Antibodies targeting cd3 and uses thereof

Abstract

This invention provides an antibody that specifically binds to CD3, a drug combination containing the antibody, a method for its preparation, and its applications.

Description

Antibodies targeting CD3 and their applications

[0001] This application claims priority to Chinese patent application CN202311782525.0 filed on December 22, 2023. Technical Field

[0002] The present disclosure belongs to the field of biotechnology, and more specifically, relates to antibodies targeting CD3 and their applications. Background Art

[0003] The statements herein merely provide background information related to the present disclosure and do not necessarily constitute prior art.

[0004] The TCR-CD3 complex, composed of the TCR-αβ heterodimer and the non-covalently associated signaling dimers of CD3εγ, CD3εδ, and CD3ζ, plays a crucial role in T cell responses and function, serving as a crucial mechanism for initiating T cell activation and development. TCR-αβ specifically recognizes and binds to antigen-peptide complexes presented by MHC molecules. It then transmits signals to the cytoplasm via the immunoreceptor tyrosine-based activation motif (ITAM) in the cytoplasmic segment of the CD3 subunit, acting as the primary activation signal to induce T cell activation. While the variable regions of the TCR heterodimer itself vary, the CD3 subunit is expressed on the surface of all T cells (including αβ and γδ T cells) and serves as the primary signal transmitter for T cell activation. Therefore, CD3 is an ideal target for regulating T cell activity.

[0005] Currently, monoclonal antibodies, bispecific antibodies or multispecific antibodies developed for the CD3 target are widely used in clinical practice. Among them, the monoclonal antibody Muromonab (OKT3) is the first monoclonal antibody approved for marketing, which is used to treat acute rejection of organ transplantation. However, it was withdrawn from the market in 2010 due to its strong immunogenicity and cytokine storm side effects. Teplizumab, a humanized and Fc-modified antibody based on this antibody, was approved by the FDA for the treatment of type 1 diabetes in November 2022. Despite this, in the TN-10 clinical trial, 57% of the treated patients still developed anti-drug antibodies (ADA), of which 46% produced neutralizing antibodies, which may affect the distribution and clinical effectiveness of the drug. Other monoclonal antibodies targeting CD3, such as Otelixizumab and Visilizumab, are also being developed for autoimmune diseases such as type 1 diabetes and ulcerative colitis. In addition, bispecific antibodies or multispecific antibodies targeting CD3 and tumor-associated antigens / tumor-specific antigens have become a hot topic in tumor immunotherapy. Several CD3 bispecific antibodies have been approved for marketing, and more CD3 bispecific antibodies are actively undergoing clinical research. However, CD3 bispecific antibodies have also shown varying degrees of ADA in clinical practice. Secondly, the CD3 antibody UCHT1 used in Muromonab (OKT3), Teplizumab, and Tebentafusp, among the currently marketed antibodies, has no obvious binding effect with CD3 derived from crab-eating macaques, which poses certain challenges to preclinical safety assessments. Summary of the Invention

[0006] The present disclosure provides an anti-CD3 antibody comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3, wherein:

[0007] a. The HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise SEQ ID 360, 361, or 362, and the amino acid sequence of the HCDR1, HCDR2, and HCDR3 of said light chain variable region comprises SEQ ID NO: 255, 278, 279, 275, 157, 281, 282, 283, 150, 151, 152, 153, 154, 155, 156, 158, 159, 160, 161, 162, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 274, 276, 277, 280, 349, 356, 357, 358, 359, 360, 361, or 362, and the amino acid sequence of the HCDR1, HCDR2, and HCDR3 of said light chain variable region comprises SEQ ID NO: 255, 278, 279, the amino acid sequence of LCDR1, LCDR2, and LCDR3 of NO: 236, 237, 238, 268, 269, 271, 272, 267, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 239, 240, 241, 242, 243, 244, 266, 270, or 273; or

[0008] the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region comprise the amino acid sequences of HCDR1, HCDR2, and HCDR3 in SEQ ID NO: 75, respectively, and the LCDR1, LCDR2, and LCDR3 of the light chain variable region comprise the amino acid sequences of LCDR1, LCDR2, and LCDR3 in SEQ ID NO: 74, respectively; or

[0009] b. the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 of SEQ ID NO: 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118 or 119, respectively, and the LCDR1, LCDR2 and LCDR3 of the light chain variable region comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 of SEQ ID NO: 101, 102, 103, 104, 105, 106 or 107, respectively; or

[0010] the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region comprise the amino acid sequences of HCDR1, HCDR2, and HCDR3 in SEQ ID NO: 60, respectively, and the LCDR1, LCDR2, and LCDR3 of the light chain variable region comprise the amino acid sequences of LCDR1, LCDR2, and LCDR3 in SEQ ID NO: 59, respectively; or

[0011] c. the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 58, and the LCDR1, LCDR2 and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 57; or

[0012] d. the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 61, and the LCDR1, LCDR2 and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 57; or

[0013] e. the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 63, and the LCDR1, LCDR2 and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 62; or

[0014] f. the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 65, and the LCDR1, LCDR2 and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 64; or

[0015] g. the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 67, and the LCDR1, LCDR2 and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 66; or

[0016] h. the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 69, and the LCDR1, LCDR2 and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 68; or

[0017] i. the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 71, and the LCDR1, LCDR2 and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 70; or

[0018] j. the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 73, and the LCDR1, LCDR2 and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 72; or

[0019] k. the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 76, and the LCDR1, LCDR2 and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 74; or

[0020] 1. the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 77, and the LCDR1, LCDR2 and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 74; or

[0021] m. the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 79, and the LCDR1, LCDR2 and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 78; or

[0022] n. the heavy chain variable region HCDR1, HCDR2 and HCDR3 respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 80, and the light chain variable region LCDR1, LCDR2 and LCDR3 respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 74; or

[0023] o. the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 82, and the LCDR1, LCDR2 and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 81; or

[0024] p. the heavy chain variable region HCDR1, HCDR2 and HCDR3 respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 84, and the light chain variable region LCDR1, LCDR2 and LCDR3 respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 83; or

[0025] q. the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 86, and the LCDR1, LCDR2 and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 85; or

[0026] r. The HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 88, and the LCDR1, LCDR2 and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 87.

[0027] In some embodiments, the anti-CD3 antibody as described above, wherein:

[0028] a. The HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise SEQ ID 360, 361, or 362, and the amino acid sequence of the HCDR1, HCDR2, and HCDR3 of said light chain variable region comprises SEQ ID NO: 255, 278, 279, 275, 157, 281, 282, 283, 150, 151, 152, 153, 154, 155, 156, 158, 159, 160, 161, 162, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 274, 276, 277, 280, 349, 356, 357, 358, 359, 360, 361, or 362, and the amino acid sequence of the HCDR1, HCDR2, and HCDR3 of said light chain variable region comprises SEQ ID NO: 255, 278, 279, the amino acid sequence of LCDR1, LCDR2 and LCDR3 of NO: 236, 237, 238, 268, 269, 271, 272, 267, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 239, 240, 241, 242, 243, 244, 266, 270 or 273; or

[0029] b. the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118 or 119, and the LCDR1, LCDR2 and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 101, 102, 103, 104, 105, 106 or 107.

[0030] In some embodiments, the anti-CD3 antibody of any of the preceding items, wherein:

[0031] (1) the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 255, and the LCDR1, LCDR2 and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 236; or

[0032] (2) the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 255, and the LCDR1, LCDR2 and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 237; or

[0033] (3) the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 255, and the LCDR1, LCDR2 and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 238; or

[0034] (4) the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2, and HCDR3 in SEQ ID NO: 278, and the LCDR1, LCDR2, and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2, and LCDR3 in SEQ ID NO: 268; or

[0035] (5) the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region comprise the amino acid sequences of HCDR1, HCDR2, and HCDR3 in SEQ ID NO: 275, respectively, and the LCDR1, LCDR2, and LCDR3 of the light chain variable region comprise the amino acid sequences of LCDR1, LCDR2, and LCDR3 in SEQ ID NO: 269, respectively; or

[0036] (6) the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2, and HCDR3 in SEQ ID NO: 278, and the LCDR1, LCDR2, and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2, and LCDR3 in SEQ ID NO: 269; or

[0037] (7) the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2, and HCDR3 in SEQ ID NO: 279, and the LCDR1, LCDR2, and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2, and LCDR3 in SEQ ID NO: 269; or

[0038] (8) the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2, and HCDR3 in SEQ ID NO: 157, and the LCDR1, LCDR2, and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2, and LCDR3 in SEQ ID NO: 236; or

[0039] (9) the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2, and HCDR3 in SEQ ID NO: 275, and the LCDR1, LCDR2, and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2, and LCDR3 in SEQ ID NO: 268; or

[0040] (10) the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 279, and the LCDR1, LCDR2 and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 268; or

[0041] (11) the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 157, and the LCDR1, LCDR2 and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 271; or

[0042] (12) the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 157, and the LCDR1, LCDR2 and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 272; or

[0043] (13) the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 281, and the LCDR1, LCDR2 and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 236; or

[0044] (14) the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 282, and the LCDR1, LCDR2 and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 236; or

[0045] (15) the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 283, and the LCDR1, LCDR2 and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 236; or

[0046] (16) the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 282, and the LCDR1, LCDR2 and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 267; or

[0047] (17) the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 282, and the LCDR1, LCDR2 and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 268; or

[0048] (18) The HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 282, and the LCDR1, LCDR2 and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 269.

[0049] In some embodiments, the anti-CD3 antibody of any of the preceding items, wherein:

[0050] (1) the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 255, and the LCDR1, LCDR2 and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 236; or

[0051] (2) the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 255, and the LCDR1, LCDR2 and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 237; or

[0052] (3) the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 255, and the LCDR1, LCDR2 and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 238; or

[0053] (4) the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2, and HCDR3 in SEQ ID NO: 278, and the LCDR1, LCDR2, and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2, and LCDR3 in SEQ ID NO: 268; or

[0054] (5) the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region comprise the amino acid sequences of HCDR1, HCDR2, and HCDR3 in SEQ ID NO: 275, respectively, and the LCDR1, LCDR2, and LCDR3 of the light chain variable region comprise the amino acid sequences of LCDR1, LCDR2, and LCDR3 in SEQ ID NO: 269, respectively; or

[0055] (6) the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2, and HCDR3 in SEQ ID NO: 278, and the LCDR1, LCDR2, and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2, and LCDR3 in SEQ ID NO: 269; or

[0056] (7) The HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences of HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 279, and the LCDR1, LCDR2 and LCDR3 of the light chain variable region respectively comprise the amino acid sequences of LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 269.

[0057] In some embodiments, the anti-CD3 antibody of any of the preceding items, the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region and the LCDR1, LCDR2, and LCDR3 of the light chain variable region are defined according to a numbering convention selected from Kabat, IMGT, Chothia, AbM, and Contact. In some embodiments, the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region and the LCDR1, LCDR2, and LCDR3 of the light chain variable region are defined according to the Kabat numbering convention. In some embodiments, the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region and the LCDR1, LCDR2, and LCDR3 of the light chain variable region are defined according to the IMGT numbering convention. In some embodiments, the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region and the LCDR1, LCDR2, and LCDR3 of the light chain variable region are defined according to the Chothia numbering convention. In some embodiments, the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region and the LCDR1, LCDR2 and LCDR3 of the light chain variable region are defined according to the AbM numbering convention. In some embodiments, the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region and the LCDR1, LCDR2 and LCDR3 of the light chain variable region are defined according to the Contact numbering convention.

[0058] In another aspect, the disclosure provides an anti-CD3 antibody, wherein:

[0059] a. the heavy chain variable region HCDR1 comprises the amino acid sequence of SEQ ID NO: 343, HCDR2 comprises the amino acid sequence of SEQ ID NO: 344, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 345, and the light chain variable region LCDR1 comprises the amino acid sequence of SEQ ID NO: 346, LCDR2 comprises the amino acid sequence of SEQ ID NO: 347, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 348, wherein

[0060] HCDR1 is selected from: SX1YX2H SEQ ID NO: 343

[0061] HCDR2 is selected from: WIX3PGX4X5X6X7X8YNEKFKG SEQ ID NO: 344

[0062] HCDR3 is selected from: DGYSYYYFDX9 SEQ ID NO: 345

[0063] LCDR1 is selected from: X 10 SSQSX 11 LX 12 X 13 RX 14 X 15 X 16 NYLA SEQ ID NO: 346

[0064] LCDR2 is selected from:X 17 ASTRES SEQ ID NO: 347

[0065] LCDR3 is selected from: KQX 18 X 19 IX 20 RT SEQ ID NO: 348

[0066] wherein X1 is selected from Y, E, K and Q, preferably Y; X2 is selected from M, I, E, N and Q, preferably M; X3 is selected from N, Q and S, preferably N or Q; X4 is selected from D and E, preferably E; X5 is selected from G and D, preferably G; X6 is selected from S and A, preferably S; X7 is selected from I and T; X8 is selected from K and S; X9 is selected from Y and F, preferably F; X 10 Selected from K and T, preferably K; X 11 Selected from L and V; X 12 Selected from N and Q, preferably N; X 13 is selected from S, D, E, K, P, Q, R and W, preferably E or P; X 14 Selected from T and S; X 15 Selected from R and Q; X 16 Selected from K and Q, preferably K; X 17 is selected from Y and W, preferably W; X 18 Selected from S and N, preferably S; X 19 Selected from F and Y; X20 Selected from L, I and V, preferably L or V; or

[0067] b. the heavy chain variable region HCDR1 comprises the amino acid sequence of SEQ ID NO: 8, HCDR2 comprises the amino acid sequence of SEQ ID NO: 400, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 401, and the light chain variable region LCDR1 comprises the amino acid sequence of SEQ ID NO: 402, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 7, wherein:

[0068] HCDR2 is selected from: NIX 21 LSX 22 GGTNYNEKFKT SEQ ID NO: 400

[0069] HCDR3 is selected from: X 23 SYSVYYFDY SEQ ID NO: 401

[0070] LCDR1 is selected from: KSSQSLLX 24 SRTRKNYLA SEQ ID NO: 402

[0071] Among them, X 21 Selected from N and Q; X 22 Selected from N and Q; X 23 Selected from D and E; X 24 selected from N and Q; or

[0072] c. HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 4, HCDR2 comprises the amino acid sequence of SEQ ID NO: 5, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 6, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 1, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 3; or

[0073] d. HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 11, HCDR2 comprises the amino acid sequence of SEQ ID NO: 12, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 13, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 1, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 7; or

[0074] e. the heavy chain variable region HCDR1 comprises the amino acid sequence of SEQ ID NO: 4, HCDR2 comprises the amino acid sequence of SEQ ID NO: 15, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 13, and the light chain variable region LCDR1 comprises the amino acid sequence of SEQ ID NO: 14, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 7; or

[0075] f. the heavy chain variable region HCDR1 comprises the amino acid sequence of SEQ ID NO: 13, HCDR2 comprises the amino acid sequence of SEQ ID NO: 18, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 19, and the light chain variable region LCDR1 comprises the amino acid sequence of SEQ ID NO: 14, LCDR2 comprises the amino acid sequence of SEQ ID NO: 16, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 17; or

[0076] g. the heavy chain variable region HCDR1 comprises the amino acid sequence of SEQ ID NO: 13, HCDR2 comprises the amino acid sequence of SEQ ID NO: 21, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 19, and the light chain variable region LCDR1 comprises the amino acid sequence of SEQ ID NO: 1, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 20; or

[0077] h. the heavy chain variable region HCDR1 comprises the amino acid sequence of SEQ ID NO: 25, HCDR2 comprises the amino acid sequence of SEQ ID NO: 26, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 27, and the light chain variable region LCDR1 comprises the amino acid sequence of SEQ ID NO: 22, LCDR2 comprises the amino acid sequence of SEQ ID NO: 23, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 24; or

[0078] i. the heavy chain variable region HCDR1 comprises the amino acid sequence of SEQ ID NO: 31, HCDR2 comprises the amino acid sequence of SEQ ID NO: 32, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 33, and the light chain variable region LCDR1 comprises the amino acid sequence of SEQ ID NO: 28, LCDR2 comprises the amino acid sequence of SEQ ID NO: 29, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 30; or

[0079] j. the heavy chain variable region HCDR1 comprises the amino acid sequence of SEQ ID NO: 37, HCDR2 comprises the amino acid sequence of SEQ ID NO: 38, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and the light chain variable region LCDR1 comprises the amino acid sequence of SEQ ID NO: 1, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 17; or

[0080] k. the heavy chain variable region HCDR1 comprises the amino acid sequence of SEQ ID NO: 34, HCDR2 comprises the amino acid sequence of SEQ ID NO: 39, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and the light chain variable region LCDR1 comprises the amino acid sequence of SEQ ID NO: 1, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 17; or

[0081] 1. the heavy chain variable region HCDR1 comprises the amino acid sequence of SEQ ID NO: 41, HCDR2 comprises the amino acid sequence of SEQ ID NO: 42, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 43, and the light chain variable region LCDR1 comprises the amino acid sequence of SEQ ID NO: 40, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 20; or

[0082] m. the heavy chain variable region HCDR1 comprises the amino acid sequence of SEQ ID NO: 34, HCDR2 comprises the amino acid sequence of SEQ ID NO: 35, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 44, and the light chain variable region LCDR1 comprises the amino acid sequence of SEQ ID NO: 1, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 17; or

[0083] n. the heavy chain variable region HCDR1 comprises the amino acid sequence of SEQ ID NO: 34, HCDR2 comprises the amino acid sequence of SEQ ID NO: 38, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and the light chain variable region LCDR1 comprises the amino acid sequence of SEQ ID NO: 1, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 17; or

[0084] o. the heavy chain variable region HCDR1 comprises the amino acid sequence of SEQ ID NO: 47, HCDR2 comprises the amino acid sequence of SEQ ID NO: 48, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 49, and the light chain variable region LCDR1 comprises the amino acid sequence of SEQ ID NO: 45, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 46; or

[0085] p. the heavy chain variable region HCDR1 comprises the amino acid sequence of SEQ ID NO: 11, HCDR2 comprises the amino acid sequence of SEQ ID NO: 52, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 53, and the light chain variable region LCDR1 comprises the amino acid sequence of SEQ ID NO: 50, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 51; or

[0086] q. HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 37, HCDR2 comprises the amino acid sequence of SEQ ID NO: 55, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 56, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 1, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 54.

[0087] In some embodiments, the anti-CD3 antibody of any of the preceding items comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises HCDR1, HCDR2, and HCDR3, and the light chain variable region comprises LCDR1, LCDR2, and LCDR3, wherein:

[0088] a. the heavy chain variable region HCDR1 comprises the amino acid sequence of SEQ ID NO: 343, HCDR2 comprises the amino acid sequence of SEQ ID NO: 344, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 345, and the light chain variable region LCDR1 comprises the amino acid sequence of SEQ ID NO: 346, LCDR2 comprises the amino acid sequence of SEQ ID NO: 347, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 348; or

[0089] b. HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 8, HCDR2 comprises the amino acid sequence of SEQ ID NO: 400, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 401, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 402, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 7.

[0090] In some embodiments, the anti-CD3 antibody of any of the preceding items, wherein:

[0091] a. the HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, 34, 193, 194, 195, 196, 197 or 199, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, 217, 214, 218, 219, 220, 221, 35, 38, 215 or 216, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 36 or 43, and the LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 189, 187, 207, 208, 210, 211, 206, 1, 96, 186, 188, 190, 191, 192, 205, 209 or 212, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2 or 136, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: NO: 185, 183, 17, 182 or 184; or b. HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 8, HCDR2 comprises the amino acid sequence of SEQ ID NO: 9, 97, 98 or 100, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 10 or 99, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 1 or 96, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 7. In some embodiments, the anti-CD3 antibody of any of the preceding items, wherein HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 403, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 404, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 405;

[0092] in:

[0093] HCDR2 selected from: WIX 25 PGEGSX 26 X 27 YNEKFKG SEQ ID NO: 403

[0094] LCDR1 is selected from: KSSQSX 28 LNX 29 RX 30 X 31 KNYLA SEQ ID NO: 404

[0095] LCDR3 is selected from: KQSX 32 IX 33 RT SEQ ID NO: 405

[0096] Among them, X 25 Selected from N and Q; X 26 Selected from I and T; X 27 Selected from K and S; X 28 Selected from L and V; X 29 Selected from P and E; X 30 Selected from T and S; X 31 Selected from R and Q; X 32 Selected from F and Y; X 33 Selected from V and L.

[0097] In some embodiments, the anti-CD3 antibody of any of the preceding items, wherein:

[0098] The HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, 214, 217, 218, 219, 220 or 221, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and the LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 189, 187, 206, 207, 208, 210 or 211, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 185 or 183.

[0099] In some embodiments, the anti-CD3 antibody of any of the preceding items, wherein

[0100] (1) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 189, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0101] (2) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 189, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 183; or

[0102] (3) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 187, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 183; or

[0103] (4) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 217, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 207, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0104] (5) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 214, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 208, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0105] (6) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 217, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 208, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0106] (7) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 218, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 208, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0107] (8) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 214, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 207, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0108] (9) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 218, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 207, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0109] (10) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 210, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0110] (11) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 211, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0111] (12) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 219, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 189, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0112] (13) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 220, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 189, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0113] (14) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 221, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 189, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0114] (15) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 220, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 206, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0115] (16) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 220, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 207, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0116] (17) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 220, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 208, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0117] (18) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 34, HCDR2 comprises the amino acid sequence of SEQ ID NO: 35, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 1, 96, 187, 189, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 17; or

[0118] (19) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 34, HCDR2 comprises the amino acid sequence of SEQ ID NO: 35, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 1 or 96, LCDR2 comprises the amino acid sequence of SEQ ID NO: 136, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 17; or

[0119] (20) the HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 34, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and the LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 1, 96, 186, 187, 188, 189, 190, 191 or 192, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 17; or

[0120] (21) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 34, HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 1 or 96, LCDR2 comprises the amino acid sequence of SEQ ID NO: 136, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 17; or

[0121] (22) the HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and the LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 1, 186, 187, 188, 189, 190, 191 or 192, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 17; or

[0122] (23) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 34, HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 1, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 182, 183, 184, or 185; or

[0123] (24) the HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 193, 194, 195, 196, 197 or 199, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and the LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 1, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 17; or

[0124] (25) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 196, HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 188, 190, 191 or 192, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 17; or

[0125] (26) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 189, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 184; or

[0126] (27) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 189, LCDR2 comprises the amino acid sequence of SEQ ID NO: 136, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 17; or

[0127] (28) the HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and the LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 187, 205, 206, 207, 208, 209 or 212, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0128] (29) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 35, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 187, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 183 or 185; or

[0129] (30) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 35, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 189, LCDR2 comprises the amino acid sequence of SEQ ID NO: 136, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 17; or

[0130] (31) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 197 or 34, HCDR2 comprises the amino acid sequence of SEQ ID NO: 35, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 189, LCDR2 comprises the amino acid sequence of SEQ ID NO: 136, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 184; or

[0131] (32) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 197, HCDR2 comprises the amino acid sequence of SEQ ID NO: 35, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 189, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 183, 184, or 185; or

[0132] (33) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 34, HCDR2 comprises the amino acid sequence of SEQ ID NO: 35, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 187, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 183 or 185; or

[0133] (34) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 194, HCDR2 comprises the amino acid sequence of SEQ ID NO: 35, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 189, LCDR2 comprises the amino acid sequence of SEQ ID NO: 136, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 183 or 185; or

[0134] (35) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 34 or 197, HCDR2 comprises the amino acid sequence of SEQ ID NO: 35, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 189, LCDR2 comprises the amino acid sequence of SEQ ID NO: 136, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 183; or

[0135] (36) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 34 or 197, HCDR2 comprises the amino acid sequence of SEQ ID NO: 35, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 189, LCDR2 comprises the amino acid sequence of SEQ ID NO: 136, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0136] (37) the HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 214, 215, 216, 217 or 218, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and the LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 189, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0137] (38) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 43, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 189, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0138] (39) the HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 214, 217 or 218, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and the LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 206, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0139] (40) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 220, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 210, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0140] (41) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 34, HCDR2 comprises the amino acid sequence of SEQ ID NO: 38, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 1, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 17.

[0141] In some embodiments, the anti-CD3 antibody of any of the preceding items, wherein:

[0142] (1) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 189, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0143] (2) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 189, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 183; or

[0144] (3) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 187, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 183; or

[0145] (4) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 217, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 207, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0146] (5) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 214, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 208, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0147] (6) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 217, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 208, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0148] (7) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 218, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 208, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0149] (8) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 214, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 207, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0150] (9) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 218, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 207, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0151] (10) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 210, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0152] (11) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 211, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0153] (12) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 219, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 189, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0154] (13) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 220, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 189, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0155] (14) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 221, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 189, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0156] (15) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 220, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 206, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0157] (16) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 220, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 207, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0158] (17) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 220, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 208, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185.

[0159] In some embodiments, the anti-CD3 antibody of any of the preceding items, wherein:

[0160] (1) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 189, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0161] (2) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 189, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 183; or

[0162] (3) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 187, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 183; or

[0163] (4) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 217, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 207, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0164] (5) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 214, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 208, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0165] (6) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 217, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 208, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0166] (7) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 218, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 208, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185.

[0167] In some embodiments, the anti-CD3 antibody of any of the preceding items, wherein

[0168] (1) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 34, HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 1 or 96, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 17; or

[0169] (2) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 34, HCDR2 comprises the amino acid sequence of SEQ ID NO: 35, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 1 or 96, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 17; or

[0170] (3) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 34, HCDR2 comprises the amino acid sequence of SEQ ID NO: 35 or 138, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 1, LCDR2 comprises the amino acid sequence of SEQ ID NO: 136, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 17.

[0171] In some embodiments, the anti-CD3 antibody of any of the preceding items, wherein:

[0172] (1) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 8, HCDR2 comprises the amino acid sequence of SEQ ID NO: 9, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 1 or 96, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 7; or

[0173] (2) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 8, HCDR2 comprises the amino acid sequence of SEQ ID NO: 97, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 1 or 96, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 7; or

[0174] (3) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 8, HCDR2 comprises the amino acid sequence of SEQ ID NO: 98, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 1 or 96, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 7; or

[0175] (4) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 8, HCDR2 comprises the amino acid sequence of SEQ ID NO: 9, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 99, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 1 or 96, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 7.

[0176] In some embodiments, in the anti-CD3 antibody of any of the preceding items, the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region and the LCDR1, LCDR2, and LCDR3 of the light chain variable region are defined according to the Kabat numbering convention.

[0177] In some embodiments, the anti-CD3 antibody as described in any of the preceding items, wherein the anti-CD3 antibody is a murine antibody, a chimeric antibody, a humanized antibody, or a fully human antibody. In some embodiments, the anti-CD3 antibody is a chimeric antibody. In some embodiments, the anti-CD3 antibody is a humanized antibody. In some embodiments, the anti-CD3 antibody as described in any of the preceding items, wherein the anti-CD3 antibody is humanized, backmutated, affinity adjusted (e.g., affinity increased or affinity decreased), T cell epitopes removed, antibody deamidation reduced, and / or antibody isomerization reduced.

[0178] In some embodiments, the anti-CD3 antibody of any of the preceding items comprises a framework region (FR) of a human antibody.

[0179] In some embodiments, for the anti-CD3 antibody of any of the preceding items, the heavy chain framework region of the human germline template used in the humanization process is derived from IGHV1-18*01, IGHV1-46*01, IGHJ6*01 and / or IGHJ2*01; the light chain framework region of the human germline template used in the humanization process is derived from IGKV4-1*01, IGKV2-28*01, IGKV1-27*01 and / or IGKJ4*01; or

[0180] The heavy chain framework region of the human germline template used in the humanization process is derived from IGHV1-46*01, IGHJ6*01 and / or IGHJ4*01; the light chain framework region of the human germline template used in the humanization process is derived from IGKV4-1*01, IGKV2-28*01, IGKV1-27*01 and / or IGKJ4*01.

[0181] In some embodiments, the anti-CD3 antibody of any of the preceding items, the heavy chain variable region has FR1, FR2, FR3 derived from IGHV1-18*01 or IGHV1-46*01 and FR4 derived from IGHJ6*01 or IGHJ2*01, and is unsubstituted or has a residue selected from 1E, 28S, 30A, 37M, 40G, 69L, 71A, 73K, 78A, 82a, R, 83T, 89I, 91F and / or 107S; and / or the light chain variable region has FR1, FR2, FR3 derived from IGKV4-1*01, IGKV2-28*01 or IGKV1-27*01 and FR4 derived from IGKJ4*01 or IGKJ1*01, and is unsubstituted or has one or more amino acid substitutions selected from the group consisting of 37Q, 43S, 45K and / or 50Y. In some embodiments, the anti-CD3 antibody, wherein the HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, 34, 193, 194, 195, 196, 197 or 199, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, 217, 214, 218, 219, 220, 221, 35, 38, 215 or 216, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 36 or 43, and the FR of the heavy chain variable region comprises one or more amino acid substitutions selected from the group consisting of 1E, 28S, 30A, 37M, 40G, 69L, 71A, 73K, 78A, 82aR, 83T, 89I, 91F and / or 107S; and the LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: NO: 189, 187, 207, 208, 210, 211, 206, 1, 96, 186, 188, 190, 191, 192, 205, 209 or 212, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2 or 136, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185, 183, 17, 182 or 184, and the FRs of the light chain variable region comprise one or more amino acid substitutions selected from the group consisting of 37Q, 43S, 45K and / or 50Y.In some embodiments, the anti-CD3 antibody comprises: a heavy chain variable region HCDR1 comprising the amino acid sequence of SEQ ID NO: 34, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 36, and a heavy chain variable region FR comprising one or more amino acid substitutions selected from the group consisting of 1E, 28S, 30A, 37M, 40G, 69L, 71A, 73K, 78A, 82aR, 83T, 89I, 91F, and / or 107S; and a light chain variable region LCDR1 comprising the amino acid sequence of SEQ ID NO: 1, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 2, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 17, and a light chain variable region FR comprising one or more amino acid substitutions selected from the group consisting of 37Q, 43S, 45K, and / or 50Y. In some embodiments, the variable regions and CDRs are defined according to the Kabat numbering convention.

[0182] In some embodiments, the anti-CD3 antibody of any of the preceding items, the heavy chain variable region has FR1, FR2, FR3 derived from IGHV1-46*01 and FR4 derived from IGHJ6*01 or IGHJ4*01, and is unsubstituted or has one or more amino acid substitutions selected from the group consisting of 1E, 28N, 69L, 71A, 73K, 78A, 83T and / or 91F; and / or the light chain variable region has FR1, FR2, FR3 derived from IGKV4-1*01, IGKV2-28*01 or IGKV1-27*01 and FR4 derived from IGKJ4*01 or IGKJ1*01, and is unsubstituted or has one or more amino acid substitutions selected from the group consisting of 37Q, 43S and / or 45K. In some embodiments, the anti-CD3 antibody, wherein the HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 8, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 9, 97, 98 or 100, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 10 or 99, and the FR of the heavy chain variable region comprises one or more amino acid substitutions selected from the group consisting of 1E, 28N, 69L, 71A, 73K, 78A, 83T and / or 91F; and the LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 1 or 96, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 7, and the FR of the light chain variable region comprises one or more amino acid substitutions selected from the group consisting of 37Q, 43S and / or 45K. In some embodiments, the anti-CD3 antibody comprises: a heavy chain variable region HCDR1 comprising the amino acid sequence of SEQ ID NO: 8, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 9, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 10, and a heavy chain variable region FR comprising one or more amino acid substitutions selected from the group consisting of 1E, 28N, 69L, 71A, 73K, 78A, 83T, and / or 91F; and a light chain variable region LCDR1 comprising the amino acid sequence of SEQ ID NO: 1, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 2, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain variable region FR comprising one or more amino acid substitutions selected from the group consisting of 37Q, 43S, and / or 45K. In some embodiments, the variable regions and CDRs are defined according to the Kabat numbering convention.

[0183] In some embodiments, the anti-CD3 antibody of any of the preceding items, wherein:

[0184] a. The heavy chain variable region comprises the same sequence as SEQ ID NO: 255, 278, 279, 275, 157, 281, 282, 283, 150, 151, 152, 153, 154, 155, 156, 158, 159, 160, 161, 162, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265 , 274, 276, 277, 280, 349, 356, 357, 358, 359, 360, 361 or 362 having at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99%) sequence identity, and the light chain variable region comprises an amino acid sequence identical to SEQ ID NO: 236, 237, 238, 268, 269, 271, 272, 267, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, an amino acid sequence having at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99%) sequence identity to 239, 240, 241, 242, 243, 244, 266, 270 or 273; or

[0185] the heavy chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO:75, and the light chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO:74; or

[0186] b. the heavy chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, or 119, and the light chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: an amino acid sequence having at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99%) sequence identity to NO: 101, 102, 103, 104, 105, 106 or 107; or

[0187] the heavy chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO:60, and the light chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO:59; or

[0188] c. the heavy chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 58, and the light chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 57; or

[0189] d. the heavy chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 61, and the light chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 57; or

[0190] e. the heavy chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 63, and the light chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 62; or

[0191] f. the heavy chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 65, and the light chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 64; or

[0192] g. the heavy chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 67, and the light chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 66; or

[0193] h. the heavy chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 69, and the light chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 68; or

[0194] i. the heavy chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 71, and the light chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 70; or

[0195] j. the heavy chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 73, and the light chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 72; or

[0196] k. the heavy chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 76, and the light chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 74; or

[0197] 1. the heavy chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 77, and the light chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 74; or

[0198] m. the heavy chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 79, and the light chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 78; or

[0199] n. the heavy chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 80, and the light chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 74; or

[0200] o. the heavy chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 82, and the light chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 81; or

[0201] p. the heavy chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 84, and the light chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 83; or

[0202] q. the heavy chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 86, and the light chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 85; or

[0203] r. the heavy chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 88, and the light chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 87.

[0204] In some embodiments, the anti-CD3 antibody of any of the preceding items, wherein:

[0205] a. The heavy chain variable region comprises the same sequence as SEQ ID NO: 255, 278, 279, 275, 157, 281, 282, 283, 150, 151, 152, 153, 154, 155, 156, 158, 159, 160, 161, 162, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265 , 274, 276, 277, 280, 349, 356, 357, 358, 359, 360, 361 or 362 having at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99%) sequence identity, and the light chain variable region comprises an amino acid sequence identical to SEQ ID NO: 236, 237, 238, 268, 269, 271, 272, 267, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, an amino acid sequence having at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99%) sequence identity to 239, 240, 241, 242, 243, 244, 266, 270 or 273; or

[0206] the heavy chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO:75, and the light chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO:74; or

[0207] b. the heavy chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, or 119, and the light chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: an amino acid sequence having at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99%) sequence identity to NO: 101, 102, 103, 104, 105, 106 or 107; or

[0208] The heavy chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO:60, and the light chain variable region comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO:59.

[0209] In some embodiments, the anti-CD3 antibody of any of the preceding items, wherein:

[0210] a. the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 255, 278, 279, 275, 157, 281, 282, 283, 150, 151, 152, 153, 154, 155, 156, 158, 159, 160, 161, 162, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 274, 276, 277, 280, 349, 356, 357, 358, 359, 360, 361 or 362, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: the amino acid sequence of NO: 236, 237, 238, 268, 269, 271, 272, 267, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 239, 240, 241, 242, 243, 244, 266, 270, or 273; or

[0211] The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 75, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 74; or

[0212] b. the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118 or 119, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 101, 102, 103, 104, 105, 106 or 107; or

[0213] The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 60, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 59.

[0214] In some embodiments, the anti-CD3 antibody of any of the preceding items, wherein: the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 255, 157, 275, 278, 279, 281, 282 or 283, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236, 237, 238, 267, 268, 269, 271 or 272.

[0215] In some embodiments, the anti-CD3 antibody of any of the preceding items, wherein:

[0216] (1) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 255, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or

[0217] (2) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 255, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 237; or

[0218] (3) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 255, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 238; or

[0219] (4) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 278, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 268; or

[0220] (5) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 275, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 269; or

[0221] (6) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 278, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 269; or

[0222] (7) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 279, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 269; or

[0223] (8) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 157, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or

[0224] (9) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 275, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 268; or

[0225] (10) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 279, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 268; or

[0226] (11) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 157, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 271; or

[0227] (12) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 157, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 272; or

[0228] (13) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 281, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or

[0229] (14) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 282, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or

[0230] (15) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 283, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or

[0231] (16) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 282, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 267; or

[0232] (17) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 282, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 268; or

[0233] (18) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 282, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 269; or

[0234] (19) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 150, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 139, 140, 141, 142, 143, 144, or 145; or

[0235] (20) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 151, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 139, 140, 141, 142, 143, 144, 145, or 146; or

[0236] (21) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 152, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 144; or

[0237] (22) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 153, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 139, 140, 141, 142, 143, 144, or 145; or

[0238] (23) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 154, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 146, 147, 148, or 149; or

[0239] (24) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 155, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 146, 147, 148, 149, 222, 223, 225, 226, 228, 229, 230, 231, 233, 234, or 235; or

[0240] (25) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 156, 157, 245, 246, 248, 249, 250, 253, 255, 256, 264, 265, or 154, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 146; or

[0241] (26) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 255, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 228, 229, 230, 231, 233, 234, 235, 239, 240, or 241; or

[0242] (27) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 249, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 230, 233, 234, or 235; or

[0243] (28) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 254, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 238, 240, or 241; or

[0244] (29) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 157 or 156, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 229; or

[0245] (30) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 157, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 231 or 273; or

[0246] (31) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 152, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 229 or 231; or

[0247] (32) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 151, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 229 or 231; or

[0248] (33) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 258 or 259, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 242; or

[0249] (34) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 258, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236, 237, or 239; or

[0250] (35) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 259, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 238 or 241; or

[0251] (36) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 251, 259 or 260, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 243; or

[0252] (37) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 251, 259 or 260, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 244; or

[0253] (38) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 258, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 243 or 244; or

[0254] (39) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 157, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 266, 267, 268, 269, or 270; or

[0255] (40) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 274, 275, 276, 277, 278, 279 or 280, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or

[0256] (41) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 275, 278 or 279, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 267; or

[0257] (42) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 282, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 271; or

[0258] (43) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 356, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or

[0259] (44) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 356, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 237; or

[0260] (45) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 356, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 238; or

[0261] (46) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 357, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 268; or

[0262] (47) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 358, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 269; or

[0263] (48) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 357, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 269; or

[0264] (49) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 359, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 269; or

[0265] (50) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 161, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or

[0266] (51) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 358, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 268; or

[0267] (52) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 359, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 268; or

[0268] (53) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 161, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 271; or

[0269] (54) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 161, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 272; or

[0270] (55) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 360, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or

[0271] (56) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 361, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or

[0272] (57) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 362, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or

[0273] (58) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 361, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 267; or

[0274] (59) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 361, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 268; or

[0275] (60) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 361, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 269.

[0276] In some embodiments, the anti-CD3 antibody of any of the preceding items, wherein:

[0277] 1) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 255, 157, 156, 158, 161, 162, 349, 356, or 274, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or

[0278] 2) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 255, 157, 156, 158, 161, 162, 349, 356, or 274, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 237; or

[0279] 3) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 255, 157, 156, 158, 161, 162, 349, 356, or 274, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 238; or

[0280] 4) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 278 or 357, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 268; or

[0281] 5) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 275 or 358, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 269; or

[0282] 6) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 278 or 357, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 269; or

[0283] 7) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 279 or 359, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 269; or

[0284] 8) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 275 or 358, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 268; or

[0285] 9) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 279 or 359, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 268; or

[0286] 10) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 157, 255, 156, 158, 161, 162, 349, 356, or 274, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 271; or

[0287] 11) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 157, 255, 156, 158, 161, 162, 349, 356, or 274, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 272; or

[0288] 12) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 281 or 360, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or

[0289] 13) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 282 or 361, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or

[0290] 14) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 283, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or

[0291] 15) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 282 or 361, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 267; or

[0292] 16) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 282 or 361, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 268; or

[0293] 17) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 282 or 361, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 269.

[0294] In some embodiments, the anti-CD3 antibody of any of the preceding items, wherein:

[0295] (1) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 255, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or

[0296] The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 157, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or

[0297] (2) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 255, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 237; or

[0298] (3) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 255, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 238; or

[0299] (4) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 278, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 268; or

[0300] (5) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 275, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 269; or

[0301] (6) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 278, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 269; or

[0302] (7) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 279, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 269; or

[0303] (8) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 275, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 268; or

[0304] (9) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 279, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 268; or

[0305] (10) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 157, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 271; or

[0306] (11) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 157, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 272; or

[0307] (12) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 281, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or

[0308] (13) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 282, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or

[0309] (14) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 283, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or

[0310] (15) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 282, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 267; or

[0311] (16) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 282, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 268; or

[0312] (17) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 282, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 269.

[0313] In some embodiments, the anti-CD3 antibody of any of the preceding items, wherein:

[0314] (1) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 255, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or

[0315] (2) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 255, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 237; or

[0316] (3) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 255, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 238; or

[0317] (4) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 278, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 268; or

[0318] (5) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 275, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 269; or

[0319] (6) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 278, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 269; or

[0320] (7) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 279, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 269.

[0321] In some embodiments, the anti-CD3 antibody of any of the preceding items, wherein:

[0322] (1) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 356, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or

[0323] The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 161, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or

[0324] (2) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 356, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 237; or

[0325] (3) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 356, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 238; or

[0326] (4) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 357, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 268; or

[0327] (5) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 358, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 269; or

[0328] (6) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 357, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 269; or

[0329] (7) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 359, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 269; or

[0330] (8) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 358, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 268; or

[0331] (9) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 359, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 268; or

[0332] (10) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 161, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 271; or

[0333] (11) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 161, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 272; or

[0334] (12) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 360, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or

[0335] (13) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 361, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or

[0336] (14) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 362, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or

[0337] (15) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 361, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 267; or

[0338] (16) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 361, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 268; or

[0339] (17) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 361, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 269.

[0340] In some embodiments, the anti-CD3 antibody of any of the preceding items, wherein:

[0341] (1) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 153, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 140, 141, 142, 143 or 144; or

[0342] (2) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 150, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 143; or

[0343] (3) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 151, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 143 or 144; or

[0344] (4) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 154, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 146, 147, or 148; or

[0345] (5) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 155, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 146 or 148.

[0346] In some embodiments, the anti-CD3 antibody of any of the preceding items, wherein:

[0347] (1) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 109, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 102, 103, 104 or 105; or

[0348] (2) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 110, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 101, 102, 103, 104, or 105; or

[0349] (3) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 111, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 102, 103, 104, or 105; or

[0350] (4) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 112, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 102, 103, 104, or 105; or

[0351] (5) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 113, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 101, 102, 103, 104, or 105; or

[0352] (6) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 115, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 106 or 107; or

[0353] (7) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 116, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 106 or 107; or

[0354] (8) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 118, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 106 or 107.

[0355] In some embodiments, the anti-CD3 antibody as described above, wherein the anti-CD3 antibody is an antigen-binding fragment (antibody fragment); in some embodiments, the antigen-binding fragment (antibody fragment) is selected from Fab, Fab′, F(ab′)2, Fd, Fv, scFv, dsFv or dAb.

[0356] In some embodiments, the anti-CD3 antibody described above comprises a heavy chain constant region and a light chain constant region. In some embodiments, the heavy chain constant region is a heavy chain constant region of human IgG1, IgG2, IgG3, IgG4, or a variant thereof, and the light chain constant region is a light chain constant region of human kappa, lambda, or a variant thereof. In some embodiments, the heavy chain constant region is a human IgG1 heavy chain constant region or a variant thereof. In some embodiments, the light chain constant region is a human kappa light chain constant region or a variant thereof. In some embodiments, the heavy chain constant region comprises the amino acid sequence of SEQ ID NO: 120, 90, 339, or 399, and the light chain constant region comprises the amino acid sequence of SEQ ID NO: 91 or 384. In some embodiments, the heavy chain constant region comprises the amino acid sequence of SEQ ID NO: 120, and the light chain constant region comprises the amino acid sequence of SEQ ID NO: 91.

[0357] In some embodiments, the anti-CD3 antibody of any of the preceding items comprises a heavy chain and a light chain, wherein:

[0358] a. The heavy chain comprises the heavy chain of SEQ ID NO: 301, 326, 323, 327, 181, 331, 332, 333, 174, 175, 176, 177, 178, 179, 180, 295, 296, 297, 298, 299, 300, 302, 309, 311, 312, 314, 315, 322, 324, 325, 328, 335, 336, 350, 351, 352, 3 53, 354, 355, 363, 364, 365, 366, 367, 368 or 369 having at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99%) sequence identity, and the light chain comprises an amino acid sequence identical to SEQ ID NO: 303, 304, 305, 319, 320, 329, 330, 318, 163, 164, 165, 166, 167, 168, 169, 170 ,171,172,173,198,284,285,286,287,288,289,290,291,292,293,294,306,30 7, 308, 310, 313, 316, 317, 321, 334 or 342 having an amino acid sequence with at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99%) sequence identity; or

[0359] the heavy chain comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO:95, and the light chain comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO:94; or

[0360] b. the heavy chain comprises an amino acid sequence having at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99%) sequence identity to SEQ ID NO: 128, 129, 130, 131, 132, 133, 134 or 135, and the light chain comprises an amino acid sequence having at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99%) sequence identity to SEQ ID NO: an amino acid sequence having at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99%) sequence identity to NO: 121, 122, 123, 124, 125, 126 or 127; or

[0361] The heavy chain comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 93, and the light chain comprises an amino acid sequence that is at least 80% (e.g., at least 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 92.

[0362] In some embodiments, the anti-CD3 antibody of any of the preceding items, wherein:

[0363] a. the heavy chain comprises the amino acid sequence of SEQ ID NO: 301, 326, 323, 327, 181, 331, 332, 333, 174, 175, 176, 177, 178, 179, 180, 295, 296, 297, 298, 299, 300, 302, 309, 311, 312, 314, 315, 322, 324, 325, 328, 335, 336, 350, 351, 352, 353, 354, 355, 363, 364, 365, 366, 367, 368 or 369, and the light chain comprises the amino acid sequence of SEQ ID NO: the amino acid sequence of NO: 303, 304, 305, 319, 320, 329, 330, 318, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 198, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 306, 307, 308, 310, 313, 316, 317, 321, 334, or 342; or

[0364] The heavy chain comprises the amino acid sequence of SEQ ID NO: 95, and the light chain comprises the amino acid sequence of SEQ ID NO: 94; or

[0365] b. the heavy chain comprises the amino acid sequence of SEQ ID NO: 128, 129, 130, 131, 132, 133, 134 or 135, and the light chain comprises the amino acid sequence of SEQ ID NO: 121, 122, 123, 124, 125, 126 or 127; or

[0366] The heavy chain comprises the amino acid sequence of SEQ ID NO: 93, and the light chain comprises the amino acid sequence of SEQ ID NO: 92.

[0367] In some embodiments, the anti-CD3 antibody of any of the preceding items, wherein:

[0368] (1) the heavy chain comprises the amino acid sequence of SEQ ID NO: 301, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or

[0369] (2) the heavy chain comprises the amino acid sequence of SEQ ID NO: 301, and the light chain comprises the amino acid sequence of SEQ ID NO: 304; or

[0370] (3) the heavy chain comprises the amino acid sequence of SEQ ID NO: 301, and the light chain comprises the amino acid sequence of SEQ ID NO: 305; or

[0371] (4) the heavy chain comprises the amino acid sequence of SEQ ID NO: 326, and the light chain comprises the amino acid sequence of SEQ ID NO: 319; or

[0372] (5) the heavy chain comprises the amino acid sequence of SEQ ID NO: 323, and the light chain comprises the amino acid sequence of SEQ ID NO: 320; or

[0373] (6) the heavy chain comprises the amino acid sequence of SEQ ID NO: 326, and the light chain comprises the amino acid sequence of SEQ ID NO: 320; or

[0374] (7) the heavy chain comprises the amino acid sequence of SEQ ID NO: 327, and the light chain comprises the amino acid sequence of SEQ ID NO: 320; or

[0375] (8) the heavy chain comprises the amino acid sequence of SEQ ID NO: 181, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or

[0376] (9) the heavy chain comprises the amino acid sequence of SEQ ID NO: 323, and the light chain comprises the amino acid sequence of SEQ ID NO: 319; or

[0377] (10) the heavy chain comprises the amino acid sequence of SEQ ID NO: 327, and the light chain comprises the amino acid sequence of SEQ ID NO: 319; or

[0378] (11) the heavy chain comprises the amino acid sequence of SEQ ID NO: 181, and the light chain comprises the amino acid sequence of SEQ ID NO: 329; or

[0379] (12) the heavy chain comprises the amino acid sequence of SEQ ID NO: 181, and the light chain comprises the amino acid sequence of SEQ ID NO: 330; or

[0380] (13) the heavy chain comprises the amino acid sequence of SEQ ID NO: 331, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or

[0381] (14) the heavy chain comprises the amino acid sequence of SEQ ID NO: 332, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or

[0382] (15) the heavy chain comprises the amino acid sequence of SEQ ID NO: 333, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or

[0383] (16) the heavy chain comprises the amino acid sequence of SEQ ID NO: 332, and the light chain comprises the amino acid sequence of SEQ ID NO: 318; or

[0384] (17) the heavy chain comprises the amino acid sequence of SEQ ID NO: 332, and the light chain comprises the amino acid sequence of SEQ ID NO: 319; or

[0385] (18) the heavy chain comprises the amino acid sequence of SEQ ID NO: 332, and the light chain comprises the amino acid sequence of SEQ ID NO: 320; or

[0386] (19) the heavy chain comprises the amino acid sequence of SEQ ID NO: 174, and the light chain comprises the amino acid sequence of SEQ ID NO: 163, 164, 165, 166, 167, 168 or 169; or

[0387] (20) the heavy chain comprises the amino acid sequence of SEQ ID NO: 175, and the light chain comprises the amino acid sequence of SEQ ID NO: 163, 164, 165, 166, 167, 168, 169, 170, 289 or 291; or

[0388] (21) the heavy chain comprises the amino acid sequence of SEQ ID NO: 176, and the light chain comprises the amino acid sequence of SEQ ID NO: 168, 289 or 291; or

[0389] (22) the heavy chain comprises the amino acid sequence of SEQ ID NO: 177, and the light chain comprises the amino acid sequence of SEQ ID NO: 163, 164, 165, 166, 167, 168 or 169; or

[0390] (23) the heavy chain comprises the amino acid sequence of SEQ ID NO: 178, and the light chain comprises the amino acid sequence of SEQ ID NO: 170, 171, 172, or 173; or

[0391] (24) the heavy chain comprises the amino acid sequence of SEQ ID NO: 179, and the light chain comprises the amino acid sequence of SEQ ID NO: 170, 171, 172, 173, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, or 294; or

[0392] (25) the heavy chain comprises the amino acid sequence of SEQ ID NO: 180, 181, 295, 296, 297, 298, 299, 300, 301, 302, 335, 336 or 178, and the light chain comprises the amino acid sequence of SEQ ID NO: 170; or

[0393] (26) the heavy chain comprises the amino acid sequence of SEQ ID NO: 301, and the light chain comprises the amino acid sequence of SEQ ID NO: 288, 289, 290, 291, 292, 293, 294, 306, 307, or 308; or

[0394] (27) the heavy chain comprises the amino acid sequence of SEQ ID NO: 298, and the light chain comprises the amino acid sequence of SEQ ID NO: 290, 292, 293 or 294; or

[0395] (28) the heavy chain comprises the amino acid sequence of SEQ ID NO: 309, and the light chain comprises the amino acid sequence of SEQ ID NO: 305, 307 or 308; or

[0396] (29) the heavy chain comprises the amino acid sequence of SEQ ID NO: 181, and the light chain comprises the amino acid sequence of SEQ ID NO: 289, 291, 317, 318, 319, 320, 321, or 334; or

[0397] (30) the heavy chain comprises the amino acid sequence of SEQ ID NO: 180, and the light chain comprises the amino acid sequence of SEQ ID NO: 289; or

[0398] (31) the heavy chain comprises the amino acid sequence of SEQ ID NO: 311, and the light chain comprises the amino acid sequence of SEQ ID NO: 303, 304, 306, 310, 313 or 316; or

[0399] (32) the heavy chain comprises the amino acid sequence of SEQ ID NO: 312, and the light chain comprises the amino acid sequence of SEQ ID NO: 305, 308, 313 or 316; or

[0400] (33) the heavy chain comprises the amino acid sequence of SEQ ID NO: 314, and the light chain comprises the amino acid sequence of SEQ ID NO: 313 or 316; or

[0401] (34) the heavy chain comprises the amino acid sequence of SEQ ID NO: 315, and the light chain comprises the amino acid sequence of SEQ ID NO: 313 or 316; or

[0402] (35) the heavy chain comprises the amino acid sequence of SEQ ID NO: 322, 323, 324, 325, 326, 327 or 328, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or

[0403] (36) the heavy chain comprises the amino acid sequence of SEQ ID NO: 323, 326, or 327, and the light chain comprises the amino acid sequence of SEQ ID NO: 318; or

[0404] (37) the heavy chain comprises the amino acid sequence of SEQ ID NO: 332, and the light chain comprises the amino acid sequence of SEQ ID NO: 329; or

[0405] (38) the heavy chain comprises the amino acid sequence of SEQ ID NO: 363, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or

[0406] (39) the heavy chain comprises the amino acid sequence of SEQ ID NO: 363, and the light chain comprises the amino acid sequence of SEQ ID NO: 304; or

[0407] (40) the heavy chain comprises the amino acid sequence of SEQ ID NO: 363, and the light chain comprises the amino acid sequence of SEQ ID NO: 305; or

[0408] (41) the heavy chain comprises the amino acid sequence of SEQ ID NO: 365, and the light chain comprises the amino acid sequence of SEQ ID NO: 319; or

[0409] (42) the heavy chain comprises the amino acid sequence of SEQ ID NO: 364, and the light chain comprises the amino acid sequence of SEQ ID NO: 320; or

[0410] (43) the heavy chain comprises the amino acid sequence of SEQ ID NO: 365, and the light chain comprises the amino acid sequence of SEQ ID NO: 320; or

[0411] (44) the heavy chain comprises the amino acid sequence of SEQ ID NO: 366, and the light chain comprises the amino acid sequence of SEQ ID NO: 320; or

[0412] (45) the heavy chain comprises the amino acid sequence of SEQ ID NO: 353, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or

[0413] (46) the heavy chain comprises the amino acid sequence of SEQ ID NO: 364, and the light chain comprises the amino acid sequence of SEQ ID NO: 319; or

[0414] (47) the heavy chain comprises the amino acid sequence of SEQ ID NO: 366, and the light chain comprises the amino acid sequence of SEQ ID NO: 319; or

[0415] (48) the heavy chain comprises the amino acid sequence of SEQ ID NO: 353, and the light chain comprises the amino acid sequence of SEQ ID NO: 329; or

[0416] (49) the heavy chain comprises the amino acid sequence of SEQ ID NO: 353, and the light chain comprises the amino acid sequence of SEQ ID NO: 330; or

[0417] (50) the heavy chain comprises the amino acid sequence of SEQ ID NO: 367, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or

[0418] (51) the heavy chain comprises the amino acid sequence of SEQ ID NO: 368, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or

[0419] (52) the heavy chain comprises the amino acid sequence of SEQ ID NO: 369, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or

[0420] (53) the heavy chain comprises the amino acid sequence of SEQ ID NO: 368, and the light chain comprises the amino acid sequence of SEQ ID NO: 318; or

[0421] (54) the heavy chain comprises the amino acid sequence of SEQ ID NO: 368, and the light chain comprises the amino acid sequence of SEQ ID NO: 319; or

[0422] (55) The heavy chain comprises the amino acid sequence of SEQ ID NO: 368, and the light chain comprises the amino acid sequence of SEQ ID NO: 320.

[0423] In some embodiments, the anti-CD3 antibody of any of the preceding items, wherein:

[0424] 1) the heavy chain comprises the amino acid sequence of SEQ ID NO: 301, 181, 180, 350, 353, 354, 355, 363, or 322, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or

[0425] 2) the heavy chain comprises the amino acid sequence of SEQ ID NO: 301, 181, 180, 350, 353, 354, 355, 363, or 322, and the light chain comprises the amino acid sequence of SEQ ID NO: 304; or

[0426] 3) the heavy chain comprises the amino acid sequence of SEQ ID NO: 301, 181, 180, 350, 353, 354, 355, 363, or 322, and the light chain comprises the amino acid sequence of SEQ ID NO: 305; or

[0427] 4) the heavy chain comprises the amino acid sequence of SEQ ID NO: 326 or 365, and the light chain comprises the amino acid sequence of SEQ ID NO: 319; or

[0428] 5) the heavy chain comprises the amino acid sequence of SEQ ID NO: 323 or 364, and the light chain comprises the amino acid sequence of SEQ ID NO: 320; or

[0429] 6) the heavy chain comprises the amino acid sequence of SEQ ID NO: 326 or 365, and the light chain comprises the amino acid sequence of SEQ ID NO: 320; or

[0430] 7) the heavy chain comprises the amino acid sequence of SEQ ID NO: 327 or 366, and the light chain comprises the amino acid sequence of SEQ ID NO: 320; or

[0431] 8) the heavy chain comprises the amino acid sequence of SEQ ID NO: 323 or 364, and the light chain comprises the amino acid sequence of SEQ ID NO: 319; or

[0432] 9) the heavy chain comprises the amino acid sequence of SEQ ID NO: 327 or 366, and the light chain comprises the amino acid sequence of SEQ ID NO: 319; or

[0433] 10) the heavy chain comprises the amino acid sequence of SEQ ID NO: 181, 301, 180, 350, 353, 354, 355, 363, or 322, and the light chain comprises the amino acid sequence of SEQ ID NO: 329; or

[0434] 11) the heavy chain comprises the amino acid sequence of SEQ ID NO: 181, 301, 180, 350, 353, 354, 355, 363, or 322, and the light chain comprises the amino acid sequence of SEQ ID NO: 330; or

[0435] 12) the heavy chain comprises the amino acid sequence of SEQ ID NO: 331 or 367, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or

[0436] 13) the heavy chain comprises the amino acid sequence of SEQ ID NO: 332 or 368, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or

[0437] 14) the heavy chain comprises the amino acid sequence of SEQ ID NO: 333 or 369, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or

[0438] 15) the heavy chain comprises the amino acid sequence of SEQ ID NO: 332 or 368, and the light chain comprises the amino acid sequence of SEQ ID NO: 318; or

[0439] 16) the heavy chain comprises the amino acid sequence of SEQ ID NO: 332 or 368, and the light chain comprises the amino acid sequence of SEQ ID NO: 319; or

[0440] 17) The heavy chain comprises the amino acid sequence of SEQ ID NO: 332 or 368, and the light chain comprises the amino acid sequence of SEQ ID NO: 320.

[0441] In some embodiments, the anti-CD3 antibody of any of the preceding items, wherein:

[0442] (1) the heavy chain comprises the amino acid sequence of SEQ ID NO: 301, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or

[0443] The heavy chain comprises the amino acid sequence of SEQ ID NO: 181, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or

[0444] (2) the heavy chain comprises the amino acid sequence of SEQ ID NO: 301, and the light chain comprises the amino acid sequence of SEQ ID NO: 304; or

[0445] (3) the heavy chain comprises the amino acid sequence of SEQ ID NO: 301, and the light chain comprises the amino acid sequence of SEQ ID NO: 305; or

[0446] (4) the heavy chain comprises the amino acid sequence of SEQ ID NO: 326, and the light chain comprises the amino acid sequence of SEQ ID NO: 319; or

[0447] (5) the heavy chain comprises the amino acid sequence of SEQ ID NO: 323, and the light chain comprises the amino acid sequence of SEQ ID NO: 320; or

[0448] (6) the heavy chain comprises the amino acid sequence of SEQ ID NO: 326, and the light chain comprises the amino acid sequence of SEQ ID NO: 320; or

[0449] (7) the heavy chain comprises the amino acid sequence of SEQ ID NO: 327, and the light chain comprises the amino acid sequence of SEQ ID NO: 320; or

[0450] (8) the heavy chain comprises the amino acid sequence of SEQ ID NO: 323, and the light chain comprises the amino acid sequence of SEQ ID NO: 319; or

[0451] (9) the heavy chain comprises the amino acid sequence of SEQ ID NO: 327, and the light chain comprises the amino acid sequence of SEQ ID NO: 319; or

[0452] (10) the heavy chain comprises the amino acid sequence of SEQ ID NO: 181, and the light chain comprises the amino acid sequence of SEQ ID NO: 329; or

[0453] (11) the heavy chain comprises the amino acid sequence of SEQ ID NO: 181, and the light chain comprises the amino acid sequence of SEQ ID NO: 330; or

[0454] (12) the heavy chain comprises the amino acid sequence of SEQ ID NO: 331, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or

[0455] (13) the heavy chain comprises the amino acid sequence of SEQ ID NO: 332, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or

[0456] (14) the heavy chain comprises the amino acid sequence of SEQ ID NO: 333, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or

[0457] (15) the heavy chain comprises the amino acid sequence of SEQ ID NO: 332, and the light chain comprises the amino acid sequence of SEQ ID NO: 318; or

[0458] (16) the heavy chain comprises the amino acid sequence of SEQ ID NO: 332, and the light chain comprises the amino acid sequence of SEQ ID NO: 319; or

[0459] (17) The heavy chain comprises the amino acid sequence of SEQ ID NO: 332, and the light chain comprises the amino acid sequence of SEQ ID NO: 320.

[0460] In some embodiments, the anti-CD3 antibody of any of the preceding items, wherein:

[0461] (1) the heavy chain comprises the amino acid sequence of SEQ ID NO: 301, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or

[0462] (2) the heavy chain comprises the amino acid sequence of SEQ ID NO: 301, and the light chain comprises the amino acid sequence of SEQ ID NO: 304; or

[0463] (3) the heavy chain comprises the amino acid sequence of SEQ ID NO: 301, and the light chain comprises the amino acid sequence of SEQ ID NO: 305; or

[0464] (4) the heavy chain comprises the amino acid sequence of SEQ ID NO: 326, and the light chain comprises the amino acid sequence of SEQ ID NO: 319; or

[0465] (5) the heavy chain comprises the amino acid sequence of SEQ ID NO: 323, and the light chain comprises the amino acid sequence of SEQ ID NO: 320; or

[0466] (6) the heavy chain comprises the amino acid sequence of SEQ ID NO: 326, and the light chain comprises the amino acid sequence of SEQ ID NO: 320; or

[0467] (7) The heavy chain comprises the amino acid sequence of SEQ ID NO: 327, and the light chain comprises the amino acid sequence of SEQ ID NO: 320.

[0468] In some embodiments, the anti-CD3 antibody of any of the preceding items, wherein:

[0469] (1) the heavy chain comprises the amino acid sequence of SEQ ID NO: 363, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or

[0470] The heavy chain comprises the amino acid sequence of SEQ ID NO: 353, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or

[0471] (2) the heavy chain comprises the amino acid sequence of SEQ ID NO: 363, and the light chain comprises the amino acid sequence of SEQ ID NO: 304; or

[0472] (3) the heavy chain comprises the amino acid sequence of SEQ ID NO: 363, and the light chain comprises the amino acid sequence of SEQ ID NO: 305; or

[0473] (4) the heavy chain comprises the amino acid sequence of SEQ ID NO: 365, and the light chain comprises the amino acid sequence of SEQ ID NO: 319; or

[0474] (5) the heavy chain comprises the amino acid sequence of SEQ ID NO: 364, and the light chain comprises the amino acid sequence of SEQ ID NO: 320; or

[0475] (6) the heavy chain comprises the amino acid sequence of SEQ ID NO: 365, and the light chain comprises the amino acid sequence of SEQ ID NO: 320; or

[0476] (7) the heavy chain comprises the amino acid sequence of SEQ ID NO: 366, and the light chain comprises the amino acid sequence of SEQ ID NO: 320; or

[0477] (8) the heavy chain comprises the amino acid sequence of SEQ ID NO: 364, and the light chain comprises the amino acid sequence of SEQ ID NO: 319; or

[0478] (9) the heavy chain comprises the amino acid sequence of SEQ ID NO: 366, and the light chain comprises the amino acid sequence of SEQ ID NO: 319; or

[0479] (10) the heavy chain comprises the amino acid sequence of SEQ ID NO: 353, and the light chain comprises the amino acid sequence of SEQ ID NO: 329; or

[0480] (11) the heavy chain comprises the amino acid sequence of SEQ ID NO: 353, and the light chain comprises the amino acid sequence of SEQ ID NO: 330; or

[0481] (12) the heavy chain comprises the amino acid sequence of SEQ ID NO: 367, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or

[0482] (13) the heavy chain comprises the amino acid sequence of SEQ ID NO: 368, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or

[0483] (14) the heavy chain comprises the amino acid sequence of SEQ ID NO: 369, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or

[0484] (15) the heavy chain comprises the amino acid sequence of SEQ ID NO: 368, and the light chain comprises the amino acid sequence of SEQ ID NO: 318; or

[0485] (16) the heavy chain comprises the amino acid sequence of SEQ ID NO: 368, and the light chain comprises the amino acid sequence of SEQ ID NO: 319; or

[0486] (17) The heavy chain comprises the amino acid sequence of SEQ ID NO: 368, and the light chain comprises the amino acid sequence of SEQ ID NO: 320.

[0487] In some embodiments, the anti-CD3 antibody of any of the preceding items, wherein:

[0488] (1) the heavy chain comprises the amino acid sequence of SEQ ID NO: 177, and the light chain comprises the amino acid sequence of SEQ ID NO: 164; or

[0489] (2) the heavy chain comprises the amino acid sequence of SEQ ID NO: 177, and the light chain comprises the amino acid sequence of SEQ ID NO: 165; or

[0490] (3) the heavy chain comprises the amino acid sequence of SEQ ID NO: 177, and the light chain comprises the amino acid sequence of SEQ ID NO: 166; or

[0491] (4) the heavy chain comprises the amino acid sequence of SEQ ID NO: 174, and the light chain comprises the amino acid sequence of SEQ ID NO: 167; or

[0492] (5) the heavy chain comprises the amino acid sequence of SEQ ID NO: 175, and the light chain comprises the amino acid sequence of SEQ ID NO: 167; or

[0493] (6) the heavy chain comprises the amino acid sequence of SEQ ID NO: 177, and the light chain comprises the amino acid sequence of SEQ ID NO: 167; or

[0494] (7) the heavy chain comprises the amino acid sequence of SEQ ID NO: 175, and the light chain comprises the amino acid sequence of SEQ ID NO: 168; or

[0495] (8) the heavy chain comprises the amino acid sequence of SEQ ID NO: 177, and the light chain comprises the amino acid sequence of SEQ ID NO: 168; or

[0496] (9) the heavy chain comprises the amino acid sequence of SEQ ID NO: 178, and the light chain comprises the amino acid sequence of SEQ ID NO: 170; or

[0497] (10) the heavy chain comprises the amino acid sequence of SEQ ID NO: 179, and the light chain comprises the amino acid sequence of SEQ ID NO: 170; or

[0498] (11) the heavy chain comprises the amino acid sequence of SEQ ID NO: 178, and the light chain comprises the amino acid sequence of SEQ ID NO: 171; or

[0499] (12) the heavy chain comprises the amino acid sequence of SEQ ID NO: 178, and the light chain comprises the amino acid sequence of SEQ ID NO: 172; or

[0500] (13) The heavy chain comprises the amino acid sequence of SEQ ID NO: 179, and the light chain comprises the amino acid sequence of SEQ ID NO: 172.

[0501] In some embodiments, the anti-CD3 antibody of any of the preceding items, wherein:

[0502] (1) the heavy chain comprises the amino acid sequence of SEQ ID NO: 128, and the light chain comprises the amino acid sequence of SEQ ID NO: 122, 123, 124 or 125; or

[0503] (2) the heavy chain comprises the amino acid sequence of SEQ ID NO: 129, and the light chain comprises the amino acid sequence of SEQ ID NO: 121, 122, 123, 124, or 125; or

[0504] (3) the heavy chain comprises the amino acid sequence of SEQ ID NO: 130, and the light chain comprises the amino acid sequence of SEQ ID NO: 122, 123, 124, or 125; or

[0505] (4) the heavy chain comprises the amino acid sequence of SEQ ID NO: 131, and the light chain comprises the amino acid sequence of SEQ ID NO: 122, 123, 124, or 125; or

[0506] (5) the heavy chain comprises the amino acid sequence of SEQ ID NO: 132, and the light chain comprises the amino acid sequence of SEQ ID NO: 121, 122, 123, 124, or 125; or

[0507] (6) the heavy chain comprises the amino acid sequence of SEQ ID NO: 133, and the light chain comprises the amino acid sequence of SEQ ID NO: 126 or 127; or

[0508] (7) the heavy chain comprises the amino acid sequence of SEQ ID NO: 134, and the light chain comprises the amino acid sequence of SEQ ID NO: 126 or 127; or

[0509] (8) The heavy chain comprises the amino acid sequence of SEQ ID NO: 135, and the light chain comprises the amino acid sequence of SEQ ID NO: 126 or 127.

[0510] In some embodiments, the present disclosure also provides an isolated anti-CD3 antibody that competes with the anti-CD3 antibody of any preceding item for binding to human CD3 or an epitope thereof.

[0511] In some embodiments, the anti-CD3 antibodies provided herein are expressed at a concentration of greater than 0.1 nM (e.g., greater than 0.5 nM, greater than 1 nM, greater than 2 nM, greater than 3 nM, greater than 4 nM, greater than 5 nM, greater than 6 nM, greater than 7 nM, greater than 8 nM, greater than 9 nM, greater than 10 nM, greater than 20 nM, greater than 30 nM, greater than 40 nM, greater than 50 nM, greater than 60 nM, greater than 70 nM, greater than 80 nM, greater than 90 nM, greater than 100 nM, greater than 150 nM, greater than 200 nM, greater than 250 nM, greater than 300 nM, greater than 350 nM, greater than Binds to human CD3 with a KD value of greater than 400 nM, greater than 450 nM, greater than 500 nM, greater than 550 nM, greater than 600 nM, greater than 650 nM, greater than 700 nM, greater than 750 nM, greater than 800 nM, greater than 850 nM, greater than 900 nM, greater than 950 nM, greater than 1000 nM, greater than 1100 nM, greater than 1200 nM, greater than 1300 nM, greater than 1400 nM, greater than 1450 nM, greater than 1500 nM, greater than 1800 nM, or greater than 2000 nM) as measured by Biacore.

[0512] In some embodiments, the anti-CD3 antibodies provided herein are expressed at a concentration of less than 2000 nM (e.g., less than 1800 nM, less than 1500 nM, less than 1450 nM, less than 1400 nM, less than 1300 nM, less than 1200 nM, less than 1100 nM, less than 1000 nM, less than 950 nM, less than 900 nM, less than 850 nM, less than 800 nM, less than 750 nM, less than 700 nM, less than 650 nM, less than 600 nM, less than 550 nM, less than 500 nM, less than 450 nM, less than 400 nM, less than 350 nM, less than 500 nM, less than 500 nM, less than 600 nM, less than 750 nM, less than 700 nM, less than 650 nM, less than 600 nM, less than 550 nM, less than 500 nM, less than 450 nM, less than 400 nM, less than 35 ... less than 0.5 nM, less than 0.2 nM) binds to human CD3 with a KD value of less than 0 nM, less than 0.1 nM, less than 0.2 nM, less than 0.5 ...

[0513] In some embodiments, the present disclosure provides an anti-CD3 antibody at a concentration of greater than 0.008 nM (e.g., greater than 0.009 nM, greater than 0.01 nM, greater than 0.1 nM, greater than 0.2 nM, greater than 0.3 nM, greater than 0.4 nM, greater than 0.5 nM, greater than 0.6 nM, greater than 0.7 nM, greater than 0.8 nM, greater than 0.9 nM, greater than 1 nM, greater than 2 nM, greater than 3 nM, greater than 4 nM, greater than 5 nM, greater than 6 nM, greater than 7 nM, greater than 8 nM, greater than 9 nM, greater than 10 nM, greater than 11 nM, greater than 12 nM, greater than 13 nM, greater than 14 nM, greater than 15 nM, greater than 16 nM, greater than 17 nM, greater than 18 nM, greater than 19 nM, greater than 20 nM, greater than 21 nM, greater than 22 nM, greater than 23 nM, greater than 24 nM, greater than 25 nM, greater than 26 nM, greater than 27 nM, greater than 28 nM, greater than 29 nM, greater than 30 nM, greater than 31 nM, greater than 32 nM, greater than 33 nM, greater than 34 nM, greater than 35 nM, greater than 36 nM, greater than 37 nM, greater than 38 nM, greater than 39 nM, greater than 40 nM, greater than 41 nM, greater than 42 nM, greater than 43 nM, greater than 44 nM, greater than 45 nM, greater than 46 nM, greater than 47 nM, greater than 48 nM, EC greater than 7 nM, greater than 8 nM, greater than 9 nM, greater than 10 nM, greater than 15 nM, greater than 20 nM, greater than 30 nM, greater than 40 nM, greater than 50 nM, greater than 60 nM, greater than 70 nM, greater than 80 nM, greater than 90 nM, greater than 100 nM, greater than 150 nM, greater than 200 nM, greater than 250 nM, greater than 300 nM, greater than 350 nM, greater than 400 nM, greater than 450 nM, greater than 500 nM) 50 The EC 50 Values ​​were measured by FACS.

[0514] In some embodiments, the anti-CD3 antibodies provided herein are expressed at less than 1500 nM (e.g., less than 1000 nM, less than 950 nM, less than 900 nM, less than 850 nM, less than 800 nM, less than 750 nM, less than 700 nM, less than 650 nM, less than 600 nM, less than 550 nM, less than 500 nM, less than 450 nM, less than 400 nM, less than 350 nM, less than 300 nM, less than 250 nM, less than 200 nM, less than 150 nM, less than 100 nM, less than 90 nM). , less than 80 nM, less than 70 nM, less than 60 nM, less than 50 nM, less than 40 nM, less than 30 nM, less than 20 nM, less than 10 nM, less than 9 nM, less than 8 nM, less than 7 nM, less than 6 nM, less than 5 nM, less than 4 nM, less than 3 nM, less than 2 nM, less than 1 nM, less than 0.9 nM, less than 0.8 nM, less than 0.7 nM, less than 0.6 nM, less than 0.5 nM, less than 0.4 nM, less than 0.3 nM, less than 0.2 nM, less than 0.1 nM, less than 0.01 nM) 50 The EC 50 Values ​​were measured by FACS.

[0515] In some embodiments, the anti-CD3 antibodies provided herein are capable of cross-binding to human and cynomolgus monkey CD3.

[0516] In some embodiments, the anti-CD3 antibody of any of the preceding items is a multispecific antibody. In some embodiments, the anti-CD3 antibody of any of the preceding items, wherein the multispecific antibody comprises a first antigen binding domain that binds to human CD3, and one to four additional antigen binding domains that bind to one or more selected from (a) a tumor antigen, or (b) a cell surface antigen, receptor, or receptor ligand. In some embodiments, the anti-CD3 antibody of any of the preceding items, wherein the tumor antigen is an antigen on a tumor cell, and the tumor cell is selected from the group consisting of: breast cancer, prostate cancer, gastric cancer, lung cancer, colorectal cancer (including colon cancer and rectal cancer), pancreatic cancer, liver cancer, ovarian cancer, oral cancer, nasopharyngeal cancer, esophageal cancer, laryngeal cancer, bone cancer, skin cancer, melanoma, uterine cancer, testicular cancer, bladder cancer, kidney cancer, brain cancer, glioblastoma, thyroid cancer, lymphoma, myeloma, and leukemia.

[0517] In another aspect, the present disclosure provides a multispecific antibody comprising an anti-CD3 antibody as described in any of the preceding items. In some embodiments, the multispecific antibody specifically binds to human CD3 and simultaneously binds to a tumor-associated antigen (TAA) or a cell surface antigen, receptor, or receptor ligand. In some embodiments, the multispecific antibody binds to human CD3 and simultaneously binds to one or more antigens selected from CD20, BCMA, and PSMA.

[0518] In some embodiments, the multispecific antibody as described above, wherein the tumor antigen is an antigen on a tumor cell, and the tumor cell is selected from the group consisting of: breast cancer, prostate cancer, gastric cancer, lung cancer, colorectal cancer (including colon cancer and rectal cancer), pancreatic cancer, liver cancer, ovarian cancer, oral cancer, nasopharyngeal cancer, esophageal cancer, laryngeal cancer, bone cancer, skin cancer, melanoma, uterine cancer, testicular cancer, bladder cancer, kidney cancer, brain cancer, glioblastoma, thyroid cancer, lymphoma, myeloma and leukemia.

[0519] In some embodiments, the multispecific antibody of any of the preceding items is a bispecific antibody. In some embodiments, the bispecific antibody is an anti-CD20 / CD3 bispecific antibody.

[0520] In some embodiments, the anti-CD20 / CD3 bispecific antibody as described above comprises a first antigen-binding domain that specifically binds to CD3 and a second antigen-binding domain that specifically binds to CD20, wherein the first antigen-binding domain that specifically binds to CD3 comprises a heavy chain variable region CD3-VH and a light chain variable region CD3-VL, and the second antigen-binding domain that specifically binds to CD20 comprises a heavy chain variable region CD20-VH and a light chain variable region CD20-VL; wherein:

[0521] (1) the CD3-VH comprises CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3, wherein the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 34, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 138 or 35, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3, wherein the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 1, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 17; or

[0522] (2) the CD3-VH comprises CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3, wherein the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 34, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 138 or 35, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3, wherein the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 96, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 17; or

[0523] (3) The CD3-VH comprises CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3, wherein the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 34, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 138 or 35, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3, wherein the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 1, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 136, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 17.

[0524] In some embodiments, the anti-CD20 / CD3 bispecific antibody of any of the preceding items, wherein:

[0525] The CD20-VH comprises CD20-HCDR1, CD20-HCDR2, and CD20-HCDR3, wherein the CD20-HCDR1 comprises the amino acid sequence of SEQ ID NO: 373, the CD20-HCDR2 comprises the amino acid sequence of SEQ ID NO: 374, and the CD20-HCDR3 comprises the amino acid sequence of SEQ ID NO: 375; and the CD20-VL comprises CD20-LCDR1, CD20-LCDR2, and CD20-LCDR3, wherein the CD20-LCDR1 comprises the amino acid sequence of SEQ ID NO: 370, the CD20-LCDR2 comprises the amino acid sequence of SEQ ID NO: 371, and the CD20-LCDR3 comprises the amino acid sequence of SEQ ID NO: 372.

[0526] In some embodiments, the anti-CD20 / CD3 bispecific antibody of any of the preceding items, wherein:

[0527] (1) the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 34, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 138 or 35, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 1, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 17;

[0528] Meanwhile, the CD20-VH comprises: a CD20-HCDR1 comprising the amino acid sequence of SEQ ID NO: 373, a CD20-HCDR2 comprising the amino acid sequence of SEQ ID NO: 374, and a CD20-HCDR3 comprising the amino acid sequence of SEQ ID NO: 375; and the CD20-VL comprises: a CD20-LCDR1 comprising the amino acid sequence of SEQ ID NO: 370, a CD20-LCDR2 comprising the amino acid sequence of SEQ ID NO: 371, and a CD20-LCDR3 comprising the amino acid sequence of SEQ ID NO: 372; or

[0529] (2) the CD3-VH comprises CD3-HCDR1, CD3-HCDR2, CD3-HCDR3, CD3-HCDR1 comprising the amino acid sequence of SEQ ID NO: 34, CD3-HCDR2 comprising the amino acid sequence of SEQ ID NO: 138 or 35, and CD3-HCDR3 comprising the amino acid sequence of SEQ ID NO: 36; and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, CD3-LCDR3, CD3-LCDR1 comprising the amino acid sequence of SEQ ID NO: 96, CD3-LCDR2 comprising the amino acid sequence of SEQ ID NO: 2, and CD3-LCDR3 comprising the amino acid sequence of SEQ ID NO: 17;

[0530] Meanwhile, the CD20-HCDR1 comprises the amino acid sequence of SEQ ID NO: 373, the CD20-HCDR2 comprises the amino acid sequence of SEQ ID NO: 374, and the CD20-HCDR3 comprises the amino acid sequence of SEQ ID NO: 375; and the CD20-LCDR1 comprises the amino acid sequence of SEQ ID NO: 370, the CD20-LCDR2 comprises the amino acid sequence of SEQ ID NO: 371, and the CD20-LCDR3 comprises the amino acid sequence of SEQ ID NO: 372; or

[0531] (3) the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 34, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 138 or 35, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 1, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 136, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 17;

[0532] At the same time, the CD20-HCDR1 comprises the amino acid sequence of SEQ ID NO: 373, the CD20-HCDR2 comprises the amino acid sequence of SEQ ID NO: 374, and the CD20-HCDR3 comprises the amino acid sequence of SEQ ID NO: 375; and the CD20-LCDR1 comprises the amino acid sequence of SEQ ID NO: 370, the CD20-LCDR2 comprises the amino acid sequence of SEQ ID NO: 371, and the CD20-LCDR3 comprises the amino acid sequence of SEQ ID NO: 372.

[0533] In some embodiments, the anti-CD20 / CD3 bispecific antibody of any of the preceding items, wherein:

[0534] (1) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 153, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 140, 141, 142, 143 or 144; or

[0535] (2) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 150, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 143; or

[0536] (3) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 151, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 143 or 144; or

[0537] (4) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 154, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 146, 147 or 148; or

[0538] (5) The CD3-VH comprises the amino acid sequence of SEQ ID NO: 155, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 146 or 148.

[0539] In some embodiments, the anti-CD20 / CD3 bispecific antibody of any of the preceding items, wherein

[0540] The CD20-VH comprises the amino acid sequence of SEQ ID NO: 338, and the CD20-VL comprises the amino acid sequence of SEQ ID NO: 337.

[0541] In some embodiments, the anti-CD20 / CD3 bispecific antibody of any of the preceding items, wherein:

[0542] (1) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 153, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 140, 141, 142, 143 or 144; and the CD20-VH comprises the amino acid sequence of SEQ ID NO: 338, and the CD20-VL comprises the amino acid sequence of SEQ ID NO: 337; or

[0543] (2) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 150, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 143; and the CD20-VH comprises the amino acid sequence of SEQ ID NO: 338, and the CD20-VL comprises the amino acid sequence of SEQ ID NO: 337; or

[0544] (3) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 151, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 143 or 144; and the CD20-VH comprises the amino acid sequence of SEQ ID NO: 338, and the CD20-VL comprises the amino acid sequence of SEQ ID NO: 337; or

[0545] (4) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 154, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 146, 147 or 148; and the CD20-VH comprises the amino acid sequence of SEQ ID NO: 338, and the CD20-VL comprises the amino acid sequence of SEQ ID NO: 337; or

[0546] (5) The CD3-VH comprises the amino acid sequence of SEQ ID NO: 155, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 146 or 148; and the CD20-VH comprises the amino acid sequence of SEQ ID NO: 338, and the CD20-VL comprises the amino acid sequence of SEQ ID NO: 337.

[0547] In some embodiments, the anti-CD20 / CD3 bispecific antibody of any of the preceding items, wherein:

[0548] The bispecific antibody further comprises a heavy chain constant region and a light chain constant region. In some embodiments, the heavy chain constant region is a human IgG1 heavy chain constant region or a variant thereof. In some embodiments, the light chain constant region is a human kappa light chain constant region or a variant thereof. In some embodiments, the heavy chain constant region comprises the amino acid sequence of SEQ ID NO: 120, 90, or 339, and the light chain constant region comprises the amino acid sequence of SEQ ID NO: 91. In some embodiments, the heavy chain constant region comprises the amino acid sequence of SEQ ID NO: 120, and the light chain constant region comprises the amino acid sequence of SEQ ID NO: 91. In some embodiments, the heavy chain constant region comprises the amino acid sequence of SEQ ID NO: 339, and the light chain constant region comprises the amino acid sequence of SEQ ID NO: 91.

[0549] In some embodiments, the anti-CD20 / CD3 bispecific antibody of any of the preceding items, wherein the bispecific antibody comprises:

[0550] (1) a first chain comprising the amino acid sequence of SEQ ID NO: 341, a second chain comprising the amino acid sequence of SEQ ID NO: 340, a third chain comprising the amino acid sequence of SEQ ID NO: 164, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 177; or

[0551] (2) a first chain comprising the amino acid sequence of SEQ ID NO: 341, a second chain comprising the amino acid sequence of SEQ ID NO: 340, a third chain comprising the amino acid sequence of SEQ ID NO: 165, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 177; or

[0552] (3) a first chain comprising the amino acid sequence of SEQ ID NO: 341, a second chain comprising the amino acid sequence of SEQ ID NO: 340, a third chain comprising the amino acid sequence of SEQ ID NO: 166, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 177; or

[0553] (4) a first chain comprising the amino acid sequence of SEQ ID NO: 341, a second chain comprising the amino acid sequence of SEQ ID NO: 340, a third chain comprising the amino acid sequence of SEQ ID NO: 167, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 174; or

[0554] (5) a first chain comprising the amino acid sequence of SEQ ID NO: 341, a second chain comprising the amino acid sequence of SEQ ID NO: 340, a third chain comprising the amino acid sequence of SEQ ID NO: 167, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 175; or

[0555] (6) a first chain comprising the amino acid sequence of SEQ ID NO: 341, a second chain comprising the amino acid sequence of SEQ ID NO: 340, a third chain comprising the amino acid sequence of SEQ ID NO: 167, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 177; or

[0556] (7) a first chain comprising the amino acid sequence of SEQ ID NO: 341, a second chain comprising the amino acid sequence of SEQ ID NO: 340, a third chain comprising the amino acid sequence of SEQ ID NO: 168, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 175; or

[0557] (8) a first chain comprising the amino acid sequence of SEQ ID NO: 341, a second chain comprising the amino acid sequence of SEQ ID NO: 340, a third chain comprising the amino acid sequence of SEQ ID NO: 168, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 177; or

[0558] (9) a first chain comprising the amino acid sequence of SEQ ID NO: 341, a second chain comprising the amino acid sequence of SEQ ID NO: 340, a third chain comprising the amino acid sequence of SEQ ID NO: 170, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 178; or

[0559] (10) a first chain comprising the amino acid sequence of SEQ ID NO: 341, a second chain comprising the amino acid sequence of SEQ ID NO: 340, a third chain comprising the amino acid sequence of SEQ ID NO: 170, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 179; or

[0560] (11) a first chain comprising the amino acid sequence of SEQ ID NO: 341, a second chain comprising the amino acid sequence of SEQ ID NO: 340, a third chain comprising the amino acid sequence of SEQ ID NO: 171, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 178; or

[0561] (12) a first chain comprising the amino acid sequence of SEQ ID NO: 341, a second chain comprising the amino acid sequence of SEQ ID NO: 340, a third chain comprising the amino acid sequence of SEQ ID NO: 172, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 178; or

[0562] (13) A first chain comprising the amino acid sequence of SEQ ID NO: 341, a second chain comprising the amino acid sequence of SEQ ID NO: 340, a third chain comprising the amino acid sequence of SEQ ID NO: 172, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 179.

[0563] In some embodiments, the bispecific antibody is an anti-BCMA / CD3 bispecific antibody.

[0564] In some embodiments, the anti-BCMA / CD3 bispecific antibody as described above comprises a first antigen-binding domain that specifically binds to CD3 and a second antigen-binding domain that specifically binds to BCMA, wherein the first antigen-binding domain that specifically binds to CD3 comprises a heavy chain variable region CD3-VH and a light chain variable region CD3-VL, and the second antigen-binding domain that specifically binds to BCMA comprises a heavy chain variable region BCMA-VH and a light chain variable region BCMA-VL; wherein:

[0565] (1) the CD3-VH comprises CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3, wherein the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3, wherein the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 189, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0566] (2) the CD3-VH comprises CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3, wherein the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3, wherein the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 189, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 183; or

[0567] (3) the CD3-VH comprises CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3, wherein the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3, wherein the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 187, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 183; or

[0568] (4) the CD3-VH comprises CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3, wherein the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 217, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3, wherein the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 207, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0569] (5) the CD3-VH comprises CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3, wherein the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 214, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3, wherein the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 208, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0570] (6) the CD3-VH comprises CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3, wherein the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 217, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3, wherein the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 208, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0571] (7) the CD3-VH comprises CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3, wherein the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 218, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3, wherein the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 208, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0572] (8) the CD3-VH comprises CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3, wherein the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 214, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3, wherein the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 207, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0573] (9) the CD3-VH comprises CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3, wherein the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3, wherein the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 210, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0574] (10) the CD3-VH comprises CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3, wherein the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3, wherein the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 211, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0575] (11) the CD3-VH comprises CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3, wherein the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 219, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3, wherein the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 189, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0576] (12) the CD3-VH comprises CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3, wherein the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 220, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3, wherein the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 189, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0577] (13) the CD3-VH comprises CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3, wherein the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 221, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3, wherein the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 189, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0578] (14) The CD3-VH comprises CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3, wherein the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 220, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3, wherein the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 208, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185.

[0579] In some embodiments, the anti-BCMA / CD3 bispecific antibody of any of the preceding items, wherein the BCMA-VH comprises BCMA-HCDR1, BCMA-HCDR2, and BCMA-HCDR3, wherein the BCMA-HCDR1 comprises the amino acid sequence of SEQ ID NO: 379, the BCMA-HCDR2 comprises the amino acid sequence of SEQ ID NO: 380, and the BCMA-HCDR3 comprises the amino acid sequence of SEQ ID NO: 381; and the BCMA-VL comprises BCMA-LCDR1, BCMA-LCDR2, and BCMA-LCDR3, wherein the BCMA-LCDR1 comprises the amino acid sequence of SEQ ID NO: 376, the BCMA-LCDR2 comprises the amino acid sequence of SEQ ID NO: 377, and the BCMA-LCDR3 comprises the amino acid sequence of SEQ ID NO: 378.

[0580] In some embodiments, the anti-BCMA / CD3 bispecific antibody as described in any of the preceding items, wherein:

[0581] (1) the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 189, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0582] (2) the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 189, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 183; or

[0583] (3) the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 187, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 183; or

[0584] (4) the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 217, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 207, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0585] (5) the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 214, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 208, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0586] (6) the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 217, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 208, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0587] (7) the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 218, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 208, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0588] (8) the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 214, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 207, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0589] (9) the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 210, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0590] (10) the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 211, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0591] (11) the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 219, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 189, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0592] (12) the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 220, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 189, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0593] (13) the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 221, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 189, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0594] (14) the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 220, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 208, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185;

[0595] Meanwhile, the BCMA-HCDR1 comprises the amino acid sequence of SEQ ID NO: 379, the BCMA-HCDR2 comprises the amino acid sequence of SEQ ID NO: 380, and the BCMA-HCDR3 comprises the amino acid sequence of SEQ ID NO: 381; and the BCMA-LCDR1 comprises the amino acid sequence of SEQ ID NO: 376, the BCMA-LCDR2 comprises the amino acid sequence of SEQ ID NO: 377, and the BCMA-LCDR3 comprises the amino acid sequence of SEQ ID NO: 378.

[0596] In some embodiments, the anti-BCMA / CD3 bispecific antibody as described in any of the preceding items, wherein:

[0597] (1) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 255, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 236; or

[0598] (2) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 255, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 237; or

[0599] (3) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 255, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 238; or

[0600] (4) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 278, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 268; or

[0601] (5) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 275, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 269; or

[0602] (6) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 278, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 269; or

[0603] (7) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 279, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 269; or

[0604] (8) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 157, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 236; or

[0605] (9) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 275, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 268; or

[0606] (10) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 157, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 271; or

[0607] (11) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 157, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 272; or

[0608] (12) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 281, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 236; or

[0609] (13) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 282, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 236; or

[0610] (14) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 283, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 236; or

[0611] (15) The CD3-VH comprises the amino acid sequence of SEQ ID NO: 282, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 269.

[0612] In some embodiments, the anti-BCMA / CD3 bispecific antibody of any of the preceding items, wherein the BCMA-VH comprises the amino acid sequence of SEQ ID NO: 383, and the BCMA-VL comprises the amino acid sequence of SEQ ID NO: 382.

[0613] In some embodiments, the anti-BCMA / CD3 bispecific antibody as described in any of the preceding items, wherein:

[0614] (1) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 255, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 236; and the BCMA-VH comprises the amino acid sequence of SEQ ID NO: 383, and the BCMA-VL comprises the amino acid sequence of SEQ ID NO: 382; or

[0615] (2) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 255, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 237; and the BCMA-VH comprises the amino acid sequence of SEQ ID NO: 383, and the BCMA-VL comprises the amino acid sequence of SEQ ID NO: 382; or

[0616] (3) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 255, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 238; and the BCMA-VH comprises the amino acid sequence of SEQ ID NO: 383, and the BCMA-VL comprises the amino acid sequence of SEQ ID NO: 382; or

[0617] (4) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 278, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 268; and the BCMA-VH comprises the amino acid sequence of SEQ ID NO: 383, and the BCMA-VL comprises the amino acid sequence of SEQ ID NO: 382; or

[0618] (5) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 275, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 269; and the BCMA-VH comprises the amino acid sequence of SEQ ID NO: 383, and the BCMA-VL comprises the amino acid sequence of SEQ ID NO: 382; or

[0619] (6) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 278, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 269; and the BCMA-VH comprises the amino acid sequence of SEQ ID NO: 383, and the BCMA-VL comprises the amino acid sequence of SEQ ID NO: 382; or

[0620] (7) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 279, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 269; and the BCMA-VH comprises the amino acid sequence of SEQ ID NO: 383, and the BCMA-VL comprises the amino acid sequence of SEQ ID NO: 382; or

[0621] (8) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 157, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 236; and the BCMA-VH comprises the amino acid sequence of SEQ ID NO: 383, and the BCMA-VL comprises the amino acid sequence of SEQ ID NO: 382; or

[0622] (9) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 275, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 268; and the BCMA-VH comprises the amino acid sequence of SEQ ID NO: 383, and the BCMA-VL comprises the amino acid sequence of SEQ ID NO: 382; or

[0623] (10) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 157, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 271; and the BCMA-VH comprises the amino acid sequence of SEQ ID NO: 383, and the BCMA-VL comprises the amino acid sequence of SEQ ID NO: 382; or

[0624] (11) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 157, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 272; and the BCMA-VH comprises the amino acid sequence of SEQ ID NO: 383, and the BCMA-VL comprises the amino acid sequence of SEQ ID NO: 382; or

[0625] (12) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 281, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 236; and the BCMA-VH comprises the amino acid sequence of SEQ ID NO: 383, and the BCMA-VL comprises the amino acid sequence of SEQ ID NO: 382; or

[0626] (13) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 282, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 236; and the BCMA-VH comprises the amino acid sequence of SEQ ID NO: 383, and the BCMA-VL comprises the amino acid sequence of SEQ ID NO: 382; or

[0627] (14) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 283, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 236; and the BCMA-VH comprises the amino acid sequence of SEQ ID NO: 383, and the BCMA-VL comprises the amino acid sequence of SEQ ID NO: 382; or

[0628] (15) The CD3-VH comprises the amino acid sequence of SEQ ID NO: 282, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 269; and the BCMA-VH comprises the amino acid sequence of SEQ ID NO: 383, and the BCMA-VL comprises the amino acid sequence of SEQ ID NO: 382.

[0629] In some embodiments, the anti-BCMA / CD3 bispecific antibody as described in any of the preceding items, wherein the anti-BCMA / CD3 bispecific antibody comprises a heavy chain constant region and a light chain constant region. In some embodiments, the anti-BCMA / CD3 bispecific antibody as described in any of the preceding items, wherein the heavy chain constant region is a heavy chain constant region of human IgG1, IgG2, IgG3, IgG4, or a variant thereof. In some embodiments, the heavy chain constant region of the anti-BCMA / CD3 bispecific antibody as described in any of the preceding items comprises an amino acid substitution of F405L or K409R. In some embodiments, the anti-BCMA / CD3 bispecific antibody as described in any of the preceding items, wherein the light chain constant region is a light chain constant region of human lambda, kappa, or a variant thereof. In some embodiments, in the anti-BCMA / CD3 bispecific antibody as described in any of the preceding items, the second antigen-binding domain that specifically binds to BCMA comprises a heavy chain constant region and a light chain constant region, the heavy chain constant region of the second antigen-binding domain that specifically binds to BCMA comprises the amino acid sequence of SEQ ID NO: 339, and the light chain constant region of the second antigen-binding domain that specifically binds to BCMA comprises the amino acid sequence of SEQ ID NO: 384. In some embodiments, in the anti-BCMA / CD3 bispecific antibody as described in any of the preceding items, the first antigen-binding domain that specifically binds to CD3 comprises a heavy chain constant region and a light chain constant region, the heavy chain constant region of the first antigen-binding domain that specifically binds to CD3 comprises the amino acid sequence of SEQ ID NO: 120, and the light chain constant region of the first antigen-binding domain that specifically binds to CD3 comprises the amino acid sequence of SEQ ID NO: 91.

[0630] In some embodiments, the anti-BCMA / CD3 bispecific antibody of any of the preceding items, wherein the bispecific antibody comprises:

[0631] (1) a first chain comprising the amino acid sequence of SEQ ID NO: 386, a second chain comprising the amino acid sequence of SEQ ID NO: 385, a third chain comprising the amino acid sequence of SEQ ID NO: 303, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 301; or

[0632] (2) a first chain comprising the amino acid sequence of SEQ ID NO: 386, a second chain comprising the amino acid sequence of SEQ ID NO: 385, a third chain comprising the amino acid sequence of SEQ ID NO: 304, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 301; or

[0633] (3) a first chain comprising the amino acid sequence of SEQ ID NO: 386, a second chain comprising the amino acid sequence of SEQ ID NO: 385, a third chain comprising the amino acid sequence of SEQ ID NO: 305, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 301; or

[0634] (4) a first chain comprising the amino acid sequence of SEQ ID NO: 386, a second chain comprising the amino acid sequence of SEQ ID NO: 385, a third chain comprising the amino acid sequence of SEQ ID NO: 319, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 326; or

[0635] (5) a first chain comprising the amino acid sequence of SEQ ID NO: 386, a second chain comprising the amino acid sequence of SEQ ID NO: 385, a third chain comprising the amino acid sequence of SEQ ID NO: 320, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 323; or

[0636] (6) a first chain comprising the amino acid sequence of SEQ ID NO: 386, a second chain comprising the amino acid sequence of SEQ ID NO: 385, a third chain comprising the amino acid sequence of SEQ ID NO: 320, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 326; or

[0637] (7) a first chain comprising the amino acid sequence of SEQ ID NO: 386, a second chain comprising the amino acid sequence of SEQ ID NO: 385, a third chain comprising the amino acid sequence of SEQ ID NO: 320, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 327; or

[0638] (8) a first chain comprising the amino acid sequence of SEQ ID NO: 386, a second chain comprising the amino acid sequence of SEQ ID NO: 385, a third chain comprising the amino acid sequence of SEQ ID NO: 303, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 181; or

[0639] (9) a first chain comprising the amino acid sequence of SEQ ID NO: 386, a second chain comprising the amino acid sequence of SEQ ID NO: 385, a third chain comprising the amino acid sequence of SEQ ID NO: 319, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 323; or

[0640] (10) a first chain comprising the amino acid sequence of SEQ ID NO: 386, a second chain comprising the amino acid sequence of SEQ ID NO: 385, a third chain comprising the amino acid sequence of SEQ ID NO: 329, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 181; or

[0641] (11) a first chain comprising the amino acid sequence of SEQ ID NO: 386, a second chain comprising the amino acid sequence of SEQ ID NO: 385, a third chain comprising the amino acid sequence of SEQ ID NO: 330, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 181; or

[0642] (12) a first chain comprising the amino acid sequence of SEQ ID NO: 386, a second chain comprising the amino acid sequence of SEQ ID NO: 385, a third chain comprising the amino acid sequence of SEQ ID NO: 303, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 331; or

[0643] (13) a first chain comprising the amino acid sequence of SEQ ID NO: 386, a second chain comprising the amino acid sequence of SEQ ID NO: 385, a third chain comprising the amino acid sequence of SEQ ID NO: 303, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 332; or

[0644] (14) a first chain comprising the amino acid sequence of SEQ ID NO: 386, a second chain comprising the amino acid sequence of SEQ ID NO: 385, a third chain comprising the amino acid sequence of SEQ ID NO: 303, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 333; or

[0645] (15) A first chain comprising the amino acid sequence of SEQ ID NO: 386, a second chain comprising the amino acid sequence of SEQ ID NO: 385, a third chain comprising the amino acid sequence of SEQ ID NO: 320, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 332.

[0646] In some embodiments, the bispecific antibody is an anti-PSMA / CD3 bispecific antibody.

[0647] In some embodiments, the anti-PSMA / CD3 bispecific antibody as described above comprises a first antigen-binding domain that specifically binds to CD3 and a second antigen-binding domain that specifically binds to PSMA, wherein the first antigen-binding domain that specifically binds to CD3 comprises a heavy chain variable region CD3-VH and a light chain variable region CD3-VL, and the second antigen-binding domain that specifically binds to PSMA comprises a heavy chain variable region PSMA-VH and a light chain variable region PSMA-VL; wherein:

[0648] (1) the CD3-VH comprises CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3, wherein the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3, wherein the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 189, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0649] (2) the CD3-VH comprises CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3, wherein the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3, wherein the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 189, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 183; or

[0650] (3) the CD3-VH comprises CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3, wherein the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3, wherein the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 187, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 183; or

[0651] (4) the CD3-VH comprises CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3, wherein the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 217, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3, wherein the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 207, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0652] (5) the CD3-VH comprises CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3, wherein the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 214, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3, wherein the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 208, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0653] (6) the CD3-VH comprises CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3, wherein the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 217, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3, wherein the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 208, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0654] (7) the CD3-VH comprises CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3, wherein the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 218, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3, wherein the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 208, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0655] (8) the CD3-VH comprises CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3, wherein the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 214, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3, wherein the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 207, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0656] (9) the CD3-VH comprises CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3, wherein the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 218, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3, wherein the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 207, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0657] (10) the CD3-VH comprises CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3, wherein the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3, wherein the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 210, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0658] (11) the CD3-VH comprises CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3, wherein the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3, wherein the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 211, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0659] (12) the CD3-VH comprises CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3, wherein the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 219, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3, wherein the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 189, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0660] (13) the CD3-VH comprises CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3, wherein the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 220, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3, wherein the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 189, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0661] (14) the CD3-VH comprises CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3, wherein the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 221, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3, wherein the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 189, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0662] (15) The CD3-VH comprises CD3-HCDR1, CD3-HCDR2, and CD3-HCDR3, wherein the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 220, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-VL comprises CD3-LCDR1, CD3-LCDR2, and CD3-LCDR3, wherein the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 208, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185.

[0663] In some embodiments, the anti-PSMA / CD3 bispecific antibody of any of the preceding items, wherein the PSMA-VH comprises PSMA-HCDR1, PSMA-HCDR2, and PSMA-HCDR3, wherein the PSMA-HCDR1 comprises the amino acid sequence of SEQ ID NO: 390, the PSMA-HCDR2 comprises the amino acid sequence of SEQ ID NO: 391, and the PSMA-HCDR3 comprises the amino acid sequence of SEQ ID NO: 392; and the PSMA-VL comprises PSMA-LCDR1, PSMA-LCDR2, and PSMA-LCDR3, wherein the PSMA-LCDR1 comprises the amino acid sequence of SEQ ID NO: 387, the PSMA-LCDR2 comprises the amino acid sequence of SEQ ID NO: 388, and the PSMA-LCDR3 comprises the amino acid sequence of SEQ ID NO: 389.

[0664] In some embodiments, the anti-PSMA / CD3 bispecific antibody of any of the preceding items, wherein:

[0665] (1) the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 189, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0666] (2) the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 189, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 183; or

[0667] (3) the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 187, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 183; or

[0668] (4) the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 217, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 207, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0669] (5) the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 214, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 208, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0670] (6) the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 217, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 208, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0671] (7) the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 218, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 208, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0672] (8) the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 214, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 207, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0673] (9) the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 218, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 207, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0674] (10) the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 210, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0675] (11) the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 211, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0676] (12) the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 219, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 189, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0677] (13) the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 220, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 189, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0678] (14) the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 221, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 189, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or

[0679] (15) the CD3-HCDR1 comprises the amino acid sequence of SEQ ID NO: 137, the CD3-HCDR2 comprises the amino acid sequence of SEQ ID NO: 220, and the CD3-HCDR3 comprises the amino acid sequence of SEQ ID NO: 36; and the CD3-LCDR1 comprises the amino acid sequence of SEQ ID NO: 208, the CD3-LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the CD3-LCDR3 comprises the amino acid sequence of SEQ ID NO: 185;

[0680] Meanwhile, the PSMA-HCDR1 comprises the amino acid sequence of SEQ ID NO: 390, the PSMA-HCDR2 comprises the amino acid sequence of SEQ ID NO: 391, and the PSMA-HCDR3 comprises the amino acid sequence of SEQ ID NO: 392; and the PSMA-LCDR1 comprises the amino acid sequence of SEQ ID NO: 387, the PSMA-LCDR2 comprises the amino acid sequence of SEQ ID NO: 388, and the PSMA-LCDR3 comprises the amino acid sequence of SEQ ID NO: 389.

[0681] In some embodiments, the anti-PSMA / CD3 bispecific antibody of any of the preceding items, wherein:

[0682] (1) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 255, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 236; or

[0683] (2) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 255, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 237; or

[0684] (3) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 255, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 238; or

[0685] (4) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 278, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 268; or

[0686] (5) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 275, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 269; or

[0687] (6) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 278, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 269; or

[0688] (7) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 279, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 269; or

[0689] (8) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 157, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 236; or

[0690] (9) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 275, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 268; or

[0691] (10) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 279, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 268; or

[0692] (11) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 157, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 271; or

[0693] (12) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 157, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 272; or

[0694] (13) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 281, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 236; or

[0695] (15) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 282, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 236; or

[0696] (15) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 283, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 236; or

[0697] (16) The CD3-VH comprises the amino acid sequence of SEQ ID NO: 282, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 269.

[0698] In some embodiments, the anti-PSMA / CD3 bispecific antibody of any of the preceding items, wherein the PSMA-VH comprises the amino acid sequence of SEQ ID NO: 394, and the PSMA-VL comprises the amino acid sequence of SEQ ID NO: 393.

[0699] In some embodiments, the anti-PSMA / CD3 bispecific antibody of any of the preceding items, wherein:

[0700] (1) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 255, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 236; and the PSMA-VH comprises the amino acid sequence of SEQ ID NO: 394, and the PSMA-VL comprises the amino acid sequence of SEQ ID NO: 393; or

[0701] (2) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 255, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 237; and the PSMA-VH comprises the amino acid sequence of SEQ ID NO: 394, and the PSMA-VL comprises the amino acid sequence of SEQ ID NO: 393; or

[0702] (3) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 255, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 238; and the PSMA-VH comprises the amino acid sequence of SEQ ID NO: 394, and the PSMA-VL comprises the amino acid sequence of SEQ ID NO: 393; or

[0703] (4) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 278, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 268; and the PSMA-VH comprises the amino acid sequence of SEQ ID NO: 394, and the PSMA-VL comprises the amino acid sequence of SEQ ID NO: 393; or

[0704] (5) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 275, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 269; and the PSMA-VH comprises the amino acid sequence of SEQ ID NO: 394, and the PSMA-VL comprises the amino acid sequence of SEQ ID NO: 393; or

[0705] (6) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 278, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 269; and the PSMA-VH comprises the amino acid sequence of SEQ ID NO: 394, and the PSMA-VL comprises the amino acid sequence of SEQ ID NO: 393; or

[0706] (7) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 279, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 269; and the PSMA-VH comprises the amino acid sequence of SEQ ID NO: 394, and the PSMA-VL comprises the amino acid sequence of SEQ ID NO: 393; or

[0707] (8) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 157, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 236; and the PSMA-VH comprises the amino acid sequence of SEQ ID NO: 394, and the PSMA-VL comprises the amino acid sequence of SEQ ID NO: 393; or

[0708] (9) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 275, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 268; and the PSMA-VH comprises the amino acid sequence of SEQ ID NO: 394, and the PSMA-VL comprises the amino acid sequence of SEQ ID NO: 393; or

[0709] (10) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 279, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 268; and the PSMA-VH comprises the amino acid sequence of SEQ ID NO: 394, and the PSMA-VL comprises the amino acid sequence of SEQ ID NO: 393; or

[0710] (11) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 157, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 271; and the PSMA-VH comprises the amino acid sequence of SEQ ID NO: 394, and the PSMA-VL comprises the amino acid sequence of SEQ ID NO: 393; or

[0711] (12) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 157, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 272; and the PSMA-VH comprises the amino acid sequence of SEQ ID NO: 394, and the PSMA-VL comprises the amino acid sequence of SEQ ID NO: 393; or

[0712] (13) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 281, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 236; and the PSMA-VH comprises the amino acid sequence of SEQ ID NO: 394, and the PSMA-VL comprises the amino acid sequence of SEQ ID NO: 393; or

[0713] (15) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 282, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 236; and the PSMA-VH comprises the amino acid sequence of SEQ ID NO: 394, and the PSMA-VL comprises the amino acid sequence of SEQ ID NO: 393; or

[0714] (15) the CD3-VH comprises the amino acid sequence of SEQ ID NO: 283, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 236; and the PSMA-VH comprises the amino acid sequence of SEQ ID NO: 394, and the PSMA-VL comprises the amino acid sequence of SEQ ID NO: 393; or

[0715] (16) The CD3-VH comprises the amino acid sequence of SEQ ID NO: 282, and the CD3-VL comprises the amino acid sequence of SEQ ID NO: 269; and the PSMA-VH comprises the amino acid sequence of SEQ ID NO: 394, and the PSMA-VL comprises the amino acid sequence of SEQ ID NO: 393.

[0716] In some embodiments, the anti-PSMA / CD3 bispecific antibody as described in any of the preceding items, wherein the anti-PSMA / CD3 bispecific antibody comprises a heavy chain constant region and a light chain constant region. In some embodiments, the anti-PSMA / CD3 bispecific antibody as described in any of the preceding items, wherein the heavy chain constant region is a heavy chain constant region of human IgG1, IgG2, IgG3, IgG4, or a variant thereof. In some embodiments, the heavy chain constant region of the anti-PSMA / CD3 bispecific antibody as described in any of the preceding items comprises an amino acid substitution of F405L or K409R. In some embodiments, the anti-PSMA / CD3 bispecific antibody as described in any of the preceding items, wherein the light chain constant region is a light chain constant region of human lambda, kappa, or a variant thereof. In some embodiments, in the anti-PSMA / CD3 bispecific antibody of any of the preceding items, the second antigen-binding domain that specifically binds to PSMA comprises a heavy chain constant region and a light chain constant region, the heavy chain constant region of the second antigen-binding domain that specifically binds to PSMA comprises the amino acid sequence of SEQ ID NO: 399, and the light chain constant region of the second antigen-binding domain that specifically binds to PSMA comprises the amino acid sequence of SEQ ID NO: 91. In some embodiments, in the anti-PSMA / CD3 bispecific antibody of any of the preceding items, the first antigen-binding domain that specifically binds to CD3 comprises a heavy chain constant region and a light chain constant region, the heavy chain constant region of the first antigen-binding domain that specifically binds to CD3 comprises the amino acid sequence of SEQ ID NO: 120, and the light chain constant region of the first antigen-binding domain that specifically binds to CD3 comprises the amino acid sequence of SEQ ID NO: 91.

[0717] In some embodiments, the anti-PSMA / CD3 bispecific antibody of any of the preceding items, wherein the bispecific antibody comprises:

[0718] (1) a first chain comprising the amino acid sequence of SEQ ID NO: 395, a second chain comprising the amino acid sequence of SEQ ID NO: 396, a third chain comprising the amino acid sequence of SEQ ID NO: 303, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 301; or

[0719] (2) a first chain comprising the amino acid sequence of SEQ ID NO: 395, a second chain comprising the amino acid sequence of SEQ ID NO: 396, a third chain comprising the amino acid sequence of SEQ ID NO: 304, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 301; or

[0720] (3) a first chain comprising the amino acid sequence of SEQ ID NO: 395, a second chain comprising the amino acid sequence of SEQ ID NO: 396, a third chain comprising the amino acid sequence of SEQ ID NO: 305, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 301; or

[0721] (4) a first chain comprising the amino acid sequence of SEQ ID NO: 395, a second chain comprising the amino acid sequence of SEQ ID NO: 396, a third chain comprising the amino acid sequence of SEQ ID NO: 319, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 326; or

[0722] (5) a first chain comprising the amino acid sequence of SEQ ID NO: 395, a second chain comprising the amino acid sequence of SEQ ID NO: 396, a third chain comprising the amino acid sequence of SEQ ID NO: 320, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 323; or

[0723] (6) a first chain comprising the amino acid sequence of SEQ ID NO: 395, a second chain comprising the amino acid sequence of SEQ ID NO: 396, a third chain comprising the amino acid sequence of SEQ ID NO: 320, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 326; or

[0724] (7) a first chain comprising the amino acid sequence of SEQ ID NO: 395, a second chain comprising the amino acid sequence of SEQ ID NO: 396, a third chain comprising the amino acid sequence of SEQ ID NO: 320, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 327; or

[0725] (8) a first chain comprising the amino acid sequence of SEQ ID NO: 395, a second chain comprising the amino acid sequence of SEQ ID NO: 396, a third chain comprising the amino acid sequence of SEQ ID NO: 303, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 181; or

[0726] (9) a first chain comprising the amino acid sequence of SEQ ID NO: 395, a second chain comprising the amino acid sequence of SEQ ID NO: 396, a third chain comprising the amino acid sequence of SEQ ID NO: 319, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 323; or

[0727] (10) a first chain comprising the amino acid sequence of SEQ ID NO: 395, a second chain comprising the amino acid sequence of SEQ ID NO: 396, a third chain comprising the amino acid sequence of SEQ ID NO: 319, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 327; or

[0728] (11) a first chain comprising the amino acid sequence of SEQ ID NO: 395, a second chain comprising the amino acid sequence of SEQ ID NO: 396, a third chain comprising the amino acid sequence of SEQ ID NO: 329, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 181; or

[0729] (12) a first chain comprising the amino acid sequence of SEQ ID NO: 395, a second chain comprising the amino acid sequence of SEQ ID NO: 396, a third chain comprising the amino acid sequence of SEQ ID NO: 330, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 181; or

[0730] (13) a first chain comprising the amino acid sequence of SEQ ID NO: 395, a second chain comprising the amino acid sequence of SEQ ID NO: 396, a third chain comprising the amino acid sequence of SEQ ID NO: 303, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 331; or

[0731] (14) a first chain comprising the amino acid sequence of SEQ ID NO: 395, a second chain comprising the amino acid sequence of SEQ ID NO: 396, a third chain comprising the amino acid sequence of SEQ ID NO: 303, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 332; or

[0732] (15) a first chain comprising the amino acid sequence of SEQ ID NO: 395, a second chain comprising the amino acid sequence of SEQ ID NO: 396, a third chain comprising the amino acid sequence of SEQ ID NO: 303, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 333; or

[0733] (16) A first chain comprising the amino acid sequence of SEQ ID NO: 395, a second chain comprising the amino acid sequence of SEQ ID NO: 396, a third chain comprising the amino acid sequence of SEQ ID NO: 320, and a fourth chain comprising the amino acid sequence of SEQ ID NO: 332.

[0734] In another aspect, the present disclosure provides a pharmaceutical composition comprising a therapeutically effective amount of an anti-CD3 antibody as described in any of the preceding items, or a multispecific antibody as described in any of the preceding items, or an anti-CD20 / CD3 bispecific antibody as described in any of the preceding items, or an anti-BCMA / CD3 bispecific antibody as described in any of the preceding items, or an anti-PSMA / CD3 bispecific antibody as described in any of the preceding items, and one or more pharmaceutically acceptable carriers, diluents, or excipients. In some embodiments, the pharmaceutical composition as described in any of the preceding items is used to activate T cells. In some embodiments, the pharmaceutical composition as described in any of the preceding items is used to treat tumors, autoimmune diseases, or inflammatory diseases.

[0735] In some embodiments, the pharmaceutical composition contains 0.01-99.99% of the anti-CD3 antibody as described in any preceding item, or the multispecific antibody as described in any preceding item, or the anti-CD20 / CD3 bispecific antibody as described in any preceding item, or the anti-BCMA / CD3 bispecific antibody as described in any preceding item, or the anti-PSMA / CD3 bispecific antibody as described in any preceding item, based on the total weight of the composition. In some embodiments, the pharmaceutical composition contains 0.1-99.9% of the anti-CD3 antibody as described in any preceding item, or the anti-CD20 / CD3 bispecific antibody as described in any preceding item, or the anti-BCMA / CD3 bispecific antibody as described in any preceding item, or the anti-PSMA / CD3 bispecific antibody as described in any preceding item. In some embodiments, the pharmaceutical composition comprises 0.5% to 99.5% of the anti-CD3 antibody, or the anti-CD20 / CD3 bispecific antibody, or the anti-BCMA / CD3 bispecific antibody, or the anti-PSMA / CD3 bispecific antibody as described in any of the preceding items. In some embodiments, the pharmaceutical composition comprises 1% to 99% of the anti-CD3 antibody, or the anti-CD20 / CD3 bispecific antibody, or the anti-BCMA / CD3 bispecific antibody, or the anti-PSMA / CD3 bispecific antibody as described in any of the preceding items. In some embodiments, the pharmaceutical composition comprises 2% to 98% of the anti-CD3 antibody, or the anti-CD20 / CD3 bispecific antibody, or the anti-BCMA / CD3 bispecific antibody, or the anti-PSMA / CD3 bispecific antibody as described in any of the preceding items.

[0736] In some embodiments, the pharmaceutical composition contains 0.01% to 99.99% of a pharmaceutically acceptable excipient, based on the total weight of the composition. In some embodiments, the pharmaceutical composition contains 0.1% to 99.9% of a pharmaceutically acceptable excipient. In some embodiments, the pharmaceutical composition contains 0.5% to 99.5% of a pharmaceutically acceptable excipient. In some embodiments, the pharmaceutical composition contains 1% to 99% of a pharmaceutically acceptable excipient. In some embodiments, the pharmaceutical composition contains 2% to 98% of a pharmaceutically acceptable excipient.

[0737] In another aspect, the present disclosure provides an isolated nucleic acid encoding the anti-CD3 antibody of any preceding item, or the multispecific antibody of any preceding item, or the anti-CD20 / CD3 bispecific antibody of any preceding item, or the anti-BCMA / CD3 bispecific antibody of any preceding item, or the anti-PSMA / CD3 bispecific antibody of any preceding item.

[0738] In another aspect, the present disclosure provides a vector comprising the nucleic acid molecule as described in any one of the preceding items.

[0739] In another aspect, the present disclosure provides a host cell comprising the isolated nucleic acid as described in any of the preceding items, or the vector as described in any of the preceding items.

[0740] In another aspect, the present disclosure provides a method for producing the anti-CD3 antibody, or the multispecific antibody, or the anti-CD20 / CD3 bispecific antibody, or the anti-BCMA / CD3 bispecific antibody, or the anti-PSMA / CD3 bispecific antibody of any preceding item, comprising culturing the host cell of any preceding item in a culture medium to form and accumulate the anti-CD3 antibody, or the multispecific antibody, or the anti-CD20 / CD3 bispecific antibody, or the anti-BCMA / CD3 bispecific antibody, or the anti-PSMA / CD3 bispecific antibody of any preceding item, and recovering the antibody, or the multispecific antibody, or the anti-CD20 / CD3 bispecific antibody, or the anti-BCMA / CD3 bispecific antibody, or the anti-PSMA / CD3 bispecific antibody of any preceding item from the culture medium.

[0741] In another aspect, the present disclosure provides an anti-CD3 antibody as described in any of the preceding items, or a multispecific antibody as described in any of the preceding items, or an anti-CD20 / CD3 bispecific antibody as described in any of the preceding items, or an anti-BCMA / CD3 bispecific antibody as described in any of the preceding items, or an anti-PSMA / CD3 bispecific antibody as described in any of the preceding items, or a pharmaceutical composition as described in any of the preceding items, or an isolated nucleic acid molecule as described in any of the preceding items, or a vector as described in any of the preceding items, or a host cell as described in any of the preceding items, as a medicament. In some embodiments, the medicament is a medicament for activating T cells. In some embodiments, the medicament is a medicament for treating, preventing, or ameliorating a disease or condition.

[0742] In another aspect, the present disclosure provides use of the anti-CD3 antibody as described in any preceding item, or the multispecific antibody as described in any preceding item, or the anti-CD20 / CD3 bispecific antibody as described in any preceding item, or the anti-BCMA / CD3 bispecific antibody as described in any preceding item, or the anti-PSMA / CD3 bispecific antibody as described in any preceding item, or the pharmaceutical composition as described in any preceding item, or the isolated nucleic acid molecule as described in any preceding item, or the vector as described in any preceding item, or the host cell as described in any preceding item in the preparation of a medicament for activating T cells.

[0743] In another aspect, the present disclosure provides use of the anti-CD3 antibody as described in any preceding item, or the multispecific antibody as described in any preceding item, or the anti-CD20 / CD3 bispecific antibody as described in any preceding item, or the anti-BCMA / CD3 bispecific antibody as described in any preceding item, or the anti-PSMA / CD3 bispecific antibody as described in any preceding item, or the pharmaceutical composition as described in any preceding item, or the isolated nucleic acid molecule as described in any preceding item, or the vector as described in any preceding item, or the host cell as described in any preceding item in the preparation of a medicament for treating, preventing, or ameliorating a disease or condition.

[0744] In another aspect, the present disclosure provides a method of activating T cells, comprising administering to a subject a therapeutically effective amount of the anti-CD3 antibody as described in any preceding item, or the multispecific antibody as described in any preceding item, or the anti-CD20 / CD3 bispecific antibody as described in any preceding item, or the anti-BCMA / CD3 bispecific antibody as described in any preceding item, or the anti-PSMA / CD3 bispecific antibody as described in any preceding item, or the pharmaceutical composition as described in any preceding item, or the isolated nucleic acid molecule as described in any preceding item, or the vector as described in any preceding item, or the host cell as described in any preceding item. In some embodiments, the method comprises administering to a subject a composition comprising a unit dose of 0.1-3000 mg (more preferably 1-1000 mg) of the multispecific antibody as described in any of the preceding items, or the anti-CD20 / CD3 bispecific antibody as described in any of the preceding items, or the anti-BCMA / CD3 bispecific antibody as described in any of the preceding items, or the anti-PSMA / CD3 bispecific antibody as described in any of the preceding items, or the pharmaceutical composition as described in any of the preceding items, or the isolated nucleic acid molecule as described in any of the preceding items, or the vector as described in any of the preceding items, or the host cell as described in any of the preceding items.

[0745] In another aspect, the present disclosure provides a method for treating, preventing, or ameliorating a disease or condition, comprising administering to a subject a therapeutically, preventively, or amelioratingly effective amount of the anti-CD3 antibody as described in any preceding item, or the multispecific antibody as described in any preceding item, or the anti-CD20 / CD3 bispecific antibody as described in any preceding item, or the anti-BCMA / CD3 bispecific antibody as described in any preceding item, or the anti-PSMA / CD3 bispecific antibody as described in any preceding item, or the pharmaceutical composition as described in any preceding item, or the isolated nucleic acid molecule as described in any preceding item, or the vector as described in any preceding item, or the host cell as described in any preceding item.

[0746] In some embodiments, the method comprises administering to a subject a composition comprising a unit dose of 0.1-3000 mg (more preferably 1-1000 mg) of the anti-CD3 antibody as described in any of the preceding items, or the multispecific antibody as described in any of the preceding items, or the anti-CD20 / CD3 bispecific antibody as described in any of the preceding items, or the anti-BCMA / CD3 bispecific antibody as described in any of the preceding items, or the anti-PSMA / CD3 bispecific antibody as described in any of the preceding items, or the pharmaceutical composition as described in any of the preceding items, or the isolated nucleic acid molecule as described in any of the preceding items, or the vector as described in any of the preceding items, or the host cell as described in any of the preceding items.

[0747] In some embodiments, the disease or disorder is a disease or disorder associated with CD3. In some embodiments, the disease or disorder is a tumor, autoimmune or inflammatory disease.

[0748] In some embodiments, the tumor as described in any of the preceding items is selected from solid tumors (including advanced solid tumors) and hematological tumors. In some embodiments, the tumor as described in any of the preceding items is selected from lymphoma, blastoma, sarcoma, and leukemia. In some embodiments, the tumor as described in any of the preceding items is selected from Hodgkin's lymphoma and non-Hodgkin's lymphoma. More specific examples of the tumor include squamous cell carcinoma, myeloma, small cell lung cancer, non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), glioma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, cutaneous T-cell lymphoma, non-Hodgkin's lymphoma, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), acute myeloid leukemia, chronic lymphocytic leukemia (CLL) (e.g., B-cell chronic lymphocytic leukemia), chronic myeloid leukemia (CML), primary mediastinal large B-cell lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma (MCL), small lymphocytic lymphoma ( SLL), T-cell / histiocyte-rich large B-cell lymphoma, multiple myeloma, myeloid cell leukemia-1 protein (Mcl-1), myelodysplastic syndrome (MDS), gastrointestinal cancer (gastric cancer), kidney cancer, ovarian cancer, liver cancer, lymphoblastic leukemia, lymphocytic leukemia, colorectal cancer (including colon and rectal cancer), endometrial cancer, kidney cancer, prostate cancer, thyroid cancer, melanoma, chondrosarcoma, neuroblastoma, pancreatic cancer, glioblastoma multiforme, stomach cancer, bone cancer, Ewing's sarcoma, cervical cancer, brain cancer, bladder cancer, hepatoma, breast cancer, colon cancer, hepatocellular carcinoma (HCC), clear cell renal cell carcinoma (RCC), head and neck cancer, pharyngeal cancer, hepatobiliary cancer cancer), central nervous system cancer, esophageal cancer, malignant pleural mesothelioma, systemic light chain amyloidosis, lymphoplasmacytic lymphoma, myelodysplastic syndrome, myeloproliferative neoplasms, neuroendocrine tumors, Merkel cell carcinoma, testicular cancer and skin cancer. In some embodiments, the tumor is breast cancer, ovarian cancer, prostate cancer, pancreatic cancer, kidney cancer, lung cancer, liver cancer, stomach cancer, colon cancer, bladder cancer, esophageal cancer, cervical cancer, gallbladder cancer, glioblastoma and melanoma.

[0749] In some embodiments, the autoimmune or inflammatory disease of any of the preceding items is selected from the group consisting of rheumatoid arthritis, psoriasis, psoriasis, psoriatic arthritis, Crohn's disease, ankylosing spondylitis, multiple sclerosis, type 1 diabetes (type 1 insulin-dependent diabetes mellitus), hepatitis (autoimmune hepatitis), myocarditis, Sjogren's syndrome, autoimmune hemolytic anemia following transplant rejection, bullous pemphigoid, Grave's disease, Hashimoto's thyroiditis, systemic lupus erythematosus (SLE), myasthenia gravis, pemphigus, pernicious anemia, inflammatory bowel disease, myasthenia gravis, celiac disease, asthma, allergic rhinitis (seasonal allergic rhinitis), effects from organ transplantation (organ transplant rejection), graft-versus-host disease (GVHD), chronic urticaria, or sepsis.

[0750] The present disclosure provides new anti-CD3 antibodies that can simultaneously bind to the CD3 antigen of humans or crab-eating macaques, and further reduce the T cell recognition epitopes of the anti-CD3 antibodies through modification, providing new therapeutic potential for autoimmune diseases and tumors and other disease areas. The anti-CD3 antibodies disclosed herein can bind to the CD3 antigen of humans or crab-eating macaques, in particular, to human or crab-eating macaque CD3ε and its heterodimers, so primates crab-eating macaques can be selected in preclinical safety and toxicology assessments, which brings convenience to preclinical pharmacology and toxicology studies. The anti-CD3 antibodies disclosed herein have excellent biological activity and can effectively activate the downstream signaling pathways of T cells to exert T cell activity regulation function. In addition, the anti-CD3 antibodies disclosed herein have few T cell recognition epitopes, further reducing the risk of immunogenicity. BRIEF DESCRIPTION OF THE DRAWINGS

[0751] Figure 1A shows the T cell activation effect of CD20 / CD3 dual antibodies CD20-82L2H3, CD20-82L3H3, CD20-82L4H3, CD20-82L8H4 and CD20-82L8H5 in the presence of Jeko-1 cells.

[0752] Figure 1B shows the T cell activation effect of CD20 / CD3 dual antibodies CD20-82L5H1, CD20-82L5H2, CD20-82L5H3 and CD20-82L6H2 in the presence of Jeko-1 cells.

[0753] Figure 1C shows the T cell activation effect of CD20 / CD3 dual antibodies CD20-82L6H3, CD20-82L9H4, CD20-82L10H4, or CD20L10H5 in the presence of Jeko-1 cells.

[0754] Figure 2A shows the killing effects of CD20 / CD3 dual antibodies CD20-82L2H3, CD20-82L3H3, CD20-82L4H3, CD20-82L8H4 and CD20-82L8H5 on Daudi-luc tumor cells.

[0755] Figure 2B shows the killing effect of CD20 / CD3 dual antibodies CD20-82L5H1, CD20-82L5H2, CD20-82L5H3 and CD20-82L6H2 on Daudi-luc tumor cells.

[0756] Figure 2C shows the killing effect of CD20 / CD3 dual antibodies CD20-82L6H3, CD20-82L9H4, CD20-82L10H4 and CD20-82L10H5 on Daudi-luc tumor cells.

[0757] Figure 3A shows the killing effect of BCMA / CD3 dual antibodies BCMA-82L8_S27e P, L94V / H7, BCMA-82L8_S27e P, L94V, T28S / H7_I57T and BCMA-82L8_S27e P, L94V, R29Q / H7_I57T on NCI-H929 tumor cells.

[0758] Figure 3B shows the killing effect of BCMA / CD3 dual antibodies BCMA-82L8_S27e P, L94V, R29Q / H7_N52Q, BCMA-82L8_S27e P, L94V, L27bV, R29Q / H7 and BCMA-82L8_S27e P, L94V / H7_I57T, K58S on NCI-H929 tumor cells.

[0759] Figure 3C shows the killing effect of BCMA / CD3 dual antibodies BCMA-82L8_S27e P, L94V, T28S / H7_N52Q and BCMA-82L8_S27e P, L94V, R29Q / H7_K58S on NCI-H929 tumor cells.

[0760] Figure 3D shows the killing effect of BCMA / CD3 dual antibodies BCMA-82L8_S27e P, L94V, L27b V, T28S / H7, BCMA-82L8_S27e P, L94V / H7_N52Q, I57T and BCMA-82L8_S27e P, L94V / H7_N52Q, K58S on NCI-H929 tumor cells.

[0761] Figure 3E shows the killing effect of BCMA / CD3 dual antibodies BCMA-82L8_S27e P,L94V / H5_I34M, BCMA-82L8_S27e P,F92Y / H5_I34M and BCMA-82L8_S27e E,F92Y / H5_I34M on NCI-H929 tumor cells.

[0762] Figure 3F shows the killing effect of BCMA / CD3 dual antibody BCMA-82L8_S27e P, L94V, R29Q / H7_N52Q, K58S on NCI-H929 tumor cells.

[0763] Figure 4A shows the killing effects of PSMA / CD3 dual antibodies PSMA-82L8_S27e P, L94V / H7, PSMA-82L8_S27e P, L94V, T28S / H7_I57T and PSMA-82L8_S27e P, L94V, R29Q / H7_I57T on LnCAP tumor cells.

[0764] Figure 4B shows the killing effect of PSMA / CD3 dual antibodies PSMA-82L8_S27e P, L94V, R29Q / H7_N52Q and PSMA-82L8_S27e P, L94V / H7_I57T, K58S on LnCAP tumor cells.

[0765] Figure 4C shows the killing effects of PSMA / CD3 dual antibodies PSMA-82L8_S27e P,L94V,R29Q / H7_K58S, PSMA-82L8_S27e P,F92Y / H5_I34M and PSMA-82L8_S27e E,F92Y / H5_I34M on LnCAP tumor cells.

[0766] Figure 4D shows the killing effect of PSMA / CD3 dual antibodies PSMA-82L8_S27e P, L94V / H5_I34M and PSMA-82L8_S27e P, L94V / H7_N52Q, K58S on LnCAP tumor cells.

[0767] Figure 4E shows the killing effect of PSMA / CD3 dual antibodies PSMA-82L8_S27e P, L94V, T28S / H7_N52Q and PSMA-82L8_S27e P, L94V, T28S / H7_K58S on LnCAP tumor cells.

[0768] Figure 4F shows the killing effect of PSMA / CD3 dual antibodies PSMA-82L8_S27e P, L94V, L27b V, R29Q / H7 and PSMA-82L8_S27e P, L94V / H7_N52Q, I57T on LnCAP tumor cells.

[0769] Figure 4G shows the killing effect of PSMA / CD3 dual antibody PSMA-82L8_S27e P, L94V, R29Q / H7_N52Q, K58S on LnCAP tumor cells.

[0770] Figure 4H shows the killing effect of PSMA / CD3 dual antibody PSMA-82L8_S27e P, L94V, L27b V, T28S / H7 on LnCAP tumor cells. DETAILED DESCRIPTION

[0771] the term

[0772] In order to make the present disclosure more easily understood, certain technical and scientific terms are described below. Unless otherwise specifically defined herein, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art.

[0773] As used in the specification and claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0774] Unless the context clearly requires otherwise, in the patent specification and claims, the words "comprising," "having," "including," and the like should be construed in the sense of "including but not limited to," rather than in an exclusive or exhaustive sense.

[0775] The term "and / or" is intended to include both "and" and "or". For example, the phrase "A, B and / or C" is intended to include each of the following: A, B and C; A, B or C; A or C; A or B; B or C; A and C; A and B; B and C; A (alone); B (alone); and C (alone).

[0776] The three letter and one letter codes for amino acids used in this disclosure are as described in J. biol. chem, 243, p3558 (1968).

[0777] The term "CD3" refers to an antigen expressed on T cells as part of a multimolecular T cell receptor (TCR) and composed of a homodimer or heterodimer formed by two of the following four receptor chains: CD3-ε (CD3E or CD3 epsilon), CD3-δ (CD3D), CD3-ζ, and CD3-γ. Human CD3-ε (hCD3ε) comprises the amino acid sequence set forth in UniProtKB / Swiss-Prot: P07766.2. Human CD3-δ (hCD3δ) comprises the amino acid sequence set forth in UniProtKB / Swiss-Prot: P04234.1. Therefore, unless specifically indicated as being from a non-human species, e.g., "mouse CD3," "monkey CD3," etc., the term "CD3" refers to human CD3.

[0778] 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.

[0779] The term "amino acid mutation" includes amino acid substitutions (also known as amino acid replacements), 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 expected that methods other than genetic engineering to alter amino acid side chain groups, such as chemical modification, may also be useful. Various names may be used herein to refer to the same amino acid mutation. Herein, the amino acid residue at a specific site may be indicated using the position+amino acid residue format. For example, 107S indicates that the amino acid residue at site 107 is S. T107S indicates that the amino acid residue at site 107 has mutated from T to S. When a claim specifies the residue at a specific site using the "position+amino acid residue format," the original residue at that site does not limit the scope of protection.

[0780] 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 and antigen-binding fragments (or antigen-binding portions), so long as they exhibit the desired antigen-binding activity.

[0781] The term "natural antibody" refers to naturally occurring immunoglobulin molecules. For example, natural IgG antibodies are heterotetrameric glycoproteins of approximately 150,000 daltons, composed of two identical light chains and two identical heavy chains bound by disulfide bonds. From N to C-terminus, each heavy chain has a variable region (VH), also known as the variable heavy domain, heavy chain variable region, followed by a heavy chain constant region. Natural IgG heavy chain constant regions typically contain three constant domains (CH1, CH2, and CH3). Similarly, from N to C-terminus, each light chain has a variable region (VL), also known as the variable light domain, or light chain variable domain, followed by a constant light domain (light chain constant region, CL).

[0782] The terms "full-length antibody," "intact antibody," and "whole antibody" are used interchangeably herein and refer to an antibody having a structure substantially similar to that of a native antibody or having a heavy chain with an Fc region as defined herein. A native intact antibody light chain comprises a light chain variable region (VL) and a constant region (CL), wherein VL is located at the amino terminus of the light chain and the light chain constant region comprises a kappa chain and a lambda chain; a heavy chain comprises a variable region (VH) and constant regions (CH1, CH2, and CH3), wherein VH is located at the amino terminus of the heavy chain and the constant region is located at the carboxyl terminus, wherein CH3 is closest to the carboxyl terminus of the polypeptide. The heavy chain may be of any isotype, including IgG (including IgG1, IgG2, IgG3, and IgG4 subtypes), IgA (including IgA1 and IgA2 subtypes), IgM, and IgE.

[0783] The term "variable region" or "variable domain" of an antibody refers to the domain of an antibody heavy or light chain involved in antigen binding. Herein, the heavy chain variable region (VH) and light chain variable region (VL) of an antibody each comprise four conserved framework regions (FRs) and three complementarity determining regions (CDRs). The term "complementarity determining region" or "CDR" refers to the region within the variable domain that primarily contributes to antigen binding; "framework" or "FR" refers to the variable domain residues excluding the CDR residues. The VH comprises three CDR regions: HCDR1, HCDR2, and HCDR3; the VL comprises three CDR regions: LCDR1, LCDR2, and LCDR3. Each VH and VL is composed of three CDRs and four FRs, arranged from the amino terminus (also called the N-terminus) to the carboxyl terminus (also called the C-terminus), in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4.

[0784] 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, and is exemplified as shown in Table 1 below.

[0785] Table 1. Relationships between CDR numbering systems

[0786] Unless otherwise indicated, the variable regions and CDRs in the disclosed embodiments are all subject to the "Kabat" numbering convention. Although the Kabat numbering convention is used to define amino acid residues in specific embodiments, corresponding technical solutions using other numbering systems will be considered equivalent technical solutions.

[0787] The term "antibody fragment" refers to a molecule other than an intact antibody that comprises a portion of an intact antibody that binds to the antigen to which the intact antibody binds. Examples of antibody fragments include, but are not limited to, Fv, dsFv, Fab, Fab', Fab'-SH, Fd, F(ab')2, single domain antibodies (sdAbs, such as VH, VL, VHH or V HH ), single-chain Fab (scFab), diabodies, linear antibodies, single-chain antibodies (e.g., scFv, sc(Fv)2); and multispecific antibodies formed from antibody fragments.

[0788] The term "antigen-binding fragment" encompasses full-length antibodies, Fab, modified Fab, Fab', Fab'-SH, modified Fab', F(ab')2, Fv, dsFv, Fab-Fv, Fab-dsFv, Fd, single domain antibodies (sdAb, e.g., VH or VL or VHH), single-chain Fab (scFab), single-chain antibodies (e.g., scFv, sc(Fv)2), diabodies, linear antibodies, bivalent or trivalent or tetravalent antibodies, Bis-scFv, diabody, tribody, triabody, tetrabody and epitope-binding fragments of any of the above (see, e.g., Holliger and Hudson, 2005, Nature Biotech. 23(9): 1126-1136; Adair and Lawson, 2005, Drug Design Reviews-Online 2(3), 209-217). Methods for generating and preparing such antigen-binding fragments are well known in the art (see, eg, Verma et al., 1998, Journal of Immunological Methods, 216, 165-181).

[0789] 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 reconstructed Fc regions. In some embodiments, the Fc region comprises two identical or different subunits. In some embodiments, the Fc region of a human IgG heavy chain is defined as extending from the amino acid residue at position Cys226 or from Pro230 to its carboxyl terminus. Suitable Fc regions for the antibodies described herein include the Fc regions of human IgG1, IgG2 (IgG2A, IgG2B), IgG3, and IgG4. In some embodiments, the boundaries of the Fc region can also vary, such as by deleting the C-terminal lysine in the Fc region (residue 447 according to the EU numbering system) or by deleting the C-terminal glycine and lysine in the Fc region (residues 446 and 447 according to the EU numbering system). Unless otherwise indicated, the numbering convention for the Fc region is the EU numbering system, also known as the EU index.

[0790] 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.

[0791] 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).

[0792] The terms "human antibody," "humanized antibody," "fully human antibody," and "completely human antibody" are used interchangeably to refer to antibodies whose variable and constant regions are human sequences. The term encompasses antibodies that are derived from human genes but have sequence alterations, for example, to reduce potential immunogenicity, increase affinity, or eliminate cysteines or glycosylation sites that may cause undesirable folding. The term encompasses antibodies that are recombinantly produced in non-human cells (which may confer glycosylation that is not characteristic of human cells). The term also encompasses antibodies that have been bred in transgenic mice containing some or all human immunoglobulin heavy and light chain loci. The term "human antibody" specifically excludes humanized antibodies that comprise non-human antigen-binding residues.

[0793] The term "CD3-VH" refers to the heavy chain variable region that specifically binds to the antigen-binding domain of CD3. The term "CD3-VL" refers to the light chain variable region that specifically binds to the antigen-binding domain of CD3. The term "CD3-HCDR1" refers to the HCDR1 of the antigen-binding domain that specifically binds to CD3. The term "CD3-HCDR2" refers to the HCDR2 of the antigen-binding domain that specifically binds to CD3. The term "CD3-HCDR3" refers to the HCDR3 of the antigen-binding domain that specifically binds to CD3. The term "CD3-LCDR1" refers to the LCDR1 of the antigen-binding domain that specifically binds to CD3. The term "CD3-LCDR2" refers to the LCDR2 of the antigen-binding domain that specifically binds to CD3. The term "CD3-LCDR3" refers to the LCDR3 of the antigen-binding domain that specifically binds to CD3.

[0794] The term "CD20-VH" refers to the heavy chain variable region of the antigen-binding domain that specifically binds to CD20. The term "CD20-VL" refers to the light chain variable region of the antigen-binding domain that specifically binds to CD20. The term "CD20-HCDR1" refers to the HCDR1 of the antigen-binding domain that specifically binds to CD20. The term "CD20-HCDR2" refers to the HCDR2 of the antigen-binding domain that specifically binds to CD20. The term "CD20-HCDR3" refers to the HCDR3 of the antigen-binding domain that specifically binds to CD20. The term "CD20-LCDR1" refers to the LCDR1 of the antigen-binding domain that specifically binds to CD20. The term "CD20-LCDR2" refers to the LCDR2 of the antigen-binding domain that specifically binds to CD20. The term "CD20-LCDR3" refers to the LCDR3 of the antigen-binding domain that specifically binds to CD20.

[0795] The term "BCMA-VH" refers to the heavy chain variable region of the antigen-binding domain that specifically binds to BCMA. The term "BCMA-VL" refers to the light chain variable region of the antigen-binding domain that specifically binds to BCMA. The term "BCMA-HCDR1" refers to the HCDR1 of the antigen-binding domain that specifically binds to BCMA. The term "BCMA-HCDR2" refers to the HCDR2 of the antigen-binding domain that specifically binds to BCMA. The term "BCMA-HCDR3" refers to the HCDR3 of the antigen-binding domain that specifically binds to BCMA. The term "BCMA-LCDR1" refers to the LCDR1 of the antigen-binding domain that specifically binds to BCMA. The term "BCMA-LCDR2" refers to the LCDR2 of the antigen-binding domain that specifically binds to BCMA. The term "BCMA-LCDR3" refers to the LCDR3 of the antigen-binding domain that specifically binds to BCMA.

[0796] The term "PSMA-VH" refers to the heavy chain variable region of the antigen-binding domain that specifically binds to PSMA. The term "PSMA-VL" refers to the light chain variable region of the antigen-binding domain that specifically binds to PSMA. The term "PSMA-HCDR1" refers to the HCDR1 of the antigen-binding domain that specifically binds to PSMA. The term "PSMA-HCDR2" refers to the HCDR2 of the antigen-binding domain that specifically binds to PSMA. The term "PSMA-HCDR3" refers to the HCDR3 of the antigen-binding domain that specifically binds to PSMA. The term "PSMA-LCDR1" refers to the LCDR1 of the antigen-binding domain that specifically binds to PSMA. The term "PSMA-LCDR2" refers to the LCDR2 of the antigen-binding domain that specifically binds to PSMA. The term "PSMA-LCDR3" refers to the LCDR3 of the antigen-binding domain that specifically binds to PSMA.

[0797] The term "affinity" refers to the overall strength of the non-covalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding ligand (e.g., an antigen). Unless otherwise indicated, as used herein, binding "affinity" refers to internal binding affinity, which reflects a 1:1 interaction between members of a binding pair (e.g., an antibody and an antigen). The affinity of a molecule X for its ligand Y can generally be represented by a dissociation constant (KD). Affinity can be measured by conventional methods known in the art, including those described herein.

[0798] As used herein, the term "kassoc" or "ka" refers to the association rate of a specific antibody-antigen interaction, and the term "kdis" or "kd" refers to the dissociation rate of a specific antibody-antigen interaction. The term "KD" refers to the dissociation constant, which is obtained 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 well known in the art. For example, a biosensor system such as a system measuring surface plasmon resonance (e.g., Biacore) is used, or affinity in a solution is measured by solution equilibrium titration (SET).

[0799] The term "surface plasmon resonance" refers to an optical phenomenon that allows analysis of real-time interactions by detecting changes in protein concentration within a biosensor matrix, for example, using a BIAcore™ system (Biacore LifeSciences division of GE Healthcare, Piscataway, NJ).

[0800] The term "effector function" refers to those biological activities attributable to the Fc region of an antibody (either a native sequence Fc region or an amino acid sequence mutated Fc region) and varies with the antibody isotype. Examples of antibody effector functions include, but are not limited to, C1q binding and complement-dependent cytotoxicity, Fc receptor binding, antibody-dependent cell-mediated cytotoxicity (ADCC), phagocytosis, downregulation of cell surface receptors (e.g., B cell receptors), and B cell activation.

[0801] 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 the natural mutations that may be present in small amounts. In contrast, polyclonal antibody preparations are typically comprised of a variety of different antibodies with different amino acid sequences in their variable domains, which are typically specific for different epitopes. "Monoclonal" represents the characteristic of an antibody obtained from a substantially homogeneous antibody population, and should not be interpreted as requiring the production of antibodies by any ad hoc method. In some embodiments, the antibody provided by the present disclosure is a monoclonal antibody.

[0802] The term "antigen" refers to a molecule or portion of a molecule that can be bound by a selective binding agent such as an antigen binding protein (including, for example, an antibody) and that can additionally be used in an animal to produce antibodies that can bind to the antigen. An antigen may have one or more epitopes that can interact with different antigen binding proteins (e.g., antibodies).

[0803] The term "epitope" refers to an area or region on an antigen that is capable of specific binding to an antibody or antigen-binding fragment thereof. An epitope can be formed by a continuous string of amino acids (linear epitope) or comprise non-contiguous amino acids (conformational epitope), for example, brought into spatial proximity by folding of the antigen (i.e., by tertiary folding of a proteinaceous antigen). Conformational epitopes differ from linear epitopes in that antibody binding to a 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 specific 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, peptide cleavage analysis, epitope excision, epitope extraction, chemical modification of the antigen (see Prot. Sci. 9 (2000) 487-496), and cross-blocking.

[0804] The term "capable of specific binding," "specific binding," or "binding" means that an antibody is capable of binding to an antigen or an epitope of the antigen with a higher affinity than to other antigens or epitopes. In some embodiments, the KD of an antibody binding to an antigen is 10% or less (e.g., 1%) of the KD of the antibody binding to a nonspecific antigen (e.g., BSA, casein). KD can be measured using known methods, for example, by However, an antibody that specifically binds to an antigen or an epitope within an antigen 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).

[0805] The term "does not bind" means that the antibody is unable to bind to a certain antigen or an epitope thereof in the manner of specific binding as described above.

[0806] The terms "anti-CD3 antibody" and "CD3-binding antibody" refer to an antibody that is capable of binding to CD3 with sufficient affinity.

[0807] The term "antibody-dependent cellular cytotoxicity," "antibody-dependent cell-mediated cytotoxicity," or "ADCC" is a mechanism of inducing cell death that relies on the interaction of antibody-coated target cells with effector cells with lytic activity (such as natural killer cells (NK), monocytes, macrophages, and neutrophils) via Fc gamma receptors (Fc gamma R) expressed on effector cells. For example, NK cells express Fc gamma RIIIa, while monocytes express Fc gamma RI, Fc gamma RII, and Fc gamma RIIIa. The ADCC activity of the antibodies provided herein can be assessed using in vitro assays using antigen-expressing cells as target cells and NK cells as effector cells. Cell lysis is detected based on markers released from the lysed cells (e.g., radioactive substrates, fluorescent dyes, or native intracellular proteins).

[0808] The term "antibody-dependent cellular phagocytosis (ADCP)" refers to a mechanism by which antibody-coated target cells are eliminated by internalization by phagocytes, such as macrophages or dendritic cells.

[0809] The term "complement-dependent cytotoxicity" or "CDC" refers to a mechanism of cell death induction in which the Fc effector domain of a target-bound antibody binds to and activates the complement component C1q, which in turn activates the complement cascade, leading to target cell death. Activation of complement can also result in the deposition of complement components on the surface of target cells, which promote CDC by binding to complement receptors (e.g., CR3) on leukocytes.

[0810] 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 nucleic acids containing known nucleotide analogs or modified backbone residues or connections, 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. Examples of such analogs include, but are not limited to, phosphorothioates, phosphoramidates, methylphosphonates, chiral-methylphosphonates, 2-O-methyl ribonucleotides, peptide-nucleic acids (PNAs). "Isolated" nucleic acid refers to a nucleic acid molecule separated from the components 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 isolated nucleic acid encoding a polypeptide or fusion protein refers to one or more nucleic acid molecules encoding a polypeptide or fusion protein, 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 mixed bases and / or deoxyinosine residues.

[0811] 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 corresponding 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.

[0812] The term sequence "identity" refers to the degree (percentage) to which the amino acids / nucleic acids of the two sequences are identical at equivalent positions when two sequences are optimally aligned, introducing gaps when necessary, to obtain maximum sequence identity percentage, and not considering any conservative substitutions as part of 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 achieving maximum alignment over the full length of the compared sequences.

[0813] 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. Some vectors can replicate autonomously (for example, bacterial vectors and additional mammalian vectors with bacterial replication origins) in the host cell in which they are introduced. 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 that can transform a host cell and contains a nucleic acid sequence for the expression of one or more heterologous coding regions that are operably connected thereto, including guidance and / or control (together with the host cell). Expression constructs can include but are not limited to affecting or controlling transcription, translation and affecting the sequence of RNA splicing of the coding region operably connected thereto when there are introns.

[0814] The terms "host cell," "host cell line," and "host cell culture" are used interchangeably and refer to cells into which exogenous nucleic acids have been introduced, including the offspring of such cells. Host cells include "transformants" and "transformed cells," which include primary transformed cells and offspring derived therefrom, without regard to the number of passages. Offspring may not be identical to the parent cell in nucleic acid content, but may contain mutations. Mutant offspring having the same function or biological activity as screened or selected in the initial transformed cells are included herein. 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 humans, mice, rats, dogs, monkeys, pigs, goats, cattle, horses, 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, Kluyveromyces lactis, Candida albicans, Aspergillus, Aspergillus nidulans, Aspergillus niger, Aspergillus oryzae, Trichoderma reesei, Chrysosporium lucknowense, Fusarium sp., Fusarium gramineum, Fusarium venenatum, Physcomitrella patens, and Neurospora crassa.

[0815] As used in this application, the expressions "cell," "cell line," and "cell culture" are used interchangeably, and all such designations include progeny. Thus, the terms "transformants" and "transformed cells" include the primary subject cell and cultures derived therefrom, regardless of the number of passages. It is also understood that not all progeny have exactly the same DNA content, due to intentional or unintentional mutations. Mutant progeny that have the same function or biological activity as the original transformed cell are included.

[0816] "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.

[0817] The term "pharmaceutical composition" refers to a mixture containing one or more anti-CD3 antibodies described herein with other chemical components, such as physiologically / pharmaceutically acceptable carriers and excipients.

[0818] The term "pharmaceutically acceptable carrier" refers to a component of a pharmaceutical formulation that is different from the active ingredient and is non-toxic to the subject. Pharmaceutically acceptable carriers include, but are not limited to, buffers, excipients, stabilizers, or preservatives.

[0819] 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, sheep, dogs, cows, chickens, amphibians and reptiles. Unless otherwise indicated, the terms "patient" or "subject" are used interchangeably herein. In certain embodiments, the individual or subject is a human.

[0820] "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.

[0821] 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.

[0822] "Treatment" and "treatment" (and grammatical variations thereof) refer to clinical interventions that attempt to alter the natural course of the individual being treated, and can be performed for prevention or during the course of clinical pathology. Desired effects of treatment include, but are not limited to, preventing the occurrence or recurrence of 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 regression or improved prognosis. In some embodiments, the antibodies of the present disclosure are used to delay the development of a disease or slow the progression of a disease.

[0823] 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.

[0824] The term "refractory" or "resistant" refers to a cancer or disease that does not respond to treatment.

[0825] "Effective amount" is generally enough to reduce the severity and / or frequency of symptoms, eliminate these symptoms and / or potential causes, prevent symptoms and / or their potential causes from occurring and / or improve or ameliorate the damage (e.g., lung disease) caused by or associated with the disease state. In some embodiments, an effective amount is a therapeutically effective amount or a prophylactic effective amount. A "therapeutically effective amount" is enough to treat a disease state or symptom, particularly a state or symptom associated with the disease state, or otherwise prevent, hinder, delay or reverse the disease state or any other undesirable symptom associated with the disease in any way. A "prophylactic effective amount" is an amount that will have a predetermined preventive effect when administered to a subject, 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 treatment or prophylactic 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 doses. A "therapeutically effective amount" and a "prophylactically effective amount" can vary depending on 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 patient.

[0826] Anti-CD3 antibodies of the present disclosure

[0827] The present disclosure provides anti-CD3 antibodies that have many favorable properties, such as in vitro T cell activation ability, killing ability, good therapeutic activity, safety, pharmacokinetic properties and drugability (such as solubility, viscosity, purity and stability, etc.).

[0828] Exemplary anti-CD3 antibodies

[0829] The embodiments disclosed herein disclose antibody series 82#, 12#, 8#, 21#, 29#, 31#, 57#, 61#, 63#, 80#, 89#, 92-2#, 93#, 96#, 103#, 104#, 105#, and 106#. The antibodies disclosed herein are described below using antibody 82# as an example.

[0830] Exemplarily, the anti-CD3 antibody of the present disclosure comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3, wherein:

[0831] The amino acid sequence of HCDR1 of the heavy chain variable region is shown in SEQ ID NO: 343, the amino acid sequence of HCDR2 is shown in SEQ ID NO: 344, and the amino acid sequence of HCDR3 is shown in SEQ ID NO: 345, and the amino acid sequence of LCDR of the light chain variable region is shown in SEQ ID NO: 346, the amino acid sequence of LCDR2 is shown in SEQ ID NO: 347, and the amino acid sequence of LCDR3 is shown in SEQ ID NO: 348, wherein:

[0832] HCDR1:SX1YX2H SEQ ID NO:343

[0833] HCDR2: WIX3PGX4X5X6X7X8YNEKFKG SEQ ID NO: 344

[0834] HCDR3: DGYSYYYFDX9 SEQ ID NO: 345

[0835] LCDR1:X 10 SSQSX 11 LX 12 X 13 RX 14 X 15 X 16 NYLA SEQ ID NO: 346

[0836] LCDR2:X 17 ASTRES SEQ ID NO: 347

[0837] LCDR3:KQX 18 X 19 IX 20 RT SEQ ID NO: 348

[0838] wherein X1 is selected from Y, E, K and Q, preferably Y; X2 is selected from M, I, E, N and Q, preferably M; X3 is selected from N, Q and S, preferably N or Q; X4 is selected from E and D, preferably E; X5 is selected from G and D, preferably G; X6 is selected from S and A, preferably S; X7 is selected from I and T; X8 is selected from K and S; X9 is selected from F and Y, preferably F; X 10 Selected from K and T, preferably K; X 11 Selected from L and V; X 12 Selected from N and Q, preferably N; X 13 is selected from E, P, S, D, K, Q, R and W, preferably E or P; X 14 Selected from T and S; X 15 Selected from R and Q; X 16 Selected from K and Q, preferably K; X 17 Selected from W and Y, preferably W; X 18 Selected from S and N, preferably S; X 19 Selected from F and Y; X 20 Selected from L, V and I, preferably L or V.

[0839] Exemplarily, the anti-CD3 antibody of the present disclosure, wherein:

[0840] the amino acid sequence of HCDR1 of the heavy chain variable region is shown in SEQ ID NO:137, the amino acid sequence of HCDR2 is shown in SEQ ID NO:403, and the amino acid sequence of HCDR3 is shown in SEQ ID NO:36, and the amino acid sequence of LCDR1 of the light chain variable region is shown in SEQ ID NO:404, the amino acid sequence of LCDR2 is shown in SEQ ID NO:2, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:405;

[0841] in:

[0842] HCDR2:WIX 25 PGEGSX 26 X 27 YNEKFKG SEQ ID NO: 403

[0843] LCDR1:KSSQSX 28 LNX 29 RX 30 X 31 KNYLA SEQ ID NO: 404

[0844] LCDR3:KQSX 32 IX 33RT SEQ ID NO: 405

[0845] Among them, X 25 Selected from N and Q; X 26 Selected from I and T; X 27 Selected from K and S; X 28 Selected from L and V; X 29 Selected from P and E; X 30 Selected from T and S; X 31 Selected from R and Q; X 32 Selected from F and Y; X 33 Selected from V and L.

[0846] In some embodiments, the anti-CD3 antibody as described above, wherein:

[0847] (1) When X 25 N, X 26 I, X 27 When K, X 28 L, X 29 P, X 30 T, X 31 R, X 32 F, X 33 is V; or

[0848] (2) When X 25 N, X 26 I, X 27 When K, X 28 L, X 29 P, X 30 T, X 31 R, X 32 Y, X 33 is L; or

[0849] (3) When X 25 N, X 26 I, X 27 When K, X 28 L, X 29 For E, X 30 T, X 31 R, X 32 Y, X 33 is L; or

[0850] (4) When X 25 N, X 26 T, X 27 When K, X 28 L, X 29 P, X 30 S, X31 R, X 32 F, X 33 is V; or

[0851] (5) When X 25 Q, X 26 I, X 27 When K, X 28 L, X 29 P, X 30 T, X 31 Q, X 32 F, X 33 is V; or

[0852] (6) When X 25 N, X 26 T, X 27 When K, X 28 L, X 29 P, X 30 T, X 31 Q, X 32 F, X 33 is V; or

[0853] (7) When X 25 N, X 26 I, X 27 When S, X 28 L, X 29 P, X 30 T, X 31 Q, X 32 F, X 33 is V; or

[0854] (8) When X 25 Q, X 26 I, X 27 When K, X 28 L, X 29 P, X 30 S, X 31 R, X 32 F, X 33 is V; or

[0855] (9) When X 25 N, X 26 I, X 27 When S, X 28 L, X 29 P, X 30 S, X 31 R, X 32 F, X 33 is V; or

[0856] (10) When X 25 N, X 26 I, X 27 When K, X 28 V, X 29 P, X 30 S, X 31 R, X 32 F, X 33 is V; or

[0857] (11) When X 25 N, X 26 I, X 27 When K, X 28 V, X 29 P, X 30 T, X 31 Q, X 32 F, X 33 is V; or

[0858] (12) When X 25 Q, X 26 T, X 27 When K, X 28 L, X 29 P, X 30 T, X 31 R, X 32 F, X 33 is V; or

[0859] (13) When X 25 Q, X 26 I, X 27 When S, X 28 L, X 29 P, X 30 T, X 31 R, X 32 F, X 33 is V; or

[0860] (14) When X 25 N, X 26 T, X 27 When S, X 28 L, X 29 P, X 30 T, X 31 R, X 32 F, X 33 is V; or

[0861] (15) When X 25 Q, X 26 I, X 27 When S, X 28V, X 29 P, X 30 T, X 31 R, X 32 F, X 33 is V; or

[0862] (16) When X 25 Q, X 26 I, X 27 When S, X 28 L, X 29 P, X 30 S, X 31 R, X 32 F, X 33 is V; or

[0863] (17) When X 25 Q, X 26 I, X 27 When S, X 28 L, X 29 P, X 30 T, X 31 Q, X 32 F, X 33 is V.

[0864] Exemplarily, the anti-CD3 antibody of the present disclosure comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3, wherein:

[0865] (1) the amino acid sequence of HCDR1 of the heavy chain variable region is shown in SEQ ID NO: 137, the amino acid sequence of HCDR2 is shown in SEQ ID NO: 138, and the amino acid sequence of HCDR3 is shown in SEQ ID NO: 36, and the amino acid sequence of LCDR1 of the light chain variable region is shown in SEQ ID NO: 189, the amino acid sequence of LCDR2 is shown in SEQ ID NO: 2, and the amino acid sequence of LCDR3 is shown in SEQ ID NO: 185; or

[0866] (2) the amino acid sequence of HCDR1 of the heavy chain variable region is shown in SEQ ID NO: 137, the amino acid sequence of HCDR2 is shown in SEQ ID NO: 138, and the amino acid sequence of HCDR3 is shown in SEQ ID NO: 36, and the amino acid sequence of LCDR1 of the light chain variable region is shown in SEQ ID NO: 189, the amino acid sequence of LCDR2 is shown in SEQ ID NO: 2, and the amino acid sequence of LCDR3 is shown in SEQ ID NO: 183; or

[0867] (3) the amino acid sequence of HCDR1 of the heavy chain variable region is set forth in SEQ ID NO: 137, the amino acid sequence of HCDR2 is set forth in SEQ ID NO: 138, and the amino acid sequence of HCDR3 is set forth in SEQ ID NO: 36, and the amino acid sequence of LCDR1 of the light chain variable region is set forth in SEQ ID NO: 187, the amino acid sequence of LCDR2 is set forth in SEQ ID NO: 2, and the amino acid sequence of LCDR3 is set forth in SEQ ID NO: 183; or

[0868] (4) the amino acid sequence of HCDR1 of the heavy chain variable region is set forth in SEQ ID NO: 137, the amino acid sequence of HCDR2 is set forth in SEQ ID NO: 217, and the amino acid sequence of HCDR3 is set forth in SEQ ID NO: 36, and the amino acid sequence of LCDR1 of the light chain variable region is set forth in SEQ ID NO: 207, the amino acid sequence of LCDR2 is set forth in SEQ ID NO: 2, and the amino acid sequence of LCDR3 is set forth in SEQ ID NO: 185; or

[0869] (5) the amino acid sequence of HCDR1 of the heavy chain variable region is shown in SEQ ID NO: 137, the amino acid sequence of HCDR2 is shown in SEQ ID NO: 214, and the amino acid sequence of HCDR3 is shown in SEQ ID NO: 36, and the amino acid sequence of LCDR1 of the light chain variable region is shown in SEQ ID NO: 208, the amino acid sequence of LCDR2 is shown in SEQ ID NO: 2, and the amino acid sequence of LCDR3 is shown in SEQ ID NO: 185; or

[0870] (6) the amino acid sequence of HCDR1 of the heavy chain variable region is shown in SEQ ID NO: 137, the amino acid sequence of HCDR2 is shown in SEQ ID NO: 217, and the amino acid sequence of HCDR3 is shown in SEQ ID NO: 36, and the amino acid sequence of LCDR1 of the light chain variable region is shown in SEQ ID NO: 208, the amino acid sequence of LCDR2 is shown in SEQ ID NO: 2, and the amino acid sequence of LCDR3 is shown in SEQ ID NO: 185; or

[0871] (7) the amino acid sequence of HCDR1 of the heavy chain variable region is shown in SEQ ID NO: 137, the amino acid sequence of HCDR2 is shown in SEQ ID NO: 218, and the amino acid sequence of HCDR3 is shown in SEQ ID NO: 36, and the amino acid sequence of LCDR1 of the light chain variable region is shown in SEQ ID NO: 208, the amino acid sequence of LCDR2 is shown in SEQ ID NO: 2, and the amino acid sequence of LCDR3 is shown in SEQ ID NO: 185; or

[0872] (8) the amino acid sequence of HCDR1 of the heavy chain variable region is shown in SEQ ID NO: 137, the amino acid sequence of HCDR2 is shown in SEQ ID NO: 214, and the amino acid sequence of HCDR3 is shown in SEQ ID NO: 36, and the amino acid sequence of LCDR1 of the light chain variable region is shown in SEQ ID NO: 207, the amino acid sequence of LCDR2 is shown in SEQ ID NO: 2, and the amino acid sequence of LCDR3 is shown in SEQ ID NO: 185; or

[0873] (9) the amino acid sequence of HCDR1 of the heavy chain variable region is shown in SEQ ID NO: 137, the amino acid sequence of HCDR2 is shown in SEQ ID NO: 218, and the amino acid sequence of HCDR3 is shown in SEQ ID NO: 36, and the amino acid sequence of LCDR1 of the light chain variable region is shown in SEQ ID NO: 207, the amino acid sequence of LCDR2 is shown in SEQ ID NO: 2, and the amino acid sequence of LCDR3 is shown in SEQ ID NO: 185; or

[0874] (10) the amino acid sequence of HCDR1 of the heavy chain variable region is shown in SEQ ID NO: 137, the amino acid sequence of HCDR2 is shown in SEQ ID NO: 138, and the amino acid sequence of HCDR3 is shown in SEQ ID NO: 36, and the amino acid sequence of LCDR1 of the light chain variable region is shown in SEQ ID NO: 210, the amino acid sequence of LCDR2 is shown in SEQ ID NO: 2, and the amino acid sequence of LCDR3 is shown in SEQ ID NO: 185; or

[0875] (11) the amino acid sequence of HCDR1 of the heavy chain variable region is shown in SEQ ID NO: 137, the amino acid sequence of HCDR2 is shown in SEQ ID NO: 138, and the amino acid sequence of HCDR3 is shown in SEQ ID NO: 36, and the amino acid sequence of LCDR1 of the light chain variable region is shown in SEQ ID NO: 211, the amino acid sequence of LCDR2 is shown in SEQ ID NO: 2, and the amino acid sequence of LCDR3 is shown in SEQ ID NO: 185; or

[0876] (12) the amino acid sequence of HCDR1 of the heavy chain variable region is shown in SEQ ID NO: 137, the amino acid sequence of HCDR2 is shown in SEQ ID NO: 219, and the amino acid sequence of HCDR3 is shown in SEQ ID NO: 36, and the amino acid sequence of LCDR1 of the light chain variable region is shown in SEQ ID NO: 189, the amino acid sequence of LCDR2 is shown in SEQ ID NO: 2, and the amino acid sequence of LCDR3 is shown in SEQ ID NO: 185; or

[0877] (13) the amino acid sequence of HCDR1 of the heavy chain variable region is shown in SEQ ID NO: 137, the amino acid sequence of HCDR2 is shown in SEQ ID NO: 220, and the amino acid sequence of HCDR3 is shown in SEQ ID NO: 36, and the amino acid sequence of LCDR1 of the light chain variable region is shown in SEQ ID NO: 189, the amino acid sequence of LCDR2 is shown in SEQ ID NO: 2, and the amino acid sequence of LCDR3 is shown in SEQ ID NO: 185; or

[0878] (14) the amino acid sequence of HCDR1 of the heavy chain variable region is shown in SEQ ID NO: 137, the amino acid sequence of HCDR2 is shown in SEQ ID NO: 221, and the amino acid sequence of HCDR3 is shown in SEQ ID NO: 36, and the amino acid sequence of LCDR1 of the light chain variable region is shown in SEQ ID NO: 189, the amino acid sequence of LCDR2 is shown in SEQ ID NO: 2, and the amino acid sequence of LCDR3 is shown in SEQ ID NO: 185; or

[0879] (15) the amino acid sequence of HCDR1 of the heavy chain variable region is shown in SEQ ID NO: 137, the amino acid sequence of HCDR2 is shown in SEQ ID NO: 220, and the amino acid sequence of HCDR3 is shown in SEQ ID NO: 36, and the amino acid sequence of LCDR1 of the light chain variable region is shown in SEQ ID NO: 206, the amino acid sequence of LCDR2 is shown in SEQ ID NO: 2, and the amino acid sequence of LCDR3 is shown in SEQ ID NO: 185; or

[0880] (16) the amino acid sequence of HCDR1 of the heavy chain variable region is shown in SEQ ID NO: 137, the amino acid sequence of HCDR2 is shown in SEQ ID NO: 220, and the amino acid sequence of HCDR3 is shown in SEQ ID NO: 36, and the amino acid sequence of LCDR1 of the light chain variable region is shown in SEQ ID NO: 207, the amino acid sequence of LCDR2 is shown in SEQ ID NO: 2, and the amino acid sequence of LCDR3 is shown in SEQ ID NO: 185; or

[0881] (17) The amino acid sequence of HCDR1 of the heavy chain variable region is shown in SEQ ID NO: 137, the amino acid sequence of HCDR2 is shown in SEQ ID NO: 220, and the amino acid sequence of HCDR3 is shown in SEQ ID NO: 36, and the amino acid sequence of LCDR1 of the light chain variable region is shown in SEQ ID NO: 208, the amino acid sequence of LCDR2 is shown in SEQ ID NO: 2, and the amino acid sequence of LCDR3 is shown in SEQ ID NO: 185.

[0882] Exemplarily, for the anti-CD3 antibodies disclosed herein, the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region and the LCDR1, LCDR2 and LCDR3 of the light chain variable region are defined according to the Kabat numbering convention.

[0883] Illustratively, the anti-CD3 antibody of the present disclosure, wherein the anti-CD3 antibody is a murine antibody, a chimeric antibody, a humanized antibody, or a fully human antibody. In some embodiments, the anti-CD3 antibody is a chimeric antibody. In some embodiments, the anti-CD3 antibody is a humanized antibody.

[0884] Exemplarily, the anti-CD3 antibody of the present disclosure comprises a heavy chain variable region and a light chain variable region, wherein:

[0885] (1) the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: 255, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO: 236; or

[0886] The amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: 157, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO: 236; or

[0887] (2) the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: 255, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO: 237; or

[0888] (3) the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: 255, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO: 238; or

[0889] (4) the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: 278, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO: 268; or

[0890] (5) the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: 275, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO: 269; or

[0891] (6) the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: 278, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO: 269; or

[0892] (7) the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: 279, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO: 269; or

[0893] (8) the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: 275, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO: 268; or

[0894] (9) the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: 279, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO: 268; or

[0895] (10) the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: 157, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO: 271; or

[0896] (11) the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: 157, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO: 272; or

[0897] (12) the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: 281, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO: 236; or

[0898] (13) the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: 282, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO: 236; or

[0899] (14) the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: 283, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO: 236; or

[0900] (15) the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: 282, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO: 267; or

[0901] (16) the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: 282, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO: 268; or

[0902] (17) The amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: 282, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO: 269.

[0903] Illustratively, the anti-CD3 antibody disclosed herein is an antigen-binding fragment; in some embodiments, the antigen-binding fragment is selected from Fab, Fab′, F(ab′)2, Fd, Fv, scFv, dsFv or dAb.

[0904] Illustratively, the anti-CD3 antibodies of the present disclosure comprise a heavy chain constant region and a light chain constant region. In some embodiments, the heavy chain constant region is a human IgG1 heavy chain constant region or a variant thereof. In some embodiments, the light chain constant region is a human kappa light chain constant region or a variant thereof. In some embodiments, the heavy chain constant region compri...

Claims

1. An anti-CD3 antibody comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3, wherein: a. the HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 343, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 344, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 345, and the LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 346, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 347, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 348; or b. the HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 8, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 400, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 401, and the LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 402, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 7; Preferably, a. the HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 403, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and the LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 404, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 405; or The HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, 34, 193, 194, 195, 196, 197 or 199, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, 217, 214, 218, 219, 220, 221, 35, 38, 215 or 216, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 36 or 43, and the LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 189, 187, 207, 208, 210, 211, 206, 1, 96, 186, 188, 190, 191, 192, 205, 209 or 212, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2 or 136, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 36 or 43. The amino acid sequence of NO: 185, 183, 17, 182 or 184; or b. the HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 8, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 9, 97, 98 or 100, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 10 or 99, and the LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 1 or 96, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 7; More preferably, the HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, 214, 217, 218, 219, 220 or 221, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and the LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 189, 187, 206, 207, 208, 210 or 211, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185 or 183; Most preferably, 1) the HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and the LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 189, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or 2) the HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and the LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 189, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 183; or 3) the HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and the LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 187, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 183; or 4) HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 217, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 207, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or 5) the HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 214, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and the LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 208, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or 6) the HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 217, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and the LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 208, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or 7) the HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 218, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and the LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 208, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or 8) the HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 214, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and the LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 207, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or 9) the HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 218, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and the LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 207, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or 10) the HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and the LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 210, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or 11) the HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 138, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and the LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 211, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or 12) the HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 219, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and the LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 189, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or 13) the HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 220, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and the LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 189, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or 14) the HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 221, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and the LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 189, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or 15) the HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 220, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and the LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 206, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or 16) the HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 220, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and the LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 207, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 185; or 17) The HCDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 137, HCDR2 comprises the amino acid sequence of SEQ ID NO: 220, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 36, and the LCDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO: 208, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and LCDR3 comprises the amino acid sequence of SEQ ID NO:

185.

2. The anti-CD3 antibody according to claim 1, which is a murine antibody, a chimeric antibody, a humanized antibody or a fully human antibody; preferably a humanized antibody.

3. The anti-CD3 antibody according to claim 1 or 2, wherein: a. the heavy chain variable region comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 255, 278, 279, 275, 157, 281, 282, 283, 150, 151, 152, 153, 154, 155, 156, 158, 159, 160, 161, 162, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 274, 276, 277, 280, 349, 356, 357, 358, 359, 360, 361 or 362, and the light chain variable region comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO: or an amino acid sequence having at least 80% sequence identity to any of the following: NO: 236, 237, 238, 268, 269, 271, 272, 267, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 239, 240, 241, 242, 243, 244, 266, 270, or 273; or The heavy chain variable region comprises an amino acid sequence that has at least 80% sequence identity to SEQ ID NO:75, and the light chain variable region comprises an amino acid sequence that has at least 80% sequence identity to SEQ ID NO:74; or b. the heavy chain variable region comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118 or 119, and the light chain variable region comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 101, 102, 103, 104, 105, 106 or 107; or the heavy chain variable region comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 60, and the light chain variable region comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 59; Preferably, a. the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 255, 278, 279, 275, 157, 281, 282, 283, 150, 151, 152, 153, 154, 155, 156, 158, 159, 160, 161, 162, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 274, 276, 277, 280, 349, 356, 357, 358, 359, 360, 361 or 362, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: The amino acid sequence of NO: 236, 237, 238, 268, 269, 271, 272, 267, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 239, 240, 241, 242, 243, 244, 266, 270 or 273; or The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 75, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 74; or b. the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118 or 119, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 101, 102, 103, 104, 105, 106 or 107; or the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 60, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 59; More preferably, 1) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 255, 157, 156, 158, 161, 162, 349, 356 or 274, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or 2) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 255, 157, 156, 158, 161, 162, 349, 356 or 274, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 237; or 3) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 255, 157, 156, 158, 161, 162, 349, 356 or 274, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 238; or 4) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 278 or 357, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 268; or 5) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 275 or 358, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 269; or 6) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 278 or 357, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 269; or 7) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 279 or 359, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 269; or 8) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 275 or 358, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 268; or 9) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 279 or 359, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 268; or 10) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 157, 255, 156, 158, 161, 162, 349, 356 or 274, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 271; or 11) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 157, 255, 156, 158, 161, 162, 349, 356 or 274, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 272; or 12) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 281 or 360, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or 13) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 282 or 361, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or 14) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 283, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or 15) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 282 or 361, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 267; or 16) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 282 or 361, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 268; or 17) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 282 or 361, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 269; Most preferably, 1) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 255, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 157, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or 2) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 255, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 237; or 3) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 255, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 238; or 4) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 278, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 268; or 5) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 275, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 269; or 6) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 278, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 269; or 7) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 279, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 269; or 8) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 275, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 268; or 9) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 279, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 268; or 10) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 157, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 271; or 11) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 157, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 272; or 12) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 281, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or 13) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 282, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or 14) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 283, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 236; or 15) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 282, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 267; or 16) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 282, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 268; or 17) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 282, and the light chain variable region comprises the amino acid sequence of SEQ ID NO:

269.

4. The anti-CD3 antibody according to any one of claims 1 to 3, wherein the anti-CD3 antibody is an antigen binding fragment; preferably, wherein the antigen binding fragment is Fab, Fab', F(ab')2, Fd, Fv, scFv, dsFv or dAb.

5. The anti-CD3 antibody according to any one of claims 1 to 3, wherein the anti-CD3 antibody comprises a heavy chain constant region and a light chain constant region; Preferably, the heavy chain constant region is a heavy chain constant region of human IgG1, IgG2, IgG3, IgG4 or a variant thereof, and the light chain constant region is a light chain constant region of human kappa, lambda or a variant thereof; Further preferably, the heavy chain constant region is a human IgG1 heavy chain constant region or a variant thereof, and the light chain constant region is a human kappa light chain constant region or a variant thereof; More preferably, the heavy chain constant region comprises the amino acid sequence of SEQ ID NO: 120, 90, 339 or 399, and the light chain constant region comprises the amino acid sequence of SEQ ID NO: 91 or 384; Most preferably, the heavy chain constant region comprises the amino acid sequence of SEQ ID NO:120, and the light chain constant region comprises the amino acid sequence of SEQ ID NO:

91.

6. The anti-CD3 antibody according to claim 5, wherein the anti-CD3 antibody comprises a heavy chain and a light chain, wherein: a. the heavy chain comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 301, 326, 323, 327, 181, 331, 332, 333, 174, 175, 176, 177, 178, 179, 180, 295, 296, 297, 298, 299, 300, 302, 309, 311, 312, 314, 315, 322, 324, 325, 328, 335, 336, 350, 351, 352, 353, 354, 355, 363, 364, 365, 366, 367, 368 or 369, and the light chain comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 303, 304, 305, 319, 320, 329, 330, 318, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 198, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 306, 307, 308, 310, 313, 316, 317, 321, 334, or 342 having an amino acid sequence with at least 80% sequence identity; or The heavy chain comprises an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 95, and the light chain comprises an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 94; or b. the heavy chain comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 128, 129, 130, 131, 132, 133, 134 or 135, and the light chain comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 121, 122, 123, 124, 125, 126 or 127; or the heavy chain comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 93, and the light chain comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 92; Preferably, a. the heavy chain comprises the amino acid sequence of SEQ ID NO: 301, 326, 323, 327, 181, 331, 332, 333, 174, 175, 176, 177, 178, 179, 180, 295, 296, 297, 298, 299, 300, 302, 309, 311, 312, 314, 315, 322, 324, 325, 328, 335, 336, 350, 351, 352, 353, 354, 355, 363, 364, 365, 366, 367, 368 or 369, and the light chain comprises the amino acid sequence of SEQ ID NO: The amino acid sequence of NO: 303, 304, 305, 319, 320, 329, 330, 318, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 198, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 306, 307, 308, 310, 313, 316, 317, 321, 334 or 342; or The heavy chain comprises the amino acid sequence of SEQ ID NO: 95, and the light chain comprises the amino acid sequence of SEQ ID NO: 94; or b. the heavy chain comprises the amino acid sequence of SEQ ID NO: 128, 129, 130, 131, 132, 133, 134 or 135, and the light chain comprises the amino acid sequence of SEQ ID NO: 121, 122, 123, 124, 125, 126 or 127; or the heavy chain comprises the amino acid sequence of SEQ ID NO: 93, and the light chain comprises the amino acid sequence of SEQ ID NO: 92; More preferably, 1) the heavy chain comprises the amino acid sequence of SEQ ID NO: 301, 181, 180, 350, 353, 354, 355, 363, or 322, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or 2) the heavy chain comprises the amino acid sequence of SEQ ID NO: 301, 181, 180, 350, 353, 354, 355, 363, or 322, and the light chain comprises the amino acid sequence of SEQ ID NO: 304; or 3) the heavy chain comprises the amino acid sequence of SEQ ID NO: 301, 181, 180, 350, 353, 354, 355, 363, or 322, and the light chain comprises the amino acid sequence of SEQ ID NO: 305; or 4) the heavy chain comprises the amino acid sequence of SEQ ID NO: 326 or 365, and the light chain comprises the amino acid sequence of SEQ ID NO: 319; or 5) the heavy chain comprises the amino acid sequence of SEQ ID NO: 323 or 364, and the light chain comprises the amino acid sequence of SEQ ID NO: 320; or 6) the heavy chain comprises the amino acid sequence of SEQ ID NO: 326 or 365, and the light chain comprises the amino acid sequence of SEQ ID NO: 320; or 7) the heavy chain comprises the amino acid sequence of SEQ ID NO: 327 or 366, and the light chain comprises the amino acid sequence of SEQ ID NO: 320; or 8) the heavy chain comprises the amino acid sequence of SEQ ID NO: 323 or 364, and the light chain comprises the amino acid sequence of SEQ ID NO: 319; or 9) the heavy chain comprises the amino acid sequence of SEQ ID NO: 327 or 366, and the light chain comprises the amino acid sequence of SEQ ID NO: 319; or 10) the heavy chain comprises the amino acid sequence of SEQ ID NO: 181, 301, 180, 350, 353, 354, 355, 363, or 322, and the light chain comprises the amino acid sequence of SEQ ID NO: 329; or 11) the heavy chain comprises the amino acid sequence of SEQ ID NO: 181, 301, 180, 350, 353, 354, 355, 363, or 322, and the light chain comprises the amino acid sequence of SEQ ID NO: 330; or 12) the heavy chain comprises the amino acid sequence of SEQ ID NO: 331 or 367, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or 13) the heavy chain comprises the amino acid sequence of SEQ ID NO: 332 or 368, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or 14) the heavy chain comprises the amino acid sequence of SEQ ID NO: 333 or 369, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or 15) the heavy chain comprises the amino acid sequence of SEQ ID NO: 332 or 368, and the light chain comprises the amino acid sequence of SEQ ID NO: 318; or 16) the heavy chain comprises the amino acid sequence of SEQ ID NO: 332 or 368, and the light chain comprises the amino acid sequence of SEQ ID NO: 319; or 17) the heavy chain comprises the amino acid sequence of SEQ ID NO: 332 or 368, and the light chain comprises the amino acid sequence of SEQ ID NO: 320; Most preferably, 1) the heavy chain comprises the amino acid sequence of SEQ ID NO: 301, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or The heavy chain comprises the amino acid sequence of SEQ ID NO: 181, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or 2) the heavy chain comprises the amino acid sequence of SEQ ID NO: 301, and the light chain comprises the amino acid sequence of SEQ ID NO: 304; or 3) the heavy chain comprises the amino acid sequence of SEQ ID NO: 301, and the light chain comprises the amino acid sequence of SEQ ID NO: 305; or 4) the heavy chain comprises the amino acid sequence of SEQ ID NO: 326, and the light chain comprises the amino acid sequence of SEQ ID NO: 319; or 5) the heavy chain comprises the amino acid sequence of SEQ ID NO: 323, and the light chain comprises the amino acid sequence of SEQ ID NO: 320; or 6) the heavy chain comprises the amino acid sequence of SEQ ID NO: 326, and the light chain comprises the amino acid sequence of SEQ ID NO: 320; or 7) the heavy chain comprises the amino acid sequence of SEQ ID NO: 327, and the light chain comprises the amino acid sequence of SEQ ID NO: 320; or 8) the heavy chain comprises the amino acid sequence of SEQ ID NO: 323, and the light chain comprises the amino acid sequence of SEQ ID NO: 319; or 9) the heavy chain comprises the amino acid sequence of SEQ ID NO: 327, and the light chain comprises the amino acid sequence of SEQ ID NO: 319; or 10) the heavy chain comprises the amino acid sequence of SEQ ID NO: 181, and the light chain comprises the amino acid sequence of SEQ ID NO: 329; or 11) the heavy chain comprises the amino acid sequence of SEQ ID NO: 181, and the light chain comprises the amino acid sequence of SEQ ID NO: 330; or 12) the heavy chain comprises the amino acid sequence of SEQ ID NO: 331, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or 13) the heavy chain comprises the amino acid sequence of SEQ ID NO: 332, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or 14) the heavy chain comprises the amino acid sequence of SEQ ID NO: 333, and the light chain comprises the amino acid sequence of SEQ ID NO: 303; or 15) the heavy chain comprises the amino acid sequence of SEQ ID NO: 332, and the light chain comprises the amino acid sequence of SEQ ID NO: 318; or 16) the heavy chain comprises the amino acid sequence of SEQ ID NO: 332, and the light chain comprises the amino acid sequence of SEQ ID NO: 319; or 17) The heavy chain comprises the amino acid sequence of SEQ ID NO: 332, and the light chain comprises the amino acid sequence of SEQ ID NO:

320.

7. A multispecific antibody comprising the anti-CD3 antibody according to any one of claims 1 to 6; preferably, it specifically binds to human CD3 and simultaneously binds to a tumor-associated antigen, or a cell surface antigen, receptor or receptor ligand; more preferably, the multispecific antibody binds to human CD3 and simultaneously binds to one or more antigens selected from CD20, BCMA and PSMA. The multispecific antibody according to claim 7 , wherein the multispecific antibody is a bispecific antibody.

9. A pharmaceutical composition comprising the anti-CD3 antibody according to any one of claims 1 to 6, or the multispecific antibody according to claim 7 or 8, and one or more pharmaceutically acceptable carriers, diluents or excipients.

10. An isolated nucleic acid molecule encoding the anti-CD3 antibody of any one of claims 1 to 6, or encoding the multispecific antibody of claim 7 or 8.

11. A host cell comprising the isolated nucleic acid molecule of claim 10.

12. A method for producing the anti-CD3 antibody according to any one of claims 1 to 6, or the multispecific antibody according to claim 7 or 8, the method comprising culturing the host cell according to claim 11 in a culture medium to form and accumulate the anti-CD3 antibody according to any one of claims 1 to 6, or the multispecific antibody according to claim 7 or 8, and recovering the antibody or the multispecific antibody from the culture.

13. A method for treating, preventing or ameliorating a disease or condition, the method comprising administering to a subject an effective amount of the anti-CD3 antibody according to any one of claims 1 to 6, or the multispecific antibody according to claim 7 or 8, or the pharmaceutical composition according to claim 9, or the nucleic acid molecule according to claim 10, or the host cell according to claim 11; Preferably, the disease or disorder is selected from tumors, autoimmune diseases and inflammatory diseases.

14. Use of the anti-CD3 antibody according to any one of claims 1 to 6, the multispecific antibody according to claim 7 or 8, the pharmaceutical composition according to claim 9, the nucleic acid molecule according to claim 10, or the host cell according to claim 11 for preparing a drug for treating, preventing or ameliorating a disease or condition; Preferably, the disease or disorder is selected from tumors, autoimmune diseases and inflammatory diseases. 15 . A method for activating T cells, the method comprising administering to a subject the anti-CD3 antibody according to any one of claims 1 to 6 , or the multispecific antibody according to claim 7 or 8 , or the pharmaceutical composition according to claim 9 .

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