thymic cancer, thymoma, metastatic thyroid cancer, and uterine cancer. In some embodiments of the use disclosed herein, the above-mentioned drug is used in combination with a second therapeutic agent. In some embodiments of the use disclosed herein, the above-mentioned second therapeutic agent is selected from the group consisting of cytokines, antibodies, chemotherapeutic agents, and small molecule drugs. [Brief explanation of the drawing]

[0122] The features and advantages of this disclosure can be understood by referring to the following detailed description shown in the exemplary embodiments and accompanying drawings that utilize the principles of this disclosure. [Figure 1-1]This shows the binding ability of chimeric antibodies to CHO-S-human-B7-H3 cells (Figure 1A) and CHO-S-Cyno-B7-H3 cells (Figure 1B). [Figure 1-2] This shows the binding ability of chimeric antibodies to CHO-S-mouse-B7-H3 (Figure 1C) and CHO-S cells (Figure 1D). [Figure 2] This shows the endocytosis efficiency of chimeric antibodies in Calu-6 cells. [Figure 3] This shows the endocytosis efficiency of chimeric antibodies in NCI-H446 cells. [Figure 4] This shows the internalization ability of humanized antibodies in Calu-6 cells (Figure 4B) and NCI-H446 cells (Figure 4A). [Figure 5] This shows the binding activity of humanized antibodies cAb1-z0-p7 (Figure 5A), cAb1-z3-p7 (Figure 5B), and cAb1-z3-p7 (Figure 5C) against B7 family proteins PD-L1, B7-H2, B7-H4, B7-H5, B7-H6, B7-1, B7-2, PD-L2, B7-H7, and Human B7-H3-His. [Modes for carrying out the invention]

[0123] The attached drawings and the detailed description of the embodiments shown below will help to provide a clearer understanding of the above-mentioned features and advantages and other features and advantages of this disclosure.

[0124] The embodiments described herein with reference to the accompanying drawings are descriptive and illustrative, and are intended to provide a general understanding of this disclosure. These embodiments should not be construed as limiting the scope of this disclosure. Identical or similar elements, or elements having the same or similar function, are indicated by the same reference number throughout this specification.

[0125] Unless otherwise specified or defined, all terms used have their ordinary meanings in the art and will be obvious to those skilled in the art. For example, Leuenberger, HGW, Nagel, B., and Klbl, H. eds., “A multilingual glossary of biotechnological terms: (IUPAC Recommendations)”, Helvetica Chimica Acta (1995), CH-4010 Basel, Switzerland; Sambrook et al., “Molecular Cloning: A Laboratory Manual” (2nd Ed.), Vols.1-3, Cold Spring Harbor Laboratory Press (1989); F. Ausubel et al. eds., “Current protocols in molecular biology”, Green Publishing and Wiley InterScience, New York (1987); Roitt et al., “Immunology” (6th Ed.), Mosby / Elsevier, Edinburgh (2001); and Janeway et al. al., “Immunobiology” (6th Ed.), Garland Science Publishing / Churchill Livingstone, New Please refer to standard manuals such as York (2005) and the general background technologies cited above.

[0126] definition In this specification, the singular forms "one," "one," "above," and "the" include multiple subjects unless the context clearly indicates otherwise. Therefore, for example, the statement "one antibody" may include multiple antibodies, and in some embodiments, the statement "one antibody" may include multiple antibodies.

[0127] Unless otherwise specified or defined, the term "includes" and its derivatives (such as "possess" and "encompass") should be understood to mean including the element or process or group of elements or processes described, and not to mean excluding any other element or process or group of elements or processes.

[0128] In this specification, the term “antibody” refers to an immunoglobulin molecule that has the ability to specifically bind to a particular antigen. This molecule typically contains two heavy chains (H) and two light chains (L) interconnected by disulfide bonds. Each heavy chain consists of a heavy chain variable region (domain) (abbreviated as VH) and a heavy chain constant region. The heavy chain constant region consists of three domains: CH1, CH2, and CH3. Each light chain consists of a light chain variable region (domain) (abbreviated as VL) and a light chain constant region. The light chain constant region consists of one domain: CL. The variable regions of the heavy and light chains of an antibody contain binding domains that interact with the antigen. The constant region of an antibody can mediate the binding of immunoglobulin to host tissues or factors (including various cells of the immune system (such as effector cells) and components of the complement system (such as C1q, the first component in the classical pathway of complement activation)).

[0129] The heavy chain of immunoglobulins is divided into three functional regions: the Fd region, the hinge region, and the Fc region (fragment crystallizable region). The Fd region contains the VH and CH1 domains and binds to the light chain to form Fab (antigen-binding fragment). The Fc fragment is responsible for the effector function of immunoglobulins, such as binding to complement and binding to allogeneic Fc receptors on effector cells. The hinge region, present in the IgG, IgA, and IgD immunoglobulin classes, acts as a flexible spacer, allowing the Fab portion to move freely in space relative to the Fc region. The hinge domain is structurally diverse, with both its sequence and length differing between immunoglobulin classes and subclasses.

[0130] Based on crystallographic studies, the hinge region of immunoglobulins can be further divided structurally and functionally into three regions: the upper hinge, the core hinge, and the lower hinge. The upper hinge contains amino acids from the carboxyl terminus of CH1 to the first residue in the hinge that restricts movement (usually the first cysteine ​​residue that forms an interchain disulfide bond between the two heavy chains). The length of the upper hinge region correlates with the segment flexibility of the antibody. The core hinge region contains the interchain disulfide bond. The lower hinge region is connected to the amino terminus of the CH2 domain and contains residues within the CH2 domain. The structure and flexibility of the polypeptide sequence in the hinge region of immunoglobulins alter its conformation, which can affect the effector function of the Fc portion of the antibody.

[0131] The "light chain variable region (VL)" or "heavy chain variable region (VH)" consists of a "framework" region divided by three "complementarity-determining regions" or "CDRs." The framework region plays a role in arranging CDRs that specifically bind to the antigen epitope. The CDRs contain amino acid residues of the antibody that are primarily responsible for antigen binding. Both the VL domain and the VH domain contain framework regions (FR) and CDR regions, namely FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4, from the amino terminus to the carboxyl terminus. In this specification, CDR1, CDR2, and CDR3 of the VL domain are also referred to as LCDR1, LCDR2, and LCDR3, respectively, and CDR1, CDR2, and CDR3 of the VH domain are also referred to as HCDR1, HCDR2, and HCDR3, respectively.

[0132] The amino acid configurations of the VL and VH domains are consistent with all conventional CDR definitions. These conventional definitions include the Kabat definition (Kabat, Sequences of Proteins of Immunological Interest (National Institutes of Health, Bethesda, MD, 1987 and 1991)); the Chothia definition (Chothia and Lesk, J.Mol.Biol.196:901-917, 1987; Chothia et al., Nature 342:878-883, 1989); the Chothia-Kabat CDR complex (CDR-H1 is a complex of Chothia CDR and Kabat CDR); the AbM definition used in Oxford Molecular's antibody modeling software; and the CONTACT definition by Martin et al. (world wide web bioinfo.org.uk / abs). Kabat provides a widely used numbering convention (the Kabat numbering system) in which the same number is assigned to corresponding residues between different heavy chains or between different light chains. In this disclosure, CDRs defined according to any of these numbering systems may be used, but in preferred embodiments, CDRs defined in Kabat are used.

[0133] Based on the amino acid sequence of the constant region of the antibody heavy chain, immunoglobulin molecules can be classified into five classes (isotypes): IgA, IgD, IgE, IgG, and IgM, and further classified into different subtypes such as IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2. Based on the amino acid sequence of the light chain, the light chain of an antibody can be classified into lambda (λ) chains and kappa (κ) chains.

[0134] In this specification, the term “antibody” should be understood in its broadest sense and encompass monoclonal antibodies (including full-length monoclonal antibodies), polyclonal antibodies, antibody fragments, and multispecific antibodies (such as bispecific antibodies) that contain at least two antigen-binding regions. Antibodies may include additional modifications such as non-natural amino acids, mutations in the Fc region, and mutations in glycosylation sites. Antibodies also include post-translationally modified antibodies, fusion proteins containing antigenic determinants of antibodies, and immunoglobulin molecules containing any other modifications of the antigen recognition site, as long as they exhibit the desired biological activity.

[0135] In this specification, the term "monoclonal antibody" refers to an antibody obtained from a substantially homogeneous antibody population; that is, the individual antibodies constituting the population are identical except for a few naturally occurring mutations. Monoclonal antibodies have high specificity and are effective against a single antigen. In this specification, "monoclonal antibody" is not limited to antibodies produced by hybridoma technology, nor should it be interpreted as requiring antibodies produced by any particular method.

[0136] In the context of this disclosure, the term “bispecific antibody” is understood to mean an antibody having two distinct antigen-binding regions defined by different antibody sequences. This is understood to include not only binding to different targets but also binding to different epitopes on a single target. In this specification, the term “bispecific antibody” is understood in its broadest sense and includes full-length bispecific antibodies and their antigen-binding fragments. Bispecific antibodies may include additional modifications such as non-natural amino acids, mutations in the Fc region, and mutations in glycosylation sites. Bispecific antibodies also include post-translation modified antibodies, fusion proteins containing antigenic determinants of the antibody, and immunoglobulin molecules containing any other modifications to the antigen recognition site, as long as they exhibit the desired biological activity.

[0137] In this specification, the term “antigen-binding fragment” of an antibody refers to one or more fragments of an antibody that retain the ability to specifically bind to an antigen. It is known that the antigen-binding function of an antibody can be exerted by fragments of a full-length antibody.

[0138] Examples of antigen-binding fragments encompassed by the term "antigen-binding portion" of an antibody include: (i) Fab fragments, which are monovalent fragments composed of VL, VH, CL, and CH1 domains; (ii) F(ab')2 fragments, which are bivalent fragments containing two Fab fragments linked by disulfide bonds in a hinge region; (iii) Fab' fragments, which are essentially Fab fragments with a partial hinge region; (iv) Fd fragments, which consist of VH and CH1 domains; (v) Fd' fragments, which have VH and CH1 domains and one or more cysteine ​​residues at the C-terminus of the CH1 domain; (vi) Fv fragments, which consist of VL and VH domains in a single arm of the antibody; (vii) dAb fragments, which consist of a VH domain; (viii) isolated complementarity-determining regions (CDRs); and (ix) nanobodies, which are heavy chain variable regions containing a single variable region and two constant regions. Furthermore, although the two domains of the Fv fragment, VL and VH, are encoded by separate genes, they can be linked using recombination with a synthetic linker to form a single protein chain (called single-chain Fv (scFv)) in which the VL and VH regions pair up to form a monovalent molecule. Such single-chain antibodies are also included in the term "antigen-binding fragment" of antibodies. This term also includes "linear antibodies" containing tandem Fd fragment pairs (VH-CH1-VH-CH1) that form an antigen-binding region together with a complementary light chain polypeptide, as well as any modified form of the aforementioned fragments that retain antigen-binding activity.

[0139] These antigen-binding fragments can be obtained using prior art known to those skilled in the art, and the fragments are screened for usefulness in the same way as complete antibodies.

[0140] As used herein, the term "bind" or "specifically bind" refers to a non-random binding reaction between two molecules, such as between an antibody and its target antigen. The binding specificity of an antibody can be determined based on affinity and / or avidity. Affinity represents the dissociation equilibrium constant (KD) of an antibody from an antigen, and is a measure indicating the binding force between an antigenic determinant and the antigen-binding site on the antibody. The smaller the KD value, the stronger the binding force between the antigenic determinant and the antibody. Alternatively, affinity can also be expressed by the affinity constant (KA), which is 1 / KD.

[0141] Avidity is a measure indicating the binding force between an antibody and its associated antigen. Avidity involves both the affinity between the antigenic determinant and the antigen-binding site of the antibody, and the number of relevant binding sites present on the antibody. Typically, the dissociation constant (KD) when an antibody binds to an antigen is 10 -5 M to 10 -12 M or less, preferably 10 -7 M to 10 -12 M or less, more preferably 10 -8 M to 10 -12 M, and / or the binding affinity is at least 10 7 M -1 , preferably at least 10 8 M -1 , more preferably at least 10 9 M -1 , for example at least 10 12 M -1 . In general, a K -4 value greater than 10 M is considered to indicate non-specific binding. Whether an antibody specifically binds to an antigen or an antigenic determinant can be determined by any suitable known means, including, for example, Scatchard analysis and / or competitive binding assays (radioimmunoassay (RIA), enzyme immunoassay (EIA), sandwich competition assays, etc.) and various modified methods known in the art. D

[0142] ​The term "epitope" refers to the site on an antigen to which an antibody binds. Epitopes can be formed from consecutive amino acids or from discontinuous amino acids juxtaposed by the folding of one or more tertiary structures of a protein. Typically, epitopes formed from consecutive amino acids (also called linear epitopes) are retained when exposed to denaturing solvents, while epitopes formed by the folding of tertiary structures (also called conformational epitopes) are usually lost when treated with denaturing solvents. Epitopes typically contain at least three, more typically at least five or eight to ten, amino acids in their own spatial arrangement. Because epitopes define the minimal binding site of an antibody, they are specific targets for the antibody or its antigen-binding fragment.

[0143] In this specification, the term "sequence identity" refers to the degree to which two sequences (amino acids) have the same residues at the same positions after alignment. For example, "an amino acid sequence is X% identical to sequence number Y" means that the amino acid sequence and sequence number Y have X% identity, and that X% of the residues in the amino acid sequence are identical to the residues in the sequence disclosed in sequence number Y. Typically, such calculations are performed by computer programs. Examples of programs for comparing and aligning sequence pairs include ALIGN (Myers and Miller, 1988), FASTA (Pearson and Lipman, 1988; Pearson, 1990), and gapped BLAST (Altschul et al., 1997), BLASTP, BLASTN, or GCG (Devereux et al., 1984).

[0144] Furthermore, when determining the degree of sequence identity between two amino acid sequences, those skilled in the art can consider so-called "conservative" amino acid substitutions. These can generally be described as amino acid substitutions in which one amino acid residue is replaced by another amino acid residue having a similar chemical structure, but which have little to no effect on the biological properties of the polypeptide, such as its function or activity. Such conservative amino acid substitutions are well known in the art.

[0145] Such conservative substitutions are preferably those in which one amino acid from the following groups (a) to (e): (a) nonpolar or weakly polar aliphatic small residues: Ala, Ser, Thr, Pro, and Gly; (b) polar negative-charged residues and their (uncharged) amides: Asp, Asn, Glu, and Gln; (c) polar positive-charged residues: His, Arg, and Lys; (d) nonpolar aliphatic large residues: Met, Leu, Ile, Val, and Cys; and (e) aromatic residues: Phe, Tyr, and Trp is replaced by another amino acid residue from the same group.

[0146] Particularly preferred conservative substitutions are as follows: Ala to Gly or Ser; Arg to Lys; Asn to Gln or His; Asp to Glu; Cys to Ser; Gln to Asn; Glu to Asp; Gly to Ala or Pro; His to Asn or Gln; Ile to Leu or Val; Leu to Ile or Val; Lys to Arg, Gln, or Glu; Met to Leu, Tyr, or Ile; Phe to Met, Leu, or Tyr; Ser to Thr; Thr to Ser; Trp to Tyr; Tyr to Trp; and / or Phe to Val, Ile, or Leu.

[0147] In this specification, the term "tumor-associated antigen" refers to an antigen that is expressed differently in cancer cells compared to normal cells and can therefore be used to target cancer cells.

[0148] B7-H3 (also known as B7homolog3, PSEC0249, UNQ309 / PRO352, CD276, or B7H3) is a single-pass transmembrane protein and a member of the B7 family, expressed as a costimulatory molecule on antigen-presenting cells. B7-H3 is thought to enhance or suppress immune activity by acting on receptors on T cells. The human B7-H3 gene is located on chromosome 15, while the mouse B7-H3 gene is located on chromosome 9.

[0149] In this specification, the term "vector" refers to a nucleic acid molecule capable of carrying other nucleic acids in a ligated state.

[0150] In this specification, the term "host cell" refers to a cell into which an expression vector has been introduced.

[0151] The term "pharmaceutically acceptable" means that the carrier or excipient is compatible with the other components of the composition, is substantially non-toxic to its recipient, and / or is approved or useful for inclusion in a pharmaceutical composition for parenteral administration to humans.

[0152] In this specification, terms such as “treatment,” “therapy,” and “procedure” refer to administering a drug or performing a procedure for the purpose of obtaining an effect. These effects may be preventive in that they completely or partially prevent a disease or its symptoms, and / or therapeutic in that they partially or completely cure a disease and / or its symptoms. In this specification, “treatment” may include treating a disease or disorder (such as cancer) in a mammal, in particular a human, and includes (a) preventing the onset of a disease (e.g., a disease that may be related to or caused by a primary disease) or symptoms in a subject that is susceptible to the disease but has not yet developed the disease; (b) suppressing the disease, i.e., preventing its progression; and (c) alleviating the disease, i.e., causing the disease to regress. Treatment may also refer to objective or subjective parameters that indicate the success of the treatment, improvement, or prevention of cancer, such as reducing symptoms; achieving remission; eliminating the symptoms of the disease or making the disease state more tolerable for the patient; reducing the rate of progression or decline; or weakening the final stage of progression. Treatment or improvement of symptoms is based on one or more objective or subjective parameters, such as the results of a physician's examination. Therefore, the term “treatment” encompasses administering any of the antibodies, compositions, or complexes disclosed herein to prevent, delay, alleviate, halt, or suppress the progression of symptoms or conditions associated with a disease (such as cancer). The term “therapeutic effect” refers to reducing, eliminating, or preventing a disease, its symptoms, or its side effects in a subject.

[0153] In this specification, the term "effective dose" refers to an amount sufficient to treat a disease when administered to a subject.

[0154] In this specification, the term “subject” refers to any mammalian subject for which diagnosis, treatment, or therapy is desired. “Mammalian for therapeutic purposes” refers to any animal classified as a mammal, such as humans, livestock, laboratory animals, zoo animals, sports animals, or pet animals, including dogs, horses, cats, cows, sheep, goats, pigs, mice, rats, rabbits, guinea pigs, and monkeys.

[0155] Anti-B7-H3 antibody This disclosure provides an antibody or its antigen-binding fragment that specifically binds to B7-H3, comprising a light chain variable region (VL) and a heavy chain variable region (VH).

[0156] In a first embodiment, the disclosure provides an antibody or antigen-binding fragment that specifically binds to B7-H3, comprising a heavy chain variable region (VH) and a light chain variable region (VL).

[0157] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 3, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 13.

[0158] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 26, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 27.

[0159] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 28, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 29.

[0160] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 30, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 29.

[0161] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 22, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 23.

[0162] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 33, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 42.

[0163] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 34, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 42.

[0164] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 33, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 41.

[0165] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 34, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 39.

[0166] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 34, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 40.

[0167] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 34, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 41.

[0168] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 1, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 2.

[0169] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 3, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 4.

[0170] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 5, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 6.

[0171] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 7, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 8.

[0172] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 9, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 10.

[0173] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 11, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 12.

[0174] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 14, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 15.

[0175] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 16, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 17.

[0176] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 18, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 19.

[0177] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 20, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 21.

[0178] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 24, and the VL comprises LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 25.

[0179] In some embodiments, the CDR sequence is defined according to the Kabat numbering system.

[0180] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), where the CDR sequence is defined according to the Kabat numbering system, the VH comprises HCDR1 as described in SEQ ID NO: 84, HCDR2 as described in SEQ ID NO: 86, and HCDR3 as described in SEQ ID NO: 88, and the VL comprises LCDR1 as described in SEQ ID NO: 173, LCDR2 as described in SEQ ID NO: 175, and LCDR3 as described in SEQ ID NO: 177.

[0181] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), where the CDR sequence is defined according to the Kabat numbering system, the VH comprises HCDR1 as described in SEQ ID NO: 84, HCDR2 as described in SEQ ID NO: 86, and HCDR3 as described in SEQ ID NO: 126, and the VL comprises LCDR1 as described in SEQ ID NO: 213, LCDR2 as described in SEQ ID NO: 175, and LCDR3 as described in SEQ ID NO: 177.

[0182] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), where the CDR sequence is defined according to the Kabat numbering system, the VH comprises HCDR1 as described in SEQ ID NO: 111, HCDR2 as described in SEQ ID NO: 113, and HCDR3 as described in SEQ ID NO: 115, and the VL comprises LCDR1 as described in SEQ ID NO: 201, LCDR2 as described in amino acid sequence NAK, and LCDR3 as described in SEQ ID NO: 205.

[0183] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), where the CDR sequence is defined according to the Kabat numbering system, the VH comprises HCDR1 as described in SEQ ID NO: 111, HCDR2 as described in SEQ ID NO: 113, and HCDR3 as described in SEQ ID NO: 115, and the VL comprises LCDR1 as described in SEQ ID NO: 201, LCDR2 as described in amino acid sequence NAK, and LCDR3 as described in SEQ ID NO: 203.

[0184] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), where the CDR sequence is defined according to the Kabat numbering system, the VH comprises HCDR1 as described in SEQ ID NO: 44, HCDR2 as described in SEQ ID NO: 46, and HCDR3 as described in SEQ ID NO: 48, and the VL comprises LCDR1 as described in SEQ ID NO: 135, LCDR2 as described in amino acid sequence YAS, and LCDR3 as described in SEQ ID NO: 139.

[0185] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), where the CDR sequence is defined according to the Kabat numbering system, the VH comprises HCDR1 as described in SEQ ID NO: 51, HCDR2 as described in SEQ ID NO: 53, and HCDR3 as described in SEQ ID NO: 55, and the VL comprises LCDR1 as described in SEQ ID NO: 142, LCDR2 as described in amino acid sequence YAS, and LCDR3 as described in SEQ ID NO: 145.

[0186] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), where the CDR sequence is defined according to the Kabat numbering system, the VH comprises HCDR1 as described in SEQ ID NO: 58, HCDR2 as described in SEQ ID NO: 60, and HCDR3 as described in SEQ ID NO: 62, and the VL comprises LCDR1 as described in SEQ ID NO: 148, LCDR2 as described in amino acid sequence KVS, and LCDR3 as described in SEQ ID NO: 152.

[0187] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), where the CDR sequence is defined according to the Kabat numbering system, the VH comprises HCDR1 as described in SEQ ID NO: 65, HCDR2 as described in SEQ ID NO: 67, and HCDR3 as described in SEQ ID NO: 69, and the VL comprises LCDR1 as described in SEQ ID NO: 154, LCDR2 as described in amino acid sequence RMS, and LCDR3 as described in SEQ ID NO: 158.

[0188] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), where the CDR sequence is defined according to the Kabat numbering system, the VH comprises HCDR1 as described in SEQ ID NO: 72, HCDR2 as described in SEQ ID NO: 74, and HCDR3 as described in SEQ ID NO: 76, and the VL comprises LCDR1 as described in SEQ ID NO: 160, LCDR2 as described in amino acid sequence GAS, and LCDR3 as described in SEQ ID NO: 164.

[0189] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), where the CDR sequence is defined according to the Kabat numbering system, the VH comprises HCDR1 as described in SEQ ID NO: 79, HCDR2 as described in SEQ ID NO: 81, and HCDR3 as described in SEQ ID NO: 83, and the VL comprises LCDR1 as described in SEQ ID NO: 166, LCDR2 as described in amino acid sequence SGS, and LCDR3 as described in SEQ ID NO: 170.

[0190] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), where the CDR sequence is defined according to the Kabat numbering system, the VH comprises HCDR1 as described in SEQ ID NO: 90, HCDR2 as described in SEQ ID NO: 92, and HCDR3 as described in SEQ ID NO: 94, and the VL comprises LCDR1 as described in SEQ ID NO: 179, LCDR2 as described in amino acid sequence FAS, and LCDR3 as described in SEQ ID NO: 183.

[0191] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), where the CDR sequence is defined according to the Kabat numbering system, the VH comprises HCDR1 as described in SEQ ID NO: 96, HCDR2 as described in SEQ ID NO: 98, and HCDR3 as described in SEQ ID NO: 100, and the VL comprises LCDR1 as described in SEQ ID NO: 185, LCDR2 as described in amino acid sequence KVS, and LCDR3 as described in SEQ ID NO: 186.

[0192] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), where the CDR sequence is defined according to the Kabat numbering system, the VH comprises HCDR1 as described in SEQ ID NO: 101, HCDR2 as described in SEQ ID NO: 102, and HCDR3 as described in SEQ ID NO: 104, and the VL comprises LCDR1 as described in SEQ ID NO: 188, LCDR2 as described in amino acid sequence DTS, and LCDR3 as described in SEQ ID NO: 192.

[0193] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1 as described in SEQ ID NO: 79, HCDR2 as described in SEQ ID NO: 107, and HCDR3 as described in SEQ ID NO: 109, and the VL comprises LCDR1 as described in SEQ ID NO: 195, LCDR2 as described in WAS, and LCDR3 as described in SEQ ID NO: 199.

[0194] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), where the CDR sequence is defined according to the Kabat numbering system, the VH comprises HCDR1 as described in SEQ ID NO: 117, HCDR2 as described in SEQ ID NO: 119, and HCDR3 as described in SEQ ID NO: 121, and the VL comprises LCDR1 as described in SEQ ID NO: 208, LCDR2 as described in DTS, and LCDR3 as described in SEQ ID NO: 211.

[0195] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 3, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 13. In some embodiments, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 3, and the VL comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 13. However, the antibody or its antigen-binding fragment, which includes a functional variant VH and a functional variant VL, is assumed to retain its ability to bind to B7-H3.

[0196] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 26, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 27. In some embodiments, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 26, and the VL includes a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 27. However, the antibody or its antigen-binding fragment comprising the VH containing the functional variant and the VL containing the functional variant retains its ability to bind to B7-H3.

[0197] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 28, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 29. In some embodiments, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 28, and the VL includes a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 29. However, the antibody or its antigen-binding fragment comprising the VH containing the functional variant and the VL containing the functional variant retains its ability to bind to B7-H3.

[0198] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 30, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 29. In some embodiments, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 30, and the VL includes a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 29. However, the antibody or its antigen-binding fragment comprising the VH containing the functional variant and the VL containing the functional variant retains its ability to bind to B7-H3.

[0199] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 22, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 23. In some embodiments, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 22, and the VL includes a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 23. However, the antibody or its antigen-binding fragment comprising the VH containing the functional variant and the VL containing the functional variant retains its ability to bind to B7-H3.

[0200] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 33, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 42. In some embodiments, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 33, and the VL includes a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 42. However, the antibody or its antigen-binding fragment comprising the VH containing the functional variant and the VL containing the functional variant retains its ability to bind to B7-H3.

[0201] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 34, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 42. In some embodiments, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 34, and the VL includes a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 42. However, the antibody or its antigen-binding fragment comprising the VH containing the functional variant and the VL containing the functional variant retains its ability to bind to B7-H3.

[0202] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 33, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 41. In some embodiments, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 33, and the VL includes a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 41. However, the antibody or its antigen-binding fragment comprising the VH containing the functional variant and the VL containing the functional variant retains its ability to bind to B7-H3.

[0203] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 34, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 39. In some embodiments, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 34, and the VL includes a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 39. However, the antibody or its antigen-binding fragment comprising the VH containing the functional variant and the VL containing the functional variant retains its ability to bind to B7-H3.

[0204] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 34, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 40. In some embodiments, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 34, and the VL includes a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 40. However, the antibody or its antigen-binding fragment, comprising the VH containing the functional variant and the VL containing the functional variant, retains its ability to bind to B7-H3.

[0205] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 34, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 41. In some embodiments, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 34, and the VL includes a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 41. However, the antibody or its antigen-binding fragment comprising the VH containing the functional variant and the VL containing the functional variant retains its ability to bind to B7-H3.

[0206] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 1, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 2. In some embodiments, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 1, and the VL comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 2. However, the antibody or its antigen-binding fragment, which includes a functional variant VH and a functional variant VL, is assumed to retain its ability to bind to B7-H3.

[0207] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 3, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 4. In some embodiments, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 3, and the VL comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 4. However, the antibody or its antigen-binding fragment, which includes a functional variant VH and a functional variant VL, is assumed to retain its ability to bind to B7-H3.

[0208] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 5, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 6. In some embodiments, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 5, and the VL comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 6. However, the antibody or its antigen-binding fragment, which includes a functional variant VH and a functional variant VL, is assumed to retain its ability to bind to B7-H3.

[0209] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 7, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 8. In some embodiments, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 7, and the VL comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 8. However, the antibody or its antigen-binding fragment, which includes a functional variant VH and a functional variant VL, is assumed to retain its ability to bind to B7-H3.

[0210] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 9, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 10. In some embodiments, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 9, and the VL comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 10. However, the antibody or its antigen-binding fragment, which includes a functional variant VH and a functional variant VL, is assumed to retain its ability to bind to B7-H3.

[0211] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 11, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 12. In some embodiments, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 11, and the VL includes a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 12. However, the antibody or its antigen-binding fragment comprising the VH containing the functional variant and the VL containing the functional variant retains its ability to bind to B7-H3.

[0212] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 14, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 15. In some embodiments, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 14, and the VL includes a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 15. However, the antibody or its antigen-binding fragment, comprising the VH containing the functional variant and the VL containing the functional variant, retains its ability to bind to B7-H3.

[0213] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 16, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 17. In some embodiments, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 16, and the VL includes a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 17. However, the antibody or its antigen-binding fragment comprising the VH containing the functional variant and the VL containing the functional variant retains its ability to bind to B7-H3.

[0214] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 18, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 19. In some embodiments, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 18, and the VL includes a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 19. However, the antibody or its antigen-binding fragment comprising the VH containing the functional variant and the VL containing the functional variant retains its ability to bind to B7-H3.

[0215] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 20, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 21. In some embodiments, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 20, and the VL includes a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 21. However, the antibody or its antigen-binding fragment comprising the VH containing the functional variant and the VL containing the functional variant retains its ability to bind to B7-H3.

[0216] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the B7-H3 antibody or antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 24, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 25. In some embodiments, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 24, and the VL includes a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 25. However, the antibody or its antigen-binding fragment comprising the VH containing the functional variant and the VL containing the functional variant retains its ability to bind to B7-H3.

[0217] The above functional variants include or consist of an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, or at least 99.9% sequence identity with respect to the amino acid sequence of the parent polypeptide.

[0218] In the context of functional variants, the number of inserted, deleted, and / or substituted amino acids is preferably 40% or less of the total number of amino acids in the parent amino acid sequence, more preferably 35% or less, even more preferably 1% to 33%, even more preferably 5% to 30%, even more preferably 10% to 25%, and even more preferably 15% to 20%. For example, the number of inserted, deleted, and / or substituted amino acids may be 1 to 20, preferably 1 to 10, more preferably 1 to 7, even more preferably 1 to 5, and most preferably 1 to 2. In a preferred embodiment, the number of inserted, deleted, and / or substituted amino acids is 1, 2, 3, 4, 5, 6, or 7.

[0219] In some embodiments, insertions, deletions, and / or substitutions may occur in framework (FR) regions (FR1, FR2, FR3, and / or FR4, etc.).

[0220] In some embodiments, the substitution of one or more amino acids may be a conservative substitution of one or more amino acids. Such conservative substitutions are preferably those in which one amino acid from the following groups (a) to (e): (a) nonpolar or weakly polar aliphatic small residues: Ala, Ser, Thr, Pro, and Gly; (b) polar negative-charged residues and their (uncharged) amides: Asp, Asn, Glu, and Gln; (c) polar positive-charged residues: His, Arg, and Lys; (d) nonpolar aliphatic large residues: Met, Leu, Ile, Val, and Cys; and (e) aromatic residues: Phe, Tyr, and Trp is substituted for another amino acid residue from the same group.

[0221] Particularly preferred conservative substitutions are as follows: Ala to Gly or Ser; Arg to Lys; Asn to Gln or His; Asp to Glu; Cys to Ser; Gln to Asn; Glu to Asp; Gly to Ala or Pro; His to Asn or Gln; Ile to Leu or Val; Leu to Ile or Val; Lys to Arg, Gln, or Glu; Met to Leu, Tyr, or Ile; Phe to Met, Leu, or Tyr; Ser to Thr; Thr to Ser; Trp to Tyr; Tyr to Trp; and / or Phe to Val, Ile, or Leu.

[0222] In a preferred embodiment, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 3, and the VL comprises the amino acid sequence described in SEQ ID NO: 13.

[0223] In a preferred embodiment, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 26, and the VL comprises the amino acid sequence described in SEQ ID NO: 27.

[0224] In a preferred embodiment, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 28, and the VL comprises the amino acid sequence described in SEQ ID NO: 29.

[0225] In a preferred embodiment, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 30, and the VL comprises the amino acid sequence described in SEQ ID NO: 29.

[0226] In a preferred embodiment, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 22, and the VL comprises the amino acid sequence described in SEQ ID NO: 23.

[0227] In a preferred embodiment, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 33, and the VL comprises the amino acid sequence described in SEQ ID NO: 42.

[0228] In a preferred embodiment, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 34, and the VL comprises the amino acid sequence described in SEQ ID NO: 42.

[0229] In a preferred embodiment, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 33, and the VL comprises the amino acid sequence described in SEQ ID NO: 41.

[0230] In a preferred embodiment, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 34, and the VL comprises the amino acid sequence described in SEQ ID NO: 39.

[0231] In a preferred embodiment, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 34, and the VL comprises the amino acid sequence described in SEQ ID NO: 40.

[0232] In a preferred embodiment, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 34, and the VL comprises the amino acid sequence described in SEQ ID NO: 41.

[0233] In a preferred embodiment, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 1, and the VL comprises the amino acid sequence described in SEQ ID NO: 2.

[0234] In a preferred embodiment, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 3, and the VL comprises the amino acid sequence described in SEQ ID NO: 4.

[0235] In a preferred embodiment, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 5, and the VL comprises the amino acid sequence described in SEQ ID NO: 6.

[0236] In a preferred embodiment, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 7, and the VL comprises the amino acid sequence described in SEQ ID NO: 8.

[0237] In a preferred embodiment, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 9, and the VL comprises the amino acid sequence described in SEQ ID NO: 10.

[0238] In a preferred embodiment, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 11, and the VL comprises the amino acid sequence described in SEQ ID NO: 12.

[0239] In a preferred embodiment, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 14, and the VL comprises the amino acid sequence described in SEQ ID NO: 15.

[0240] In a preferred embodiment, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 16, and the VL comprises the amino acid sequence described in SEQ ID NO: 17.

[0241] In a preferred embodiment, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 18, and the VL comprises the amino acid sequence described in SEQ ID NO: 19.

[0242] In a preferred embodiment, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 20, and the VL comprises the amino acid sequence described in SEQ ID NO: 21.

[0243] In a preferred embodiment, the B7-H3 antibody or its antigen-binding fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence described in SEQ ID NO: 24, and the VL comprises the amino acid sequence described in SEQ ID NO: 25.

[0244] In some embodiments of the antibodies or antigen-binding fragments disclosed herein, the antibody is a mouse antibody, a chimeric antibody, a humanized antibody, or a human antibody.

[0245] In some embodiments, the antibody is a mouse antibody, a chimeric antibody, a humanized antibody, or a human antibody.

[0246] Based on the amino acid sequence of the constant region of the antibody heavy chain, immunoglobulin molecules can be classified into five classes (isotypes): IgA, IgD, IgE, IgG, and IgM, and further classified into different subtypes such as IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2. Based on the amino acid sequence of the light chain, the light chain of an antibody can be classified into a lambda (λ) chain and a kappa (κ) chain. The antibodies disclosed herein may belong to any of the above classes or subtypes.

[0247] In some embodiments, the antibody is an isotype selected from the group consisting of IgG, IgA, IgM, IgE, and IgD. In some embodiments, the antibody is a subtype selected from the group consisting of IgG1, IgG2, IgG3, and IgG4. In a preferred embodiment, the antibody is an IgG1 antibody.

[0248] The antibodies disclosed herein may be complete antibodies or their antigen-binding fragments. The antigen-binding fragment may be any fragment of an antibody that retains the ability to specifically bind to B7-H3. Examples of antigen-binding fragments, but are not limited to, include Fab fragments, F(ab')2 fragments, Fab' fragments, Fd fragments, Fd' fragments, Fv fragments, scFv fragments, dAb fragments, isolated complementarity-determining regions (CDRs), nanobodies, linear antibodies composed of tandem Fd fragment pairs (VH-CH1-VH-CH1), and modified forms of the aforementioned fragments that retain antigen-binding activity.

[0249] In some embodiments, the antigen-binding fragment is selected from the group consisting of Fab, Fab', F(ab')2, Fv, scFv, and ds-scFv. In a preferred embodiment, the antigen-binding fragment is Fab. In another preferred embodiment, the antigen-binding fragment is Fv. In yet another preferred embodiment, the antigen-binding fragment is scFv.

[0250] In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 230, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 231. In some embodiments, the heavy chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 230, provided that the functional variant retains its ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 231, provided that the functional variant retains its ability to bind to B7-H3. The above functional variants include or consist of an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, or at least 99.9% sequence identity with respect to the amino acid sequence of the parent polypeptide.

[0251] In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 248, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 249. In some embodiments, the heavy chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 248, provided that the functional variant retains its ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 249, provided that the functional variant retains its ability to bind to B7-H3. The above functional variants include or consist of an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, or at least 99.9% sequence identity with respect to the amino acid sequence of the parent polypeptide.

[0252] In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 250, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 251. In some embodiments, the heavy chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 250, provided that the functional variant retains its ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 251, provided that the functional variant retains its ability to bind to B7-H3. The above functional variants include or consist of an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, or at least 99.9% sequence identity with respect to the amino acid sequence of the parent polypeptide.

[0253] In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 252, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 251. In some embodiments, the heavy chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 252, provided that the functional variant retains its ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 251, provided that the functional variant retains its ability to bind to B7-H3. The above functional variants include or consist of an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, or at least 99.9% sequence identity with respect to the amino acid sequence of the parent polypeptide.

[0254] In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 240, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 241. In some embodiments, the heavy chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 240, provided that the functional variant retains its ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 241, provided that the functional variant retains its ability to bind to B7-H3. The above functional variants include or consist of an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, or at least 99.9% sequence identity with respect to the amino acid sequence of the parent polypeptide.

[0255] In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 255, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 264. In some embodiments, the heavy chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 255, provided that the functional variant retains its ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 264, provided that the functional variant retains its ability to bind to B7-H3. The above functional variants include or consist of an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, or at least 99.9% sequence identity with respect to the amino acid sequence of the parent polypeptide.

[0256] In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 256, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 264. In some embodiments, the heavy chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 256, provided that the functional variant retains its ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 264, provided that the functional variant retains its ability to bind to B7-H3. The above functional variants include or consist of an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, or at least 99.9% sequence identity with respect to the amino acid sequence of the parent polypeptide.

[0257] In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 255, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 263. In some embodiments, the heavy chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 255, provided that the functional variant retains its ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 263, provided that the functional variant retains its ability to bind to B7-H3. The above functional variants include or consist of an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, or at least 99.9% sequence identity with respect to the amino acid sequence of the parent polypeptide.

[0258] In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 256, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 261. In some embodiments, the heavy chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 256, provided that the functional variant retains its ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 261, provided that the functional variant retains its ability to bind to B7-H3. The above functional variants include or consist of an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, or at least 99.9% sequence identity with respect to the amino acid sequence of the parent polypeptide.

[0259] In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 256, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 262. In some embodiments, the heavy chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 256, provided that the functional variant retains its ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 262, provided that the functional variant retains its ability to bind to B7-H3. The above functional variants include or consist of an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, or at least 99.9% sequence identity with respect to the amino acid sequence of the parent polypeptide.

[0260] In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 256, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 263. In some embodiments, the heavy chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 256, provided that the functional variant retains its ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 263, provided that the functional variant retains its ability to bind to B7-H3. The above functional variants include or consist of an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, or at least 99.9% sequence identity with respect to the amino acid sequence of the parent polypeptide.

[0261] In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 218, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 219. In some embodiments, the heavy chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 218, provided that the functional variant retains its ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 219, provided that the functional variant retains its ability to bind to B7-H3. The above functional variants include or consist of an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, or at least 99.9% sequence identity with respect to the amino acid sequence of the parent polypeptide.

[0262] In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 220, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 221. In some embodiments, the heavy chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 220, provided that the functional variant retains its ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 221, provided that the functional variant retains its ability to bind to B7-H3. The above functional variants include or consist of an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, or at least 99.9% sequence identity with respect to the amino acid sequence of the parent polypeptide.

[0263] In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 222, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 223. In some embodiments, the heavy chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 222, provided that the functional variant retains its ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 223, provided that the functional variant retains its ability to bind to B7-H3. The above functional variants include or consist of an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, or at least 99.9% sequence identity with respect to the amino acid sequence of the parent polypeptide.

[0264] In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 224, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 225. In some embodiments, the heavy chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 224, provided that the functional variant retains its ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 225, provided that the functional variant retains its ability to bind to B7-H3. The above functional variants include or consist of an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, or at least 99.9% sequence identity with respect to the amino acid sequence of the parent polypeptide.

[0265] In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 226, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 227. In some embodiments, the heavy chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 226, provided that the functional variant retains its ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 227, provided that the functional variant retains its ability to bind to B7-H3. The above functional variants include or consist of an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, or at least 99.9% sequence identity with respect to the amino acid sequence of the parent polypeptide.

[0266] In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 228, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 229. In some embodiments, the heavy chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 228, provided that the functional variant retains its ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 229, provided that the functional variant retains its ability to bind to B7-H3. The above functional variants include or consist of an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, or at least 99.9% sequence identity with respect to the amino acid sequence of the parent polypeptide.

[0267] In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 232, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 233. In some embodiments, the heavy chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 232, provided that the functional variant retains its ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 233, provided that the functional variant retains its ability to bind to B7-H3. The above functional variants include or consist of an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, or at least 99.9% sequence identity with respect to the amino acid sequence of the parent polypeptide.

[0268] In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 234, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 235. In some embodiments, the heavy chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 234, provided that the functional variant retains its ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 235, provided that the functional variant retains its ability to bind to B7-H3. The above functional variants include or consist of an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, or at least 99.9% sequence identity with respect to the amino acid sequence of the parent polypeptide.

[0269] In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 236, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 237. In some embodiments, the heavy chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 236, provided that the functional variant retains its ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 237, provided that the functional variant retains its ability to bind to B7-H3. The above functional variants include or consist of an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, or at least 99.9% sequence identity with respect to the amino acid sequence of the parent polypeptide.

[0270] In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 238, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 239. In some embodiments, the heavy chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 238, provided that the functional variant retains its ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 239, provided that the functional variant retains its ability to bind to B7-H3. The above functional variants include or consist of an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, or at least 99.9% sequence identity with respect to the amino acid sequence of the parent polypeptide.

[0271] In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 242, and the light chain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 243. In some embodiments, the heavy chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 242, provided that the functional variant retains its ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant formed by inserting, deleting, and / or substituting one or more amino acids into the amino acid sequence described in SEQ ID NO: 243, provided that the functional variant retains its ability to bind to B7-H3. The above functional variants include or consist of an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, or at least 99.9% sequence identity with respect to the amino acid sequence of the parent polypeptide.

[0272] In some embodiments, the number of amino acids inserted, deleted, and / or substituted is preferably 40% or less of the total number of amino acids in the parent amino acid sequence, more preferably 35% or less, even more preferably 1% to 33%, more preferably 5% to 30%, more preferably 10% to 25%, and more preferably 15% to 20%. For example, the number of amino acids inserted, deleted, and / or substituted may be 1 to 50, preferably 1 to 20, more preferably 1 to 10, and even more preferably 1 to 5. In preferred embodiments, the number of amino acids inserted, deleted, and / or substituted is 1, 2, 3, 4, 5, 6, or 7.

[0273] In some embodiments, insertions, deletions, and / or substitutions may be performed in framework (FR) regions (FR1, FR2, FR3, and / or FR4, etc.) and / or steady-state regions (CL, CH1, CH2, and / or CH3, etc.).

[0274] In some embodiments, the substitution of one or more amino acids may be a conservative substitution of one or more amino acids. Examples of conservative substitutions include those described above.

[0275] In a preferred embodiment, the antibody comprises a heavy chain containing the amino acid sequence described in SEQ ID NO: 230 and a light chain containing the amino acid sequence described in SEQ ID NO: 231. In a preferred embodiment, the antibody comprises a heavy chain containing the amino acid sequence described in SEQ ID NO: 248 and a light chain containing the amino acid sequence described in SEQ ID NO: 249. In a preferred embodiment, the antibody comprises a heavy chain containing the amino acid sequence described in SEQ ID NO: 250 and a light chain containing the amino acid sequence described in SEQ ID NO: 251. In a preferred embodiment, the antibody comprises a heavy chain containing the amino acid sequence described in SEQ ID NO: 252 and a light chain containing the amino acid sequence described in SEQ ID NO: 251. In a preferred embodiment, the antibody comprises a heavy chain containing the amino acid sequence described in SEQ ID NO: 240 and a light chain containing the amino acid sequence described in SEQ ID NO: 241. In a preferred embodiment, the antibody comprises a heavy chain containing the amino acid sequence described in SEQ ID NO: 255 and a light chain containing the amino acid sequence described in SEQ ID NO: 264. In a preferred embodiment, the antibody comprises a heavy chain containing the amino acid sequence described in SEQ ID NO: 256 and a light chain containing the amino acid sequence described in SEQ ID NO: 264. In a preferred embodiment, the antibody comprises a heavy chain containing the amino acid sequence described in SEQ ID NO: 255 and a light chain containing the amino acid sequence described in SEQ ID NO: 263. In a preferred embodiment, the antibody comprises a heavy chain containing the amino acid sequence described in SEQ ID NO: 256 and a light chain containing the amino acid sequence described in SEQ ID NO: 261. In a preferred embodiment, the antibody comprises a heavy chain containing the amino acid sequence described in SEQ ID NO: 256 and a light chain containing the amino acid sequence described in SEQ ID NO: 262. In a preferred embodiment, the antibody comprises a heavy chain containing the amino acid sequence described in SEQ ID NO: 256 and a light chain containing the amino acid sequence described in SEQ ID NO: 263. In a preferred embodiment, the antibody comprises a heavy chain containing the amino acid sequence described in SEQ ID NO: 218 and a light chain containing the amino acid sequence described in SEQ ID NO: 219. In a preferred embodiment, the antibody comprises a heavy chain containing the amino acid sequence described in SEQ ID NO: 220 and a light chain containing the amino acid sequence described in SEQ ID NO: 221. In a preferred embodiment, the antibody comprises a heavy chain containing the amino acid sequence described in SEQ ID NO: 222 and a light chain containing the amino acid sequence described in SEQ ID NO: 223.In a preferred embodiment, the antibody comprises a heavy chain containing the amino acid sequence described in SEQ ID NO: 224 and a light chain containing the amino acid sequence described in SEQ ID NO: 225. In a preferred embodiment, the antibody comprises a heavy chain containing the amino acid sequence described in SEQ ID NO: 226 and a light chain containing the amino acid sequence described in SEQ ID NO: 227. In a preferred embodiment, the antibody comprises a heavy chain containing the amino acid sequence described in SEQ ID NO: 228 and a light chain containing the amino acid sequence described in SEQ ID NO: 229. In a preferred embodiment, the antibody comprises a heavy chain containing the amino acid sequence described in SEQ ID NO: 232 and a light chain containing the amino acid sequence described in SEQ ID NO: 233. In a preferred embodiment, the antibody comprises a heavy chain containing the amino acid sequence described in SEQ ID NO: 234 and a light chain containing the amino acid sequence described in SEQ ID NO: 235. In a preferred embodiment, the antibody comprises a heavy chain containing the amino acid sequence described in SEQ ID NO: 236 and a light chain containing the amino acid sequence described in SEQ ID NO: 237. In a preferred embodiment, the antibody comprises a heavy chain containing the amino acid sequence described in SEQ ID NO: 238 and a light chain containing the amino acid sequence described in SEQ ID NO: 239. In a preferred embodiment, the antibody comprises a heavy chain containing the amino acid sequence described in SEQ ID NO: 242 and a light chain containing the amino acid sequence described in SEQ ID NO: 243.

[0276] In other embodiments, the antibody is a bispecific antibody or a multispecific antibody. In some embodiments, the antibody is a bispecific antibody further comprising a second antigen-binding region that binds to a second antigen. In some embodiments, the second antigen is a tumor-associated antigen or an immune cell antigen.

[0277] Numerous tumor-associated antigens (TIAs) associated with specific cancers have been identified in the field. In some embodiments, TIAs are antigens capable of inducing a significant tumor-specific immune response. Some of these antigens are encoded by normal cells, but not necessarily expressed. These antigens can be characterized as antigens that are normally silent (i.e., not expressed) in normal cells, antigens that are expressed only at specific stages of differentiation, and antigens that are expressed over time, such as embryonic or fetal antigens. Other cancer cell antigens are encoded by oncogenes (e.g., activated ras oncogenes), suppressor genes (e.g., P53 variants), and mutant cell genes such as fusion proteins resulting from internal deletions or chromosomal translocations. Other cancer antigens can be encoded by viral genes, such as those held by RNA and DNA oncoviruses. Many other TIAs are known and / or commercially available, and can be prepared by those skilled in the art.

[0278] The antibody that specifically binds to B7-H3 in this disclosure includes an Fc region. The Fc region is not particularly limited, but may be any isotype such as IgG1, IgG2, IgG3, and IgG4, and may contain one or more mutations or modifications. In one embodiment, the Fc region is an IgG1 isotype or derived therefrom and may contain one or more mutations or modifications. In another embodiment, the Fc region is an IgG4 isotype or derived therefrom and may contain one or more mutations or modifications. In one embodiment, the Fc region is human IgG1 Fc.

[0279] In one embodiment, the Fc region has reduced effector function, for example, reduced binding to ADCC, ADCP, CDC, and / or C1q, FcγRI, FcγRII, or FcγRIIIA. For example, the Fc region may be an IgG1 isotype or a non-IgG1 type (IgG2, IgG3, or IgG4, etc.), which are mutated to have reduced or even lost ability to mediate effector function. Such mutations are described, for example, in Dall'Acqua WF et al., J Immunol. 177(2):1129-1138 (2006) and Hezareh M, J Virol.; 75(24):12161-12168 (2001). For example, the Fc region may contain an amino acid sequence having one or more amino acid substitutions compared to the wild-type sequence, such as E233P, L234A, L234F, L235A, L235E, G237A, N297A, N297D, P331S, and P329G.

[0280] In one embodiment, the Fc region includes a mutation that removes the acceptor site for Asn-linked glycosylation, or is otherwise manipulated to alter the glycosylation characteristics. For example, in the IgG1 Fc region, the Asn-linked glycosylation site may be removed using the N297Q mutation. Thus, in certain embodiments, the Fc region includes an IgG1 sequence having the N297Q mutation.

[0281] In further embodiments, the Fc region is glycotechnically modified to reduce fucose, thereby enhancing ADCC by adding the compound to the culture medium during antibody production, as described in US2009317869 or van Berkel et al. (2010) Biotechnol. Bioeng. 105:350, or by using FUT8 knockout cells, as described in Yamane-Ohnuki et al. (2004) Biotechnol. Bioeng. 87:614, etc. Alternatively, ADCC can be optimized using the method described in Umana et al., (1999), Nature Biotech 17:176. In another embodiment, the Fc region is modified to enhance complement activation, as described in Natsume et al. (2009) Cancer Sci. 100:2411, etc.

[0282] In some embodiments, the Fc region includes modifications or mutations that can suppress Fc homodimerization. In some embodiments, the Fc region includes a variant of the human IgG1 Fc wild-type sequence. This variant may include amino acid substitutions at the T366 and Y407 (Kabat numbering) positions in human IgG1. Preferably, T366 is substituted with L (leucine). Preferably, Y407 is substituted with I (isoleucine), F (phenylalanine), L (leucine), M (methionine), H (histidine), K (lysine), S (serine), Q (glutamine), T (threonine), W (tryptophan), A (alanine), G (glycine), or N (asparagine). More preferably, Y407 is substituted with H. In one embodiment, T366 is substituted with L and Y407 is substituted with H.

[0283] In some embodiments, the Fc region may be monomeric human IgG1 Fc (e.g., mFc7.2) as described in PCT application number PCT / US2018 / 016524 (all incorporated herein by reference).

[0284] nucleic acid The present disclosure provides a nucleic acid comprising a nucleotide sequence encoding the antibody or antigen-binding fragment thereof disclosed herein.

[0285] The term "nucleic acid" includes single-stranded and double-stranded nucleotide polymers. The nucleic acid may be a ribonucleotide or a deoxyribonucleotide, or a modified form of any type of nucleotide. Modifications 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, phenylthiophosphate, phosphoroanilidate, and phosphoramidate.

[0286] For example, the present disclosure provides a nucleic acid molecule encoding any one of the heavy chain variable region sequences disclosed herein. The present disclosure also provides a nucleic acid molecule that is at least 90%, at least 95%, at least 98%, or at least 99% identical to a nucleic acid encoding any one of the heavy chain variable region sequences disclosed herein.

[0287] For example, the present disclosure provides a nucleic acid molecule encoding any one of the light chain variable region sequences disclosed herein. The present disclosure also provides a nucleic acid molecule that is at least 90%, at least 95%, at least 98%, or at least 99% identical to a nucleic acid encoding any one of the light chain variable region sequences disclosed herein.

[0288] For example, the present disclosure provides a nucleic acid molecule encoding a heavy chain variable region sequence comprising the CDR sequence of any one of the heavy chain variable region sequences disclosed herein. The present disclosure also provides a nucleic acid molecule encoding a heavy chain variable region sequence comprising a CDR sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the CDR sequence of any one of the heavy chain variable region sequences disclosed herein.

[0289] For example, this disclosure provides nucleic acid molecules encoding a light chain variable region sequence that includes one of the CDR sequences disclosed herein. This disclosure also provides nucleic acid molecules encoding a light chain variable region sequence that includes a CDR sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to one of the CDR sequences disclosed herein.

[0290] In some embodiments, the nucleic acid is ribonucleic acid (RNA) or deoxyribonucleic acid (DNA). In some embodiments, the disclosure provides ribonucleic acid (RNA) comprising a nucleotide sequence encoding the antibody disclosed herein. In some embodiments, the disclosure provides deoxyribonucleic acid (DNA) comprising a deoxynucleotide sequence encoding the antibody disclosed herein.

[0291] In some embodiments, the deoxyribonucleic acid (DNA) can be introduced into human cells in vivo. In some embodiments, the deoxyribonucleic acid (DNA) of the Disclosure is contained in a carrier or delivery agent. In some embodiments, the deoxyribonucleic acid (DNA) of the Disclosure is incorporated into the genome of a cell.

[0292] In some embodiments, the ribonucleic acid (RNA) described above can be introduced into human cells in vivo. In some embodiments, the ribonucleic acid (RNA) of this disclosure is contained in a carrier or delivery agent.

[0293] vector This disclosure provides vectors comprising nucleic acids disclosed herein.

[0294] In some embodiments, the vector is an expression vector capable of expressing a polypeptide containing the heavy chain variable region or light chain variable region of an antibody. For example, this disclosure provides an expression vector containing any one of the nucleic acid molecules described above.

[0295] In some embodiments, the vector is an expression vector capable of expressing a polypeptide comprising the heavy or light chain of an antibody. For example, this disclosure provides an expression vector comprising any one of the nucleic acid molecules described above.

[0296] Any of the vectors described herein may be suitably used. In some embodiments, the vector is a viral vector. In some embodiments, the vector is a retroviral vector, a DNA vector, a mouse leukemia virus vector, an SFG vector, a plasmid, an RNA vector, an adenovirus vector, a baculovirus vector, an Epstein-Barr virus vector, a papovavirus vector, a vaccinia virus vector, a herpes simplex virus vector, an adeno-associated virus (AAV) vector, a lentivirus vector, or a combination thereof. Examples of suitable vectors include pGAR, pBABE-puro, pBABE-neo largeTcDNA, pBABE-hygro-hTERT, pMKO.1 GFP, MSCV-IRES-GFP, pMSCV PIG (Puro IRES GFP empty plasmid), pMSCV-loxp-dsRed-loxp-eGFP-Puro-WPRE, MSCV IRES Luciferase, pMIG, MDH1-PGK-GFP_2.0, TtRMPVIR, pMSCV-IRES-mCherry FP, pRetroX GFP T2A Cre, pRXTN, pLncEXP, and pLXIN-Luc.

[0297] The expression vector described above may be any suitable recombinant expression vector. Suitable vectors include plasmids and viruses, etc., designed for proliferation and amplification, or expression, or both. For example, the vector may be selected from the pUC series (Fermentas Life Sciences, Glen Burnie, Md.), the pBluescript series (Stratagene, LaJolla, Calif.), the pET series (Novagen, Madison, Wis.), the pGEX series (Pharmacia Biotech, Uppsala, Sweden), and the pEX series (Clontech, Palo Alto, Calif.). Phage vectors such as λGT10, λGT11, λZapII (Stratagene), λEMBL4, and λNM1149 can also be used. Examples of plant expression vectors useful in this disclosure include pBI01, pBI101.2, pBI101.3, pBI121, and pBIN19 (Clontech). Examples of animal expression vectors useful in this disclosure include pcDNA, pEUK-C1, pMAM, and pMAMneo (Clontech).

[0298] Recombinant expression vectors can be prepared using standard recombinant DNA techniques described in Sambrook et al., Molecular Cloning: A Laboratory Manual, 3rd ed., Cold Spring Harbor Press, Cold Spring Harbor, NY, 2001; and Ausubel et al., Current Protocols in Molecular Biology, Greene Publishing Associates and John Wiley & Sons, NY, 1994, etc. Circular or linear expression vector constructs can be prepared to include replication system function in prokaryotic or eukaryotic host cells. The replication system can be derived from COLEL, 2μ plasmid, λ, SV40, or bovine papillomavirus, etc.

[0299] For example, the vector may be an adenovirus vector containing a nucleotide sequence encoding the antibody disclosed herein. After administering the vector to a target, the nucleotide sequence encoding the antibody disclosed herein may be introduced into the target cells in vivo to integrate it into the cell genome. Subsequently, the cells express the antibody disclosed herein.

[0300] host cell This disclosure provides host cells comprising nucleic acids or vectors disclosed herein.

[0301] Any cell can be used as the host cell for the nucleic acids or vectors of this disclosure. In some embodiments, the cell may be a prokaryotic cell, a fungal cell, a yeast cell, or a higher eukaryotic cell such as a mammalian cell. Suitable prokaryotic cells include, but are not limited to, Enterobacteria such as Escherichia (E. coli), Enterobacter, Erwinia, Klebsiella, Proteus, Salmonella (Salmonella typhimurium), Serratia (Serratia marcescans), and Shigella; Bacilli (B. subtilis and B. licheniformis); Pseudomonas (P. aeruginosa); and Gram-negative or Gram-positive organisms such as Streptomyces. In some embodiments, the cell is a human cell. In some embodiments, the cell is an immune cell. In some embodiments, the host cells include CHO cells such as CHOS cells and CHO-K1 cells, and HEK293 cells such as HEK293A, HEK293T, and HEK293FS.

[0302] The host cells of this disclosure are prepared by introducing the vectors or nucleic acids disclosed herein in vitro or ex vivo. The host cells of this disclosure may be administered to a subject, and the host cells express the antibodies disclosed herein in vivo.

[0303] This disclosure provides host cells into which one of the vectors described above has been introduced. This disclosure also provides a method for preparing an antibody of this disclosure, comprising (a) culturing a host cell according to a fourth aspect of this disclosure under conditions suitable for the production of the antibody, and (b) obtaining the antibody from the culture.

[0304] Pharmaceutical composition This disclosure provides pharmaceutical compositions comprising an antibody or its antigen-binding fragment disclosed herein, or a bispecific antibody or its antigen-binding fragment disclosed herein, and a pharmaceutically acceptable carrier or excipient.

[0305] The antibodies or their antigen-binding fragments or drugs (hereinafter also referred to as “active compounds”), as well as their derivatives, fragments, analogs, and homologs, may be incorporated into pharmaceutical compositions suitable for administration. Such compositions typically comprise the antibody or its antigen-binding fragment or drug and a pharmaceutically acceptable carrier. The term “pharmaceutically acceptable carrier” herein is intended to include any solvent, dispersion medium, coating, antimicrobial agent, antifungal agent, isotonic agent, and absorption retarder suitable for the administration of the drug. Preferred examples of such carriers or excipients, though not particularly limited, include water, physiological saline, Ringer's solution, glucose solution, and 5% human serum albumin. Non-aqueous vehicles such as liposomes and non-volatile oils may also be used. The use of such media and drugs as pharmaceutically active substances is well known in the art. Unless conventional media or drugs are incompatible with the active compound, their use in the compositions is considered. Auxiliary active compounds may be incorporated into the compositions.

[0306] In some embodiments, the above pharmaceutical composition further comprises a second therapeutic agent. In some embodiments, the second therapeutic agent is selected from the group consisting of cytokines, antibodies, chemotherapeutic agents, and small molecule drugs. In some embodiments, the second therapeutic agent is selected from interleukins (such as IL-2), Bruton's tyrosine kinase (BTK) inhibitors, PI3K inhibitors, HDAC inhibitors, ERK inhibitors, MAPK inhibitors, PD-1 inhibitors, PD-L1 inhibitors, CTLA-4 inhibitors, TIGIT inhibitors, TIM3 inhibitors, VEGF inhibitors, LAG3 inhibitors, and glucocorticoids.

[0307] In some embodiments, the second therapeutic agent is a cytokine. Examples of cytokines include, but are not particularly limited to, interleukins (such as IL-2, IL-7, IL-10, IL-12, IL-15) and interferons (such as IFNα, IFNγ). In some embodiments, the second therapeutic agent is an interleukin. In a preferred embodiment, the second therapeutic agent is IL-2.

[0308] In some embodiments, the second therapeutic agent is a chemotherapeutic agent. Examples of the chemotherapeutic agent include cytotoxic agents, antimetabolites (such as folate antagonists, purine analogs, pyrimidine analogs), topoisomerase inhibitors (such as camptothecin derivatives, anthraquinones, anthracyclines, epipodophyllotoxins, quinoline alkaloids), microtubule inhibitors (such as taxanes, vinca alkaloids), protein synthesis inhibitors (such as cephalotaxine, camptothecin derivatives, quinoline alkaloids), alkylating agents (such as alkyl sulfonates, aziridines, nitrogen mustards, nitrosoureas, platinum derivatives, triazenes), alkaloids, terpenoids, kinase inhibitors, and the like.

[0309] The pharmaceutical compositions of this disclosure may be formulated to suit the intended route of administration. Examples of routes of administration include intravenous, intradermal, subcutaneous, oral (e.g., inhalation), transdermal (e.g., topical), transmucosal, and parenteral administration such as rectal administration. Solutions or suspensions for parenteral, intradermal, or subcutaneous administration may contain components such as sterile diluents such as sterile water for injection, physiological saline, non-volatile oils, polyethylene glycol, glycerol, or synthetic solvents such as propylene glycol; antimicrobial agents such as benzyl alcohol or methylparaben; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethylenediaminetetraacetic acid (EDTA); buffering agents such as acetates, citrates, or phosphates; and tonicity adjusters such as sodium chloride or dextrose. The pH can be adjusted with an acid or base such as hydrochloric acid or sodium hydroxide. Parenteral formulations may be sealed in glass or plastic ampoules, disposable syringes, or multi-dose vials.

[0310] Suitable pharmaceutical compositions for injection include sterile aqueous solutions (if water-soluble) or dispersions, and sterile powders for the immediate preparation of sterile injection solutions or dispersions. For intravenous administration, suitable carriers include physiological saline, bacteriostatic water, Cremophor EL™ (BASF, Parsippany, NJ), or phosphate-buffered saline (PBS). In all cases, the composition must be sterile and should be a fluid that can be easily injected. It must be stable under preparation and storage conditions and protected from contamination by microorganisms such as bacteria and fungi. The carrier may be a solvent or dispersion medium containing water, ethanol, polyols (glycerol, propylene glycol, and liquid polyethylene glycol, etc.), and suitable mixtures thereof. Suitable fluidity may be maintained by using coatings such as lecithin to maintain the required particle size in the case of dispersions, and by using surfactants. Microbial action may be prevented by various antimicrobial and antifungal agents such as parabens, chlorobutanol, phenol, ascorbic acid, and thimerosal. It is often preferable to incorporate sugars, polyols such as mannitol or sorbitol, or isotonic agents such as sodium chloride into the above composition. The absorption of the injectable composition may also be extended by incorporating absorption-delaying agents such as aluminum monostearate and gelatin into the composition.

[0311] Sterile injectable solutions may be prepared by mixing a desired amount of the active compound in a suitable solvent containing one or a combination thereof of the components listed above (if necessary), followed by filtration and sterilization. Dispersions are typically prepared by introducing the active compound into a sterile vehicle containing a basic dispersion medium and other necessary components listed above. In the case of sterile powders used in the preparation of sterile injectable solutions, the preparation methods are vacuum drying and freeze-drying, yielding a powder containing the active ingredient and other desired components from a pre-sterile filtered solution.

[0312] Oral compositions typically contain an inert diluent or food carrier. These can be encapsulated in gelatin capsules or compressed into tablets. For oral therapeutic administration, the active compound may be mixed with an excipient and used as a tablet, lozenge, or capsule. Oral compositions may also be prepared using a fluid carrier and used as a mouthwash, in which case the compound in the fluid carrier is orally administered, gargled with, and then spat out or swallowed. Pharmaceutically suitable binders and / or adjuvants may be incorporated as part of the above composition. Tablets, pills, capsules, and lozenges may contain any of the following components or compounds with similar properties: binders such as microcrystalline cellulose, tragacanth gum, or gelatin; excipients such as starch or lactose; disintegrants such as alginic acid, Primogel, or corn starch; lubricants such as magnesium stearate or Sterotes; flow enhancers such as colloidal silica; sweeteners such as sucrose or saccharin; or flavorings such as peppermint oil, methyl salicylate, or orange flavoring.

[0313] When administered by inhalation, the above-mentioned compounds are delivered as an aerosol spray from a pressurized container or a dispenser or nebulizer containing a suitable propellant (e.g., a gas such as carbon dioxide).

[0314] Furthermore, systemic administration can be carried out by transmucosal or transdermal means. In the case of transmucosal or transdermal administration, a penetration agent suitable for the target barrier is used in the formulation. Such penetration agents are generally known in the art, and examples of transmucosal administration include cleansing agents, bile salts, and fusidic acid derivatives. Transmucosal administration may be carried out using nasal sprays or suppositories. In the case of transdermal administration, the active compound is formulated as an ointment, salve, gel, or cream, which are well known in the art.

[0315] The active compound may also be formulated as a suppository or retained enema for rectal delivery (for example, using conventional suppository bases such as cocoa butter and other glycerides).

[0316] In one embodiment, the active compound is prepared with a carrier that protects the compound from rapid elimination in the body, such as a sustained-release formulation including an implant and a microencapsulation delivery system. Biodegradable, biocompatible polymers such as ethylene vinyl acetate, polyacid anhydride, polyglycolic acid, collagen, polyorthoester, and polylactic acid may be used. Methods for preparing such formulations will be obvious to those skilled in the art.

[0317] This disclosure provides therapeutic compositions comprising the antibody or its antigen-binding fragment. The therapeutic compositions according to this disclosure are administered with suitable carriers, excipients, and other agents incorporated into the formulation to improve distribution, delivery, and tolerability. Many suitable formulations can be found in any formulation known to medicinal chemists (Remington's Pharmaceutical Sciences, Mack Publishing Company, Easton, PA). Such formulations include, for example, powders, pastes, ointments, jellies, waxes, oils, lipids, (cationic or anionic) vesicle-containing lipids such as LIPOFECTIN®, DNA complexes, anhydrous absorbent pastes, oil-in-water or water-in-oil emulsions, polyethylene glycol emulsions (polyethylene glycol of various molecular weights), semi-solid gels, and semi-solid mixtures containing polyethylene glycol. See also Powell et al., “Compendium of excipients for parenteral formulations,” PDA (1998) J Pharm Sci Technol 52:238-311.

[0318] complex This disclosure provides an antibody or its antigen-binding fragment as disclosed herein, or a complex comprising a bispecific antibody or its antigen-binding fragment as disclosed herein and a chemical moiety bound thereto.

[0319] In the context of this disclosure, a “complex” is a structure in which an antibody or antibody fragment (such as an antigen-binding fragment) is covalently linked to a chemical portion. Examples of chemical portions include drugs, toxins, therapeutic agents, detectable labels, proteins, nucleic acids, lipids, nanoparticles, carbohydrates, or recombinant viruses. Antibody complexes are generally referred to as “immune complexes.” When a complex includes an antibody linked to a drug (such as a cytotoxic agent), the complex is generally referred to as an “antibody-drug conjugate” or “ADC.”

[0320] The terms "conjugated" or "linked" may refer to combining two polypeptides into a single, continuous polypeptide molecule. In one embodiment, the antibody is linked to a chemical moiety. In another embodiment, to increase the in vivo half-life, the antibody linked to the chemical moiety may be further linked to a lipid or other molecule, or to a protein or peptide. Linking may be carried out chemically or recombinantly. In one embodiment, linking is chemical, in which case a covalent bond is formed between the two molecules by a reaction between the antibody moiety and the chemical moiety to obtain a single molecule. Optionally, a peptide linker (short peptide sequence) may be included between the antibody and the chemical moiety.

[0321] The chemical moiety can be linked to the antibody of this disclosure by any number of means known to those skilled in the art. Both covalent and non-covalent linking means can be used. The procedure for linking the chemical moiety to the antibody varies depending on the chemical structure of the chemical moiety. Polypeptides typically contain various functional groups, such as carboxylic acid (COOH), free amine (-NH2), or sulfhydryl (-SH) moieties, which react with suitable functional groups of the antibody to link the chemical moiety. Alternatively, the antibody may be derivatized to expose or link another reactive functional group. Derivatization may involve linking one of many known linker molecules. The linker may be any molecule used to link the antibody and the chemical moiety. The linker can form covalent bonds with both the antibody and the chemical moiety. Suitable linkers are well known to those skilled in the art and are not particularly limited, but include linear or branched carbon linkers, heterocyclic carbon linkers, or peptide linkers. If the antibody and chemical moieties are polypeptides, the linker may be linked to the constituent amino acids via their side chain groups (e.g., via disulfide bonds with cysteine) or to the α-carbon amino group and carboxyl group of the terminal amino acids.

[0322] In some cases, it is desirable for an immune complex to release a chemical portion from the antibody upon reaching the target site. Therefore, in such cases, the immune complex will contain cleavage sites near the target site.

[0323] The linker can be cleaved by enzymatic activity or conditions experienced by the immune complex within or near the target cell, releasing a chemical portion from the antibody.

[0324] Given the numerous reported methods for conjugating various radiodiagnostic compounds, radiotherapeutic compounds, labels (such as enzymes or fluorescent molecules), drugs, toxins, and other agents to antibodies, those skilled in the art will be able to determine a suitable method for conjugating a given agent to an antibody or other polypeptide.

[0325] The antibodies disclosed herein can be derivatized or ligated to other molecules (such as other peptides or proteins). Typically, the derivatization of an antibody or a portion thereof is carried out in such a way that the derivatization or labeling does not adversely affect binding to the target antigen. For example, an antibody can be functionally ligated (by chemical bonding, gene fusion, non-covalent bonding, etc.) to one or more other molecular entities, such as another antibody (such as a bispecific antibody or a bivalent antibody), a detection agent, a pharmaceutical agent, and / or a protein or peptide (such as a streptavidin core region or polyhistidine tag) capable of mediating the binding of the antibody or antibody portion to another molecule.

[0326] A single derivatized antibody can be obtained by crosslinking two or more antibodies (of the same or different types). Suitable crosslinking agents include hetero-bifunctional or homo-bifunctional crosslinking agents (such as disuccinimidyl suberate) having two different reactive moieties (such as m-maleimidobenzoyl-N-hydroxysuccinimidyl) separated by a suitable spacer. Such linkers are commercially available.

[0327] In some embodiments of the complexes disclosed herein, the chemical portion is selected from the group consisting of therapeutic agents, detectable portions, and immunostimulatory molecules.

[0328] Treatment method This disclosure provides a method for treating a target cancer, comprising administering to the target in an effective amount an antibody or its antigen-binding fragment, nucleic acid, vector, host cell, pharmaceutical composition, or complex disclosed herein.

[0329] In some embodiments of the methods disclosed herein, the cancer is a B7-H3 positive cancer. In some embodiments, the cancer is an adrenal tumor, an AIDS-related cancer, a hydatidiform soft part sarcoma, an astrocytoma, an adrenal cancer, a bladder cancer, a bone cancer, a brain and spinal cord cancer, a metastatic brain tumor, a B-cell cancer, a breast cancer, a carotid bulb tumor, a cervical cancer, a chondrosarcoma, a chordoma, a chromophobe renal cell carcinoma, a clear cell carcinoma, a colon cancer, a colorectal cancer, a benign fibrous histiocytoma, a fibroplastic round cell tumor, an ependymoma, a Ewing tumor, an extraskeletal myxoid chondrosarcoma, a fibrous dysplasia, a fibrous dysplasia, a gallbladder or bile duct cancer, a gastric cancer, a gestational trophoblastic disease, a germ cell tumor, a head and neck cancer, a hepatocellular carcinoma, a pancreatic islet cell tumor, a Kaposi's positivity tumor. The group consists of sarcoma, renal cancer, leukemia, liposarcoma / malignant lipomatous tumor, liver cancer, lymphoma, lung cancer, medulloblastoma, melanoma, meningioma, multiple endocrine neoplasia, multiple myeloma, myelodysplastic syndrome, neuroblastoma, neuroendocrine tumor, ovarian cancer, pancreatic cancer, papillary thyroid carcinoma, parathyroid tumor, childhood cancer, peripheral nerve sheath tumor, pheochromocytoma, pituitary tumor, prostate cancer, posterior uveal melanoma, renal metastasis, rhabdoid tumor, rhabdomyosarcoma, sarcoma, skin cancer, soft tissue sarcoma, squamous cell carcinoma, gastric cancer, synovial sarcoma, testicular cancer, thymic carcinoma, thymoma, metastatic thyroid cancer, and uterine cancer.

[0330] In some embodiments, the dose administered to a subject may vary depending on the embodiment, the drug used, the method of administration, and the site and subject being treated. However, the dose should be sufficient to produce a therapeutic response. A clinician can determine the effective dose to administer to a subject such as a human to treat a medical disorder. The exact amount required to be therapeutically effective may vary depending on several factors, such as antibody activity and route of administration.

[0331] The doses of antibodies, compositions, or conjugates disclosed herein may be administered to mammals as a single dose, or as needed, as a series of partial doses over a suitable period, such as once daily, twice weekly, weekly, bi-weekly, twice monthly, bi-monthly, twice annually, or annually. An effective amount of antibody, composition, or conjugate may be administered as a single daily dose, or the total daily dose may be administered as two, three, four, or more divided doses per day, as desired.

[0332] The preferred mode of administration may be selected by the physician. The route of administration may be parenteral, such as by injection, nasal administration, pulmonary administration, or transdermal administration. Systemic or local administration may be carried out by intravenous, intramuscular, intraperitoneal, or subcutaneous injection. In some embodiments, the antibody, composition, or complex described above is selected for parenteral delivery, inhalation, or delivery via the gastrointestinal tract, for example, orally. The dosage and method of administration may vary depending on the subject's weight, age, condition, etc., and may be selected as appropriate.

[0333] In some embodiments, the above method further includes administering a second therapeutic agent to the subject. In certain embodiments, the antibody, composition, or complex disclosed herein is administered before, substantially simultaneously with, or after the administration of the second therapeutic agent.

[0334] Medical use This disclosure provides the use of antibodies or their antigen-binding fragments disclosed herein, bispecific antibodies or their antigen-binding fragments disclosed herein, nucleic acids, host cells, pharmaceutical compositions, or complexes in the manufacture of pharmaceuticals for the treatment of target cancers.

[0335] This disclosure also provides antibodies or antigen-binding fragments thereof, bispecific antibodies or antigen-binding fragments thereof, pharmaceutical compositions thereof, or complexes thereof, which are used to treat a target cancer.

[0336] In some embodiments of the uses disclosed herein, the cancer is B7-H3 positive cancer. In some embodiments, the cancer is adrenal tumor, AIDS-related cancer, hydatidiform soft part sarcoma, astrocytoma, adrenal cancer, bladder cancer, bone cancer, brain and spinal cord cancer, metastatic brain tumor, B-cell cancer, breast cancer, carotid bulb tumor, cervical cancer, chondrosarcoma, chordoma, chromophobe renal cell carcinoma, clear cell carcinoma, colon cancer, colorectal cancer, benign fibrous histiocytoma, fibrinogenic small round cell tumor, ependymoma, Ewing's tumor, extraskeletal myxoid chondrosarcoma, fibrous dysplasia, fibrous dysplasia, gallbladder or bile duct cancer, gastric cancer, gestational trophoblastic disease, germ cell tumor, head and neck cancer, hepatocellular carcinoma, pancreatic islet cell tumor, Kaposi's positivity The group consists of sarcoma, renal cancer, leukemia, liposarcoma / malignant lipomatous tumor, liver cancer, lymphoma, lung cancer, medulloblastoma, melanoma, meningioma, multiple endocrine neoplasia, multiple myeloma, myelodysplastic syndrome, neuroblastoma, neuroendocrine tumor, ovarian cancer, pancreatic cancer, papillary thyroid carcinoma, parathyroid tumor, childhood cancer, peripheral nerve sheath tumor, pheochromocytoma, pituitary tumor, prostate cancer, posterior uveal melanoma, renal metastasis, rhabdoid tumor, rhabdomyosarcoma, sarcoma, skin cancer, soft tissue sarcoma, squamous cell carcinoma, gastric cancer, synovial sarcoma, testicular cancer, thymic carcinoma, thymoma, metastatic thyroid cancer, and uterine cancer.

[0337] Diagnostic and detection methods This disclosure provides a method for detecting the B7-H3 protein in vitro or in vivo. B7-H3 expression may be detected in biological samples. Such samples may be any sample, but are not limited to, blood samples, biopsy tissues, autopsy specimens, and pathological specimens. Biological samples may also be bodily fluids such as blood, serum, plasma, sputum, cerebrospinal fluid, or urine. Biological samples are usually obtained from mammals such as humans or non-human primates.

[0338] This disclosure also provides a method for determining whether a subject has B7-H3 positive cancer by contacting a sample derived from the subject with the anti-B7-H3 antibody disclosed herein and detecting the binding of the antibody to the sample. If the binding of the antibody to the sample is increased compared to the binding of the antibody to a control sample, it is confirmed that the subject has cancer.

[0339] In another embodiment, the Disclosure provides a method for diagnosing B7-H3 positive cancer in a subject by contacting a sample derived from the subject with the anti-B7-H3 antibody disclosed herein and detecting the binding of the antibody to the sample. If the binding of the antibody to the sample is increased compared to the binding of the antibody to a control sample, the diagnosis of cancer in the subject is confirmed.

[0340] In some embodiments, the control sample is a sample derived from a subject that does not have cancer. In certain embodiments, the sample is a blood sample or a tissue sample.

[0341] In some embodiments of the diagnostic and detection method, the anti-B7-H3 antibody is directly labeled with a detectable label. In another embodiment, the anti-B7-H3 antibody (primary antibody) is unlabeled, and a secondary antibody or other molecule capable of binding to the primary antibody is labeled. As is well known to those skilled in the art, the secondary antibody is selected to be capable of specifically binding to a particular species and class of primary antibody. For example, if the primary antibody is human IgG, the secondary antibody may be anti-human IgG. Other molecules capable of binding to the antibody include, but are not limited to, Protein A and Protein G, both of which are commercially available.

[0342] Suitable labels for antibodies or secondary antibodies include various enzymes, prosthetic groups, fluorescent substances, luminescent substances, magnetic agents, and radioactive substances. Suitable enzymes include, but are not limited to, horseradish peroxidase, alkaline phosphatase, β-galactosidase, or acetylcholinesterase. Suitable prosthetic group complexes include, but are not limited to, streptavidin / biotin and avidin / biotin. Suitable fluorescent substances include, but are not limited to, umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansilchloride, or phycoerythrin. A suitable luminescent substance is luminol, but is not limited to, luminol. A suitable magnetic agent is gadolinium, but is not limited to, luminol. A suitable radioactive label includes, but is not limited to, 125I, 131I, 35S, or 3H.

[0343] In another embodiment, B7-H3 can be measured in a biological sample by a competitive immunoassay using a B7-H3 protein standard labeled with a detectable substance and an unlabeled anti-B7-H3 antibody. In this assay, the biological sample, the labeled B7-H3 protein standard, and the anti-B7-H3 antibody are mixed, and the amount of the labeled B7-H3 protein standard bound to the unlabeled antibody is measured. The amount of B7-H3 in the biological sample is inversely proportional to the amount of the labeled protein standard bound to the anti-B7-H3 antibody.

[0344] The immunoassays and methods disclosed herein can be used for a variety of purposes. In one embodiment, the anti-B7-H3 antibody can be used to detect the production of B7-H3 in cells in a cell culture. In another embodiment, the antibody can be used to measure the amount of B7-H3 in a biological sample such as a tissue sample or a blood or serum sample. In some examples, the B7-H3 is cell surface B7-H3.

[0345] kit This disclosure provides a pharmaceutical package or kit comprising one or more containers containing one or more components of a pharmaceutical composition described herein, such as an antibody or its antigen-binding fragment disclosed herein.

[0346] In certain embodiments, the kit comprises a first container containing the antibody disclosed herein. In certain embodiments, the kit comprises a first container which is a vial containing the antibody as a sterile powder lyophilized under vacuum, and a second container containing a pharmaceutically acceptable fluid.

[0347] In certain embodiments, the invention provided herein is an injection device containing an antibody. In certain embodiments, the injection device contains the antibody in a sterile solution. In certain embodiments, the injection device is a syringe.

[0348] In one embodiment, the kit is used to detect B7-H3 in a biological sample, such as a blood sample or a tissue sample. For example, a biopsy may be performed to obtain a tissue sample for histological examination in order to confirm the diagnosis of a target cancer. Kits for detecting polypeptides typically contain an anti-B7-H3 antibody, such as one of the monoclonal antibodies disclosed herein. In another embodiment, the antibody is labeled (e.g., by fluorescence, radioactivity, or enzyme labeling).

[0349] In one embodiment, the kit includes explanatory materials disclosing the use of the anti-B7-H3 antibody. These explanatory materials may be in written, electronic (e.g., on a computer floppy disk or optical disk), or visual (e.g., a video file). The kit may also include additional components to facilitate the application for which it is designed. For example, the kit may further include means for detecting the label (e.g., an enzyme substrate for enzyme labeling, a filter set for fluorescent labeling detection, a suitable secondary label such as a secondary antibody). The kit may also include buffers and other reagents commonly used to carry out a particular method. Such kits and suitable contents are well known to those skilled in the art.

[0350] In one embodiment, the diagnostic kit includes an immunoassay. A method for detecting B7-H3 in a biological sample typically involves contacting the biological sample with an anti-B7-H3 antibody. The antibody is specifically bound under immunoreaction conditions to form an immune complex, and the presence of this immune complex (bound antibody) is detected directly or indirectly. [Examples]

[0351] The following embodiments are presented for illustrative purposes to illustrate various embodiments of the Disclosure, but are not intended to limit the Disclosure in any way. These embodiments and the methods described herein are representative of preferred embodiments at present, are illustrative, and are not intended to limit the scope of the Disclosure. Those skilled in the art will be able to conceive of variations and other uses that are included in the spirit of the Disclosure and defined by the claims.

[0352] Example 1: Preparation of antibody hybridomas 1.1 Mouse Immunity All mice were housed in a barrier system. Ten 6-8 week old female Balb / c mice (SPF grade) were immunized by subcutaneous injection at multiple sites with a fusion protein of human-derived B7-H3 protein (UniProt KB:Q5ZPR3, Leu29-Pro245) and Fc (UniProt KB:P01857, Pro100-Lys330) as an antigen. Each mouse was initially immunized with 100 μg of the antigen, followed by 50 μg of the antigen per mouse. Serum titers of the mice were measured after three immunizations.

[0353] 1.2 Cell Fusion Five mice with favorable immunosuppression results were immunized intraperitoneally with Human B7-H3-His protein (ACRO, B73-H52E2) + CHO-S-Mouse-B7-H3 recombinant cell line (purchased from iCarTab Biotechnology, AKD052A). Three days later, the mice were euthanized by cervical dislocation. Under sterile conditions, the mouse spleens were obtained, and a single-cell suspension of B cells was prepared and mixed with non-secretory SP2 / 0 myeloma cells in a 1:1 ratio. Cell fusion was performed using a BTX cell electrofusion apparatus. After electrofusion, all cells were immediately suspended in complete medium (DMEM, 20% FBS, and HAT (a mixture of hypoxanthine, aminopterin, and thymidine)), seeded in 96-well plates, and cultured in a CO2 incubator.

[0354] 1.3 Hybridoma Screening Twelve days after fusion, 100 μL of the culture supernatant was collected from a 96-well plate and subjected to an ELISA assay using different species of B7-H3 antigen proteins. Based on the detection results of fusion titer, clones with high OD values ​​and good proliferation were selected. Further screening by flow cytometry was performed to select clones capable of binding to cells overexpressing human, cynomolgus monkey, or mouse B7-H3 (CHO-S-human B7-H3, CHO-S-Cyno B7-H3, or CHO-S-mouse B7-H3). Positive clones were selected based on the ELISA and FACS results, and subcloning was performed twice to form monoclonals.

[0355] The specific experimental procedures for ELISA and FACS are as follows: (1) ELISA screening A 96-well ELISA plate was coated overnight at 4°C with 100 μL of Human B7-H3-His, Cyno B7-H3-His, or Mouse B7-H3-Fc recombinant protein (final concentration 0.5 μg / mL). After washing three times with PBST (containing 0.5% Tween), blocking buffer (3% BSA) was added to the wells and blocked at 37°C for 2 hours, and the plate was washed three times with PBST. 100 μL of hybridoma supernatant was added and incubated at room temperature for 1 hour. After washing three times with PBST, 100 μL of 10,000-fold diluted HRP anti-mouse IgG H&L (Biodragon, CAT#BF03001) was added to each well. The plate was incubated at room temperature for 1 hour and washed three times. 100 μL of TMB substrate solution was added per well, and the plate was incubated in the dark at room temperature for 10 minutes. The reaction was stopped by adding 50 μL of stop solution, and the OD values ​​in the wells were read using a microplate reader. (2) FACS screening CHO-S cell line, CHO-S-human B7-H3 cell line, CHO-S-Cyno B7-H3 cell line, and CHO-S-mouse B7-H3 cell line were each measured in 3 × 10⁻¹⁰ samples. 5Cells were dispensed individually. 50 μL of hybridoma supernatant was incubated with each target cell, thoroughly mixed, and incubated at room temperature for 1 hour. The cells were washed three times with PBS, PE-labeled anti-human IgG (Invitrogen, CAT#12-4998-82) was added, thoroughly mixed, and incubated in the dark at room temperature for 30 minutes. The cells were washed three times with PBS and detected by flow cytometry. 1.4 Sequencing of monoclonal antibodies Based on the results of ELISA and FACS, single monoclonal hybridoma cells that met the requirements were selected and cultured. The cells were lysed with Trizol, and total RNA was extracted from the hybridoma cells according to standard procedures. After reverse transcription of the total RNA into a cDNA sample using a reverse transcription kit, the heavy chain and light chain variable regions of the antibody were amplified by PCR using hybridoma sequencing primers. After purification and recovery, the PCR product fragments were subcloned into a T vector, and clones were selected and sequenced.

[0356] Example 2: Preparation and Characterization of Chimeric Antibodies 2.1 Production of Chimeric Antibodies After sequencing, the heavy chain variable region (VH) and light chain variable region (VL) sequences of the antibody were obtained as shown in Table 1. Underlined sequences in Table 1 are CDR regions as defined by the Kabat system. The heavy chain variable region gene fragment of the mouse antibody was constructed in the binding region of the multicloning site of the eukaryotic expression plasmid pCDNA3.4-IgG1 to construct a heavy chain expression plasmid. pCDNA3.4-IgG1 was obtained by ligating the nucleic acid encoding the heavy chain constant region fragment (GenBank:ACK87036.1, Seq2-330) to the backbone plasmid pCDNA3.4 (purchased from Invitrogen, A14697). The light chain expression plasmid was constructed by constructing the nucleic acid encoding the light chain variable region gene of the mouse antibody in the binding region of the multicloning site of the eukaryotic expression plasmid pCDNA3.4-IgKc. pCDNA3.4-IgKc was obtained by ligating a light chain constant region fragment (GenBank: AAA59000.1, Seq31-137) to the backbone pCDNA3.4. The constructed light chain expression plasmid and heavy chain expression plasmid were used to transform E. coli DH5a competent cells. After selecting single colonies and confirming their sequences, the plasmids were extracted in large quantities to obtain the expression plasmids for the chimeric antibody light chain and the chimeric antibody heavy chain.

[0357] Plasmids containing heavy chain genes and light chain genes were transiently and simultaneously transfected into 293F (Gibco, R79007) cells. The transfected cells were cultured for 4-6 days and centrifuged at 8000 rpm for 20 minutes. The cell culture supernatant containing the target protein was collected and loaded onto a Protein A affinity chromatography column to obtain purified antibodies.

[0358] The sequence of the positive control antibody M30-H1-L4 was derived from patent CN103687945A and was expressed and purified similarly using the method described above.

[0359] The sequence of the positive control antibody hmAb-C was derived from CN109069633A, and was expressed and purified in the same manner as described above. [Table 1-1] [Table 1-2] [Table 1-3] [Table 2-1] [Table 2-2] [Table 2-3] [Table 3-1] [Table 3-2] [Table 3-3] [Table 4-1] [Table 4-2] [Table 4-3] [Table 4-4] [Table 4-5] [Table 4-6] [Table 4-7] [Table 4-8] [Table 4-9]

[0360] 2.2 Characterization of Chimeric Antibodies 2.2.1 Affinity Verification of Chimeric Antibodies Detection was performed using a Fortebio Octet R2 as follows. Mouse monoclonal antibodies were immobilized using an AMQ sensor with PBST (PBS + 0.02% tween20) as buffer. Human B7-H3-His protein samples were diluted to 12.5 nM, 6.25 nM, 3.13 nM, 1.56 nM, and 0 nM. Antibody protein concentrations were set to 100 nM, 50 nM, 25 nM, 12.5 nM, 6.25 nM, and 0 nM. Equilibrium was set to 150 seconds, binding to 180 seconds, dissociation to 300 seconds, and the detection temperature to 25°C. Dynamic parameters for binding to Human B7-H3-His (ka: binding rate, kd: dissociation rate, kD: binding-dissociation equilibrium constant) were obtained for each sample. The results are shown in Table 4. [Table 5]

[0361] 2.2.2 Verification of FACS binding and species specificity of chimeric antibodies CHO-S cell line, CHO-S-human B7-H3 cell line (recombinantly expressing human B7-H3), CHO-Cyno B7-H3 cell line (recombinantly expressing cynomolgus monkey B7-H3), and CHO-mouse B7-H3 cell line (recombinantly expressing mouse B7-H3) were each measured in 3 × 10⁶ cells. 5Cells were dispensed individually. 100 μL of chimeric antibody supernatant was incubated with each target cell. The B7-H3 antibody concentration for detection using human B7-H3 overexpressing cells CHO-S-human B7-H3 and monkey B7-H3 overexpressing cells CHO-Cyno B7-H3 was 1 μg / mL, while the B7-H3 antibody concentration for detection using mouse B7-H3 overexpressing cells CHO-mouse B7-H3 and blank CHO cells CHO-S was 10 μg / mL. After thorough mixing, the cells were incubated at room temperature for 1 hour. The cells were washed three times with PBS, and PE-labeled anti-human IgG (Invitrogen, CAT#12-4998-82) was added. After thorough mixing, the cells were incubated in the dark at room temperature for 30 minutes. The cells were washed three times with PBS and measured using a flow cytometer. The results are shown in Figure 1.

[0362] The results in Figures 1A to 1D show that the sequences 16-B6-G3-E10, 48-B4-D3-E3, 48-B4-F4-E4, 41-G9-G4-D3, 19-F1-E9-B11, 9-F1-D9-F10, 16-D10-E1-E1, 28-B5-B6-C6, 10-A3-C5-C8, 29-A9-G8-F6, 9-A2-G3-H11, 28-B1-E8-C11, and 28-F8-C4-A8 are all capable of binding to CHO-S-human B7-H3 cells. Of these, 48-B4-F4-E4, 19-F1-E9-B11, 9-F1-D9-F10, 16-D10-E1-E1, 28-B5-B6-C6, 29-A9-G8-F6, and 9-A2-G3-H11 can cross-binding to human, mouse, and monkey B7-H3.

[0363] 2.2.3 Verification of Endocytosis Efficiency of Chimeric Antibodies The internalization efficiency of chimeric antibodies 16-B6-G3-E10 (CE10), 19-F1-E9-B11 (CB11), 48-B4-F4-E4 (CE4), 28-B1-E8-C11 (CC11), and the positive control antibody M30-H1-L4 into Calu-6 (lung cancer cells) and NCI-H446 (small cell lung cancer cells) was verified by a killing assay of chimeric antibodies conjugated with the toxin DT3C. Calu-6 cells or NCI-H446 cells in the logarithmic growth phase were resuspended in culture medium to a suitable concentration and seeded at 500 cells / 40 μL / well. After incubation overnight, the chimeric antibodies were incubated with DT3C in a 1:2 ratio at room temperature for 30 minutes to form antibody-DT3C conjugates. These were then added to 384-well white cell culture plates and incubated at 37°C for 3 days. Subsequently, 20 μL / well of CellTiter-Glo Reagen reagent from the CellTiter Glo assay kit (Promega, G7573) was added for detection. The inhibition rate was calculated using the following formula. %Inhibition=100-(Signalcmpd-SignalAve_PC) / (SignalAve_VC-SignalAve_PC)×100 In the formula, %Inhibition represents the inhibition rate, Signalcmpd represents the mean luminescence value of the test sample, SignalAve_PC represents the mean luminescence value of the blank positive control, and SignalAve_VC represents the mean luminescence value of the negative control (0.1% DMSO).

[0364] The results are shown in Figures 2 and 3. The results show that 16-B6-G3-E10(CE10), 19-F1-E9-B11(CB11), and 48-B4-F4-E4(CE4) showed better internalization efficiency in Calu-6 and NCI-H446 compared to the positive control M30-H1-L4, and 28-B1-E8-C11(CC11) had an internalization rate in Calu-6 and NCI-H446 equivalent to that of the positive control M30-H1-L4.

[0365] Example 3 Humanized antibody 3.1 Humanization design, removal of post-translational modification sites, and plasmid construction Humanized antibody engineering was performed using 48-B4-F4-E4 and 28-B1-E8-C11, selected according to the performance of chimeric antibodies in various configurations. Homology models of the antibodies were obtained by modeling based on the heavy and light chain amino acid sequences of the selected mouse antibodies, and framework amino acids within the CDR range, which typically affect the CDR's three-dimensional structure or antigen-binding activity, were analyzed. Human germline cells were obtained by IMGT analysis. After splicing the framework of the selected human germline cells with the antibody's CDR, the designed humanized antibody and the framework sequences of the original antibody were aligned. Based on the results of the homology modeling analysis of the parent antibody, amino acids similar to the surface residues of the human antibody were selected and substituted, while antibody activity was maintained and heterogeneity was minimized. Post-translational modification (PTM) hotspots in the variable region were altered to reduce the risk of PTM. After validating the template sequence and codon optimization, the heavy chain variable region sequence was synthesized and constructed into the pCDNA3.4-uIgG1 plasmid containing human heavy chain CH1, hinge, CH2, and CH3 fragments. The pCDNA3.4-uIgG1 plasmid was obtained by ligating the nucleic acid encoding the heavy chain constant region fragment (GenBank: QBK47475.1 Seq145-474) to the backbone plasmid pCDNA3.4. The light chain variable region sequence was synthesized and constructed into the plasmid pCDNA3.4-IgKc containing the human light chain constant region fragment. The constructed plasmids had the same constant region but contained different site mutations in the heavy chain variable region and the light chain variable region. [Table 6-1] [Table 6-2]

[0366] 3.2 Production of humanized antibodies Expi293F cells were co-transfected with the pCDNA3.4 plasmid containing the heavy chain variable region (VH) and light chain variable region (VL) genes of the antibody. After culturing the cells for 6 days, the supernatant was collected. The supernatant was automatically loaded onto a Protein A (MabSelect SuRe, GE-17543804) affinity chromatography column using an AKTA sample injection system. After sample loading, the column was washed with 0.1 M Tris-HCl, pH 7.0 equilibration buffer, and then the target protein was eluted and recovered with 0.1 M glycine, pH 3.5 elution buffer. The sequences of the resulting humanized antibodies are shown in Tables 6, 7, and 8. cAb1-z0-p7, cAb1-z3-p7, and cAb1-z5-p7 are humanized sequences of 48-B4-F4-E4 (also known as cAb1-uIgG1K). cAb2-z0-p9, cAb2-z1-p9, cAb2-z2-p6, cAb2-z3-p6, cAb2-z4-p6, and cAb2-z5-p6 are humanized sequences of 28-B1-E8-C11. [Table 7-1] [Table 7-2] [Table 8-1] [Table 8-2] [Table 8-3] [Table 9-1] [Table 9-2] [Table 9-3] [Table 10-1] [Table 10-2] [Table 10-3] [Table 10-4] [Table 11-1] [Table 11-2] [Table 11-3] [Table 11-4] [Table 11-5] [Table 11-6]

[0367] Example 4: Characterization of humanized antibodies 4.1 Affinity validation of humanized antibodies - FACS binding NCI-H446 cells 1 × 10 5The cells were transferred to a 96-well U-bottom plate at a cell / well density, centrifuged, and the supernatant was removed. The prepared test supernatant was diluted to 146 μg / mL with 1XPBS + 1% BSA, and then serially diluted 5-fold. The diluted solution was added to the centrifuged 96-well plate and incubated at 4°C for 1 hour. Subsequently, the cells were washed twice with 1XPBS + 1% BSA, resuspended in 100 μL of the prepared secondary antibody (goat anti-human Fc, 1:100 dilution), and incubated in the dark at 4°C for 30 minutes. After washing the cells twice with 1XPBS + 1% BSA, the cells were filtered through a 200-mesh filter and resuspended in 100 μL of 1XPBS + 1% BSA. Fluorescence intensity was measured using a flow cytometer (BD Canto II) and analyzed with FlowJo. EC50 was calculated using GraphPad Prism 5. [Table 12]

[0368] 4.2 Affinity validation of humanized antibodies - SPR The affinity of humanized antibodies to the B7-H3 Human-His antigen was detected using the SPR method with Biacore 8K. Humanized antibodies were captured by anti-human IgG Fc antibodies immobilized on a CM5 chip. Seven sequential dilutions of the analyte B7-H3 Human-His (18.75, 37.5, 75, 150, 300, 600, and 1200 nM) and buffer were flowed through the chip channel at an inflow rate of 30 μL / min, resulting in a binding time of 180 seconds and a dissociation time of 3600 seconds. After each binding and dissociation, the chip surface was regenerated by treatment with 10 mM Glycine-HCl, pH 1.5 buffer. The final binding-dissociation curve is the result of subtracting the reference channel (Fc1) and buffer channel. Dynamic data was obtained by fitting the experimental data to a 1:1 binding model. The results are shown in Table 11. [Table 13]

[0369] 4.3 Detection of the endogenization ability of humanized antibodies - FACS Test antibodies were labeled using the pHAb Amine and Thiol Reactive Dyes kit (Promega, G9845), and their internalization ability in Calu-6 cells and NCI-H446 cells was detected.

[0370] Calu-6 and NCI-H446 cells were revived and passaged at least twice. Cells were harvested when they reached the logarithmic growth phase. Cells were seeded at 1 × 10⁵ cells / well in 24-well cell culture plates and cultured overnight at 37°C and 5% CO₂. The following day, the original medium was replaced with an antibody solution labeled with the pHAb Amine and Thiol Reactive Dyes kit, prepared in cell medium at a concentration of 10 μg / mL. The culture dishes were incubated in an incubator at 37°C for 0, 2, 4, 6, 12, 24, and 48 hours, respectively. After incubation, cells were harvested and the mean fluorescence intensity (MFI) of the PE channel (pHAb dye) was measured on-machine. Integration dynamics analysis was performed using a 4-parameter equation in GraphPad Prism 8.0, plotting a time-MFI curve with time on the x-axis and the mean MFI on the y-axis. The results are shown in Figure 4.

[0371] Endocytosis assay results showed that the candidate antibodies cAb1-z0-p7, cAb1-z3-p7, and cAb1-z5-p7 all exhibited endocytotic effects on Calu-6 and NCI-H446 cells. The cAb1-z5-p7 antibody showed the strongest internalization ability, while the internalization abilities of the cAb1-z0-p7 and cAb1-z3-p7 antibodies were substantially identical.

[0372] 4.4 Species Specificity of Humanized Antibodies - FACS The affinity of humanized antibodies to the B7-H3 Cyno-His antigen was detected using the SPR method with Biacore 8K. Humanized antibodies were captured by anti-human IgG Fc antibodies immobilized on a CM5 chip. Seven serial dilutions of the analyte B7-H3 Cyno-His (18.75 nM, 37.5 nM, 75 nM, 150 nM, 300 nM, 600 nM, and 1200 nM) and buffer were injected into the chip channel at a rate of 30 μL / min, resulting in a binding time of 180 seconds and a dissociation time of 3600 seconds. After each binding and dissociation, the chip surface was regenerated by treatment with 10 mM Glycine-HCl, pH 1.5 buffer. The final binding-dissociation curve is the result of subtracting the reference channel (Fc1) and buffer channel. Dynamic data was obtained by fitting the experimental data to a 1:1 binding model. The results are shown in Table 12. [Table 14]

[0373] Tables 11 and 12 show that the humanized antibody can bind to both human B7-H3 and cynomolgus monkey B7-H3.

[0374] 4.5 Target binding specificity of humanized antibodies - ELISA We selected the following B7-H3 family His-tag antigen proteins from Acro: hB7-H1 (PD-L1), B7-H2, B7-H4, B7-H5, B7-H6, B7-1, B7-2, PD-L2, B7-H7, and Human B7-H3-His (ACRO, CAT#B7B-H52E7). The antigen proteins were diluted to a final concentration of 1 μg / mL with sterile CBS and added at a rate of 100 μL per well to a 96-well plate. After washing three times with PBST (containing 0.5% Tween), 200 μL / well of 3% BSA was added and the plate was blocked at 37°C for 2 hours. After washing, 100 μL of serially diluted test humanized antibodies cAb1-z0-p7, cAb1-z3-p7, and cAb1-z5-p7 (starting concentration 10 μg / mL, 7 points of 5-fold dilution) were added to each well, incubated at room temperature for 1 hour, and washed three times with PBST. 100 μL of HRP-Protein A (1:10000 dilution) was added and incubated at room temperature for 1 hour. After washing with PBST, 100 μL / well of TMB substrate was added. The OD450 values ​​in the wells were read using a microplate reader.

[0375] The results are shown in Figure 5. The results show that the three humanized antibody candidates, cAb1-z0-p7, cAb1-z3-p7, and cAb1-z5-p7, all show strong binding to B7-H3, while not binding to other proteins, indicating binding specificity to B7-H3.

Claims

1. An antibody or antigen-binding fragment that specifically binds to B7-H3, wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), (1) The above VH includes HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 3, and the above VL includes LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 13; (2) The above VH includes HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 26, and the above VL includes LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 27; (3) The above VH includes HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 28, and the above VL includes LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 29; (4) The above VH includes HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 30, and the above VL includes LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 29; (5) The above VH includes HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 22, and the above VL includes LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 23; (6) The above VH includes HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 33, and the above VL includes LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 42; (7) The above VH includes HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 34, and the above VL includes LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 42; (8) The above VH includes HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 33, and the above VL includes LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 41; (9) The above VH includes HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 34, and the above VL includes LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 39; (10) The above VH includes HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 34, and the above VL includes LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 40; (11) The above VH includes HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 34, and the above VL includes LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 41; (12) The above VH includes HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 1, and the above VL includes LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 2; (13) The above VH includes HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 3, and the above VL includes LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 4; (14) The above VH includes HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 5, and the above VL includes LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 6; (15) The above VH includes HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 7, and the above VL includes LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 8; (16) The above VH includes HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 9, and the above VL includes LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 10; (17) The above VH includes HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 11, and the above VL includes LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 12; (18) The above VH includes HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 14, and the above VL includes LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 15; (19) The above VH includes HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 16, and the above VL includes LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 17; (20) The above VH includes HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 18, and the above VL includes LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 19; (21) The above VH includes HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 20, and the above VL includes LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO: 21; or (22) The above VH includes HCDR1, HCDR2, and HCDR3 in the heavy chain variable region having the amino acid sequence described in SEQ ID NO: 24, and the above VL includes LCDR1, LCDR2, and LCDR3 in the light chain variable region having the amino acid sequence described in SEQ ID NO:

25. An antibody or its antigen-binding fragment.

2. (1) The above VH includes HCDR1 described in SEQ ID NO: 84, HCDR2 described in SEQ ID NO: 86, and HCDR3 described in SEQ ID NO: 88, and the above VL includes LCDR1 described in SEQ ID NO: 173, LCDR2 described in SEQ ID NO: 175, and LCDR3 described in SEQ ID NO: 177; (2) The above VH includes HCDR1 described in SEQ ID NO: 84, HCDR2 described in SEQ ID NO: 86, and HCDR3 described in SEQ ID NO: 126, and the above VL includes LCDR1 described in SEQ ID NO: 213, LCDR2 described in SEQ ID NO: 175, and LCDR3 described in SEQ ID NO: 177; (3) The above VH includes HCDR1 described in SEQ ID NO: 111, HCDR2 described in SEQ ID NO: 113, and HCDR3 described in SEQ ID NO: 115, and the above VL includes LCDR1 described in SEQ ID NO: 201, LCDR2 described in amino acid sequence NAK, and LCDR3 described in SEQ ID NO: 205; (4) The above VH includes HCDR1 described in SEQ ID NO: 111, HCDR2 described in SEQ ID NO: 113, and HCDR3 described in SEQ ID NO: 115, and the above VL includes LCDR1 described in SEQ ID NO: 201, LCDR2 described in amino acid sequence NAK, and LCDR3 described in SEQ ID NO: 203; (5) The above VH includes HCDR1 described in SEQ ID NO: 44, HCDR2 described in SEQ ID NO: 46, and HCDR3 described in SEQ ID NO: 48, and the above VL includes LCDR1 described in SEQ ID NO: 135, LCDR2 described in amino acid sequence YAS, and LCDR3 described in SEQ ID NO: 139; (6) The above VH includes HCDR1 described in SEQ ID NO: 51, HCDR2 described in SEQ ID NO: 53, and HCDR3 described in SEQ ID NO: 55, and the above VL includes LCDR1 described in SEQ ID NO: 142, LCDR2 described in amino acid sequence YAS, and LCDR3 described in SEQ ID NO: 145; (7) The above VH includes HCDR1 as described in SEQ ID NO: 58, HCDR2 as described in SEQ ID NO: 60, and HCDR3 as described in SEQ ID NO: 62, and the above VL includes LCDR1 as described in SEQ ID NO: 148, LCDR2 as described in amino acid sequence KVS, and LCDR3 as described in SEQ ID NO: 152; (8) The above VH includes HCDR1 as described in SEQ ID NO: 65, HCDR2 as described in SEQ ID NO: 67, and HCDR3 as described in SEQ ID NO: 69, and the above VL includes LCDR1 as described in SEQ ID NO: 154, LCDR2 as described in amino acid sequence RMS, and LCDR3 as described in SEQ ID NO: 158; (9) The above VH includes HCDR1 as described in SEQ ID NO: 72, HCDR2 as described in SEQ ID NO: 74, and HCDR3 as described in SEQ ID NO: 76, and the above VL includes LCDR1 as described in SEQ ID NO: 160, LCDR2 as described in amino acid sequence GAS, and LCDR3 as described in SEQ ID NO: 164; (10) The above VH includes HCDR1 as described in SEQ ID NO: 79, HCDR2 as described in SEQ ID NO: 81, and HCDR3 as described in SEQ ID NO: 83, and the above VL includes LCDR1 as described in SEQ ID NO: 166, LCDR2 as described in amino acid sequence SGS, and LCDR3 as described in SEQ ID NO: 170; (11) The above VH includes HCDR1 as described in SEQ ID NO: 90, HCDR2 as described in SEQ ID NO: 92, and HCDR3 as described in SEQ ID NO: 94, and the above VL includes LCDR1 as described in SEQ ID NO: 179, LCDR2 as described in amino acid sequence FAS, and LCDR3 as described in SEQ ID NO: 183; (12) The above VH includes HCDR1 as described in SEQ ID NO: 96, HCDR2 as described in SEQ ID NO: 98, and HCDR3 as described in SEQ ID NO: 100, and the above VL includes LCDR1 as described in SEQ ID NO: 185, LCDR2 as described in amino acid sequence KVS, and LCDR3 as described in SEQ ID NO: 186; (13) The above VH includes HCDR1 as described in SEQ ID NO: 101, HCDR2 as described in SEQ ID NO: 102, and HCDR3 as described in SEQ ID NO: 104, and the above VL includes LCDR1 as described in SEQ ID NO: 188, LCDR2 as described in amino acid sequence DTS, and LCDR3 as described in SEQ ID NO: 192; (14) The above VH includes HCDR1 as described in SEQ ID NO: 79, HCDR2 as described in SEQ ID NO: 107, and HCDR3 as described in SEQ ID NO: 109, and the above VL includes LCDR1 as described in SEQ ID NO: 195, LCDR2 as described in amino acid sequence WAS, and LCDR3 as described in SEQ ID NO: 199; or (15) The above VH includes HCDR1 described in SEQ ID NO: 117, HCDR2 described in SEQ ID NO: 119, and HCDR3 described in SEQ ID NO: 121, and the above VL includes LCDR1 described in SEQ ID NO: 208, LCDR2 described in amino acid sequence DTS, and LCDR3 described in SEQ ID NO:

211. The antibody or antigen-binding fragment according to claim 1.

3. (1) The above VH contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 3, and the above VL contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 13; (2) The above VH contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 26, and the above VL contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 27; (3) The above VH contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 28, and the above VL contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 29; (4) The above VH contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 30, and the above VL contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 29; (5) The above VH contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 22, and the above VL contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 23; (6) The above VH contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 33, and the above VL contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 42; (7) The above VH contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 34, and the above VL contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 42; (8) The above VH contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 33, and the above VL contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 41; (9) The above VH contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 34, and the above VL contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 39; (10) The above VH contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 34, and the above VL contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 40; (11) The above VH contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 34, and the above VL contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 41; (12) The above VH contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 1, and the above VL contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 2; (13) The above VH contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 3, and the above VL contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 4; (14) The above VH contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 5, and the above VL contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 6; (15) The above VH contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 7, and the above VL contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 8; (16) The above VH contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 9, and the above VL contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 10; (17) The above VH contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 11, and the above VL contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 12; (18) The above VH contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 14, and the above VL contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 15; (19) The above VH contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 16, and the above VL contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 17; (20) The above VH contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 18, and the above VL contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 19; (21) The above VH contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 20, and the above VL contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 21; or (22) The above VH includes an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 24, and the above VL includes an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

25. The antibody or its antigen-binding fragment according to claim 1 or 2.

4. (1) The above VH includes the amino acid sequence described in SEQ ID NO: 3, and the above VL includes the amino acid sequence described in SEQ ID NO: 13; (2) The above VH includes the amino acid sequence described in SEQ ID NO: 26, and the above VL includes the amino acid sequence described in SEQ ID NO: 27; (3) The above VH includes the amino acid sequence described in SEQ ID NO: 28, and the above VL includes the amino acid sequence described in SEQ ID NO: 29; (4) The above VH includes the amino acid sequence described in SEQ ID NO: 30, and the above VL includes the amino acid sequence described in SEQ ID NO: 29; (5) The above VH includes the amino acid sequence described in SEQ ID NO: 22, and the above VL includes the amino acid sequence described in SEQ ID NO: 23; (6) The above VH includes the amino acid sequence described in SEQ ID NO: 33, and the above VL includes the amino acid sequence described in SEQ ID NO: 42; (7) The above VH includes the amino acid sequence described in SEQ ID NO: 34, and the above VL includes the amino acid sequence described in SEQ ID NO: 42; (8) The above VH includes the amino acid sequence described in SEQ ID NO: 33, and the above VL includes the amino acid sequence described in SEQ ID NO: 41; (9) The above VH includes the amino acid sequence described in SEQ ID NO: 34, and the above VL includes the amino acid sequence described in SEQ ID NO: 39; (10) The above VH includes the amino acid sequence described in SEQ ID NO: 34, and the above VL includes the amino acid sequence described in SEQ ID NO: 40; (11) The above VH includes the amino acid sequence described in SEQ ID NO: 34, and the above VL includes the amino acid sequence described in SEQ ID NO: 41; (12) The above VH includes the amino acid sequence described in SEQ ID NO: 1, and the above VL includes the amino acid sequence described in SEQ ID NO: 2; (13) The above VH includes the amino acid sequence described in SEQ ID NO: 3, and the above VL includes the amino acid sequence described in SEQ ID NO: 4; (14) The above VH includes the amino acid sequence described in SEQ ID NO: 5, and the above VL includes the amino acid sequence described in SEQ ID NO: 6; (15) The above VH includes the amino acid sequence described in SEQ ID NO: 7, and the above VL includes the amino acid sequence described in SEQ ID NO: 8; (16) The above VH includes the amino acid sequence described in SEQ ID NO: 9, and the above VL includes the amino acid sequence described in SEQ ID NO: 10; (17) The above VH includes the amino acid sequence described in SEQ ID NO: 11, and the above VL includes the amino acid sequence described in SEQ ID NO: 12; (18) The above VH includes the amino acid sequence described in SEQ ID NO: 14, and the above VL includes the amino acid sequence described in SEQ ID NO: 15; (19) The above VH includes the amino acid sequence described in SEQ ID NO: 16, and the above VL includes the amino acid sequence described in SEQ ID NO: 17; (20) The above VH includes the amino acid sequence described in SEQ ID NO: 18, and the above VL includes the amino acid sequence described in SEQ ID NO: 19; (21) The above VH includes the amino acid sequence described in SEQ ID NO: 20, and the above VL includes the amino acid sequence described in SEQ ID NO: 21; or (22) The above VH includes the amino acid sequence described in SEQ ID NO: 24, and the above VL includes the amino acid sequence described in SEQ ID NO:

25. The antibody or antigen-binding fragment according to claim 3.

5. The antibody or its antigen-binding fragment according to any one of claims 1 to 4, wherein the antibody is a mouse antibody, a chimeric antibody, a humanized antibody, or a human antibody.

6. The antibody or its antigen-binding fragment according to any one of claims 1 to 5, wherein the antibody is an isotype selected from the group consisting of IgG, IgA, IgM, IgE, and IgD.

7. The antibody or its antigen-binding fragment according to any one of claims 1 to 6, wherein the antibody is a subtype selected from the group consisting of IgG1, IgG2, IgG3, and IgG4.

8. The antibody or antigen-binding fragment according to any one of claims 1 to 7, wherein the antigen-binding fragment is selected from the group consisting of Fab, Fab', F(ab')2, Fv, scFv, and ds-scFv.

9. The antibody or its antigen-binding fragment according to any one of claims 1 to 8, wherein the antibody is a monoclonal antibody.

10. The above antibody includes a light chain and a heavy chain. (1) The heavy chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 230, and the light chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 231; (2) The heavy chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 248, and the light chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 249; (3) The heavy chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 250, and the light chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 251; (4) The heavy chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 252, and the light chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 251; (5) The heavy chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 240, and the light chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 241; (6) The heavy chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 255, and the light chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 264; (7) The heavy chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 256, and the light chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 264; (8) The heavy chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 255, and the light chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 263; (9) The heavy chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 256, and the light chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 261; (10) The heavy chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 256, and the light chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 262; (11) The heavy chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 256, and the light chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 263; (12) The heavy chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 218, and the light chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 219; (13) The heavy chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 220, and the light chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 221; (14) The heavy chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 222, and the light chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 223; (15) The heavy chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 224, and the light chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 225; (16) The heavy chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 226, and the light chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 227; (17) The heavy chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 228, and the light chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 229; (18) The heavy chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 232, and the light chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 233; (19) The heavy chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 234, and the light chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 235; (20) The heavy chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 236, and the light chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 237; (21) The heavy chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 238, and the light chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 239; or (22) The heavy chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 242, and the light chain contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 243, The antibody or antigen-binding fragment according to claim 9.

11. The antibody or its antigen-binding fragment according to any one of claims 1 to 10, wherein the antibody is a bispecific antibody or a multispecific antibody.

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

13. A vector comprising the nucleic acid according to claim 12.

14. A host cell comprising the nucleic acid described in claim 12 or the vector described in claim 13.

15. (i) an antibody or antigen-binding fragment according to any one of claims 1 to 11, a nucleic acid according to claim 12, a vector according to claim 13, or a host cell according to claim 14, and (ii) a pharmaceutically acceptable carrier or excipient.

16. The pharmaceutical composition according to claim 15, further comprising a second therapeutic agent.

17. The pharmaceutical composition according to claim 16, wherein the second therapeutic agent is selected from the group consisting of cytokines, antibodies, chemotherapeutic agents, and small molecule drugs.

18. A complex comprising an antibody or its antigen-binding fragment according to any one of claims 1 to 11, and a chemical portion bound thereto.

19. The complex according to claim 18, wherein the above chemical portion is selected from the group consisting of a therapeutic agent, a detectable portion, and an immunostimulatory molecule.

20. Use of an antibody or antigen-binding fragment according to any one of claims 1 to 11, a nucleic acid according to claim 12, a vector according to claim 13, or a host cell according to claim 14, a pharmaceutical composition according to any one of claims 15 to 17, or a complex according to claim 18 or 19, in the manufacture of a pharmaceutical for treating a target cancer, wherein the cancer is a B7-H3 positive cancer.

21. The cancers listed above include adrenal tumors, AIDS-related cancers, hydatidiform soft part sarcomas, astrocytomas, adrenal cancers, bladder cancers, bone cancers, brain and spinal cord cancers, metastatic brain tumors, B-cell carcinomas, breast cancers, carotid bulb tumors, cervical cancers, chondrosarcomas, chordomas, chromophobe renal cell carcinomas, clear cell carcinomas, colon cancers, colorectal cancers, benign fibrous histiocytomas, fibrinogenic round cell tumors, ependymomas, Ewing's tumors, extraskeletal myxoid chondrosarcomas, fibrous dysplasia, fibrous dysplasia, gallbladder or bile duct cancers, gastric cancers, gestational trophoblastic disease, germ cell tumors, head and neck cancers, hepatocellular carcinomas, islet cell tumors, Kaposi's sarcoma, kidney cancers, leukemias, and adipose tissue cancers. The use according to claim 20, selected from the group consisting of sarcoma / malignant lipomatous tumor, liver cancer, lymphoma, lung cancer, medulloblastoma, melanoma, meningioma, multiple endocrine neoplasia, multiple myeloma, myelodysplastic syndrome, neuroblastoma, neuroendocrine tumor, ovarian cancer, pancreatic cancer, papillary thyroid cancer, parathyroid tumor, childhood cancer, peripheral nerve sheath tumor, pheochromocytoma, pituitary tumor, prostate cancer, posterior uveal melanoma, renal metastasis, rhabdoid tumor, rhabdomyosarcoma, sarcoma, skin cancer, soft tissue sarcoma, squamous cell carcinoma, gastric cancer, synovial sarcoma, testicular cancer, thymic cancer, thymoma, metastatic thyroid cancer, and uterine cancer.

22. The use according to claim 20 or 21, wherein the above-mentioned drug is used in combination with a second therapeutic agent.

23. The use according to claim 22, wherein the second therapeutic agent is selected from the group consisting of cytokines, antibodies, chemotherapeutic agents, and small molecule drugs.

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