Anti-CD3 antibody

Abstract

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

Description

[Technical Field]

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

[0002] background Technical Field The present disclosure generally relates to anti-CD3 antibodies, compositions and methods using the same. Such antibodies are useful, for example, for targeting T cells, for example, as a treatment for cancer or autoimmunity. Such antibodies can also be useful, for example, as a targeting arm in bispecific or other multispecific antibodies. [Background technology]

[0003] 2. Description of Related Art Cluster of differentiation 3 (CD3) is a multimeric protein complex containing four distinct CD3 polypeptide chains (epsilon (ε), gamma (γ), delta (δ), and zeta (ζ)), which assemble and function as three pairs of dimers (εγ, εδ, ζζ). The assembled CD3 protein acts as a T cell coreceptor, noncovalently associating with the T cell receptor (TCR). The CD3 protein complex is a defining characteristic of the T cell lineage, and as a result, anti-CD3 antibodies can be effectively used as a T cell marker.

[0004] Anti-CD3 antibodies are clinically used for immunosuppression of autoimmune T cell-mediated diseases, including organ transplant rejection and type 1 diabetes mellitus. Anti-CD3 bispecific or multispecific antibodies represent an emerging immuno-oncology therapy. In addition to the CD3-binding arm, such bispecific or multispecific antibodies also contain arms that bind to tumor-associated antigens expressed on tumor cells, allowing them to simultaneously bind to tumor cells and T cells. This simultaneous binding leads to T cell activation, proliferation, and secretion of 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. One advantage of using anti-CD3 bispecific or multispecific antibodies over engineered T cell therapy is that any T cell, regardless of TCR specificity, can function as an effector cell. Because TCR signaling does not require engagement of the antigen-binding domain of the TCR but is initiated via CD3, anti-CD3 bispecific or multispecific antibodies can utilize all available T cells and are not limited to tumor-specific T cells. In contrast, effective immune checkpoint therapy requires the availability of tumor-specific T cells. Although an 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 these antibodies have been identified as potential causes of these failures. See, for example, Vafa O and Trinklein ND, Front. Oncol., 2020, vol. 10, doi: 10.3389 / fonc.2020.00446. Thus, there remains a need to identify additional anti-CD3 binding antibodies, bispecific antibodies, and multispecific antibodies, for example, with improved efficacy or better safety profiles in patients. [Prior art documents] [Non-patent literature]

[0005] [Non-Patent Document 1] Vafa O and Trinklein ND, Front. Oncol., 2020, vol. 10, doi: 10.3389 / fonc.2020.00446 Summary of the Invention [Means for solving the problem]

[0006] Disclosure Overview The present disclosure relates to antibodies that bind to CD3. More specifically, the disclosure relates to chimeric anti-CD3 antibodies generated from AlivaMab® 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 to 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 an HCDR1 disclosed herein, an HCDR2 disclosed herein, an HCDR3 disclosed herein, an LCDR1 disclosed herein, an LCDR2 disclosed herein, and an LCDR3 disclosed herein.

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

[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 the heavy chain variable ("VH") region of an antibody disclosed herein. The anti-CD3 antibody or antigen-binding fragment thereof may comprise the 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 derived from an antibody selected from the group consisting of ABL-CD3-1 through ABL-CD3-113, ABL-CD3-1A through ABL-CD3-113A, and ABL-CD3-85B.In some embodiments, the CDRs, VH, and / or VL are 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-CD3-5 3, 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, A BL-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 The antibody may be derived from an antibody selected from the group consisting of 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 to 457. In some embodiments, HCDR2 may comprise an amino acid sequence selected from the group consisting of SEQ ID NOs: 458 to 573. HCDR3 may comprise an amino acid sequence selected from the group consisting of SEQ ID NOs: 574 to 687. In some embodiments, LCDR1 may comprise an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 113. LCDR2 may comprise an amino acid sequence selected from the group consisting of SEQ ID NOs: 114 to 226. In some embodiments, LCDR3 may comprise an amino acid sequence selected from the group consisting of SEQ ID NOs: 227 to 344. In some embodiments, the VL region may comprise an amino acid sequence selected from the group consisting of SEQ ID NOs: 688 to 914. The VH region may comprise an amino acid sequence selected from the group consisting of SEQ ID NOs: 915 to 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, an scFv, a bispecific antibody, a multispecific antibody, an Fab, an 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 antibody may be an IgG4 antibody. In some embodiments, the anti-CD3 antibody is a variant of an IgG antibody, e.g., an IgG1, IgG2, IgG3, or IgG4 variant, or a combination thereof. The anti-CD3 antibody may have reduced or no effector function. In some embodiments, the anti-CD3 antibody is engineered to reduce or eliminate effector function.

[0015] An additional 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 including 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 linked 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), where n is an integer from 1 to 5. In some embodiments, the first linker comprises the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1237), where 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), where n is 4.

[0018] In some embodiments, the targeting antibody is an anti-tumor antibody. In some embodiments, the anti-tumor antibody or antigen-binding fragment thereof comprises a second Fc domain. In some embodiments, the anti-tumor antibody or antigen-binding fragment thereof is operably linked 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 variable-length Gly-Ser linker. 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), where n is an integer from 1 to 5. In some embodiments, the second linker comprises the amino acid sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1146), where 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), where n is 4.

[0019] In some embodiments, the first and second Fc domains comprise mutations that 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-SIn 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 according to EU numbering.

[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. In some embodiments, the anti-CD33 antibody comprises the VH of gemtuzumab. In some embodiments, the anti-CD33 antibody comprises the VL of gemtuzumab. In some embodiments, the anti-CD33 antibody comprises the VH and VL of gemtuzumab. 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 antigen-binding fragment thereof, 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 antigen-binding fragment thereof, or an anti-CD3 multispecific antibody of the present disclosure. Another aspect of the present disclosure provides a vector, e.g., an expression vector, comprising the recombinant polynucleotide. Another aspect of the present disclosure provides an isolated host cell comprising the recombinant polynucleotide or vector. Additional aspects of the present disclosure provide methods for producing an anti-CD3 antibody or antigen-binding fragment thereof, 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 antigen-binding fragment thereof, 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 of treating or preventing cancer in a subject in need thereof by administering to the subject an anti-CD3 antibody or antigen-binding fragment thereof, or bispecific or multispecific antibody, or antibody or fragment, or composition comprising the bispecific or multispecific antibody of the present disclosure. One aspect of the present disclosure provides a method of maintaining cancer remission in a subject in need thereof by administering to the subject an anti-CD3 antibody or antigen-binding fragment thereof, or bispecific or multispecific antibody, or antibody or fragment, or composition comprising the bispecific antibody of the present disclosure. An additional aspect of the present disclosure provides a method of redirecting T cells to tumor cells, the method comprising contacting the T cells with an anti-CD3 bispecific or multispecific antibody or antigen-binding fragment thereof, or a composition comprising the bispecific or multispecific antibody or fragment of the present disclosure. 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 of treating cancer by 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 a subject in need thereof an anti-CD3 antibody or antigen-binding fragment thereof, or bispecific or multispecific antibody, or a composition comprising the antibody or fragment, or bispecific or multispecific antibody of the present disclosure. [Brief explanation of the drawings]

[0026] [Figure 1]Figures 1A and 1B provide the results of flow cytometry analysis of purified monoclonal antibodies. Briefly, flow cytometry was performed on Jurkat wild-type and knockout cells and human pan-T cells at a concentration of 1 μg / ml. Logarithmic geometric mean fluorescence intensity (gMFI) values ​​were plotted for each hit comparing Jurkat wild-type and knockout cells (Figure 1A) and Jurkat wild-type and pan-T cells (Figure 1B).

[0027] [Figure 2] FIG. 2 provides a schematic diagram of the formation of a CD3-CD33 bispecific antibody.

[0028] [Figure 3A] Figure 3A provides a schematic of the killing immunolytic response (KILR) HL60 T cell redirection assay protocol. Figure 3B demonstrates the evaluation of CD-3 x CD33 bispecific antibodies for their ability to mediate interactions between effector and target cells resulting in target-mediated cytotoxicity. [Figure 3B] Figure 3A provides a schematic of the killing immunolytic response (KILR) HL60 T cell redirection assay protocol. Figure 3B demonstrates the evaluation of CD-3 x CD33 bispecific antibodies for their ability to mediate interactions between effector and target cells resulting in target-mediated cytotoxicity.

[0029] [Figure 4A] Figures 4A and 4B provide the results of quantitative ELISA assays for the cytokines IL2 (Figure 4A) and IFNγ (Figure 4B). [Figure 4B] Figures 4A and 4B provide the results of quantitative ELISA assays for the cytokines IL2 (Figure 4A) and IFNγ (Figure 4B).

[0030] [Figure 5A]Figures 5A-5D provide the results of killing immunolytic response (KILR) T cell redirection (TCR) assays for four human PBMC donors: donor 1 (Figure 5A), donor 2 (Figure 5B), donor 3 (Figure 5C), and donor 0 (Figure 5D). [Figure 5B] Figures 5A-5D provide the results of killing immunolytic response (KILR) T cell redirection (TCR) assays for four human PBMC donors: donor 1 (Figure 5A), donor 2 (Figure 5B), donor 3 (Figure 5C), and donor 0 (Figure 5D). [Figure 5C] Figures 5A-5D provide the results of killing immunolytic response (KILR) T cell redirection (TCR) assays for four human PBMC donors: donor 1 (Figure 5A), donor 2 (Figure 5B), donor 3 (Figure 5C), and donor 0 (Figure 5D). [Figure 5D] Figures 5A-5D provide the results of killing immunolytic response (KILR) T cell redirection (TCR) assays for four human PBMC donors: donor 1 (Figure 5A), donor 2 (Figure 5B), donor 3 (Figure 5C), and donor 0 (Figure 5D).

[0031] [Figure 6A] Figure 6A provides the results of an ELISA used to measure polyspecific / nonspecific antibody binding to ds and ss DNA, cardiolipin, insulin, lipopolysaccharide, and hemocyanin. Figure 6B provides the results of an ELISA used to measure polyspecific / nonspecific antibody-bound baculovirus particles. Figure 6C provides the results of antibody retention times measured on a HIC-butyl column, with less hydrophobic species eluting earlier and more hydrophobic species eluting later. [Figure 6B]Figure 6A provides the results of an ELISA used to measure polyspecific / nonspecific antibody binding to ds and ss DNA, cardiolipin, insulin, lipopolysaccharide, and hemocyanin. Figure 6B provides the results of an ELISA used to measure polyspecific / nonspecific antibody-bound baculovirus particles. Figure 6C provides the results of antibody retention times measured on a HIC-butyl column, with less hydrophobic species eluting earlier and more hydrophobic species eluting later. [Figure 6C] Figure 6A provides the results of an ELISA used to measure polyspecific / nonspecific antibody binding to ds and ss DNA, cardiolipin, insulin, lipopolysaccharide, and hemocyanin. Figure 6B provides the results of an ELISA used to measure polyspecific / nonspecific antibody-bound baculovirus particles. Figure 6C provides the results of antibody retention times measured on a HIC-butyl column, with less hydrophobic species eluting earlier and more hydrophobic species eluting later. DETAILED DESCRIPTION OF THE INVENTION

[0032] A brief description of arrays [Table 1A-1] [Table 1A-2] [Table 1A-3] [Table 1A-4] [Table 1A-5] [Table 1A-6] [Table 1A-7] Table 1B-1 Table 1B-2 Table 1B-3 Table 1B-4 Table 1B-5 Table 1B-6 Table 1B-7 Table 1B-8

Table 1C-1

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Table 1F-1

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Table 1F-6

Table 1F-7

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

[0034] Portions of the variable regions from the disclosed antibodies can include all or a combination of the VH and / or VL complementarity-determining regions (CDRs). The variable regions can be formatted in a standard antibody structure (two heavy chains and two light chains) with native or optionally modified constant regions for either up- or down-regulation of various effector functions. The variable regions can also be formatted as multispecific antibodies, e.g., bispecific antibodies that bind to two different epitopes on the CD3 protein or 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 regions can also be formatted as antibody fragments, e.g., single domain antibodies comprising a single VH or VL, Fab, Fab'2, scFv, or chimeric antigen receptors (CARs). The antibodies may also be used as antibody-drug conjugates or may have other additions such as small molecule toxins, or may be included as part thereof with biotoxins, radioisotopes, cytokines, oligopeptides, RNA, or CAR-T cells to increase the treatment modality and / or increase safety.

[0035] The practice of the present disclosure will employ conventional methods of virology, immunology, microbiology, molecular biology, and recombinant DNA techniques within the skill of the art, many of which are described below for illustrative purposes, unless specifically indicated to the contrary. 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 ed., 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 biological systems, which can vary. It should also be understood that the terminology used herein is for the purpose of describing only specific exemplary embodiments and is not intended to be limiting. The terms used herein generally have their ordinary meanings in the art within the context of the present disclosure and in the specific context in which each term is used. Certain terms are discussed below or elsewhere herein to provide additional guidance to practitioners in describing the compositions and methods of the present disclosure and how to make and use them. The scope and meaning of any use of a term will be apparent from the specific context in which the term is used. Therefore, the definitions set forth herein are intended to provide exemplary guidance in identifying specific embodiments of the present disclosure, without limiting them to specific compositions or biological systems.

[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," will be understood to imply the inclusion of a stated element or group of elements, but not the exclusion of any other element or group of elements. "Comprising" can be synonymous with "including" or "containing."

[0039] Whenever an embodiment is described herein using the word "comprising," it should be understood that otherwise similar embodiments described with the terms "consisting of" and / or "consisting essentially of" are also provided. As used herein, "consisting of" is a closed term including only the specific recited elements, while "consisting essentially of" includes the specific recited elements and may include additional, unrecited, non-material elements.

[0040] As used herein, the term "about" modifying the quantity of an ingredient, parameter, calculation, or measurement in a composition or used in a method of the present disclosure refers to variations in numerical value that may exist, for example, due to typical measuring and liquid handling procedures used to make isolated antibodies or pharmaceutical compositions in the real world, due to unintentional errors in these procedures, due to differences in the manufacture, origin, or purity of the ingredients used to make 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%, more typically even within 5%, of a given value or range. Whether modified by the term "about," the present disclosure includes the equivalent to the quantity. Reference herein to "about" a value or parameter includes (and describes) embodiments that are directed to that value or parameter itself. For example, a statement referring to "about X" includes the statement "X." Numerical ranges include the numbers defining the range. Also, all ranges disclosed herein should be understood to encompass any and all subranges subsumed therein.

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

[0042] Antibodies or Ig molecules typically contain two identical heavy chains and two identical light chains linked together through disulfide bonds. Both the heavy (IgH) and light (IgL) chains contain a variable (V) region or domain and a constant (C) region or domain. The portion of the IgH locus encoding the V region contains multiple copies of variable (V), diversity (D), and joining (J) gene segments. The portion of the IgL locus encoding the V region contains multiple copies of V and J gene segments. The V region encoding portions of the IgH and IgL loci undergo gene segment rearrangement to develop diverse antigen specificities in antibodies. For example, different combinations of V, D, and J gene segments arrange to form IgH and IgL variable regions (VH and VL, respectively). Each variable region contains three hypervariable complementarity-determining regions (CDRs) interspersed among less variable framework regions (FRs). The heavy chain contains HCDR1, HCDR2, and HCDR3. The light chain contains LCDR1, LCDR2, and LCDR3. The secreted form of the IgH C region of most antibodies is composed of three C domains, CH1, CH2, and CH3, and a hinge region, except for Cμ, which contains the CH4 region and lacks the hinge region. The membrane-bound form of the IgH C region also has membrane and intracellular domains. The IgH constant region determines the antibody's isotype, e.g., IgM, IgD, IgG1, IgG2, IgG3, IgG4, IgA, and IgE. It is recognized that non-human mammals, e.g., AlivaMab® mice, which encode multiple Ig isotypes, are capable of isotype class switching. 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 set of immune cells, each a clone of a unique parent cell. Monoclonal antibodies are monospecific, have the same sequence, and bind to the same epitope in the same way.

[0044] The term "antigen-binding fragment," as used herein, refers to a polypeptide fragment containing at least one CDR of an immunoglobulin heavy and / or light chain that binds to CD3. In this regard, an antigen-binding fragment of an antibody may contain one, two, three, four, five, or all six CDRs of the VH and VL sequences described herein from the anti-CD3 antibodies disclosed herein. In some embodiments, an antigen-binding fragment of an anti-CD3 antibody contains all six CDRs of the VH and VL sequences described herein from the anti-CD3 antibodies disclosed herein. An antigen-binding fragment of a CD3-specific antibody disclosed herein can bind to a CD3 protein, preferably the receptor binding domain (RBD) of the CD3 protein.

[0045] In some embodiments, the antibodies and antigen-binding fragments thereof disclosed herein comprise a set of heavy and light chain CDRs inserted between a set of heavy and light chain framework regions (FRs), which 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 designated "CDR1," "CDR2," and "CDR3," respectively. The antigen-binding site therefore comprises six CDRs, including the CDR sets from each of the heavy and light chain V regions.

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

[0047] The C-terminal portion of IgH, a crystallizable fragment of the antibody after papain digestion, contains the CH2 and CH3 domains and is referred to as the "Fc" domain. The Fc domain is the portion of Ig that is recognized by cellular receptors, such as FcR, and to which the complement-activating protein C1q binds. The lower hinge region, encoded in the 5' portion of the CH2 exon, provides flexibility within the antibody for binding to the Fc receptor. Although the boundaries of the Fc domain may vary, the human IgG heavy chain Fc domain, as defined herein, comprises residue E216 of the CH3 domain (or the CH4 domain for IgM and IgE antibodies) to its carboxyl terminus, where numbering is in the EU format described by Edelman. The term "Fc domain" can 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. Polymorphisms have been observed at several Fc domain positions, including but not limited to positions 270, 272, 312, 315, 356, and 358 according to EU numbering, so slight differences between the sequences presented in the prior art may exist.

[0048] The term "EU format as described by 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 is also in 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 may be determined by aligning the antibody at the region of homology with the sequence of an antibody having a "standard" EU numbering sequence. Unless indicated to the contrary, all residue numbering of constant regions herein follows EU numbering.

[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 n 91-3242. Variable region CDRs (CDR L1, CDR L2, CDR L3, CDR H1, CDR H2, CDR H3) are identified according to contacts based on the crystal structure defined in Karpusas et al. Structure. Apr 4;9(4):321-9 (2001) and numbered according to the Kabat numbering system. Unless otherwise indicated, all residue numbering in the variable region is according to Kabat.

[0050] An "Fv" fragment comprises a non-covalently linked VH::VL heterodimer comprising an antigen-binding site. In certain embodiments, single-chain Fv (scFv) antibodies are contemplated. scFvs are covalently linked VH::VL heterodimers expressed from a gene fusion comprising VH and VL encoding genes linked by a peptide-encoded linker (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, which are incorporated herein by reference). As used herein, the term "linker" refers to a polypeptide sequence joining two or more antibody domains. The properties of linkers and their suitability for particular purposes are known in the art. See, for example, Chen et al. Adv Drug Deliv Rev. October 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. A linker may be flexible, rigid, or in vivo cleavable. Preferably, the linker is flexible. Flexible linkers typically contain small nonpolar amino acids (e.g., Gly) or polar amino acids (e.g., Ser or Thr). The most commonly used flexible linker has a sequence consisting primarily of a stretch of Gly and Ser residues ("GS" linker). Optionally, the flexible linker contains five repeats of Gly and Ser residues.

[0051] When bispecific antibodies are used, they may be conventional bispecific antibodies, which may be synthesized by various methods (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 Discovery Today. 20(7), 838-47 (2015); Spiess C, Zhai Q, Carter PJ. Mol Immunol. 67(2 Pt A), 95-106 (2015); Labrijn AF, Janmaat ML, Reichert JM, Parren PWHI. Nat Rev Drug Disov. 18(8), 585-608 (2019)), for example, can be prepared chemically or from a hybrid hybridoma, or can be any of the bispecific antibody fragments described above.

[0052] As used herein, the term "chimeric antibody" refers to an antibody encoded by a polynucleotide sequence that contains polynucleotide sequences from two or more species, e.g., human and mouse. Chimeric antibody, as used herein, can also refer to an antibody that includes regions from two or more different antibodies.

[0053] As used herein, the term "chimeric Ig chain" refers to an Ig heavy chain or an Ig light chain encoded by a polynucleotide sequence containing polynucleotide sequences from two or more species, for example, human and mouse. For example, a chimeric Ig heavy chain may include a human VH domain, DH domain, JH domain, CH1 domain, and upper hinge region, and 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 having variable and constant regions derived from human germline immunoglobulin sequences. Human antibodies can 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 mutation in vivo). The term "human antibody," however, does not include antibodies in which CDR sequences are derived from the germline of another mammalian species, such as a mouse, and grafted onto human framework sequences (i.e., humanized antibodies). The term includes antibodies with sequences derived from human genes that have been altered, for example, to reduce potential immunogenicity, increase affinity, reduce effector function, or eliminate cysteines that may cause undesired folding. The term also includes such antibodies containing human amino acid sequences recombinantly produced in non-human cells, which may confer glycosylation patterns that are not typical of 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 from other biological molecules present in the cells used to produce it. Other biological molecules that an isolated antibody or fragment is at least partially free from include nucleic acid molecules, proteins, lipids, carbohydrates, cellular debris, and culture medium. The term "isolated" antibody or fragment does not require, but includes, the complete absence of such other biological molecules. 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, a molecule that is chemically synthesized or synthesized in a cell-free system is "isolated" from its naturally associated components. A molecule may also be "isolated" using purification techniques well known in the art. Similarly, the term "isolated" polynucleotide or nucleic acid molecule, as used herein, refers to a polynucleotide of genomic, mRNA, cDNA, or synthetic origin, or a combination of portions thereof, where (1) the "isolated nucleic acid" is not associated with all or part of a polynucleotide with which it is associated in nature, (2) it is operably linked to a polynucleotide with which it is not linked in nature, or (3) it is not found in nature as part of a larger sequence. An isolated polynucleotide "comprising" a particular 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, a V domain, a C domain, or an antibody.

[0057] As used herein, the term "amino acid modification" refers to the substitution, insertion, deletion, or mutation of at least one amino acid in an amino acid sequence compared to the wild-type amino acid sequence. Such modifications are within the ordinary skill of a person skilled in the art. Certain modifications, including deletions, substitutions, and additions of amino acids in the Fc domain, have been shown to alter binding of the Fc domain to its ligands and / or receptors, resulting in concomitant modifications of effector function (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 V et al., J Virol. 75: 12161-12168 (2001), each of which is incorporated herein by reference in its entirety). al. Acta Crystallogr D Biol Crystallogr; 64: 700-704 (2008);Schlothauer T et al. Protein Eng Des Sel. Oct; 29(10):457-466 (2016);Tao MH et al. J. Immunol. 143: 2595-2601 (1989);Von Kreudenstein TS et al. MAbs. 5(5):646-654 (2013);Wang X et al. Protein Cell. 9(1):63-73 (2018); U.S. Patent Publication Nos. 20040132101; 20070111260; 20110287032; 20180194860; U.S. Patent No. 8,409,568; and International Publication No. WO2017 / 177337). Amino acid deletions are indicated by "Δ" and insertions are indicated by "In." For example, a deletion of the amino acid sequence E216 to E222 is indicated as ΔE216-E222.An insertion of arginine (R) between amino acid residues 234 and 235 is indicated, for example, as InR234 / 235.

[0058] A "conservative amino acid substitution" replaces an amino acid residue with a different amino acid residue having similar biochemical properties (e.g., charge, hydrophobicity, or size). Generally, conservative amino acid substitutions do not substantially change the functional properties of a protein. When comparing proteins containing conservative substitutions, the percent 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 below provides some of the biochemical properties of the 20 naturally occurring amino acids. Table 3 below provides non-limiting examples of conservative amino acid substitutions for each of the naturally occurring amino acids. [Table 2] [Table 3]

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

[0060] Sequence alignment (e.g., to determine percent amino acid sequence identity or sequence similarity, such as between a wild-type protein and its mutein) can be accomplished in a variety of ways within the skill of the art, for example, using publicly available sequence analysis computer software, such as BLAST, BLAST-2, ALIGN, Megalign (DNASTAR), Gap, BESTFIT®, and other programs in the Wisconsin Package version 10.0 or programs in the Genetics Computer Group (GCG), Madison, Wisconsin software. Those skilled in the art can determine appropriate parameters for aligning sequences, including any algorithms needed to achieve maximal alignment over the entire length of the sequences being compared. Polypeptide sequences can also be compared using FASTA, using default or recommended parameters. In the context of polypeptide sequences, FASTA takes a query amino acid sequence and searches sequence databases using local sequence alignments to identify similar sequences within the databases (Pearson, Methods Enzymol. 183:63-98 (1990); Pearson, Methods Mol. Biol. 132:185-219 (2000); Pearson Curr Protoc Bioinformatics. Mar 24;53:3.9.1-25 (2016); each incorporated herein by reference). BLAST, particularly blastp or tblastn, using default parameters may also be used to compare a query sequence to a database containing sequences from different organisms. 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 may be grouped based on 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 substitutions 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 response of cells of the immune system elicited by the interaction of antibodies and antibody-antigen complexes. These effector functions typically involve one of three major 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 bound to target cells, resulting in the secretion of substances that mediate the destruction of the target cells, such as lytic enzymes, perforin, granzymes, and tumor necrosis factors. In CDC, cell death is induced via activation of the complement cascade. See Daeron, Annu. Rev. Immunol., 15:203-234 (1997); Ward and Ghetie, Therapeutic Immunol., 2:77-94 (1995); and Ravetch and Kinet, Annu. Rev. Immunol. 9:457-492 (1991). In opsonization and phagocytosis, the Fc domain of an antibody bound to a pathogen binds to an Fc receptor on the surface of a phagocyte, inducing phagocytosis. Such effector functions generally require an Fc domain in combination with a binding domain (e.g., an antibody variable domain) and can be evaluated using standard assays known in the art (see, e.g., WO05 / 018572, WO05 / 003175, and U.S. Pat. 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 cell surface Fcγ receptor family and to Clq of the complement system. Ligation of effector proteins by clustered antibodies induces a variety of responses, including the release of inflammatory cytokines, modulation of antigen production, endocytosis, and cell killing. These responses can lead to unwanted side effects, such as inflammation and thrombosis.Accordingly, the present disclosure further relates to anti-CD3 antibodies with altered effector functions, including antibodies in which one or more effector functions are reduced or eliminated.

[0063] As used herein, the term "altered effector function" refers to an Fc domain that has one or more effector functions that differ from a wild-type immunoglobulin Fc domain. In some embodiments, one or more effector functions are reduced. Optionally, one or more effector functions are eliminated. The altered or reduced effector function may be the result of lower binding affinity of the Fc domain of an antibody disclosed herein to an effector molecule (e.g., FcγR and / or C1q). For example, an anti-CD3 antibody disclosed herein may have reduced Fc receptor binding and complement activation compared to that of a wild-type anti-CD3 antibody. In some embodiments, the variant Fc domain has reduced antibody-dependent cell-mediated cytotoxicity (ADCC). The effector functions of an anti-CD3 antibody may 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% compared to the effector function of a wild-type antibody.

[0064] The strength or affinity of an immunological binding interaction is determined by the dissociation constant (K D ), where the smaller K Drepresents a higher affinity. The immunological binding properties of a selected polypeptide can be quantified using methods well known in the art. One such method involves measuring the rates of antigen-binding site / antigen complex formation and dissociation, where these rates depend on the concentrations of the complex partners, the affinity of the interaction, and geometric parameters that affect the rates in both directions equally. Therefore, the "on rate constant" (k on ) and the "off rate constant" (k off ) can both be determined by calculation of the concentrations and the actual rates of association and dissociation. off / k on The ratio of allows the cancellation of all parameters not related to affinity and therefore the dissociation constant K D See generally Davies et al. (1990) Annual Rev. Biochem. 59:439-473. Antibodies are D High affinity antibodies are generally considered to specifically bind to an antigen when their affinity is ≦1 μM, preferably ≦100 nM. -9 ) range of K D and very high affinity antibodies generally have a potency of picomolar (10 -12 ) range of K D K DThe binding affinity constant can be measured by surface plasmon resonance, for example, using the BIACORE® 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. D K may also be measured using the KINEXA® system (Sapidyne Instruments, Hanover, Germany and Boise, ID). D may also be measured by biolayer interferometry (BLI) using the OCTET® system (Sartorius AG, Goettingen, Germany). An antibody or antigen-binding fragment thereof is said to "specifically bind," "immunologically bind," and / or "immunologically reactive" 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, an antibody or antigen-binding fragment thereof specifically binds to CD3.

[0065] As used herein, the term "avidity" refers to the overall strength of an antibody-antigen complex. Avidity relates to three major 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 moieties. As used herein, "avidity" describes the increased affinity that results from multiple antigen-binding sites on an immunoglobulin.

[0066] As used herein, the terms "polynucleotide" and "nucleic acid molecule" are used interchangeably and refer to a polymer of nucleic acid linked together by chemical bonds. Polynucleotides include, but are not limited to, DNA, cDNA, RNA, mRNA, and gene sequences and segments. Polynucleotides may be isolated from living sources, such as eukaryotic cells, prokaryotic cells, or viruses, or may be derived through in vitro manipulation using standard techniques of molecular biology, by DNA synthesis, or by a combination of techniques. Polynucleotides may contain ribonucleotides, deoxynucleotides, modified forms of any type of nucleotide, or combinations thereof. Polynucleotides may be single-stranded or double-stranded. Reference herein to a nucleotide sequence includes its complement, unless otherwise specified. Therefore, a reference to a polynucleotide having a particular sequence should be understood to encompass its complementary strand, with its complementary sequence.

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

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

[0069] As used herein, the term "vector" refers to a polynucleotide molecule capable of replicating in a cell into which another polynucleotide fragment can be incorporated without losing the vector's ability to replicate. Vectors may originate from viruses, plasmids, or cells of higher organisms. Vectors are utilized to introduce foreign or recombinant DNA into host cells where the vector replicates. 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 cationic condensing agents, DNA or RNA expression vectors encapsulated in liposomes, and certain eukaryotic cells, such as producer cells. In some embodiments, vectors autonomously replicate in the host cell into which they are introduced. Optionally, vectors integrate into the genome of the host cell and replicate along with the host genome. Vectors may be capable of directing the expression of coding sequences contained within them. Such vectors are referred to herein as "recombinant expression vectors" or "expression vectors."

[0070] Polynucleotides can be contained in vectors, which can facilitate the manipulation of polynucleotides, including the introduction of polynucleotides into target cells.Vector can be a cloning vector that is useful for maintaining polynucleotides.If polynucleotides encode RNA, the vector can be an expression vector that contains regulatory elements useful for expressing polynucleotides in addition to polynucleotides, for the purpose of expressing the encoded RNA in specific cells, for the subsequent translation of RNA into polypeptides, or for the subsequent transregulatory activity of RNA in cells.Expression vectors can contain expression elements necessary for achieving, for example, the continuous transcription of coding polynucleotides, or regulatory elements can be operably linked to polynucleotides before they are cloned into vectors.

[0071] Expression vectors generally contain a promoter sequence, which can provide for constitutive expression of the coding polynucleotide; a polyA sequence; and ribosome recognition sites or internal ribosome entry sites, or other regulatory elements that can be tissue-specific, such as enhancers, or, optionally, inducible, tissue-specific, or developmental stage-specific expression. Vectors can also contain elements necessary for replication in prokaryotic or eukaryotic host systems, or both, as desired. Such vectors, including plasmid vectors and viral vectors, e.g., bacteriophage, baculovirus, retrovirus, lentivirus, adenovirus, vaccinia virus, alphavirus, and adeno-associated virus vectors, are well known and can be purchased from commercial sources (Promega, Madison Wis.; Agilent technologies, Santa Clara Calif.; Thermo Fisher Scientific, Waltham, Mass.), or can be constructed by one of skill in the art (e.g., Meth. Enzymol., Vol. 185, Goeddel, ed. (Academic Press, Inc., 1990); Jolly, Canc. Gene Ther. 1:51-64, 1994; Flotte, J. Bioenerg. Biomemb 25:37-42, 1993; Kirshenbaum et al., J. Clin. Invest, 92:381-387, 1993, each of which is incorporated herein by reference).

[0072] The term "polynucleotide construct" as used herein refers to a sequence of DNA that is artificially constructed by genetic engineering, recombination, or synthesis. In some embodiments, the DNA construct is linearized before recombination. In other embodiments, the DNA construct is not linearized before 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 particular subject cell but also the progeny of such a cell. Because certain modifications may occur in subsequent generations due to either mutation or environmental influences, such progeny may not actually be identical to the parent cell, but are still included within the scope of the term "host cell" as used herein, provided that they still contain the vector, polynucleotide, or portion thereof, either episomally maintained or integrated into the host cell genome.

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

[0075] The terms "treating" and "treatment" with respect to a subject refer to improving at least one symptom of a disease or disorder in a subject. Treating includes curing, improving, or at least partially ameliorating a disease or disorder, or any symptom of a disease or disorder. With respect to cancer, these terms refer to increased life expectancy of an individual with cancer, or reducing one or more symptoms of cancer. The terms also encompass a reduced risk of malignant disease in a subject with cancer. With respect to the treatment of autoimmune diseases, treating can refer to weakening 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 reducing one or more symptoms thereof, in a subject as a result of administration of an anti-CD3 antibody of the present disclosure. For example, in the context of cancer, "prevent," "preventing," and "prevention" refer to inhibiting, reducing, or delaying the onset of cancer in a subject, preventing or delaying the recurrence, onset, or occurrence of one or more symptoms associated with cancer, and maintaining remission in a subject. Also, in the context of autoimmune disease, "prevent," "preventing," and "prevention" refer to inhibiting, reducing, or delaying the onset or onset of an autoimmune response, or preventing or delaying the recurrence, onset, or occurrence of one or more symptoms associated with an autoimmune response.

[0077] As used herein, the term "therapeutically effective amount" refers to an amount of a therapeutic agent administered as a single agent or in combination with one or more additional agents that relieves to some extent one or more of the symptoms of the condition being treated. With respect to the treatment of cancer, a therapeutically effective amount refers to an amount that has at least one of the following effects: alleviating, 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 the present disclosure varies depending on the mode of administration, the age, weight, and overall health of the subject. Appropriate amounts and dosage regimens can be determined using routine skill 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 dose is used in subjects in remission, and the prophylactically effective amount may be less than the therapeutically effective amount.

[0079] As used herein, the terms "pharmaceutically acceptable carrier" and "pharmaceutically acceptable excipient" are used interchangeably and refer to any and all physiologically compatible solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, etc. 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, PA (1984), which is incorporated herein by reference. These carriers may be included, but are not limited to, in the FDA Abstracts of Generally Regarded as Safe (GRAS) excipients (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, etc., and combinations thereof. In many cases, it will be preferable 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 antibodies.Pharmaceutical compositions may be prepared by mixing an antibody disclosed herein with an acceptable carrier, excipient, or stabilizer, for example, in the form of 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; Lieberman, et al. (eds.) (1990) Pharmaceutical Dosage Forms: Tablets, Marcel Dekker, NY; Lieberman, et al. (eds.) (1990) Pharmaceutical Dosage Forms: Disperse Systems, Marcel Dekker, NY). Dekker, NY; Weiner and Kotkoskie (2000) Excipient Toxicity and Safety, Marcel Dekker, Inc., New York, NY; each incorporated herein by reference).

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

[0081] Each embodiment herein should be applied mutatis mutandis to every other embodiment unless expressly stated otherwise.

[0082] Standard techniques may be used for recombinant DNA, oligonucleotide synthesis, and tissue culture and transformation (e.g., electroporation, lipofection). Enzymatic reactions and purification techniques may be performed according to manufacturer's specifications or as generally established in the art or as described herein. These and related techniques and procedures may generally be performed according to conventional methods well known in the art, as well as as described in the various general and more specific references cited and discussed throughout the specification. Unless specific definitions are provided, the nomenclature utilized in connection with, and the laboratory procedures and techniques of, molecular biology, analytical chemistry, synthetic organic chemistry, and medicinal and pharmaceutical chemistry described herein are those well known and commonly used in the art. Standard techniques may be used for recombinant technology, molecular biology, microbiology, chemical synthesis, chemical analysis, pharmaceutical preparation, formulation, and delivery, and treatment of patients.

[0083] Anti-CD3 antibody AlivaMab® mouse anti-CD3 antibodies were generated using both AlivaMab® XKL mice (a cross between AlivaMab® Kappa-Lambda mice and another genetic background) and AlivaMab® mouse Lambda Only mice. The antibody produced by AlivaMab® XKL mice contains a chimeric immunoglobulin heavy (IgH) chain and a human immunoglobulin kappa (Igκ) light chain or a human immunoglobulin lambda (Igλ) light chain. The antibody produced by AlivaMab® Lambda Only mice contains a chimeric IgH chain and a human immunoglobulin lambda (Igλ) light chain. The chimeric IgH chain of an AlivaMab® mouse antibody contains a human variable region including 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 (excluding 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 chimeric anti-CD3 antibody can be readily added to a fully human constant region while maintaining the antigen-binding properties of the parent chimeric antibody generated in vivo in an AlivaMab® mouse. In some embodiments, the human heavy chain variable region, CH1, and, optionally, the upper hinge region of the chimeric antibody are added to a human hinge, a human CH2 domain, and a 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 may 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 NOs: 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 an anti-CD3 antibody or antigen-binding fragment thereof can be mixed and matched among the CDRs of the antibody clones disclosed herein. In some embodiments, the anti-CD3 antibody or antigen-binding fragment thereof comprises an HCDR1 comprising any HCDR1 sequence disclosed herein, an HCDR2 comprising any HCDR2 sequence disclosed herein, and an 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 an LCDR1 comprising any LCDR1 sequence disclosed herein, an LCDR2 comprising any LCDR2 sequence disclosed herein, and an 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 may be the same anti-CD3 clone from which the HCDR1, HCDR2, and HCDR3 were selected.

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

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

[0091] The CDRs, VH and / or VL may be selected from any one of 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 CDRs, VH, and / or VL are 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-CD3-5 3, 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, A BL-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 The antibody may be derived from an antibody selected from the group consisting of 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, the anti-CD3 antibody or antigen-binding fragment thereof comprises i) a heavy chain variable region comprising an HCDR1 disclosed herein, an HCDR2 disclosed herein, and an HCDR3 disclosed herein; and ii) a light chain variable region comprising an LCDR1 disclosed herein, an LCDR2 disclosed herein, and an LCDR3 disclosed herein. HCDR1 may comprise an amino acid sequence selected from the group consisting of SEQ ID NOs: 345-457. In some embodiments, HCDR2 may comprise 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.

[0093] It is known in the art that during processing and expression of Fc-containing proteins (e.g., antibody heavy chains), the C-terminal lysine can be cleaved (also known in the art as C-terminal lysine clipping). Thus, for each sequence disclosed herein that contains a C-terminal lysine, the corresponding sequence without the C-terminal lysine (i.e., a C-terminal lysine cleavage product) is 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 that additional C-terminal residues are truncated. Thus, for each sequence disclosed herein containing a C-terminal lysine, a corresponding sequence without the two C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein containing a C-terminal lysine, a corresponding sequence without the three C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein containing a C-terminal lysine, a corresponding sequence without the four C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein containing a C-terminal lysine, a corresponding sequence without the five C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein containing a C-terminal lysine, a corresponding sequence without the six C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein containing a C-terminal lysine, a corresponding sequence without the seven C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein containing a C-terminal lysine, a corresponding sequence without the eight C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein containing a C-terminal lysine, the corresponding sequence without the 9 C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein containing a C-terminal lysine, the corresponding sequence without the 10 C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein containing a C-terminal lysine, the corresponding sequence without the 11 C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein containing a C-terminal lysine, the corresponding sequence without the 12 C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein containing a C-terminal lysine, the corresponding sequence without the 13 C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein containing a C-terminal lysine, the corresponding sequence without the 14 C-terminal residue is also contemplated. In some embodiments, for each sequence disclosed herein containing a C-terminal lysine, the corresponding sequence without the 15 C-terminal residue 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 an 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 an 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 N-terminally to C-terminally in a VH-to-VL orientation or a VL-to-VH orientation. As used herein, the term "scFv_VH-VL" refers to an scFv fragment arranged N-terminally to C-terminally in a VH-to-VL orientation. Similarly, the term "scFv_VL-VH" refers to an scFv fragment arranged N-terminally to C-terminally in a VL-to-VH orientation.

[0096] In some embodiments, the VH comprises a G44C substitution according to Kabat numbering. In some embodiments, the VL comprises a G100C substitution according to Kabat numbering. In some embodiments, the VH comprises a G44C substitution and the VL comprises a G100C substitution according to Kabat numbering. In rare cases, the parent sequence of VH44 may be an amino acid residue other than G. In such instances, the VH44 residue (according to Kabat) is further mutated to a cysteine. In more common, but still relatively rare, cases, the parent sequence of VL at position 100 may be an amino acid other than G. In such instances, the VL100 residue (according to Kabat) is further mutated to a cysteine. Without being bound by theory, the introduction of such a complementary cysteine ​​residue may result in a disulfide bond, stabilizing the antibody fragment (e.g., scFv). Other Cys substitutions are known and may be used, including, but not limited to, positions 99, 100a, and 101 of the VL (see Weatherill et al, PEDS (2012) 25:321-9). In some embodiments, the free cysteine ​​residues in the VH and / or VL may 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 in 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 in 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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 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 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 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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), where 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 an...

Claims

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

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

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

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

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

6. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 5, wherein the antibody is selected from a single variable domain antibody, a single-chain antibody, an scFv, a bispecific antibody, a multispecific antibody, a Fab, an 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 Fc domain and a second Fc domain.

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

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

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

12. The antibody or antigen-binding fragment thereof according to 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 to 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 through a first linker.

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

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

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

18. The antibody or antigen-binding fragment thereof according to 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 according to any one of claims 8 to 19, wherein the first Fc domain and the second Fc domain comprise complementary mutations selected from knobs-into-holes (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. (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 a S354C / T366W mutation and the (4) the first Fc domain comprises Y349C / T366S / L368A / Y407V mutations and the second Fc domain comprises S354C / T366W mutations; (5) the first Fc domain comprises S354C / T366W mutations and the second Fc domain comprises (6) the first Fc domain comprises Y349C / T366S / L368A / Y407V / H435R / Y436F mutations and the second Fc domain comprises S354C / T366W mutations; or (7) the first Fc domain comprises S354C / T366W / H435R / Y436F mutations.

21. The antibody or antigen-binding fragment thereof of claim 20, wherein: 8) the first Fc domain comprises Y349C / T366S / L368A / Y407V mutations and the second Fc domain comprises Y349C / T366S / L368A / Y407V mutations; or 9) the first Fc domain comprises Y349C / T366S / L368A / Y407V mutations and the second Fc domain comprises S354C / T366W / H435R / Y436F mutations.

22. 21. The antibody or antigen-binding fragment thereof of claim 20, wherein (1) the first Fc domain and the second Fc domain comprise the amino acid sequences of SEQ ID NOs: 1142 and 1143, respectively; or (2) the first Fc domain and the second Fc domain 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. (1) the first Fc domain comprises a 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 a S364H mutation; (3) the first Fc domain comprises a 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 a F405A mutation; (5) the first Fc domain comprises a S364H / T394F mutation and the 21. The antibody or antigen-binding fragment thereof of claim 20, wherein: (1) the second Fc domain comprises a Y349T / F405A mutation; (2) the first Fc domain comprises a Y349T / F405A mutation and the second Fc domain comprises a S364H / T394F mutation; (3) the first Fc domain comprises a S364H / F405A mutation and the second Fc domain comprises a Y349T / T394F mutation; or (4) the first Fc domain comprises a Y349T / T394F mutation and the second Fc domain comprises a S364H / F405A mutation.

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

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

27. (1) the first Fc domain comprises D399M / Y407A mutations and the second Fc domain comprises T366V / K409V mutations; (2) the first Fc domain comprises T366V / K409V mutations and the second Fc domain comprises D399M / Y407A mutations; or (3) the first Fc domain comprises K360D / D399M / Y407A mutations and the second Fc domain comprises E345R / 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 E357D / S364Q / Y407A mutations. (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; 21. The antibody or antigen-binding fragment thereof of claim 20, wherein: (1) the first Fc domain comprises Y349S / K370Y / T366M / K409V mutations; (2) the first Fc domain comprises Y349S / K370Y / T366M / K409V mutations and the second Fc domain comprises E357D / S364R / Y407A mutations; or (3) the first Fc domain comprises E357D / S364R / Y407A mutations and the second Fc domain comprises Y349S / K370Y / T366M / K409V mutations.

28. (1) the first Fc domain comprises K409D / K392D mutations and the second Fc domain comprises D399K / E356K mutations; (2) the first Fc domain comprises D399K / E356K mutations and the second Fc domain comprises K409D / K392D mutations; (3) the first Fc domain comprises K409E / K392D mutations and the second Fc domain comprises K409E / K392D mutations. (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 a D399R / E356 (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 K409E / K392D mutations and the second Fc domain comprises K409E / K392D mutations; 21. The antibody or antigen-binding fragment thereof of claim 20, wherein (1) 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. (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; or (4) the first Fc domain comprises a Q347R / D399V / F405T mutation.

21. The antibody or antigen-binding fragment thereof of claim 20, wherein: (1) the first Fc domain comprises a K360E / K409W mutation, and the second Fc domain comprises a K360E / K409W mutation; (2) the first Fc domain comprises a K360E / K409W / Y349C mutation, and the second Fc domain comprises a Q347R / D399V / F405T / S354C mutation; or (3) the first Fc domain comprises a Q347R / D399V / F405T / S354C mutation, and the second Fc domain comprises a K360E / K409WY349C mutation.

30. 21. 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 GA SEED domain and the second Fc domain comprises an AG SEED domain.

31. (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 E (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 / K (8) the first Fc domain comprises E357M / D399V / F405T mutations 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 K370D / K409W mutations; (11) the first Fc domain comprises E357D / S364W / K370E mutations, and the second Fc domain comprises E357N / K370H mutations; (12) the first Fc domain comprises E357N / K370H mutations, and the second Fc domain comprises E357A / S364Y / K370E mutations; (13) the first Fc domain comprises E357G / S364W / K370E mutations, and the second Fc domain comprises E357N mutations;(14) The antibody or antigen-binding fragment thereof of claim 20, wherein the first Fc domain comprises an E357N mutation and the second Fc domain comprises an E357G / S364W / DK70E mutation; (15) the first Fc domain comprises an E357N / S364W / K370E mutation and the second Fc domain comprises an E357N mutation; or (16) the first Fc domain comprises an E357N mutation and the second Fc domain comprises an E357N / S364W / DK70E mutation.

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

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

34. The antibody or antigen-binding fragment thereof according to 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 according to any one of claims 1 to 39, wherein the antibody is selected from 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 an IgG1 antibody, an IgG2 antibody, an IgG3 antibody, or an IgG4 antibody.

43. 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 modified Fc domain from the IgG1 molecule comprises: E216, R217, K218, C219, C220, C226, C229, P230, E233, L234, L235, G236, G237, P238, S239, V240, F241, K246, L251, T260, D265, V266, H268, W277, N297, E318, K322, 44. The antibody or antigen-binding fragment thereof of claim 43, comprising an amino acid modification at any one of positions selected from the group consisting of P329, A330, P331, Q347, N348, T350, L351, K360, T366, N390, K392, T394, D399, S400, F405, Y407, K409, and T411, or a combination of such amino acid modifications.

45. the modified Fc domain derived from IgG1 is 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, T366M, T366V, N390R, N390K, N390D, K392V, K392M, K39 2R, K392L, K392F, K392E, T394W, D399R, D399W, D399K, S400E, S400D, S400R, S400K, F405A, F405I, F405M, F405T, F405S, F 405V, F405W, Y407A, Y407I, Y407L, Y407V, K409F, K409I, K409S, K409W, T411N, T411R, T411Q, T411K, T411D, T411E, T411 W, ΔE216-E222, K246R / L251E / T260R, InR234 / 235, InV235 / 236, InR236 / 237, InR237 / 238, InV238 / 239, InN238 / 239, InL 44. The antibody or antigen-binding fragment thereof of claim 43, comprising amino acid modifications selected from the group consisting of In238 / 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. 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. 43. The antibody or antigen-binding fragment thereof of claim 42, wherein the antibody comprises a modified Fc domain derived from an IgG2 molecule.

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

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

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

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

52. 52. The antibody or antigen-binding fragment thereof of claim 51 , wherein the modified Fc domain derived from the IgG4 molecule comprises an amino acid modification at any one of 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. 54. An expression vector comprising the recombinant polynucleotide of claim 53.

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

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

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

58. 53. A method for producing the antibody or antigen-binding fragment thereof of any one of claims 1 to 52, said 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 according to any one of claims 1 to 52 and a physiologically acceptable carrier.

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

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

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

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

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

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

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