Anti-CD3 antibodies

Abstract

The present disclosure provides anti-CD3 monoclonal antibodies and related compositions that can be used in any of a variety of therapeutic and diagnostic methods to treat diseases and disorders, such as cancer and autoimmune diseases and disorders. The disclosure also relates to bispecific antibodies comprising an anti-CD3 antibody. The disclosure further relates to methods of treatment using such anti-CD3 monoclonal antibodies and bispecific antibodies.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to and the benefit of U.S. Provisional Application No. 63 / 419,257, filed on October 25, 2022, and U.S. Provisional Application No. 63 / 425,248, filed on November 14, 2022, the contents of each of which are hereby incorporated by reference in their entirety. background Technical Field

[0002] The present disclosure generally relates to anti-CD3 antibodies, compositions thereof, and methods of use thereof. Such antibodies can be used, for example, to target T cells, for example, as a therapeutic approach for cancer or autoimmunity. Such antibodies can also be used, for example, as targeting arms in bispecific antibodies or other multispecific antibodies. Related technical description

[0003] Cluster of differentiation 3 (CD3) is a multimeric protein complex that contains four different CD3 polypeptide chains (ε, γ, δ, and ζ) that assemble and function as three pairs of dimers (εγ, εδ, and ζζ). The assembled CD3 protein acts as a T cell co-receptor, which non-covalently associates with the T cell receptor (TCR). The CD3 protein complex is a defining feature of the T cell lineage, making anti-CD3 antibodies useful as T cell markers.

[0004] Anti-CD3 antibodies have been used clinically for immunosuppression of autoimmune T cell-mediated diseases, including organ transplant rejection and type 1 diabetes. Anti-CD3 bispecific or multispecific antibodies represent emerging immuno-oncology therapies. In addition to the CD3 binding arm, such bispecific or multispecific antibodies also contain an arm that binds to a tumor-associated antigen expressed on tumor cells, and can therefore bind to tumor cells and T cells simultaneously. This simultaneous binding causes T cells to activate, proliferate, and secrete cytolytic molecules that kill tumor cells. Some anti-CD3 binding domains deployed in some bispecific or multispecific antibodies can stimulate the secretion of inflammatory cytokines to detectable levels. Compared to engineered T cell therapy, one advantage of using anti-CD3 bispecific or multispecific antibodies is that any T cell can act as an effector cell, regardless of TCR specificity. Since TCR signaling does not require the participation of the TCR antigen binding domain, but is initiated via CD3, anti-CD3 bispecific or multispecific antibodies can utilize all available T cells, not just tumor-specific T cells. In contrast, effective immune checkpoint therapy requires the availability of tumor-specific T cells.

[0005] Although the anti-CD3 / anti-CD19 bispecific antibody (blinatumomab) has been approved for use in the treatment of B-cell malignancies, other anti-CD3 bispecific antibodies have failed in early clinical trials, and the specific anti-CD3 binding domains used in those antibodies have been identified as potential causes of those failures. See, for example, Vafa O and Trinklein ND, Front. Oncol. [Oncology Frontier], 2020, Vol. 10, doi: 10.3389 / fonc.2020.00446. Therefore, there is still a need to identify other anti-CD3 binding antibodies, bispecific antibodies, and multispecific antibodies, for example, to improve efficacy or optimize safety characteristics in patients. Summary of the Invention

[0006] The present disclosure relates to antibodies that bind to CD3. More particularly, it relates to antibodies that bind to The present invention relates to chimeric anti-CD3 antibodies produced in mice (Ablexis, LLC); fully human anti-CD3 antibodies produced therefrom; bispecific and multispecific antibodies produced therefrom; compositions comprising such chimeric, human, and bispecific or multispecific antibodies; polynucleotides, vectors, and host cells that produce such chimeric, human, and bispecific or multispecific antibodies; and methods of making and using such chimeric, human, and bispecific or multispecific antibodies.

[0007] One aspect of the present disclosure provides an isolated anti-CD3 antibody or antigen-binding fragment thereof comprising one to six complementarity determining regions (CDRs) disclosed herein. The one to six CDRs may comprise an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-687.

[0008] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a heavy chain CDR3 (HCDR3) disclosed herein. The HCDR3 may comprise an amino acid sequence selected from the group consisting of SEQ ID NOs: 574-687. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a light chain CDR3 (LCDR3) disclosed herein. The LCDR3 may comprise an amino acid sequence selected from the group consisting of SEQ ID NOs: 227-344.

[0009] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a HCDR1 disclosed herein, a HCDR2 disclosed herein, a HCDR3 disclosed herein, a LCDR1 disclosed herein, a LCDR2 disclosed herein, and a LCDR3 disclosed herein.

[0010] In some embodiments, an anti-CD3 antibody or antigen-binding fragment thereof comprises i) a heavy chain variable region comprising a HCDR1 disclosed herein, a HCDR2 disclosed herein, and a HCDR3 disclosed herein, and ii) a light chain variable region comprising a LCDR1 disclosed herein, a LCDR2 disclosed herein, and a LCDR3 disclosed herein. The HCDR1 may comprise an amino acid sequence selected from the group consisting of SEQ ID NOs: 345-457. In some embodiments, the HCDR2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 458-573. The HCDR3 may comprise an amino acid sequence selected from the group consisting of SEQ ID NOs: 574-687. In some embodiments, the LCDR1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-113. The LCDR2 may comprise an amino acid sequence selected from the group consisting of SEQ ID NOs: 114-226. In some embodiments, the LCDR3 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 227-344.

[0011] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of an antibody disclosed herein. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises i) a heavy chain variable region comprising the HCDR1, HCDR2, and HCDR3 of an antibody disclosed herein, and ii) a light chain variable region comprising the LCDR1, LCDR2, and LCDR3 of the same antibody. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a heavy chain variable ("VH") region of an antibody disclosed herein. The anti-CD3 antibody or antigen-binding fragment thereof may comprise a light chain variable ("VL") region of an antibody disclosed herein. In some embodiments, the antibody or antigen-binding fragment thereof comprises the VH and VL of an antibody disclosed herein. The CDRs, VH, and / or VL may be from an antibody selected from the group consisting of: ABL-CD3-1 to ABL-CD3-113, ABL-CD3-1A to ABL-CD3-113A, and ABL-CD3-85B.In some embodiments, the CDR, VH, and / or VL may be derived from an antibody selected from the group consisting of: ABL-CD3-18, ABL-CD3-20, ABL-CD3-21, ABL-CD3-22, ABL-CD3-27, ABL-CD3-29, ABL-CD3-31, ABL-CD3-34, ABL-CD3-36, ABL-CD3-37, ABL-CD3-39, ABL-CD3-40, ABL-CD3-41, ABL-CD3-43, ABL-CD3-44, ABL-CD3-45, ABL-CD3-47, ABL-CD3-49, ABL-CD3-52, ABL-CD3-53, ABL-CD3-56, ABL-CD3-57, ABL-CD3-61, ABL-CD3-62, ABL-CD3-63, ABL-CD3-64, ABL-CD3-65, ABL-CD3-66, ABL-CD3-68, ABL-CD3-71, ABL-CD3-72, ABL-CD3-74, ABL-CD3-76, ABL-CD3-77, ABL-CD3-79, ABL-CD3-81, ABL-CD3-85, ABL-CD3-87, ABL-CD3-88, ABL-CD3-89, ABL-CD3-18A, ABL-CD3-20A, ABL-CD3-21A, ABL-CD3-22A, ABL-CD3-27A, ABL-CD3-29A, ABL-CD3-31A, ABL-CD3-34A, ABL-CD3-36A, ABL-CD3-37A, ABL-CD3-39A, ABL-CD3-40A, ABL-CD3-41A, ABL-CD3-43A, ABL-CD3-44A, ABL-CD3-45A, ABL-CD3-47A, ABL-CD3-49A, ABL-CD3-52A, ABL-CD3-53A, ABL-CD3-56A, ABL-CD3-57A, ABL-CD3-61A, ABL-CD3-62A, ABL-CD3-63A, ABL-CD3-64A, ABL-CD3-65A, ABL-CD3-66A, ABL-CD3-68A, ABL-CD3-71A, ABL-CD3-72A, ABL-CD3-74A, ABL-CD3-76A, ABL-CD3-77A, ABL-CD3-79A, ABL-CD3-81A, ABL-CD3-85A, ABL-CD3-85B, ABL-CD3-87A, ABL-CD3-88A, and ABL-CD3-89A.

[0012] HCDR1 may comprise an amino acid sequence selected from the group consisting of SEQ ID NOs: 345-457. In some embodiments, HCDR2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 458-573. HCDR3 may comprise an amino acid sequence selected from the group consisting of SEQ ID NOs: 574-687. In some embodiments, LCDR1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-113. LCDR2 may comprise an amino acid sequence selected from the group consisting of SEQ ID NOs: 114-226. In some embodiments, LCDR3 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 227-344. In some embodiments, the VL region comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 688-914. The VH region may comprise an amino acid sequence selected from the group consisting of SEQ ID NOs: 915-1141.

[0013] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof is human. In some embodiments, the antibody is chimeric. In certain embodiments, the antibody is selected from a single variable domain antibody, a single chain antibody, a scFv, a bispecific antibody, a multispecific antibody, a Fab, a F(ab')2, and a whole antibody. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof is a bispecific antibody.

[0014] In some embodiments, the anti-CD3 antibody is an IgG antibody. The anti-CD3 antibody may be an IgM antibody. In some embodiments, the anti-CD3 antibody is an IgA antibody. The anti-CD3 antibody may be an IgD antibody. The anti-CD3 antibody may be an IgE antibody. In some embodiments, the anti-CD3 antibody is an IgG1 antibody. The anti-CD3 antibody may be an IgG2 antibody. In some embodiments, the anti-CD3 antibody is an IgG3 antibody. The anti-CD3 may be an IgG4 antibody. In some embodiments, the anti-CD3 antibody is a variant of an IgG antibody, such as a variant of IgG1, IgG2, IgG3, or IgG4, or a combination thereof. The anti-CD3 antibody may have reduced effector function or no effector function. In some embodiments, the anti-CD3 antibody is engineered to reduce or eliminate effector function.

[0015] Another aspect of the present disclosure provides an anti-CD3 bispecific antibody. In some embodiments, the anti-CD3 bispecific antibody further comprises a targeting antibody or an antigen-binding fragment thereof. In some embodiments, the targeting antibody is an anti-tumor antibody or an antigen-binding fragment thereof.

[0016] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a complete heavy chain (which comprises a first Fc domain) and a complete light chain. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a single-chain Fv (scFv), Fab, Fab', F(ab')2, or Fv fragment operably linked to the first Fc domain. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a single-chain Fv (scFv) operably linked to the first Fc domain.

[0017] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a first Fc domain. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof is operably connected to the first Fc domain via a first linker. In some embodiments, the first linker is an antibody hinge region. In some embodiments, the first linker is a variable length Gly-Ser linker. In some embodiments, the first linker comprises a linker selected from the group consisting of: (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1238), (Ser-Ser-Ser-Ser-Gly)n (SEQ ID NO: 1147), (Gly-Ser-Ser-Gly-Gly)n (SEQ ID NO: 1148), and (Gly-Gly-Ser-Gly-Gly)n (SEQ ID NO: 1149), wherein n is an integer between 1 and 5. In some embodiments, the first linker comprises the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1237), wherein n is 1. In some embodiments, the first linker comprises the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4.

[0018] In some embodiments, the targeting antibody is an anti-tumor antibody. In some embodiments, the anti-tumor antibody or its antigen-binding fragment comprises a second Fc domain. In some embodiments, the anti-tumor antibody or its antigen-binding fragment is operably connected to the second Fc domain via a second linker. In some embodiments, the second linker is an antibody hinge region. In some embodiments, the second linker is a Gly-Ser linker of variable length. In some embodiments, the second linker comprises a linker selected from the group consisting of: (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1238), (Ser-Ser-Ser-Ser-Gly)n (SEQ ID NO: 1147), (Gly-Ser-Ser-Gly-Gly)n (SEQ ID NO: 1148) and (Gly-Gly-Ser-Gly-Gly)n (SEQ ID NO: 1149), wherein n is an integer between 1 and 5. In some embodiments, the second linker comprises the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 1. In some embodiments, the second linker comprises the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4.

[0019] In some embodiments, the first and second Fc domains comprise mutations to promote heterodimer formation. In some embodiments, the first Fc domain comprises a T366W mutation and the second Fc domain comprises a T366S / L368A / Y407V mutation. In some embodiments, the first Fc domain comprises a T366S / L368A / Y407V mutation and the second Fc domain comprises a T366W mutation. In some embodiments, the first and second Fc domains comprise a KIH S-SMutations. In some embodiments, the first Fc domain comprises S354C / T366W mutations and the second Fc domain comprises Y349C / T366S / L368A / Y407V mutations. In some embodiments, the first Fc domain comprises Y349C / T366S / L368A / Y407V mutations and the second Fc domain comprises S354C / T366W mutations. In some embodiments, the first Fc domain comprises S354C / T366W mutations and the second Fc domain comprises Y349C / T366S / L368A / Y407V / H435R / Y436F mutations. In some embodiments, the first Fc domain comprises Y349C / T366S / L368A / Y407V / H435R / Y436F mutations and the second Fc domain comprises S354C / T366W mutations. In some embodiments, the first Fc domain comprises S354C / T366W / H435R / Y436F mutations and the second Fc domain comprises Y349C / T366S / L368A / Y407V mutations. In some embodiments, the first Fc domain comprises Y349C / T366S / L368A / Y407V mutations and the second Fc domain comprises S354C / T366W / H435R / Y436F mutations. Each of the foregoing mutations is numbered according to EU.

[0020] In some embodiments, the first Fc domain comprises the amino acid sequence of SEQ ID NO: 1142. In some embodiments, the first Fc domain comprises the amino acid sequence of SEQ ID NO: 1143. In some embodiments, the second Fc domain comprises the amino acid sequence of SEQ ID NO: 1142. In some embodiments, the second Fc domain comprises the amino acid sequence of SEQ ID NO: 1143. In some embodiments, the first and second Fc domains comprise the amino acid sequences of SEQ ID NOs: 1142 and 1143, respectively. In some embodiments, the first and second Fc domains comprise the amino acid sequences of SEQ ID NOs: 1143 and 1142, respectively. In some embodiments, the anti-CD3 antibody comprises a constant region comprising the amino acid sequence of SEQ ID NO: 1144. In some embodiments, the anti-CD3 antibody comprises a constant region comprising the amino acid sequence of SEQ ID NO: 1145. In some embodiments, the anti-tumor antibody comprises a constant region comprising the amino acid sequence of SEQ ID NO: 1144. In some embodiments, the anti-tumor antibody comprises a constant region comprising the amino acid sequence of SEQ ID NO: 1145. In some embodiments, the anti-CD3 antibody comprises a constant region comprising the amino acid sequence of SEQ ID NO: 1144, and the anti-tumor antibody comprises a constant region comprising the amino acid sequence of SEQ ID NO: 1145. In some embodiments, the anti-CD3 antibody comprises a constant region comprising the amino acid sequence of SEQ ID NO: 1145, and the anti-tumor antibody comprises a constant region comprising the amino acid sequence of SEQ ID NO: 1144.

[0021] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof is operably linked to a constant region comprising the amino acid sequence of SEQ ID NO: 1144. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof is operably linked to a constant region comprising the amino acid sequence of SEQ ID NO: 1145. In some embodiments, the anti-tumor antibody or antigen-binding fragment thereof is operably linked to a constant region comprising the amino acid sequence of SEQ ID NO: 1144. In some embodiments, the anti-tumor antibody or antigen-binding fragment thereof is operably linked to a constant region comprising the amino acid sequence of SEQ ID NO: 1145. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof is operably linked to a constant region comprising the amino acid sequence of SEQ ID NO: 1144, and the anti-tumor antibody or antigen-binding fragment thereof is operably linked to a constant region comprising the amino acid sequence of SEQ ID NO: 1145. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof is operably linked to a constant region comprising the amino acid sequence of SEQ ID NO: 1145, and the anti-tumor antibody or antigen-binding fragment thereof is operably linked to a constant region comprising the amino acid sequence of SEQ ID NO: 1144.

[0022] In some embodiments, the anti-tumor antibody is an anti-CD33 antibody. In some embodiments, the anti-CD33 antibody comprises the six CDRs of gemtuzumab tuzumab. In some embodiments, the anti-CD33 antibody comprises the VH of gemtuzumab tuzumab. In some embodiments, the anti-CD33 antibody comprises the VL of gemtuzumab tuzumab. In some embodiments, the anti-CD33 antibody comprises the VH and VL of gemtuzumab tuzumab. In some embodiments, the heavy chain of the anti-CD33 antibody comprises the amino acid sequence of SEQ ID NO: 1150. In some embodiments, the light chain of the anti-CD33 antibody comprises the amino acid sequence of SEQ ID NO: 1151. In some embodiments, the heavy chain of the anti-CD33 antibody comprises the amino acid sequence of SEQ ID NO: 1150, and the light chain of the anti-CD33 antibody comprises the amino acid sequence of SEQ ID NO: 1151.

[0023] One aspect of the present disclosure provides a recombinant polynucleotide encoding an anti-CD3 antibody or its antigen-binding fragment or an anti-CD3 bispecific antibody of the present disclosure. Another aspect of the present disclosure provides a recombinant polynucleotide encoding an anti-CD3 antibody or its antigen-binding fragment or an anti-CD3 multispecific antibody of the present disclosure. Another aspect of the present disclosure provides a vector comprising the recombinant polynucleotide, such as an expression vector. Another aspect of the present disclosure provides an isolated host cell comprising the recombinant polynucleotide or the vector. Another aspect of the present disclosure provides a method for preparing an anti-CD3 antibody or its antigen-binding fragment or an anti-CD3 bispecific antibody of the present disclosure. One aspect of the present disclosure provides a composition comprising an anti-CD3 antibody or its antigen-binding fragment or an anti-CD3 bispecific antibody of the present disclosure and a physiologically acceptable carrier.

[0024] A further aspect of the present disclosure provides a method for treating or preventing cancer in a subject in need thereof, the method being by administering to a subject in need thereof an anti-CD3 antibody or its antigen-binding fragment or bispecific or multispecific antibody of the present disclosure, or a composition comprising the antibody or fragment or bispecific or multispecific antibody. One aspect of the present disclosure provides a method for maintaining cancer remission in a subject, the method being by administering to a subject in need thereof an anti-CD3 antibody or its antigen-binding fragment or bispecific or multispecific antibody of the present disclosure, or a composition comprising the antibody or fragment or bispecific antibody. Another aspect of the present disclosure provides a method for redirecting T cells to tumor cells, wherein the method comprises contacting the T cells with an anti-CD3 bispecific or multispecific antibody or its antigen-binding fragment of the present disclosure, or a composition comprising the bispecific or multispecific antibody or fragment. In some embodiments, the bispecific or multispecific antibody or fragment further comprises a tumor targeting arm. A further aspect of the present invention provides a method for treating cancer, comprising administering to a subject in need thereof an anti-CD3 bispecific or multispecific antibody or antigen-binding fragment thereof of the present disclosure, or a composition comprising the antibody or fragment, wherein the bispecific or multispecific antibody or fragment further comprises a tumor-targeting arm.

[0025] Another aspect of the present disclosure provides a method of treating or preventing an autoimmune disease or disorder in a subject in need thereof, by administering to the subject in need thereof an anti-CD3 antibody or antigen-binding fragment thereof, or a bispecific or multispecific antibody of the present disclosure, or a composition comprising the antibody or fragment, or bispecific or multispecific antibody. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1A and Figure 1BThe results of flow cytometric analysis of purified monoclonal antibodies are presented. Briefly, flow cytometry was performed on Jurkat wild-type and knockout cells and human Pan-T cells at a concentration of 1 μg / ml. The logarithmic geometric mean fluorescence intensity (gMFI) values ​​of each hit were plotted, comparing Jurkat wild-type and knockout cells ( Figure 1A ) and Jurkat wild-type and Pan-T cells ( Figure 1B ).

[0027] Figure 2 A schematic diagram of the formation of CD3-CD33 bispecific antibodies is provided.

[0028] Figure 3A A schematic diagram of the Killer Immune Lysis Response (KILR) HL60 T cell redirection assay protocol is provided. Figure 3B Demonstrated is the evaluation of the ability of CD-3xCD33 bispecific antibodies to mediate interactions between effector and target cells, leading to target-mediated cytotoxicity.

[0029] Figure 4A and Figure 4B Provides a target for the cytokine IL2 ( Figure 4A ) and IFNγ( Figure 4B ) were analyzed by quantitative ELISA.

[0030] Figures 5A-5D Four human PBMC donors (donor 1 ( Figure 5A ), donor 2 ( Figure 5B ), donor 3( Figure 5C ) and donor 0( Figure 5D ))'s results from the killer immune lytic response (KILR) T cell redirection (TCR) assay.

[0031] Figure 6A Results are presented for ELISAs measuring multispecific / nonspecific antibodies binding to ds and ss DNA, cardiolipin, insulin, lipopolysaccharide, and hemocyanin. Figure 6B Results of an ELISA measuring multispecific / nonspecific antibody binding to baculovirus particles are presented. Figure 6C Results of antibody retention times measured on a HIC-Butyl column are provided, where less hydrophobic substances elute earlier and more hydrophobic substances elute later. Sequence Description Table 1A. Anti-CD3 Antibody Amino Acid Sequence Identifiers Table 1B. LCDR sequences Table 1C. HCDR sequences Table 1D. VL sequences Table 1E. VH sequences Table 1F. scFv sequences DETAILED DESCRIPTION

[0032] This disclosure relates to anti-CD3 antibodies. Applicants have used proprietary Mouse technology (see WO 2010 / 039900 and WO 2011 / 123708, incorporated herein by reference in their entirety) was used to generate a panel of monoclonal antibodies (mAbs) that can target CD3 on T cells. Mice were immunized with purified human CD3ε / δ heterodimers and boosted with purified human CD3ε / δ and cynomolgus monkey CD3ε / γ heterodimers and human T cells. Thus, the antibodies have the potential to bind to CD3ε alone (human and / or cynomolgus monkey), CD3δ alone (human and / or cynomolgus monkey), CD3γ alone (human and / or cynomolgus monkey), the interface between these subunits, and conformational epitopes between these subunits that exist only in certain assemblies.

[0033] Embodiments of the present disclosure relate to the use of anti-CD3 antibodies or antigen-binding fragments thereof for the diagnosis, assessment, and treatment of cancer and autoimmunity.

[0034] The variable region portion from the disclosed antibody may include all or a combination of the complementary determining regions (CDRs) of VH and / or VL. The variable region can be formatted in a standard antibody structure (two heavy chains and two light chains) with a constant region (whether natural or modified as desired to induce upregulation or downregulation of various effector functions). The variable region can also be formatted as a multispecific antibody, for example, a bispecific antibody that binds to two different epitopes on the CD3 protein or to two different antigens (one of which is CD3). In some embodiments, the antibody is a bispecific antibody. In some embodiments, the bispecific antibody comprises a tumor targeting arm. The variable region can also be formatted as an antibody fragment, for example, a single domain antibody, Fab, Fab'2, scFv or chimeric antigen receptor (CAR) comprising a single VH or VL. Antibodies can also be used as antibody-drug conjugates, or carry other additives, such as small molecule toxins or incorporated as part thereof, biotoxins, radioisotopes, cytokines, oligopeptides, RNA or CAR-T cells to enhance therapeutic modalities and / or improve safety.

[0035] Unless expressly indicated to the contrary, the practice of the present disclosure will adopt conventional methods of virology, immunology, microbiology, molecular biology and recombinant DNA technology within the skill of the art, many of which are described below for illustrative purposes. Such techniques are fully explained in the literature. See, for example, Current Protocols in Molecular Biology or Current Protocols in Immunology, John Wiley & Sons, New York, NY (2009); Ausubel et al., Short Protocols in Molecular Biology, 5th edition, Wiley & Sons, 2002; Sambrook and Russell, Molecular Cloning: A Laboratory Manual (4th edition, 2012); and other similar references.

[0036] The present disclosure is not limited to specific compositions or biosystems, which may be different. It should also be understood that the terms used herein are only used to describe the purpose of specific illustrative embodiments and are not intended to be limiting. The terms used in this specification generally have their ordinary meanings in the art in the context of the present disclosure and in the specific context in which each term is used. Certain terms are discussed elsewhere below or in the specification to provide additional guidance to practitioners when describing the compositions and methods of the present disclosure and how to prepare and use them. The scope and meaning of any use of the terms will be apparent from the specific context in which the terms are used. Therefore, the definitions listed herein are intended to provide illustrative guidance in determining the specific embodiments of the present disclosure, without being limited to specific compositions or biosystems.

[0037] As used in this disclosure and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the content clearly dictates otherwise.

[0038] Throughout this disclosure and the appended claims, unless the context requires otherwise, the word "comprise" or variations such as "comprises" or "comprising" should be understood to imply the inclusion of stated elements or groups of elements but not the exclusion of any other elements or groups of elements. "Comprise" may be synonymous with "including" or "containing."

[0039] It should be understood that regardless of the circumstances in which an embodiment is described herein using the language "comprising," additional similar embodiments are also provided that are described using the term "consisting of" and / or "consisting essentially of. As used herein, "consisting of is a closed term that includes only the specified elements listed, and "consisting essentially of includes the specified elements listed and may include additional, non-material elements that are not listed.

[0040] As used herein, the term "about" to modify the quantity of an ingredient, parameter, calculation or measurement used in the composition of the present disclosure or in the method of the present disclosure refers to a variation in the numerical quantity that may occur, for example, by typical measurements and liquid handling procedures used in the real world to prepare isolated antibodies or pharmaceutical compositions; by unintentional errors in these procedures; by differences in the manufacture, source or purity of the ingredients used to prepare the composition or perform the method; etc., without having a substantial effect on the chemical or physical properties of the composition or method of the present disclosure. Such variations may be within 10% of a given value or range, more typically still within 5%. Whether or not modified by the term "about", the present disclosure includes equivalents of the quantity. Reference herein to "about" values ​​or parameters includes (and describes) embodiments for the value or parameter itself. For example, a description referring to "about X" includes a description of "X". Numerical ranges include the numbers defining the range. In addition, all ranges disclosed herein should be understood to encompass any and all subranges contained therein.

[0041] The terms "antibody" (Ab) and "immunoglobulin" (Ig) are used interchangeably herein and refer to molecules (e.g., complete antibodies, antibody fragments, or modified antibodies) that can recognize and bind to a specific target or antigen (e.g., carbohydrates, polynucleotides, lipids, polypeptides, etc.) through at least one antigen recognition site located in the variable region of the molecule. Antibodies can be membrane-bound or secreted. As used herein, the terms encompass not only complete (intact) or "complete (whole)" polyclonal or monoclonal antibodies, but also fragments thereof (e.g., single variable domain (VH, VL, or a combination thereof), Fab, Fab', F(ab')2, Fv, single chain (ScFv), synthetic variants thereof, naturally occurring variants, fusion proteins comprising an antibody portion of an antigen-binding fragment with the desired specificity, humanized antibodies, chimeric antibodies, chimeric antigen receptors (CARs), and any other modified configurations of immunoglobulin molecules comprising an antigen-binding site or fragment (epitope recognition site) of the desired specificity.

[0042] Antibodies or Ig molecules typically comprise two identical heavy chains and two identical light chains linked together by disulfide bonds. Both heavy chains (IgH) and light chains (IgL) contain variable (V) regions or domains and constant (C) regions or domains. The IgH locus portion encoding the V region comprises multiple copies of variable (V), diversity (D) and junction (J) gene segments. The IgL locus portion encoding the V region comprises multiple copies of V and J gene segments. The V region coding portion of the IgH and IgL loci undergoes gene segment rearrangement, for example, different combinations of V, (D) and J gene segments are arranged to form IgH and IgL variable regions (VH and VL, respectively) to develop different antigenic specificities in antibodies. Each variable region comprises three highly variable complementary determining regions (CDRs), which are interspersed between framework regions (FRs) with lower variability. The heavy chain comprises HCDR1, HCDR2 and HCDR3. The light chain comprises LCDR1, LCDR2 and LCDR3. The secretory form of the IgH C region of most antibodies consists of three C domains (CH1, CH2, CH3) and a hinge region, with the exception of Cμ, which includes a CH4 region and lacks a hinge region. The membrane-bound form of the IgH C region also has membrane and intracellular domains. The IgH constant region determines the isotype of the antibody, such as IgM, IgD, IgG1, IgG2, IgG3, IgG4, IgA, and IgE. It should be understood that non-human mammals (e.g., There are two types of human IgL: Igκ and Igλ.

[0043] As used herein, the term "monoclonal antibody" or "mAb" refers to an antibody produced by an identical collection of immune cells, each of which is a clone of a unique parent cell. Monoclonal antibodies are single-specific, have identical sequences, and bind to the same epitope in the same manner.

[0044] As used herein, the term "antigen-binding fragment" refers to a polypeptide fragment containing at least one immunoglobulin heavy chain and / or light chain CDR that binds to CD3. In this regard, the antigen-binding fragment of an antibody may comprise 1, 2, 3, 4, 5, or all 6 CDRs from the VH and VL sequences listed herein of the anti-CD3 antibodies disclosed herein. In some embodiments, the antigen-binding fragment of an anti-CD3 antibody comprises all 6 CDRs from the VH and VL sequences listed herein of the anti-CD3 antibodies disclosed herein. The antigen-binding fragments of the CD3-specific antibodies disclosed herein are capable of binding to the CD3 protein, preferably to the receptor binding domain (RBD) of the CD3 protein.

[0045] In some embodiments, the antibodies and antigen-binding fragments thereof disclosed herein include heavy and light chain CDR sets, which are inserted between the heavy and light chain framework regions (FR) sets, respectively. The framework regions provide conformational support for the CDRs and define the spatial relationship of the CDRs relative to each other. As used herein, the term "CDR set" refers to the three hypervariable regions of the heavy or light chain V region. Starting from the N-terminus of the heavy or light chain, these regions are represented as "CDR1," "CDR2," and "CDR3," respectively. Thus, the antigen binding site includes six CDRs comprising a CDR set from each of the heavy and light chain V regions.

[0046] A "Fab" domain or fragment comprises the N-terminal portion of an IgH, including the V region and CH1 domain of the IgH, and the entire IgL. A "F(ab')2" domain comprises the Fab domain and a portion of the hinge region, wherein two IgHs are linked together via a disulfide bond in the middle hinge region. Both Fab and F(ab')2 are non-limiting examples of "antigen-binding fragments."

[0047] The C-terminal portion of IgH is a fragment that can be crystallized after papain digestion of the antibody and contains the CH2 and CH3 domains, referred to as the "Fc" domain. The Fc domain is the part of Ig that is recognized by cellular receptors (e.g., FcRs), and the complement activating protein C1q binds to it. The lower hinge region is encoded in the 5' portion of the CH2 exon and provides flexibility within the antibody for binding to Fc receptors. Although the boundaries of the Fc domain may vary, the human IgG heavy chain Fc domain defined herein comprises residues E216 to the carboxyl terminus of the CH3 domain (or CH4 domain for IgM and IgE antibodies), with numbering using the EU format outlined in Edelman. The term "Fc domain" may refer to this sequence in isolation, or in the context of an antibody, antibody fragment, or Fc fusion protein. The amino acid sequence of a non-naturally occurring Fc domain (also referred to herein as a "variant Fc domain") may contain one or more amino acid modifications. Polymorphism has been observed at various Fc domain positions, including but not limited to positions 270, 272, 312, 315, 356, and 358 (according to EU numbering), and therefore, slight differences may exist between the shown sequence and sequences in the prior art.

[0048] The term "EU format as set out in Edelman" refers to the residue numbering of the human IgG1 EU antibody as described in Edelman GM et al., (1969) Proc. Natl. Acad. USA, 63, 78-85. Human IgG2 and human IgG4 residue numbering also uses the EU format (see Dillon TM, et al., J Biol Chem. Jun 6;283(23):16206-15 (2008); Aalberse RC et al., Immunology 105:9-19 (2002); and Scholthauer T et al., Protein Engineering, Design and Selection, 29(10):457-466, (2016). The EU numbering of residues can be determined by aligning the antibody sequence with the "standard" EU numbering format at regions homologous to the antibody sequence. Unless otherwise indicated, all residue numbering of the constant regions herein will be according to the EU numbering format.

[0049] The term "Kabat numbering" refers to the variable region residue numbering as described in Kabat et al., (1991) US Department of Health and Human Services, NIH Publication No. 91-3242. The variable region CDRs (CDR L1, CDR L2, CDR L3, CDR H1, CDR H2, CDR H3) are identified based on contacts based on the crystal structure as defined in: Karpusas et al. Structure. Apr 4;9(4):321-9 (2001) and are numbered according to the Kabat numbering system. Unless otherwise indicated, all residue numbering of the variable region will be according to Kabat.

[0050] "Fv" fragments include non-covalent VH::VL heterodimers that include an antigen binding site. In certain embodiments, single-chain Fv (scFv) antibodies are contemplated. scFv is a covalently linked VH::VL heterodimer expressed by a gene fusion comprising a VH encoding gene and a VL encoding gene connected by a linker encoding a peptide (see, e.g., Huston et al. (1988) Proc. Nat. Acad. Sci. USA 85(16):5879-5883 and Byrd et al. (1988) Science, 242:423-6, incorporated herein by reference). As used herein, the term "linker" refers to a polypeptide sequence that connects two or more antibody domains. The characteristics of linkers and their suitability for a particular purpose are known in the art. See, e.g., Chen et al. Adv Drug Deliv Rev. Oct 15;65(10):1357-1369 (2013) (disclosing various types of linkers, their properties, and related linker design tools and databases), which is incorporated herein by reference. Linkers can be flexible, rigid, or cleavable in vivo. Preferably, the linker is flexible. Flexible linkers typically contain small non-polar (e.g., Gly) or polar (e.g., Ser or Thr) amino acids. The most commonly used flexible linkers have a sequence consisting primarily of stretches of Gly and Ser residues ("GS" linkers). Optionally, the flexible linker contains a repeating sequence of 5 Gly and Ser residues.

[0051] Where bispecific antibodies are to be used, these may be conventional bispecific antibodies, which can be prepared in a variety of ways (see, e.g., Holliger, P. and Winter G. Current Opinion Biotechnol. 4, 446-449 (1993); Brinkmann U, Kontermann RE. MAbs. 9(2), 182-212 (2017); Brinkmann U, Kontermann RE. Science. 372(6545), 916-917 (2021); Kontermann RE, Brinkmann U. Bispecific antibodies. Drug Discov Today. 20(7), 838-47 (2015); Spiess C, Zhai Q, Carter PJ. Mol Immunol. 67(2 Pt 1997). A), 95-106 (2015); Labrijn AF, Janmaat ML, Reichert JM, Parren PWHI. Nat Rev Drug Discov. [Nature Review Drug Discovery] 18(8), 585-608 (2019), incorporated herein by reference), for example, chemically prepared or prepared by a hybridoma, or can be any of the above-mentioned bispecific antibody fragments.

[0052] As used herein, "chimeric antibody" refers to an antibody encoded by a polynucleotide sequence containing polynucleotide sequences from two or more species (e.g., human and mouse). As used herein, a chimeric antibody may also refer to an antibody comprising regions from two or more different antibodies.

[0053] As used herein, "chimeric Ig chain" refers to an Ig heavy chain or Ig light chain encoded by a polynucleotide sequence containing polynucleotide sequences from two or more species (e.g., human and mouse). For example, a chimeric Ig heavy chain can include a human VH domain, a DH domain, a JH domain, a CH1 domain, and an upper hinge region, as well as mouse CH2 and CH3 domains. In some embodiments, the middle hinge region is mouse. In some embodiments, the middle hinge region is human. In some embodiments, the middle hinge region is chimeric.

[0054] As used herein, the term "human antibody" refers to an antibody with a variable region and a constant region derived from a human germline immunoglobulin sequence. Human antibodies may include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-specific mutagenesis in vitro or by somatic mutations in vivo). However, the term "human antibody" does not encompass antibodies (i.e., humanized antibodies) in which CDR sequences are derived from the germline of another mammalian species (e.g., mouse) and have been transplanted onto human framework sequences. The term encompasses antibodies with sequences derived from human genes but altered, for example, to reduce possible immunogenicity, increase affinity, reduce effector functions, eliminate cysteine ​​that may cause undesirable folding, etc. The term also encompasses antibodies comprising human amino acid sequences recombinantly produced in non-human cells, which may confer atypical glycosylation patterns on human cells.

[0055] As used herein, the term "isolated" antibody or antigen-binding fragment refers to an antibody or fragment that is at least partially free of other biomolecules present in the cells used to produce it. Other biomolecules that an isolated antibody or fragment is at least partially free of include nucleic acid molecules, proteins, lipids, carbohydrates, cell debris, and culture medium. The term "isolated" antibody or fragment does not require, but does encompass, the complete absence of such other biomolecules. The term "isolated" antibody or fragment also does not refer to the complete absence of other molecules, such as water, buffers, salts, or components of pharmaceutical formulations. Thus, molecules synthesized chemically or in a cell-free system will be "separated" from their naturally associated components. Purification techniques well known in the art can also be used to "isolate" molecules. Similarly, as used herein, the term "isolated" polynucleotide or nucleic acid molecule refers to a polynucleotide of genomic, mRNA, cDNA, synthetic origin, or some combination thereof, which (1) is not associated with all or part of a polynucleotide with which the "isolated nucleic acid" is associated in nature, (2) is operably linked to a polynucleotide to which it is not linked in nature, or (3) does not occur as part of a larger sequence in nature. An isolated polynucleotide "comprising" a specified sequence may also include coding sequences for other proteins or immunoglobulin chains, expression control sequences, or vector sequences.

[0056] As used herein, the terms "polypeptide," "peptide," or "protein" are used interchangeably herein to describe a chain of amino acids linked together by chemical bonds. Non-limiting examples of polypeptides or proteins include IgH, IgL, V domains, C domains, or antibodies.

[0057] As used herein, the term "amino acid modification" refers to at least one amino acid substitution, insertion, deletion or mutation in an amino acid sequence compared to the wild-type amino acid sequence. Such modifications are within the ordinary skill of those skilled in the art. Some modifications of the Fc domain, including amino acid deletions, substitutions, and additions, have been shown to alter the binding of the Fc domain to its ligands and / or receptors, resulting in concomitant modifications of effector function (see, e.g., Shields et al., J Biol Chem 276:6591-6604 (2001); Presta et al., Biochem Soc Trans 30:487-490 (2002); Escobar-Cabrera E et al. Antibodies. 6:7 (2017); Duncan AR et al. Nature. 1988;332:738–740 (1988); Duncan AR et al. Nature. 332:563-564 (1988); Hezareh M et al. J Virol. 75:12161-12168 (2001); Oganesyan et al. J Virology 75:12171-12178 (2002). V et al. Acta Crystallogr D Biol Crystallogr [Acta Crystallogr D: Biological Crystallography]; 64:700–704 (2008); Schlothauer T et al. Protein Eng Des Sel. [Protein Engineering, Design and Selection] Oct; 29(10):457-466 (2016); Tao MH et al. J. Immunol. [Journal of Immunology] 143:2595-2601 (1989); Von Kreudenstein TS et al. MAbs. [Monoclonal Antibodies] 5(5):646–654 (2013); Wang X et al. Protein Cell. [Protein and Cell] 9(1):63-73(2018); U.S. Patent Publication Nos. 20040132101; 20070111260; 20110287032; 20180194860; U.S. Patent No. US 8409568; International Publication No. WO 2017 / 177337, each of which is incorporated by reference in its entirety. Amino acid deletions are indicated by "Δ" and insertions are indicated by "In". For example, a deletion of the amino acid sequence from E216 to E222 is indicated as ΔE216-E222. An insertion of arginine (R) between amino acid residues 234 and 235, for example, would be indicated as InR234 / 235.

[0058] "Conservative amino acid substitutions" replace an amino acid residue with a different amino acid residue that has similar biochemical properties (e.g., charge, hydrophobicity, or size). In general, conservative amino acid substitutions do not significantly change the functional properties of a protein. When comparing proteins comprising conservative substitutions, the percentage of sequence similarity can be adjusted to account for the conservative nature of the substitution. Such adjustments are well known in the art. See, for example, Pearson, Methods Mol. Biol. 243: 307-31 (1994). Table 2 (see below) provides some of the biochemical properties of twenty naturally occurring amino acids. Table 3 (see below) provides non-limiting examples of conservative amino acid substitutions for each of the naturally occurring amino acids. Table 2. Table 3.

[0059] In the context of polypeptide (or polynucleotide) sequences, the term "percentage of sequence identity" is defined as the percentage of amino acid (or nucleic acid) residues in a candidate sequence that are identical to those in a reference polypeptide (or polynucleotide) sequence, after aligning the sequences and introducing gaps (if necessary) to achieve the maximum percentage of sequence identity and not counting any conservative substitutions as differences. Such conservative substitutions (in addition to identical residues) are taken into account when calculating the "percentage of sequence similarity" between two sequences. Residue positions that are not identical but similar differ by conservative amino acid substitutions.

[0060] Sequence alignment (e.g., for determining percent amino acid sequence identity or percent sequence similarity, e.g., between a wild-type protein and a mutant thereof) can be achieved in various ways that are within the skill in the art, for example, using publicly available sequence analysis computer software such as BLAST, BLAST-2, ALIGN, Megalign (DNASTAR), Gap, As well as other programs in Wisconsin Package Version 10.0 or Genetics Computer Group (GCG) (Madison, Wisconsin) software. Those skilled in the art can determine the appropriate parameters for aligning sequences, including any algorithm required for achieving maximum alignment over the full length of the compared sequences. FASTA can also be used to compare polypeptide sequences using default or recommended parameters. In the context of polypeptide sequences, FASTA uses a query amino acid sequence and uses a local sequence alignment to search a sequence database to identify similar sequences within the database (Pearson, Methods Enzymol. [Enzymology Methods] 183: 63-98 (1990); Pearson, Methods Mol. Biol. [Molecular Biology Methods] 132: 185-219 (2000); Pearson Curr Protoc Bioinformatics. [Bioinformatics Experiment Guide] March 24; 53: 3.9.1-25 (2016); each of which is incorporated herein by reference). BLAST, particularly blastp or tblastn, can be used to compare a query sequence to a database containing sequences from different organisms using default parameters. See, e.g., Altschul et al., J. Mol. Biol. 215:403-410 (1990); Altschul et al., Nucleic Acids Res. 25:3389-402 (1997); Eser et al., PLoS One. 22;9(12):e115445 (2014), each of which is incorporated herein by reference.

[0061] Amino acids can be grouped according to their similar biochemical properties. Such groupings that can be used to define conservative substitutions include: 1) amino acid residues with aliphatic side chains: glycine, alanine, valine, leucine, and isoleucine; 2) amino acid residues with aliphatic hydroxyl side chains: serine and threonine; 3) amino acid residues with amide-containing side chains: asparagine and glutamine; 4) amino acid residues with aromatic side chains: phenylalanine, tyrosine, and tryptophan; 5) amino acid residues with basic side chains: lysine, arginine, and histidine; 6) amino acid residues with acidic side chains: aspartic acid and glutamic acid; and 7) amino acid residues with sulfur-containing side chains: cysteine ​​and methionine. Non-limiting examples of preferred conservative amino acid substitution groups include: valine-leucine-isoleucine, phenylalanine-tyrosine, lysine-arginine, alanine-valine, glutamic acid-aspartic acid, and asparagine-glutamine.

[0062] As used herein, the term "effector function" refers to the cellular response of the immune system triggered by the interaction of antibodies and antibody-antigen complexes. These effector functions are generally related to one of three main mechanisms: antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and opsonization and phagocytosis. In ADCC, Fc receptors on cytotoxic T cells, natural killer (NK) cells, or macrophages bind to the Fc domain of antibodies that bind to target cells, resulting in the secretion of substances (such as lytic enzymes, perforins, granzymes, and tumor necrosis factors) that mediate the destruction of the target cells. In CDC, cell death is induced via activation of the complement cascade. See Daeron, Annu. Rev. Immunol. [Annals of Immunology], 15: 203-234 (1997); Ward and Ghetie, Therapeutic Immunol. [Therapeutic Immunology], 2: 77-94 (1995); and Ravetch and Kinet, Annu. Rev. Immunol. [Annals of Immunology] 9: 457-492 (1991). In opsonization and phagocytosis, the Fc domain of the pathogen-binding antibody binds to the Fc receptor on the surface of the phagocyte, thereby inducing phagocytosis. Such effector functions generally require the Fc domain to be combined with a binding domain (e.g., an antibody variable domain) and can be assessed using standard assays known in the art (see, e.g., WO 05 / 018572, WO05 / 003175, and U.S. Patent No. 6,242,195). The Fc domain of an antibody mediates immune effector mechanisms. IgG antibodies activate effector pathways of the immune system by binding to members of the Fcγ receptor family on cell surfaces and C1q of the complement system. Linking effector proteins via clustered antibodies triggers a variety of responses, including the release of inflammatory cytokines, modulation of antigen production, endocytosis, and cell killing. These responses can lead to adverse side effects, such as inflammation and thrombosis. Therefore, the present disclosure further relates to anti-CD3 antibodies with modified effector functions, including antibodies in which one or more effector functions are reduced or eliminated.

[0063] As used herein, the term "modified effector function" refers to an Fc domain having one or more effector functions that are different from the wild-type immunoglobulin Fc domain. In some embodiments, one or more effector functions are reduced. Optionally, one or more effector functions are eliminated. The modified or reduced effector function may be due to the low binding affinity of the Fc domain of the antibody disclosed herein to effector molecules (e.g., FcγR and / or C1q). For example, compared to wild-type anti-CD3 antibodies, the anti-CD3 antibodies disclosed herein may have reduced Fc receptor binding and complement activation. In some embodiments, the variant Fc domain has reduced antibody-dependent cell-mediated cytotoxicity (ADCC). The effector function of the anti-CD3 antibody can be determined using one of many known assays, including CDC assays, ADCC assays, and phagocytosis assays (see Xu-Rong Jiang et al., Nature Reviews Drug Discovery 10:101-111 (2011) and Liu et al., The Journal of Biological Chemistry 292:1876-1883 (2017). One or more of the effector functions of the antibody may be reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% relative to the effector function of the wild-type antibody.

[0064] The strength or affinity of an immunological binding interaction can be expressed in terms of the dissociation constant (K) of the interaction. D ) to represent the smaller K D Indicates greater affinity. The immunological binding properties of a selected polypeptide can be quantified using methods well known in the art. One such method requires measuring the rates of formation and dissociation of antigen binding sites / antigen complexes, where these rates depend on the concentration of the complex partners, the affinity of the interaction, and geometric parameters that affect the rates equally in both directions. Thus, the "association rate constant" (k on ) and the “dissociation rate constant” (k off ) can be determined by calculating the concentration and the actual rates of association and dissociation. off / k on The ratio of these two factors cancels out all affinity-independent parameters and is therefore equal to the dissociation constant K. D See, Davies et al. (1990) Annual Rev. Biochem. 59:439-473. D Antibodies are considered to specifically bind to antigens when their affinity is ≤1 μM, preferably ≤100 nM. High affinity antibodies typically have low affinity in the low nanomolar (10-9 ) in the range of K D , while very high affinity antibodies typically have a binding affinity in the picomolar (10 -12 ) in the range of K D .K D Binding affinity constants can be measured by surface plasmon resonance, e.g. using System (Cytiva Life Sciences, Uppsala, Sweden and Piscataway, NJ). See also Jonsson et al., Ann. Biol. Clin. 51:19-26 (1993); Jonsson et al., Biotechniques 11:620-627 (1991); Jonsson et al., J. Mol. Recognit. 8:125-131 (1995); Johnsson et al., Anal. Biochem. 198:268-277 (1991); Hearty S et al., Methods Mol Biol. 907:411-42 (2012), each of which is incorporated herein by reference. K D You can also use The system (Sapidyne Instruments, Hannover, Germany and Boise, Idaho) was used to measure K D You can also use The antibody or antigen-binding fragment thereof is measured by biolayer interferometry (BLI) using the ELISA system (Sartorius AG, Göttingen, Germany). An antibody or antigen-binding fragment thereof is said to "specifically bind," "immunologically bind," and / or "immunoreactive" with CD3 if it reacts with CD3 at a detectable level (e.g., in an ELISA assay) and does not detectably react with unrelated polypeptides under similar conditions. In some embodiments, the antibody or antigen-binding fragment thereof specifically binds CD3.

[0065] As used herein, the term "avidity" refers to the overall strength of an antibody-antigen complex. Avidity involves three main parameters: the affinity of the antibody for the epitope; the valency of both the antibody and the antigen; and the structural arrangement of the interacting parts. As used herein, "avidity" describes the increased affinity that occurs due to multiple antigen-binding sites on an immunoglobulin.

[0066] As used herein, the terms "polynucleotide" and "nucleic acid molecule" are used interchangeably and refer to nucleic acid polymers linked together by chemical bonds. Polynucleotides include, but are not limited to, DNA, cDNA, RNA, mRNA, and gene sequences and segments. Polynucleotides can be isolated from living sources such as eukaryotic cells, prokaryotic cells, or viruses, or can be derived by in vitro manipulation using standard molecular biology techniques, or by DNA synthesis, or by a combination of various techniques. Polynucleotides can comprise ribonucleotides, deoxynucleotides, modified forms of any type of nucleotide, or a combination thereof. Polynucleotides can be single-stranded or double-stranded. Unless otherwise indicated, reference to a nucleotide sequence herein encompasses its complementary sequence. Therefore, reference to a polynucleotide having a specific sequence should be understood to encompass its complementary chain and its complementary sequence.

[0067] As used herein, the term "high stringency conditions" refers to hybridization to filter-bound DNA in 0.1x sodium chloride / sodium citrate (SSC) at 65° C., followed by one or more washes in 0.1x SSC, 0.1% SDS at 50-65° C. (Ausubel et al., eds., 1989, Current Protocols in Molecular Biology, Vol. 1, Green Publishing Associates, Inc., and John Wiley & Sons, Inc., New York, at page 2.10.3).

[0068] As used herein, the term "operably connected" refers to two structures that have been placed in a functional relationship between each other. For example, in the context of an antibody, a targeting structure can be operably connected to a structure that imparts effector function. For example, the antigen-binding sequence (e.g., variable region or VH or VL domain) of an antibody can be operably connected to an Fc domain. In the context of a polynucleotide, a coding sequence can be operably connected to a non-coding regulatory sequence, such as a promoter, enhancer, signal sequence, ribosome binding sequence, splice acceptor sequence, splice donor sequence, terminator sequence, etc. Two operably connected structures can be directly connected. Alternatively, two operably connected structures can be connected via one or more intermediate structures. For example, the antigen-binding portion of an antibody can be operably connected to an Fc domain via a CH1 domain, a hinge region, and / or a linker sequence. Similarly, operably connected non-coding regulatory sequences include sequences that act in cis and are adjacent to the coding sequence, and sequences that act in trans or maintain a certain distance to control the coding sequence.

[0069] As used herein, the term "vector" refers to a polynucleotide molecule that can be replicated in a cell, and another polynucleotide fragment can be integrated into the cell without losing the replication ability of the vector. The vector can be derived from a virus, a plasmid or a cell of a higher organism. The vector is used to introduce exogenous or recombinant DNA into a host cell, wherein the vector is replicated. Non-limiting examples of vectors include viral vectors, naked DNA or RNA expression vectors, bacterial vectors, mammalian vectors, plasmids, cosmids, phage vectors, DNA or RNA expression vectors associated with a cationic condensing agent, DNA or RNA expression vectors encapsulated in liposomes, and certain eukaryotic cells, such as production cells. In certain embodiments, the vector replicates autonomously in the introduced host cell. Optionally, the vector is integrated into the genome of the host cell and replicates together with the host genome. The vector may be able to direct the expression of the coding sequence it contains. Such a vector is referred to as a "recombinant expression vector" or "expression vector" in this article.

[0070] The polynucleotide can be contained in a vector, which can promote the operation of the polynucleotide, including introducing the polynucleotide into a target cell. The vector can be a cloning vector, which can be used to maintain the polynucleotide. In the case of polynucleotide encoding RNA, in order to express the encoded RNA in a specific cell, so that the RNA is subsequently translated into a polypeptide or subsequently in the cell, trans-regulatory activity is carried out by RNA, the vector can be an expression vector, which, in addition to the polynucleotide, also includes a regulatory element for expressing the polynucleotide. The expression vector can contain the necessary expression elements for realizing, for example, the continuous transcription of the encoding polynucleotide, or the regulatory element can be operably connected to the polynucleotide before the polynucleotide is cloned into the vector.

[0071] Expression vectors typically contain a promoter sequence that can provide constitutive expression of the encoding polynucleotide or, if desired, inducible, tissue-specific, or developmental stage-specific expression; a poly A sequence; and a ribosome recognition site or internal ribosome entry site, or other regulatory elements, such as enhancers, which can be tissue-specific. The vector may also contain elements required for replication in a prokaryotic or eukaryotic host system, or both, as desired. Such vectors (including plasmid vectors and viral vectors, e.g., phage, baculovirus, retrovirus, lentivirus, adenovirus, vaccinia virus, alphavirus, and adeno-associated virus vectors) are well known and available from commercial sources (Promega, Madison, Wis.; Agilent Technologies, Santa Clara, Calif.; Thermo Fisher Scientific, Waltham, Mass.) or can be constructed by one skilled in the art (see, e.g., Meth. Enzymol., Vol. 185, Goeddel, ed. (Academic Press, Inc., 1990); Jolly, Canc. Genet., et al., 1996). Ther. [Cancer Gene Ther.] 1:51-64, 1994; Flotte, J. Bioenerg. Biomemb. [Bioenergetics and Biomembranes] 25:37-42, 1993; Kirshenbaum et al., J. Clin. Invest [Clinical Research Journal], 92:381-387, 1993; each of which is incorporated herein by reference).

[0072] As used herein, the term "polynucleotide construct" refers to a DNA sequence artificially constructed by genetic engineering, recombinant engineering, or synthesis. In some embodiments, the DNA construct is linearized prior to recombination. In another embodiment, the DNA construct is not linearized prior to recombination.

[0073] As used herein, the term "host cell" refers to a cell into which a polynucleotide or vector has been introduced. It should be understood that "host cell" includes not only the specific subject cell, but also the progeny of such cells. Because certain modifications may occur in subsequent generations due to mutations or environmental influences, such progeny may actually be different from the parent cell, but are still included in the scope of the term "host cell" as used herein, as long as they still contain the vector, polynucleotide or portion thereof, whether maintained episomally or integrated into the host cell genome.

[0074] The terms "patient," "subject," and "individual" are used interchangeably herein and refer to a human or non-human animal in need of treatment. These terms include mammals, such as humans, primates (e.g., monkeys), livestock (e.g., cattle, sheep, pigs, horses, and goats), and companion animals (e.g., dogs and cats). Optionally, the subject is a human. In some embodiments, the subject has or is at risk of developing cancer.

[0075] With respect to a subject, the terms "treating" and "treatment" refer to improving at least one symptom of a disease or disorder in a subject. Treatment includes curing, ameliorating, or at least partially alleviating a disease or disorder or any symptom of the disease or disorder. With respect to cancer, these terms refer to increasing the life expectancy of an individual with cancer, or alleviating one or more of the symptoms of cancer. These terms also encompass reducing the risk of developing a malignancy in a subject with cancer. With respect to the treatment of an autoimmune disease, treatment can refer to suppressing the body's immune response and controlling the autoimmune reaction.

[0076] As used herein, the terms "prevent," "preventing," and "prevention" refer to preventing or delaying the recurrence or onset of a disease or disorder, or alleviating one or more symptoms thereof, in a subject as a result of administering an anti-CD3 antibody of the present disclosure. For example, in the context of cancer, "prevent," "preventing," and "prevention" refer to inhibiting, alleviating, delaying the development of one or more symptoms associated with cancer in a subject, preventing or delaying the recurrence, onset, or development thereof, and maintaining remission in a subject. Additionally, in the context of an autoimmune disease, "prevent," "preventing," and "prevention" refer to inhibiting, alleviating, or delaying the development or onset of an autoimmune response, or preventing or delaying the recurrence, onset, or development of one or more symptoms associated with an autoimmune response.

[0077] As used herein, the term "therapeutically effective amount" refers to the amount of a therapeutic agent administered as a single agent or in combination with one or more additional agents, which will alleviate one or more of the symptoms of the treated condition to a certain extent. In the case of cancer treatment, a therapeutically effective amount refers to an amount with at least one of the following effects: slowing down, improving, stabilizing, reversing, preventing, slowing down or delaying the progression of cancer (and / or symptoms associated with cancer). The effective amount that can be used in this disclosure varies according to the mode of administration, the age, weight and overall health of the subject. Appropriate amounts and dosage regimens can be determined using conventional techniques in the art.

[0078] A "prophylactically effective amount" refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired prophylactic result. Typically, a prophylactic amount may be less than a therapeutically effective amount because a prophylactic dose is used in subjects in remission.

[0079] As used herein, the terms "pharmaceutically acceptable carrier" and "pharmaceutically acceptable excipient" are used interchangeably and refer to any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic agents, and absorption delaying agents that are physiologically compatible. Pharmaceutically acceptable carriers are well known in the art. See, for example, Remington's Pharmaceutical Sciences and US Pharmacopeia: National Formulary, Mack Publishing Company, Easton, Pennsylvania (1984), incorporated herein by reference. These carriers, but not limited to, may be included in the FDA Generally Recognized as Safe (GRAS) excipients compilation (https: / / www.fda.gov / food / food-ingredients-packaging / generally-recognized-safe-gras). Some examples of pharmaceutically acceptable carriers are water, saline, phosphate-buffered saline, dextrose, glycerol, ethanol, and the like, and combinations thereof. In many cases, it is preferred to include isotonic agents, for example, sugars, polyalcohols such as mannitol, sorbitol, or sodium chloride in the composition. Additional examples of pharmaceutically acceptable substances are wetting agents or minor amounts of auxiliary substances, such as wetting or emulsifying agents, preservatives, or buffers, which enhance the shelf life or effectiveness of the antibody.Pharmaceutical compositions can be prepared by mixing an antibody disclosed herein with an acceptable carrier, excipient, or stabilizer in the form of, for example, a lyophilized powder, a slurry, an aqueous solution, or a suspension (see, e.g., Hardman, et al. (2001) Goodman and Gilman's The Pharmacological Basis of Therapeutics, McGraw-Hill, New York, NY; Gennaro (2000) Remington: The Science and Practice of Pharmacy, Lippincott, Williams, and Wilkins, New York, NY; Avis, et al. (eds.) (1993) Pharmaceutical Dosage Forms: Parenteral Medications, Marcel Dekker, NY). Dekker, New York, NY; Lieberman, et al. (eds.) (1990) Pharmaceutical Dosage Forms: Tablets, Marcel Dekker, Inc., New York, NY; Lieberman, et al. (eds.) (1990) Pharmaceutical Dosage Forms: Disperse Systems, Marcel Dekker, Inc., New York, NY; Weiner and Kotkoskie (2000) Excipient Toxicity and Safety, Marcel Dekker, Inc., New York, NY; each of which is incorporated herein by reference).

[0080] As used herein, the term "administering" refers to any means of transferring, delivering, introducing, or transporting a pharmaceutical composition or other agent (eg, an anti-CD3 antibody) to a subject. For cancer therapy, such administration is typically parenteral, such as intravenous.

[0081] Unless expressly stated otherwise, each embodiment in this specification should be applicable to every other embodiment mutatis mutandis.

[0082] Standard techniques can be used for recombinant DNA, oligonucleotide synthesis and tissue culture and conversion (for example, electroporation, lipofection). Enzymatic reaction and purification techniques can be carried out according to the manufacturer's instructions or as usually completed in this area or as described herein. These and related techniques and procedures are normally carried out according to conventional methods well known in the art and as described in the different general and more specific references cited and discussed in this specification sheet in its entirety. Unless specific definition is provided, the nomenclature and laboratory procedures and techniques thereof used in relation to molecular biology as herein described, analytical chemistry, synthetic organic chemistry and medical science and pharmaceutical chemistry are well known in the art and commonly used. Standard techniques can be used for recombinant technology, molecular biology, microbiology, chemosynthesis, chemical analysis, pharmaceutical preparation, formulation and delivery and patient treatment. anti-CD3 antibodies

[0083] Mouse anti-CD3 antibody was used XKL mice ( Crosses between κ-λ mice and another genetic background) and Mice are generated only by λ mice. XKL mice produce antibodies containing chimeric immunoglobulin heavy chains (IgH) and either human immunoglobulin kappa (Igκ) light chains or human immunoglobulin lambda (Igλ) light chains. Only lambda mice produce antibodies containing chimeric IgH chains and human immunoglobulin lambda (Igλ) light chains. The chimeric IgH chain of the mouse antibody comprises a human variable region containing a human variable heavy (VH) domain, a human diversity heavy (DH) domain, and a human joining heavy (JH) domain, a human constant heavy 1 (CH1) domain, a human upper hinge region (except for Cμ, which naturally lacks an upper hinge region), a mouse middle hinge region, a mouse CH2 domain, and a mouse CH3 domain. The human heavy chain variable region of any of the chimeric anti-CD3 antibodies can be easily attached to a fully human constant region while maintaining the Antigen binding properties of parent chimeric antibodies produced in mice. In some embodiments, the human heavy chain variable region, CH1, and, optionally, upper hinge region of a chimeric antibody are appended to a human hinge, human CH2 domain, and human CH3 domain to produce a fully human antibody.

[0084] A first aspect of the present disclosure provides an anti-CD3 antibody or antigen-binding fragment thereof. The anti-CD3 antibody or antigen-binding fragment thereof can be human. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof of the present disclosure is chimeric. In some embodiments, the chimeric anti-CD3 antibody or antigen-binding fragment thereof comprises a chimeric IgH chain and a human Igκ chain. In some embodiments, the chimeric anti-CD3 antibody or antigen-binding fragment thereof comprises a chimeric IgH chain and a human Igλ chain. In some embodiments, the chimeric anti-CD3 antibody comprises human and mouse sequences. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof of the present disclosure is a bispecific antibody. In some embodiments, the bispecific antibody further comprises a tumor targeting arm.

[0085] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises one to six complementarity determining regions (CDRs) disclosed herein. The one to six CDRs may comprise an amino acid sequence selected from the group consisting of: SEQ ID NO: 1-687.

[0086] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a heavy chain CDR3 (HCDR3) disclosed herein. The HCDR3 may comprise an amino acid sequence selected from the group consisting of SEQ ID NOs: 574-687. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a light chain CDR3 (LCDR3) disclosed herein. The LCDR3 may comprise an amino acid sequence selected from the group consisting of SEQ ID NOs: 227-344.

[0087] In some embodiments, the CDRs of the anti-CD3 antibodies or antigen-binding fragments thereof can be mixed and matched between the CDRs of the antibody clones disclosed herein. In some embodiments, the anti-CD3 antibodies or antigen-binding fragments thereof comprise a HCDR1 comprising any HCDR1 sequence disclosed herein, a HCDR2 comprising any HCDR2 sequence disclosed herein, and a HCDR3 comprising any HCDR3 sequence disclosed herein. In some embodiments, the HCDR1, HCDR2, and HCDR3 are selected from three different anti-CD3 clones disclosed herein. In some embodiments, the HCDR1, HCDR2, and HCDR3 are selected from two different anti-CD3 clones disclosed herein. In some embodiments, the HCDR1, HCDR2, and HCDR3 are from a single anti-CD3 clone disclosed herein.

[0088] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a LCDR1 comprising any LCDR1 sequence disclosed herein, a LCDR2 comprising any LCDR2 sequence disclosed herein, and a LCDR3 comprising any LCDR3 sequence disclosed herein. In some embodiments, the LCDR1, LCDR2, and LCDR3 are selected from three different anti-CD3 clones disclosed herein. In some embodiments, the LCDR1, LCDR2, and LCDR3 are selected from two different anti-CD3 clones disclosed herein. In some embodiments, the LCDR1, LCDR2, and LCDR3 are derived from a single anti-CD3 clone disclosed herein. The single anti-CD3 clone can be the same anti-CD3 clone from which the HCDR1, HCDR2, and HCDR3 are selected.

[0089] In some embodiments, the six CDRs of the anti-CD3 antibody or antigen-binding fragment thereof are derived from the same anti-CD3 antibody clone disclosed herein. In some embodiments, the six CDRs of the anti-CD3 antibody or antigen-binding fragment thereof are selected from the corresponding VH and VL of a single clone disclosed herein. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises: 1) HCDR1, HCDR2, and HCDR3 selected from the HCDR1, HCDR2, and HCDR3 of a VH selected from any of the VH regions disclosed herein; and 2) LCDR1, LCDR2, and LCDR3 selected from the LCDR1, LCDR2, and LCDR3 of a VL selected from any of the VL regions disclosed herein. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 within the corresponding VH and VL amino acid sequences of a single clone as disclosed herein.

[0090] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VH comprising any of the VH regions disclosed herein. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising any of the VL regions disclosed herein. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a single clone of the corresponding VH and VL.

[0091] The CDRs, VH and / or VL may be selected from any one of the clones from the group consisting of ABL-CD3-1 to ABL-CD3-113, ABL-CD3-1A to ABL-CD3-113A, and ABL-CD3-85B.In some embodiments, the CDR, VH, and / or VL can be from an antibody selected from the group consisting of: ABL-CD3-18, ABL-CD3-20, ABL-CD3-21, ABL-CD3-22, ABL-CD3-27, ABL-CD3-29, ABL-CD3-31, ABL-CD3-34, ABL-CD3-36, ABL-CD3-37, ABL-CD3-39, ABL-CD3-40, ABL-CD3-41, ABL-CD3-43, ABL-CD3-44, ABL-CD3-45, ABL-CD3-47, ABL-CD3-49, ABL-CD3-52, ABL-CD3-53, ABL-CD3-56, ABL-CD3-57, ABL-CD3-61, ABL-CD3-62, ABL-CD3-63, ABL-CD3-64, ABL-CD3-65, ABL-CD3-66, ABL-CD3-68, ABL-CD3-71, ABL-CD3-72, ABL-CD3-74, ABL-CD3-76, ABL-CD3-77, ABL-CD3-79, ABL-CD3-81, ABL-CD3-85, ABL-CD3-87, ABL-CD3-88, ABL-CD3-89, ABL-CD3-18A, ABL-CD3-20A, ABL-CD3-21A, ABL-CD3-22A, ABL-CD3-27A, ABL-CD3-29A, ABL-CD3-31A, ABL-CD3-34A, ABL-CD3-36A, ABL-CD3-37A, ABL-CD3-39A, ABL-CD3-40A, ABL-CD3-41A, ABL-CD3-43A, ABL-CD3-44A, ABL-CD3-45A, ABL-CD3-47A, ABL-CD3-49A, ABL-CD3-52A, ABL-CD3-53A, ABL-CD3-56A, ABL-CD3-57A, ABL-CD3-61A, ABL-CD3-62A, ABL-CD3-63A, ABL-CD3-64A, ABL-CD3-65A, ABL-CD3-66A, ABL-CD3-68A, ABL-CD3-71A, ABL-CD3-72A, ABL-CD3-74A, ABL-CD3-76A, ABL-CD3-77A, ABL-CD3-79A, ABL-CD3-81A, ABL-CD3-85A, ABL-CD3-85B, ABL-CD3-87A, ABL-CD3-88A, and ABL-CD3-89A.

[0092] In some embodiments, an anti-CD3 antibody or antigen-binding fragment thereof comprises i) a heavy chain variable region comprising a HCDR1 disclosed herein, a HCDR2 disclosed herein, and a HCDR3 disclosed herein, and ii) a light chain variable region comprising a LCDR1 disclosed herein, a LCDR2 disclosed herein, and a LCDR3 disclosed herein. The HCDR1 may comprise an amino acid sequence selected from the group consisting of SEQ ID NOs: 345-457. In some embodiments, the HCDR2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 458-573. The HCDR3 may comprise an amino acid sequence selected from the group consisting of SEQ ID NOs: 574-687. In some embodiments, the LCDR1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-113. The LCDR2 may comprise an amino acid sequence selected from the group consisting of SEQ ID NOs: 114-226. In some embodiments, the LCDR3 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 227-344. In some embodiments, the VL region comprises an amino acid sequence selected from the group consisting of: SEQ ID NOs: 688-914. The VH region may comprise an amino acid sequence selected from the group consisting of: SEQ ID NOs: 915-1141.

[0093] It is known in the art that during the processing and expression of Fc-containing proteins (e.g., antibody heavy chains), the C-terminal lysine may be cleaved (also referred to in the art as C-terminal lysine shearing). Therefore, for each sequence disclosed herein containing a C-terminal lysine, corresponding sequences not containing the C-terminal lysine (i.e., C-terminal lysine cleavage products) are also contemplated. In some embodiments, the first monomer comprises a C-terminal lysine. In some embodiments, the first monomer lacks a C-terminal lysine. In some embodiments, the second monomer comprises a C-terminal lysine. In some embodiments, the second monomer lacks a C-terminal lysine.

[0094] It is also known in the art that the C-terminal cleavage process is imprecise and may cleave additional C-terminal residues. Therefore, for each sequence disclosed herein that contains a C-terminal lysine, a corresponding sequence that does not contain two C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein that contains a C-terminal lysine, a corresponding sequence that does not contain three C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein that contains a C-terminal lysine, a corresponding sequence that does not contain four C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein that contains a C-terminal lysine, a corresponding sequence that does not contain five C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein that contains a C-terminal lysine, a corresponding sequence that does not contain six C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein that contains a C-terminal lysine, a corresponding sequence that does not contain seven C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein that contains a C-terminal lysine, a corresponding sequence that does not contain eight C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein that contains a C-terminal lysine, a corresponding sequence that does not contain nine C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein that contains a C-terminal lysine, a corresponding sequence that does not contain ten C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein that contains a C-terminal lysine, a corresponding sequence that does not contain eleven C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein that contains a C-terminal lysine, a corresponding sequence that does not contain twelve C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein that contains a C-terminal lysine, a corresponding sequence that does not contain thirteen C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein that contains a C-terminal lysine, a corresponding sequence that does not contain fourteen C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein that contains a C-terminal lysine, a corresponding sequence that does not contain fifteen C-terminal residues is also contemplated.

[0095] In some embodiments, the anti-CD3 antibody is a whole antibody. In some embodiments, the anti-CD3 antibody is a single-chain antibody. In some embodiments, the anti-CD3 antibody is a scFv. In some embodiments, the anti-CD3 antibody is a Fab. In some embodiments, the anti-CD3 antibody is a Fab'. In some embodiments, the anti-CD3 antibody is a F(ab')2. In some embodiments, the anti-CD3 antibody is an Fv. In some embodiments, the anti-CD3 antibody is a scFv comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 1155-1236. Those skilled in the art will recognize that scFv fragments can be arranged from the N-terminus to the C-terminus in a VH to VL orientation or in a VL to VH orientation. As used herein, the term "scFv-VH-VL" refers to an scFv fragment arranged from the N-terminus to the C-terminus in a VH to VL orientation. Similarly, the term "scFv-VL-VH" refers to an scFv fragment arranged from the N-terminus to the C-terminus in a VL to VH orientation.

[0096] In some embodiments, VH comprises a G44C substitution (according to Kabat numbering). In some embodiments, VL comprises a G100C substitution (according to Kabat numbering). In some embodiments, VH comprises a G44C substitution, and VL comprises a G100C substitution (according to Kabat numbering). In rare cases, the parent sequence at VH44 may be an amino acid residue different from G. In this case, the VH44 residue (according to Kabat) is still mutated to cysteine. In more common but still relatively rare cases, the parent sequence at VL position 100 may be an amino acid other than G. In this case, the VL100 residue (according to Kabat) is still mutated to cysteine. Without being bound by theory, the introduction of such complementary cysteine ​​residues can produce disulfide bonds, which can stabilize antibody fragments (e.g., scFv). Although not exhaustive, other Cys substitutions are known and can be adopted (see Weatherill et al., PEDS (2012) 25:321-9), including VL positions 99, 100a, and 101. In some embodiments, free cysteine ​​residues in VH and / or VL can be substituted with non-cysteine ​​residues.

[0097] In some embodiments, the anti-CD3 antibody is a bispecific antibody. In some embodiments, the anti-CD3 bispecific antibody further comprises a targeting antibody or an antigen-binding fragment thereof. In some embodiments, the targeting antibody binds to a specific tissue. It is within the skill of the art to select an appropriate targeting antibody based on the tissue to be targeted. In some embodiments, the targeting antibody is an anti-tumor antibody or an antigen-binding fragment thereof. In some embodiments, the targeting antibody binds to a specific tissue. It is within the skill of the art to select an appropriate targeting antibody based on the tumor to be targeted.

[0098] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-1 and ABL-CD3-1A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 1, 114, and 227, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 345, 458, and 574, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-1. The VL may comprise the amino acid sequence of SEQ ID NO: 688. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-1. The VH may comprise the amino acid sequence of SEQ ID NO: 915. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-1. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 688, and a VH comprising the amino acid sequence of SEQ ID NO: 915. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-1A. The VL may comprise the amino acid sequence of SEQ ID NO: 801. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-1A. The VH may comprise the amino acid sequence of SEQ ID NO: 1028. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-1A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 801, and a VH comprising the amino acid sequence of SEQ ID NO: 1028. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-1_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 915; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 688. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-1_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 688; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 915. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-1A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1028; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 801. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-1A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 801; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1028.

[0099] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-2 and ABL-CD3-2A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 2, 115, and 228, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 346, 459, and 575, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-2. The VL may comprise the amino acid sequence of SEQ ID NO: 689. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-2. The VH may comprise the amino acid sequence of SEQ ID NO: 916. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-2. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 689 and a VH comprising the amino acid sequence of SEQ ID NO: 916. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-2A. The VL may comprise the amino acid sequence of SEQ ID NO: 802. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-2A. The VH may comprise the amino acid sequence of SEQ ID NO: 1029. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-2A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 802 and a VH comprising the amino acid sequence of SEQ ID NO: 1029. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-2_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 916; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 689. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-2_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 689; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 916. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-2A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1029; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 802. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-2A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 802; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1029.

[0100] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-3 and ABL-CD3-3A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 3, 116, and 229, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 347, 460, and 576, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-3. The VL may comprise the amino acid sequence of SEQ ID NO: 690. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-3. The VH may comprise the amino acid sequence of SEQ ID NO: 917. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-3. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 690, and a VH comprising the amino acid sequence of SEQ ID NO: 917. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-3A. The VL may comprise the amino acid sequence of SEQ ID NO: 803. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-3A. The VH may comprise the amino acid sequence of SEQ ID NO: 1030. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-3A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 803, and a VH comprising the amino acid sequence of SEQ ID NO: 1030. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-3_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 917; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 690. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-3_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 690; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 917. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-3A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1030; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 803. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-3A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 803; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1030.

[0101] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-4 and ABL-CD3-4A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 4, 117, and 230, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 348, 461, and 577, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-4. The VL may comprise the amino acid sequence of SEQ ID NO: 691. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-4. The VH may comprise the amino acid sequence of SEQ ID NO: 918. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-4. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 691 and a VH comprising the amino acid sequence of SEQ ID NO: 918. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-4A. The VL may comprise the amino acid sequence of SEQ ID NO: 804. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-4A. The VH may comprise the amino acid sequence of SEQ ID NO: 1031. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-4A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 804 and a VH comprising the amino acid sequence of SEQ ID NO: 1031. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-4_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 918; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 691. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-4_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 691; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 918. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-4A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1031; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 804. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-4A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 804; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1031.

[0102] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-5 and ABL-CD3-5A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 5, 118, and 231, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 349, 462, and 578, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-5. The VL may comprise the amino acid sequence of SEQ ID NO: 692. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-5. The VH may comprise the amino acid sequence of SEQ ID NO: 919. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-5. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 692, and a VH comprising the amino acid sequence of SEQ ID NO: 919. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-5A. The VL may comprise the amino acid sequence of SEQ ID NO: 805. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-5A. The VH may comprise the amino acid sequence of SEQ ID NO: 1032. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-5A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 805, and a VH comprising the amino acid sequence of SEQ ID NO: 1032. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-5_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 919; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 692. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-5_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 692; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 919. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-5A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1032; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 805. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-5A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 805; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1032.

[0103] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-6 and ABL-CD3-6A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 6, 119, and 232, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 350, 463, and 579, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-6. The VL may comprise the amino acid sequence of SEQ ID NO: 693. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-6. The VH may comprise the amino acid sequence of SEQ ID NO: 920. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-6. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 693 and a VH comprising the amino acid sequence of SEQ ID NO: 920. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-6A. The VL may comprise the amino acid sequence of SEQ ID NO: 806. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-6A. The VH may comprise the amino acid sequence of SEQ ID NO: 1033. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-6A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 806 and a VH comprising the amino acid sequence of SEQ ID NO: 1033. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-6_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 920; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 693. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-6_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 693; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 920. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-6A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1033; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 806. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-6A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 806; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1033.

[0104] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-7 and ABL-CD3-7A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 7, 120, and 233, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 351, 464, and 580, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-7. The VL may comprise the amino acid sequence of SEQ ID NO: 694. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-7. The VH may comprise the amino acid sequence of SEQ ID NO: 921. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-7. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 694 and a VH comprising the amino acid sequence of SEQ ID NO: 921. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-7A. The VL may comprise the amino acid sequence of SEQ ID NO: 807. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-7A. The VH may comprise the amino acid sequence of SEQ ID NO: 1034. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-7A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 807 and a VH comprising the amino acid sequence of SEQ ID NO: 1034. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-7_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 921; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 694. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-7_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 694; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 921. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-7A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1034; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 807. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-7A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 807; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1034.

[0105] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-8 and ABL-CD3-8A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 8, 121, and 234, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 352, 465, and 581, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-8. The VL may comprise the amino acid sequence of SEQ ID NO: 695. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-8. The VH may comprise the amino acid sequence of SEQ ID NO: 922. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-8. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 695 and a VH comprising the amino acid sequence of SEQ ID NO: 922. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-8A. The VL may comprise the amino acid sequence of SEQ ID NO: 808. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-8A. The VH may comprise the amino acid sequence of SEQ ID NO: 1035. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-8A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 808 and a VH comprising the amino acid sequence of SEQ ID NO: 1035. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-8_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 922; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 695. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-8_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 695; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 922. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-8A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1035; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 808. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-8A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 808; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1035.

[0106] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-9 and ABL-CD3-9A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 9, 122, and 235, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 353, 466, and 582, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-9. The VL may comprise the amino acid sequence of SEQ ID NO: 696. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-9. The VH may comprise the amino acid sequence of SEQ ID NO: 923. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-9. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 696 and a VH comprising the amino acid sequence of SEQ ID NO: 923. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-9A. The VL may comprise the amino acid sequence of SEQ ID NO: 809. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-9A. The VH may comprise the amino acid sequence of SEQ ID NO: 1036. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-9A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 809 and a VH comprising the amino acid sequence of SEQ ID NO: 1036. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-9_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 923; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 696. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-9_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 696; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 923. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-9A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1036; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 809. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-9A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 809; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1036.

[0107] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-10 and ABL-CD3-10A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 10, 123, and 236, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 354, 467, and 583, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-10. The VL may comprise the amino acid sequence of SEQ ID NO: 697. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-10. The VH may comprise the amino acid sequence of SEQ ID NO: 924. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-10. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 697 and a VH comprising the amino acid sequence of SEQ ID NO: 924. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-10A. The VL may comprise the amino acid sequence of SEQ ID NO: 810. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-10A. The VH may comprise the amino acid sequence of SEQ ID NO: 1037. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-10A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 810 and a VH comprising the amino acid sequence of SEQ ID NO: 1037. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-10_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 924; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 697. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-10_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 697; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 924. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-10A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1037; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 810. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-10A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 810; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1037.

[0108] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-11 and ABL-CD3-11A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 11, 124, and 237, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 355, 468, and 584, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-11. The VL may comprise the amino acid sequence of SEQ ID NO: 698. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-11. The VH may comprise the amino acid sequence of SEQ ID NO: 925. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-11. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 698 and a VH comprising the amino acid sequence of SEQ ID NO: 925. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-11A. The VL may comprise the amino acid sequence of SEQ ID NO: 811. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-11A. The VH may comprise the amino acid sequence of SEQ ID NO: 1038. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-11A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 811 and a VH comprising the amino acid sequence of SEQ ID NO: 1038. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-11_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 925; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 698. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-11_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 698; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 925. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-11A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1038; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 811. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-11A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 811; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1038.

[0109] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-12 and ABL-CD3-12A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 12, 125, and 238, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 356, 469, and 585, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-12. The VL may comprise the amino acid sequence of SEQ ID NO: 699. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-12. The VH may comprise the amino acid sequence of SEQ ID NO: 926. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-12. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 699 and a VH comprising the amino acid sequence of SEQ ID NO: 926. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-12A. The VL may comprise the amino acid sequence of SEQ ID NO: 812. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-12A. The VH may comprise the amino acid sequence of SEQ ID NO: 1039. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-12A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 812 and a VH comprising the amino acid sequence of SEQ ID NO: 1039. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-12_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 926; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 699. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-12_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 699; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 926. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-12A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1039; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 812. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-12A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 812; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1039.

[0110] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-13 and ABL-CD3-13A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 13, 126, and 239, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 357, 470, and 586, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-13. The VL may comprise the amino acid sequence of SEQ ID NO: 700. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-13. The VH may comprise the amino acid sequence of SEQ ID NO: 927. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-13. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 700 and a VH comprising the amino acid sequence of SEQ ID NO: 927. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-13A. The VL may comprise the amino acid sequence of SEQ ID NO: 813. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-13A. The VH may comprise the amino acid sequence of SEQ ID NO: 1040. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-13A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 813 and a VH comprising the amino acid sequence of SEQ ID NO: 1040. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-13_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 927; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 700. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-13_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 700; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 927. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-13A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1040; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 813. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-13A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 813; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1040.

[0111] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-14 and ABL-CD3-14A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 14, 127, and 240, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 358, 471, and 587, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-14. The VL may comprise the amino acid sequence of SEQ ID NO: 701. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-14. The VH may comprise the amino acid sequence of SEQ ID NO: 928. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-14. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 701 and a VH comprising the amino acid sequence of SEQ ID NO: 928. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-14A. The VL may comprise the amino acid sequence of SEQ ID NO: 814. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-14A. The VH may comprise the amino acid sequence of SEQ ID NO: 1041. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-14A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 814 and a VH comprising the amino acid sequence of SEQ ID NO: 1041. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-14_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 928; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 701. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-14_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 701; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 928. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-14A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1041; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 814. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-14A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 814; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1041.

[0112] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-15 and ABL-CD3-15A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 15, 128, and 241, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 359, 472, and 588, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-15. The VL may comprise the amino acid sequence of SEQ ID NO: 702. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-15. The VH may comprise the amino acid sequence of SEQ ID NO: 929. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-15. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 702, and a VH comprising the amino acid sequence of SEQ ID NO: 929. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-15A. The VL may comprise the amino acid sequence of SEQ ID NO: 815. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-15A. The VH may comprise the amino acid sequence of SEQ ID NO: 1042. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-15A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 815, and a VH comprising the amino acid sequence of SEQ ID NO: 1042. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-15_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 929; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 702. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-15_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 702; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 929. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-15A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1042; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 815. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-15A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 815; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1042.

[0113] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-16 and ABL-CD3-16A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 16, 129, and 242, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 360, 473, and 589, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-16. The VL may comprise the amino acid sequence of SEQ ID NO: 703. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-16. The VH may comprise the amino acid sequence of SEQ ID NO: 930. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-16. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 703 and a VH comprising the amino acid sequence of SEQ ID NO: 930. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-16A. The VL may comprise the amino acid sequence of SEQ ID NO: 816. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-16A. The VH may comprise the amino acid sequence of SEQ ID NO: 1043. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-16A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 816 and a VH comprising the amino acid sequence of SEQ ID NO: 1043. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-16_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 930; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 703. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-16_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 703; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 930. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-16A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1043; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 816. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-16A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 816; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1043.

[0114] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-17 and ABL-CD3-17A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 17, 130, and 243, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 361, 474, and 590, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-17. The VL may comprise the amino acid sequence of SEQ ID NO: 704. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-17. The VH may comprise the amino acid sequence of SEQ ID NO: 931. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-17. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 704, and a VH comprising the amino acid sequence of SEQ ID NO: 931. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-17A. The VL may comprise the amino acid sequence of SEQ ID NO: 817. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-17A. The VH may comprise the amino acid sequence of SEQ ID NO: 1044. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-17A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 817, and a VH comprising the amino acid sequence of SEQ ID NO: 1044. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-17_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 931; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 704. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-17_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 704; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 931. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-17A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1044; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 817. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-17A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 817; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1044.

[0115] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-18 and ABL-CD3-18A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 18, 131, and 244, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 362, 475, and 591, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-18. The VL may comprise the amino acid sequence of SEQ ID NO: 705. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-18. The VH may comprise the amino acid sequence of SEQ ID NO: 932. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-18. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 705, and a VH comprising the amino acid sequence of SEQ ID NO: 932. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-18A. The VL may comprise the amino acid sequence of SEQ ID NO: 818. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-18A. The VH may comprise the amino acid sequence of SEQ ID NO: 1045. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-18A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 818, and a VH comprising the amino acid sequence of SEQ ID NO: 1045. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-18_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 932; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 705. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-18_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 705; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 932. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-18A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1155. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-18A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1196.

[0116] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-19 and ABL-CD3-19A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 19, 132, and 245, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 363, 476, and 592, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-19. The VL may comprise the amino acid sequence of SEQ ID NO: 706. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-19. The VH may comprise the amino acid sequence of SEQ ID NO: 933. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-19. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 706 and a VH comprising the amino acid sequence of SEQ ID NO: 933. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-19A. The VL may comprise the amino acid sequence of SEQ ID NO: 819. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-19A. The VH may comprise the amino acid sequence of SEQ ID NO: 1046. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-19A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 819 and a VH comprising the amino acid sequence of SEQ ID NO: 1046. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-19_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 933; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 706. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-19_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 706; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 933. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-19A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1046; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 819. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-19A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 819; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1046.

[0117] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-20 and ABL-CD3-20A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 20, 133, and 246, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 364, 477, and 593, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-20. The VL may comprise the amino acid sequence of SEQ ID NO: 707. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-20. The VH may comprise the amino acid sequence of SEQ ID NO: 934. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-20. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 707 and a VH comprising the amino acid sequence of SEQ ID NO: 934. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-20A. The VL may comprise the amino acid sequence of SEQ ID NO: 820. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-20A. The VH may comprise the amino acid sequence of SEQ ID NO: 1047. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-20A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 820 and a VH comprising the amino acid sequence of SEQ ID NO: 1047. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-20_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 934; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 707. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-20_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 707; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 934. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-20A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1156. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-20A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1197.

[0118] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-21 and ABL-CD3-21A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 21, 134, and 247, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 365, 478, and 594, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-21. The VL may comprise the amino acid sequence of SEQ ID NO: 708. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-21. The VH may comprise the amino acid sequence of SEQ ID NO: 935. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-21. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 708, and a VH comprising the amino acid sequence of SEQ ID NO: 935. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-21A. The VL may comprise the amino acid sequence of SEQ ID NO: 821. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-21A. The VH may comprise the amino acid sequence of SEQ ID NO: 1048. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-21A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 821, and a VH comprising the amino acid sequence of SEQ ID NO: 1048. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-21_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 935; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 708. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-21_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 708; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 935. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-21A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1157. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-21A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1198.

[0119] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-22 and ABL-CD3-22A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 22, 135, and 248, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 366, 479, and 595, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-22. The VL may comprise the amino acid sequence of SEQ ID NO: 709. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-22. The VH may comprise the amino acid sequence of SEQ ID NO: 936. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-22. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 709, and a VH comprising the amino acid sequence of SEQ ID NO: 936. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-22A. The VL may comprise the amino acid sequence of SEQ ID NO: 822. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-22A. The VH may comprise the amino acid sequence of SEQ ID NO: 1049. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-22A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 822, and a VH comprising the amino acid sequence of SEQ ID NO: 1049. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-22_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 936; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 709. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-22_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 709; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 936. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-22A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1158. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-22A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1199.

[0120] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-23 and ABL-CD3-23A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 23, 136, and 249, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 367, 480, and 596, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-23. The VL may comprise the amino acid sequence of SEQ ID NO: 710. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-23. The VH may comprise the amino acid sequence of SEQ ID NO: 937. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-23. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 710, and a VH comprising the amino acid sequence of SEQ ID NO: 937. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-23A. The VL may comprise the amino acid sequence of SEQ ID NO: 823. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-23A. The VH may comprise the amino acid sequence of SEQ ID NO: 1050. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-23A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 823, and a VH comprising the amino acid sequence of SEQ ID NO: 1050. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-23_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 937; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 710. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-23_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 710; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 937. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-23A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1050; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 823. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-23A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 823; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1050.

[0121] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-24 and ABL-CD3-24A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 24, 137, and 250, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 368, 481, and 597, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-24. The VL may comprise the amino acid sequence of SEQ ID NO: 711. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-24. The VH may comprise the amino acid sequence of SEQ ID NO: 938. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-24. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 711 and a VH comprising the amino acid sequence of SEQ ID NO: 938. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-24A. The VL may comprise the amino acid sequence of SEQ ID NO: 824. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-24A. The VH may comprise the amino acid sequence of SEQ ID NO: 1051. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-24A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 824 and a VH comprising the amino acid sequence of SEQ ID NO: 1051. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-24_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 938; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 711. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-24_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 711; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 938. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-24A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1051; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 824. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-24A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 824; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1051.

[0122] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-25 and ABL-CD3-25A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 25, 138, and 251, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 369, 482, and 598, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-25. The VL may comprise the amino acid sequence of SEQ ID NO: 712. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-25. The VH may comprise the amino acid sequence of SEQ ID NO: 939. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-25. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 712, and a VH comprising the amino acid sequence of SEQ ID NO: 939. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-25A. The VL may comprise the amino acid sequence of SEQ ID NO: 825. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-25A. The VH may comprise the amino acid sequence of SEQ ID NO: 1052. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-25A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 825, and a VH comprising the amino acid sequence of SEQ ID NO: 1052. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-25_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 939; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 712. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-25_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 712; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 939. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-25A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1052; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 825. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-25A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 825; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1052.

[0123] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-26 and ABL-CD3-26A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 26, 139, and 252, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 370, 483, and 599, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-26. The VL may comprise the amino acid sequence of SEQ ID NO: 713. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-26. The VH may comprise the amino acid sequence of SEQ ID NO: 940. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-26. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 713, and a VH comprising the amino acid sequence of SEQ ID NO: 940. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-26A. The VL may comprise the amino acid sequence of SEQ ID NO: 826. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-26A. The VH may comprise the amino acid sequence of SEQ ID NO: 1053. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-26A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 826, and a VH comprising the amino acid sequence of SEQ ID NO: 1053. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-26_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 940; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 713. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-26_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 713; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 940. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-26A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1053; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 826. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-26A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 826; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1053.

[0124] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of the antibody ABL-CD3-27. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 27, 140, and 253, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 371, 484, and 600, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of the antibody ABL-CD3-27A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 27, 140, and 253, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 371, 484, and 687, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of the antibody ABL-CD3-27. The VL may comprise the amino acid sequence of SEQ ID NO: 714. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-27. The VH may comprise the amino acid sequence of SEQ ID NO: 941. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-27. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 714 and a VH comprising the amino acid sequence of SEQ ID NO: 941. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-27A. The VL may comprise the amino acid sequence of SEQ ID NO: 827. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-27A. The VH may comprise the amino acid sequence of SEQ ID NO: 1054. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-27A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 827, and a VH comprising the amino acid sequence of SEQ ID NO: 1054. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-27_scFv_VH-VL.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 941; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 714. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-27_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 714; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 941. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-27A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1159. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-27A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1200.

[0125] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-28 and ABL-CD3-28A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 28, 141, and 254, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 372, 485, and 601, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-28. The VL may comprise the amino acid sequence of SEQ ID NO: 715. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-28. The VH may comprise the amino acid sequence of SEQ ID NO: 942. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-28. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 715, and a VH comprising the amino acid sequence of SEQ ID NO: 942. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-28A. The VL may comprise the amino acid sequence of SEQ ID NO: 828. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-28A. The VH may comprise the amino acid sequence of SEQ ID NO: 1055. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-28A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 828, and a VH comprising the amino acid sequence of SEQ ID NO: 1055. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-28_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 942; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 715. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-28_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 715; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 942. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-28A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1055; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 828. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-28A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 828; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1055.

[0126] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-29 and ABL-CD3-29A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 29, 142, and 255, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 373, 486, and 602, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-29. The VL may comprise the amino acid sequence of SEQ ID NO: 716. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-29. The VH may comprise the amino acid sequence of SEQ ID NO: 943. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-29. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 716 and a VH comprising the amino acid sequence of SEQ ID NO: 943. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-29A. The VL may comprise the amino acid sequence of SEQ ID NO: 829. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-29A. The VH may comprise the amino acid sequence of SEQ ID NO: 1056. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-29A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 829 and a VH comprising the amino acid sequence of SEQ ID NO: 1056. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-29_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 943; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 716. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-29_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 716; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 943. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-29A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1160. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-29A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1201.

[0127] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-30 and ABL-CD3-30A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 30, 143, and 256, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 374, 487, and 603, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-30. The VL may comprise the amino acid sequence of SEQ ID NO: 717. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-30. The VH may comprise the amino acid sequence of SEQ ID NO: 944. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-30. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 717 and a VH comprising the amino acid sequence of SEQ ID NO: 944. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-30A. The VL may comprise the amino acid sequence of SEQ ID NO: 830. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-30A. The VH may comprise the amino acid sequence of SEQ ID NO: 1057. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-30A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 830 and a VH comprising the amino acid sequence of SEQ ID NO: 1057. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-30_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 944; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 717. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-30_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 717; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 944. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-30A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1057; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 830. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-30A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 830; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1057.

[0128] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-31 and ABL-CD3-31A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 31, 144, and 257, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 375, 488, and 604, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-31. The VL may comprise the amino acid sequence of SEQ ID NO: 718. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-31. The VH may comprise the amino acid sequence of SEQ ID NO: 945. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-31. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 718, and a VH comprising the amino acid sequence of SEQ ID NO: 945. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-31A. The VL may comprise the amino acid sequence of SEQ ID NO: 831. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-31A. The VH may comprise the amino acid sequence of SEQ ID NO: 1058. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-31A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 831, and a VH comprising the amino acid sequence of SEQ ID NO: 1058. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-31_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 945; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 718. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-31_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 718; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 945. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-31A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1161. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-31A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1202.

[0129] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-32 and ABL-CD3-32A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 32, 145, and 258, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 376, 489, and 605, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-32. The VL may comprise the amino acid sequence of SEQ ID NO: 719. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-32. The VH may comprise the amino acid sequence of SEQ ID NO: 946. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-32. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 719 and a VH comprising the amino acid sequence of SEQ ID NO: 946. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-32A. The VL may comprise the amino acid sequence of SEQ ID NO: 832. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-32A. The VH may comprise the amino acid sequence of SEQ ID NO: 1059. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-32A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 832 and a VH comprising the amino acid sequence of SEQ ID NO: 1059. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-32_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 946; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 719. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-32_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 719; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 946. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-32A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1059; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 832. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-32A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 832; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1059.

[0130] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-33 and ABL-CD3-33A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 33, 146, and 259, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 377, 490, and 606, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-33. The VL may comprise the amino acid sequence of SEQ ID NO: 720. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-33. The VH may comprise the amino acid sequence of SEQ ID NO: 947. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-33. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 720, and a VH comprising the amino acid sequence of SEQ ID NO: 947. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-33A. The VL may comprise the amino acid sequence of SEQ ID NO: 833. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-33A. The VH may comprise the amino acid sequence of SEQ ID NO: 1060. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-33A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 833, and a VH comprising the amino acid sequence of SEQ ID NO: 1060. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-33_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 947; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 720. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-33_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 720; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 947. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-33A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1060; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 833. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-33A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 833; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1060.

[0131] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-34 and ABL-CD3-34A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 34, 147, and 260, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 378, 491, and 607, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-34. The VL may comprise the amino acid sequence of SEQ ID NO: 721. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-34. The VH may comprise the amino acid sequence of SEQ ID NO: 948. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-34. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 721 and a VH comprising the amino acid sequence of SEQ ID NO: 948. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-34A. The VL may comprise the amino acid sequence of SEQ ID NO: 834. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-34A. The VH may comprise the amino acid sequence of SEQ ID NO: 1061. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-34A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 834 and a VH comprising the amino acid sequence of SEQ ID NO: 1061. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-34_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 948; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 721. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-34_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 721; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 948. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-34A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1162. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-34A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1203.

[0132] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-35 and ABL-CD3-35A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 35, 148, and 261, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 379, 492, and 608, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-35. The VL may comprise the amino acid sequence of SEQ ID NO: 722. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-35. The VH may comprise the amino acid sequence of SEQ ID NO: 949. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-35. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 722, and a VH comprising the amino acid sequence of SEQ ID NO: 949. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-35A. The VL may comprise the amino acid sequence of SEQ ID NO: 835. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-35A. The VH may comprise the amino acid sequence of SEQ ID NO: 1062. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-35A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 835, and a VH comprising the amino acid sequence of SEQ ID NO: 1062. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-35_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 949; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 722. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-35_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 722; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 949. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-35A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1062; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 835. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-35A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 835; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1062.

[0133] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibody ABL-CD3-36. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 36, 149, and 262, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 380, 493, and 609, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibody ABL-CD3-36A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 36, 149, and 262, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 380, 571, and 609, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-36. The VL may comprise the amino acid sequence of SEQ ID NO: 723. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-36. The VH may comprise the amino acid sequence of SEQ ID NO: 950. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-36. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 723 and a VH comprising the amino acid sequence of SEQ ID NO: 950. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-36A. The VL may comprise the amino acid sequence of SEQ ID NO: 836. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-36A. The VH may comprise the amino acid sequence of SEQ ID NO: 1063. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-36A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 836 and a VH comprising the amino acid sequence of SEQ ID NO: 1063. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-36_scFv_VH-VL.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 950; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 723. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-36_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 723; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 950. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-36A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1163. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-36A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1204.

[0134] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-37 and ABL-CD3-37A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 37, 150, and 263, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 381, 494, and 610, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-37. The VL may comprise the amino acid sequence of SEQ ID NO: 724. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-37. The VH may comprise the amino acid sequence of SEQ ID NO: 951. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-37. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 724, and a VH comprising the amino acid sequence of SEQ ID NO: 951. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-37A. The VL may comprise the amino acid sequence of SEQ ID NO: 837. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-37A. The VH may comprise the amino acid sequence of SEQ ID NO: 1064. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-37A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 837, and a VH comprising the amino acid sequence of SEQ ID NO: 1064. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-37_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 951; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 724. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-37_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 724; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 951. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-37A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1164. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-37A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1205.

[0135] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-38 and ABL-CD3-38A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 38, 151, and 264, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 382, ​​495, and 611, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-38. The VL may comprise the amino acid sequence of SEQ ID NO: 725. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-38. The VH may comprise the amino acid sequence of SEQ ID NO: 952. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-38. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 725, and a VH comprising the amino acid sequence of SEQ ID NO: 952. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-38A. The VL may comprise the amino acid sequence of SEQ ID NO: 838. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-38A. The VH may comprise the amino acid sequence of SEQ ID NO: 1065. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-38A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 838, and a VH comprising the amino acid sequence of SEQ ID NO: 1065. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-38_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 952; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 725. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-38_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 725; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 952. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-38A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1065; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 838. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-38A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 838; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1065.

[0136] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-39 and ABL-CD3-39A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 39, 152, and 265, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 383, 496, and 612, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-39. The VL may comprise the amino acid sequence of SEQ ID NO: 726. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-39. The VH may comprise the amino acid sequence of SEQ ID NO: 953. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-39. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 726 and a VH comprising the amino acid sequence of SEQ ID NO: 953. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-39A. The VL may comprise the amino acid sequence of SEQ ID NO: 839. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-39A. The VH may comprise the amino acid sequence of SEQ ID NO: 1066. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-39A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 839 and a VH comprising the amino acid sequence of SEQ ID NO: 1066. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-39_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 953; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 726. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-39_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 726; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 953. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-39A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1165. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-39A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1206.

[0137] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-40 and ABL-CD3-40A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 40, 153, and 266, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 384, 497, and 613, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-40. The VL may comprise the amino acid sequence of SEQ ID NO: 727. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-40. The VH may comprise the amino acid sequence of SEQ ID NO: 954. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-40. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 727 and a VH comprising the amino acid sequence of SEQ ID NO: 954. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-40A. The VL may comprise the amino acid sequence of SEQ ID NO: 840. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-40A. The VH may comprise the amino acid sequence of SEQ ID NO: 1067. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-40A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 840 and a VH comprising the amino acid sequence of SEQ ID NO: 1067. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-40_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 954; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 727. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-40_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 727; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 954. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-40A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1166. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-40A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1207.

[0138] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibody ABL-CD3-41. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 41, 154, and 267, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 385, 498, and 614, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibody ABL-CD3-41A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 41, 154, and 340, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 385, 498, and 614, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-41. The VL may comprise the amino acid sequence of SEQ ID NO: 728. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-41. The VH may comprise the amino acid sequence of SEQ ID NO: 955. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-41. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 728 and a VH comprising the amino acid sequence of SEQ ID NO: 955. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-41A. The VL may comprise the amino acid sequence of SEQ ID NO: 841. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-41A. The VH may comprise the amino acid sequence of SEQ ID NO: 1068. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-41A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 841 and a VH comprising the amino acid sequence of SEQ ID NO: 1068. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-41_scFv_VH-VL.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 955; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 728. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-41_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 728; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 955. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-41A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1167. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-41A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1208.

[0139] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-42 and ABL-CD3-42A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 42, 155, and 268, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 386, 499, and 615, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-42. The VL may comprise the amino acid sequence of SEQ ID NO: 729. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-42. The VH may comprise the amino acid sequence of SEQ ID NO: 956. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-42. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 729 and a VH comprising the amino acid sequence of SEQ ID NO: 956. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-42A. The VL may comprise the amino acid sequence of SEQ ID NO: 842. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-42A. The VH may comprise the amino acid sequence of SEQ ID NO: 1069. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-42A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 842 and a VH comprising the amino acid sequence of SEQ ID NO: 1069. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-42_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 956; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 729. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-42_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 729; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 956. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-42A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1069; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 842. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-42A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 842; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1069.

[0140] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibody ABL-CD3-43. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 43, 156, and 269, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 387, 500, and 616, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibody ABL-CD3-43A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 43, 156, and 341, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 387, 500, and 616, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-43. The VL may comprise the amino acid sequence of SEQ ID NO: 730. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-43. The VH may comprise the amino acid sequence of SEQ ID NO: 957. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-43. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 730 and a VH comprising the amino acid sequence of SEQ ID NO: 957. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-43A. The VL may comprise the amino acid sequence of SEQ ID NO: 843. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-43A. The VH may comprise the amino acid sequence of SEQ ID NO: 1070. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-43A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 843, and a VH comprising the amino acid sequence of SEQ ID NO: 1070. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-43_scFv_VH-VL.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 957; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 730. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-43_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 730; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 957. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-43A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1168. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-43A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1209.

[0141] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-44 and ABL-CD3-44A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 44, 157, and 270, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 388, 501, and 617, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-44. The VL may comprise the amino acid sequence of SEQ ID NO: 731. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-44. The VH may comprise the amino acid sequence of SEQ ID NO: 958. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-44. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 731 and a VH comprising the amino acid sequence of SEQ ID NO: 958. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-44A. The VL may comprise the amino acid sequence of SEQ ID NO: 844. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-44A. The VH may comprise the amino acid sequence of SEQ ID NO: 1071. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-44A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 844 and a VH comprising the amino acid sequence of SEQ ID NO: 1071. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-44_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 958; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 731. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-44_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 731; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 958. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-44A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1169. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-44A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1210.

[0142] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-45 and ABL-CD3-45A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 45, 158, and 271, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 389, 502, and 618, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-45. The VL may comprise the amino acid sequence of SEQ ID NO: 732. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-45. The VH may comprise the amino acid sequence of SEQ ID NO: 959. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-45. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 732, and a VH comprising the amino acid sequence of SEQ ID NO: 959. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-45A. The VL may comprise the amino acid sequence of SEQ ID NO: 845. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-45A. The VH may comprise the amino acid sequence of SEQ ID NO: 1072. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-45A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 845, and a VH comprising the amino acid sequence of SEQ ID NO: 1072. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-45_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 959; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 732. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-45_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 732; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 959. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-45A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1170. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-45A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1211.

[0143] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-46 and ABL-CD3-46A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 46, 159, and 272, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 390, 503, and 619, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-46. The VL may comprise the amino acid sequence of SEQ ID NO: 733. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-46. The VH may comprise the amino acid sequence of SEQ ID NO: 960. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-46. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 733 and a VH comprising the amino acid sequence of SEQ ID NO: 960. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-46A. The VL may comprise the amino acid sequence of SEQ ID NO: 846. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-46A. The VH may comprise the amino acid sequence of SEQ ID NO: 1073. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-46A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 846 and a VH comprising the amino acid sequence of SEQ ID NO: 1073. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-46_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 960; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 733. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-46_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 733; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 960. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-46A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1073; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 846. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-46A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 846; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1073.

[0144] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-47 and ABL-CD3-47A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 47, 160, and 273, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 391, 504, and 620, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-47. The VL may comprise the amino acid sequence of SEQ ID NO: 734. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-47. The VH may comprise the amino acid sequence of SEQ ID NO: 961. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-47. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 734, and a VH comprising the amino acid sequence of SEQ ID NO: 961. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-47A. The VL may comprise the amino acid sequence of SEQ ID NO: 847. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-47A. The VH may comprise the amino acid sequence of SEQ ID NO: 1074. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-47A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 847, and a VH comprising the amino acid sequence of SEQ ID NO: 1074. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-47_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 961; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 734. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-47_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 734; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 961. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-47A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1171. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-47A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1212.

[0145] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-48 and ABL-CD3-48A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 48, 161, and 274, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 392, 505, and 621, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-48. The VL may comprise the amino acid sequence of SEQ ID NO: 735. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-48. The VH may comprise the amino acid sequence of SEQ ID NO: 962. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-48. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 735 and a VH comprising the amino acid sequence of SEQ ID NO: 962. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-48A. The VL may comprise the amino acid sequence of SEQ ID NO: 848. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-48A. The VH may comprise the amino acid sequence of SEQ ID NO: 1075. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-48A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 848 and a VH comprising the amino acid sequence of SEQ ID NO: 1075. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-48_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 962; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 735. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-48_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 735; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 962. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-48A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1075; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 848. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-48A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 848; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1075.

[0146] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibody ABL-CD3-49. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 49, 162, and 275, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 393, 506, and 622, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibody ABL-CD3-49A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 49, 162, and 342, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 393, 506, and 622, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-49. The VL may comprise the amino acid sequence of SEQ ID NO: 736. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-49. The VH may comprise the amino acid sequence of SEQ ID NO: 963. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-49. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 736 and a VH comprising the amino acid sequence of SEQ ID NO: 963. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-49A. The VL may comprise the amino acid sequence of SEQ ID NO: 849. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-49A. The VH may comprise the amino acid sequence of SEQ ID NO: 1076. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-49A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 849 and a VH comprising the amino acid sequence of SEQ ID NO: 1076. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-49_scFv_VH-VL.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 963; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 736. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-49_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 736; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 963. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-49A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1172. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-49A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1213.

[0147] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-50 and ABL-CD3-50A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 50, 163, and 276, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 394, 507, and 623, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-50. The VL may comprise the amino acid sequence of SEQ ID NO: 737. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-50. The VH may comprise the amino acid sequence of SEQ ID NO: 964. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-50. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 737 and a VH comprising the amino acid sequence of SEQ ID NO: 964. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-50A. The VL may comprise the amino acid sequence of SEQ ID NO: 850. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-50A. The VH may comprise the amino acid sequence of SEQ ID NO: 1077. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-50A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 850 and a VH comprising the amino acid sequence of SEQ ID NO: 1077. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-50_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 964; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 737. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-50_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 737; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 964. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-50A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1077; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 850. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-50A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 850; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1077.

[0148] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-51 and ABL-CD3-51A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 51, 164, and 277, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 395, 508, and 624, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-51. The VL may comprise the amino acid sequence of SEQ ID NO: 738. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-51. The VH may comprise the amino acid sequence of SEQ ID NO: 965. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-51. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 738 and a VH comprising the amino acid sequence of SEQ ID NO: 965. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-51A. The VL may comprise the amino acid sequence of SEQ ID NO: 851. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-51A. The VH may comprise the amino acid sequence of SEQ ID NO: 1078. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-51A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 851 and a VH comprising the amino acid sequence of SEQ ID NO: 1078. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-51_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 965; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 738. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-51_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 738; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 965. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-51A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1078; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 851. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-51A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 851; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1078.

[0149] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-52 and ABL-CD3-52A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 52, 165, and 278, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 396, 509, and 625, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-52. The VL may comprise the amino acid sequence of SEQ ID NO: 739. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-52. The VH may comprise the amino acid sequence of SEQ ID NO: 966. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-52. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 739 and a VH comprising the amino acid sequence of SEQ ID NO: 966. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-52A. The VL may comprise the amino acid sequence of SEQ ID NO: 852. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-52A. The VH may comprise the amino acid sequence of SEQ ID NO: 1079. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-52A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 852 and a VH comprising the amino acid sequence of SEQ ID NO: 1079. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-52_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 966; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 739. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-52_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 739; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 966. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-52A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1173. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-52A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1214.

[0150] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-53 and ABL-CD3-53A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 53, 166, and 279, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 397, 510, and 626, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-53. The VL may comprise the amino acid sequence of SEQ ID NO: 740. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-53. The VH may comprise the amino acid sequence of SEQ ID NO: 967. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-53. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 740, and a VH comprising the amino acid sequence of SEQ ID NO: 967. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-53A. The VL may comprise the amino acid sequence of SEQ ID NO: 853. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-53A. The VH may comprise the amino acid sequence of SEQ ID NO: 1080. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-53A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 853, and a VH comprising the amino acid sequence of SEQ ID NO: 1080. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-53_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 967; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 740. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-53_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 740; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 967. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-53A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1174. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-53A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1215.

[0151] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-54 and ABL-CD3-54A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 54, 167, and 280, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 398, 511, and 627, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-54. The VL may comprise the amino acid sequence of SEQ ID NO: 741. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-54. The VH may comprise the amino acid sequence of SEQ ID NO: 968. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-54. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 741 and a VH comprising the amino acid sequence of SEQ ID NO: 968. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-54A. The VL may comprise the amino acid sequence of SEQ ID NO: 854. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-54A. The VH may comprise the amino acid sequence of SEQ ID NO: 1081. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-54A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 854 and a VH comprising the amino acid sequence of SEQ ID NO: 1081. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-54_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 968; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 741. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-54_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 741; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 968. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-54A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1081; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 854. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-54A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 854; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1081.

[0152] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-55 and ABL-CD3-55A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 55, 168, and 281, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 399, 512, and 628, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-55. The VL may comprise the amino acid sequence of SEQ ID NO: 742. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-55. The VH may comprise the amino acid sequence of SEQ ID NO: 969. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-55. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 742, and a VH comprising the amino acid sequence of SEQ ID NO: 969. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-55A. The VL may comprise the amino acid sequence of SEQ ID NO: 855. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-55A. The VH may comprise the amino acid sequence of SEQ ID NO: 1082. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-55A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 855, and a VH comprising the amino acid sequence of SEQ ID NO: 1082. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-55_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 969; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 742. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-55_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 742; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 969. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-55A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1082; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 855. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-55A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 855; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1082.

[0153] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-56 and ABL-CD3-56A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 56, 169, and 282, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 400, 513, and 629, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-56. The VL may comprise the amino acid sequence of SEQ ID NO: 743. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-56. The VH may comprise the amino acid sequence of SEQ ID NO: 970. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-56. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 743, and a VH comprising the amino acid sequence of SEQ ID NO: 970. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-56A. The VL may comprise the amino acid sequence of SEQ ID NO: 856. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-56A. The VH may comprise the amino acid sequence of SEQ ID NO: 1083. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-56A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 856, and a VH comprising the amino acid sequence of SEQ ID NO: 1083. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-56_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 970; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 743. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-56_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 743; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 970. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-56A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1175. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-56A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1216.

[0154] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-57 and ABL-CD3-57A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 57, 170, and 283, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 401, 514, and 630, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-57. The VL may comprise the amino acid sequence of SEQ ID NO: 744. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-57. The VH may comprise the amino acid sequence of SEQ ID NO: 971. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-57. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 744, and a VH comprising the amino acid sequence of SEQ ID NO: 971. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-57A. The VL may comprise the amino acid sequence of SEQ ID NO: 857. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-57A. The VH may comprise the amino acid sequence of SEQ ID NO: 1084. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-57A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 857, and a VH comprising the amino acid sequence of SEQ ID NO: 1084. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-57_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 971; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 744. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-57_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 744; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 971. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-57A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1176. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-57A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 1217.

[0155] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-58 and ABL-CD3-58A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 58, 171, and 284, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 402, 515, and 631, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-58. The VL may comprise the amino acid sequence of SEQ ID NO: 745. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-58. The VH may comprise the amino acid sequence of SEQ ID NO: 972. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-58. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 745, and a VH comprising the amino acid sequence of SEQ ID NO: 972. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-58A. The VL may comprise the amino acid sequence of SEQ ID NO: 858. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-58A. The VH may comprise the amino acid sequence of SEQ ID NO: 1085. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-58A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 858, and a VH comprising the amino acid sequence of SEQ ID NO: 1085. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-58_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 972; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 745. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-58_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 745; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 972. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-58A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1085; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 858. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-58A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 858; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1085.

[0156] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-59 and ABL-CD3-59A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 59, 172, and 285, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 403, 516, and 632, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-59. The VL may comprise the amino acid sequence of SEQ ID NO: 746. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-59. The VH may comprise the amino acid sequence of SEQ ID NO: 973. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-59. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 746 and a VH comprising the amino acid sequence of SEQ ID NO: 973. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-59A. The VL may comprise the amino acid sequence of SEQ ID NO: 859. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-59A. The VH may comprise the amino acid sequence of SEQ ID NO: 1086. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-59A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 859 and a VH comprising the amino acid sequence of SEQ ID NO: 1086. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-59_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 973; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 746. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-59_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 746; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 973. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-59A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1086; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 859. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-59A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 859; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1086.

[0157] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-60 and ABL-CD3-60A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 60, 173, and 286, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NOs: 404, 517, and 633, respectively. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-60. The VL may comprise the amino acid sequence of SEQ ID NO: 747. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-60. The VH may comprise the amino acid sequence of SEQ ID NO: 974. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-60. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 747 and a VH comprising the amino acid sequence of SEQ ID NO: 974. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL of antibody ABL-CD3-60A. The VL may comprise the amino acid sequence of SEQ ID NO: 860. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VH of antibody ABL-CD3-60A. The VH may comprise the amino acid sequence of SEQ ID NO: 1087. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the VL and VH of antibody ABL-CD3-60A. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 860 and a VH comprising the amino acid sequence of SEQ ID NO: 1087. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-60_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 974; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 747. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-60_scFv_VL-VH.In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 747; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 974. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-60A_scFv_VH-VL. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of SEQ ID NO: 1087; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VL comprising the amino acid sequence of SEQ ID NO: 860. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises ABL-CD3-60A_scFv_VL-VH. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises, from N-terminus to C-terminus, a VL comprising the amino acid sequence of SEQ ID NO: 860; a linker comprising the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), wherein n is 4; and a VH comprising the amino acid sequence of SEQ ID NO: 1087.

[0158] In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises the six CDRs of antibodies ABL-CD3-61 and ABL-CD3-61A. The anti-CD3 antibody or antigen-binding fragment thereof may comprise LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 61, 174, and 287, respectively; and HCDR1, HCDR2, and HCDR3 comprising the amino ...

Claims

1. An isolated anti-CD3 antibody or antigen-binding fragment thereof, comprising: i) a heavy chain variable region comprising a VHCDR1 selected from any one of SEQ ID NOs: 345-457, a VHCDR2 selected from any one of SEQ ID NOs: 458-573, and a VHCDR3 selected from any one of SEQ ID NOs: 574-687, and ii) a light chain variable region comprising a VLCDR1 selected from any one of SEQ ID NOs: 1-113, a VLCDR2 selected from any one of SEQ ID NOs: 114-226, and a VLCDR3 selected from any one of SEQ ID NOs: 227-377.

2. The antibody or antigen-binding fragment thereof according to claim 1, wherein the VH is selected from any one of SEQ ID NOs: 915-1141.

3. The antibody or antigen-binding fragment thereof of claim 1 or claim 2, wherein the VL is selected from any one of SEQ ID NOs: 688-914.

4. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 3, wherein the antibody is a human antibody.

5. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 3, wherein the antibody is a chimeric antibody.

6. The antibody or antigen-binding fragment thereof of any one of claims 1 to 5, wherein the antibody is selected from the group consisting of a single variable domain antibody, a single chain antibody, a scFv, a bispecific antibody, a multispecific antibody, a Fab, a F(ab')2, and a whole antibody.

7. The antibody or antigen-binding fragment thereof according to claim 6, wherein the antibody is a multispecific antibody.

8. The antibody or antigen-binding fragment thereof of claim 6, wherein the antibody is a bispecific antibody comprising a first and a second Fc domain.

9. The antibody or antigen-binding fragment thereof according to claim 8, wherein the bispecific antibody further comprises a targeting antibody.

10. The antibody or antigen-binding fragment thereof according to claim 9, wherein the targeting antibody is an anti-tumor antibody or antigen-binding fragment thereof.

11. The antibody or antigen-binding fragment thereof of any one of claims 6 to 10, wherein the anti-CD3 antibody or antigen-binding fragment thereof comprises a scFv.

12. The antibody or antigen-binding fragment thereof of claim 6 or claim 11, wherein the anti-CD3 scFv antibody comprises an amino acid sequence selected from any one of SEQ ID NOs: 1155-1236.

13. The antibody or antigen-binding fragment thereof of claim 11 or 12, wherein the anti-CD3 scFv antibody is operably linked to the first Fc domain.

14. The antibody or antigen-binding fragment thereof of claim 13, wherein the anti-CD3 scFv antibody is operably linked to the first Fc domain via a first linker.

15. The antibody or antigen-binding fragment thereof according to any one of claims 9 to 14, wherein the targeting antibody or antigen-binding fragment thereof comprises a Fab fragment or a F(ab')2 fragment.

16. The antibody or antigen-binding fragment thereof of claim 15, wherein the targeting Fab or F(ab')2 fragment is operably linked to the second Fc domain.

17. The antibody or antigen-binding fragment thereof of claim 16, wherein the targeting Fab or F(ab')2 fragment is operably linked to the second Fc domain via a second linker.

18. The antibody or antigen-binding fragment thereof of claim 15 or 17, wherein the first linker or the second linker is a Gly-Ser linker of variable length.

19. The antibody or antigen-binding fragment thereof of claim 18, wherein the first linker and the second linker are independently selected from SEQ ID NOs: 1146-1149 and 1237-1238.

20. The antibody or antigen-binding fragment thereof of any one of claims 8 to 19, wherein the first and second Fc domains comprise complementary mutations selected from the group consisting of knob-to-hole KIH mutations, K409R / F405L, HA-TF and related mutations, skew mutations, ZW mutations, 7.8.60 mutations or related mutations, DD-KK mutations or related mutations, EW-RVT mutations or related mutations, strand exchange engineered domains (SEEDs), Duobody mutations, CrossMAb mutations, and A107 mutations or related mutations.

21. The antibody or antigen-binding fragment thereof of claim 20, wherein (1) the first Fc domain comprises a T366W mutation and the second Fc domain comprises a T366S / L368A / Y407V mutation; (2) the first Fc domain comprises a T366S / L368A / Y407V mutation and the second Fc domain comprises a T366W mutation; (3) the first Fc domain comprises an S354C / T366W mutation and the second Fc domain comprises a Y349C / T366S / L368A / Y407V mutation; (4) the first Fc domain comprises a Y349C / T366S / L368A / Y407V mutation and the second Fc domain comprises an S354C / T366W mutation; (5) the first Fc domain comprises an S354C / T366S / L368A / Y407V mutation. 6W mutations and the second Fc domain comprises Y349C / T366S / L368A / Y407V / H435R / Y436F mutations; (6) the first Fc domain comprises Y349C / T366S / L368A / Y407V / H435R / Y436F mutations and the second Fc domain comprises S354C / T366W mutations; 7) the first Fc domain comprises S354C / T366W / H435R / Y436F mutations and the second Fc domain comprises Y349C / T366S / L368A / Y407V mutations; or 8) the first Fc domain comprises Y349C / T366S / L368A / Y407V mutations and the second Fc domain comprises S354C / T366W / H435R / Y436F mutations.

22. The antibody or antigen-binding fragment thereof of claim 20, wherein (1) the first and second Fc domains comprise the amino acid sequences of SEQ ID NOs: 1142 and 1143, respectively; or (2) the first and second Fc domains comprise the amino acid sequences of SEQ ID NOs: 1143 and 1142, respectively.

23. The antibody or antigen-binding fragment thereof of claim 20, wherein (1) the anti-CD3 antibody comprises a constant region comprising the amino acid sequence of SEQ ID NO: 1144, and the anti-tumor antibody comprises a constant region comprising the amino acid sequence of SEQ ID NO: 1145; or (2) the anti-CD3 antibody comprises a constant region comprising the amino acid sequence of SEQ ID NO: 1145, and the anti-tumor antibody comprises a constant region comprising the amino acid sequence of SEQ ID NO: 1144.

24. The antibody or antigen-binding fragment thereof of claim 20, wherein (1) the first Fc domain comprises an S364H mutation and the second Fc domain comprises a Y349T mutation; (2) the first Fc domain comprises a Y349T mutation and the second Fc domain comprises an S364H mutation; (3) the first Fc domain comprises an F405A mutation and the second Fc domain comprises a T394F mutation; (4) the first Fc domain comprises a T394F mutation and the second Fc domain comprises an F405A mutation; (5) the first Fc domain comprises an F405A mutation (6) the first Fc domain comprises Y349T / F405A mutations and the second Fc domain comprises S364H / T394F mutations; (7) the first Fc domain comprises S364H / F405A mutations and the second Fc domain comprises Y349T / T394F mutations; or (8) the first Fc domain comprises Y349T / T394F mutations and the second Fc domain comprises S364H / F405A mutations.

25. The antibody or antigen-binding fragment thereof of claim 20, wherein (1) the first Fc domain comprises an S364K / E357Q mutation and the second Fc domain comprises an L368D / K370S mutation; (2) the first Fc domain comprises an L368D / K370S mutation and the second Fc domain comprises an S364K / E357Q mutation; (3) the first Fc domain comprises an L368D / K370S mutation and the second Fc domain comprises an S364K mutation; (4) the first Fc domain comprises an S364K mutation and the second Fc domain comprises an L368D / K370S mutation; (5) the first Fc domain comprises L368E / K370S mutation and the second Fc domain comprises S364K mutation; (6) the first Fc domain comprises S364K mutation and the second Fc domain comprises L368E / K370S mutation; (7) the first Fc domain comprises T411E / K360E / Q362E mutation and the second Fc domain comprises D401K mutation; (8) the first Fc domain comprises D401K mutation and the second Fc domain comprises T411E / K360E / Q362E mutation; (9) the first Fc The first Fc domain comprises an L368D / K370S mutation and the second Fc domain comprises an S364K / E357L mutation; (10) the first Fc domain comprises an S364K / E357L mutation and the second Fc domain comprises an L368D / K370S mutation; (11) the first Fc domain comprises a K370S mutation and the second Fc domain comprises an S364K / E357Q mutation; (12) the first Fc domain comprises an S364K / E357Q mutation and the second Fc domain comprises a K370S mutation; (13) the first Fc domain comprises a T366S / L3 68A / Y407V mutations and the second Fc domain comprises a T366W mutation; (14) the first Fc domain comprises a T366W mutation and the second Fc domain comprises a T366S / L368A / Y407V mutation; (15) the first Fc domain comprises a T366S / L368A / Y407V / Y349C mutation and the second Fc domain comprises a T366W / S354C mutation; or (16) the first Fc domain comprises a T366W / S354C mutation and the second Fc domain comprises a T366S / L368A / Y407V / Y349C mutation.

26. The antibody or antigen-binding fragment thereof of claim 20, wherein (1) the first Fc domain comprises a F405A / Y407V mutation and the second Fc domain comprises a T394W mutation; (2) the first Fc domain comprises a T394W mutation and the second Fc domain comprises a F405A / Y407V mutation; (3) the first Fc domain comprises a F405A / Y407V mutation and the second Fc domain comprises a T366I / T394W mutation; (4) the first Fc domain comprises a T366I / T394W mutation and the second Fc domain comprises a F405A / Y407V mutation. mutations; (5) the first Fc domain comprises F405A / Y407V mutations and the second Fc domain comprises T366L / T394W mutations; (6) the first Fc domain comprises T366L / T394W mutations and the second Fc domain comprises F405A / Y407V mutations; (7) the first Fc domain comprises F405A / Y407V mutations and the second Fc domain comprises T366L / K392M / T394W mutations; (8) the first Fc domain comprises T366L / K392M / T394W mutations and the second Fc domain comprises F405A / Y407V mutations mutations; (9) the first Fc domain comprises L351Y / F405A / Y407V mutations and the second Fc domain comprises T366L / K329M / T394W mutations; (10) the first Fc domain comprises T366L / K329M- / T394W mutations and the second Fc domain comprises L351Y / F405A / Y407V mutations; (11) the first Fc domain comprises T350V / L351Y / F405A / Y407V mutations and the second Fc domain comprises T350V / T366L / K392M / T394W mutations; (12) the first Fc domain comprises T366L / K329M- / T394W mutations wherein the first Fc domain comprises T350V / T366L / K392M / T394W mutations and the second Fc domain comprises T350V / L351Y / F405A / Y407V mutations; (13) the first Fc domain comprises T350V / L351Y / F405A / Y407V mutations and the second Fc domain comprises T350V / T366L- / K392L / T394W mutations; or (14) the first Fc domain comprises T350V / T366L / K392L- / T394W mutations and the second Fc domain comprises T350V / L351Y / F405A / Y407V mutations.

27. The antibody or antigen-binding fragment thereof of claim 20, wherein (1) the first Fc domain comprises a D399M / Y407A mutation and the second Fc domain comprises a T366V / K409V mutation; (2) the first Fc domain comprises a T366V / K409V mutation and the second Fc domain comprises a D399M / Y407A mutation; (3) the first Fc domain comprises a K360D / D399M / Y407A mutation and the second Fc domain comprises an E360D / D399M / Y407A mutation. 345R / Q347R / T366V / K409V mutations; (4) the first Fc domain comprises E345R / Q347R / T366V / K409V mutations and the second Fc domain comprises K360D / D399M / Y407A mutations; (5) the first Fc domain comprises Y349S / K370Y / T366V- / K409V mutations and the second Fc domain comprises E357D / S364Q / Y407A mutations; (6) the first Fc domain comprises (7) the first Fc domain comprises Y349S / K370Y / T366M / K409V mutations and the second Fc domain comprises E356G / E357D / S364Q / Y407A mutations; (8) the first Fc domain comprises E356G / E357D / S364Q / Y407A mutations and the second Fc domain comprises Y349S / K370Y / T366V / K409V mutations The second Fc domain comprises Y349S / K370Y / T366M / K409V mutations; (9) the first Fc domain comprises Y349S / K370Y / T366M / K409V mutations and the second Fc domain comprises E357D / S364R / Y407A mutations; or (10) the first Fc domain comprises E357D / S364R / Y407A mutations and the second Fc domain comprises Y349S / K370Y / T366M / K409V mutations.

28. The antibody or antigen-binding fragment thereof of claim 20, wherein (1) the first Fc domain comprises a K409D / K392D mutation and the second Fc domain comprises a D399K / E356K mutation; (2) the first Fc domain comprises a D399K / E356K mutation and the second Fc domain comprises a K409D / K392D mutation; (3) the first Fc domain comprises a K409E / K392D mutation and the second Fc domain comprises a D399R / E356K mutation; (4) the first Fc domain comprises a D399R / E356K mutation and the second Fc domain comprises a K409E / K392D mutation; (5) the first Fc domain comprises a K409D / K392D mutation and the second Fc domain comprises a D399R / E356K mutation; (6) the first Fc domain comprises D399R / E356K mutations and the second Fc domain comprises K409D / K392D mutations; (7) the first Fc domain comprises K409E / K392D mutations and the second Fc domain comprises D399K / E356K mutations; (8) the first Fc domain comprises D399K / E356K mutations and the second Fc domain comprises K409E / K392D mutations; (9) the first Fc domain comprises K409D / K392D / K370D mutations and the second Fc domain comprises D399K / E356K / -E357K mutations; or (10) the first Fc domain comprises D399K / E356K / E357K mutations and the second Fc domain comprises K409D / K392D / K370D mutations.

29. The antibody or antigen-binding fragment thereof of claim 20, wherein (1) the first Fc domain comprises a K409W mutation and the second Fc domain comprises a F405T / D399V mutation; (2) the first Fc domain comprises a F405T / D399V mutation and the second Fc domain comprises a K409W mutation; (3) the first Fc domain comprises a K360E / K409W mutation and the second Fc domain comprises a Q347R / D399V / F405T mutation; (4) the first Fc domain comprises a K409W mutation and the second Fc domain comprises a Q347R / D399V / F405T mutation; (5) the first Fc domain comprises Q347R / D399V / F405T mutations and the second Fc domain comprises K360E / K409W mutations; (6) the first Fc domain comprises Q347R / D399V / F405T / S354C mutations and the second Fc domain comprises K360E / K409WY349C mutations.

30. The antibody or antigen-binding fragment thereof of claim 20, wherein (1) the first Fc domain comprises an AG SEED domain and the second Fc domain comprises a GA SEED domain, or (2) the first Fc domain comprises a GASEED domain and the second Fc domain comprises an AG SEED domain.

31. The antibody or antigen-binding fragment thereof of claim 20, wherein (1) the first Fc domain comprises K370E / K409W mutations and the second Fc domain comprises E357N / D399V / F405T mutations; (2) the first Fc domain comprises E357N / D399V / F405T mutations and the second Fc domain comprises K370E / K409W mutations; (3) the first Fc domain comprises K370E / K409W mutations and the second Fc domain comprises E357I / S364T / D399V / F405T mutations; (4) the first Fc domain comprises E357I / S364T / D399V / F405 T mutation and the second Fc domain comprises K370E / K409W mutations; (5) the first Fc domain comprises K370M / K409W mutations and the second Fc domain comprises E357M / S364W / D399V / F405T mutations; (6) the first Fc domain comprises E357M / S364W / D399V / F405T mutations and the second Fc domain comprises K370M / K409W mutations; (7) the first Fc domain comprises K370D / K409W mutations and the second Fc domain comprises E357M / D399V / F405T mutations; (8) the first Fc domain comprises E357M / D399V / F 405T mutation and the second Fc domain comprises K370D / K409W mutations; (9) the first Fc domain comprises E357D / S364W / K370E mutations and the second Fc domain comprises E357N / K370R mutations; (10) the first Fc domain comprises E357N / K370R mutations and the second Fc domain comprises E357D / S364W / K370E mutations; (11) the first Fc domain comprises E357A / S364Y / K370E mutations and the second Fc domain comprises E357N / K370H mutations; (12) the first Fc domain comprises E357N / K370H mutations and the second two Fc domains comprising E357A / S364Y / K370E mutations; (13) the first Fc domain comprising E357G / S364W / K370E mutations and the second Fc domain comprising E357N mutation; (14) the first Fc domain comprising E357N mutation and the second Fc domain comprising E357G / S364W / DK70E mutations; (15) the first Fc domain comprising E357N / S364W / K370E mutations and the second Fc domain comprising E357N mutation; or (16) the first Fc domain comprising E357N mutation and the second Fc domain comprising E357N / S364W / DK70E mutations.

32. The antibody or antigen-binding fragment thereof of any one of claims 8-31, wherein the first and / or second Fc domains are independently engineered to have improved pharmacokinetic (PK).

33. The antibody or antigen-binding fragment thereof of claim 32, wherein the first and / or second Fc domain comprises amino acid substitutions M428L and / or N434S.

34. The antibody or antigen-binding fragment thereof of claim 10, wherein the anti-tumor antibody is an anti-CD33 antibody.

35. The antibody or antigen-binding fragment thereof of claim 34, wherein the anti-CD33 antibody comprises the six CDRs of gemtuzumab.

36. The antibody or antigen-binding fragment thereof of claim 35, wherein the anti-CD33 antibody comprises the VH of gemtuzumab.

37. The antibody or antigen-binding fragment thereof of claim 35 or 36, wherein the anti-CD33 antibody comprises the VL of gemtuzumab.

38. The antibody or antigen-binding fragment thereof of claim 34, wherein the anti-CD33 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 1151.

39. The antibody or antigen-binding fragment thereof of claim 34 or 38, wherein the anti-CD33 antibody comprises a VL comprising the amino acid sequence of SEQ ID NO: 1152.

40. The antibody or antigen-binding fragment thereof of any one of claims 1 to 39, wherein the antibody is selected from the group consisting of an IgG antibody, an IgM antibody, an IgA antibody, an IgD antibody, and an IgE antibody.

41. The antibody or antigen-binding fragment thereof of claim 40, wherein the antibody is an IgG antibody.

42. The antibody or antigen-binding fragment thereof of claim 41, wherein the antibody is a variant of an IgG antibody selected from the group consisting of an IgG1 antibody, an IgG2 antibody, an IgG3 antibody, and an IgG4 antibody.

43. The antibody or antigen-binding fragment thereof of claim 42, wherein the antibody comprises a modified Fc domain derived from an IgG1 molecule.

44. The antibody or antigen-binding fragment thereof of claim 43, wherein the modified Fc domain derived from an IgG1 molecule comprises an amino acid modification, wherein the amino acid modification is at any one of the positions selected from the group consisting of: E216, R217, K218, C219, C220, C226, C229, P230, E233, L234, L235, G236, G237, P238, S239, V240, V241, V242, V243, V244, V245, V246, V247, V248, V249, V250, V251, V252, V253, V254, V255, V256, V257, V258, V259, V260, V261, V262, V263, V264, V265, V266, V267, V268, V269, V270, V271, V272, V273, V274, V275, V276, V277, V278, V279, V271, V272, V273, V274, V275 98, T350, L351, K360, T366, N390, K392, T394, D399, S400, F405, Y407, K409, T411, or a combination of such amino acid modifications.

45. The antibody or antigen-binding fragment thereof of claim 43, wherein the modified Fc domain derived from IgG1 comprises an amino acid modification selected from the group consisting of: C220S, C226S, C229S, P230S, E233P, L234A, L234F, L234V, L235A, L235E, L235V, G236E, G237A, P238S, D265S, D265A, H268Q, W277T, N297G, N297Q, N297D, N297A, E318A, K322A, P329G, P329A, A330S, P331S, Q347R, Q347E, Q347K, T350V, L351Y, K360D, K360E, T366A, T366I, T366L, T 366M, T366V, N390R, N390K, N390D, K392V, K392M, K392R, K392L, K392F, K392E, T394W, D399R, D399W, D399K, S400E, S40 0D, S400R, S400K, F405A, F405I, F405M, F405T, F405S, F405V, F405W, Y407A, Y407I, Y407L, Y407V, K409F, K409I, K409 S, K409W, T411N, T411R, T411Q, T411K, T411D, T411E, T411W, ΔE216-E222, K246R / L251E / T260R, InR234 / 235, InV235 / 2 36, InR236 / 237, InR237 / 238, InV238 / 239, InN238 / 239, InL238 / 239, InE238 / 239, InG238 / 239, InS239 / 240, InG240 / 241, InE240 / 241, InG240 / 241, InL238 / 239 / P238Q, InE238 / 239 / N348A, InS239 / 240 / V266A and InR237 / 238 / G236A or a combination thereof.

46. ​​The antibody or antigen-binding fragment thereof of claim 45, wherein the modified Fc domain derived from IgG1 comprises L234F / L235E / P331S mutations.

47. The antibody or antigen-binding fragment thereof of claim 42, wherein the antibody comprises a modified Fc domain derived from an IgG2 molecule.

48. The antibody or antigen-binding fragment thereof of claim 47, wherein the modified Fc domain derived from an IgG2 molecule comprises an amino acid modification, wherein the amino acid modification is at any one of the positions selected from the group consisting of: V234, G237, P238, H268, V309, A330, and P331, or a combination thereof.

49. The antibody or antigen-binding fragment thereof of claim 48, wherein the modified Fc domain derived from an IgG2 molecule comprises an amino acid modification, wherein the amino acid modification is at any one of the positions selected from the group consisting of V234A, G237A, P238S, H268Q, H268A, V309L, A330S, P331S, or a combination thereof.

50. The antibody or antigen-binding fragment thereof of claim 42, wherein the antibody comprises a modified Fc domain derived from an IgG4 molecule.

51. The antibody or antigen-binding fragment thereof of claim 50, wherein the modified Fc domain derived from an IgG4 molecule comprises an amino acid modification, wherein the amino acid modification is at any one of the positions selected from the group consisting of: S228, L235, L236, G237, E318, and N297, or a combination thereof.

52. The antibody or antigen-binding fragment thereof of claim 51, wherein the modified Fc domain derived from an IgG4 molecule comprises an amino acid modification, wherein the amino acid modification is at any one of the positions selected from the group consisting of S228P, L235A, L235E, L236E, G237A, E318A, and N297Q, or a combination thereof.

53. A recombinant polynucleotide encoding the anti-CD3 antibody or antigen-binding fragment thereof according to any one of claims 1 to 52.

54. An expression vector comprising the recombinant polynucleotide of claim 53.

55. A first recombinant polynucleotide and a second recombinant polynucleotide, wherein the first recombinant polynucleotide encodes a heavy chain, wherein the heavy chain is the heavy chain of the anti-CD3 antibody or antigen-binding fragment thereof of any one of claims 1-52, and the second recombinant polynucleotide encodes a light chain, wherein the light chain is the light chain of the anti-CD3 antibody or antigen-binding fragment thereof of any one of claims 1-52.

56. A first expression vector and a second expression vector, wherein the first expression vector comprises the first recombinant polynucleotide of claim 55, and the second expression vector comprises the second recombinant polynucleotide of claim 55.

57. An isolated host cell comprising the recombinant polynucleotide of claim 53, the expression vector of claim 54, the first and second recombinant polynucleotides of claim 55, or the first and second expression vectors of claim 56.

58. A method for producing the antibody or antigen-binding fragment thereof of any one of claims 1 to 52, the method comprising culturing the host cell of claim 57 under conditions suitable for expression of the antibody or fragment.

59. A composition comprising the antibody or antigen-binding fragment thereof of any one of claims 1-52 and a physiologically acceptable carrier.

60. A method of treating or preventing cancer in a subject in need thereof, the method comprising administering to the subject in need thereof the antibody or antigen-binding fragment thereof of any one of claims 1-52 or the composition of claim 59.

61. A method of maintaining cancer remission in a subject, the method comprising administering to a subject in need thereof the antibody or antigen-binding fragment thereof of any one of claims 1-52 or the composition of claim 59.

62. A method of targeting T cells to tumor cells, wherein the method comprises contacting the T cells with the antibody or antigen-binding fragment thereof of any one of claims 8-52 or the composition of claim 59.

63. The method of any one of claims 60-62, wherein the anti-CD3 antibody is an anti-CD3 bispecific antibody, wherein the bispecific antibody further comprises an anti-tumor antibody.

64. A method of treating or preventing an autoimmune disease or disorder in a subject in need thereof, the method comprising administering to the subject in need thereof the antibody or antigen-binding fragment thereof of any one of claims 1-52 or the composition of claim 59.

65. The method of claim 64, wherein the autoimmune disease or disorder is graft-versus-host disease or type 1 diabetes.

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