Antigen binding molecule specifically binding to DLL3 and CD3 and medical use thereof

Abstract

The present disclosure relates to antigen binding molecules that specifically bind to DLL3 and CD3, which can be used in the treatment of cancer, and medical uses thereof.

Description

Antigen binding molecules specifically binding to DLL3 and CD3 and their medical uses Technical Field

[0001] The present disclosure belongs to the field of biotechnology, and more specifically, relates to DLL3 / CD3 antigen binding molecules and applications thereof. Background Art

[0002] The statements herein merely provide background information related to the present disclosure and do not necessarily constitute prior art.

[0003] Small cell lung cancer (SCLC) is a relatively malignant type of lung cancer, accounting for 10%-15% of all lung cancer cases. Small cell lung cancer tumors grow rapidly and are prone to metastasis, with a 5-year survival rate of less than 7%. Treatment options for small cell lung cancer are limited, primarily consisting of chemotherapy, such as platinum / etoposide combination chemotherapy. Small cell lung cancer patients respond well to chemotherapy initially, but are very prone to developing drug resistance and relapse. In recent years, immunotherapies, such as PD-L1 and PD1 antibodies, have shown some effectiveness in SCLC patients, but the efficacy is approximately 15%. Currently, no specific targeted therapy has been developed.

[0004] DLL3 is a ligand that inhibits Notch. Normally, DLL3 resides on the Golgi apparatus. In cancer cells (such as small cell lung cancer), DLL3 is expressed on the cell surface. DLL3 binds to Notch in a cis-acting manner, hindering cell-cell binding and Notch internalization in target cells, thereby inhibiting the Notch signaling pathway and promoting tumor cell growth. DLL3 is primarily expressed in neural or neuroendocrine tumors, including small cell lung cancer, large cell neuroendocrine carcinoma, gastrointestinal neuroendocrine tumors, small cell bladder cancer, glioblastoma multiforme, metastatic castration-resistant prostate cancer, and melanoma. DLL3 is particularly expressed in SCLC, with over 80% of SCLCs expressing DLL3, whereas normal lung cancer tissue and adjacent adjacent tissues are negative. This differential expression makes DLL3 a promising therapeutic target for the treatment of SCLC.

[0005] CD3 is a homotypic or heterotypic dimeric antigen expressed on T cells. Functional CD3 is formed by dimerization of two of four different chains: ε, ζ, δ, and γ. CD3 dimer arrangements include γ / ε, δ / ε, and ζ / ζ. CD3 binds to the T cell receptor complex (TCR) and is required for T cell activation. Therefore, the use of anti-CD3 antibodies that activate T cells has been proposed for the treatment of cancer. However, the administration of anti-CD3 antibodies may trigger T cell activation and related cytokine release. Excessive cytokine release leads to severe cytokine release syndrome (CRS), which is an important challenge in the clinical use of anti-CD3 antibodies.

[0006] Summary of the Invention

[0007] The present disclosure provides an antigen binding molecule that specifically binds to DLL3 and CD3.

[0008] In one aspect, the present disclosure provides an antigen binding molecule comprising at least one antigen binding moiety that specifically binds to DLL3 and at least one antigen binding moiety that specifically binds to CD3, wherein the antigen binding moiety that specifically binds to DLL3 comprises a heavy chain variable region DLL3-VH and a light chain variable region DLL3-VL, and the antigen binding moiety that specifically binds to CD3 comprises a heavy chain variable region CD3-VH and a light chain variable region CD3-VL.

[0009] In some embodiments, the antigen binding molecule as described above, wherein:

[0010] (i) the DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of SEQ ID NO: 12, 56 or 57, respectively, and the DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of SEQ ID NO: 13, 63, 64, 65, 66 or 67, respectively, or

[0011] (ii) the DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of SEQ ID NO: 14, 79, 80, 81 or 82, respectively, and the DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of SEQ ID NO: 15, respectively, or

[0012] (iii) the DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of SEQ ID NO: 16, 91, 92, 93 or 94, respectively, and the DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of SEQ ID NO: 17, respectively, or

[0013] (iv) the DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 in the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 in SEQ ID NO: 18, 107, 108, 109, 110, 112, 113, 114 or 115, respectively, and the DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 in the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 in SEQ ID NO: 19, respectively.

[0014] In some embodiments, the antigen binding molecule as described above, wherein:

[0015] (i) the DLL3-HCDR1, DLL3-HCDR2, and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2, and DLL3-HCDR3, respectively, in SEQ ID NO: 12, and the DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3, respectively, in SEQ ID NO: 13; or

[0016] the DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3, respectively, of SEQ ID NO: 54, and the DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3, respectively, of SEQ ID NO: 64; or

[0017] the DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3, respectively, of SEQ ID NO: 54, and the DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3, respectively, of SEQ ID NO: 63; or

[0018] the DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3, respectively, of SEQ ID NO: 56, and the DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3, respectively, of SEQ ID NO: 65; or

[0019] the DLL3-HCDR1, DLL3-HCDR2, and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2, and DLL3-HCDR3, respectively, of SEQ ID NO: 56, and the DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3, respectively, of SEQ ID NO: 66; or

[0020] the DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3, respectively, of SEQ ID NO: 56, and the DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3, respectively, of SEQ ID NO: 67; or

[0021] the DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3, respectively, of SEQ ID NO: 57, and the DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3, respectively, of SEQ ID NO: 65; or

[0022] the DLL3-HCDR1, DLL3-HCDR2, and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2, and DLL3-HCDR3, respectively, of SEQ ID NO: 57, and the DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3, respectively, of SEQ ID NO: 66; or

[0023] the DLL3-HCDR1, DLL3-HCDR2, and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2, and DLL3-HCDR3, respectively, of SEQ ID NO: 57, and the DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3, respectively, of SEQ ID NO: 67; or

[0024] (ii) the DLL3-HCDR1, DLL3-HCDR2, and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2, and DLL3-HCDR3, respectively, in SEQ ID NO: 14, and the DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3, respectively, in SEQ ID NO: 15; or

[0025] the DLL3-HCDR1, DLL3-HCDR2, and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2, and DLL3-HCDR3, respectively, of SEQ ID NO:81, and the DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3, respectively, of SEQ ID NO:77; or

[0026] the DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of SEQ ID NO: 79, 80 or 82, respectively, and the DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of SEQ ID NO: 77, respectively; or

[0027] (iii) the DLL3-HCDR1, DLL3-HCDR2, and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2, and DLL3-HCDR3, respectively, of SEQ ID NO: 16, and the DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3, respectively, of SEQ ID NO: 17; or

[0028] the DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3, respectively, of SEQ ID NO:91, and the DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3, respectively, of SEQ ID NO:87; or

[0029] the DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of SEQ ID NO: 92, 93 or 94, respectively, and the DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of SEQ ID NO: 87, respectively; or

[0030] (iv) the DLL3-HCDR1, DLL3-HCDR2, and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2, and DLL3-HCDR3, respectively, in SEQ ID NO: 18, and the DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3, respectively, in SEQ ID NO: 19; or

[0031] the DLL3-HCDR1, DLL3-HCDR2, and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2, and DLL3-HCDR3, respectively, of SEQ ID NO: 109, and the DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3, respectively, of SEQ ID NO: 100; or

[0032] The DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 in the DLL3-VH respectively comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 in SEQ ID NO: 107, 108, 110, 112, 113, 114 or 115, and the DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 in the DLL3-VL respectively comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 in SEQ ID NO: 100.

[0033] In some embodiments, the DLL3-HCDR1, DLL3-HCDR2, DLL3-HCDR3, DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3 are defined according to Kabat, IMGT, Chothia, AbM, or Contact numbering conventions.

[0034] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0035] i) the DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 24, 71, 72 or 73, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25 or 74; or

[0036] ii) the DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 26 or 84, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 27 or 85, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 28 or 83; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31; or

[0037] iii) the DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 32, 96, 97, 98 or 99, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 33; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 34, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 36; or

[0038] iv) the DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 37, 117, 118, 119 or 120, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 38; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 39, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 40.

[0039] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0040] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 24, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or

[0041] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 24, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25;

[0042] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or

[0043] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 72, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or

[0044] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 73, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or

[0045] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74; or

[0046] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 72, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74; or

[0047] The DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 73, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74.

[0048] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0049] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or

[0050] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 24, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or

[0051] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 72, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or

[0052] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 69, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74; or

[0053] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74; or

[0054] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 69, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 73, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74; or

[0055] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 73, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74; or

[0056] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 69, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or

[0057] The DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25.

[0058] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0059] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 26, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 85, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 83; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31; or

[0060] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 26, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 27, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 83; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31; or

[0061] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 84, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 27, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 83; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31; or

[0062] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 84, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 85, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 83; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31; or

[0063] The DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 26, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 27, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 28; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31.

[0064] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0065] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 33; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 34, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 36; or

[0066] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 97, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 33; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 34, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 36; or

[0067] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 98, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 33; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 34, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 36; or

[0068] The DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 99, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 33; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 34, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 36.

[0069] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0070] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 119, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 38; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 39, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 40; or

[0071] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 117, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 38; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 39, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 40; or

[0072] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 118, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 38; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 39, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 40; or

[0073] The DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 120, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 38; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 39, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 40.

[0074] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0075] The DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25.

[0076] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0077] The DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 24, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25.

[0078] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0079] The DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 26, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 85, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 83; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31.

[0080] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0081] The DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 33; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 34, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 36.

[0082] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0083] The DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 119, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 38; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 39, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 40.

[0084] In some embodiments, in the antigen binding molecule of any of the preceding items, the DLL3-HCDR1, DLL3-HCDR2, DLL3-HCDR3, DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3 are defined according to the Kabat numbering convention.

[0085] In some embodiments, the antigen binding molecule as described in any of the preceding items is less than 4×10 -9 M, 3×10 -9 M, 2×10 -9 M, 1×10 -9 M, 9×10 -10 M, 8×10 -10 M, 7×10 -10 M, 6×10 -10 M, 5×10 -10 M, 4×10 -10 M, 3×10 -10 M, 2×10 -10 M, 1×10 -10 M, 9×10 -11 M binds to human DLL3 with a KD as measured by surface plasmon resonance.

[0086] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the DLL3-VH and DLL3-VL are humanized, and comprise the FR regions of human antibodies.

[0087] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0088] (i) the DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N and 93A; and

[0089] the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 24, 71, 72 or 73, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25 or 74, and the FR region of the DLL3-VL comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0090] (ii) the DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 26 or 84, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 27 or 85, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 28 or 83; and

[0091] the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31, and the FR regions of the DLL3-VL comprise one or more amino acid substitutions selected from the group consisting of 42G, 44V, and 71Y; or

[0092] (iii) the DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 32, 96, 97, 98 or 99, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 33, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 24T, 44S, 71V and 73K; and

[0093] the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 34, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 36, and the FR regions of the DLL3-VL comprise one or more amino acid substitutions selected from the group consisting of 1N, 9K, 43S, 68A, and 85D; or

[0094] (iv) the DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 37, 117, 118, 119 or 120, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 38, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 3R, 5Q, 7F, 9P, 10V, 12V, 40S, 41H, 44S, 48I, 67A, 69L, 71V, 73K, 75S and 83T; and

[0095] The DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 39, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 40; and the FR region of the DLL3-VL comprises one or more amino acid substitutions selected from the group consisting of 9K, 43S, 60D, 68A, 87H and 100S.

[0096] In some embodiments, the antigen binding molecule as described in any of the preceding items has a density of less than 4×10 -9 M, 3×10 -9 M, 2×10 -9 M, 1×10 -9 M, 9×10 -10 M, 8×10 -10 M, 7×10 -10 M, 6×10 -10 M, 5×10 -10 M, 4×10 -10 M, 3×10 -10 M, 2×10 -10 M, 1×10 -10 M, 9×10 -11 M binds to human DLL3 with a KD as measured by surface plasmon resonance.

[0097] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0098] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N, and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 24, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25. NO: 25, and the DLL3-LCDR3 of the DLL3-VL FR region comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0099] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 69, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N, and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 24, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25. NO: 25, and the DLL3-LCDR3 of the DLL3-VL FR region comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0100] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N, and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 24, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25. NO: 25, and the DLL3-LCDR3 of the DLL3-VL FR region comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0101] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 24. NO: 25, and the DLL3-LCDR3 of the DLL3-VL FR region comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0102] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 72, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 73. NO: 25, and the DLL3-LCDR3 of the DLL3-VL FR region comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0103] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 73, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 24. NO: 25, and the DLL3-LCDR3 of the DLL3-VL FR region comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0104] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: NO: 74, and the DLL3-LCDR3 of the DLL3-VL FR region comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0105] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 72, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 73. NO: 74, and the DLL3-LCDR3 of the DLL3-VL FR region comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0106] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 73, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 24. The DLL3-LCDR3 comprises the amino acid sequence of NO: 74, and the FR region of the DLL3-VL comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D.

[0107] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0108] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: NO: 25, and the DLL3-LCDR3 of the DLL3-VL FR region comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0109] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N, and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 24, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25. NO: 25, and the DLL3-LCDR3 of the DLL3-VL FR region comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0110] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 72, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: NO: 25, and the DLL3-LCDR3 of the DLL3-VL FR region comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0111] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 69, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: NO: 74, and the DLL3-LCDR3 of the DLL3-VL FR region comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0112] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: NO: 74, and the DLL3-LCDR3 of the DLL3-VL FR region comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0113] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 69, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 73, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: NO: 74, and the DLL3-LCDR3 of the DLL3-VL FR region comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0114] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 73, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: NO: 74, and the DLL3-LCDR3 of the DLL3-VL FR region comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0115] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 69, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: NO: 25, and the DLL3-LCDR3 of the DLL3-VL FR region comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0116] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: The DLL3-LCDR3 comprises the amino acid sequence of NO: 25, and the FR region of the DLL3-VL comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D.

[0117] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0118] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 26, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 85, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 83; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31, and the FR region of the DLL3-VL comprises one or more amino acid substitutions selected from the group consisting of 42G, 44V, and 71Y; or

[0119] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 26, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 27, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 83; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31, and the FR region of the DLL3-VL comprises one or more amino acid substitutions selected from the group consisting of 42G, 44V, and 71Y; or

[0120] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 84, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 27, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 83; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31, and the FR region of the DLL3-VL comprises one or more amino acid substitutions selected from the group consisting of 42G, 44V, and 71Y; or

[0121] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 84, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 85, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 83; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31, and the FR region of the DLL3-VL comprises one or more amino acid substitutions selected from the group consisting of 42G, 44V, and 71Y; or

[0122] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 26, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 27, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 28; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31, and the FR region of the DLL3-VL comprises one or more amino acid substitutions selected from the group consisting of 42G, 44V and 71Y.

[0123] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0124] The DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 33, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 24T, 44S, 71V and 73K; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 34, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 36, and the FR region of the DLL3-VL comprises one or more amino acid substitutions selected from the group consisting of 1N, 9K, 43S, 68A and 85D.

[0125] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0126] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 119, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 38, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 3R, 5Q, 7F, 9P, 10V, 12V, 40S, 41H, 44S, 48I, 67A, 69L, 71V, 73K, 75S and 83T; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 39, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 38. The DLL3-LCDR3 has the amino acid sequence of NO: 40, and the FR region of the DLL3-VL comprises one or more amino acid substitutions selected from the group consisting of 9K, 43S, 60D, 68A, 87H and 100S.

[0127] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0128] The CD3-VH has: CD3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 129, CD3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 130, and CD3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 131; and the CD3-VL has: CD3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 132, CD3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 133, and CD3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 134.

[0129] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0130] The CD3-VH has: CD3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 129, CD3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 130, and CD3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 135; and the CD3-VL has: CD3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 132, CD3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 133, and CD3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 134.

[0131] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0132] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 50, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of Q1E, Q43K, M48I, V67A, I69L, R71V, T73K, and S76N in the FR region of SEQ ID NO: 50.

[0133] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0134] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 51, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of Q1E, 5Q, R38K, V68A, F69L, L71V, T73K, V75S, and S76N in the FR region of SEQ ID NO: 51.

[0135] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0136] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 52, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of F27Y, S30T, I69L, R71V, D73K, and T93A in the FR region of SEQ ID NO: 52.

[0137] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0138] The DLL3-VL comprises the amino acid sequence of SEQ ID NO: 62, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of F36L, A43S, P44F, S46G, T69A, F71Y, and T85D in the FR region of SEQ ID NO: 62.

[0139] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0140] The DLL3-VL comprises the amino acid sequence of SEQ ID NO: 68, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of Y36L, Q42K, L46G, T69A, F71Y, E79Q, and V85D in the FR region of SEQ ID NO: 68.

[0141] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0142] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 78, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions in the FR region of SEQ ID NO: 78.

[0143] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0144] The DLL3-VL comprises the amino acid sequence of SEQ ID NO: 75, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of K42G, P44V, and F71Y in the FR region of SEQ ID NO: 75.

[0145] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0146] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 95, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of Q1E, A24T, R44S, R71V, and T73K in the FR region of SEQ ID NO: 95.

[0147] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0148] The DLL3-VL comprises the amino acid sequence of SEQ ID NO: 88, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of D1N, D9K, P43S, G68A, and V85D in the FR region of SEQ ID NO: 88.

[0149] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0150] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 116, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of Q1E, Q3R, V5Q, S7F, A9P, E10V, K12V, A40S, P41H, R44S, M48I, V67A, I69L, R71V, T73K, A75S, and R83T in the FR region of SEQ ID NO: 116.

[0151] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0152] The DLL3-VL comprises the amino acid sequence of SEQ ID NO: 100, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of D9K, P43S, G68A, and Y87H in the FR region of SEQ ID NO: 100.

[0153] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0154] The DLL3-VL comprises the amino acid sequence of SEQ ID NO: 103, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of A43S, S60D, and Q100S in the FR region of SEQ ID NO: 103.

[0155] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0156] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 56, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions in the FR region of SEQ ID NO: 56.

[0157] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0158] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 57, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions in the FR region of SEQ ID NO: 57.

[0159] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0160] The DLL3-VL comprises the amino acid sequence of SEQ ID NO: 63, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions in the FR region of SEQ ID NO: 63; in some embodiments, the amino acid substitutions are selected from one or more amino acid substitutions selected from the group consisting of A43S and P44F.

[0161] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0162] The DLL3-VL comprises the amino acid sequence of SEQ ID NO: 64, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions in the FR region of SEQ ID NO: 64; in some embodiments, the amino acid substitutions are selected from one or more amino acid substitutions selected from the group consisting of A43S and P44F.

[0163] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0164] The DLL3-VL comprises the amino acid sequence of SEQ ID NO: 65, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions in the FR region of SEQ ID NO: 65; in some embodiments, the amino acid substitutions are selected from one or more amino acid substitutions selected from the group consisting of A43S and P44F.

[0165] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0166] The DLL3-VL comprises the amino acid sequence of SEQ ID NO: 66, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions in the FR region of SEQ ID NO: 66; in some embodiments, the amino acid substitutions are selected from one or more amino acid substitutions selected from the group consisting of A43S and P44F.

[0167] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0168] The DLL3-VL comprises the amino acid sequence of SEQ ID NO: 67, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions in the FR region of SEQ ID NO: 67.

[0169] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0170] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 79, 80, 81 or 82, or a variant of SEQ ID NO: 79, 80, 81 or 82. In some embodiments, the variant comprises one or more amino acid substitutions in the FR region of SEQ ID NO: 79, 80, 81 or 82; and

[0171] The DLL3-VL comprises the amino acid sequence of SEQ ID NO: 75, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of K42G, P44V, and F71Y in the FR region of SEQ ID NO: 75.

[0172] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0173] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 91, 92, 93 or 94, or a variant of SEQ ID NO: 91, 92, 93 or 94. In some embodiments, the variant comprises one or more amino acid substitutions in the FR region of SEQ ID NO: 91, 92, 93 or 94; and

[0174] The DLL3-VL comprises the amino acid sequence of SEQ ID NO: 88, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of D1N, D9K, P43S, G68A, and V85D in the FR region of SEQ ID NO: 88.

[0175] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0176] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 107, 108, 109 or 110, or a variant of SEQ ID NO: 107, 108, 109 or 110. In some embodiments, the variant comprises one or more amino acid substitutions in the FR regions of SEQ ID NO: 107, 108, 109 or 110; in some embodiments, the amino acid substitutions are selected from the group consisting of V5Q, S7F, A9P, E10V, K12V, A40S, P41H, M48I, V67A, A75S and R83T.

[0177] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0178] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 112, or a variant of SEQ ID NO: 112. In some embodiments, the variant comprises one or more amino acid substitutions in the FR region of SEQ ID NO: 112; in some embodiments, the amino acid substitutions are selected from the group consisting of V5Q, A9P, K12V, A40S, P41H, 4M8I, V67A, and R83T.

[0179] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0180] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 113, or a variant of SEQ ID NO: 113. In some embodiments, the variant comprises one or more amino acid substitutions in the FR region of SEQ ID NO: 113; in some embodiments, the amino acid substitutions are selected from the group consisting of V5Q, S7F, A9P, E10V, K12V, A40S, P41H, A75S, and R83T.

[0181] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0182] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 114, or a variant of SEQ ID NO: 114. In some embodiments, the variant comprises one or more amino acid substitutions in the FR region of SEQ ID NO: 114; in some embodiments, the amino acid substitutions are selected from the group consisting of V5Q, S7F, A9P, E10V, K12V, M48I, V67A, A75S, and R83T.

[0183] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0184] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 115, or a variant of SEQ ID NO: 115. In some embodiments, the variant comprises one or more amino acid substitutions in the FR region of SEQ ID NO: 115; in some embodiments, the amino acid substitutions are selected from the group consisting of V5Q, A9P, K12V, A40S, P41H, M48I, and V67A.

[0185] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0186] The DLL3-VL comprises the amino acid sequence of SEQ ID NO: 100, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of D9K, P43S, G68A, and Y87H in the FR region of SEQ ID NO: 100.

[0187] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0188] The DLL3-VL comprises the amino acid sequence of SEQ ID NO: 103, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of A43S, S60D, and Q100S in the FR region of SEQ ID NO: 103.

[0189] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0190] i) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 12, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56 or 57, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 13, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67 or 68; or

[0191] ii) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 14, 78, 79, 80, 81 or 82, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 15, 75, 76 or 77; or

[0192] iii) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 16, 89, 90, 91, 92, 93, 94 or 95, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 17, 86, 87 or 88; or

[0193] iv) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 18, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115 or 116, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 19, 100, 101, 102, 103 or 104.

[0194] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0195] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 43, 44 or 45, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 58, 59 or 60; or

[0196] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 47, 48, 49, 53, 54 or 55, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 59; or

[0197] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 43, 44 or 45, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 60; or

[0198] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 46, 48, 53, 54 or 55, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 61; or

[0199] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 54, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 63 or 64; or

[0200] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 56 or 57, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 65, 66 or 67.

[0201] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0202] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 78 or 79, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 75, 76 or 77; or

[0203] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 78, 79, 80, 81 or 82, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 77.

[0204] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0205] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 89, 90, 91, 92, 93 or 94, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 86 or 87; or

[0206] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 95, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 87.

[0207] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0208] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 105, 106, 107, 108, 109, 110, or 111, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 100, 101, or 102; or

[0209] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 112, 113, 114 or 115, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 100, 103 or 104; or

[0210] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 109, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 103.

[0211] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0212] i) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 54, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 63; or

[0213] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 54, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 61; or

[0214] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 54, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 64; or

[0215] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 56, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 65; or

[0216] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 56, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 66; or

[0217] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 56, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 67; or

[0218] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 57, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 65; or

[0219] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 57, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 66; or

[0220] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 57, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 67; or

[0221] ii) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 81, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 77; or

[0222] iii) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 91, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 87; or

[0223] iv) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 109, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 100.

[0224] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0225] i) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 12, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 13; or

[0226] ii) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 14, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 15; or

[0227] iii) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 16, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 17; or

[0228] iv) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 18, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 19.

[0229] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0230] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 54, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 63.

[0231] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0232] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 54, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 61.

[0233] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0234] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 81, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 77.

[0235] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0236] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 91, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 87.

[0237] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0238] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 109, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 100.

[0239] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0240] The CD3-VH comprises the amino acid sequence of SEQ ID NO: 136, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137.

[0241] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0242] The CD3-VH comprises the amino acid sequence of SEQ ID NO: 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137.

[0243] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the antigen binding moiety that specifically binds to DLL3 or the antigen binding moiety that specifically binds to CD3 comprises a titin chain and an obscurin chain that can form a dimer.

[0244] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the antigen binding moiety that specifically binds to DLL3 comprises a titin chain and an obscurin chain that can form a dimer.

[0245] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the antigen binding moiety that specifically binds to CD3 comprises a titin chain and an obscurin chain that can form a dimer.

[0246] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the titin chain comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 192 to SEQ ID NO: 210, and the obscurin chain comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 211 to SEQ ID NO: 251.

[0247] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the titin chain comprises the amino acid sequence of SEQ ID NO: 208.

[0248] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the Obscurin chain comprises the amino acid sequence of SEQ ID NO: 246.

[0249] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the titin chain comprises the amino acid sequence of SEQ ID NO: 208, and the obscurin chain comprises the amino acid sequence of SEQ ID NO: 246.

[0250] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the antigen binding molecule comprises an Fc region.

[0251] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the antigen binding molecule comprises a human IgG Fc region.

[0252] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the antigen binding molecule comprises a human IgG1 Fc region.

[0253] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the antigen binding molecule comprises an Fc region, and the Fc region comprises one or more amino acid substitutions that can reduce the binding of the Fc region to an Fcγ receptor.

[0254] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the antigen binding molecule comprises an Fc region, the Fc region is a human IgG1 Fc region, and the amino acids at positions 234 and 235 are A, and the numbering is according to the EU index.

[0255] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the antigen binding molecule comprises an Fc region, the Fc region comprises a first subunit Fc1 and a second subunit Fc2 that can associate with each other, and the Fc1 and Fc2 each independently have one or more amino acid substitutions that reduce homodimerization of the Fc region.

[0256] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the antigen binding molecule comprises an Fc region, the Fc region comprises a first subunit Fc1 and a second subunit Fc2 that can associate with each other, the Fc1 has a protrusion structure according to the knob-and-mortar technique, and the Fc2 has a hole structure according to the knob-and-mortar technique.

[0257] In some embodiments, an antigen binding molecule as described in any of the preceding items, wherein the antigen binding molecule comprises an Fc region, the Fc region comprising a first subunit Fc1 and a second subunit Fc2 that can associate with each other, the Fc1 having a protrusion structure according to the knob-and-mortar technique, and the Fc2 having a hole structure according to the knob-and-mortar technique, the amino acid at position 366 of the Fc1 is W; and the amino acid at position 366 of the Fc2 is S, the amino acid at position 368 is A, and the amino acid at position 407 is V, and the numbering is according to the EU index.

[0258] In some embodiments, an antigen binding molecule as described in any of the preceding items, wherein the antigen binding molecule comprises an Fc region, wherein the Fc region comprises a first subunit Fc1 and a second subunit Fc2 that can associate with each other, wherein the Fc1 has a protrusion structure according to the knob-and-mortar technique, and wherein the Fc2 has a hole structure according to the knob-and-mortar technique, wherein the amino acid at position 354 of the Fc1 is C and the amino acid at position 366 is W; and the amino acid at position 349 of the Fc2 is C, the amino acid at position 366 is S, the amino acid at position 368 is A, and the amino acid at position 407 is V, and the numbering is according to the EU index.

[0259] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the antigen binding molecule comprises an Fc region, the Fc region comprising a first subunit Fc1 and a second subunit Fc2 that can associate with each other, wherein the Fc1 comprises the amino acid sequence of SEQ ID NO: 143; and the Fc2 comprises the amino acid sequence of SEQ ID NO: 144.

[0260] In some embodiments, the antigen binding molecule is as described in any of the preceding items, wherein the antigen binding molecule comprises an Fc region, the Fc region comprising a first subunit Fc1 and a second subunit Fc2 that can associate with each other, wherein the amino acid at position 349 of the Fc1 is C, the amino acid at position 366 is W, and the amino acid at position 237 is A; and the amino acid at position 354 of the Fc2 is C, the amino acid at position 366 is S, the amino acid at position 368 is A, the amino acid at position 407 is V, and the amino acid at position 237 is A, and the numbering is according to the EU index.

[0261] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the antigen binding molecule comprises an Fc region, the Fc region comprising a first subunit Fc1 and a second subunit Fc2 that can associate with each other, wherein the Fc1 comprises the amino acid sequence of SEQ ID NO: 145; and the Fc2 comprises the amino acid sequence of SEQ ID NO: 146.

[0262] It should be understood that the ordinal numbers "first", "second", "Formula a", "Formula b", "Fc1", "Linker 3", etc. in the present disclosure are only used to distinguish different technical features, elements, components, and steps, and are not intended to limit the level, sequence, or quantity.

[0263] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the antigen binding molecule comprises an antigen binding moiety that specifically binds to DLL3 and an antigen binding moiety that specifically binds to CD3.

[0264] In some embodiments, the antigen binding molecule of any of the preceding items, wherein the antigen binding molecule comprises one antigen binding moiety that specifically binds to DLL3 and one antigen binding moiety that specifically binds to CD3, wherein:

[0265] The antigen binding moiety that specifically binds to DLL3 is a Fab; the antigen binding moiety that specifically binds to CD3 is a substituted Fab comprising a titin chain and an obscurin chain that can form a dimer.

[0266] In some embodiments, the antigen binding molecule of any of the preceding items, wherein the antigen binding molecule comprises one antigen binding moiety that specifically binds to DLL3 and one antigen binding moiety that specifically binds to CD3, wherein:

[0267] The antigen binding moiety that specifically binds to CD3 is a Fab, and the antigen binding moiety that specifically binds to DLL3 is a substituted Fab comprising a titin chain and an obscurin chain that can form a dimer.

[0268] In some embodiments, the antigen-binding molecule as described in any of the preceding items comprises a first chain having a structure represented by formula (a), a second chain having a structure represented by formula (b), a third chain having a structure represented by formula (c), and a fourth chain having a structure represented by formula (d).

[0269] (a) [DLL3-VH]-[Linker 1]-[Titin chain] / [Obscurin chain]-[Fc2] / [Fc1],

[0270] (b) [DLL3-VL]-[Linker 2]-[Obscurin chain] / [Titin chain],

[0271] (c)[CD3-VH]-[CH1]-[Fc1] / [Fc2],

[0272] (d) [CD3-VL]-[CL],

[0273] Wherein: Linker 1 and Linker 2 are identical or different peptide linkers; the structures represented by formulas (a), (b), (c), and (d) are arranged from the N-terminus to the C-terminus; " / " represents "or", i.e., Fc1 and Fc2 can be interchanged, and the titin chain and obscurin chain can be interchanged.

[0274] In some embodiments, the antigen-binding molecule as described in any of the preceding items comprises a first chain having a structure represented by formula (a), a second chain having a structure represented by formula (b), a third chain having a structure represented by formula (c), and a fourth chain having a structure represented by formula (d).

[0275] (a) [DLL3-VH]-[Linker 1]-[Titin chain]-[Fc2],

[0276] (b) [DLL3-VL]-[Linker 2]-[Obscurin chain],

[0277] (c) [CD3-VH]-[CH1]-[Fc1],

[0278] (d) [CD3-VL]-[CL],

[0279] Wherein: the linker 1 and the linker 2 are the same or different peptide linkers; the structures shown in formulas (a), (b), (c) and (d) are arranged from the N-terminus to the C-terminus; Fc1 and Fc2 can be interchanged, and the titin chain and obscurin chain can be interchanged.

[0280] In some embodiments, the antigen-binding molecule as described in any of the preceding items comprises a first chain having a structure represented by formula (a), a second chain having a structure represented by formula (b), a third chain having a structure represented by formula (c), and a fourth chain having a structure represented by formula (d).

[0281] (a) [DLL3-VH]-[Linker 1]-[Titin chain]-[Fc2],

[0282] (b) [DLL3-VL]-[Linker 2]-[Obscurin chain],

[0283] (c) [CD3-VH]-[CH1]-[Fc1],

[0284] (d) [CD3-VL]-[CL],

[0285] Wherein: the linker 1 and the linker 2 are the same or different peptide linkers; the structures shown in formulas (a), (b), (c) and (d) are arranged from the N-terminus to the C-terminus.

[0286] In some embodiments, the antigen-binding molecule as described in any of the preceding items comprises a first chain having a structure represented by formula (a'), a second chain having a structure represented by formula (b'), a third chain having a structure represented by formula (c'), and a fourth chain having a structure represented by formula (d').

[0287] (a') [CD3-VH]-[Linker 1]-[Titin chain] / Obscurin chain]-[Fc2] / [Fc1],

[0288] (b') [CD3-VL]-[Linker 2]-[Obscurin chain] / [Titin chain],

[0289] (c')[DLL3-VH]-[CH1]-[Fc1] / [Fc2],

[0290] (d')[DLL3-VL]-[CL],

[0291] Wherein: Linker 1 and Linker 2 do not exist, i.e., Linker 1 and Linker 2 are both peptide bonds; the structures represented by formulas (a'), (b'), (c'), and (d') are arranged from the N-terminus to the C-terminus. " / " represents "or", i.e., Fc1 and Fc2 can be interchanged, and the titin chain and obscurin chain can be interchanged.

[0292] In some embodiments, the antigen-binding molecule as described in any of the preceding items comprises a first chain having a structure represented by formula (a'), a second chain having a structure represented by formula (b'), a third chain having a structure represented by formula (c'), and a fourth chain having a structure represented by formula (d').

[0293] (a') [CD3-VH]-[Linker 1]-[Titin chain]-[Fc2],

[0294] (b') [CD3-VL]-[Linker 2]-[Obscurin chain],

[0295] (c')[DLL3-VH]-[CH1]-[Fc1],

[0296] (d')[DLL3-VL]-[CL],

[0297] Wherein: the linker 1 and the linker 2 do not exist, that is, the linker 1 and the linker 2 are both peptide bonds; the structures represented by formulas (a'), (b'), (c') and (d') are arranged from the N-terminus to the C-terminus; Fc1 and Fc2 are interchangeable, and the titin chain and the obscurin chain are interchangeable.

[0298] In some embodiments, the antigen-binding molecule as described in any of the preceding items comprises a first chain having a structure represented by formula (a), a second chain having a structure represented by formula (b), a third chain having a structure represented by formula (c), and a fourth chain having a structure represented by formula (d).

[0299] (a') [CD3-VH]-[Linker 1]-[Titin chain]-[Fc2],

[0300] (b') [CD3-VL]-[Linker 2]-[Obscurin chain],

[0301] (c')[DLL3-VH]-[CH1]-[Fc1],

[0302] (d')[DLL3-VL]-[CL],

[0303] Wherein: the linker 1 and the linker 2 do not exist, that is, the linker 1 and the linker 2 are both peptide bonds; the structures shown in formulas (a), (b), (c) and (d) are arranged from the N-terminus to the C-terminus.

[0304] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0305] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 24, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; and

[0306] The CD3-VH comprises: a CD3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 129, a CD3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 130, and a CD3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 131 or 135; and the CD3-VL comprises: a CD3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 132, a CD3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 133, and a CD3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 134.

[0307] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0308] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; and

[0309] The CD3-VH has: CD3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 129, CD3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 130, and CD3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 131; and the CD3-VL has: CD3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 132, CD3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 133, and CD3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 134.

[0310] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0311] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; and

[0312] The CD3-VH comprises the amino acid sequence of SEQ ID NO: 136, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137.

[0313] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0314] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 26, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 85, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 83; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31; and

[0315] The CD3-VH comprises: a CD3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 129, a CD3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 130, and a CD3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 131 or 135; and the CD3-VL comprises: a CD3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 132, a CD3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 133, and a CD3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 134.

[0316] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0317] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 33; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 34, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 36; and

[0318] The CD3-VH comprises: a CD3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 129, a CD3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 130, and a CD3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 131 or 135; and the CD3-VL comprises: a CD3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 132, a CD3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 133, and a CD3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 134.

[0319] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0320] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 33; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 34, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 36; and

[0321] The CD3-VH has: CD3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 129, CD3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 130, and CD3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 131; and the CD3-VL has: CD3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 132, CD3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 133, and CD3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 134.

[0322] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0323] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 33; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 34, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 36; and

[0324] The CD3-VH has: CD3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 129, CD3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 130, and CD3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 135; and the CD3-VL has: CD3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 132, CD3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 133, and CD3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 134.

[0325] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0326] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 119, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 38; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 39, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 40; and

[0327] The CD3-VH comprises: a CD3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 129, a CD3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 130, and a CD3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 131 or 135; and the CD3-VL comprises: a CD3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 132, a CD3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 133, and a CD3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 134.

[0328] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0329] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 33; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 34, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 36; and

[0330] The CD3-VH has: CD3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 129, CD3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 130, and CD3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 131; and the CD3-VL has: CD3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 132, CD3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 133, and CD3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 134.

[0331] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0332] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 54, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 61; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137.

[0333] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0334] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 54, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 63; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137.

[0335] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0336] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 54, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 63; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137.

[0337] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0338] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 81, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 77; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137.

[0339] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0340] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 91, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 87; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137.

[0341] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0342] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 109, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 100; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137.

[0343] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0344] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 91, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 87; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137.

[0345] In some embodiments, the antigen-binding molecule described in any of the preceding items, wherein the titin chain and obscurin chain are any of the titin chains and obscurin chains that can form dimers as described in Tables 3-1 and 3-2 of the present disclosure. In some embodiments, the antigen-binding molecule described in any of the preceding items, wherein the titin chain comprises the amino acid sequence of SEQ ID NO: 208. In some embodiments, the antigen-binding molecule described in any of the preceding items, wherein the obscurin chain comprises the amino acid sequence of SEQ ID NO: 246.

[0346] In some embodiments, the antigen binding molecules as described in any of the preceding items, wherein the linker 1 and linker 2 are peptide linkers known in the art, as long as the antigen binding molecules can exhibit the desired antigen binding activity. For example, the peptide linker can be a flexible peptide having 1-50 or 3-20 amino acid residues. In some embodiments, the length of the peptide linker is 3-15 amino acid residues. In some embodiments, the peptide linker 1 and linker 2 each independently have a structure of (GGGGS)n, wherein n is 1, 2 or 3. In some embodiments, the sequences of the linker 1 and linker 2 are both GGGGS (SEQ ID NO: 147).

[0347] In some embodiments, the antigen-binding molecule of any of the preceding items, wherein the CH1 is the CH1 sequence of IgG. In some embodiments, the CH1 is the CH1 of IgG1. In some embodiments, the CH1 comprises the amino acid sequence of SEQ ID NO: 141.

[0348] In some embodiments, the antigen-binding molecule as described in any of the preceding items, wherein the CL is the light chain constant region of an antibody. In some embodiments, the antigen-binding molecule as described in any of the preceding items, wherein the CL is the light chain constant region of a kappa chain or a lamada chain. In some embodiments, wherein the CL comprises the amino acid sequence of SEQ ID NO: 142.

[0349] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the antigen binding molecule has:

[0350] a first chain comprising the amino acid sequence of SEQ ID NO: 171, a second chain comprising the amino acid sequence of SEQ ID NO: 172, a third chain comprising the amino acid sequence of SEQ ID NO: 154, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 155; or

[0351] a first chain comprising the amino acid sequence of SEQ ID NO: 171, a second chain comprising the amino acid sequence of SEQ ID NO: 172, a third chain comprising the amino acid sequence of SEQ ID NO: 156, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 155; or

[0352] a first chain comprising the amino acid sequence of SEQ ID NO: 152, a second chain comprising the amino acid sequence of SEQ ID NO: 153, a third chain comprising the amino acid sequence of SEQ ID NO: 154, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 155; or

[0353] a first chain comprising the amino acid sequence of SEQ ID NO: 152, a second chain comprising the amino acid sequence of SEQ ID NO: 153, a third chain comprising the amino acid sequence of SEQ ID NO: 156, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 155; or

[0354] a first chain comprising the amino acid sequence of SEQ ID NO: 164, a second chain comprising the amino acid sequence of SEQ ID NO: 165, a third chain comprising the amino acid sequence of SEQ ID NO: 154, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 155; or

[0355] a first chain comprising the amino acid sequence of SEQ ID NO: 164, a second chain comprising the amino acid sequence of SEQ ID NO: 165, a third chain comprising the amino acid sequence of SEQ ID NO: 156, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 155; or

[0356] a first chain comprising the amino acid sequence of SEQ ID NO: 178, a second chain comprising the amino acid sequence of SEQ ID NO: 179, a third chain comprising the amino acid sequence of SEQ ID NO: 154, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 155; or

[0357] A first chain comprising the amino acid sequence of SEQ ID NO: 178, a second chain comprising the amino acid sequence of SEQ ID NO: 179, a third chain comprising the amino acid sequence of SEQ ID NO: 156, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 155.

[0358] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the antigen binding molecule has:

[0359] A first chain comprising the amino acid sequence of SEQ ID NO: 171, a second chain comprising the amino acid sequence of SEQ ID NO: 172, a third chain comprising the amino acid sequence of SEQ ID NO: 154, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 155.

[0360] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the antigen binding molecule comprises an antigen binding moiety that specifically binds to DLL3 and an antigen binding moiety that specifically binds to CD3, wherein the antigen binding moiety that specifically binds to DLL3 is a Fab; and the antigen binding moiety that specifically binds to CD3 is an scFv. In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the antigen binding molecule comprises a first chain having a structure represented by formula (e), a second chain having a structure represented by formula (f), and a third chain having a structure represented by formula (g).

[0361] (e)[DLL3-VL]-[CL],

[0362] (f)[DLL3-VH]-[CH1]-[Fc2] / [Fc1],

[0363] (g) [CD3-VH]-[Linker 3]-[CD3-VL]-[Linker 4]-[Fc1] / [Fc2],

[0364] Wherein: the linker 3 and the linker 4 are the same or different peptide linkers;

[0365] The structures shown in formulas (e), (f), and (g) are arranged from the N-terminus to the C-terminus. " / " represents "or", meaning that Fc1 and Fc2 can be interchanged.

[0366] In some embodiments, the antigen-binding molecule as described in any of the preceding items comprises a first chain having a structure represented by formula (e), a second chain having a structure represented by formula (f), and a third chain having a structure represented by formula (g).

[0367] (e)[DLL3-VL]-[CL],

[0368] (f) [DLL3-VH]-[CH1]-[Fc2],

[0369] (g) [CD3-VH]-[Linker 3]-[CD3-VL]-[Linker 4]-[Fc1],

[0370] Wherein: the linker 3 and the linker 4 are the same or different peptide linkers;

[0371] The structures shown in formulas (e), (f), and (g) are arranged from the N-terminus to the C-terminus; Fc1 and Fc2 can be positioned interchangeably.

[0372] In some embodiments, the antigen-binding molecule as described in any of the preceding items comprises a first chain having a structure represented by formula (e), a second chain having a structure represented by formula (f), and a third chain having a structure represented by formula (g).

[0373] (e)[DLL3-VL]-[CL],

[0374] (f) [DLL3-VH]-[CH1]-[Fc2],

[0375] (g) [CD3-VH]-[Linker 3]-[CD3-VL]-[Linker 4]-[Fc1],

[0376] Wherein: the linker 3 and the linker 4 are the same or different peptide linkers;

[0377] The structures represented by formulae (e), (f) and (g) are arranged from the N-terminus to the C-terminus.

[0378] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the antigen binding molecule comprises an antigen binding moiety that specifically binds to DLL3 and an antigen binding moiety that specifically binds to CD3, the antigen binding moiety that specifically binds to DLL3 is scFv; the antigen binding moiety that specifically binds to CD3 is Fab.

[0379] In some embodiments, the antigen-binding molecule as described in any of the preceding items comprises a first chain having a structure represented by formula (e'), a second chain having a structure represented by formula (f'), and a third chain having a structure represented by formula (g').

[0380] (e')[CD3-VL]-[CL],

[0381] (f')[CD3-VH]-[CH1]-[Fc2] / [Fc1],

[0382] (g') [DLL3-VH]-[Linker 3]-[DLL3-VL]-[Linker 4]-[Fc1] / [Fc2],

[0383] Wherein: the linker 3 and the linker 4 are the same or different peptide linkers;

[0384] The structures represented by formulas (e'), (f') and (g') are arranged from the N-terminus to the C-terminus. " / " represents "or".

[0385] In some embodiments, the antigen-binding molecule as described in any of the preceding items comprises a first chain having a structure represented by formula (e'), a second chain having a structure represented by formula (f'), and a third chain having a structure represented by formula (g').

[0386] (e')[CD3-VL]-[CL],

[0387] (f') [CD3-VH]-[CH1]-[Fc2],

[0388] (g') [DLL3-VH]-[Linker 3]-[DLL3-VL]-[Linker 4]-[Fc1],

[0389] Wherein: the linker 3 and the linker 4 are the same or different peptide linkers;

[0390] The structures represented by formulas (e'), (f') and (g') are arranged from the N-terminus to the C-terminus; Fc1 and Fc2 can be positioned interchangeably.

[0391] In some embodiments, the antigen-binding molecule as described in any of the preceding items comprises a first chain having a structure represented by formula (e'), a second chain having a structure represented by formula (f'), and a third chain having a structure represented by formula (g').

[0392] (e')[CD3-VL]-[CL],

[0393] (f') [CD3-VH]-[CH1]-[Fc2],

[0394] (g') [DLL3-VH]-[Linker 3]-[DLL3-VL]-[Linker 4]-[Fc1],

[0395] Wherein: the linker 3 and the linker 4 are the same or different peptide linkers;

[0396] The structures represented by formulae (e'), (f') and (g') are arranged from the N-terminus to the C-terminus.

[0397] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0398] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 24, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; and

[0399] The CD3-VH comprises: a CD3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 129, a CD3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 130, and a CD3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 131 or 135; and the CD3-VL comprises: a CD3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 132, a CD3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 133, and a CD3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 134.

[0400] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0401] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 26, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 85, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 83; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31; and

[0402] The CD3-VH comprises: a CD3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 129, a CD3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 130, and a CD3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 131 or 135; and the CD3-VL comprises: a CD3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 132, a CD3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 133, and a CD3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 134.

[0403] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0404] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 33; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 34, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 36; and

[0405] The CD3-VH comprises: a CD3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 129, a CD3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 130, and a CD3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 131 or 135; and the CD3-VL comprises: a CD3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 132, a CD3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 133, and a CD3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 134.

[0406] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0407] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 119, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 38; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 39, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 40; and

[0408] The CD3-VH comprises: a CD3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 129, a CD3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 130, and a CD3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 131 or 135; and the CD3-VL comprises: a CD3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 132, a CD3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 133, and a CD3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 134.

[0409] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0410] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 33; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 34, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 36; and

[0411] The CD3-VH has: CD3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 129, CD3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 130, and CD3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 135; and the CD3-VL has: CD3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 132, CD3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 133, and CD3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 134.

[0412] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0413] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 54, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 61; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137.

[0414] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0415] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 54, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 63; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137.

[0416] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0417] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 91, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 87; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137.

[0418] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0419] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 81, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 77; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137.

[0420] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0421] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 109, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 100; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137.

[0422] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0423] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 91, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 87; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137.

[0424] In some embodiments, the antigen binding molecules as described in any of the preceding items, wherein the linker 3 and linker 4 are peptide linkers known in the art, as long as the antigen binding molecules can exhibit the desired antigen binding activity. For example, the peptide linker can be a flexible peptide having 1-50 or 3-20 amino acid residues. In some embodiments, the length of the peptide linker is 3-15 amino acid residues. In some embodiments, the peptide linker 3 and linker 4 each independently have a structure of (GGGGS)n, wherein n is 1-5. In some embodiments, n is 1, 2, 3 or 4. In some embodiments, the sequence of the linker 3 is GGGGSGGGGSGGGGS (SEQ ID NO: 148). In some embodiments, the sequence of the linker 4 is GGGGS (SEQ ID NO: 147).

[0425] In some embodiments, the antigen-binding molecule of any of the preceding items, wherein the CH1 is the CH1 sequence of IgG. In some embodiments, the CH1 is the CH1 of IgG1. In some embodiments, the CH1 comprises the amino acid sequence of SEQ ID NO: 141.

[0426] In some embodiments, the antigen-binding molecule as described in any of the preceding items, wherein the CL is the light chain constant region of an antibody. In some embodiments, the antigen-binding molecule as described in any of the preceding items, wherein the CL is the light chain constant region of a kappa chain or a lamada chain. In some embodiments, wherein the CL comprises the amino acid sequence of SEQ ID NO: 142.

[0427] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the antigen binding molecule has:

[0428] a first chain comprising the amino acid sequence of SEQ ID NO: 173, a second chain comprising the amino acid sequence of SEQ ID NO: 174, and a third chain comprising the amino acid sequence of SEQ ID NO: 160; or

[0429] a first chain comprising the amino acid sequence of SEQ ID NO: 173, a second chain comprising the amino acid sequence of SEQ ID NO: 174, and a third chain comprising the amino acid sequence of SEQ ID NO: 159; or

[0430] a first chain comprising the amino acid sequence of SEQ ID NO: 157, a second chain comprising the amino acid sequence of SEQ ID NO: 158, and a third chain comprising the amino acid sequence of SEQ ID NO: 159; or

[0431] a first chain comprising the amino acid sequence of SEQ ID NO: 157, a second chain comprising the amino acid sequence of SEQ ID NO: 158, and a third chain comprising the amino acid sequence of SEQ ID NO: 160; or

[0432] a first chain comprising the amino acid sequence of SEQ ID NO: 166, a second chain comprising the amino acid sequence of SEQ ID NO: 167, and a third chain comprising the amino acid sequence of SEQ ID NO: 159; or

[0433] a first chain comprising the amino acid sequence of SEQ ID NO: 166, a second chain comprising the amino acid sequence of SEQ ID NO: 167, and a third chain comprising the amino acid sequence of SEQ ID NO: 160; or

[0434] a first chain comprising the amino acid sequence of SEQ ID NO: 180, a second chain comprising the amino acid sequence of SEQ ID NO: 181, and a third chain comprising the amino acid sequence of SEQ ID NO: 159; or

[0435] A first chain comprising the amino acid sequence of SEQ ID NO: 180, a second chain comprising the amino acid sequence of SEQ ID NO: 181, and a third chain comprising the amino acid sequence of SEQ ID NO: 160.

[0436] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the antigen binding molecule has:

[0437] A first chain comprising the amino acid sequence of SEQ ID NO: 173, a second chain comprising the amino acid sequence of SEQ ID NO: 174, and a third chain comprising the amino acid sequence of SEQ ID NO: 160.

[0438] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the antigen binding molecule comprises an antigen binding moiety that specifically binds to DLL3 and an antigen binding moiety that specifically binds to CD3,

[0439] The antigen-binding molecule comprises a first chain having a structure represented by formula (h) and a second chain having a structure represented by formula (i).

[0440] (h) [DLL3-VL]-[Linker 5]-[CD3-VH]-[Linker 6]-[Fc1] / [Fc1],

[0441] (i) [CD3-VL]-[Linker 7]-[DLL3-VH]-[Linker 8]-[Fc2] / [Fc2],

[0442] Wherein: the linker 5, linker 6, linker 7 and linker 8 are the same or different peptide linkers;

[0443] The structures shown in formulas (h) and (i) are arranged from the N-terminus to the C-terminus. " / " represents "or", meaning that Fc1 and Fc2 can be interchanged.

[0444] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the antigen binding molecule comprises an antigen binding moiety that specifically binds to DLL3 and an antigen binding moiety that specifically binds to CD3,

[0445] The antigen-binding molecule comprises a first chain having a structure represented by formula (h) and a second chain having a structure represented by formula (i).

[0446] (h) [DLL3-VL]-[Linker 5]-[CD3-VH]-[Linker 6]-[Fc1],

[0447] (i) [CD3-VL]-[Linker 7]-[DLL3-VH]-[Linker 8]-[Fc2],

[0448] Wherein: the linker 5, linker 6, linker 7 and linker 8 are the same or different peptide linkers;

[0449] The structures shown in formulas (h) and (i) are arranged from the N-terminus to the C-terminus; Fc1 and Fc2 can be positioned interchangeably.

[0450] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the antigen binding molecule comprises an antigen binding moiety that specifically binds to DLL3 and an antigen binding moiety that specifically binds to CD3,

[0451] The antigen-binding molecule comprises a first chain having a structure represented by formula (h) and a second chain having a structure represented by formula (i).

[0452] (h) [DLL3-VL]-[Linker 5]-[CD3-VH]-[Linker 6]-[Fc1],

[0453] (i) [CD3-VL]-[Linker 7]-[DLL3-VH]-[Linker 8]-[Fc2],

[0454] Wherein: the linker 5, linker 6, linker 7 and linker 8 are the same or different peptide linkers;

[0455] The structures shown in formulae (h) and (i) are arranged from the N-terminus to the C-terminus.

[0456] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the antigen binding molecule comprises an antigen binding moiety that specifically binds to DLL3 and an antigen binding moiety that specifically binds to CD3,

[0457] The antigen-binding molecule comprises a first chain having a structure represented by formula (h') and a second chain having a structure represented by formula (i').

[0458] (h') [CD3-VL]-[Linker 5]-[DLL3-VH]-[Linker 6]-[Fc1] / [Fc2],

[0459] (I') [DLL3-VL]-[Linker 7]-[CD3-VH]-[Linker 8]-[Fc2] / [Fc1],

[0460] Wherein: the linker 5, linker 6, linker 7 and linker 8 are the same or different peptide linkers;

[0461] The structures represented by formula (h') and (i') are arranged from the N-terminus to the C-terminus. " / " represents "or".

[0462] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the antigen binding molecule comprises an antigen binding moiety that specifically binds to DLL3 and an antigen binding moiety that specifically binds to CD3,

[0463] The antigen-binding molecule comprises a first chain having a structure represented by formula (h') and a second chain having a structure represented by formula (i').

[0464] (h') [CD3-VL]-[Linker 5]-[DLL3-VH]-[Linker 6]-[Fc1],

[0465] (I') [DLL3-VL]-[Linker 7]-[CD3-VH]-[Linker 8]-[Fc2],

[0466] Wherein: the linker 5, linker 6, linker 7 and linker 8 are the same or different peptide linkers;

[0467] The structures represented by formulas (h') and (i') are arranged from the N-terminus to the C-terminus; Fc1 and Fc2 can be positioned interchangeably.

[0468] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the antigen binding molecule comprises an antigen binding moiety that specifically binds to DLL3 and an antigen binding moiety that specifically binds to CD3,

[0469] The antigen-binding molecule comprises a first chain having a structure represented by formula (h') and a second chain having a structure represented by formula (i').

[0470] (h') [CD3-VL]-[Linker 5]-[DLL3-VH]-[Linker 6]-[Fc1],

[0471] (I') [DLL3-VL]-[Linker 7]-[CD3-VH]-[Linker 8]-[Fc2],

[0472] Wherein: the linker 5, linker 6, linker 7 and linker 8 are the same or different peptide linkers;

[0473] The structures represented by formulae (h') and (i') are arranged from the N-terminus to the C-terminus.

[0474] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0475] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; and

[0476] The CD3-VH comprises: a CD3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 129, a CD3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 130, and a CD3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 131 or 135; and the CD3-VL comprises: a CD3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 132, a CD3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 133, and a CD3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 134.

[0477] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0478] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 24, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; and

[0479] The CD3-VH comprises: a CD3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 129, a CD3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 130, and a CD3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 131 or 135; and the CD3-VL comprises: a CD3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 132, a CD3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 133, and a CD3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 134.

[0480] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0481] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 72, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; and

[0482] The CD3-VH comprises: a CD3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 129, a CD3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 130, and a CD3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 131 or 135; and the CD3-VL comprises: a CD3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 132, a CD3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 133, and a CD3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 134.

[0483] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0484] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 69, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74; and

[0485] The CD3-VH comprises: a CD3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 129, a CD3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 130, and a CD3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 131 or 135; and the CD3-VL comprises: a CD3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 132, a CD3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 133, and a CD3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 134.

[0486] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0487] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74; and

[0488] The CD3-VH comprises: a CD3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 129, a CD3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 130, and a CD3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 131 or 135; and the CD3-VL comprises: a CD3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 132, a CD3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 133, and a CD3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 134.

[0489] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0490] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 69, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 73, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74; and

[0491] The CD3-VH comprises: a CD3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 129, a CD3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 130, and a CD3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 131 or 135; and the CD3-VL comprises: a CD3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 132, a CD3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 133, and a CD3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 134.

[0492] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0493] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 73, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74; and

[0494] The CD3-VH comprises: a CD3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 129, a CD3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 130, and a CD3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 131 or 135; and the CD3-VL comprises: a CD3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 132, a CD3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 133, and a CD3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 134.

[0495] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0496] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 69, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; and

[0497] The CD3-VH comprises: a CD3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 129, a CD3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 130, and a CD3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 131 or 135; and the CD3-VL comprises: a CD3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 132, a CD3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 133, and a CD3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 134.

[0498] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0499] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; and

[0500] The CD3-VH comprises: a CD3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 129, a CD3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 130, and a CD3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 131 or 135; and the CD3-VL comprises: a CD3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 132, a CD3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 133, and a CD3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 134.

[0501] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0502] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 26, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 85, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 83; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31; and

[0503] The CD3-VH comprises: a CD3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 129, a CD3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 130, and a CD3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 131 or 135; and the CD3-VL comprises: a CD3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 132, a CD3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 133, and a CD3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 134.

[0504] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0505] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 33; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 34, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 36; and

[0506] The CD3-VH comprises: a CD3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 129, a CD3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 130, and a CD3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 131 or 135; and the CD3-VL comprises: a CD3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 132, a CD3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 133, and a CD3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 134.

[0507] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0508] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 119, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 38; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 39, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 40; and

[0509] The CD3-VH comprises: a CD3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 129, a CD3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 130, and a CD3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 131 or 135; and the CD3-VL comprises: a CD3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 132, a CD3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 133, and a CD3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 134.

[0510] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0511] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 33; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 34, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 36; and

[0512] The CD3-VH has: CD3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 129, CD3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 130, and CD3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 135; and the CD3-VL has: CD3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 132, CD3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 133, and CD3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 134.

[0513] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0514] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; and

[0515] The CD3-VH has: CD3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 129, CD3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 130, and CD3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 131; and the CD3-VL has: CD3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 132, CD3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 133, and CD3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 134.

[0516] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0517] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 54, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 61; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137.

[0518] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0519] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 54, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 63; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137.

[0520] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0521] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 54, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 64; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137.

[0522] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0523] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 56, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 65; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137.

[0524] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0525] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 56, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 66; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137.

[0526] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0527] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 56, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 67; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137.

[0528] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0529] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 57, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 65; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137.

[0530] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0531] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 57, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 66; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137.

[0532] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0533] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 57, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 67; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137.

[0534] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0535] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 91, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 87; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137.

[0536] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0537] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 81, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 77; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137.

[0538] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0539] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 109, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 100; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137.

[0540] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein:

[0541] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 54, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 63; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137;

[0542] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the linker 5, linker 6, linker 7 and linker 8 are all peptide linkers known in the art, as long as the antigen binding molecule can exhibit the desired antigen binding activity. For example, the peptide linker can be a flexible peptide comprising 1-50 or 3-20 amino acid residues. In some embodiments, the length of the peptide linker is 1-15 amino acid residues. In some embodiments, the linker 5 has a structure of (GGGS)nGm, wherein n is 1-5, preferably 1, 2 or 3; m is 1-10, preferably 4, 5, 6, 7 or 8. In some embodiments, the sequence of the linker 5 is GGGSGGGG (SEQ ID NO: 149). In some embodiments, the linkers linker 6 and linker 8 have a structure of Gm, wherein m is 1-5, preferably 1, 2 or 3. In some embodiments, the sequence of linker 6 and linker 8 is G (SEQ ID NO: 150). In some embodiments, the linker 7 has a structure of (GGGGS)nGm, wherein n is 1-5, preferably 1, 2 or 3; m is 1-10, preferably 4, 5, 6, 7 or 8. In some embodiments, the sequence of linker 7 is GGGGSGGGG (SEQ ID NO: 151).

[0543] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the antigen binding molecule has:

[0544] a first chain comprising the amino acid sequence of SEQ ID NO: 185 and a second chain comprising the amino acid sequence of SEQ ID NO: 162; or

[0545] a first chain comprising the amino acid sequence of SEQ ID NO: 161 and a second chain comprising the amino acid sequence of SEQ ID NO: 162; or

[0546] a first chain comprising the amino acid sequence of SEQ ID NO: 163 and a second chain comprising the amino acid sequence of SEQ ID NO: 162; or

[0547] a first chain comprising the amino acid sequence of SEQ ID NO: 259 and a second chain comprising the amino acid sequence of SEQ ID NO: 162; or

[0548] a first chain comprising the amino acid sequence of SEQ ID NO: 260 and a second chain comprising the amino acid sequence of SEQ ID NO: 162; or

[0549] a first chain comprising the amino acid sequence of SEQ ID NO: 168 and a second chain comprising the amino acid sequence of SEQ ID NO: 169; or

[0550] a first chain comprising the amino acid sequence of SEQ ID NO: 170 and a second chain comprising the amino acid sequence of SEQ ID NO: 169; or

[0551] a first chain comprising the amino acid sequence of SEQ ID NO: 175 and a second chain comprising the amino acid sequence of SEQ ID NO: 176; or

[0552] a first chain comprising the amino acid sequence of SEQ ID NO: 177 and a second chain comprising the amino acid sequence of SEQ ID NO: 176; or

[0553] a first chain comprising the amino acid sequence of SEQ ID NO: 182 and a second chain comprising the amino acid sequence of SEQ ID NO: 183; or

[0554] a first chain comprising the amino acid sequence of SEQ ID NO: 184 and a second chain comprising the amino acid sequence of SEQ ID NO: 183; or

[0555] a first chain comprising the amino acid sequence of SEQ ID NO: 186 and a second chain comprising the amino acid sequence of SEQ ID NO: 162; or

[0556] a first chain comprising the amino acid sequence of SEQ ID NO: 187 and a second chain comprising the amino acid sequence of SEQ ID NO: 188; or

[0557] a first chain comprising the amino acid sequence of SEQ ID NO: 187 and a second chain comprising the amino acid sequence of SEQ ID NO: 189; or

[0558] a first chain comprising the amino acid sequence of SEQ ID NO: 190 and a second chain comprising the amino acid sequence of SEQ ID NO: 188; or

[0559] a first chain comprising the amino acid sequence of SEQ ID NO: 190 and a second chain comprising the amino acid sequence of SEQ ID NO: 189; or

[0560] a first chain comprising the amino acid sequence of SEQ ID NO: 191 and a second chain comprising the amino acid sequence of SEQ ID NO: 188; or

[0561] A first chain comprising the amino acid sequence of SEQ ID NO: 191 and a second chain comprising the amino acid sequence of SEQ ID NO: 189.

[0562] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the antigen binding molecule has:

[0563] A first chain comprising the amino acid sequence of SEQ ID NO: 185 and a second chain comprising the amino acid sequence of SEQ ID NO: 162.

[0564] In another aspect, the present disclosure further provides an anti-DLL3 antibody capable of specifically binding to DLL3, wherein the anti-DLL3 antibody comprises a heavy chain variable region DLL3-VH and a light chain variable region DLL3-VL, wherein:

[0565] (i) the DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of SEQ ID NO: 12, 56 or 57, respectively, and the DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of SEQ ID NO: 13, 63, 64, 65, 66 or 67, respectively, or

[0566] (ii) the DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of SEQ ID NO: 14, 79, 80, 81 or 82, respectively, and the DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of SEQ ID NO: 15, respectively, or

[0567] (iii) the DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of SEQ ID NO: 16, 91, 92, 93 or 94, respectively, and the DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of SEQ ID NO: 17, respectively, or

[0568] (iv) the DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 in the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 in SEQ ID NO: 18, 107, 108, 109, 110, 112, 113, 114 or 115, respectively, and the DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 in the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 in SEQ ID NO: 19, respectively.

[0569] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0570] (i) the DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3, respectively, in SEQ ID NO: 12, and the DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3, respectively, in SEQ ID NO: 13, or

[0571] the DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3, respectively, of SEQ ID NO: 54, and the DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3, respectively, of SEQ ID NO: 64; or

[0572] the DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3, respectively, of SEQ ID NO: 54, and the DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3, respectively, of SEQ ID NO: 63; or

[0573] the DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3, respectively, of SEQ ID NO: 56, and the DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3, respectively, of SEQ ID NO: 65; or

[0574] the DLL3-HCDR1, DLL3-HCDR2, and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2, and DLL3-HCDR3, respectively, of SEQ ID NO: 56, and the DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3, respectively, of SEQ ID NO: 66; or

[0575] the DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3, respectively, of SEQ ID NO: 56, and the DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3, respectively, of SEQ ID NO: 67; or

[0576] the DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3, respectively, of SEQ ID NO: 57, and the DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3, respectively, of SEQ ID NO: 65; or

[0577] the DLL3-HCDR1, DLL3-HCDR2, and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2, and DLL3-HCDR3, respectively, of SEQ ID NO: 57, and the DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3, respectively, of SEQ ID NO: 66; or

[0578] the DLL3-HCDR1, DLL3-HCDR2, and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2, and DLL3-HCDR3, respectively, of SEQ ID NO: 57, and the DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3, respectively, of SEQ ID NO: 67; or

[0579] (ii) the DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3, respectively, in SEQ ID NO: 14, and the DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3, respectively, in SEQ ID NO: 15, or

[0580] the DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of SEQ ID NO: 81, respectively, and the DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of SEQ ID NO: 77, respectively, or

[0581] the DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of SEQ ID NO: 79, 80 or 82, respectively, and the DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of SEQ ID NO: 77, respectively; or

[0582] (iii) the DLL3-HCDR1, DLL3-HCDR2, and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2, and DLL3-HCDR3, respectively, of SEQ ID NO: 16, and the DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3, respectively, of SEQ ID NO: 17; or

[0583] the DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3, respectively, of SEQ ID NO:91, and the DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3, respectively, of SEQ ID NO:87; or

[0584] the DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 of SEQ ID NO: 92, 93 or 94, respectively, and the DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 of SEQ ID NO: 87, respectively; or

[0585] (iv) the DLL3-HCDR1, DLL3-HCDR2, and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2, and DLL3-HCDR3, respectively, in SEQ ID NO: 18, and the DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3, respectively, in SEQ ID NO: 19; or

[0586] the DLL3-HCDR1, DLL3-HCDR2, and DLL3-HCDR3 of the DLL3-VH comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2, and DLL3-HCDR3, respectively, of SEQ ID NO: 109, and the DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3 of the DLL3-VL comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3, respectively, of SEQ ID NO: 100; or

[0587] The DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 in the DLL3-VH respectively comprise the amino acid sequences of DLL3-HCDR1, DLL3-HCDR2 and DLL3-HCDR3 in SEQ ID NO: 107, 108, 110, 112, 113, 114 or 115, and the DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 in the DLL3-VL respectively comprise the amino acid sequences of DLL3-LCDR1, DLL3-LCDR2 and DLL3-LCDR3 in SEQ ID NO: 100.

[0588] In some embodiments, the DLL3-HCDR1, DLL3-HCDR2, DLL3-HCDR3, DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3 are defined according to Kabat, IMGT, Chothia, AbM, or Contact numbering conventions.

[0589] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0590] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 24, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25;

[0591] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or

[0592] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 72, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or

[0593] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 73, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or

[0594] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74; or

[0595] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 72, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74; or

[0596] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 73, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74; or

[0597] ii) the DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 26 or 84, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 27 or 85, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 28 or 83; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31; or

[0598] iii) the DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 32, 96, 97, 98 or 99, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 33; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 34, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 36; or

[0599] iv) the DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 37, 117, 118, 119 or 120, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 38; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 39, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 40.

[0600] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0601] i) the DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 69, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 24, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or

[0602] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 24, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or

[0603] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or

[0604] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 72, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or

[0605] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74; or

[0606] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 73, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74; or

[0607] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 73, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or

[0608] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 72, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74; or

[0609] The DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 73, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74.

[0610] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0611] i) the DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or

[0612] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 24, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or

[0613] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 72, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or

[0614] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 69, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74; or

[0615] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74; or

[0616] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 69, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 73, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74; or

[0617] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 73, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74; or

[0618] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 69, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or

[0619] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or

[0620] ii) the DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO:26, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO:85, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO:83; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO:29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO:30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO:31; or

[0621] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 26, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 27, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 83; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31; or

[0622] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 84, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 27, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 83; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31; or

[0623] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 84, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 85, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 83; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31; or

[0624] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 26, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 27, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 28; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31; or

[0625] iii) the DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO:20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO:96, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO:33; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO:34, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO:35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO:36; or

[0626] iv) the DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO:20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO:119, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO:38; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO:39, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO:35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO:40.

[0627] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0628] The DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25.

[0629] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0630] The DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 24, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25.

[0631] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0632] The DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 26, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 85, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 83; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31.

[0633] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0634] The DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 33; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 34, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 36.

[0635] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0636] The DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 119, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 38; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 39, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 40.

[0637] In some embodiments, in the anti-DLL3 antibody of any of the preceding items, the DLL3-HCDR1, DLL3-HCDR2, DLL3-HCDR3, DLL3-LCDR1, DLL3-LCDR2, and DLL3-LCDR3 are defined according to the Kabat numbering convention.

[0638] In some embodiments, the anti-DLL3 antibody of any of the preceding items has a concentration of less than 4×10 -9 M, 3×10 -9 M, 2×10 -9 M, 1×10 -9 M, 9×10 -10 M, 8×10 -10 M, 7×10 -10 M, 6×10 -10 M, 5×10 -10 M, 4×10 -10 M, 3×10 -10 M, 2×10 -10 M, 1×10 -10 M, 9×10 -11 M binds to human DLL3 with a KD as measured by surface plasmon resonance.

[0639] In some embodiments, the anti-DLL3 antibody as described above, wherein:

[0640] (i) the DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N and 93A; and

[0641] the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 24, 71, 72 or 73, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25 or 74, and the FR region of the DLL3-VL comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0642] (ii) the DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 26 or 84, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 27 or 85, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 28 or 83; and

[0643] the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31, and the FR regions of the DLL3-VL comprise one or more amino acid substitutions selected from the group consisting of 42G, 44V, and 71Y; or

[0644] (iii) the DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 32, 96, 97, 98 or 99, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 33, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 24T, 44S, 71V and 73K; and

[0645] the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 34, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 36, and the FR regions of the DLL3-VL comprise one or more amino acid substitutions selected from the group consisting of 1N, 9K, 43S, 68A, and 85D; or

[0646] (iv) the DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 37, 117, 118, 119 or 120, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 38, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 3R, 5Q, 7F, 9P, 10V, 12V, 40S, 41H, 44S, 48I, 67A, 69L, 71V, 73K, 75S and 83T; and

[0647] The DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 39, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 40; and the FR region of the DLL3-VL comprises one or more amino acid substitutions selected from the group consisting of 9K, 43S, 60D, 68A, 87H and 100S.

[0648] In some embodiments, the antigen binding molecule as described in any of the preceding items has a density of less than 4×10 -9 M, 3×10 -9 M, 2×10 -9 M, 1×10 -9 M, 9×10 -10 M, 8×10 -10 M, 7×10 -10 M, 6×10 -10 M, 5×10 -10 M, 4×10 -10 M, 3×10 -10 M, 2×10 -10 M, 1×10 -10 M, 9×10 -11 M binds to human DLL3 with a KD as measured by surface plasmon resonance.

[0649] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0650] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N, and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 24, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25. NO: 25, and the DLL3-LCDR3 of the DLL3-VL FR region comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0651] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 69, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N, and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 24, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25. NO: 25, and the DLL3-LCDR3 of the DLL3-VL FR region comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0652] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N, and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 24, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25. NO: 25, and the DLL3-LCDR3 of the DLL3-VL FR region comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0653] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 24. NO: 25, and the DLL3-LCDR3 of the DLL3-VL FR region comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0654] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 72, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 73. NO: 25, and the DLL3-LCDR3 of the DLL3-VL FR region comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0655] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 73, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 24. NO: 25, and the DLL3-LCDR3 of the DLL3-VL FR region comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0656] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 24. NO: 74, and the DLL3-LCDR3 of the DLL3-VL FR region comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0657] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 72, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 73. NO: 74, and the DLL3-LCDR3 of the DLL3-VL FR region comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0658] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 73, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 24. The DLL3-LCDR3 comprises the amino acid sequence of NO: 74, and the FR region of the DLL3-VL comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D.

[0659] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0660] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: NO: 25, and the DLL3-LCDR3 of the DLL3-VL FR region comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0661] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 72, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25, and the FR region of the DLL3-VL comprises: The region comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0662] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 69, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: NO: 74, and the DLL3-LCDR3 of the DLL3-VL FR region comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0663] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: NO: 74, and the DLL3-LCDR3 of the DLL3-VL FR region comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0664] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 69, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 73, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: NO: 74, and the DLL3-LCDR3 of the DLL3-VL FR region comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0665] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 73, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74, and the FR region of the DLL3-VL comprises: The region comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0666] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 69, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: NO: 25, and the DLL3-LCDR3 of the DLL3-VL FR region comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D; or

[0667] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N and 93A; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: The DLL3-LCDR3 comprises the amino acid sequence of NO: 25, and the FR region of the DLL3-VL comprises one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D.

[0668] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0669] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 26, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 85, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 83; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31, and the FR region of the DLL3-VL comprises one or more amino acid substitutions selected from the group consisting of 42G, 44V, and 71Y; or

[0670] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 26, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 27, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 83; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31, and the FR region of the DLL3-VL comprises one or more amino acid substitutions selected from the group consisting of 42G, 44V, and 71Y; or

[0671] the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 84, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 85, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 83; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31, and the FR region of the DLL3-VL comprises one or more amino acid substitutions selected from the group consisting of 42G, 44V, and 71Y; or

[0672] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 26, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 27, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 28; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31, and the FR region of the DLL3-VL comprises one or more amino acid substitutions selected from the group consisting of 42G, 44V and 71Y.

[0673] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0674] The DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 33, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 24T, 44S, 71V and 73K; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 34, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 36, and the FR region of the DLL3-VL comprises one or more amino acid substitutions selected from the group consisting of 1N, 9K, 43S, 68A and 85D.

[0675] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0676] The DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 119, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 38, and the FR region of the DLL3-VH comprises one or more amino acid substitutions selected from the group consisting of 1E, 3R, 5Q, 7F, 9P, 10V, 12V, 40S, 41H, 44S, 48I, 67A, 69L, 71V, 73K, 75S and 83T; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 39, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 38. The DLL3-LCDR3 has the amino acid sequence of NO: 40, and the FR region of the DLL3-VL comprises one or more amino acid substitutions selected from the group consisting of 9K, 43S, 60D, 68A, 87H and 100S.

[0677] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0678] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 50, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of Q1E, Q43K, M48I, V67A, I69L, R71V, T73K, and S76N in the FR region of SEQ ID NO: 50.

[0679] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0680] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 51, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of Q1E, 5Q, R38K, V68A, F69L, L71V, T73K, V75S, and S76N in the FR region of SEQ ID NO: 51.

[0681] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0682] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 52, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of F27Y, S30T, I69L, R71V, D73K, and T93A in the FR region of SEQ ID NO: 52.

[0683] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0684] The DLL3-VL comprises the amino acid sequence of SEQ ID NO: 62, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of F36L, A43S, P44F, S46G, T69A, F71Y, and T85D in the FR region of SEQ ID NO: 62.

[0685] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0686] The DLL3-VL comprises the amino acid sequence of SEQ ID NO: 68, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of Y36L, Q42K, L46G, T69A, F71Y, E79Q, and V85D in the FR region of SEQ ID NO: 68.

[0687] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0688] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 78, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions in the FR region of SEQ ID NO: 78.

[0689] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0690] The DLL3-VL comprises the amino acid sequence of SEQ ID NO: 75, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of K42G, P44V, and F71Y in the FR region of SEQ ID NO: 75.

[0691] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0692] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 95, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of Q1E, A24T, R44S, R71V, and T73K in the FR region of SEQ ID NO: 95.

[0693] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0694] The DLL3-VL comprises the amino acid sequence of SEQ ID NO: 88, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of D1N, D9K, P43S, G68A, and V85D in the FR region of SEQ ID NO: 88.

[0695] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0696] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 116, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of Q1E, Q3R, V5Q, S7F, A9P, E10V, K12V, A40S, P41H, R44S, M48I, V67A, I69L, R71V, T73K, A75S, and R83T in the FR region of SEQ ID NO: 116.

[0697] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0698] The DLL3-VL comprises the amino acid sequence of SEQ ID NO: 100, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of D9K, P43S, G68A, and Y87H in the FR region of SEQ ID NO: 100.

[0699] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0700] The DLL3-VL comprises the amino acid sequence of SEQ ID NO: 103, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of A43S, S60D, and Q100S in the FR region of SEQ ID NO: 103.

[0701] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0702] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 56, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions in the FR region of SEQ ID NO: 56.

[0703] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0704] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 57, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions in the FR region of SEQ ID NO: 57.

[0705] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0706] The DLL3-VL comprises the amino acid sequence of SEQ ID NO: 63, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions in the FR region of SEQ ID NO: 63; in some embodiments, the amino acid substitutions are selected from one or more amino acid substitutions selected from the group consisting of A43S and P44F.

[0707] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0708] The DLL3-VL comprises the amino acid sequence of SEQ ID NO: 64, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions in the FR region of SEQ ID NO: 64; in some embodiments, the amino acid substitutions are selected from one or more amino acid substitutions selected from the group consisting of A43S and P44F.

[0709] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0710] The DLL3-VL comprises the amino acid sequence of SEQ ID NO: 65, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions in the FR region of SEQ ID NO: 65; in some embodiments, the amino acid substitutions are selected from one or more amino acid substitutions selected from the group consisting of A43S and P44F.

[0711] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0712] The DLL3-VL comprises the amino acid sequence of SEQ ID NO: 66, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions in the FR region of SEQ ID NO: 66; in some embodiments, the amino acid substitutions are selected from one or more amino acid substitutions selected from the group consisting of A43S and P44F.

[0713] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0714] The DLL3-VL comprises the amino acid sequence of SEQ ID NO: 67, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions in the FR region of SEQ ID NO: 67.

[0715] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0716] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 79, 80, 81 or 82, or a variant of SEQ ID NO: 79, 80, 81 or 82. In some embodiments, the variant comprises one or more amino acid substitutions in the FR region of SEQ ID NO: 79, 80, 81 or 82; and

[0717] The DLL3-VL comprises the amino acid sequence of SEQ ID NO: 75, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of K42G, P44V, and F71Y in the FR region of SEQ ID NO: 75.

[0718] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0719] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 91, 92, 93 or 94, or a variant of SEQ ID NO: 91, 92, 93 or 94. In some embodiments, the variant comprises one or more amino acid substitutions in the FR region of SEQ ID NO: 91, 92, 93 or 94; and

[0720] The DLL3-VL comprises the amino acid sequence of SEQ ID NO: 88, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of D1N, D9K, P43S, G68A, and V85D in the FR region of SEQ ID NO: 88.

[0721] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0722] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 107, 108, 109 or 110, or a variant of SEQ ID NO: 107, 108, 109 or 110. In some embodiments, the variant comprises one or more amino acid substitutions in the FR regions of SEQ ID NO: 107, 108, 109 or 110; in some embodiments, the amino acid substitutions are selected from the group consisting of V5Q, S7F, A9P, E10V, K12V, A40S, P41H, M48I, V67A, A75S and R83T.

[0723] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0724] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 112, or a variant of SEQ ID NO: 112. In some embodiments, the variant comprises one or more amino acid substitutions in the FR region of SEQ ID NO: 112; in some embodiments, the amino acid substitutions are selected from the group consisting of V5Q, A9P, K12V, A40S, P41H, 4M8I, V67A, and R83T.

[0725] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0726] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 113, or a variant of SEQ ID NO: 113. In some embodiments, the variant comprises one or more amino acid substitutions in the FR region of SEQ ID NO: 113; in some embodiments, the amino acid substitutions are selected from the group consisting of V5Q, S7F, A9P, E10V, K12V, A40S, P41H, A75S, and R83T.

[0727] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0728] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 114, or a variant of SEQ ID NO: 114. In some embodiments, the variant comprises one or more amino acid substitutions in the FR region of SEQ ID NO: 114; in some embodiments, the amino acid substitutions are selected from the group consisting of V5Q, S7F, A9P, E10V, K12V, M48I, V67A, A75S, and R83T.

[0729] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0730] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 115, or a variant of SEQ ID NO: 115. In some embodiments, the variant comprises one or more amino acid substitutions in the FR region of SEQ ID NO: 115; in some embodiments, the amino acid substitutions are selected from the group consisting of V5Q, A9P, K12V, A40S, P41H, M48I, and V67A.

[0731] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0732] The DLL3-VL comprises the amino acid sequence of SEQ ID NO: 100, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of D9K, P43S, G68A, and Y87H in the FR region of SEQ ID NO: 100.

[0733] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0734] The DLL3-VL comprises the amino acid sequence of SEQ ID NO: 103, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of A43S, S60D, and Q100S in the FR region of SEQ ID NO: 103.

[0735] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0736] i) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56 or 57, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 63, 64, 65, 66 or 67; or

[0737] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 56 or 57, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 58, 59, 60, 61, 62, 63, 64, 65, 66, 67 or 68; or

[0738] ii) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 78, 79, 80, 81 or 82, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 75, 76 or 77; or

[0739] iii) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 89, 90, 91, 92, 93, 94 or 95, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 86, 87 or 88; or

[0740] iv) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115 or 116, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 100, 101, 102, 103 or 104.

[0741] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0742] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 43, 44 or 45, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 58, 59 or 60; or

[0743] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 47, 48, 49, 53, 54 or 55, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 59; or

[0744] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 43, 44 or 45, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 60; or

[0745] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 46, 48, 53, 54 or 55, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 61; or

[0746] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 54, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 63 or 64; or

[0747] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 56 or 57, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 65, 66 or 67.

[0748] In some embodiments, the anti-DLL3 antibody as described in any preceding clause, wherein:

[0749] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 78 or 79, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 75, 76 or 77; or

[0750] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 78, 79, 80, 81 or 82, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 77.

[0751] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0752] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 89, 90, 91, 92, 93 or 94, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 86 or 87; or

[0753] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 95, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 87.

[0754] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0755] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 105, 106, 107, 108, 109, 110, or 111, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 100, 101, or 102; or

[0756] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 112, 113, 114 or 115, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 100, 103 or 104; or

[0757] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 109, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 103.

[0758] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0759] i) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 54, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 63; or

[0760] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 54, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 61; or

[0761] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 54, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 64; or

[0762] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 56, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 65; or

[0763] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 56, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 66; or

[0764] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 56, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 67; or

[0765] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 57, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 65; or

[0766] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 57, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 66; or

[0767] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 57, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 67; or

[0768] ii) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 81, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 77; or

[0769] iii) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 91, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 87; or

[0770] iv) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 109, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 100.

[0771] In some embodiments, the anti-DLL3 antibody as described above, wherein:

[0772] i) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 12, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 13; or

[0773] ii) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 14, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 15; or

[0774] iii) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 16, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 17; or

[0775] iv) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 18, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 19.

[0776] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0777] the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 54, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 63; or

[0778] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 54, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 61.

[0779] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0780] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 81, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 77.

[0781] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0782] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 91, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 87.

[0783] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein:

[0784] The DLL3-VH comprises the amino acid sequence of SEQ ID NO: 109, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 100.

[0785] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein the anti-DLL3 antibody is an antibody fragment.

[0786] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein the antibody fragment is Fab, Fab', F(ab')2, Fd, Fv, scFv, dsFv or dAb.

[0787] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein the anti-DLL3 antibody comprises a heavy chain constant region and a light chain constant region.

[0788] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein the heavy chain constant region is a heavy chain constant region of human IgG.

[0789] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein the light chain constant region is a human kappa or lambda light chain constant region.

[0790] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein the heavy chain constant region is a heavy chain constant region of human IgG1.

[0791] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein the light chain constant region is a human kappa light chain constant region.

[0792] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein the heavy chain constant region comprises the amino acid sequence of SEQ ID NO: 41.

[0793] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein the light chain constant region comprises the amino acid sequence of SEQ ID NO: 42.

[0794] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein the anti-DLL3 antibody comprises a heavy chain and a light chain, wherein:

[0795] the heavy chain comprising an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identical to SEQ ID NO: 121, and the light chain comprising an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identical to SEQ ID NO: 122; or

[0796] the heavy chain comprising an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identical to SEQ ID NO: 123, and the light chain comprising an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identical to SEQ ID NO: 124; or

[0797] the heavy chain comprising an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identical to SEQ ID NO: 125, and the light chain comprising an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identical to SEQ ID NO: 126; or

[0798] The heavy chain comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identical to SEQ ID NO: 127, and the light chain comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identical to SEQ ID NO: 128.

[0799] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein the anti-DLL3 antibody comprises a heavy chain and a light chain, wherein:

[0800] The heavy chain comprises the amino acid sequence of SEQ ID NO: 121, and the light chain comprises the amino acid sequence of SEQ ID NO: 122; or

[0801] the heavy chain comprises the amino acid sequence of SEQ ID NO: 123, and the light chain comprises the amino acid sequence of SEQ ID NO: 124;

[0802] The heavy chain comprises the amino acid sequence of SEQ ID NO: 125, and the light chain comprises the amino acid sequence of SEQ ID NO: 126; or

[0803] The heavy chain comprises the amino acid sequence of SEQ ID NO: 127, and the light chain comprises the amino acid sequence of SEQ ID NO: 128.

[0804] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein the anti-DLL3 antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 121, and the light chain comprises the amino acid sequence of SEQ ID NO: 122.

[0805] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein the anti-DLL3 antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 125, and the light chain comprises the amino acid sequence of SEQ ID NO: 126.

[0806] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein the anti-DLL3 antibody is a bispecific antibody.

[0807] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein the anti-DLL3 antibody is a bispecific antibody that specifically binds to DLL3 and CD3.

[0808] In another aspect, the present disclosure provides a pharmaceutical composition comprising: a therapeutically effective amount of any of the aforementioned antigen-binding molecules or any of the aforementioned anti-DLL3 antibodies, and one or more pharmaceutically acceptable carriers, diluents, buffers, or excipients. In some embodiments, the pharmaceutical composition further comprises at least one second therapeutic agent. In one embodiment, the second therapeutic agent is any agent that is advantageously combined with the CD3 / DLL3 bispecific antigen-binding molecule. In some embodiments, the second therapeutic agent is an antibody that specifically binds to CD28. In some embodiments, the second therapeutic agent is a bispecific antibody that specifically binds to CD28 and a tumor cell surface antigen (TAA). In some embodiments, the second therapeutic agent is a bispecific antibody that specifically binds to CD28 and DLL3.

[0809] In another aspect, the present disclosure also provides an isolated nucleic acid encoding any of the aforementioned antigen binding molecules or any of the aforementioned anti-DLL3 antibodies.

[0810] In another aspect, the present disclosure also provides a vector comprising the aforementioned isolated nucleic acid.

[0811] In another aspect, the present disclosure also provides a host cell comprising the aforementioned isolated nucleic acid or vector.

[0812] In another aspect, the present disclosure also provides a method for treating tumors or cancers, comprising administering to a subject a therapeutically effective amount of any of the aforementioned antigen binding molecules or any of the aforementioned anti-DLL3 antibodies or any of the aforementioned pharmaceutical compositions.

[0813] In another aspect, the present disclosure also provides use of any of the aforementioned antigen-binding molecules, or any of the aforementioned antibodies, or any of the aforementioned pharmaceutical compositions in the preparation of drugs for treating tumors or cancers.

[0814] In another aspect, the present disclosure also provides any of the aforementioned antigen binding molecules or any of the aforementioned anti-DLL3 antibodies or any of the aforementioned pharmaceutical compositions for use as a medicament. In some embodiments, the medicament is for treating a tumor or cancer.

[0815] In some embodiments, the tumor or cancer as described in any of the preceding items is selected from the group consisting of: head and neck squamous cell carcinoma, head and neck cancer, brain cancer, glioma, glioblastoma multiforme, neuroblastoma, central nervous system cancer, neuroendocrine tumors, pharyngeal cancer, pharyngeal squamous cell carcinoma, oral squamous cell carcinoma, nasopharyngeal cancer, esophageal cancer, thyroid cancer, malignant pleural mesothelioma, lung cancer, breast cancer, liver cancer, hepatobiliary cancer, pancreatic cancer, gastric cancer, gastrointestinal cancer, intestinal cancer, colon cancer, colorectal cancer, kidney cancer, clear cell renal cell carcinoma, ovarian cancer, endometrial cancer, cervical cancer, bladder cancer, prostate cancer, testicular cancer, skin cancer, melanoma, large cell lung cancer, triple-negative breast cancer, lymphoma and small cell lung cancer.

[0816] In some embodiments, the tumor or cancer as described above is a cancer that expresses DLL3.

[0817] In some embodiments, the tumor or cancer as described above is a solid tumor.

[0818] In some embodiments, the aforementioned tumor or cancer is lung cancer.

[0819] In some embodiments, the aforementioned tumor or cancer is small cell lung cancer.

[0820] In some embodiments, the method for treating a tumor or cancer as described above further comprises the use of a second therapeutic agent. In some embodiments, the second therapeutic agent comprises an anti-tumor agent, radiotherapy, an antibody drug conjugate, a bispecific antibody, a bispecific antibody conjugated to an anti-tumor agent, an immune checkpoint inhibitor, or a combination thereof.

[0821] In some embodiments, as described above for treating tumors or cancer, the second therapeutic agent is any agent that is advantageously combined with a CD3 / DLL3 bispecific antigen binding molecule. In some embodiments, the second therapeutic agent is an antibody that specifically binds to CD28. In some embodiments, the second therapeutic agent is a bispecific antibody that specifically binds to CD28 and a tumor cell surface antigen (TAA). In some embodiments, the second therapeutic agent is a bispecific antibody that specifically binds to CD28 and DLL3.

[0822] In some embodiments, in the method for treating tumors or cancer as described above, the second therapeutic agent is administered simultaneously, sequentially, or separately with the antigen binding molecule described in any one of the disclosures.

[0823] The antigen-binding molecules provided by the present disclosure have the characteristics of good therapeutic activity, safety, pharmacokinetic properties and drugability (such as stability). BRIEF DESCRIPTION OF THE DRAWINGS

[0824] FIG1A shows a schematic diagram of the structure of Format 1 of the DLL3-CD3 bispecific antibody, wherein Ob stands for Obscurin.

[0825] FIG1B shows a schematic diagram of the structure of Format 2 of the DLL3-CD3 bispecific antibody.

[0826] FIG1C shows a schematic diagram of the structure of Format 3 of the DLL3-CD3 bispecific antibody.

[0827] Figure 2A shows the experimental results of the binding of bispecific antibodies to DLL1. The results show that the DLL3-CD3 bispecific antibodies disclosed herein do not bind to DLL1.

[0828] Figure 2B shows the experimental results of the binding of bispecific antibodies to DLL4. The results show that the DLL3-CD3 bispecific antibodies disclosed herein do not bind to DLL4.

[0829] Figure 3 shows the results of the cell-killing experiment of the bispecific antibody. The results show that the bispecific antibody disclosed herein has no killing effect on H460 cells that do not express DLL3.

[0830] FIG4A shows the experimental results of the bispecific antibody activation of T cells, which show that the bispecific antibody disclosed herein has a significant effect of activating T cells in the presence of DLL3 / H82 cells expressing DLL3.

[0831] FIG4B shows that the bispecific antibodies of the present disclosure do not activate T cells in the presence of negative cells H460 that do not express DLL3.

[0832] FIG5A shows the experimental results of cytokine release of the bispecific antibody, which shows that in the presence of H1184 cells, the bispecific antibody of the present disclosure stimulates PBMC cells to secrete very low levels of IFNγ.

[0833] FIG5B shows that in the presence of H1184 cells, the bispecific antibodies of the present disclosure stimulated PBMC cells to secrete very low amounts of IL-6. DETAILED DESCRIPTION

[0834] the term

[0835] The terms used herein are for the purpose of describing the embodiments only and are not intended to be limiting. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs.

[0836] Unless the context clearly requires otherwise, throughout the specification and claims, the words "comprising," "having," "including," and the like should be understood to have an inclusive meaning, rather than an exclusive or exhaustive meaning; that is, to mean "including, but not limited to." Unless otherwise indicated, "comprising" includes "consisting of." For example, a reference to a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20 specifically encompasses a DLL3-HCDR1 having the amino acid sequence set forth in SEQ ID NO: 20.

[0837] The three letter and one letter codes for amino acids used in this disclosure are as described in J. biol. chem, 243, p3558 (1968).

[0838] The term "and / or," such as "X and / or Y," should be understood to mean "X and Y" or "X or Y" and should be used to provide clear support for both meanings or either meaning.

[0839] Unless specified as being from a non-human species (e.g., "mouse CD3," "mouse CD3 fragment," "monkey CD3," "monkey CD3 fragment," etc.), "CD3" and "CD3 fragment" as used herein refer to the well-known human CD3 protein or a fragment thereof.

[0840] The term "amino acid" refers to naturally occurring and synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function in a manner similar to naturally occurring amino acids. Naturally occurring amino acids are those encoded by the genetic code, as well as those that are later modified, such as hydroxyproline, γ-carboxyglutamate, and O-phosphoserine. Amino acid analogs refer to compounds that have the same basic chemical structure as naturally occurring amino acids (i.e., an alpha carbon bound to a hydrogen, a carboxyl group, an amino group, and an R group), such as homoserine, norleucine, methionine sulfoxide, and methionine methylsulfonium. Such analogs have modified R groups (e.g., norleucine) or modified peptide backbones, but retain the same basic chemical structure as naturally occurring amino acids. Amino acid mimetics refer to chemical compounds that have a structure that is different from the general chemical structure of an amino acid, but function in a manner similar to naturally occurring amino acids.

[0841] The term "amino acid mutation" includes amino acid substitutions, deletions, insertions, and modifications. Any combination of substitutions, deletions, insertions, and modifications can be performed to achieve the final construct, as long as the final construct possesses the desired properties, such as reduced binding to Fc receptors. Amino acid sequence deletions and insertions include deletions and insertions at the amino and / or carboxyl termini of the polypeptide chain. Specific amino acid mutations can be amino acid substitutions. In one embodiment, the amino acid mutation is a non-conservative amino acid substitution, i.e., replacing one amino acid with another amino acid having different structural and / or chemical properties. Amino acid substitutions include replacement with non-naturally occurring amino acids or with derivatives of the 20 natural amino acids (e.g., 4-hydroxyproline, 3-methylhistidine, ornithine, homoserine, 5-hydroxylysine). Amino acid mutations can be generated using genetic or chemical methods known in the art. Genetic methods can include site-directed mutagenesis, PCR, gene synthesis, and the like. It is anticipated that methods other than genetic engineering to alter amino acid side chain groups, such as chemical modification, are also useful. Various names may be used herein to refer to the same amino acid mutation. Herein, the amino acid residue at a specific position can be represented by position + amino acid residue, for example, 366W means that the amino acid residue at position 366 is W. T366W means that the amino acid residue at position 366 has mutated from T to W.

[0842] The term "antigen binding molecule" is used in the broadest sense to encompass various molecules that specifically bind to antigens, including but not limited to antibodies, other polypeptides with antigen binding activity, and antibody fusion proteins formed by fusion of the two, as long as they exhibit the desired antigen binding activity. The antigen binding molecules herein comprise a variable region (VH) and a variable region (VL), which together constitute an antigen binding domain. Exemplary, the antigen binding molecules herein are bispecific antigen binding molecules (e.g., bispecific antibodies).

[0843] The term "antibody" is used in the broadest sense and encompasses various antibody structures, including but not limited to monoclonal antibodies, polyclonal antibodies; monospecific antibodies, multispecific antibodies (e.g., bispecific antibodies), full-length antibodies, and antibody fragments (or antigen-binding fragments, or antibody fragments, or antigen-binding portions), as long as they exhibit the desired antigen-binding activity. Depending on the context, a skilled person can determine the specific meaning of "antibody".

[0844] "Natural antibody" refers to naturally occurring immunoglobulin molecules. For example, natural IgG antibodies are heterotetrameric glycoproteins of approximately 150,000 daltons, consisting of two light chains and two heavy chains bound by disulfide bonds. From N to C-terminus, each heavy chain has a variable region (VH, also known as variable heavy domain, heavy chain variable region), followed by three constant domains (CH1, CH2 and CH3). Similarly, from N to C-terminus, each light chain has a variable region (VL, also known as variable light domain, or light chain variable domain), followed by a constant light domain (light chain constant region, CL). The terms "full-length antibody", "complete antibody" and "whole antibody" are used interchangeably herein and refer to antibodies having a structure substantially similar to that of natural antibody structure or having a heavy chain containing an Fc region as defined herein.

[0845] The term "bispecific antibody" refers to an antibody (including an antibody or its antigen-binding fragment, such as a single-chain antibody) that can specifically bind to two different antigens or at least two different antigenic epitopes of the same antigen. Prior art has disclosed bispecific antibodies of various structures. Based on the integrity of the IgG molecule, they can be divided into IgG-like bispecific antibodies and antibody fragment-type bispecific antibodies; based on the number of antigen-binding regions, they can be divided into bivalent, trivalent, tetravalent, or higher-valent bispecific antibodies; and based on whether the structure is bilaterally symmetrical, they can be divided into symmetrical bispecific antibodies and asymmetrical bispecific antibodies. Among them, bispecific antibodies based on antibody fragments, such as Fab fragments lacking Fc fragments, are formed by combining two or more Fab fragments into one molecule. They have low immunogenicity, small molecular weight, and high tumor tissue penetration. Typical antibody structures of this type include F(ab)2, scFv-Fab, (scFv)2-Fab and other bispecific antibodies; IgG-like bispecific antibodies (for example, with Fc fragments) have a relatively large molecular weight. The Fc fragment helps in the later purification of the antibody and improves its solubility and stability. The Fc part may also bind to the receptor FcRn to increase the antibody serum half-life. Typical bispecific antibody structural models include KiH, CrossMAb, Triomab quadroma, FcΔAdp, ART-Ig, BiMAb, Biclonics, BEAT, DuoBody, Azymetric, XmAb, 2:1TCBs, 1Fab-IgG TDB, FynomAb, two-in-one / DAF, scFv-Fab-IgG, DART-Fc, LP-DART, CODV-Fab-TL, HLE-BiTE, F(ab)2-CrossMAb, IgG-(scFv)2, Bs4Ab, DVD-Ig, Tetravalent-DART-Fc, (scFv)4-Fc, CODV-Ig, mAb2, F(ab)4-CrossMAb and other bispecific antibodies (see Aran F. Labrijn et al., Nature Reviews Drug Discovery volume 18, pages 585–608 (2019); Chen S1 et al., J Immunol Res. 2019 Feb 11; 2019: 4516041).

[0846] The term "variable region" or "variable domain" refers to the domain of an antigen-binding molecule that binds to an antigen. Herein, the heavy chain variable region in an antigen-binding moiety that specifically binds to CD3 is designated as CD3-VH, and the light chain variable region is designated as CD3-VL; the heavy chain variable region in an antigen-binding moiety that specifically binds to CD3 is designated as CD3-VH, and the light chain variable region is designated as CD3-VL. VH and VL each contain four conserved framework regions (FRs) and three complementarity-determining regions (CDRs). The term "complementarity-determining regions" or "CDRs" refers to the region within the variable domain that primarily contributes to antigen binding; "framework" or "FRs" refers to the variable domain residues excluding the CDR residues. VH contains three CDR regions: HCDR1, HCDR2, and HCDR3; VL contains three CDR regions: LCDR1, LCDR2, and LCDR3. Herein, the three CDR regions in CD3-VH are designated as CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3; the three CDR regions in CD3-VL are designated as CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3; the three CDR regions in CD3-VH are designated as CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3; and the three CDR regions in CD3-VL are designated as CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3. From N-terminus to C-terminus, each VH and VL consists of: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. A single VH or VL may be sufficient to confer antigen-binding specificity.

[0847] The amino acid sequence boundaries of CDRs can be determined by various well-known schemes, for example: "Kabat" numbering convention (see Kabat et al. (1991), "Sequences of Proteins of Immunological Interest", 5th edition, Public Health Service, National Institutes of Health, Bethesda, MD), "Chothia" numbering convention, "ABM" numbering convention, "contact" numbering convention (see Martin, ACR. Protein Sequence and Structure Analysis of Antibody Variable Domains [J]. 2001) and ImMunoGenTics (IMGT) numbering convention (Lefranc, MP et al., Dev. Comp. Immunol., 27, 55-77 (2003); Front Immunol. 2018 Oct 16; 9: 2278), etc. The correspondence between various numbering systems is well known to those skilled in the art. The numbering convention of the present disclosure is shown in Table 1 below.

[0848] Table 1. Relationships between CDR numbering systems

[0849] Unless otherwise specified, the variable region and CDR sequences in the disclosed embodiments are all numbered using the "Kabat" convention.

[0850] The term "antibody fragment" or "antigen-binding fragment" refers to a molecule other than an intact antibody that comprises a portion of an intact antibody that retains the antigen-binding ability of the intact antibody. Examples of antibody fragments include, but are not limited to, Fv, Fab, Fab', Fab'-SH, F(ab')2, single-domain antibodies, single-chain Fab (scFab), diabodies, linear antibodies, single-chain antibody molecules (e.g., scFv); and multispecific antibodies formed from antibody fragments.

[0851] The term "Fc region" or "fragment crystallizable region" is used to define the C-terminal region of the antibody heavy chain, including native Fc regions and modified Fc regions. In some embodiments, the Fc region comprises two identical or different subunits. In some embodiments, the Fc region of the human IgG heavy chain is defined as extending from the amino acid residue at position Cys226 or from Pro230 to its carboxyl terminus. Suitable native sequence Fc regions for the antibodies described herein include human IgG1, IgG2 (IgG2A, IgG2B), IgG3, and IgG4. Unless otherwise indicated, the numbering convention for the Fc region is the EU index.

[0852] The term "Titin chain" refers to a peptide segment of 78-118 amino acids in the titin protein containing the titin Ig-like 152 domain or a functional variant thereof, wherein the titin chain can bind to the obscurin Ig-like 1 or obscurin-like Ig-like 1 domain to form a dimerization complex.

[0853] The term "Obscurin chain" refers to a peptide segment of 87-117 amino acids in length on the Obscurin protein containing the Obscurin Ig-like 1 domain or a functional variant thereof, or a peptide segment of 78-118 amino acids in length on the Obscurin-like 1 protein containing the Obscurin-like Ig-like 1 domain or a functional variant thereof.

[0854] The obscurin chain can bind to the titin chain to form a dimerization complex. The titin chain and the obscurin chain disclosed herein can be used to replace CH1 and CL in Fab, respectively, to form a replaced Fab (Fab-S), and the replacement does not affect the binding of the antigen-binding molecule to the antigen.

[0855] The term "chimeric" antibody refers to an antibody in which a portion of the heavy and / or light chain is derived from a particular source or species, while the remainder of the heavy and / or light chain is derived from a different source or species.

[0856] The term "humanized" antibody is an antibody that retains the reactivity of a non-human antibody while having lower immunogenicity in humans. For example, this can be achieved by retaining the non-human CDR regions and replacing the rest of the antibody with their human counterparts (i.e., the constant region and the framework region portion of the variable region).

[0857] The term "affinity" refers to the overall intensity of non-covalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen). Unless otherwise indicated, as used herein, "binding affinity" refers to internal binding affinity, which reflects 1:1 interactions between members of a binding pair (e.g., an antibody and an antigen). The affinity of molecule X to its part Y can generally be represented by an equilibrium dissociation constant (KD). Affinity can be measured by conventional methods known in the art (including those described herein). The term "kassoc" or "ka" refers to the association rate of a specific antibody-antigen interaction, and the term "kdis" or "kd" as used herein is intended to refer to the dissociation rate of a specific antibody-antigen interaction. As used herein, the term "KD" refers to an equilibrium dissociation constant, which is derived from the ratio of kd to ka (i.e., kd / ka) and is expressed as molar concentration (M). The KD value of an antibody can be measured using methods known in the art, such as surface plasmon resonance, ELISA, or solution equilibrium titration (SET).

[0858] The term "monoclonal antibody" refers to a group of substantially homogeneous antibodies, i.e., the amino acid sequences of the antibody molecules contained in the group are identical, except for possible natural mutations that may be present in small amounts. In contrast, polyclonal antibody preparations typically contain a variety of different antibodies with different amino acid sequences in their variable domains, which are typically specific for different epitopes. In some embodiments, the antibodies provided herein are monoclonal antibodies.

[0859] The term "antigen" refers to a molecule or portion of a molecule that can be bound by a selective binding agent of an antigen binding molecule (e.g., an antibody). An antigen may have one or more epitopes that can interact with different antigen binding molecules (e.g., antibodies).

[0860] The term "epitope" refers to an area or region on an antigen that is capable of specific binding to an antibody or its antigen-binding fragment. An epitope can be formed by contiguous amino acids (linear epitope) or comprise non-contiguous amino acids (conformational epitope), for example, when the non-contiguous amino acids are brought into spatial proximity due to the folding of the antigen (i.e., by the tertiary folding of the antigen in the case of proteinaceous properties). Conformational epitopes differ from linear epitopes in that antibody binding to the conformational epitope is lost in the presence of denaturing solvents. An epitope comprises at least 3, at least 4, at least 5, at least 6, at least 7, or 8-10 amino acids in a unique spatial conformation. Screening for antibodies that bind to a particular epitope (i.e., those that bind to the same epitope) can be performed using routine methods in the art, such as, but not limited to, alanine scanning, peptide blotting (see Meth. Mol. Biol. 248 (2004) 443-463), peptide cleavage analysis, epitope excision, epitope extraction, chemical modification of antigens (see Prot. Sci. 9 (2000) 487-496), and cross-blocking (see "Antibodies", Harlow and Lane (Cold Spring Harbor Press, Cold Spring Harb., NY)).

[0861] The terms "capable of specific binding", "specific binding" or "binding" refer to the ability of an antigen-binding molecule to bind to an antigen or epitope with a higher affinity than to other antigens or epitopes. -7 M or less (e.g., about 1×10 -8 In some embodiments, the antibody binds to the antigen with an equilibrium dissociation constant (KD) of 4 M or less. In some embodiments, the antibody binds to the antigen with a KD that is 10% or less (e.g., 1%) of the KD of the antibody bound to a nonspecific antigen (e.g., BSA, casein). KD can be measured using known methods, such as those measured by FACS or surface plasmon resonance assays. However, an antibody that specifically binds to an antigen or its epitope may have cross-reactivity to other related antigens, for example, to corresponding antigens from other species (homologous) such as humans or monkeys, e.g., Macaca fascicularis (cynomolgus, cyno), Pan troglodytes (chimpanzee, chimp), or Callithrix jacchus (common marmoset, marmoset).

[0862] The term "not binding" means that the antigen-binding molecule is unable to bind to an antigen or its epitope in the manner of specific binding described above. For example, when the antibody is about 1×10 -6The present invention binds to the antigen or its epitope with an equilibrium dissociation constant (KD) of M or greater.

[0863] The term "antigen binding moiety" refers to a polypeptide molecule that specifically binds to a target antigen. Specific antigen binding moieties include the antigen binding domains of antibodies, for example, comprising heavy chain variable regions and light chain variable regions. The term "antigen binding moiety that specifically binds to CD3" refers to a module that is capable of binding to CD3 or its epitope with sufficient affinity so that the molecule containing the module can be used as a diagnostic and / or therapeutic agent targeting CD3. For example, an antigen binding moiety that specifically binds to CD3 has the following equilibrium dissociation constant (KD): <about 10 nM, which is measured by surface plasmon resonance assay. Antigen binding moieties include antibody fragments as defined herein, such as Fab, substituted Fab or scFv.

[0864] The term "linker" refers to a connecting unit that connects two polypeptide fragments. As used herein, linkers appearing in the same structural formula may be the same or different. A linker may be a peptide linker comprising one or more amino acids, typically comprising about 1-30, 2-24, or 3-15 amino acids. The linkers used herein may be the same or different. When "-" appears in a structural formula, it indicates that the units on either side are directly connected by a covalent bond.

[0865] "Tm" is the melting denaturation temperature (intrinsic fluorescence). When a protein denatures (by heat or denaturants), the tertiary structure opens up, the microenvironment of the aromatic amino acids changes, and the emitted fluorescence spectrum shifts. For purposes of this disclosure, Tm1 refers to the temperature at which fluorescence reaches half its maximum value.

[0866] "Tonset" is the denaturation onset temperature. It refers to the temperature at which the protein begins to denature, that is, the temperature at which the fluorescence value begins to change.

[0867] "Tagg" stands for aggregation onset temperature. Aggregates are detected by static light scattering at two wavelengths, 266 nm and 473 nm, to measure the temperature at which the sample begins to aggregate. Tagg 266 refers to the aggregation onset temperature measured at 266 nm.

[0868] The term "nucleic acid" is used interchangeably with the term "polynucleotide" in this article, and refers to deoxyribonucleotides or ribonucleotides and polymers thereof in single-stranded or double-stranded form. The term encompasses backbone residues or connected nucleic acids containing known nucleotide analogs or modifications, which are synthetic, naturally occurring, and non-naturally occurring, with binding properties similar to reference nucleic acids, and metabolized in a manner similar to reference nucleotides. The example of such analogs includes, but is not limited to, phosphorothioate, phosphoramidate, methylphosphonate, chiral-methylphosphonate, 2-O-methyl ribonucleotides, peptide-nucleic acids (PNAs). "Isolated" nucleic acid refers to a nucleic acid molecule separated from the component of its natural environment. Isolation nucleic acid is included in the nucleic acid molecule contained in the following cells, which cells typically contain the nucleic acid molecule, but the nucleic acid molecule is present in extrachromosomal or in a chromosomal position different from its natural chromosomal position. The nucleic acid encoding the separation of the antigen binding molecules refers to one or more nucleic acid molecules encoding antibody heavy and light chains (or its fragment), including such one or more nucleic acid molecules in a single vector or a separate vector, and such one or more nucleic acid molecules present in one or more positions in a host cell. Unless otherwise indicated, a particular nucleic acid sequence also implicitly encompasses conservatively modified variants thereof (e.g., degenerate codon substitutions) and complementary sequences as well as explicitly indicated sequences. Specifically, as described in detail below, degenerate codon substitutions can be obtained by generating sequences in which the third position of one or more selected (or all) codons is substituted with a degenerate base and / or deoxyinosine residue.

[0869] It should be understood that although no specific coding nucleotide sequence is provided in the present disclosure, a skilled person can determine the corresponding coding nucleotide sequence based on the amino acid sequence according to codon rules and host codon preferences.

[0870] The terms "polypeptide" and "protein" are used interchangeably herein to refer to a polymer of amino acid residues. The term applies to amino acid polymers in which one or more amino acid residues is an artificial chemical mimetic of a naturally occurring amino acid, as well as to naturally occurring amino acid polymers and non-naturally occurring amino acid polymers. Unless otherwise indicated, a particular polypeptide sequence also implicitly encompasses conservatively modified variants thereof.

[0871] The term sequence "identity" refers to the degree (percentage) at which the amino acid / nucleic acid of the two sequences are identical in the equivalent position when two sequences are optimally aligned. In the alignment process, it may be allowed, if necessary, to introduce a gap to obtain maximum sequence identity percentage, but any conservative substitution is not considered to constitute a part for sequence identity. For measuring sequence identity percentage, alignment can be achieved by techniques known in the art, for example, using publicly available computer software such as BLAST, BLAST-2, ALIGN, ALIGN-2 or Megalign (DNASTAR) software. Those skilled in the art can determine the parameters applicable to measuring alignment, including any algorithm required for maximum alignment, which is included in the full length of the sequence being compared.

[0872] The term "fused" or "linked" means that the components (eg, an antigen binding moiety and an Fc domain) are covalently linked directly or via a linker.

[0873] The term "vector" means a polynucleotide molecule capable of transporting another polynucleotide connected thereto. One type of vector is a "plasmid", which refers to a circular double-stranded DNA loop, wherein additional DNA segments can be connected. Another type of vector is a viral vector, such as an adeno-associated viral vector (AAV or AAV2), in which additional DNA segments can be connected to the viral genome. Certain vectors can replicate autonomously in the host cell in which they are introduced (for example, bacterial vectors and additional mammalian vectors with bacterial replication origins). Other vectors (for example, non-additional mammalian vectors) can be integrated into the genome of the host cell after being introduced into the host cell, thereby replicating together with the host genome. The term "expression vector" or "expression construct" refers to a vector suitable for transforming a host cell and containing a nucleic acid sequence for guiding and / or controlling (together with the host cell) the expression of one or more heterologous coding regions operably connected thereto. An expression construct can include but is not limited to affecting or controlling transcription, translation and affecting the sequence of RNA splicing of the coding region operably connected thereto when introns are present.

[0874] The terms "host cell", "host cell line", and "host cell culture" are used interchangeably and refer to cells into which exogenous nucleic acid has been introduced, including the progeny of such cells. Host cells include "transformants" and "transformed cells", which include the primary transformed cell and the progeny derived therefrom, without regard to the number of passages. The progeny may not be completely identical to the parent cell in nucleic acid content, but may contain mutations. As used herein, the term includes mutant progeny that have the same function or biological activity as the cell screened or selected in the primary transformed cell. Host cells include prokaryotic and eukaryotic host cells, wherein eukaryotic host cells include, but are not limited to, mammalian cells, insect cell lines, plant cells, and fungal cells. Mammalian host cells include human, mouse, rat, dog, monkey, pig, goat, cow, horse, and hamster cells, including but not limited to Chinese hamster ovary (CHO) cells, NSO, SP2 cells, HeLa cells, baby hamster kidney (BHK) cells, monkey kidney cells (COS), human hepatocellular carcinoma cells (e.g., Hep G2), A549 cells, 3T3 cells, and HEK-293 cells.Fungal cells include yeast and filamentous fungal cells, including, for example, Pichia pastoris, Pichia finlandica, Pichia trehalophila, Pichia koclamae, Pichia membranaefaciens, Pichia minuta (Ogataea minuta, Pichia lindneri), Pichia truncatula, Pichia thermotolerans, Pichia salictaria, Pichia guercuum, Pichia pijperi, Pichia stiptis, Pichia methanolica, Pichia sp., Saccharomyces cerevisiae, Saccharomyces cerevisiae, Hansenula polymorpha, polymorpha), Kluyveromyces spp., Kluyveromyces lactis, Candida albicans, Aspergillus nidulans, Aspergillus niger, Aspergillus oryzae, Trichoderma reesei, Chrysosporium lucknowense, Fusarium sp., Fusarium gramineum, Fusarium venenatum, Physcomitrella patens, and Neurospora crassa. Pichia, any Saccharomyces, Hansenula polymorpha, any Kluyveromyces, Candida albicans, any Aspergillus, Trichoderma reesei, Chrysosporium lucknowense, any Fusarium, Yarrowia lipolytica, and Neurospora crassa. The host cells of this patent do not include subject matter not authorized under patent law.

[0875] "Optional" or "optionally" means that the subsequently described event or circumstance may but need not occur, and that the description includes instances where the event or circumstance occurs and instances where it does not.

[0876] The term "pharmaceutical composition" refers to a mixture containing one or more antigen binding molecules or antibodies described herein with other chemical components, such as physiologically / pharmaceutically acceptable carriers and excipients.

[0877] The term "pharmaceutically acceptable carrier, diluent, buffer, or excipient" refers to an ingredient in a pharmaceutical formulation that is different from the active ingredient and is non-toxic to the subject. Pharmaceutically acceptable carriers, diluents, buffers, or excipients include, but are not limited to, buffers, excipients, stabilizers, or preservatives.

[0878] The term "subject" or "individual" includes humans and non-human animals. Non-human animals include all vertebrates (e.g., mammals and non-mammals) such as non-human primates (e.g., cynomolgus monkeys), sheep, dogs, cows, chickens, amphibians, and reptiles. Unless explicitly stated, the terms "patient" or "subject" are used interchangeably herein. As used herein, the term "cynomolgus monkey" or "cynomolgus monkey" refers to cynomolgus monkeys (Macaca fascicularis). In certain embodiments, the individual or subject is a human.

[0879] "Administering" or "administering," as it applies to an animal, human, experimental subject, cell, tissue, organ or biological fluid, refers to the contact of an exogenous drug, therapeutic agent, diagnostic agent or composition with the animal, human, subject, cell, tissue, organ or biological fluid.

[0880] The term "sample" refers to a collection of similar fluids, cells, or tissues isolated from a subject, as well as fluids, cells, or tissues present in a subject. Exemplary samples are biological fluids such as blood, serum and serosal fluid, plasma, lymph, urine, saliva, cystic fluid, tears, feces, sputum, mucosal secretions of secretory tissues and organs, vaginal secretions, ascites, pleura, pericardium, peritoneum, fluids of the abdominal cavity and other body cavities, fluids collected by bronchial lavage, synovial fluid, liquid solutions in contact with a subject or biological source, such as cell and organ culture media (including cell or organ conditioned media), lavage fluids, etc., tissue biopsy samples, fine needle aspirations, surgically resected tissues, organ cultures, or cell cultures.

[0881] "Treatment" and "treatment" (and grammatical variations thereof) refer to a clinical intervention attempted to be applied to the treated individual and can be implemented for preventive purposes or during the course of clinical pathology. The desired effects of treatment include, but are not limited to, preventing the occurrence or recurrence of the disease, alleviating symptoms, alleviating / reducing any direct or indirect pathological consequences of the disease, preventing metastasis, reducing the rate of disease progression, improving or alleviating the disease state, and resolving or improving the prognosis. In some embodiments, the antigen binding molecules of the present disclosure are used to delay the formation of the disease or slow the progression of the disease.

[0882] The terms "recurrence," "relapse," and "relapsed" refer to the return of a cancer or disease after clinical assessment of disease resolution. A diagnosis of distant metastasis or local recurrence may be considered a relapse.

[0883] An "effective amount" is generally an amount sufficient to reduce the severity and / or frequency of symptoms, eliminate these symptoms and / or potential causes, prevent the occurrence of symptoms and / or their potential causes, and / or ameliorate or improve the damage caused by or associated with the disease state. In some embodiments, an effective amount is a therapeutically effective amount or a prophylactically effective amount.

[0884] A "therapeutically effective amount" is an amount sufficient to treat a disease state or symptoms, particularly a state or symptoms associated with the disease state, or otherwise prevent, hinder, delay or reverse the progression of the disease state or any other undesirable symptoms in any way associated with the disease.

[0885] A "prophylactically effective amount" is an amount that, when administered to a subject, will have a predetermined preventive effect, such as preventing or delaying the onset (or recurrence) of the disease state, or reducing the likelihood of the onset (or recurrence) of the disease state or associated symptoms. A complete therapeutic or preventive effect may not occur after administering one dose, but may occur after administering a series of doses. Thus, a therapeutically or prophylactically effective amount can be administered in one or more administrations. "Therapeutically effective amount" and "prophylactically effective amount" may vary depending on a variety of factors: such as the disease state, age, sex, and weight of the individual, and the ability of the therapeutic agent or combination of therapeutic agents to elicit a desired response in the individual. Exemplary indicators of an effective therapeutic agent or combination of therapeutic agents include, for example, improved health status of the subject.

[0886] Antigen-binding molecules of the present disclosure

[0887] The present disclosure provides antigen-binding molecules that have many advantageous properties, such as good in vitro killing activity, therapeutic activity, safety, pharmacokinetic properties, and drugability (such as yield, purity, and stability).

[0888] Exemplary Antigen Binding Molecules

[0889] The antigen-binding molecules disclosed herein include bispecific antigen-binding molecules (e.g., bispecific antibodies) and anti-DLL3 antibodies that specifically bind to DLL3 and CD3. In particular, the antigen-binding molecules disclosed herein have any of the following properties:

[0890] a. High affinity for DLL3. In some embodiments, the anti-DLL3 antibody or antigen-binding molecule has a binding affinity of less than 4×10 -9 M, 3×10 -9 M, 2×10 -9 M, 1×10 -9 M, 9×10 -10 M, 8×10 -10 M, 7×10 -10 M, 6×10 -10 M, 5×10 -10 M, 4×10 -10 M, 3×10 -10 M, 2×10 -10 M, 1×10 -10 M, 9×10 -11 In some embodiments, the anti-antigen binding agent binds to human DLL3 with a K of less than 0.5 nM, 0.4 nM, 0.3 nM, 0.2 nM, 0.1 nM, 0.09 nM, 0.08 nM, or 0.07 nM as measured by ELISA.

[0891] b. High affinity for cell surface expressed DLL3. In some embodiments, the anti-DLL3 antibody binds to H1184 cells with an EC50 of less than 0.2 nM, 0.1 nM, 0.09 nM, 0.08 nM, 0.07 nM, 0.06 nM, 0.05 nM, or 0.04 nM.

[0892] c. Specific cytotoxicity against DLL3-expressing cells. In some embodiments, the antigen-binding molecules can specifically kill SHP77 cells and H1184 cells expressing DLL3, wherein the IC50 for killing H1184 cells is less than 30 pM, 25 pM, 20 pM, 15 pM, 14 pM, 13 pM, 12 pM, 11 pM, 10 pM, 9 pM, 8 pM, or 7 pM.

[0893] d. In vitro activation activity on T cells. In some embodiments, the antigen binding molecule activates Jurkat Lucia with an EC50 of less than 20 pM, 19 pM, 18 pM, 17 pM, 16 pM, 15 pM, 14 pM, 13 pM, 12 pM, 11 pM, 10 pM, 9 pM, 8 pM, or 7 pM. TM NFAT cells.

[0894] e. Induce low levels of cytokine (IL6 and IFNγ) release.

[0895] e. Stronger in vivo therapeutic activity. In some embodiments, the antigen-binding molecules can significantly inhibit the growth of subcutaneous transplanted tumors of SHP77 and H1184 cells in mice.

[0896] The present disclosure provides an antigen-binding molecule comprising at least one antigen-binding moiety that specifically binds to DLL3 and at least one antigen-binding moiety that specifically binds to CD3, wherein the antigen-binding moiety that specifically binds to DLL3 comprises DLL3-VH and DLL3-VL, and the antigen-binding moiety that specifically binds to CD3 comprises CD3-VH and CD3-VL. The present disclosure also provides an anti-DLL3 antibody that specifically binds to DLL3, wherein the antibody comprises DLL3-VH and DLL3-VL. Specifically, the Examples herein disclose antibody series 6, 98, 110, and 30. Antibodies 6 and 110 are used as examples to describe the antibodies or antigen-binding molecules herein.

[0897] An antigen binding molecule that specifically binds to DLL3 and CD3, wherein:

[0898] The DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 24, 71, 72 or 73, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25 or 74.

[0899] An antigen-binding molecule or anti-DLL3 antibody that specifically binds to DLL3 and CD3, wherein:

[0900] The DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 32, 96, 97, 98 or 99, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 33; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 34, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 36.

[0901] An antigen binding molecule that specifically binds to DLL3 and CD3, wherein:

[0902] The DLL3-VH comprises a DLL3-HCDR1 as set forth in SEQ ID NO: 20, a DLL3-HCDR2 as set forth in SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 as set forth in SEQ ID NO: 22, and the DLL3-VL comprises a DLL3-LCDR1 as set forth in SEQ ID NO: 23, a DLL3-LCDR2 as set forth in SEQ ID NO: 24, 71, 72 or 73, and a DLL3-LCDR3 as set forth in SEQ ID NO: 25 or 74.

[0903] An antigen-binding molecule or anti-DLL3 antibody that specifically binds to DLL3 and CD3, wherein:

[0904] The DLL3-VH comprises a DLL3-HCDR1 as shown in SEQ ID NO: 20, a DLL3-HCDR2 as shown in SEQ ID NO: 32, 96, 97, 98 or 99, and a DLL3-HCDR3 as shown in SEQ ID NO: 33, and the DLL3-VL comprises a DLL3-LCDR1 as shown in SEQ ID NO: 34, a DLL3-LCDR2 as shown in SEQ ID NO: 35, and a DLL3-LCDR3 as shown in SEQ ID NO: 36.

[0905] An antigen binding molecule that specifically binds to DLL3 and CD3, wherein:

[0906] The DLL3-VH comprises DLL3-HCDR1 as shown in SEQ ID NO:20, DLL3-HCDR2 as shown in SEQ ID NO:21, and DLL3-HCDR3 as shown in SEQ ID NO:22; and the DLL3-VL comprises DLL3-LCDR1 as shown in SEQ ID NO:23, DLL3-LCDR2 as shown in SEQ ID NO:71, and DLL3-LCDR3 as shown in SEQ ID NO:25.

[0907] An antigen-binding molecule or anti-DLL3 antibody that specifically binds to DLL3 and CD3, wherein:

[0908] the DLL3-VH comprises a DLL3-HCDR1 as set forth in SEQ ID NO: 20, a DLL3-HCDR2 as set forth in SEQ ID NO: 21, and a DLL3-HCDR3 as set forth in SEQ ID NO: 22; and the DLL3-VL comprises a DLL3-LCDR1 as set forth in SEQ ID NO: 23, a DLL3-LCDR2 as set forth in SEQ ID NO: 24, and a DLL3-LCDR3 as set forth in SEQ ID NO: 25; or

[0909] the DLL3-VH comprises a DLL3-HCDR1 as set forth in SEQ ID NO:20, a DLL3-HCDR2 as set forth in SEQ ID NO:21, and a DLL3-HCDR3 as set forth in SEQ ID NO:22; and the DLL3-VL comprises a DLL3-LCDR1 as set forth in SEQ ID NO:23, a DLL3-LCDR2 as set forth in SEQ ID NO:72, and a DLL3-LCDR3 as set forth in SEQ ID NO:25; or

[0910] the DLL3-VH comprises a DLL3-HCDR1 as set forth in SEQ ID NO:20, a DLL3-HCDR2 as set forth in SEQ ID NO:69, and a DLL3-HCDR3 as set forth in SEQ ID NO:22; and the DLL3-VL comprises a DLL3-LCDR1 as set forth in SEQ ID NO:23, a DLL3-LCDR2 as set forth in SEQ ID NO:71, and a DLL3-LCDR3 as set forth in SEQ ID NO:74; or

[0911] the DLL3-VH comprises a DLL3-HCDR1 as set forth in SEQ ID NO:20, a DLL3-HCDR2 as set forth in SEQ ID NO:69, and a DLL3-HCDR3 as set forth in SEQ ID NO:22; and the DLL3-VL comprises a DLL3-LCDR1 as set forth in SEQ ID NO:23, a DLL3-LCDR2 as set forth in SEQ ID NO:24, and a DLL3-LCDR3 as set forth in SEQ ID NO:74; or

[0912] the DLL3-VH comprises a DLL3-HCDR1 as set forth in SEQ ID NO:20, a DLL3-HCDR2 as set forth in SEQ ID NO:69, and a DLL3-HCDR3 as set forth in SEQ ID NO:22; and the DLL3-VL comprises a DLL3-LCDR1 as set forth in SEQ ID NO:23, a DLL3-LCDR2 as set forth in SEQ ID NO:71, and a DLL3-LCDR3 as set forth in SEQ ID NO:25; or

[0913] the DLL3-VH comprises a DLL3-HCDR1 as set forth in SEQ ID NO:20, a DLL3-HCDR2 as set forth in SEQ ID NO:70, and a DLL3-HCDR3 as set forth in SEQ ID NO:22; and the DLL3-VL comprises a DLL3-LCDR1 as set forth in SEQ ID NO:23, a DLL3-LCDR2 as set forth in SEQ ID NO:71, and a DLL3-LCDR3 as set forth in SEQ ID NO:25; or

[0914] The DLL3-VH comprises a DLL3-HCDR1 as set forth in SEQ ID NO:20, a DLL3-HCDR2 as set forth in SEQ ID NO:70, and a DLL3-HCDR3 as set forth in SEQ ID NO:22; and the DLL3-VL comprises a DLL3-LCDR1 as set forth in SEQ ID NO:23, a DLL3-LCDR2 as set forth in SEQ ID NO:24, and a DLL3-LCDR3 as set forth in SEQ ID NO:74.

[0915] An antigen-binding molecule or anti-DLL3 antibody that specifically binds to DLL3 and CD3, wherein:

[0916] The DLL3-VH comprises a DLL3-HCDR1 as shown in SEQ ID NO:20, a DLL3-HCDR2 as shown in SEQ ID NO:96, and a DLL3-HCDR3 as shown in SEQ ID NO:33; and the DLL3-VL comprises a DLL3-LCDR1 as shown in SEQ ID NO:34, a DLL3-LCDR2 as shown in SEQ ID NO:35, and a DLL3-LCDR3 as shown in SEQ ID NO:36.

[0917] In some embodiments, the antigen binding molecules or anti-DLL3 antibodies described above, the DLL3-VH and / or the DLL3-VL are murine or humanized. In some embodiments, the DLL3-VH and / or the DLL3-VL are humanized.

[0918] In some embodiments, the FR1, FR2, FR3, and FR4 of the humanized DLL3-VH have at least 60%, 70%, 80%, or 90% sequence identity with the FR1, FR2, FR3, and FR4 of SEQ ID NO: 50, 51, or 52; and the FR1, FR2, FR3, and FR4 of the humanized DLL3-VL have at least 60%, 70%, 80%, or 90% sequence identity with the FR1, FR2, FR3, and FR4 of SEQ ID NO: 62 or 68.

[0919] In some embodiments, the humanized DLL3-VH has FR1, FR2, FR3 derived from IGHV1-3*01, IGHV7-4-1*02, or IGHV3-73*01, and FR4 derived from IGHJ6*01, and is unsubstituted or has a nucleotide sequence selected from 1E, 5Q, 27Y, 30T, 38K, 43K, 48I, 67A, 68A, 69L, 71V, 73K, 75S, 76N, and 9 and / or the humanized DLL3-VL has FR1, FR2, FR3 derived from IGKV1-16*01 or IGKV3-20*02 and FR4 derived from IGKJ4*01, and is unsubstituted or has one or more amino acid substitutions selected from the group consisting of 1N, 36L, 42K, 43S, 44F, 46G, 69A, 71Y, 79Q and 85D. In some embodiments, the amino acid positions in the variable regions are defined according to the Kabat numbering convention.

[0920] In some embodiments, the humanized DLL3-VH comprises the amino acid sequence of SEQ ID NO: 50, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of 1E, 43K, 48I, 67A, 69L, 71V, 73K, and 76N in the FR region of SEQ ID NO: 50.

[0921] In some embodiments, the humanized DLL3-VH comprises the amino acid sequence of SEQ ID NO: 51, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of 1E, 5Q, 38K, 68A, 69L, 71V, 73K, 75S, and 76N in the FR region of SEQ ID NO: 51.

[0922] In some embodiments, the humanized DLL3-VH comprises the amino acid sequence of SEQ ID NO: 52, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of 27Y, 30T69L, 71V, 73K, and 93A in the FR region of SEQ ID NO: 52.

[0923] In some embodiments, the humanized DLL3-VL comprises the amino acid sequence of SEQ ID NO: 62, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of 36L, 43S, 44F, 46G, 69A, 71Y, and 85D in the FR region of SEQ ID NO: 62.

[0924] In some embodiments, the humanized DLL3-VL comprises the amino acid sequence of SEQ ID NO: 68, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of 36L, 42K, 46G, 69A, 71Y, 79Q, and 85D in the FR region of SEQ ID NO: 68.

[0925] In some embodiments, the FR1, FR2, FR3, and FR4 of the humanized DLL3-VH have at least 60%, 70%, 80%, or 90% sequence identity with the FR1, FR2, FR3, and FR4 of SEQ ID NO: 95; and the FR1, FR2, FR3, and FR4 of the humanized DLL3-VL have at least 60%, 70%, 80%, or 90% sequence identity with the FR1, FR2, FR3, and FR4 of SEQ ID NO: 88.

[0926] In some embodiments, the humanized DLL3-VH has FR1, FR2, FR3 derived from IGHV1-3*01 and FR4 derived from IGHJ6*01, and is unsubstituted or has one or more amino acid substitutions selected from the group consisting of 1E, 24T, 44S, 71V, and 73K; and / or the humanized DLL3-VL has FR1, FR2, FR3 derived from IGKV4-1*01 and FR4 derived from IGKJ2*01, and is unsubstituted or has one or more amino acid substitutions selected from the group consisting of 1N, 9K, 43S, 68A, and 85D. In some embodiments, the amino acid positions in the variable regions are defined according to the Kabat numbering convention.

[0927] In some embodiments, the humanized DLL3-VH comprises the amino acid sequence of SEQ ID NO: 95, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of 1E, 24T, 44S, 71V, and 73K in the FR region of SEQ ID NO: 95. In some embodiments, the humanized DLL3-VL comprises the amino acid sequence of SEQ ID NO: 88, or a variant thereof. In some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of 1N, 9K, 43S, 68A, and 85D in the FR region of SEQ ID NO: 88.

[0928] In some embodiments, the humanized DLL3-VH comprises the amino acid sequence of SEQ ID NO: 51, or a variant thereof; in some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of 1E, 38K, 68A, 69L, 71V, 73K, 75S, and 76N in the FR region of SEQ ID NO: 51; and the humanized DLL3-VL comprises the amino acid sequence of SEQ ID NO: 63, or a variant thereof; in some embodiments, the variant comprises one or more amino acid substitutions in the FR region of SEQ ID NO: 63; in some embodiments, the amino acid substitutions are selected from the group consisting of one or more amino acid substitutions of 43S and 44F.

[0929] In some embodiments, the humanized DLL3-VH comprises the amino acid sequence of SEQ ID NO: 91, or a variant of SEQ ID NO: 91; in some embodiments, the variant comprises one or more amino acid substitutions in the FR region of SEQ ID NO: 91; and

[0930] The humanized DLL3-VL comprises the amino acid sequence of SEQ ID NO: 88, or a variant thereof; in some embodiments, the variant comprises one or more amino acid substitutions selected from the group consisting of 1N, 9K, 43S, 68A, and 85D in the FR region of SEQ ID NO: 88.

[0931] In some embodiments, the variable regions and CDRs described above are defined according to the Kabat numbering convention.

[0932] In some embodiments, the antigen binding molecule of any of the preceding items, wherein the amino acid sequence of the DLL3-VH has at least 90%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 12, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56 or 57, and the amino acid sequence of the DLL3-VL has at least 90%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 13, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67 or 68. In some embodiments, the amino acid sequence of the DLL3-VH is as shown in SEQ ID NO: 12, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56 or 57, and the amino acid sequence of the DLL3-VL is as shown in SEQ ID NO: 13, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67 or 68.

[0933] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein the amino acid sequence of the DLL3-VH has at least 90%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56 or 57, and the amino acid sequence of the DLL3-VL has at least 90%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 63, 64, 65, 66 or 67. In some embodiments, the amino acid sequence of the DLL3-VH is as shown in SEQ ID NO:43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56 or 57, and the amino acid sequence of the DLL3-VL is as shown in SEQ ID NO:63, 64, 65, 66 or 67.

[0934] In some embodiments, the anti-DLL3 antibody of any of the preceding items, wherein the amino acid sequence of the DLL3-VH has at least 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 56 or 57, and the amino acid sequence of the DLL3-VL has at least 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, or 68. In some embodiments, the amino acid sequence of the DLL3-VH is as set forth in SEQ ID NO: 56 or 57, and the amino acid sequence of the DLL3-VL is as set forth in SEQ ID NO: 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, or 68.

[0935] In some embodiments, in the antigen binding molecule or anti-DLL3 antibody of any preceding item, the amino acid sequence of the DLL3-VH is as shown in SEQ ID NO: 54, and the amino acid sequence of the DLL3-VL is as shown in SEQ ID NO: 63; or

[0936] The amino acid sequence of the DLL3-VH is shown in SEQ ID NO: 54, and the amino acid sequence of the DLL3-VL is shown in SEQ ID NO: 61; or

[0937] The amino acid sequence of the DLL3-VH is shown in SEQ ID NO: 54, and the amino acid sequence of the DLL3-VL is shown in SEQ ID NO: 64; or

[0938] The amino acid sequence of the DLL3-VH is shown in SEQ ID NO: 56, and the amino acid sequence of the DLL3-VL is shown in SEQ ID NO: 65; or

[0939] The amino acid sequence of the DLL3-VH is shown in SEQ ID NO: 56, and the amino acid sequence of the DLL3-VL is shown in SEQ ID NO: 67; or

[0940] The amino acid sequence of the DLL3-VH is shown in SEQ ID NO: 56, and the amino acid sequence of the DLL3-VL is shown in SEQ ID NO: 65; or

[0941] The amino acid sequence of the DLL3-VH is shown in SEQ ID NO: 57, and the amino acid sequence of the DLL3-VL is shown in SEQ ID NO: 65; or

[0942] The amino acid sequence of the DLL3-VH is shown in SEQ ID NO: 57, and the amino acid sequence of the DLL3-VL is shown in SEQ ID NO: 67; or

[0943] The amino acid sequence of the DLL3-VH is shown in SEQ ID NO: 57, and the amino acid sequence of the DLL3-VL is shown in SEQ ID NO: 65.

[0944] In some embodiments, the antigen binding molecule or anti-DLL3 antibody of any of the preceding items, wherein the amino acid sequence of the DLL3-VH has at least 90%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 16, 89, 90, 91, 92, 93, 94 or 95, and the amino acid sequence of the DLL3-VL has at least 90%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 17, 86, 87 or 88. In some embodiments, the amino acid sequence of the DLL3-VH is as shown in SEQ ID NO: 16, 89, 90, 91, 92, 93, 94 or 95, and the amino acid sequence of the DLL3-VL is as shown in SEQ ID NO: 17, 86, 87 or 88.

[0945] In some embodiments, in the antigen binding molecule or anti-DLL3 antibody of any preceding item, the amino acid sequence of the DLL3-VH is shown in SEQ ID NO: 91, and the amino acid sequence of the DLL3-VL is shown in SEQ ID NO: 87.

[0946] In some embodiments, the anti-DLL3 antibody of any of the preceding items comprises a heavy chain and a light chain, wherein:

[0947] The amino acid sequence of the heavy chain is shown in SEQ ID NO: 121, and the amino acid sequence of the light chain is shown in SEQ ID NO: 122; or

[0948] The amino acid sequence of the heavy chain is shown in SEQ ID NO: 125, and the amino acid sequence of the light chain is shown in SEQ ID NO: 126.

[0949] In some embodiments, the antigen binding molecule as described above, wherein:

[0950] i) the CD3-VH comprises CD3-HCDR1 as shown in SEQ ID NO: 129, CD3-HCDR2 as shown in SEQ ID NO: 130, and CD3-HCDR3 as shown in SEQ ID NO: 131; and the CD3-VL comprises CD3-LCDR1 as shown in SEQ ID NO: 132, CD3-LCDR2 as shown in SEQ ID NO: 133, and CD3-LCDR3 as shown in SEQ ID NO: 134; or

[0951] ii) the CD3-VH comprises CD3-HCDR1 as shown in SEQ ID NO: 129, CD3-HCDR2 as shown in SEQ ID NO: 130, and CD3-HCDR3 as shown in SEQ ID NO: 135; and the CD3-VL comprises CD3-LCDR1 as shown in SEQ ID NO: 132, CD3-LCDR2 as shown in SEQ ID NO: 133, and CD3-LCDR3 as shown in SEQ ID NO: 134.

[0952] In some embodiments, the variable regions and CDRs described above are defined according to the Kabat numbering convention.

[0953] In some embodiments, the antigen binding molecule of any of the preceding items, the CD3-VH and / or the CD3-VL are murine or humanized. In some embodiments, the CD3-VH and / or the CD3-VL are humanized.

[0954] In some embodiments, the antigen binding molecule as described in any of the preceding items, wherein the amino acid sequence of the CD3-VH is shown in SEQ ID NO: 136 or 138, and the amino acid sequence of the CD3-VL is shown in SEQ ID NO: 137.

[0955] In some embodiments, the antigen binding molecule of any of the preceding items comprises:

[0956] The first chain shown in SEQ ID NO: 152, the second chain shown in SEQ ID NO: 153, the third chain shown in SEQ ID NO: 154, and the fourth chain shown in SEQ ID NO: 155; or

[0957] The first chain is shown as SEQ ID NO:152, the second chain is shown as SEQ ID NO:153, the third chain is shown as SEQ ID NO:156, and the fourth chain is shown as SEQ ID NO:155.

[0958] In some embodiments, the antigen binding molecule of any of the preceding items comprises:

[0959] The first chain shown in SEQ ID NO: 157, the second chain shown in SEQ ID NO: 158, and the third chain shown in SEQ ID NO: 159; or

[0960] The first strand is shown as SEQ ID NO:157, the second strand is shown as SEQ ID NO:158, and the third strand is shown as SEQ ID NO:160.

[0961] In some embodiments, the antigen binding molecule of any of the preceding items comprises:

[0962] The first chain shown in SEQ ID NO: 161 and the second chain shown in SEQ ID NO: 162; or

[0963] The first strand set forth in SEQ ID NO: 163 and the second strand set forth in SEQ ID NO: 162; or

[0964] The first strand set forth in SEQ ID NO: 185 and the second strand set forth in SEQ ID NO: 162; or

[0965] The first strand set forth in SEQ ID NO: 186 and the second strand set forth in SEQ ID NO: 162; or

[0966] The first strand set forth in SEQ ID NO: 259 and the second strand set forth in SEQ ID NO: 162; or

[0967] The first strand set forth in SEQ ID NO: 260 and the second strand set forth in SEQ ID NO: 162; or

[0968] The first strand set forth in SEQ ID NO: 187 and the second strand set forth in SEQ ID NO: 188; or

[0969] The first strand set forth in SEQ ID NO: 187 and the second strand set forth in SEQ ID NO: 189; or

[0970] The first chain shown in SEQ ID NO: 190 and the second chain shown in SEQ ID NO: 188; or

[0971] The first chain shown in SEQ ID NO: 190 and the second chain shown in SEQ ID NO: 189; or

[0972] The first chain shown in SEQ ID NO: 191 and the second chain shown in SEQ ID NO: 188; or

[0973] The first strand is shown as SEQ ID NO:191 and the second strand is shown as SEQ ID NO:189.

[0974] In some embodiments, the antigen binding molecule of any of the preceding items comprises:

[0975] The first chain shown in SEQ ID NO: 171, the second chain shown in SEQ ID NO: 172, the third chain shown in SEQ ID NO: 154, and the fourth chain shown in SEQ ID NO: 155; or

[0976] The first chain is shown as SEQ ID NO:171, the second chain is shown as SEQ ID NO:172, the third chain is shown as SEQ ID NO:156, and the fourth chain is shown as SEQ ID NO:155.

[0977] In some embodiments, the antigen binding molecule of any of the preceding items comprises:

[0978] The first chain shown in SEQ ID NO: 173, the second chain shown in SEQ ID NO: 174, and the third chain shown in SEQ ID NO: 159; or

[0979] The first chain is shown as SEQ ID NO:173, the second chain is shown as SEQ ID NO:174, and the third chain is shown as SEQ ID NO:160.

[0980] In some embodiments, the antigen binding molecule of any of the preceding items comprises:

[0981] The first strand set forth in SEQ ID NO: 175 and the second strand set forth in SEQ ID NO: 176; or

[0982] The first strand is shown as SEQ ID NO: 177 and the second strand is shown as SEQ ID NO: 176.

[0983] The antigen binding molecules comprising antibody series 98 and 30 disclosed in the examples herein have the same technical solution scope as the antibody series 6 and 110 described above.

[0984] Structure of antigen-binding molecules

[0985] The bispecific antigen binding molecules disclosed herein are not limited to a specific molecular structure, as long as they have the desired antigen binding function. For example, the bispecific antigen binding molecules herein can be bivalent (1+1), trivalent (2+1) or quadrivalent (2+2). The antigen binding moiety in the antigen binding molecule can be any antibody fragment with antigen binding activity, which is fused through a peptide linker. The peptide linkers (such as linkers 1 to 8) disclosed herein can be any suitable peptide chain, as long as the antigen binding molecule can exhibit the desired antigen binding activity. For example, a peptide linker can be a flexible peptide comprising 1-50 or 3-20 amino acid residues. In some embodiments, the peptide linkers each independently have a structure of (GGGGS)n, wherein n is 1, 2 or 3. In some embodiments, the sequences of linker 1 and linker 2 are both GGGGS (SEQ ID NO: 147). In some embodiments, the sequence of linker 3 is GGGGSGGGGSGGGGS (SEQ ID NO: 148). In some embodiments, the sequence of linker 4 is GGGGS (SEQ ID NO: 147). In some embodiments, the sequence of linker 5 is GGGSGGGG (SEQ ID NO: 149). In some embodiments, the sequence of linker 6 and linker 8 is G (SEQ ID NO: 150). In some embodiments, the sequence of linker 7 is GGGGSGGGG (SEQ ID NO: 151).

[0986] Exemplarily, the antigen-binding molecule disclosed herein has a first chain having a structure as shown in formula (a-1), a second chain having a structure as shown in formula (b-1), a third chain having a structure as shown in formula (c), and a fourth chain having a structure as shown in formula (d).

[0987] (a-1)[DLL3-VH]-[GGGGS]-[Titin chain]-[Fc2],

[0988] (b-1) [DLL3-VL]-[GGGGS]-[Obscurin chain],

[0989] (c) [CD3-VH]-[CH1]-[Fc1],

[0990] (d) [CD3-VL]-[CL],

[0991] The structures represented by formulae (a-1), (b-1), (c) and (d) are arranged from the N-terminus to the C-terminus.

[0992] Exemplary antigen binding molecules include:

[0993] a first strand set forth in SEQ ID NO: 171, a second strand set forth in SEQ ID NO: 172, a third strand set forth in SEQ ID NO: 154, and a fourth strand set forth in SEQ ID NO: 155; or

[0994] a first strand set forth in SEQ ID NO: 171, a second strand set forth in SEQ ID NO: 172, a third strand set forth in SEQ ID NO: 156, and a fourth strand set forth in SEQ ID NO: 155; or

[0995] a first strand set forth in SEQ ID NO: 152, a second strand set forth in SEQ ID NO: 153, a third strand set forth in SEQ ID NO: 154, and a fourth strand set forth in SEQ ID NO: 155; or

[0996] a first strand set forth in SEQ ID NO: 152, a second strand set forth in SEQ ID NO: 153, a third strand set forth in SEQ ID NO: 156, and a fourth strand set forth in SEQ ID NO: 155; or

[0997] a first strand set forth in SEQ ID NO: 164, a second strand set forth in SEQ ID NO: 165, a third strand set forth in SEQ ID NO: 154, and a fourth strand set forth in SEQ ID NO: 155; or

[0998] a first strand set forth in SEQ ID NO: 164, a second strand set forth in SEQ ID NO: 165, a third strand set forth in SEQ ID NO: 156, and a fourth strand set forth in SEQ ID NO: 155; or

[0999] a first strand set forth in SEQ ID NO: 178, a second strand set forth in SEQ ID NO: 179, a third strand set forth in SEQ ID NO: 154, and a fourth strand set forth in SEQ ID NO: 155; or

[1000] A first strand as shown in SEQ ID NO:178, a second strand as shown in SEQ ID NO:179, a third strand as shown in SEQ ID NO:156, and a fourth strand as shown in SEQ ID NO:155.

[1001] Exemplarily, the antigen-binding molecule comprises a first chain having a structure represented by formula (e), a second chain having a structure represented by formula (f), and a third chain having a structure represented by formula (g-1).

[1002] (e)[DLL3-VL]-[CL],

[1003] (f) [DLL3-VL]-[CH1]-[Fc2],

[1004] (g-1)[CD3-VH]-[GGGGSGGGGSGGGGS]-[CD3-VL]-[GGGGS]-[Fc1],

[1005] The structures represented by formulae (e), (f), and (g-1) are arranged from the N-terminus to the C-terminus.

[1006] Exemplary antigen binding molecules have:

[1007] a first strand set forth in SEQ ID NO: 173, a second strand set forth in SEQ ID NO: 174, and a third strand set forth in SEQ ID NO: 160; or

[1008] a first strand set forth in SEQ ID NO: 173, a second strand set forth in SEQ ID NO: 174, and a third strand set forth in SEQ ID NO: 159; or

[1009] a first strand set forth in SEQ ID NO: 157, a second strand set forth in SEQ ID NO: 158, and a third strand set forth in SEQ ID NO: 159; or

[1010] a first strand set forth in SEQ ID NO: 157, a second strand set forth in SEQ ID NO: 158, and a third strand set forth in SEQ ID NO: 160; or

[1011] a first strand set forth in SEQ ID NO: 166, a second strand set forth in SEQ ID NO: 167, and a third strand set forth in SEQ ID NO: 159; or

[1012] a first strand set forth in SEQ ID NO: 166, a second strand set forth in SEQ ID NO: 167, and a third strand set forth in SEQ ID NO: 160; or

[1013] a first strand set forth in SEQ ID NO: 180, a second strand set forth in SEQ ID NO: 181, and a third strand set forth in SEQ ID NO: 159; or

[1014] A first strand as shown in SEQ ID NO:180, a second strand as shown in SEQ ID NO:181 and a third strand as shown in SEQ ID NO:160.

[1015] Exemplarily, the antigen-binding molecule comprises a first chain having a structure represented by formula (i-1) and a second chain having a structure represented by formula (h-1).

[1016] (h-1)[DLL3-VL]-[GGGSGGGG]-[CD3-VH]-[G]-[Fc1],

[1017] (i-1)[CD3-VL]-[GGGGSGGGG]-[DLL3-VH]-[G]-[Fc2],

[1018] The structures represented by formulae (h-1) and (i-1) are arranged from the N-terminus to the C-terminus.

[1019] Exemplary antigen binding molecules have:

[1020] a first strand as shown in SEQ ID NO: 185 and a second strand as shown in SEQ ID NO: 162; or

[1021] a first strand as shown in SEQ ID NO: 161 and a second strand as shown in SEQ ID NO: 162; or

[1022] a first strand as set forth in SEQ ID NO: 163 and a second strand as set forth in SEQ ID NO: 162; or

[1023] a first strand as set forth in SEQ ID NO: 259 and a second strand as set forth in SEQ ID NO: 162; or

[1024] a first strand as shown in SEQ ID NO: 260 and a second strand as shown in SEQ ID NO: 162; or

[1025] a first strand as set forth in SEQ ID NO: 168 and a second strand as set forth in SEQ ID NO: 169; or

[1026] a first strand as shown in SEQ ID NO: 170 and a second strand as shown in SEQ ID NO: 169; or

[1027] a first strand as set forth in SEQ ID NO: 175 and a second strand as set forth in SEQ ID NO: 176; or

[1028] A first strand as set forth in SEQ ID NO: 177 and a second strand as set forth in SEQ ID NO: 176; or

[1029] a first strand as shown in SEQ ID NO: 182 and a second strand as shown in SEQ ID NO: 183; or

[1030] a first strand as set forth in SEQ ID NO: 184 and a second strand as set forth in SEQ ID NO: 183; or

[1031] a first strand as set forth in SEQ ID NO: 186 and a second strand as set forth in SEQ ID NO: 162; or

[1032] a first strand as set forth in SEQ ID NO: 187 and a second strand as set forth in SEQ ID NO: 188; or

[1033] a first strand as set forth in SEQ ID NO: 187 and a second strand as set forth in SEQ ID NO: 189; or

[1034] a first strand as shown in SEQ ID NO: 190 and a second strand as shown in SEQ ID NO: 188; or

[1035] a first strand as shown in SEQ ID NO: 190 and a second strand as shown in SEQ ID NO: 189; or

[1036] a first strand as set forth in SEQ ID NO: 191 and a second strand as set forth in SEQ ID NO: 188; or

[1037] A first strand as shown in SEQ ID NO:191 and a second strand as shown in SEQ ID NO:189.

[1038] Variants of antigen-binding molecules

[1039] In certain embodiments, the amino acid sequence variants of the antigen binding molecules provided herein are encompassed.For example, it is desirable to improve the binding affinity and / or other biological properties of the antibody. Suitable modifications can be introduced into the nucleotide sequence encoding the antibody, or the amino acid sequence variants of the antibody can be prepared by peptide synthesis. Such modifications include, for example, deletion and / or insertion and / or replacement of the residues in the amino acid sequence of the antigen binding molecules. Any combination of deletion, insertion a...

Claims

1. An antigen binding molecule that specifically binds to DLL3 and CD3, comprising at least one antigen binding moiety that specifically binds to DLL3 and at least one antigen binding moiety that specifically binds to CD3, The antigen binding moiety that specifically binds to DLL3 comprises a heavy chain variable region DLL3-VH and a light chain variable region DLL3-VL, The antigen binding moiety that specifically binds to CD3 comprises a heavy chain variable region CD3-VH and a light chain variable region CD3-VL; wherein: i) the DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, 24, 72 or 73, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25 or 74; or ii) the DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 26 or 84, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 85 or 27, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 83 or 28; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31; or iii) the DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 96, 32, 97, 98 or 99, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 33; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 34, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 36; or iv) the DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 119, 37, 117, 118 or 120, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 38; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 39, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 40; Preferably, i) the DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 24, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 72, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 69, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74; or the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74; or the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 69, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 73, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74; or the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 73, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74; or the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 69, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or ii) the DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO:26, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO:85, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO:83; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO:29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO:30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO:31; or the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 26, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 27, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 83; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31; or the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 84, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 27, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 83; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31; or the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 84, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 85, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 83; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31; or the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 26, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 27, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 28; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31; or iii) the DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO:20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO:96, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO:33; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO:34, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO:35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO:36; or iv) the DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 119, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 38; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 39, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 40; More preferably, The antigen-binding molecule has a mass of less than 4×10 -9 M binds to human DLL3 with a KD as measured by surface plasmon resonance.

2. The antigen-binding molecule that specifically binds to DLL3 and CD3 according to claim 1, wherein: i) the CD3-VH comprises: a CD3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 129, a CD3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 130, and a CD3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 131; and the CD3-VL comprises: a CD3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 132, a CD3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 133, and a CD3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 134; or ii) the CD3-VH comprises: CD3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 129, CD3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 130, and CD3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 135; and the CD3-VL comprises: CD3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 132, CD3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 133, and CD3-LCDR3 comprising the amino acid sequence of SEQ ID NO:

134.

3. The antigen-binding molecule that specifically binds to DLL3 and CD3 according to claim 1 or 2, wherein: i) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 54, 12, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 55, 56 or 57, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 63, 13, 58, 59, 60, 61, 62, 64, 65, 66, 67 or 68; or ii) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 81, 14, 78, 79, 80 or 82, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 77, 15, 75 or 76; or iii) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 91, 16, 89, 90, 92, 93, 94 or 95, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 87, 17, 86 or 88; or iv) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 109, 18, 105, 106, 107, 108, 110, 111, 112, 113, 114, 115 or 116, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 100, 19, 101, 102, 103 or 104; Preferably, i) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 54, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 63; or the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 54, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 61; or the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 54, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 64; or the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 56, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 65; or the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 56, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 66; or the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 56, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 67; or the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 57, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 65; or the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 57, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 66; or the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 57, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 67; or ii) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 81, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 77; or iii) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 91, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 87; or iv) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 109, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO:

100.

4. The antigen-binding molecule that specifically binds to DLL3 and CD3 according to any one of claims 1 to 3, wherein: i) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137; or ii) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO:

137.

5. The antigen-binding molecule that specifically binds to DLL3 and CD3 according to any one of claims 1 to 4, wherein: The antigen binding moiety that specifically binds to DLL3 comprises a titin chain and an obscurin chain that can form a dimer; or The antigen binding module that specifically binds to CD3 comprises a titin chain and an obscurin chain that can form a dimer; Preferably, The titin chain comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 192 to SEQ ID NO: 210, The Obscurin chain comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 211 to SEQ ID NO: 251; More preferably, The titin chain comprises the amino acid sequence of SEQ ID NO: 208, and the obscurin chain comprises the amino acid sequence of SEQ ID NO:

246.

6. The antigen-binding molecule that specifically binds to DLL3 and CD3 according to any one of claims 1 to 5, comprising an Fc region, wherein the Fc region is preferably a human IgG Fc region, more preferably a human IgG1 Fc region; More preferably, the Fc region comprises one or more amino acid substitutions that can reduce the binding of the Fc region to Fcγ receptors; Most preferably, the Fc region is a human IgG1 Fc region and the amino acids at positions 234 and 235 are A, numbering according to the EU index.

7. The antigen-binding molecule that specifically binds to DLL3 and CD3 according to any one of claims 1 to 6, comprising an Fc region comprising a first subunit Fc1 and a second subunit Fc2 capable of associating with each other, wherein the Fc1 and Fc2 each independently have one or more amino acid substitutions that reduce homodimerization of the Fc region; Preferably, the Fc1 has a protrusion structure according to the pestle-and-mortar technique, and the Fc2 has a hole structure according to the pestle-and-mortar technique; More preferably, the amino acid at position 366 of Fc1 is W; and the amino acid at position 366 of Fc2 is S, the amino acid at position 368 is A, and the amino acid at position 407 is V, numbering according to the EU index; Most preferably, the Fc1 comprises the amino acid sequence of SEQ ID NO: 143; and the Fc2 comprises the amino acid sequence of SEQ ID NO: 144; or the Fc1 comprises the amino acid sequence of SEQ ID NO: 145; and the Fc2 comprises the amino acid sequence of SEQ ID NO:

146.

8. The antigen-binding molecule that specifically binds to DLL3 and CD3 according to claim 7, wherein the antigen-binding molecule comprises one antigen-binding moiety that specifically binds to DLL3 and one antigen-binding moiety that specifically binds to CD3, the antigen-binding moiety that specifically binds to DLL3 is a substituted Fab comprising a titin chain and an obscurin chain that can form a dimer; and the antigen-binding moiety that specifically binds to CD3 is a Fab; or The antigen binding moiety that specifically binds to DLL3 is a Fab, and the antigen binding moiety that specifically binds to CD3 is a substituted Fab comprising a titin chain and an obscurin chain that can form a dimer; Preferably, The antigen-binding molecule that specifically binds to DLL3 and CD3 comprises a first chain having a structure represented by formula (a), a second chain having a structure represented by formula (b), a third chain having a structure represented by formula (c), and a fourth chain having a structure represented by formula (d). Formula (a): [DLL3-VH]-[Linker 1]-[Titin chain]-[Fc2], Formula (b) [DLL3-VL]-[Linker 2]-[Obscurin chain], Formula (c) [CD3-VH]-[CH1]-[Fc1], Formula (d) [CD3-VL]-[CL], in: The linker 1 and linker 2 are the same or different peptide linkers; or the linker 1 and / or linker 2 do not exist; The structures shown in formulas (a), (b), (c) and (d) are arranged from the N-terminus to the C-terminus; The titin chain and the obscurin chain are interchangeable; The Fc1 and the Fc2 are interchangeable; More preferably, the antigen binding molecule that specifically binds to DLL3 and CD3 has: a first chain comprising the amino acid sequence of SEQ ID NO: 171, a second chain comprising the amino acid sequence of SEQ ID NO: 172, a third chain comprising the amino acid sequence of SEQ ID NO: 154, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 155; or a first chain comprising the amino acid sequence of SEQ ID NO: 171, a second chain comprising the amino acid sequence of SEQ ID NO: 172, a third chain comprising the amino acid sequence of SEQ ID NO: 156, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 155; or a first chain comprising the amino acid sequence of SEQ ID NO: 152, a second chain comprising the amino acid sequence of SEQ ID NO: 153, a third chain comprising the amino acid sequence of SEQ ID NO: 154, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 155; or a first chain comprising the amino acid sequence of SEQ ID NO: 152, a second chain comprising the amino acid sequence of SEQ ID NO: 153, a third chain comprising the amino acid sequence of SEQ ID NO: 156, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 155; or a first chain comprising the amino acid sequence of SEQ ID NO: 164, a second chain comprising the amino acid sequence of SEQ ID NO: 165, a third chain comprising the amino acid sequence of SEQ ID NO: 154, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 155; or a first chain comprising the amino acid sequence of SEQ ID NO: 164, a second chain comprising the amino acid sequence of SEQ ID NO: 165, a third chain comprising the amino acid sequence of SEQ ID NO: 156, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 155; or a first chain comprising the amino acid sequence of SEQ ID NO: 178, a second chain comprising the amino acid sequence of SEQ ID NO: 179, a third chain comprising the amino acid sequence of SEQ ID NO: 154, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 155; or A first chain comprising the amino acid sequence of SEQ ID NO: 178, a second chain comprising the amino acid sequence of SEQ ID NO: 179, a third chain comprising the amino acid sequence of SEQ ID NO: 156, and a fourth chain comprising the amino acid sequence of SEQ ID NO:

155.

9. The antigen-binding molecule that specifically binds to DLL3 and CD3 according to claim 7, wherein the antigen-binding molecule comprises an antigen-binding moiety that specifically binds to DLL3 and an antigen-binding moiety that specifically binds to CD3, wherein the antigen-binding moiety that specifically binds to DLL3 is a Fab; and the antigen-binding moiety that specifically binds to CD3 is a scFv; Preferably, The antigen-binding molecule that specifically binds to DLL3 and CD3 comprises a first chain having a structure represented by formula (e), a second chain having a structure represented by formula (f), and a third chain having a structure represented by formula (g). Formula (e) [DLL3-VL]-[CL], Formula (f) [DLL3-VH]-[CH1]-[Fc2], Formula (g): [CD3-VH]-[Linker 3]-[CD3-VL]-[Linker 4]-[Fc1], in: The linker 3 and linker 4 are the same or different peptide linkers; The structures shown in formulas (e), (f), and (g) are arranged from the N-terminus to the C-terminus; The Fc1 and the Fc2 are interchangeable; More preferably, the antigen binding molecule that specifically binds to DLL3 and CD3 has: a first chain comprising the amino acid sequence of SEQ ID NO: 173, a second chain comprising the amino acid sequence of SEQ ID NO: 174, and a third chain comprising the amino acid sequence of SEQ ID NO: 160; or a first chain comprising the amino acid sequence of SEQ ID NO: 173, a second chain comprising the amino acid sequence of SEQ ID NO: 174, and a third chain comprising the amino acid sequence of SEQ ID NO: 159; or a first chain comprising the amino acid sequence of SEQ ID NO: 157, a second chain comprising the amino acid sequence of SEQ ID NO: 158, and a third chain comprising the amino acid sequence of SEQ ID NO: 159; or a first chain comprising the amino acid sequence of SEQ ID NO: 157, a second chain comprising the amino acid sequence of SEQ ID NO: 158, and a third chain comprising the amino acid sequence of SEQ ID NO: 160; or a first chain comprising the amino acid sequence of SEQ ID NO: 166, a second chain comprising the amino acid sequence of SEQ ID NO: 167, and a third chain comprising the amino acid sequence of SEQ ID NO: 159; or a first chain comprising the amino acid sequence of SEQ ID NO: 166, a second chain comprising the amino acid sequence of SEQ ID NO: 167, and a third chain comprising the amino acid sequence of SEQ ID NO: 160; or a first chain comprising the amino acid sequence of SEQ ID NO: 180, a second chain comprising the amino acid sequence of SEQ ID NO: 181, and a third chain comprising the amino acid sequence of SEQ ID NO: 159; or A first chain comprising the amino acid sequence of SEQ ID NO: 180, a second chain comprising the amino acid sequence of SEQ ID NO: 181, and a third chain comprising the amino acid sequence of SEQ ID NO:

160.

10. The antigen-binding molecule that specifically binds to DLL3 and CD3 according to claim 7, wherein the antigen-binding molecule comprises one antigen-binding moiety that specifically binds to DLL3 and one antigen-binding moiety that specifically binds to CD3, The antigen-binding molecule that specifically binds to DLL3 and CD3 comprises a first chain having a structure represented by formula (h) and a second chain having a structure represented by formula (i). Formula (h): [DLL3-VL]-[Linker 5]-[CD3-VH]-[Linker 6]-[Fc1], Formula (i): [CD3-VL]-[Linker 7]-[DLL3-VH]-[Linker 8]-[Fc2], in: The linker 5, linker 6, linker 7 and linker 8 are the same or different peptide linkers; The structures shown in formula (h) and (i) are arranged from the N-terminus to the C-terminus; The Fc1 and the Fc2 are interchangeable; Preferably, wherein: i) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 54, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 63; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137; or the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 54, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 61; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137; or the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 54, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 64; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137; or the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 56, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 65; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137; or the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 56, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 66; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137; or the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 56, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 67; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137; or the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 57, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 65; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137; or the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 57, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 66; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137; or the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 57, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 67; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137; or ii) the DLL3-VH comprises the amino acid sequence of SEQ ID NO:91, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO:87; and the CD3-VH comprises the amino acid sequence of SEQ ID NO:136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO:137; or iii) the DLL3-VH comprises the amino acid sequence of SEQ ID NO:81, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO:77; and the CD3-VH comprises the amino acid sequence of SEQ ID NO:136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO:137; or iv) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 109, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 100; and the CD3-VH comprises the amino acid sequence of SEQ ID NO: 136 or 138, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 137; More preferably, the antigen binding molecule that specifically binds to DLL3 and CD3 has: a first chain comprising the amino acid sequence of SEQ ID NO: 185 and a second chain comprising the amino acid sequence of SEQ ID NO: 162; or a first chain comprising the amino acid sequence of SEQ ID NO: 161 and a second chain comprising the amino acid sequence of SEQ ID NO: 162; or a first chain comprising the amino acid sequence of SEQ ID NO: 163 and a second chain comprising the amino acid sequence of SEQ ID NO: 162; or a first chain comprising the amino acid sequence of SEQ ID NO: 259 and a second chain comprising the amino acid sequence of SEQ ID NO: 162; or a first chain comprising the amino acid sequence of SEQ ID NO: 260 and a second chain comprising the amino acid sequence of SEQ ID NO: 162; or a first chain comprising the amino acid sequence of SEQ ID NO: 168 and a second chain comprising the amino acid sequence of SEQ ID NO: 169; or a first chain comprising the amino acid sequence of SEQ ID NO: 170 and a second chain comprising the amino acid sequence of SEQ ID NO: 169; or a first chain comprising the amino acid sequence of SEQ ID NO: 175 and a second chain comprising the amino acid sequence of SEQ ID NO: 176; or a first chain comprising the amino acid sequence of SEQ ID NO: 177 and a second chain comprising the amino acid sequence of SEQ ID NO: 176; or a first chain comprising the amino acid sequence of SEQ ID NO: 182 and a second chain comprising the amino acid sequence of SEQ ID NO: 183; or a first chain comprising the amino acid sequence of SEQ ID NO: 184 and a second chain comprising the amino acid sequence of SEQ ID NO: 183; or a first chain comprising the amino acid sequence of SEQ ID NO: 186 and a second chain comprising the amino acid sequence of SEQ ID NO: 162; or a first chain comprising the amino acid sequence of SEQ ID NO: 187 and a second chain comprising the amino acid sequence of SEQ ID NO: 188; or a first chain comprising the amino acid sequence of SEQ ID NO: 187 and a second chain comprising the amino acid sequence of SEQ ID NO: 189; or a first chain comprising the amino acid sequence of SEQ ID NO: 190 and a second chain comprising the amino acid sequence of SEQ ID NO: 188; or a first chain comprising the amino acid sequence of SEQ ID NO: 190 and a second chain comprising the amino acid sequence of SEQ ID NO: 189; or a first chain comprising the amino acid sequence of SEQ ID NO: 191 and a second chain comprising the amino acid sequence of SEQ ID NO: 188; or A first chain comprising the amino acid sequence of SEQ ID NO: 191 and a second chain comprising the amino acid sequence of SEQ ID NO:

189.

11. An anti-DLL3 antibody capable of specifically binding to DLL3, said anti-DLL3 antibody comprising a heavy chain variable region DLL3-VH and a light chain variable region DLL3-VL, wherein: i) the DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 24, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 72, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 73, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74; or the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 72, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74; or the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, 69 or 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 73, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74; or ii) the DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 26 or 84, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 85 or 27, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 83 or 28; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31; or iii) the DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 96, 32, 97, 98 or 99, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 33; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 34, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 36; or iv) the DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 119, 37, 117, 118 or 120, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 38; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 39, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 40; Preferably, i) the DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 72, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 69, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74; or the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74; or the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 69, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 73, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74; or the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 73, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 74; or the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 69, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 70, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 22; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 23, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 71, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 25; or ii) the DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO:26, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO:85, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO:83; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO:29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO:30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO:31; or the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 26, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 27, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 83; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31; or the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 84, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 27, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 83; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31; or the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 84, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 85, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 83; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31; or the DLL3-VH comprising: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 26, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 27, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 28; and the DLL3-VL comprising: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 29, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 31; or iii) the DLL3-VH has: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO:20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO:96, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO:33; and the DLL3-VL has: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO:34, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO:35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO:36; or iv) the DLL3-VH comprises: a DLL3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a DLL3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 119, and a DLL3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 38; and the DLL3-VL comprises: a DLL3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 39, a DLL3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a DLL3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 40; More preferably, The anti-DLL3 antibody was expressed at a concentration of less than 4×10 -9 M binds to human DLL3 with a KD as measured by surface plasmon resonance.

12. The anti-DLL3 antibody of claim 11, comprising a heavy chain variable region DLL3-VH and a light chain variable region DLL3-VL, wherein: i) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 54, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 55, 56 or 57, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 63, 64, 65, 66 or 67; or the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 56 or 57, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 58, 59, 60, 61, 62, 63, 64, 65, 66, 67 or 68; or ii) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 81, 78, 79, 80 or 82, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 77, 75 or 76; or iii) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 91, 89, 90, 92, 93, 94 or 95, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 87, 86 or 88; or iv) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 109, 105, 106, 107, 108, 110, 111, 112, 113, 114, 115 or 116, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 100, 101, 102, 103 or 104; Preferably, i) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 54, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 63; or the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 54, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 61; or the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 54, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 64; or the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 56, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 65; or the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 56, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 66; or the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 56, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 67; or the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 57, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 65; or the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 57, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 66; or the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 57, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 67; or ii) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 81, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 77; or iii) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 91, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO: 87; or iv) the DLL3-VH comprises the amino acid sequence of SEQ ID NO: 109, and the DLL3-VL comprises the amino acid sequence of SEQ ID NO:

100.

13. The anti-DLL3 antibody according to claim 11 or 12, wherein the anti-DLL3 antibody is an antibody fragment; preferably, the antibody fragment is Fab, Fab', F(ab')2, Fd, Fv, scFv, dsFv or dAb.

14. The anti-DLL3 antibody according to any one of claims 11 to 13, comprising a heavy chain constant region and a light chain constant region; preferably, the heavy chain constant region comprises the amino acid sequence of SEQ ID NO: 41, and / or the light chain constant region comprises the amino acid sequence of SEQ ID NO:

42.

15. The anti-DLL3 antibody of claim 14, comprising a heavy chain and a light chain, wherein: the heavy chain comprises an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 121, and the light chain comprises an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 122; or the heavy chain comprises an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 123, and the light chain comprises an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 124; or the heavy chain comprises an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 125, and the light chain comprises an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 126; or the heavy chain comprises an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 127, and the light chain comprises an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 128; Preferably, The heavy chain comprises the amino acid sequence of SEQ ID NO: 121, and the light chain comprises the amino acid sequence of SEQ ID NO: 122; or The heavy chain comprises the amino acid sequence of SEQ ID NO: 123, and the light chain comprises the amino acid sequence of SEQ ID NO: 124; or The heavy chain comprises the amino acid sequence of SEQ ID NO: 125, and the light chain comprises the amino acid sequence of SEQ ID NO: 126; or The heavy chain comprises the amino acid sequence of SEQ ID NO: 127, and the light chain comprises the amino acid sequence of SEQ ID NO:

128.

16. A pharmaceutical composition comprising: A therapeutically effective amount of the antigen binding molecule that specifically binds to DLL3 and CD3 of any one of claims 1 to 10, or the anti-DLL3 antibody of any one of claims 11 to 15, and one or more pharmaceutically acceptable carriers, diluents, buffers or excipients.

17. An isolated nucleic acid encoding the antigen binding molecule that specifically binds to DLL3 and CD3 according to any one of claims 1 to 10, or the anti-DLL3 antibody according to any one of claims 11 to 15.

18. A host cell comprising the isolated nucleic acid of claim 17.

19. Use of the antigen binding molecule that specifically binds to DLL3 and CD3 according to any one of claims 1 to 10, or the anti-DLL3 antibody according to any one of claims 11 to 15, or the pharmaceutical composition according to claim 16 in the preparation of a medicament for treating a tumor or cancer; preferably, the tumor or cancer is selected from: Head and neck squamous cell carcinoma, head and neck cancer, brain cancer, glioma, glioblastoma multiforme, neuroblastoma, central nervous system cancer, neuroendocrine tumors, pharyngeal cancer, pharyngeal squamous cell carcinoma, oral squamous cell carcinoma, nasopharyngeal cancer, esophageal cancer, thyroid cancer, malignant pleural mesothelioma, lung cancer, breast cancer, liver cancer, hepatobiliary cancer, pancreatic cancer, stomach cancer, gastrointestinal cancer, intestinal cancer, colon cancer, colorectal cancer, kidney cancer, clear cell renal cell carcinoma, ovarian cancer, endometrial cancer, cervical cancer, bladder cancer, prostate cancer, testicular cancer, skin cancer, melanoma, large cell lung cancer, triple-negative breast cancer, lymphoma, and small cell lung cancer; More preferably, the tumor or cancer is a tumor or cancer expressing DLL3.

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