Antibodies binding b7-h3 and uses thereof

Abstract

The present application provides anti-B7-H3 monoclonal antibodies, in particular, high affinity B7-H3 humanized monoclonal antibodies having cross-activity with humans, cynomolgus monkeys and mice, as well as nucleic acids encoding the antibodies, vectors comprising the nucleic acids, and host cells comprising the nucleic acids or vectors. Also disclosed are pharmaceutical compositions and conjugates comprising the antibodies, as well as methods of treatment using the antibodies.

Description

Antibodies that bind to B7-H3 and their uses Field of the Invention

[0001] The present invention relates to the field of biomedicine, and in particular to antibodies binding to B7-H3 and their use in cancer treatment. Background Art

[0002] B7-H3 (CD276), a member of the B7 family of proteins, plays a key role in cancer development. As a target of immune checkpoints, B7-H3 is selectively expressed in tumor cells and immune cells within the tumor microenvironment, participating in tumor cell proliferation and metastasis and associated with treatment resistance. B7-H3 protein expression levels vary significantly between normal and tumor tissues. B7-H3 is highly expressed in various tumor tissues, such as prostate cancer, pancreatic cancer, and hepatocellular carcinoma, but rarely expressed in normal tissues (Zhou WT, Jin WL. B7-H3 / CD276: An Emerging Cancer Immunotherapy. Front Immunol. 2021;12:701006.). By exploiting this property, drugs targeting B7-H3 can specifically kill cancer tissue while minimizing damage to healthy cells. These properties make B7-H3 a promising target for cancer therapy.

[0003] Summary of the Invention

[0004] The present disclosure provides novel antibodies or antigen-binding fragments thereof that target B7-H3.

[0005] In a first aspect, the present disclosure provides an antibody or antigen-binding fragment thereof that specifically binds to B7-H3, wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL).

[0006] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 3, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 13.

[0007] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 26, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 27.

[0008] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 28, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 29.

[0009] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 30, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 29.

[0010] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 22, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 23.

[0011] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 33, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 42.

[0012] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 34, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 42.

[0013] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 33, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 41.

[0014] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 34, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 39.

[0015] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 34, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 40.

[0016] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 34, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 41.

[0017] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 1, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 2.

[0018] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 3, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 4.

[0019] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 5, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 6.

[0020] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 7, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 8.

[0021] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 9, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 10.

[0022] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 11, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 12.

[0023] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 14, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 15.

[0024] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 16, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 17.

[0025] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 18, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 19.

[0026] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 20, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 21.

[0027] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 24, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 25.

[0028] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises HCDR1 as set forth in SEQ ID NO:84, HCDR2 as set forth in SEQ ID NO:86, and HCDR3 as set forth in SEQ ID NO:88, and the VL comprises LCDR1 as set forth in SEQ ID NO:173, LCDR2 as set forth in SEQ ID NO:175, and LCDR3 as set forth in SEQ ID NO:177.

[0029] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), the VH comprising HCDR1 as set forth in SEQ ID NO:84, HCDR2 as set forth in SEQ ID NO:86, and HCDR3 as set forth in SEQ ID NO:126, and the VL comprising LCDR1 as set forth in SEQ ID NO:213, LCDR2 as set forth in SEQ ID NO:175, and LCDR3 as set forth in SEQ ID NO:177.

[0030] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), the VH comprising HCDR1 as set forth in SEQ ID NO: 111, HCDR2 as set forth in SEQ ID NO: 113, and HCDR3 as set forth in SEQ ID NO: 115, and the VL comprising LCDR1 as set forth in SEQ ID NO: 201, LCDR2 as set forth in the amino acid sequence NAK, and LCDR3 as set forth in SEQ ID NO: 205.

[0031] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), the VH comprising HCDR1 as set forth in SEQ ID NO: 111, HCDR2 as set forth in SEQ ID NO: 113, and HCDR3 as set forth in SEQ ID NO: 115, and the VL comprising LCDR1 as set forth in SEQ ID NO: 201, LCDR2 as set forth in the amino acid sequence NAK, and LCDR3 as set forth in SEQ ID NO: 203.

[0032] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), the VH comprising HCDR1 as set forth in SEQ ID NO:44, HCDR2 as set forth in SEQ ID NO:46, and HCDR3 as set forth in SEQ ID NO:48, and the VL comprising LCDR1 as set forth in SEQ ID NO:135, LCDR2 as set forth in the amino acid sequence YAS, and LCDR3 as set forth in SEQ ID NO:139.

[0033] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), the VH comprising HCDR1 as set forth in SEQ ID NO: 51, HCDR2 as set forth in SEQ ID NO: 53, and HCDR3 as set forth in SEQ ID NO: 55, and the VL comprising LCDR1 as set forth in SEQ ID NO: 142, LCDR2 as set forth in the amino acid sequence YAS, and LCDR3 as set forth in SEQ ID NO: 145.

[0034] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), the VH comprising HCDR1 as set forth in SEQ ID NO: 58, HCDR2 as set forth in SEQ ID NO: 60, and HCDR3 as set forth in SEQ ID NO: 62, and the VL comprising LCDR1 as set forth in SEQ ID NO: 148, LCDR2 as set forth in the amino acid sequence KVS, and LCDR3 as set forth in SEQ ID NO: 152.

[0035] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), the VH comprising HCDR1 as set forth in SEQ ID NO: 65, HCDR2 as set forth in SEQ ID NO: 67, and HCDR3 as set forth in SEQ ID NO: 69, and the VL comprising LCDR1 as set forth in SEQ ID NO: 154, LCDR2 as set forth in the amino acid sequence RMS, and LCDR3 as set forth in SEQ ID NO: 158.

[0036] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), the VH comprising HCDR1 as set forth in SEQ ID NO: 72, HCDR2 as set forth in SEQ ID NO: 74, and HCDR3 as set forth in SEQ ID NO: 76, and the VL comprising LCDR1 as set forth in SEQ ID NO: 160, LCDR2 as set forth in the amino acid sequence GAS, and LCDR3 as set forth in SEQ ID NO: 164.

[0037] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), the VH comprising HCDR1 as set forth in SEQ ID NO: 79, HCDR2 as set forth in SEQ ID NO: 81, and HCDR3 as set forth in SEQ ID NO: 83, and the VL comprising LCDR1 as set forth in SEQ ID NO: 166, LCDR2 as set forth in the amino acid sequence SGS, and LCDR3 as set forth in SEQ ID NO: 170.

[0038] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), the VH comprising HCDR1 as set forth in SEQ ID NO:90, HCDR2 as set forth in SEQ ID NO:92, and HCDR3 as set forth in SEQ ID NO:94, and the VL comprising LCDR1 as set forth in SEQ ID NO:179, LCDR2 as set forth in the amino acid sequence FAS, and LCDR3 as set forth in SEQ ID NO:183.

[0039] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), the VH comprising HCDR1 as set forth in SEQ ID NO:96, HCDR2 as set forth in SEQ ID NO:98, and HCDR3 as set forth in SEQ ID NO:100, and the VL comprising LCDR1 as set forth in SEQ ID NO:185, LCDR2 as set forth in the amino acid sequence KVS, and LCDR3 as set forth in SEQ ID NO:186.

[0040] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), the VH comprising HCDR1 as set forth in SEQ ID NO: 101, HCDR2 as set forth in SEQ ID NO: 102, and HCDR3 as set forth in SEQ ID NO: 104, and the VL comprising LCDR1 as set forth in SEQ ID NO: 188, LCDR2 as set forth in the amino acid sequence DTS, and LCDR3 as set forth in SEQ ID NO: 192.

[0041] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), the VH comprising HCDR1 as set forth in SEQ ID NO: 79, HCDR2 as set forth in SEQ ID NO: 107, and HCDR3 as set forth in SEQ ID NO: 109, and the VL comprising LCDR1 as set forth in SEQ ID NO: 195, LCDR2 as set forth in the amino acid sequence WAS, and LCDR3 as set forth in SEQ ID NO: 199.

[0042] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), the VH comprising HCDR1 as set forth in SEQ ID NO: 117, HCDR2 as set forth in SEQ ID NO: 119, and HCDR3 as set forth in SEQ ID NO: 121, and the VL comprising LCDR1 as set forth in SEQ ID NO: 208, LCDR2 as set forth in the amino acid sequence DTS, and LCDR3 as set forth in SEQ ID NO: 211.

[0043] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 13.

[0044] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 27.

[0045] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 29.

[0046] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 29.

[0047] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 23.

[0048] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 42.

[0049] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 42.

[0050] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 41.

[0051] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 39.

[0052] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 40.

[0053] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 41.

[0054] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 2.

[0055] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO:4.

[0056] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO:6.

[0057] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO:8.

[0058] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 10.

[0059] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 12.

[0060] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 15.

[0061] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 17.

[0062] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 19.

[0063] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 21.

[0064] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 25.

[0065] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 3, and the VL comprises the amino acid sequence shown in SEQ ID NO: 13.

[0066] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 26, and the VL comprises the amino acid sequence shown in SEQ ID NO: 27.

[0067] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 28, and the VL comprises the amino acid sequence shown in SEQ ID NO: 29.

[0068] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 30, and the VL comprises the amino acid sequence shown in SEQ ID NO: 29.

[0069] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 22, and the VL comprises the amino acid sequence shown in SEQ ID NO: 23.

[0070] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 33, and the VL comprises the amino acid sequence shown in SEQ ID NO: 42.

[0071] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 34, and the VL comprises the amino acid sequence shown in SEQ ID NO: 42.

[0072] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 33, and the VL comprises the amino acid sequence shown in SEQ ID NO: 41.

[0073] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 34, and the VL comprises the amino acid sequence shown in SEQ ID NO: 39.

[0074] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 34, and the VL comprises the amino acid sequence shown in SEQ ID NO: 40.

[0075] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 34, and the VL comprises the amino acid sequence shown in SEQ ID NO: 41.

[0076] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 1, and the VL comprises the amino acid sequence shown in SEQ ID NO: 2.

[0077] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 3, and the VL comprises the amino acid sequence shown in SEQ ID NO: 4.

[0078] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 5, and the VL comprises the amino acid sequence shown in SEQ ID NO: 6.

[0079] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 7, and the VL comprises the amino acid sequence shown in SEQ ID NO: 8.

[0080] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 9, and the VL comprises the amino acid sequence shown in SEQ ID NO: 10.

[0081] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 11, and the VL comprises the amino acid sequence shown in SEQ ID NO: 12.

[0082] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 14, and the VL comprises the amino acid sequence shown in SEQ ID NO: 15.

[0083] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 16, and the VL comprises the amino acid sequence shown in SEQ ID NO: 17.

[0084] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 18, and the VL comprises the amino acid sequence shown in SEQ ID NO: 19.

[0085] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 20, and the VL comprises the amino acid sequence shown in SEQ ID NO: 21.

[0086] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 24, and the VL comprises the amino acid sequence shown in SEQ ID NO: 25.

[0087] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the antibody is a murine antibody, a chimeric antibody, a humanized antibody, or a human antibody.

[0088] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the antibody is of an isotype selected from IgG, IgA, IgM, IgE, and IgD.

[0089] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the antibody is of a subtype selected from IgG1, IgG2, IgG3, and IgG4.

[0090] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the antigen-binding fragment is selected from the group consisting of Fab, Fab', F(ab')2, Fv, scFv, and ds-scFv.

[0091] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the antibody is a monoclonal antibody.

[0092] In some embodiments of the antibodies or antigen-binding fragments thereof 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 to 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 to SEQ ID NO: 231.

[0093] In some embodiments of the antibodies or antigen-binding fragments thereof 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 to 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 to SEQ ID NO: 249.

[0094] In some embodiments of the antibodies or antigen-binding fragments thereof 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 to 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 to SEQ ID NO: 251;

[0095] In some embodiments of the antibodies or antigen-binding fragments thereof 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 to 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 to SEQ ID NO: 251.

[0096] In some embodiments of the antibodies or antigen-binding fragments thereof 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 to 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 to SEQ ID NO: 241.

[0097] In some embodiments of the antibodies or antigen-binding fragments thereof 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 to 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 to SEQ ID NO: 264.

[0098] In some embodiments of the antibodies or antigen-binding fragments thereof 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 to 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 to SEQ ID NO: 264.

[0099] In some embodiments of the antibodies or antigen-binding fragments thereof 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 to 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 to SEQ ID NO: 263.

[0100] In some embodiments of the antibodies or antigen-binding fragments thereof 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 to 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 to SEQ ID NO: 261.

[0101] In some embodiments of the antibodies or antigen-binding fragments thereof 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 to 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 to SEQ ID NO: 262.

[0102] In some embodiments of the antibodies or antigen-binding fragments thereof 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 to 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 to SEQ ID NO: 263.

[0103] In some embodiments of the antibodies or antigen-binding fragments thereof 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 to 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 to SEQ ID NO: 219.

[0104] In some embodiments of the antibodies or antigen-binding fragments thereof 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 to 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 to SEQ ID NO: 221.

[0105] In some embodiments of the antibodies or antigen-binding fragments thereof 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 to 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 to SEQ ID NO: 223.

[0106] In some embodiments of the antibodies or antigen-binding fragments thereof 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 to 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 to SEQ ID NO: 225.

[0107] In some embodiments of the antibodies or antigen-binding fragments thereof 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 to 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 to SEQ ID NO: 227.

[0108] In some embodiments of the antibodies or antigen-binding fragments thereof 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 to 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 to SEQ ID NO: 229.

[0109] In some embodiments of the antibodies or antigen-binding fragments thereof 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 to 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 to SEQ ID NO: 233.

[0110] In some embodiments of the antibodies or antigen-binding fragments thereof 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 to 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 to SEQ ID NO: 235.

[0111] In some embodiments of the antibodies or antigen-binding fragments thereof 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 to 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 to SEQ ID NO: 237.

[0112] In some embodiments of the antibodies or antigen-binding fragments thereof 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 to 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 to SEQ ID NO: 239.

[0113] In some embodiments of the antibodies or antigen-binding fragments thereof 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 to 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 to SEQ ID NO: 243.

[0114] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the antibody is a bispecific antibody or a multispecific antibody.

[0115] In a second aspect, the present disclosure provides a nucleic acid encoding the antibody or antigen-binding fragment thereof according to the first aspect of the present disclosure.

[0116] In a third aspect, the present disclosure provides a vector comprising the nucleic acid according to the second aspect of the present disclosure.

[0117] In a fourth aspect, the present disclosure provides a host cell comprising the nucleic acid according to the second aspect of the present disclosure or the vector according to the third aspect of the present disclosure.

[0118] In a fifth aspect, the present disclosure provides a pharmaceutical composition comprising (i) the antibody or antigen-binding fragment thereof described in the first aspect of the disclosure, the nucleic acid described in the second aspect of the disclosure, the vector described in the third aspect of the disclosure, or the host cell described in the fourth aspect of the disclosure; and (ii) a pharmaceutically acceptable carrier or excipient. In some embodiments of the pharmaceutical composition disclosed herein, the composition further comprises a second therapeutic agent. In some embodiments of the pharmaceutical composition disclosed herein, the composition further comprises a second therapeutic agent selected from a cytokine, an antibody, a chemotherapeutic agent, and a small molecule drug.

[0119] In a sixth aspect, the present disclosure provides a conjugate comprising the antibody or antigen-binding fragment thereof of the first aspect of the present disclosure, and a chemical moiety conjugated thereto. In some embodiments of the conjugates disclosed herein, the chemical moiety conjugated to the antibody or antigen-binding fragment is selected from a therapeutic agent, a detectable moiety, and an immunostimulatory molecule.

[0120] In the seventh aspect, the present disclosure provides the use of the antibody or antigen-binding fragment thereof of the first aspect of the present disclosure, the nucleic acid of the second aspect of the present disclosure, the vector of the third aspect of the present disclosure, or the host cell of the fourth aspect of the present disclosure, the pharmaceutical composition of the fifth aspect of the present disclosure, or the conjugate of the sixth aspect of the present disclosure in the preparation of a medicament for treating cancer in a subject. In some embodiments, the cancer is a B7-H3 positive cancer. In some embodiments of the uses disclosed herein, the cancer is selected from the group consisting of: adrenal tumors, AIDS-related cancers, alveolar sarcomas of soft tissue, astrocytomas, adrenal cancer, bladder cancer, bone cancer, brain and spinal cord cancer, metastatic brain tumors, B Cell carcinoma, breast cancer, carotid body tumor, cervical cancer, chondrosarcoma, chordoma, chromophobe renal cell carcinoma, clear cell carcinoma, colon cancer, colorectal cancer, benign fibrous histiocytoma of the skin, desmoplastic small round cell tumor, ependymoma, Ewing's tumor, extraskeletal myxoid chondrosarcoma, incomplete fibroplasia of bone, fibrous dysplasia of bone, gallbladder cancer or bile duct cancer, gastric cancer, gestational trophoblastic disease, germ cell tumor, head and neck cancer, hepatocellular carcinoma, pancreatic islet cell tumor, cardiomyopathy, Boss's sarcoma, renal cancer, leukemia, liposarcoma / malignant lipoma, 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, pediatric cancer, peripheral nerve sheath tumor, pheochromocytoma, pituitary tumor, prostate cancer, posterious uveal melanoma, metastatic renal cancer, 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 uses disclosed herein, wherein the drug is combined with a second therapeutic agent. In some embodiments of the uses disclosed herein, wherein the second therapeutic agent is selected from cytokines, antibodies, chemotherapeutic agents and small molecule drugs.

[0121] In an eighth aspect, the present disclosure provides a method for treating cancer in a subject, comprising administering to the subject an effective amount of the antibody or antigen-binding fragment thereof of the first aspect of the present disclosure, the nucleic acid of the second aspect of the present disclosure, the vector of the third aspect of the present disclosure, or the host cell of the fourth aspect of the present disclosure, the pharmaceutical composition of the fifth aspect of the present disclosure, or the conjugate of the sixth aspect of the present disclosure. In some embodiments, the cancer is a B7-H3 positive cancer. In some embodiments of the uses disclosed herein, the cancer is selected from the group consisting of: adrenal tumors, AIDS-related cancers, soft tissue alveolar sarcomas, astrocytomas, adrenal cancer, bladder cancer, bone cancer, brain and spinal cord cancer, metastatic brain tumors, B cell cancer, breast cancer, carotid body tumors, cervical cancer, chondrosarcomas, chordomas, chromophobe renal cell carcinomas, clear cell carcinomas, colon cancer, colorectal cancer, benign fibrous histiocytoma of the skin, desmoplastic small round cell tumors, ependymomas, Ewing's tumors, extraskeletal myxoid chondrosarcomas, incomplete fibroplasia of bone, fibroplasia of bone In some embodiments of the invention, the drug is combined with a second therapeutic agent. In some embodiments of the uses disclosed herein, the second therapeutic agent is selected from the group consisting of a cytokine, an antibody, a chemotherapeutic agent, and a small molecule drug.

[0122] In the ninth aspect, the present disclosure provides the antibody or antigen-binding fragment thereof of the first aspect of the present disclosure, the nucleic acid of the second aspect of the present disclosure, the vector of the third aspect of the present disclosure, or the host cell of the fourth aspect of the present disclosure, the pharmaceutical composition of the fifth aspect of the present disclosure, or the conjugate of the sixth aspect of the present disclosure for treating cancer in a subject. In some embodiments, the cancer is a B7-H3 positive cancer. In some embodiments of the use disclosed herein, the cancer is selected from the group consisting of: adrenal tumors, AIDS-related cancers, soft tissue alveolar sarcomas, astrocytomas, adrenal cancer, bladder cancer, bone cancer, brain and spinal cord cancer, metastatic brain tumors, B cell cancer, breast cancer, carotid body tumors, cervical cancer, chondrosarcomas, chordomas, chromophobe renal cell carcinomas, clear cell carcinomas, colon cancer, colorectal cancer, benign fibrous histiocytoma of the skin, desmoplastic small round cell tumors, ependymomas, Ewing's tumors, extraskeletal myxoid chondrosarcomas, incomplete fibroplasia of bone, fibroplasia of bone In some embodiments of the invention, the drug is combined with a second therapeutic agent. In some embodiments of the uses disclosed herein, the second therapeutic agent is selected from the group consisting of a cytokine, an antibody, a chemotherapeutic agent, and a small molecule drug. BRIEF DESCRIPTION OF THE DRAWINGS

[0123] An understanding of the features and advantages of the present invention may be obtained by reference to the following detailed description of exemplary embodiments and the accompanying drawings as shown, which utilize the principles of the invention:

[0124] Figure 1 shows the binding ability of the chimeric antibody to CHO-S-human-B7-H3 cells (Figure 1A), CHO-S-Cyno-B7-H3 cells (Figure 1B), CHO-S-mouse-B7-H3 (Figure 1C), and CHO-S cells (Figure 1D).

[0125] FIG2 shows the internalization efficiency of chimeric antibodies in Calu-6 cells.

[0126] FIG3 shows the internalization efficiency of chimeric antibodies in NCI-H446 cells.

[0127] FIG4 shows the internalization ability of humanized antibodies in Calu-6 cells ( FIG4B ) and NCI-H446 cells ( FIG4A ).

[0128] Figure 5 shows the binding activity of humanized antibodies cAb1-z0-p7 (Figure 5A), cAb1-z3-p7 (Figure 5B) and cAb1-z3-p7 (Figure 5C) to 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. DETAILED DESCRIPTION

[0129] The above features and advantages of the present invention and additional features and advantages will be more clearly understood from the following detailed description of embodiments taken in conjunction with the accompanying drawings.

[0130] The embodiments described herein with reference to the accompanying drawings are illustrative, exemplary, and are used for a general understanding of the present invention. The embodiments should not be construed as limiting the scope of the present invention. Identical or similar elements and elements with identical or similar functions are represented by the same reference numerals throughout the specification.

[0131] Unless otherwise mentioned or defined, all terms used have the ordinary meaning in the art that is clear to those skilled in the art. Reference is made, for example, to standard manuals, such as Leuenberger, HGW, Nagel, B. and Klbl, H. eds., "A mμltilingual 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 molecμlar biology", Green Publishing and Wiley InterScience, New York (1987); Roitt et al., "Immunology (6th Ed.), Mosby / Elsevier, Edinburgh (2001); and Janeway et al., "Immunobiology" (6th Ed.), Garland Science Publishing / Churchill Livingstone, New York (2005), and the general background art cited above.

[0132] definition

[0133] As used herein, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "an antibody" includes a plurality of antibodies and in some embodiments, reference to "an antibody" includes a plurality of antibodies, and so forth.

[0134] Unless otherwise stated or defined, the term “comprise” and variations such as “include” and “comprising” will be understood to imply the inclusion of stated elements or steps or groups of elements or steps but not the exclusion of any other elements or steps or groups of elements or steps.

[0135] As used herein, the term "antibody" refers to an immunoglobulin molecule that has the ability to specifically bind to a specific antigen. Such molecules typically comprise two heavy (H) chains and two light (L) chains interconnected by disulfide bonds. Each heavy chain consists of a heavy chain variable region (or domain) (abbreviated herein 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 (or domain) (abbreviated herein 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 a binding domain that interacts with an antigen. The constant region of an antibody can mediate the binding of an 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).

[0136] The heavy chain of an immunoglobulin can be divided into three functional regions: the Fd region, the hinge region, and the Fc region (crystallizable fragment). The Fd region comprises the VH and CH1 domains and combines with the light chain to form the Fab (antigen binding fragment). The Fc fragment is responsible for immunoglobulin effector functions, including, for example, complement fixation and binding to the cognate Fc receptors of effector cells. The hinge region found in 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 different sequences and lengths between immunoglobulin classes and subclasses.

[0137] Based on crystallographic studies, the immunoglobulin hinge region can be further subdivided into three regions in terms of structure and function: the upper hinge, the core hinge, and the lower hinge. The upper hinge encompasses the amino acids from the carboxyl terminus of CH1 to the first residue in the hinge that restricts movement, typically the first cysteine ​​residue that forms an interchain disulfide bond between the two heavy chains. The length of the upper hinge region is associated with the fragment flexibility of the antibody. The core hinge region contains inter-heavy chain disulfide bonds. The lower hinge region connects to the amino terminus of the CH2 domain and includes residues within the CH2 domain. The conformational changes permitted by the structure and flexibility of the immunoglobulin hinge region polypeptide sequence can influence the effector functions of the antibody Fc portion.

[0138] A "light chain variable region" (VL) or "heavy chain variable region" (VH) consists of a "framework" region separated by three "complementarity determining regions" or "CDRs." The framework regions serve to align the CDRs that specifically bind to an antigenic epitope. The CDRs include the amino acid residues in the antibody that are primarily responsible for antigen binding. Both the VL and VH domains comprise the following framework (FR) and CDR regions from amino-terminus to carboxyl-terminus: FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4. The CDR1, CDR2, and CDR3 of the VL domain are also referred to herein as LCDR1, LCDR2, and LCDR3, respectively; the CDR1, CDR2, and CDR3 of the VH domain are also referred to herein as HCDR1, HCDR2, and HCDR3, respectively.

[0139] The amino acid arrangement of each VL domain and VH domain is consistent with any conventional definition of CDR. 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); a composite of the Chothia Kabat CDR, wherein CDR-H1 is a composite of the Chothia CDR and the Kabat CDR; the AbM definition used by Oxford Molecule's antibody modeling software; and the CONTACT definition of Martin et al. (world wide web bioinfo.org.uk / abs). Kabat provides a widely used numbering convention (Kabat numbering system), in which corresponding residues between different heavy chains or between different light chains are given the same number. The present disclosure may utilize CDRs defined according to any of these numbering systems, but preferred embodiments utilize the Kabat defined CDRs.

[0140] Based on the amino acid sequence of the constant region of the antibody heavy chain, immunoglobulin molecules can be divided into five classes (isotypes): IgA, IgD, IgE, IgG, and IgM, and can be further divided into different subtypes, such as IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, etc. Based on the amino acid sequence of the light chain, the light chain of the antibody can be divided into lambda (λ) chain and kappa (κ) chain.

[0141] As used herein, the term "antibody" should be understood in its broadest sense and includes monoclonal antibodies (including full-length monoclonal antibodies), polyclonal antibodies, antibody fragments, and multispecific antibodies (e.g., bispecific antibodies) containing at least two antigen-binding regions. Antibodies may contain additional modifications, such as non-naturally occurring 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 to antigen recognition sites, as long as these antibodies exhibit the desired biological activity.

[0142] As used herein, the term "monoclonal antibody" refers to an antibody obtained from a substantially homogeneous population of antibodies. That is, except for a small number of naturally occurring mutations, each antibody comprising the population is identical. Monoclonal antibodies are highly specific and are directed against a single antigen. The term "monoclonal antibody" herein is not limited to antibodies produced by hybridoma technology, nor should it be construed as requiring antibodies produced by any particular method.

[0143] The term "bispecific antibody" should be understood in the context of the present invention as an antibody having two different antigen-binding regions defined by different antibody sequences. This can be understood as binding to different targets, but also includes binding to different epitopes of a target. The term "bispecific antibody" as used herein should be understood in its broadest sense, including full-length bispecific antibodies and antigen-binding fragments thereof. Bispecific antibodies may contain additional modifications, such as non-naturally occurring amino acids, mutations in the Fc region, and mutations in glycosylation sites. Bispecific antibodies also include post-translationally modified antibodies, fusion proteins containing the antigenic determinants of antibodies, and immunoglobulin molecules containing any other modifications to the antigen recognition site, as long as these antibodies exhibit the desired biological activity.

[0144] As used herein, 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 has been shown that the antigen-binding function of an antibody can be performed by fragments of a full-length antibody.

[0145] Examples of antigen-binding fragments encompassed by the term "antigen-binding portion" of an antibody include: (i) a Fab fragment, a monovalent fragment consisting of the VL, VH, CL and CH1 domains; (ii) a F(ab')2 fragment, a bivalent fragment comprising two Fab fragments linked by a disulfide bond at the hinge region; (iii) a Fab' fragment, which is essentially a Fab with a partial hinge region; (iv) a Fd fragment, which consists of the VH and CH1 domains; (v) a Fd' fragment, which has the VH and CH1 domains and one or more cysteine ​​residues at the C-terminus of the CH1 domain; (vi) an Fv fragment, which consists of the VL and VH domains of a single arm of an antibody; (vii) a dAb fragment, which consists of the VH domain; (viii) isolated complementarity determining regions (CDRs); and (ix) nanobodies, heavy chain variable regions containing a single variable domain and two constant domains. In addition, although the two domains VL and VH of the Fv fragment are encoded by different genes, they can be connected by synthetic linkers using recombinant methods so that they can be made into a single protein chain, in which the VL and VH regions are paired to form a monovalent molecule (called single-chain Fv (scFv)). Such single-chain antibodies are also intended to be encompassed within the term "antigen-binding fragment" of an antibody. In addition, the term also includes a "straight-chain antibody" comprising a pair of tandem Fd fragments (VH-CH1-VH-CH1), which together with a complementary light chain polypeptide form an antigen-binding region, as well as modified forms of any of the aforementioned fragments that retain antigen-binding activity.

[0146] These antigen-binding fragments can be obtained using conventional techniques known to those with skill in the art, and the fragments are screened for utility in the same manner as are intact antibodies.

[0147] As used herein, the term "binding" or "specific binding" refers to a non-random binding reaction between two molecules, such as an antibody and its target antigen. The binding specificity of an antibody can be determined based on affinity and / or avidity. Avidity represents the equilibrium constant (KD) for the dissociation of an antigen from an antibody and is a measure of the binding strength between an antigenic determinant and the antigen binding site of an antibody: the smaller the value of KD, the stronger the binding strength between the antigenic determinant and the antibody. Alternatively, affinity can also be expressed as an affinity constant (KA), which is 1 / KD.

[0148] Avidity is a measure of the strength of binding between an antibody and its associated antigen. Avidity is related to the affinity between an antigenic determinant and the antigen-binding site of an antibody and the number of associated binding sites present on the antibody. Typically, an antibody binding to an antigen will bind to the antigen with the following dissociation constant (KD): 10 -5 M to 10 -12 M or less, and preferably 10 -7 M to 10 -12 M or less, and more preferably 10-8 M to 10 -12 M, and / or have the following binding affinity: at least 10 7 M -1 , preferably at least 10 8 M -1 , more preferably at least 10 9 M -1 , such as at least 10 12 M -1 It is generally believed that any value greater than 10 -4 M's K D The values ​​represent non-specific binding. Specific binding of an antibody to an antigen or antigenic determinant can be determined in any known suitable manner, including for example Scatchard analysis and / or competitive binding assays, such as radioimmunoassay (RIA), enzyme immunoassay (EIA) and sandwich competition assays, and different variations thereof known in the art.

[0149] The term "epitope" refers to the site on an antigen to which an antibody binds. An epitope can be formed by continuous amino acids or by non-continuous amino acids juxtaposed by the tertiary folding of one or more proteins. Epitopes formed by continuous amino acids (also referred to as linear epitopes) are typically retained in exposure to denaturing solvents, while epitopes formed by tertiary folding (also referred to as conformational epitopes) are typically lost in the treatment of denaturing solvents. An epitope typically includes at least 3, more typically at least 5 or 8-10 amino acids in a unique spatial conformation. An epitope defines the minimum binding site of an antibody and is therefore the specific target of an antibody or its antigen-binding fragment.

[0150] As used herein, the term "sequence identity" refers to the degree to which two sequences (amino acids) are aligned to have identical residues at identical positions. For example, "an amino acid sequence is X% identical to SEQ ID NO: Y" means that the amino acid sequence is X% identical to SEQ ID NO: Y and is stated as X% of the residues in the amino acid sequence being identical to the residues in the sequence disclosed in SEQ ID NO: Y. Typically, such calculations are performed using computer programs. Exemplary 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).

[0151] In addition, when determining the degree of sequence identity between two amino acid sequences, one of skill in the art may consider so-called "conservative" amino acid substitutions, which can generally be described as amino acid substitutions in which an amino acid residue is replaced with another amino acid residue of a similar chemical structure, which has little or essentially no effect on the function, activity, or other biological properties of the polypeptide. Such conservative amino acid substitutions are well known in the art.

[0152] Such conservative substitutions are preferably substitutions in which one amino acid from the following groups (a) to (e) is replaced by another amino acid residue from the same group: (a) small aliphatic, nonpolar or weakly polar residues: Ala, Ser, Thr, Pro and Gly; (b) polar, negatively charged residues and their (uncharged) amides: Asp, Asn, Glu and Gln; (c) polar, positively charged residues: His, Arg and Lys; (d) large aliphatic, nonpolar residues: Met, Leu, Ile, Val and Cys; and (e) aromatic residues: Phe, Tyr and Trp.

[0153] Particularly preferred conservative substitutions are as follows: Ala to Gly or to Ser; Arg to Lys; Asn to Gln or to His; Asp to Glu; Cys to Ser; Gln to Asn; Glu to Asp; Gly to Ala or to Pro; His to Asn or to Gln; Ile to Leu or to Val; Leu to Ile or to Val; Lys to Arg, to Gln or to Glu; Met to Leu, to Tyr or to Ile; Phe to Met, to Leu or to Tyr; Ser to Thr; Thr to Ser; Trp to Tyr; Tyr to Trp; and / or Phe to Val, to Ile or to Leu.

[0154] As used herein, the term "tumor-associated antigen" refers to an antigen that is differentially expressed in cancer cells compared to normal cells and, therefore, can be used to target cancer cells.

[0155] B7-H3, also known as B7 homolog 3, PSEC0249, UNQ309 / PRO352, CD276, or B7H3, is a single-span membrane protein. It is a member of the B7 family and is expressed on antigen-presenting cells as a co-stimulatory molecule. It is believed to act on receptors on T cells to enhance or suppress immune activity. The human B7-H3 gene is located on chromosome 15, and the mouse B7-H3 gene is located on chromosome 9.

[0156] As used herein, the term "vector" is intended to refer to a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked.

[0157] As used herein, the term "host cell" refers to a cell into which an expression vector has been introduced.

[0158] The term "pharmaceutically acceptable" means that the carrier or excipient is compatible with the other ingredients of the composition and not substantially deleterious to the recipient thereof, and / or such carrier or excipient is approved or available for inclusion in pharmaceutical compositions for parenteral administration to humans.

[0159] As used herein, the terms "treat," "therapy," "treatment," and the like refer to the administration of an agent or the performance of a procedure for the purpose of obtaining an effect. These effects may be preventive in terms of completely or partially preventing a disease or its symptoms, and / or therapeutic in terms of achieving a partial or complete cure of a disease and / or disease symptoms. As used herein, "treatment" may include treating a disease or condition (e.g., cancer) in a mammal, particularly a human, and includes: (a) preventing the occurrence of a disease or disease symptom in a subject who may be susceptible to the disease (e.g., including a disease that may be associated with or caused by the primary disease) but has not yet been diagnosed with the disease; (b) inhibiting the disease, i.e., arresting its development; and (c) alleviating the disease, i.e., causing regression of the disease. Treatment may refer to any indicator of success in the treatment, improvement, or prevention of cancer, including any objective or subjective parameter, such as a reduction in symptoms; relief; elimination of disease symptoms or making the disease condition more tolerable for the patient; slowing the rate of deterioration or decline; or reducing the final stage of deterioration. Treatment or improvement of symptoms is based on one or more objective or subjective parameters; including the results of a doctor's examination. Thus, the term "treatment" includes the administration of an antibody, composition, or conjugate disclosed herein to prevent or delay, alleviate, or arrest or inhibit the development of symptoms or conditions associated with a disease (e.g., cancer). The term "therapeutic effect" refers to the reduction, elimination, or prevention of a disease, disease symptom, or disease side effect in a subject.

[0160] As used herein, the term "effective amount" refers to the amount administered to a subject for treating a disease that is sufficient to effect treatment for the disease.

[0161] As used herein, the term "subject" refers to any mammalian subject for whom diagnosis, treatment, or therapy is desired. "Mammal" for therapeutic purposes refers to any animal classified as a mammal, including humans, livestock, and laboratory, zoo, sports, or pet animals such as dogs, horses, cats, cows, sheep, goats, pigs, mice, rats, rabbits, guinea pigs, monkeys, and the like.

[0162] Anti-B7-H3 antibody

[0163] The present disclosure provides an antibody or antigen-binding fragment thereof that specifically binds to B7-H3, comprising a light chain variable region (VL) and a heavy chain variable region (VH).

[0164] In a first aspect, the present disclosure provides an antibody or antigen-binding fragment thereof that specifically binds to B7-H3, wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL).

[0165] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 3, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 13.

[0166] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 26, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 27.

[0167] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 28, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 29.

[0168] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 30, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 29.

[0169] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 22, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 23.

[0170] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 33, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 42.

[0171] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 34, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 42.

[0172] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 33, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 41.

[0173] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 34, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 39.

[0174] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 34, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 40.

[0175] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 34, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 41.

[0176] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 1, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 2.

[0177] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 3, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 4.

[0178] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 5, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 6.

[0179] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 7, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 8.

[0180] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 9, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 10.

[0181] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 11, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 12.

[0182] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 14, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 15.

[0183] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 16, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 17.

[0184] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 18, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 19.

[0185] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 20, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 21.

[0186] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the heavy chain variable region having the amino acid sequence shown in SEQ ID NO: 24, and the VL comprises LCDR1, LCDR2, and LCDR3 of the light chain variable region having the amino acid sequence shown in SEQ ID NO: 25.

[0187] In some embodiments, CDR sequences are defined according to the Kabat numbering system.

[0188] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and when the CDR sequences are defined according to the Kabat numbering system, the VH comprises HCDR1 as set forth in SEQ ID NO:84, HCDR2 as set forth in SEQ ID NO:86, and HCDR3 as set forth in SEQ ID NO:88, and the VL comprises LCDR1 as set forth in SEQ ID NO:173, LCDR2 as set forth in SEQ ID NO:175, and LCDR3 as set forth in SEQ ID NO:177.

[0189] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and when the CDR sequences are defined according to the Kabat numbering system, the VH comprises HCDR1 as set forth in SEQ ID NO:84, HCDR2 as set forth in SEQ ID NO:86, and HCDR3 as set forth in SEQ ID NO:126, and the VL comprises LCDR1 as set forth in SEQ ID NO:213, LCDR2 as set forth in SEQ ID NO:175, and LCDR3 as set forth in SEQ ID NO:177.

[0190] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and when the CDR sequences are defined according to the Kabat numbering system, the VH comprises HCDR1 as set forth in SEQ ID NO: 111, HCDR2 as set forth in SEQ ID NO: 113, and HCDR3 as set forth in SEQ ID NO: 115, and the VL comprises LCDR1 as set forth in SEQ ID NO: 201, LCDR2 as set forth in the amino acid sequence NAK, and LCDR3 as set forth in SEQ ID NO: 205.

[0191] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and when the CDR sequences are defined according to the Kabat numbering system, the VH comprises HCDR1 as set forth in SEQ ID NO: 111, HCDR2 as set forth in SEQ ID NO: 113, and HCDR3 as set forth in SEQ ID NO: 115, and the VL comprises LCDR1 as set forth in SEQ ID NO: 201, LCDR2 as set forth in the amino acid sequence NAK, and LCDR3 as set forth in SEQ ID NO: 203.

[0192] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and when the CDR sequences are defined according to the Kabat numbering system, the VH comprises HCDR1 as set forth in SEQ ID NO:44, HCDR2 as set forth in SEQ ID NO:46, and HCDR3 as set forth in SEQ ID NO:48, and the VL comprises LCDR1 as set forth in SEQ ID NO:135, LCDR2 as set forth in the amino acid sequence YAS, and LCDR3 as set forth in SEQ ID NO:139.

[0193] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and when the CDR sequences are defined according to the Kabat numbering system, the VH comprises HCDR1 as set forth in SEQ ID NO:51, HCDR2 as set forth in SEQ ID NO:53, and HCDR3 as set forth in SEQ ID NO:55, and the VL comprises LCDR1 as set forth in SEQ ID NO:142, LCDR2 as set forth in the amino acid sequence YAS, and LCDR3 as set forth in SEQ ID NO:145.

[0194] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and when the CDR sequences are defined according to the Kabat numbering system, the VH comprises HCDR1 as set forth in SEQ ID NO:58, HCDR2 as set forth in SEQ ID NO:60, and HCDR3 as set forth in SEQ ID NO:62, and the VL comprises LCDR1 as set forth in SEQ ID NO:148, LCDR2 as set forth in the amino acid sequence KVS, and LCDR3 as set forth in SEQ ID NO:152.

[0195] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and when the CDR sequences are defined according to the Kabat numbering system, the VH comprises HCDR1 as set forth in SEQ ID NO:65, HCDR2 as set forth in SEQ ID NO:67, and HCDR3 as set forth in SEQ ID NO:69, and the VL comprises LCDR1 as set forth in SEQ ID NO:154, LCDR2 as set forth in the amino acid sequence RMS, and LCDR3 as set forth in SEQ ID NO:158.

[0196] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and when the CDR sequences are defined according to the Kabat numbering system, the VH comprises HCDR1 as set forth in SEQ ID NO:72, HCDR2 as set forth in SEQ ID NO:74, and HCDR3 as set forth in SEQ ID NO:76, and the VL comprises LCDR1 as set forth in SEQ ID NO:160, LCDR2 as set forth in the amino acid sequence GAS, and LCDR3 as set forth in SEQ ID NO:164.

[0197] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and when the CDR sequences are defined according to the Kabat numbering system, the VH comprises HCDR1 as set forth in SEQ ID NO:79, HCDR2 as set forth in SEQ ID NO:81, and HCDR3 as set forth in SEQ ID NO:83, and the VL comprises LCDR1 as set forth in SEQ ID NO:166, LCDR2 as set forth in the amino acid sequence SGS, and LCDR3 as set forth in SEQ ID NO:170.

[0198] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and when the CDR sequences are defined according to the Kabat numbering system, the VH comprises HCDR1 as set forth in SEQ ID NO:90, HCDR2 as set forth in SEQ ID NO:92, and HCDR3 as set forth in SEQ ID NO:94, and the VL comprises LCDR1 as set forth in SEQ ID NO:179, LCDR2 as set forth in the amino acid sequence FAS, and LCDR3 as set forth in SEQ ID NO:183.

[0199] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and when the CDR sequences are defined according to the Kabat numbering system, the VH comprises HCDR1 as set forth in SEQ ID NO:96, HCDR2 as set forth in SEQ ID NO:98, and HCDR3 as set forth in SEQ ID NO:100, and the VL comprises LCDR1 as set forth in SEQ ID NO:185, LCDR2 as set forth in the amino acid sequence KVS, and LCDR3 as set forth in SEQ ID NO:186.

[0200] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and when the CDR sequences are defined according to the Kabat numbering system, the VH comprises HCDR1 as set forth in SEQ ID NO: 101, HCDR2 as set forth in SEQ ID NO: 102, and HCDR3 as set forth in SEQ ID NO: 104, and the VL comprises LCDR1 as set forth in SEQ ID NO: 188, LCDR2 as set forth in the amino acid sequence DTS, and LCDR3 as set forth in SEQ ID NO: 192.

[0201] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), the VH comprising HCDR1 as set forth in SEQ ID NO: 79, HCDR2 as set forth in SEQ ID NO: 107, and HCDR3 as set forth in SEQ ID NO: 109, and the VL comprising LCDR1 as set forth in SEQ ID NO: 195, LCDR2 as set forth in SEQ ID NO: 199, and LCDR3 as set forth in SEQ ID NO: 199.

[0202] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and when the CDR sequences are defined according to the Kabat numbering system, the VH comprises HCDR1 as set forth in SEQ ID NO: 117, HCDR2 as set forth in SEQ ID NO: 119, and HCDR3 as set forth in SEQ ID NO: 121, and the VL comprises LCDR1 as set forth in SEQ ID NO: 208, LCDR2 as set forth in DTS, and LCDR3 as set forth in SEQ ID NO: 211.

[0203] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 13. In some embodiments, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises a functional variant of the amino acid sequence as shown in SEQ ID NO:3, which is formed by inserting, deleting and / or substituting one or more amino acids therein, and the VL comprises a functional variant of the amino acid sequence as shown in SEQ ID NO:13, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the antibody or antigen-binding fragment thereof comprising the VH comprising the functional variant and the VL comprising the functional variant retains the ability to bind to B7-H3.

[0204] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 27. In some embodiments, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises a functional variant of the amino acid sequence as shown in SEQ ID NO: 26, which is formed by inserting, deleting and / or substituting one or more amino acids therein, and the VL comprises a functional variant of the amino acid sequence as shown in SEQ ID NO: 27, which is formed by inserting, deleting and / or substituting one or more amino acids therein, with the proviso that the antibody or antigen-binding fragment thereof comprising the VH comprising the functional variant and the VL comprising the functional variant retains the ability to bind to B7-H3.

[0205] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 29. In some embodiments, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises a functional variant of the amino acid sequence as shown in SEQ ID NO: 28, which is formed by inserting, deleting and / or substituting one or more amino acids therein, and the VL comprises a functional variant of the amino acid sequence as shown in SEQ ID NO: 29, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the antibody or antigen-binding fragment thereof comprising the VH comprising the functional variant and the VL comprising the functional variant retains the ability to bind to B7-H3.

[0206] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 29. In some embodiments, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises a functional variant of the amino acid sequence as shown in SEQ ID NO:30, which is formed by inserting, deleting and / or substituting one or more amino acids therein, and the VL comprises a functional variant of the amino acid sequence as shown in SEQ ID NO:29, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the antibody or antigen-binding fragment thereof comprising the VH comprising the functional variant and the VL comprising the functional variant retains the ability to bind to B7-H3.

[0207] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 23. In some embodiments, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises a functional variant of the amino acid sequence as shown in SEQ ID NO: 22, which is formed by inserting, deleting and / or substituting one or more amino acids therein, and the VL comprises a functional variant of the amino acid sequence as shown in SEQ ID NO: 23, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the antibody or antigen-binding fragment thereof comprising the VH comprising the functional variant and the VL comprising the functional variant retains the ability to bind to B7-H3.

[0208] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 42. In some embodiments, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises a functional variant of the amino acid sequence as shown in SEQ ID NO:33, which is formed by inserting, deleting and / or substituting one or more amino acids therein, and the VL comprises a functional variant of the amino acid sequence as shown in SEQ ID NO:42, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the antibody or antigen-binding fragment thereof comprising the VH comprising the functional variant and the VL comprising the functional variant retains the ability to bind to B7-H3.

[0209] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 42. In some embodiments, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises a functional variant of the amino acid sequence as shown in SEQ ID NO:34, which is formed by inserting, deleting and / or substituting one or more amino acids therein, and the VL comprises a functional variant of the amino acid sequence as shown in SEQ ID NO:42, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the antibody or antigen-binding fragment thereof comprising the VH comprising the functional variant and the VL comprising the functional variant retains the ability to bind to B7-H3.

[0210] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 41. In some embodiments, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises a functional variant of the amino acid sequence as shown in SEQ ID NO:33, which is formed by inserting, deleting and / or substituting one or more amino acids therein, and the VL comprises a functional variant of the amino acid sequence as shown in SEQ ID NO:41, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the antibody or antigen-binding fragment thereof comprising the VH comprising the functional variant and the VL comprising the functional variant retains the ability to bind to B7-H3.

[0211] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 39. In some embodiments, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises a functional variant of the amino acid sequence as shown in SEQ ID NO: 34, which is formed by inserting, deleting and / or substituting one or more amino acids therein, and the VL comprises a functional variant of the amino acid sequence as shown in SEQ ID NO: 39, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the antibody or antigen-binding fragment thereof comprising the VH comprising the functional variant and the VL comprising the functional variant retains the ability to bind to B7-H3.

[0212] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 40. In some embodiments, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises a functional variant of the amino acid sequence as shown in SEQ ID NO:34, which is formed by inserting, deleting and / or substituting one or more amino acids therein, and the VL comprises a functional variant of the amino acid sequence as shown in SEQ ID NO:40, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the antibody or antigen-binding fragment thereof comprising the VH comprising the functional variant and the VL comprising the functional variant retains the ability to bind to B7-H3.

[0213] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 41. In some embodiments, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises a functional variant of the amino acid sequence as shown in SEQ ID NO:34, which is formed by insertion, deletion and / or substitution of one or more amino acids therein, and the VL comprises a functional variant of the amino acid sequence as shown in SEQ ID NO:41, which is formed by insertion, deletion and / or substitution of one or more amino acids therein, provided that the antibody or antigen-binding fragment thereof comprising the VH comprising the functional variant and the VL comprising the functional variant retains the ability to bind to B7-H3.

[0214] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 2. In some embodiments, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises a functional variant of the amino acid sequence as shown in SEQ ID NO: 1, which is formed by inserting, deleting and / or substituting one or more amino acids therein, and the VL comprises a functional variant of the amino acid sequence as shown in SEQ ID NO: 2, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the antibody or antigen-binding fragment thereof comprising the VH comprising the functional variant and the VL comprising the functional variant retains the ability to bind to B7-H3.

[0215] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO:4. In some embodiments, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises a functional variant of the amino acid sequence as shown in SEQ ID NO:3, which is formed by inserting, deleting and / or substituting one or more amino acids therein, and the VL comprises a functional variant of the amino acid sequence as shown in SEQ ID NO:4, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the antibody or antigen-binding fragment thereof comprising the VH comprising the functional variant and the VL comprising the functional variant retains the ability to bind to B7-H3.

[0216] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO:6. In some embodiments, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises a functional variant of the amino acid sequence as shown in SEQ ID NO:5, which is formed by inserting, deleting and / or substituting one or more amino acids therein, and the VL comprises a functional variant of the amino acid sequence as shown in SEQ ID NO:6, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the antibody or antigen-binding fragment thereof comprising the VH comprising the functional variant and the VL comprising the functional variant retains the ability to bind to B7-H3.

[0217] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO:8. In some embodiments, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises a functional variant of the amino acid sequence as shown in SEQ ID NO:7, which is formed by inserting, deleting and / or substituting one or more amino acids therein, and the VL comprises a functional variant of the amino acid sequence as shown in SEQ ID NO:8, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the antibody or antigen-binding fragment thereof comprising the VH comprising the functional variant and the VL comprising the functional variant retains the ability to bind to B7-H3.

[0218] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 10. In some embodiments, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises a functional variant of the amino acid sequence as shown in SEQ ID NO:9, which is formed by inserting, deleting and / or substituting one or more amino acids therein, and the VL comprises a functional variant of the amino acid sequence as shown in SEQ ID NO:10, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the antibody or antigen-binding fragment thereof comprising the VH comprising the functional variant and the VL comprising the functional variant retains the ability to bind to B7-H3.

[0219] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 12. In some embodiments, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises a functional variant of the amino acid sequence as shown in SEQ ID NO: 11, which is formed by inserting, deleting and / or substituting one or more amino acids therein, and the VL comprises a functional variant of the amino acid sequence as shown in SEQ ID NO: 12, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the antibody or antigen-binding fragment thereof comprising the VH comprising the functional variant and the VL comprising the functional variant retains the ability to bind to B7-H3.

[0220] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 15. In some embodiments, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises a functional variant of the amino acid sequence as shown in SEQ ID NO: 14, which is formed by inserting, deleting and / or substituting one or more amino acids therein, and the VL comprises a functional variant of the amino acid sequence as shown in SEQ ID NO: 15, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the antibody or antigen-binding fragment thereof comprising the VH comprising the functional variant and the VL comprising the functional variant retains the ability to bind to B7-H3.

[0221] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 17. In some embodiments, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises a functional variant of the amino acid sequence as shown in SEQ ID NO: 16, which is formed by inserting, deleting and / or substituting one or more amino acids therein, and the VL comprises a functional variant of the amino acid sequence as shown in SEQ ID NO: 17, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the antibody or antigen-binding fragment thereof comprising the VH comprising the functional variant and the VL comprising the functional variant retains the ability to bind to B7-H3.

[0222] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 19. In some embodiments, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises a functional variant of the amino acid sequence as shown in SEQ ID NO: 18, which is formed by inserting, deleting and / or substituting one or more amino acids therein, and the VL comprises a functional variant of the amino acid sequence as shown in SEQ ID NO: 19, which is formed by inserting, deleting and / or substituting one or more amino acids therein, with the proviso that the antibody or antigen-binding fragment thereof comprising the VH comprising the functional variant and the VL comprising the functional variant retains the ability to bind to B7-H3.

[0223] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 21. In some embodiments, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises a functional variant of the amino acid sequence as shown in SEQ ID NO: 20, which is formed by inserting, deleting and / or substituting one or more amino acids therein, and the VL comprises a functional variant of the amino acid sequence as shown in SEQ ID NO: 21, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the antibody or antigen-binding fragment thereof comprising the VH comprising the functional variant and the VL comprising the functional variant retains the ability to bind to B7-H3.

[0224] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 to 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 to SEQ ID NO: 25. In some embodiments, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises a functional variant of the amino acid sequence as shown in SEQ ID NO: 24, which is formed by inserting, deleting and / or substituting one or more amino acids therein, and the VL comprises a functional variant of the amino acid sequence as shown in SEQ ID NO: 25, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the antibody or antigen-binding fragment thereof comprising the VH comprising the functional variant and the VL comprising the functional variant retains the ability to bind to B7-H3.

[0225] A functional variant comprises or consists 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 to the amino acid sequence of the parent polypeptide.

[0226] In the context of a functional variant, the number of inserted, deleted and / or substituted amino acids preferably does not exceed 40% of the total number of amino acids in the parent amino acid sequence, more preferably does not exceed 35%, more preferably 1% to 33%, and more preferably 5% to 30%, more preferably 10% to 25%, and 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, still 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.

[0227] In some embodiments, insertions, deletions and / or substitutions may be made in the framework (FR) regions, eg, in FR1, FR2, FR3 and / or FR4.

[0228] In some embodiments, the substitution of one or more amino acids can be a conservative substitution of one or more amino acids. Such conservative substitutions are preferably substitutions in which one amino acid in the following groups (a) to (e) is substituted with another amino acid residue in the same group: (a) small aliphatic, nonpolar or weakly polar residues: Ala, Ser, Thr, Pro and Gly; (b) polar, negatively charged residues and their (uncharged) amides: Asp, Asn, Glu and Gln; (c) polar, positively charged residues: His, Arg and Lys; (d) large aliphatic, nonpolar residues: Met, Leu, He, Val and Cys; and (e) aromatic residues: Phe, Tyr and Trp.

[0229] Particularly preferred conservative substitutions are as follows: Ala to Gly or to Ser; Arg to Lys; Asn to Gln or to His; Asp to Glu; Cys to Ser; Gln to Asn; Glu to Asp; Gly to Ala or to Pro; His to Asn or to Gln; Ile to Leu or to Val; Leu to Ile or to Val; Lys to Arg, to Gln or to Glu; Met to Leu, to Tyr or to Ile; Phe to Met, to Leu or to Tyr; Ser to Thr; Thr to Ser; Trp to Tyr; Tyr to Trp; and / or Phe to Val, to Ile or to Leu.

[0230] In a preferred embodiment, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 3, and the VL comprises the amino acid sequence shown in SEQ ID NO: 13.

[0231] In a preferred embodiment, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 26, and the VL comprises the amino acid sequence shown in SEQ ID NO: 27.

[0232] In a preferred embodiment, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 28, and the VL comprises the amino acid sequence shown in SEQ ID NO: 29.

[0233] In a preferred embodiment, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 30, and the VL comprises the amino acid sequence shown in SEQ ID NO: 29.

[0234] In a preferred embodiment, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 22, and the VL comprises the amino acid sequence shown in SEQ ID NO: 23.

[0235] In a preferred embodiment, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 33, and the VL comprises the amino acid sequence shown in SEQ ID NO: 42.

[0236] In a preferred embodiment, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 34, and the VL comprises the amino acid sequence shown in SEQ ID NO: 42.

[0237] In a preferred embodiment, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 33, and the VL comprises the amino acid sequence shown in SEQ ID NO: 41.

[0238] In a preferred embodiment, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 34, and the VL comprises the amino acid sequence shown in SEQ ID NO: 39.

[0239] In a preferred embodiment, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 34, and the VL comprises the amino acid sequence shown in SEQ ID NO: 40.

[0240] In a preferred embodiment, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 34, and the VL comprises the amino acid sequence shown in SEQ ID NO: 41.

[0241] In a preferred embodiment, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 1, and the VL comprises the amino acid sequence shown in SEQ ID NO: 2.

[0242] In a preferred embodiment, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 3, and the VL comprises the amino acid sequence shown in SEQ ID NO: 4.

[0243] In a preferred embodiment, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 5, and the VL comprises the amino acid sequence shown in SEQ ID NO: 6.

[0244] In a preferred embodiment, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 7, and the VL comprises the amino acid sequence shown in SEQ ID NO: 8.

[0245] In a preferred embodiment, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 9, and the VL comprises the amino acid sequence shown in SEQ ID NO: 10.

[0246] In a preferred embodiment, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 11, and the VL comprises the amino acid sequence shown in SEQ ID NO: 12.

[0247] In a preferred embodiment, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 14, and the VL comprises the amino acid sequence shown in SEQ ID NO: 15.

[0248] In a preferred embodiment, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 16, and the VL comprises the amino acid sequence shown in SEQ ID NO: 17.

[0249] In a preferred embodiment, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 18, and the VL comprises the amino acid sequence shown in SEQ ID NO: 19.

[0250] In a preferred embodiment, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 20, and the VL comprises the amino acid sequence shown in SEQ ID NO: 21.

[0251] In a preferred embodiment, the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises the amino acid sequence shown in SEQ ID NO: 24, and the VL comprises the amino acid sequence shown in SEQ ID NO: 25.

[0252] In some embodiments of the antibodies or antigen-binding fragments thereof disclosed herein, the antibody is a murine antibody, a chimeric antibody, a humanized antibody, or a human antibody.

[0253] In some embodiments, the antibody is a murine antibody, a chimeric antibody, a humanized antibody, or a human antibody.

[0254] Based on the amino acid sequence of the constant region of the antibody heavy chain, immunoglobulin molecules can be divided into five classes (isotypes): IgA, IgD, IgE, IgG and IgM, and can be further divided into different subtypes, such as IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, etc. Based on the amino acid sequence of the light chain, the light chain of the antibody can be divided into lambda (λ) chain and kappa (κ) chain. The antibodies disclosed herein can be any of the above classes or subtypes.

[0255] In some embodiments, the antibody is of an isotype selected from IgG, IgA, IgM, IgE, and IgD. In some embodiments, the antibody is of a subtype selected from IgG1, IgG2, IgG3, and IgG4. In a preferred embodiment, the antibody is an IgG1 antibody.

[0256] The antibodies disclosed herein may be intact antibodies or antigen-binding fragments thereof. An 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 include, but are not limited to, 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 consisting of a pair of tandem Fd fragments (VH-CH1-VH-CH1), and modified forms of any of the foregoing fragments that retain antigen-binding activity.

[0257] In some embodiments, the antigen-binding fragment is selected from 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 another preferred embodiment, the antigen-binding fragment is scFv.

[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 to 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 to SEQ ID NO: 231. In some embodiments, the heavy chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 230, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 231, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. A functional variant comprises or consists 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 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 to 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 to SEQ ID NO: 249. In some embodiments, the heavy chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 248, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 249, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. A functional variant comprises or consists 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 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 to 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 to SEQ ID NO: 251. In some embodiments, the heavy chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 250, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 251, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. A functional variant comprises or consists 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 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 to 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 to SEQ ID NO: 251. In some embodiments, the heavy chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 252, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 251, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. A functional variant comprises or consists 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 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 to 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 to SEQ ID NO: 241. In some embodiments, the heavy chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 240, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 241, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. A functional variant comprises or consists 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 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 to 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 to SEQ ID NO: 264. In some embodiments, the heavy chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 255, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 264, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. A functional variant comprises or consists 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 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 to 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 to SEQ ID NO: 264. In some embodiments, the heavy chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 256, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 264, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. A functional variant comprises or consists 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 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 to 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 to SEQ ID NO: 263. In some embodiments, the heavy chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 255, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 263, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. A functional variant comprises or consists 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 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 to 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 to SEQ ID NO: 261. In some embodiments, the heavy chain comprises a functional variant of the amino acid sequence as shown in SEQ ID NO: 256, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant of the amino acid sequence as shown in SEQ ID NO: 261, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. A functional variant comprises or consists 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 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 to 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 to SEQ ID NO: 262. In some embodiments, the heavy chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 256, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 262, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. A functional variant comprises or consists 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 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 to 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 to SEQ ID NO: 263. In some embodiments, the heavy chain comprises a functional variant of the amino acid sequence as shown in SEQ ID NO: 256, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant of the amino acid sequence as shown in SEQ ID NO: 263, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. A functional variant comprises or consists 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 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 to 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 to SEQ ID NO: 219. In some embodiments, the heavy chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 218, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 219, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. A functional variant comprises or consists 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 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 to 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 to SEQ ID NO: 221. In some embodiments, the heavy chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 220, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 221, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. A functional variant comprises or consists 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 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 to 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 to SEQ ID NO: 223. In some embodiments, the heavy chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 222, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 223, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. A functional variant comprises or consists 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 to the amino acid sequence of the parent polypeptide.

[0272] 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 to 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 to SEQ ID NO: 225. In some embodiments, the heavy chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 224, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 225, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. A functional variant comprises or consists 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 to the amino acid sequence of the parent polypeptide.

[0273] 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 to 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 to SEQ ID NO: 227. In some embodiments, the heavy chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 226, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 227, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. A functional variant comprises or consists 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 to the amino acid sequence of the parent polypeptide.

[0274] 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 to 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 to SEQ ID NO: 229. In some embodiments, the heavy chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 228, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 229, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. A functional variant comprises or consists 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 to the amino acid sequence of the parent polypeptide.

[0275] 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 to 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 to SEQ ID NO: 233. In some embodiments, the heavy chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 232, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 233, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. A functional variant comprises or consists 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 to the amino acid sequence of the parent polypeptide.

[0276] 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 to 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 to SEQ ID NO: 235. In some embodiments, the heavy chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 234, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 235, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. A functional variant comprises or consists 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 to the amino acid sequence of the parent polypeptide.

[0277] 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 to 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 to SEQ ID NO: 237. In some embodiments, the heavy chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 236, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 237, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. A functional variant comprises or consists 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 to the amino acid sequence of the parent polypeptide.

[0278] 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 to 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 to SEQ ID NO: 239. In some embodiments, the heavy chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 238, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 239, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. A functional variant comprises or consists 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 to the amino acid sequence of the parent polypeptide.

[0279] 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 to 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 to SEQ ID NO: 243. In some embodiments, the heavy chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 242, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. In some embodiments, the light chain comprises a functional variant of the amino acid sequence as set forth in SEQ ID NO: 243, which is formed by inserting, deleting and / or substituting one or more amino acids therein, provided that the functional variant retains the ability to bind to B7-H3. A functional variant comprises or consists 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 to the amino acid sequence of the parent polypeptide.

[0280] In some embodiments, the number of inserted, deleted and / or substituted amino acids is preferably no more than 40% of the total number of amino acids in the parent amino acid sequence, more preferably no more than 35%, more preferably 1% to 33%, and more preferably 5% to 30%, more preferably 10% to 25%, and more preferably 15% to 20%. For example, the number of inserted, deleted and / or substituted amino acids can 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 inserted, deleted and / or substituted amino acids is 1, 2, 3, 4, 5, 6 or 7.

[0281] In some embodiments, insertions, deletions and / or substitutions may be made in the framework (FR) regions, e.g., FR1, FR2, FR3 and / or FR4; and / or constant regions, e.g., CL, CH1, CH2 and / or CH3.

[0282] In some embodiments, the substitution of one or more amino acids can be a conservative substitution of one or more amino acids. Examples of conservative substitutions are described above.

[0283] In a preferred embodiment, the antibody comprises a light chain and a heavy chain, the heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 230, and the light chain comprising the amino acid sequence set forth in SEQ ID NO: 231. In a preferred embodiment, the antibody comprises a light chain and a heavy chain, the heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 248, and the light chain comprising the amino acid sequence set forth in SEQ ID NO: 249. In a preferred embodiment, the antibody comprises a light chain and a heavy chain, the heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 250, and the light chain comprising the amino acid sequence set forth in SEQ ID NO: 251. In a preferred embodiment, the antibody comprises a light chain and a heavy chain, the heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 252, and the light chain comprising the amino acid sequence set forth in SEQ ID NO: 251. In a preferred embodiment, the antibody comprises a light chain and a heavy chain, the heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 240, and the light chain comprising the amino acid sequence set forth in SEQ ID NO: 241. In a preferred embodiment, the antibody comprises a light chain and a heavy chain, the heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 255, and the light chain comprising the amino acid sequence set forth in SEQ ID NO: 264. In a preferred embodiment, the antibody comprises a light chain and a heavy chain, the heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 256, and the light chain comprising the amino acid sequence set forth in SEQ ID NO: 264. In a preferred embodiment, the antibody comprises a light chain and a heavy chain, the heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 255, and the light chain comprising the amino acid sequence set forth in SEQ ID NO: 263. In a preferred embodiment, the antibody comprises a light chain and a heavy chain, the heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 256, and the light chain comprising the amino acid sequence set forth in SEQ ID NO: 261. In a preferred embodiment, the antibody comprises a light chain and a heavy chain, the heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 256, and the light chain comprising the amino acid sequence set forth in SEQ ID NO: 262. In a preferred embodiment, the antibody comprises a light chain and a heavy chain, the heavy chain comprising the amino acid sequence shown in SEQ ID NO: 256, and the light chain comprising the amino acid sequence shown in SEQ ID NO: 263. In a preferred embodiment, the antibody comprises a light chain and a heavy chain, the heavy chain comprising the amino acid sequence shown in SEQ ID NO: 218, and the light chain comprising the amino acid sequence shown in SEQ ID NO: 219.In a preferred embodiment, the antibody comprises a light chain and a heavy chain, the heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 220, and the light chain comprising the amino acid sequence set forth in SEQ ID NO: 221. In a preferred embodiment, the antibody comprises a light chain and a heavy chain, the heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 222, and the light chain comprising the amino acid sequence set forth in SEQ ID NO: 223. In a preferred embodiment, the antibody comprises a light chain and a heavy chain, the heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 224, and the light chain comprising the amino acid sequence set forth in SEQ ID NO: 225. In a preferred embodiment, the antibody comprises a light chain and a heavy chain, the heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 226, and the light chain comprising the amino acid sequence set forth in SEQ ID NO: 227. In a preferred embodiment, the antibody comprises a light chain and a heavy chain, the heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 228, and the light chain comprising the amino acid sequence set forth in SEQ ID NO: 229. In a preferred embodiment, the antibody comprises a light chain and a heavy chain, the heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 232, and the light chain comprising the amino acid sequence set forth in SEQ ID NO: 233. In a preferred embodiment, the antibody comprises a light chain and a heavy chain, the heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 234, and the light chain comprising the amino acid sequence set forth in SEQ ID NO: 235. In a preferred embodiment, the antibody comprises a light chain and a heavy chain, the heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 236, and the light chain comprising the amino acid sequence set forth in SEQ ID NO: 237. In a preferred embodiment, the antibody comprises a light chain and a heavy chain, the heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 238, and the light chain comprising the amino acid sequence set forth in SEQ ID NO: 239. In a preferred embodiment, the antibody comprises a light chain and a heavy chain, the heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 242, and the light chain comprising the amino acid sequence set forth in SEQ ID NO: 243.

[0284] 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.

[0285] Many tumor-associated antigens relevant to specific cancers have been identified in this area. In some embodiments, tumor-associated antigens are antigens that can stimulate a significant tumor-specific immune response. Some of these antigens are encoded by normal cells, but are not necessarily expressed by normal cells. These antigens can be characterized as antigens that are usually silent (i.e., not expressed) in normal cells, antigens that are only expressed at certain stages of differentiation, and antigens expressed over time such as embryonic and fetal antigens. Other cancer cell antigens are encoded by mutant cell genes such as oncogenes (e.g., activated ras oncogenes), suppressor genes (e.g., P53 mutants), and fusion proteins produced by internal deletions or chromosomal translocations. Other cancer antigens can be encoded by genes carried by viral genes such as RNA and DNA tumor viruses. Many other tumor-associated antigens and antibodies against them are known and / or commercially available, and can also be prepared by those skilled in the art.

[0286] The antibodies of the present disclosure that specifically bind to B7-H3 comprise an Fc region. The Fc region can be of any isotype, including but not limited to IgG1, IgG2, IgG3, and IgG4, and can comprise one or more mutations or modifications. In one embodiment, the Fc region is an IgG1 isotype or derived therefrom, optionally with one or more mutations or modifications. In another embodiment, the Fc region is an IgG4 isotype or derived therefrom, optionally with one or more mutations or modifications. In one embodiment, the Fc region is a human IgG1 Fc.

[0287] In one embodiment, the Fc region has reduced effector function, such as reduced ADCC, ADCP, CDC and / or C1q, FcγRI, FcγRII or FcγRIIIA binding. For example, the Fc region can be an IgG1 isotype, or a non-IgG1 type, such as IgG2, IgG3 or IgG4, which has been mutated so that the ability to mediate effector function is reduced or even eliminated. Such mutations have been 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 comprise an amino acid sequence having one or more of the following amino acid substitutions compared to the wild-type sequence: E233P, L234A, L234F, L235A, L235E, G237A, N297A, N297D, P331S, and P329G.

[0288] In one embodiment, the Fc region comprises a mutation that removes an acceptor site for Asn-linked glycosylation or is otherwise manipulated to alter glycosylation properties. For example, in an IgG1 Fc region, an N297Q mutation can be used to remove an Asn-linked glycosylation site. Thus, in a specific embodiment, the Fc region comprises an IgG1 sequence having an N297Q mutation.

[0289] In a further embodiment, the Fc region is glycoengineered to reduce fucose and thereby enhance ADCC, for example by adding compounds to the culture medium during antibody production, as described in US2009317869 or as described in van Berkel et al. (2010) Biotechnol. Bioeng. 105:350, or by using FUT8 knockout cells, for example as described in Yamane-Ohnuki et al. (2004) Biotechnol. Bioeng 87:614. Alternatively, one can use et al. (1999) Nature Biotech 17: 176 to optimize ADCC. In another embodiment, the Fc region is engineered to enhance complement activation, for example as described in Natsume et al. (2009) Cancer Sci. 100: 2411.

[0290] In some embodiments, the Fc region comprises a modification or mutation that can inhibit Fc homodimerization. In some embodiments, the Fc region comprises a variant of the human IgG1 Fc wild-type sequence. The variant may be included in amino acid substitutions at positions (Kabat numbering) of human IgG1 T366 and Y407. Preferably, T366 is replaced by L (leucine). Preferably, Y407 is replaced by 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 replaced by H. In one embodiment, T366 is replaced by L, and Y407 is replaced by H.

[0291] In some embodiments, the Fc region can be a monomeric human IgG1 Fc (e.g., mFc7.2), as described in PCT Application No. PCT / US2018 / 016524, which is incorporated herein by reference in its entirety.

[0292] Nucleic Acids

[0293] The present disclosure provides nucleic acids comprising a nucleotide sequence encoding an antibody or antigen-binding fragment thereof disclosed herein.

[0294] The term "nucleic acid" includes single-stranded and double-stranded nucleotide polymers. Nucleic acids can be modified forms of ribonucleotides or deoxyribonucleotides or any type of nucleotide. The modifications include base modifications such as bromouridine and inosine derivatives, ribose modifications such as 2', 3'-dideoxyribose, internucleotide linkage modifications such as phosphorothioates, phosphorodithioates, selenophosphates, diselenphosphates, phenylthiophosphates, aniline phosphates, and phosphoramidates.

[0295] For example, the present invention provides nucleic acid molecules encoding any of the heavy chain variable region sequences disclosed herein. The present invention also provides nucleic acid molecules that are at least 90%, at least 95%, at least 98%, or at least 99% identical to the nucleic acid encoding any of the heavy chain variable region sequences disclosed herein.

[0296] For example, the present invention provides nucleic acid molecules encoding any one of the light chain variable region sequences disclosed herein. The present invention also provides nucleic acid molecules that are at least 90%, at least 95%, at least 98%, or at least 99% identical to the nucleic acid encoding any one of the light chain variable region sequences disclosed herein.

[0297] For example, the present invention provides a nucleic acid molecule encoding a heavy chain variable region sequence comprising a CDR sequence of any one of the heavy chain variable region sequences disclosed herein. The present invention 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 a CDR sequence of any one of the heavy chain variable region sequences disclosed herein.

[0298] For example, the present invention provides a nucleic acid molecule encoding a light chain variable region sequence, the light chain variable region sequence comprising the CDR sequence of any one of the light chain variable region sequences disclosed herein. The present invention also provides a nucleic acid molecule encoding a light chain variable region sequence, the light 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 light chain variable region sequences disclosed herein.

[0299] In some embodiments, the nucleic acid is ribonucleic acid (RNA) or deoxyribonucleic acid (DNA). In some embodiments, the present invention provides ribonucleic acid (RNA) comprising a nucleotide sequence encoding an antibody disclosed herein. In some embodiments, the present invention provides deoxyribonucleic acid (DNA) comprising a deoxynucleotide sequence encoding an antibody disclosed herein.

[0300] In some embodiments, the deoxyribonucleic acid (DNA) can be introduced into human cells in vivo. In some embodiments, the deoxyribonucleic acid (DNA) of the present invention is contained in a carrier or delivery agent. In some embodiments, the deoxyribonucleic acid (DNA) of the present invention is integrated into the genome of the cell.

[0301] In some embodiments, the ribonucleic acid (RNA) can be introduced into human cells in vivo.In some embodiments, the ribonucleic acid (RNA) of the present invention is contained in a vector or delivery agent.

[0302] carrier

[0303] The present disclosure provides vectors comprising the nucleic acids disclosed herein.

[0304] In some embodiments, the vector is an expression vector capable of expressing a polypeptide comprising the heavy chain variable region or the light chain variable region of an antibody.For example, the present invention provides an expression vector comprising any of the above-mentioned nucleic acid molecules.

[0305] In some embodiments, the vector is an expression vector capable of expressing a polypeptide comprising a heavy chain or a light chain of an antibody.For example, the present invention provides an expression vector comprising any of the nucleic acid molecules described above.

[0306] Any vector may be suitable for use in the present disclosure. In some embodiments, the vector is a viral vector. In some embodiments, the vector is a retroviral vector, a DNA vector, a murine leukemia virus vector, a SFG vector, a plasmid, an RNA vector, an adenoviral vector, a baculoviral vector, an Epstein Barr virus vector, a papovaviral vector, a vaccinia virus vector, a herpes simplex virus vector, an adenovirus-associated vector (AAV), a lentiviral vector, or any combination thereof. Suitable exemplary vectors include, for example, pGAR, pBABE-puro, pBABE-neo largeT cDNA, pBABE-hygro-hTERT, pMKO.1GFP, 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.

[0307] The expression vector can be any suitable recombinant expression vector. Suitable vectors include vectors designed for propagation and amplification or for expression or both, such as plasmids and viruses. For example, vectors can be selected from pUC series (Fermentas Life Sciences, Glen Burnie, Md.), pBluescript series (Stratagene, LaJolla, Calif.), pET series (Novagen, Madison, Wis.), pGEX series (Pharmacia Biotech, Uppsala, Sweden) and 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 that can be used for the present disclosure include pBI01, pBI101.2, pBI101.3, pBI121 and pBIN19 (Clontech). Examples of animal expression vectors that can be used in the present disclosure include pcDNA, pEUK-Cl, pMAM, and pMAMneo (Clontech).

[0308] Recombinant expression vectors can be prepared using standard recombinant DNA techniques as described, for example, in Sambrook et al., Molecule Cloning: A Laboratory Manual, 3rd ed., Cold Spring Harbor Press, Cold Spring Harbor, NY 2001; and Ausubel et al., Current Protocols in Molecule Biology, Greene Publishing Associates and John Wiley & Sons, NY, 1994. Circular or linear expression vector constructs can be prepared to contain replication systems functional in prokaryotic or eukaryotic host cells. Replication systems can be derived, for example, from COLEL, 2μ plasmids, lambda, SV40, bovine papilloma virus, and the like.

[0309] For example, the vector can be an adenovirus vector comprising a nucleotide sequence encoding an antibody disclosed herein. The vector can be administered to a subject, and then enters the subject's cells in vivo, thereby integrating the nucleotide sequence encoding the antibody disclosed herein into the genome of the cells, and then the cells express the antibody disclosed herein.

[0310] host cells

[0311] The present disclosure provides host cells comprising a nucleic acid disclosed herein or a vector disclosed herein.

[0312] Any cell can be used as the host cell of nucleic acid or vector of the present disclosure. In some embodiments, the cell can 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 true bacteria, such as Gram-negative or Gram-positive organisms, such as Enterobacteriaceae (Enterobactehaceae), such as Escherichia (Escherichia), such as Escherichia coli (E.coli); Enterobacter (Enterobacter); Erwinia (Erwinia); Klebsiella (Klebsiella); Proteus (Proteus); Salmonella (Salmonella), such as Salmonella typhimurium (Salmonella typhimurium); Serratia (Serratia), such as Serratia marcescens (Serratia marcescens). marcescans and Shigella; Bacilli, such as Bacillus subtilis and Bacillus licheniformis; Pseudomonas, such as Pseudomonas aeruginosa; and Streptomyces. In some embodiments, the cell is a human cell. In some embodiments, the cell is an immune cell. In some embodiments, the host cell includes, for example, CHO cells, such as CHOS cells and CHO-K1 cells, or HEK293 cells, such as HEK293A, HEK293T, and HEK293FS.

[0313] The host cells of the present invention are prepared by introducing the vectors disclosed herein or the nucleic acids disclosed herein in vitro or ex vivo. The host cells of the present invention can be administered to a subject, and the host cells express the antibodies disclosed herein in vivo.

[0314] The present invention provides a host cell into which any of the above vectors has been introduced. The present invention also provides a method for preparing an antibody of the present invention, the method comprising a) culturing the host cell of the fourth aspect of the present invention under conditions suitable for producing the antibody; and b) obtaining the antibody from the culture.

[0315] Pharmaceutical composition

[0316] The present disclosure provides a pharmaceutical composition comprising an antibody or antigen-binding fragment thereof disclosed herein, or a bispecific antibody or antigen-binding fragment thereof disclosed herein, and a pharmaceutically acceptable carrier or excipient.

[0317] The antibodies or antigen-binding fragments thereof or agents of the present invention (also referred to herein as "active compounds") and their derivatives, fragments, analogs and homologs can be incorporated into pharmaceutical compositions suitable for administration. Such compositions typically comprise an antibody or antigen-binding fragment thereof or agent and a pharmaceutically acceptable carrier. As used herein, the term "pharmaceutically acceptable carrier" is intended to include any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, etc. that are compatible with pharmaceutical administration. Preferred examples of such carriers or excipients include, but are not limited to, water, saline, Ringer's solution, dextrose solution, and 5% human serum albumin. Liposomes and non-aqueous vehicles such as fixed oils can also be used. The use of such media and agents for pharmaceutically active substances is well known in the art. Unless any conventional media or agents are incompatible with the active compound, it is considered to be used in the composition. Supplementary active compounds can also be incorporated into the composition.

[0318] In some embodiments, the pharmaceutical composition further comprises a second therapeutic agent. In some embodiments, the second therapeutic agent is selected from 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.

[0319] In some embodiments, the second therapeutic agent is a cytokine. Examples of cytokines include, but are not limited to, interleukins (e.g., IL-2, IL-7, IL-10, IL-12, IL-15) and interferons (e.g., IFNα, IFNγ). In some embodiments, the second therapeutic agent is an interleukin. In preferred embodiments, the second therapeutic agent is IL-2.

[0320] In some embodiments, the second therapeutic agent is a chemotherapeutic agent. Chemotherapeutic agents may include, for example, cytotoxic agents, antimetabolites (e.g., folic acid antagonists, purine analogs, pyrimidine analogs, etc.), topoisomerase inhibitors (e.g., camptothecin derivatives, anthraquinones, anthracyclines, epipodophyllotoxins, quinoline alkaloids, etc.), antimicrotubule agents (e.g., taxanes, vinca alkaloids), protein synthesis inhibitors (e.g., cephalotaxine, camptothecin derivatives, quinoline alkaloids), alkylating agents (e.g., alkyl sulfonates, aziridines, nitrogen mustards, nitrosoureas, platinum derivatives, triazenes, etc.), alkaloids, terpenoids, and kinase inhibitors.

[0321] The pharmaceutical composition of the present invention can be formulated to be compatible with its intended route of administration. Examples of routes of administration include parenteral administration, such as intravenous, intradermal, subcutaneous, oral (e.g., inhalation), transdermal (i.e., topical), transmucosal, and rectal administration. Solutions or suspensions for parenteral, intradermal, or subcutaneous application may include the following components: a sterile diluent, such as water for injection, saline solution, fixed oil, polyethylene glycol, glycerol, propylene glycol, or other synthetic solvents; an antibacterial agent, such as benzyl alcohol or methyl paraben; an antioxidant, such as ascorbic acid or sodium bisulfite; a chelating agent, such as tetraethylammonium oxalate (EDTA); a buffer, such as acetate, citrate, or phosphate; and an agent for adjusting tension, such as sodium chloride or dextrose. The pH value can be adjusted with an acid or base, such as hydrochloric acid or sodium hydroxide. Parenteral formulations can be packaged in ampoules, disposable syringes, or multiple-dose vials made of glass or plastic.

[0322] Pharmaceutical compositions suitable for injectable applications include sterile aqueous solutions (if water-soluble) or dispersions and sterile powders for the temporary preparation of sterile injectable solutions or dispersions. For intravenous administration, suitable carriers include physiological saline, antibacterial 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 is easy to inject. It must be stable under preparation and storage conditions and must prevent the contamination of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium, and the solvent or dispersion medium contains, for example, water, ethanol, polyols (such as glycerol, propylene glycol and liquid polyethylene glycol, etc.), and suitable mixtures thereof. Suitable mobility can be maintained, for example, by using a coating such as lecithin, by keeping the particle size required in the case of dispersions and by using a surfactant. The effect of microorganisms can be prevented by various antimicrobial and antifungal agents, such as parabens, chlorobutanol, phenol, ascorbic acid, thimerosal, etc. In many cases, it will be preferable to include isotonic agents, for example, sugars, polyalcohols such as mannitol, sorbitol, sodium chloride in the composition. Prolonged absorption of the injectable compositions can be brought about by including in the composition an agent which delays absorption, for example, aluminum monostearate and gelatin.

[0323] Sterile injectable solutions can be prepared by mixing the required amount of the active compound with one or a combination of ingredients listed above (as needed) in an appropriate solvent, followed by filtration sterilization. Typically, dispersions are prepared by introducing the active compound into a sterile vehicle containing a basic dispersion medium and other ingredients required from those listed above. In the case of sterile powders for the preparation of sterile injectable solutions, the preparation method is vacuum drying and freeze drying to produce a powder of the active ingredient plus any other desired ingredients from a previously sterile-filtered solution thereof.

[0324] Oral compositions typically include an inert diluent or edible carrier. They can be encapsulated in gelatin capsules or compressed into tablets. For the purpose of oral therapeutic administration, the active compound can be mixed with excipients and used in the form of tablets, lozenges, or capsules. Oral compositions can also be prepared using a fluid carrier used as a mouthwash, wherein the compound in the fluid carrier is administered orally and swished into the mouth and expectorated or swallowed. Pharmaceutically compatible binders and / or adjuvant materials can be included as part of the composition. Tablets, pills, capsules, lozenges, etc. may contain any of the following ingredients or compounds of similar properties: binders such as microcrystalline cellulose, tragacanth, or gelatin; excipients such as starch or lactose; disintegrants such as alginic acid, Primogel, or corn starch; lubricants such as magnesium stearate or Sterotes; glidants such as colloidal silicon dioxide; sweeteners such as sucrose or saccharin; or flavorings such as peppermint oil, methyl salicylate, or orange flavoring.

[0325] For administration by inhalation, the compounds are delivered in the form of an aerosol spray from a pressurized container or dispenser or nebulizer which contains a suitable propellant, eg, a gas such as carbon dioxide.

[0326] Systemic administration can also be carried out by transmucosal or transdermal means. For transmucosal or transdermal administration, penetrants suitable for the barrier to be penetrated are used in the formulation. Such penetrants are generally known in the art and include, for example, detergents, bile salts, and fusidic acid derivatives for transmucosal administration. Transmucosal administration can be accomplished by using nasal sprays or suppositories. For transdermal administration, the active compound is formulated into ointments, salves, gels, or creams well known in the art.

[0327] The active compounds can also be formulated in the form of suppositories (eg, with conventional suppository bases such as cocoa butter and other glycerides) or retention enemas for rectal delivery.

[0328] In one embodiment, the active compound is prepared with a carrier that will protect the compound from rapid elimination from the body (such as a controlled release formulation, including implants and microencapsulated delivery systems). Biodegradable, biocompatible polymers such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, and polylactic acid can be used. Methods for preparing such formulations will be apparent to those skilled in the art.

[0329] The present invention provides therapeutic compositions comprising the antibodies or antigen-binding fragments thereof of the present invention. The therapeutic compositions according to the present invention will be administered with suitable carriers, excipients, and other agents incorporated into formulations to provide improved transfer, delivery, tolerability, and the like. Many suitable formulations are available in the formulary known to all pharmaceutical chemists: Remington's Pharmaceutical Sciences, Mack Publishing Company, Easton, PA. These formulations include, for example, powders, pastes, ointments, jellies, waxes, oils, lipids, vesicles containing lipids (cationic or anionic) (e.g., LIPOFECTIN TM ), DNA conjugates, anhydrous absorption pastes, oil-in-water and water-in-oil emulsions, polyethylene glycol emulsions (polyethylene glycol of various molecular weights), semisolid gels, and semisolid mixtures containing polyethylene glycol. See also Powell et al. "Compendium of excipients for parenteral formations" PDA (1998) J Pharm Sci Technol 52:238-311.

[0330] Conjugate

[0331] The present disclosure provides conjugates comprising an antibody or antigen-binding fragment thereof disclosed herein or a bispecific antibody or antigen-binding fragment thereof disclosed herein, and a chemical moiety conjugated thereto.

[0332] In the context of the present disclosure, a "conjugate" is an antibody or antibody fragment (such as an antigen binding fragment) covalently linked to a chemical moiety. The chemical moiety can be, for example, a drug, a toxin, a therapeutic agent, a detectable label, a protein, a nucleic acid, a lipid, a nanoparticle, a carbohydrate, or a recombinant virus. Antibody conjugates are often referred to as "immunoconjugates." When the conjugate comprises an antibody linked to a drug (e.g., a cytotoxic agent), the conjugate is often referred to as an "antibody-drug conjugate" or "ADC."

[0333] The term "conjugated" or "connected" can refer to making two polypeptides into one continuous polypeptide molecule. In one embodiment, the antibody is connected to a chemical moiety. In another embodiment, the antibody connected to the chemical moiety is further connected to a lipid or other molecule to the protein or peptide to increase its half-life in vivo. The connection can be carried out by chemical or recombinant means. In one embodiment, the connection is chemical, wherein the reaction between the antibody portion and the chemical portion produces a covalent bond formed between the two molecules to form one molecule. A peptide linker (short peptide sequence) can optionally be included between the antibody and the chemical moiety.

[0334] Chemical moieties can be connected to the antibodies of the present invention using any number of methods known to those skilled in the art. Covalent and non-covalent attachment methods can be used. The procedure for attaching chemical moieties to antibodies varies according to the chemical structure of the chemical moiety. Polypeptides typically contain a variety of functional groups; such as carboxylic acid (COOH), free amine (-NH2) or sulfhydryl (-SH) moieties, which can be used to react with suitable functional groups on antibodies to cause the combination of chemical moieties. Alternatively, antibodies are derivatized to expose or attach additional reactive functional groups. Derivatization can involve attaching any of many known linker molecules. Linkers can be any molecule for connecting antibodies to chemical moieties. Linkers can form covalent bonds with both antibodies and chemical moieties. Suitable linkers are well known to those skilled in the art, and include but are not limited to straight or branched carbon linkers, heterocyclic carbon linkers or peptide linkers. In the case where the antibody and chemical moiety are polypeptides, linkers can be connected to the constituent amino acids (such as by disulfide bonds to cysteine) or to the α-carbon amino and carboxyl groups of the terminal amino acids through their side groups.

[0335] In some cases, it is desirable to release the chemical moiety from the antibody when the immunoconjugate reaches its target site. Thus, in these cases, the immunoconjugate will contain a linkage that is cleavable near the target site.

[0336] Enzymatic activity or conditions to which the immunoconjugate is subjected within the target cell or near the target site may cause cleavage of the linker to release the chemical moiety from the antibody.

[0337] Given the multitude of methods reported for attaching various radiodiagnostic compounds, radiotherapeutic compounds, labels (such as enzymes or fluorescent molecules), drugs, toxins, and other agents to antibodies, one skilled in the art will be able to determine the appropriate method for attaching a given agent to an antibody or other polypeptide.

[0338] The antibodies disclosed herein can be derivatized or linked to another molecule (such as another peptide or protein). Typically, the antibody or portion thereof is derivatized so that binding to the target antigen is not adversely affected by derivatization or labeling. For example, the antibody can be functionally linked (by chemical coupling, genetic fusion, non-covalent association or other means) to one or more other molecular entities, such as another antibody (e.g., a bispecific antibody or a bivalent antibody), a detection agent, a pharmaceutical agent, and / or a protein or peptide that can mediate the association of the antibody or antibody portion with another molecule (such as a streptavidin core region or a polyhistidine tag).

[0339] One type of derivatized antibody is produced by cross-linking two or more antibodies (of the same or different types). Suitable cross-linking agents include heterobifunctional cross-linkers having two distinct reactive moieties (e.g., m-maleimidobenzoyl-N-hydroxysuccinimide ester) separated by a suitable spacer, or homobifunctional cross-linkers (e.g., disuccinimidyl suberate). Such linkers are commercially available.

[0340] In some embodiments of the presently disclosed conjugates, the chemical moiety is selected from the group consisting of a therapeutic agent, a detectable moiety, and an immunostimulatory molecule.

[0341] Treatment

[0342] The present disclosure provides methods of treating cancer in a subject, comprising administering to the subject an effective amount of an antibody or antigen-binding fragment thereof, nucleic acid, vector, host cell, pharmaceutical composition, or conjugate disclosed herein.

[0343] In some embodiments of the methods disclosed herein, the cancer is a B7-H3 positive cancer. In some embodiments, the cancer is selected from the group consisting of: adrenal tumors, AIDS-related cancers, alveolar sarcomas of soft tissue, astrocytomas, adrenal cancer, bladder cancer, bone cancer, brain and spinal cord cancer, metastatic brain tumors, B cell cancers, breast cancer, carotid body tumors, cervical cancer, chondrosarcomas, chordomas, chromophobe renal cell carcinoma, clear cell carcinoma, colon cancer, colorectal cancer, benign fibrous histiocytoma of the skin, desmoplastic small round cell tumors, ependymomas, Ewing's tumors, extraskeletal myxoid chondrosarcomas, incomplete fibroplasia of bone, fibrous dysplasia of bone, gallbladder cancer or bile duct cancer, gastric cancer, gestational trophoblastic disease, germ cell tumor, head and neck cancer, hepatocellular carcinoma, islet cell tumor, Kaposi's sarcoma, kidney cancer, leukemia, liposarcoma / malignant lipoma, 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, pediatric cancer, peripheral nerve sheath tumor, pheochromocytoma, pituitary tumor, prostate cancer, posterious uveal melanoma, metastatic kidney cancer, 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.

[0344] In some embodiments, the dosage administered to a subject may vary with the embodiment, the drug used, the method of administration, and the site and subject to be treated. However, the dosage should be sufficient to provide a therapeutic response. A clinician can determine the effective amount to administer to a human or other subject to treat a medical condition. The precise amount required for effective treatment may depend on many factors, such as the activity of the antibody and the route of administration.

[0345] The dosage of the antibodies, compositions or conjugates described herein can be administered to a mammal at once or in a series of sub-doses over an appropriate time period, for example, daily, semi-weekly, weekly, bi-weekly, semi-monthly, bi-monthly, semi-annually or annually as needed. A dosage unit comprising an effective amount of the antibody, composition or conjugate can be administered in a single daily dose, or the total daily dose can be administered in two, three, four or more divided doses administered daily as needed.

[0346] Suitable modes of administration can be selected by a physician. The route of administration can be parenteral administration, for example, by injection, nasal administration, pulmonary administration or transdermal administration. Systemic or local administration can be performed by intravenous injection, intramuscular injection, intraperitoneal injection, subcutaneous injection. In some embodiments, the antibody, composition or conjugate is selected for parenteral delivery, for inhalation or for delivery through the digestive tract, for example, orally. The dosage and method of administration can vary according to the weight, age, condition, etc. of the subject and can be appropriately selected.

[0347] In some embodiments, the method further comprises administering to the subject a second therapeutic agent.In certain embodiments, the antibody, composition, or conjugate disclosed herein is administered prior to, substantially simultaneously with, or after administration of the second therapeutic agent.

[0348] Medical uses

[0349] The present disclosure provides use of an antibody or antigen-binding fragment thereof, a bispecific antibody or antigen-binding fragment thereof, a nucleic acid, a host cell, a pharmaceutical composition, or a conjugate disclosed herein in the preparation of a medicament for treating cancer in a subject.

[0350] The present disclosure also provides an antibody or antigen-binding fragment thereof disclosed herein, a bispecific antibody or antigen-binding fragment thereof disclosed herein, a pharmaceutical composition disclosed herein, or a conjugate disclosed herein for use in treating cancer in a subject.

[0351] In some embodiments of the uses disclosed herein, the cancer is a B7-H3 positive cancer. In some embodiments, the cancer is selected from the group consisting of: adrenal tumors, AIDS-related cancers, alveolar sarcomas of soft tissue, astrocytomas, adrenal cancer, bladder cancer, bone cancer, brain and spinal cord cancer, metastatic brain tumors, B cell cancers, breast cancer, carotid body tumors, cervical cancer, chondrosarcomas, chordomas, chromophobe renal cell carcinoma, clear cell carcinoma, colon cancer, colorectal cancer, benign fibrous histiocytoma of the skin, desmoplastic small round cell tumors, ependymomas, Ewing's tumors, extraskeletal myxoid chondrosarcomas, incomplete fibroplasia of bone, fibrous dysplasia of bone, gallbladder cancer or bile duct cancer, gastric cancer, gestational trophoblastic disease, germ cell tumor, head and neck cancer, hepatocellular carcinoma, islet cell tumor, Kaposi's sarcoma, kidney cancer, leukemia, liposarcoma / malignant lipoma, 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, pediatric cancer, peripheral nerve sheath tumor, pheochromocytoma, pituitary tumor, prostate cancer, posterious uveal melanoma, metastatic kidney cancer, 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.

[0352] Diagnosis and testing methods

[0353] The present disclosure provides methods for detecting B7-H3 protein in vitro or in vivo. In some cases, B7-H3 expression is detected in a biological sample. The sample can be any sample, including but not limited to a blood sample, tissue from a biopsy, autopsy, and pathology specimens. Biological samples also include body fluids such as blood, serum, plasma, sputum, cerebrospinal fluid, or urine. Biological samples are typically obtained from mammals, such as humans or non-human primates.

[0354] The present disclosure also provides methods for determining whether a subject has a B7-H3-positive cancer by contacting a sample from the subject with an anti-B7-H3 antibody disclosed herein; and detecting binding of the antibody to the sample. Increased binding of the antibody to the sample compared to binding of the antibody to a control sample identifies the subject as having cancer.

[0355] In another embodiment, the present disclosure provides a method for diagnosing a B7-H3-positive cancer in a subject by contacting a sample from the subject with an anti-B7-H3 antibody disclosed herein; and detecting binding of the antibody to the sample. Increased binding of the antibody to the sample compared to binding of the antibody to a control sample confirms a diagnosis of cancer in the subject.

[0356] In some embodiments, the control sample is a sample from a subject without cancer.In certain embodiments, the sample is a blood or tissue sample.

[0357] In some embodiments of the diagnostic and detection methods, the anti-B7-H3 antibody is directly labeled with a detectable label. In another embodiment, the anti-B7-H3 antibody (primary antibody) is unlabeled, while the secondary antibody or other molecule that can bind to the primary antibody is labeled. As is well known to those skilled in the art, the secondary antibody is selected to specifically bind to the primary antibody of a particular species and class. For example, if the primary antibody is human IgG, the secondary antibody can be anti-human IgG. Other molecules that can bind to the antibody include, but are not limited to, protein A and protein G, both of which are commercially available.

[0358] Suitable labels for antibodies or secondary antibodies include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, magnetic agents, and radioactive materials. Non-limiting examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, β-galactosidase, or acetylcholinesterase. Non-limiting examples of suitable prosthetic group complexes include streptavidin / biotin and avidin / biotin. Non-limiting examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride, or phycoerythrin. A non-limiting exemplary luminescent material is luminol; a non-limiting exemplary magnetic agent is gadolinium, and non-limiting exemplary radioactive labels include 125I, 131I, 35S, or 3H.

[0359] In an alternative embodiment, B7-H3 can be measured in a biological sample by a competitive immunoassay that utilizes 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 combined, and the amount of the labeled B7-H3 protein standard bound to the unlabeled antibody is determined. The amount of B7-H3 in the biological sample is inversely proportional to the amount of the labeled B7-H3 protein standard bound to the anti-B7-H3 antibody.

[0360] The immunoassays and methods disclosed herein can be used for a variety of purposes. In one embodiment, anti-B7-H3 antibodies can be used to detect the production of B7-H3 in cells in cell culture. In another embodiment, the antibodies can be used to detect the amount of B7-H3 in a biological sample (such as a tissue sample or a blood or serum sample). In some instances, the B7-H3 is cell surface B7-H3.

[0361] Reagent test kit

[0362] The present disclosure provides pharmaceutical packs or kits comprising one or more containers filled with one or more ingredients of the pharmaceutical compositions described herein, such as the antibodies or antigen-binding fragments disclosed herein.

[0363] In a specific embodiment, the kit comprises a first container comprising an antibody disclosed herein. In a specific embodiment, the kit comprises a first container which is a vial containing the antibody as a lyophilized sterile powder under vacuum, and the kit further comprises a second container comprising a pharmaceutically acceptable fluid.

[0364] In a specific embodiment, provided herein is an injection device comprising an antibody. In a specific embodiment, the injection device comprises an antibody in a sterile solution. In a specific embodiment, the injection device is a syringe.

[0365] In one embodiment, the kit is provided for detecting B7-H3 in a biological sample (e.g., a blood sample or a tissue sample). For example, to confirm a cancer diagnosis in a subject, a biopsy can be performed to obtain a tissue sample for histological examination. The kit for detecting the polypeptide typically comprises an anti-B7-H3 antibody, such as any monoclonal antibody disclosed herein. In further embodiments, the antibody is labeled (e.g., with a fluorescent, radioactive, or enzymatic label).

[0366] In one embodiment, the kit includes instructional materials disclosing how to use the anti-B7-H3 antibody. The instructional materials can be written, electronic (e.g., a computer floppy disk or CD), or visual (e.g., a video file). The kit can also include additional components to facilitate the application for which the kit is designed. Thus, for example, the kit can additionally contain means for detecting the label (e.g., an enzyme substrate for an enzymatic label, a filter set for detecting a fluorescent label, a suitable secondary label such as a secondary antibody, etc.). The kit can also include buffers and other reagents routinely used to practice a particular method. Such kits and appropriate contents are well known to those skilled in the art.

[0367] In one embodiment, the diagnostic kit includes an immunoassay. The method for detecting B7-H3 in a biological sample generally comprises the steps of contacting the biological sample with an anti-B7-H3 antibody, allowing the antibody to specifically bind under immunoreactive conditions to form an immune complex, and directly or indirectly detecting the presence of the immune complex (bound antibody).

[0368] Example

[0369] The following examples are provided for the purpose of illustrating various embodiments of the present invention, but are not intended to limit the present invention in any way. The present examples and the methods described herein currently represent preferred embodiments and are exemplary and are not intended to limit the scope of the present invention. Those skilled in the art will appreciate variations and other uses that are encompassed within the spirit of the present invention as defined by the scope of the claims.

[0370] Example 1. Production of Antibody Hybridomas

[0371] 1.1 Immunization of mice

[0372] All mice were housed in a barrier system. Ten 6-8 week old female Balb / c mice (SPF) were immunized subcutaneously at multiple sites with a fusion protein of human B7-H3 protein (Sequence Number: Leu 29 to Pro 245 of UniProt KB: Q5ZPR3) and Fc (Sequence Number: Pro 100 to Lys 330 of UniProt KB: P01857) as the antigen. Each mouse received 100 μg of antigen for the first immunization, and 50 μg for subsequent immunizations. Serum titers were measured after three immunizations.

[0373] 1.2 Cell fusion

[0374] Five mice with high immunogenicity were intraperitoneally injected with human B7-H3-His protein (ACRO, B73-H52E2) and CHO-S-Mouse-B7-H3 recombinant cells (purchased from Aikonde Biotechnology, AKD052A) for pulse immunization. Three days later, the mice were sacrificed by cervical dislocation, and spleens were aseptically harvested. B cell single-cell suspensions were prepared and mixed with non-secreting SP2 / 0 myeloma cells at a 1:1 ratio. Cell fusion was performed using a BTX cell electrofusion instrument. After electrofusion, all cells were immediately suspended in complete culture medium (DMEM, 20% FBS, and HAT (a mixture of hypoxantine, aminopterin, and thymidin)), seeded into 96-well plates, and cultured in a CO2 incubator.

[0375] 1.3 Hybridoma Screening

[0376] After 12 days of fusion, 100 μL of culture supernatant was collected from the 96-well plate and assayed by ELISA with B7-H3 antigen proteins from different species. Based on the fusion titer test results, clones with high OD values ​​and good growth were selected. Flow cytometry was then used to screen clones capable of binding to cells overexpressing human, cynomolgus macaque, 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 subcloned twice until a single clone was established.

[0377] The specific ELISA and FACS experimental procedures are as follows:

[0378] 1) ELISA screening:

[0379] A 96-well microtiter plate was coated 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) at 4°C overnight. The plates were washed three times with PBST (containing 0.5% Tween) and blocked with blocking buffer (3% BSA) at 37°C for 2 hours. The plates were washed three times with PBST. 100 μl of hybridoma supernatant was added and incubated at room temperature for 1 hour. The plates were washed three times with PBST, and 100 μl of a 10,000-fold diluted HRP Anti-Mouse IgG H&L (Biolong, CAT#BF03001) was added to each well and incubated at room temperature for 1 hour. The plates were washed three times, and 100 μl / well of TMB colorimetric solution was added and incubated at room temperature in the dark for 10 minutes. The reaction was terminated by adding 50 μl of stop solution, and the OD values ​​in the wells were read using a microtiter plate reader.

[0380] 2) FACS screening

[0381] 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 divided into several aliquots, with the number of cells in each aliquot being 3×10 5 For each cell, 50 μL of hybridoma supernatant was incubated with target cells, mixed thoroughly, and 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 mixing thoroughly, the cells were incubated at room temperature in the dark for 30 minutes. The cells were washed three times with PBS and analyzed by flow cytometry.

[0382] 1.4 Sequencing of monoclonal antibodies

[0383] Based on the ELISA and FACS results, select positive monoclonal hybridoma cells that meet the requirements and expand the culture. Lyse the cells using Trizol, and extract total RNA from the hybridoma cells according to standard methods. After reverse transcription of the total RNA into cDNA using a reverse transcription kit, amplify the heavy and light chain variable regions of the antibody using PCR using hybridoma sequencing primers. After purification and recovery, the PCR product fragments are subcloned into a T-vector, and clones are selected for sequencing.

[0384] Example 2. Production and characterization of chimeric antibodies

[0385] 2.1 Production of chimeric antibodies

[0386] After sequencing, the antibody heavy chain variable region sequence (VH) and light chain variable region sequence (VL) were obtained, as shown in Table 1. The underlined sequences in Table 1 are CDR regions defined by the Kabat system. The mouse antibody heavy chain variable region gene fragment was constructed into the multiple cloning site binding region on the eukaryotic expression plasmid pCDNA3.4-IgG1, thereby constructing a heavy chain expression plasmid. pCDNA3.4-IgG1 was obtained by connecting the coding nucleic acid of the heavy chain constant region fragment (GenBank: ACK87036.1, Seq 2-330) to the backbone plasmid pCDNA3.4 (purchased from Invitrogen, A14697). The coding nucleic acid of the mouse antibody light chain variable region gene was constructed into the multiple cloning site binding region on the eukaryotic expression plasmid pCDNA3.4-IgKc, thereby constructing a light chain expression plasmid. pCDNA3.4-IgKc was generated by ligating the light chain constant region fragment (GenBank: AAA59000.1, Seq 31-137) into the pCDNA3.4 backbone. The constructed light chain expression plasmid and heavy chain expression plasmid were transformed into Ecoli.DH5a competent cells, and single colonies were picked. After correct sequencing, the plasmids were extracted in large quantities to obtain expression plasmids for the chimeric antibody light chain and chimeric antibody heavy chain.

[0387] Plasmids containing the heavy chain gene and the light chain gene were transiently co-transfected into 293F (Gibco, R79007) cells. After culturing for 4-6 days, the cells were centrifuged at 8000 rpm for 20 minutes, and the cell culture supernatant containing the target protein was collected and loaded onto a Protein A affinity chromatography column to obtain purified antibodies.

[0388] The positive control antibody M30-H1-L4 sequence was derived from patent CN103687945A and was also expressed and purified using the above method.

[0389] The positive control antibody hmAb-C sequence was derived from CN109069633A and was also expressed and purified using the above method.

[0390] Table 1. Amino acid sequences of the light and heavy chain variable regions of mouse anti-B7-H3 antibodies

[0391] Table 3. Amino acid sequences of light and heavy chains of mouse anti-B7-H3 chimeric antibodies

[0392] 2.2 Characterization of chimeric antibodies

[0393] 2.2.1 Affinity verification of chimeric antibodies:

[0394] Detection was performed using a Fortebio Octet R2: AMQ sensors were used to immobilize mouse monoclonal antibodies in PBST (PBS + 0.02% tween 20) 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, and the antibody concentrations were 100 nM, 50 nM, 25 nM, 12.5 nM, 6.25 nM, and 0 nM. The assay was performed with 150 s equilibration, 180 s association, and 300 s dissociation. The assay was performed at 25°C. Kinetic parameters for binding of each sample to human B7-H3-His (ka: association rate; kd: dissociation rate; kD: association-dissociation equilibrium constant) were determined. The results are shown in Table 4.

[0395] Table 4. Affinity results of chimeric antibodies and human B7-H3His protein

[0396] 2.2.2 FACS binding and species specificity verification of chimeric antibodies

[0397] CHO-S cell lines, CHO-S-human B7-H3 cell lines recombinantly expressing human B7-H3, CHO-Cyno B7-H3 cell lines recombinantly expressing cynomolgus monkey B7-H3, and CHO-mouse B7-H3 cell lines recombinantly expressing mouse B7-H3 were aliquoted into several aliquots, with 3 x 10^5 cells per aliquot. 100 μL of chimeric antibody expression supernatant was incubated with the target cells. The B7-H3 antibody concentration for detection of CHO-S-human B7-H3 and CHO-Cyno B7-H3 cells overexpressing human B7-H3 was 1 μg / mL, while the B7-H3 antibody concentration for detection of CHO-mouse B7-H3 and CHO-S cells overexpressing mouse B7-H3 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, PE-labeled Anti-human IgG (Invitrogen, CAT#12-4998-82) was added, mixed thoroughly, and incubated at room temperature in the dark for 30 minutes; the cells were washed three times with PBS and detected by flow cytometry. The results are shown in Figure 1.

[0398] 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 can all bind to CHO-S-human B7-H3 cells. Among them, 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-bind to human, mouse and monkey B7-H3.

[0399] 2.2.3 Verification of the endocytic efficiency of chimeric antibodies

[0400] 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 was verified using a DT3C-conjugated chimeric antibody killing assay in Calu-6 (lung cancer) and NCI-H446 (small cell lung cancer) cells. Calu-6 or NCI-H446 cells in logarithmic growth phase were resuspended in culture medium to the appropriate concentration and seeded at 500 cells / 40 μl per well. After overnight incubation, the chimeric antibody was incubated with DT3C at a 1:2 ratio at room temperature for 30 minutes to form the antibody-DT3C conjugate. The cells were then added to a 384-well white plate and incubated at 37°C for 3 days. CellTiter-Glo Reagen reagent (Promega, G7573) was then added to the plate for detection. The percentage of inhibition was calculated using the following formula: % Inhibition = 100 - (Signalcmpd - SignalAve_PC) / (SignalAve_VC - SignalAve_PC) × 100

[0401] Wherein, %Inhibition represents the inhibition rate, Sigmalcmpd represents the average luminescence value of the sample to be tested, SignalAve_PC represents the average luminescence value of the blank positive control, and SignalAve_VC represents the average luminescence value of the negative control (0.1% DMSO).

[0402] The results are shown in Figures 2 and 3. The results showed that compared with the positive control M30-H1-L4, 16-B6-G3-E10 (CE10), 19-F1-E9-B11 (CB11), and 48-B4-F4-E4 (CE4) had better internalization efficiencies in Calu-6 and NCI-H446, and 28-B1-E8-C11 (CC11) had comparable internalization rates to the positive control M30-H1-L4 in Calu-6 and NCI-H446.

[0403] Example 3. Humanized Antibodies

[0404] 3.1 Humanization design, removal of post-translational modification sites, and plasmid construction

[0405] Based on the various performance characteristics of the chimeric antibody, 48-B4-F4-E4 and 28-B1-E8-C11 were selected for humanized antibody engineering. Based on the amino acid sequence information of the selected murine antibody heavy and light chains, a homology model of the antibody was generated through modeling. The framework amino acids within the CDR region were analyzed, as these amino acid positions often influence the conformation or antigen-binding activity of the CDR. The humanized germline was obtained through IMGT analysis. After splicing the selected human germline framework with the antibody's CDRs, the framework region sequences of the designed humanized antibody were compared with those of the original antibody. By analyzing the homology modeling results of the parental antibody, amino acids similar to those on the surface of human antibodies were selected for replacement, while maintaining antibody activity and minimizing heterology. Hotspots for post-translational modifications (PTMs) in the variable regions were altered to reduce PTM risks. After template sequence verification and codon optimization, the heavy chain variable region sequence was synthesized and constructed into the pCDNA3.4-uIgG1 plasmid, which contains the human heavy chain CH1, hinge, CH2, and CH3 segments. pCDNA3.4-uIgG1 was generated by ligating the coding nucleic acid for the heavy chain constant region segment (GenBank: QBK47475.1 Seq 145-474) into the backbone plasmid pCDNA3.4. The light chain variable region sequence was synthesized and constructed into the plasmid pCDNA3.4-IgKc, which contains the human light chain constant region segment. The constructed plasmids have identical constant regions but contain different site mutations in the heavy and light chain variable regions.

[0406] Table 5. Amino acid sequences of the heavy and light chain variable regions of humanized antibodies

[0407] 3.2 Production of humanized antibodies

[0408] The pCDNA3.4 plasmid containing the antibody heavy chain variable region (VH) and light chain variable region (VL) genes was co-transfected into Expi293F cells. After the cells were cultured for 6 days, the supernatant was collected. Using the AKTA sample injection system, the supernatant was automatically loaded onto a protein A (MabSelect SuRe, GE-17543804) affinity chromatography column. After loading, the chromatography column was washed with 0.1M Tris-HCl, pH 7.0 equilibration buffer, and then the target protein was eluted and collected with 0.1M glycine pH3.5 elution buffer. The sequences of the obtained humanized antibodies are shown in Tables 6, 7 and 8. cAb1-z0-p7, cAb1-z3-p7 and cAb1-z5-p7 are the sequences after humanization 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 the humanized sequences of 28-B1-E8-C11.

[0409] Table 6. Amino acid sequences of the heavy and light chain variable regions of humanized antibodies

[0410] Example 4. Characterization of humanized antibodies

[0411] 4.1 Affinity Verification of Humanized Antibodies - FACS Binding

[0412] NCI-H446 cells were cultured at 1x10 5Cells were transferred to a 96-well U-shaped plate at a density of 100 cells / well and centrifuged to remove the supernatant. The prepared supernatant to be tested was diluted to 146 μg / mL with 1X PBS + 1% BSA, then serially diluted 5-fold and added to the centrifuged 96-well plate and incubated at 4°C for 1 hour. The cells were then washed twice with 1X PBS + 1% BSA, resuspended in 100 μL of the prepared secondary antibody (Goat anti-human Fc, 1:100 dilution), and incubated at 4°C in the dark for 30 minutes. After washing the cells twice with 1X PBS + 1% BSA, the cells were filtered through a 200-mesh filter and resuspended in 100 μL of 1X PBS + 1% BSA. Fluorescence intensity was measured by flow cytometry (BD Canto II), analyzed using FlowJo, and the EC50 was calculated using Graphpad Prism 5.

[0413] Table 10. EC50 of humanized antibodies and their parent chimeric antibodies binding to NCI-H446 cells

[0414] 4.2 Affinity Verification of Humanized Antibodies - SPR

[0415] The affinity of humanized antibodies binding to the B7-H3 Human-His antigen was determined using SPR technology on a Biacore 8K system. The humanized antibodies were captured using an anti-human IgG Fc antibody coated on a CM5 chip. Seven serial 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 channels at an injection rate of 30 μL / min, with an association time of 180 s and a dissociation time of 3600 s. After each binding and dissociation cycle, the chip surface was regenerated by treatment with 10 mM Glycine-HCl, pH 1.5 buffer. The final binding and dissociation curves were calculated after subtracting the reference channel (Fc1) and the buffer channel. Kinetic data were fitted using a 1:1 binding model. The results are shown in Table 11.

[0416] Table 11. Affinity of humanized antibodies and their parent chimeric antibodies binding to B7-H3 Human-His antigen

[0417] 4.3 Internalization Ability Detection of Humanized Antibodies - FACS

[0418] The test antibodies were labeled using pHAb Amine and Thiol Reactive Dyes kit (Promega, G9845), and the internalization ability of the antibodies in Calu-6 cells and NCI-H446 cells was detected.

[0419] Calu-6 cells and NCI-H446 cells were revived and passaged more than 2 times. When the cells were cultured to the logarithmic growth phase, the cells were collected. The cells were plated in a 24-well cell culture plate at 1*10E5 / well and cultured overnight at 37°C and 5% CO2. The next day, 10 μg / mL of antibody solution labeled with pHAb Amine and Thiol Reactive Dyes kit (Promega, G9845) was prepared in cell culture medium to replace the original culture medium. The culture dish was placed in a 37°C incubator and incubated for 0h, 2h, 4h, 6h, 12h, 24h and 48h respectively. After incubation, the cells were collected and the mean fluorescence intensity (MFI) of the PE channel (pHAb dye) was measured on the machine. With time as the horizontal axis and the mean MFI as the vertical axis, the time-MFI curve was plotted using the four-parameter equation in GraphPad Prism 8.0 for internalization kinetic analysis. The results are shown in Figure 4.

[0420] According to the results of endocytosis experiments, candidate antibodies cAb1-z0-p7, cAb1-z3-p7, and cAb1-z5-p7 all exhibited endocytosis in Calu-6 and NCI-H446 cells. cAb1-z5-p7 had the strongest internalization ability, while cAb1-z0-p7 and cAb1-z3-p7 had similar internalization abilities.

[0421] 4.4 Humanized Antibody Species Specificity - FACS

[0422] The binding affinity of a humanized antibody to the B7-H3 Cyno-His antigen was determined using SPR technology on a Biacore 8K system. The humanized antibody was captured using an anti-human IgG Fc antibody coated 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 flowed through the chip channels at an injection rate of 30 μL / min. The association time was 180 s and the dissociation time was 3600 s. After each binding and dissociation cycle, the chip surface was regenerated by treatment with 10 mM Glycine-HCl, pH 1.5 buffer. The final binding and dissociation curves were calculated after subtracting the reference channel (Fc1) and the buffer channel. Kinetic data were fitted using a 1:1 binding model. The results are shown in Table 12.

[0423] Table 12. Affinity of humanized antibodies and their parent chimeric antibodies binding to B7-H3 Cyno-His antigen

[0424] It can be seen from Tables 11 and 12 that the humanized antibodies can bind to human B7-H3 and cynomolgus monkey B7-H3.

[0425] 4.5 Target Binding Specificity of Humanized Antibodies - ELISA

[0426] Select B7-H3 family His-tagged antigen proteins 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) purchased from Acro. Dilute the antigen protein to a final concentration of 1 μg / mL in sterile CBS, and add 100 μL per well to a 96-well plate. Wash three times with PBST (containing 0.5% Tween) and block with 200 μL / well of 3% BSA at 37°C for 2 hours. After washing, 100 μL of gradient dilutions of the humanized antibodies to be tested, cAb1-z0-p7, cAb1-z3-p7, and cAb1-z5-p7 (starting concentration of 10 μg / ml, 7 points of 5-fold dilution) were added to each well, incubated at room temperature for 1 hour, and washed 3 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 color development solution was added; and the OD450 value in the well was read using a microplate reader.

[0427] The results are shown in Figure 5. The results showed that the three humanized candidate antibodies cAb1-z0-p7, cAb1-z3-p7, and cAb1-z5-p7 all strongly bound to B7-H3 but did not bind to other proteins, indicating that they had binding specificity for B7-H3.

Claims

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

25.

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

211.

3. The antibody or antigen-binding fragment thereof according to claim 1 or 2, wherein (1) 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 to 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 to SEQ ID NO:13; (2) 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 to 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 to SEQ ID NO: 27; (3) 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 to 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 to SEQ ID NO: 29; (4) 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 to 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 to SEQ ID NO:29; (5) 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 to 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 to SEQ ID NO: 23; (6) 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 to 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 to SEQ ID NO:42; (7) 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 to 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 to SEQ ID NO:42; (8) 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 to 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 to SEQ ID NO:41; (9) 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 to 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 to SEQ ID NO:39; (10) 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 to 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 to SEQ ID NO:40; (11) 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 to 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 to SEQ ID NO:41 (12) 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 to 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 to SEQ ID NO: 2; (13) 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 to 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 to SEQ ID NO:4; (14) 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 to 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 to SEQ ID NO:6; (15) 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 to 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 to SEQ ID NO:8; (16) 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 to 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 to SEQ ID NO: 10; (17) 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 to 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 to SEQ ID NO: 12; (18) 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 to 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 to SEQ ID NO: 15; (19) 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 to 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 to SEQ ID NO: 17; (20) 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 to 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 to SEQ ID NO: 19; (21) 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 to 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 to SEQ ID NO: 21; or (22) The VH comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO:24, and the VL comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO:

25.

4. The antibody or antigen-binding fragment thereof according to claim 3, wherein (1) the VH comprises the amino acid sequence shown in SEQ ID NO: 3, and the VL comprises the amino acid sequence shown in SEQ ID NO: 13; (2) the VH comprises the amino acid sequence shown in SEQ ID NO: 26, and the VL comprises the amino acid sequence shown in SEQ ID NO: 27; (3) the VH comprises the amino acid sequence shown in SEQ ID NO: 28, and the VL comprises the amino acid sequence shown in SEQ ID NO: 29; (4) the VH comprises the amino acid sequence shown in SEQ ID NO: 30, and the VL comprises The amino acid sequence shown in SEQ ID NO:29; (5) the VH comprises the amino acid sequence shown in SEQ ID NO: 22, and the VL comprises the amino acid sequence shown in SEQ ID NO: 23; (6) the VH comprises the amino acid sequence shown in SEQ ID NO:33, and the VL comprises the amino acid sequence shown in SEQ ID NO:42; (7) the VH comprises the amino acid sequence shown in SEQ ID NO:34, and the VL comprises the amino acid sequence shown in SEQ ID NO:42; (8) the VH comprises the amino acid sequence shown in SEQ ID NO:33, and the VL comprises the amino acid sequence shown in SEQ ID NO:41; (9) the VH comprises the amino acid sequence shown in SEQ ID NO:34, and the VL comprises the amino acid sequence shown in SEQ ID NO:39; (10) the VH comprises the amino acid sequence shown in SEQ ID NO:34, and the VL comprises the amino acid sequence shown in SEQ ID NO:40; (11) the VH comprises the amino acid sequence shown in SEQ ID NO:34, and the VL comprises the amino acid sequence shown in SEQ ID NO:41 (12) the VH comprises the amino acid sequence shown in SEQ ID NO: 1, and the VL comprises the amino acid sequence shown in SEQ ID NO: 2; (13) the VH comprises the amino acid sequence shown in SEQ ID NO:3, and the VL comprises the amino acid sequence shown in SEQ ID NO:4; (14) the VH comprises the amino acid sequence shown in SEQ ID NO:5, and the VL comprises the amino acid sequence shown in SEQ ID NO:6; (15) the VH comprises the amino acid sequence shown in SEQ ID NO:7, and the VL comprises the amino acid sequence shown in SEQ ID NO:8; (16) the VH comprises the amino acid sequence shown in SEQ ID NO:9, and the VL comprises the amino acid sequence shown in SEQ ID NO:10; (17) the VH comprises the amino acid sequence shown in SEQ ID NO: 11, and the VL comprises the amino acid sequence shown in SEQ ID NO: 12; (18) the VH comprises the amino acid sequence shown in SEQ ID NO: 14, and the VL comprises the amino acid sequence shown in SEQ ID NO: 15; (19) the VH comprises the amino acid sequence shown in SEQ ID NO: 16, and the VL comprises the amino acid sequence shown in SEQ ID NO: 17; (20) the VH comprises the amino acid sequence shown in SEQ ID NO: 18, and the VL comprises the amino acid sequence shown in SEQ ID NO: 19; (21) the VH comprises the amino acid sequence shown in SEQ ID NO: 20, and the VL comprises the amino acid sequence shown in SEQ ID NO: 21; or (22) The VH comprises the amino acid sequence shown in SEQ ID NO:24, and the VL comprises the amino acid sequence shown in SEQ ID NO:

25.

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

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

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

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

10. The antibody or antigen-binding fragment thereof according to claim 9, wherein the antibody comprises a light chain and a heavy chain, wherein (1) the heavy chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 230, and the light chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 231; (2) the heavy chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 248, and the light chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 249; (3) the heavy chain comprises an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 250, and the light chain comprises an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 251; (4) the heavy chain comprises an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 252, and the light chain comprises an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 251; (5) the heavy chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 240, and the light chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 241; (6) the heavy chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 255, and the light chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 264; (7) the heavy chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 256, and the light chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO:

264. amino acid sequences with at least 98%, at least 99%, or 100% sequence identity; (8) the heavy chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 255, and the light chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 263; (9) the heavy chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 256, and the light chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 261; (10) the heavy chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 256, and the light chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 262; (11) the heavy chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 256, and the light chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 263; (12) the heavy chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 218, and the light chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 219; (13) the heavy chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 220, and the light chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 221; (14) the heavy chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 222, and the light chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 223; (15) the heavy chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 224, and the light chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 225; (16) the heavy chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 226, and the light chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 227; (17) The heavy chain comprises at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 229, 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 to SEQ ID NO: 229; (18) the heavy chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 232, and the light chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 233; (19) the heavy chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 234, and the light chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 235; (20) the heavy chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 236, and the light chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 237; (21) the heavy chain comprises an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% identical to SEQ ID NO: 238, and the light chain comprises an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% identical to SEQ ID NO: 239; or (22) The heavy chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO:242, and the light chain comprises an amino acid sequence that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO:

243. 11 . The antibody or antigen-binding fragment thereof 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 the antibody or antigen-binding fragment thereof 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 according to claim 12 or the vector according to claim 13.

15. A pharmaceutical composition comprising (i) an antibody or antigen-binding fragment thereof 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 of claim 15, further comprising a second therapeutic agent.

17. The pharmaceutical composition of claim 16, wherein the second therapeutic agent is selected from the group consisting of a cytokine, an antibody, a chemotherapeutic agent, and a small molecule drug.

18. A conjugate comprising the antibody or antigen-binding fragment thereof according to any one of claims 1 to 11, and a chemical moiety conjugated thereto.

19. The conjugate of claim 18, wherein the chemical moiety is selected from the group consisting of a therapeutic agent, a detectable moiety, and an immunostimulatory molecule.

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

21. The method of claim 20, wherein the cancer is selected from the group consisting of: adrenal tumors, AIDS-related cancers, alveolar sarcomas of soft tissue, astrocytomas, adrenal cancer, bladder cancer, bone cancer, brain and spinal cord cancer, metastatic brain tumors, B-cell cancer, breast cancer, carotid body tumors, cervical cancer, chondrosarcoma, chordoma, chromophobe renal cell carcinoma, clear cell carcinoma, colon cancer, colorectal cancer, benign fibrous histiocytoma of the skin, desmoplastic small round cell tumor, ependymoma, Ewing's tumor, extraskeletal myxoid chondrosarcoma, incomplete fibroplasia of bone, fibroplasia of bone abnormalities, gallbladder or bile duct cancer, gastric cancer, gestational trophoblastic disease, germ cell tumors, head and neck cancer, hepatocellular carcinoma, islet cell tumors, Kaposi's sarcoma, kidney cancer, leukemia, liposarcoma / malignant lipoma, liver cancer, lymphoma, lung cancer, medulloblastoma, melanoma, meningioma, multiple endocrine neoplasms, multiple myeloma, myelodysplastic syndrome, neuroblastoma, neuroendocrine tumors, ovarian cancer, pancreatic cancer, papillary thyroid cancer, parathyroid tumors, pediatric cancer, peripheral nerve sheath tumors, pheochromocytoma, pituitary tumors, prostate cancer, posterious uveal melanoma, metastatic kidney cancer, 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 medicament is combined 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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