Anti-CD3 antibodies and uses thereof

Abstract

Aspects of the application provide anti-CD3 antibodies and methods of using the same in treating cancer, infection, or autoimmune disorders.

Description

ANTI-CD3 ANTIBODIES AND USES THEREOFRELATED APPLICATIONS

[0001] This application claims the benefit under 35 U.S.C. § 119(e) of U.S. Provisional Application No. 63 / 664,036, filed on June 25, 2024, the entire contents of which are hereby incorporated by reference in their entirety.REFERENCE TO AN ELECTRONIC SEQUENCE LISTING

[0002] The contents of the electronic sequence listing (A136170023WO00-SEQ- EMB.xml; Size: 32,898 bytes; Date of Creation: June 25, 2025) is herein incorporated by reference in its entirety.BACKGROUND

[0003] CD3 is a cell surface protein complex expressed by T lymphocytes and forms an essential part of the T cell receptor (TCR) complex. T cells are central to the adaptive immune system, mediating protective responses against infected or malignant cells. Bispecific T cell engagers (TCEs) are a promising class of engineered antibody-based therapeutics designed to redirect T cell cytotoxicity toward tumor cells. These molecules typically comprise two antigen-binding domains: one targeting CD3 (e.g., CD3s) on T cells and the other targeting a tumor-associated antigen (TAA) on malignant cells. By simultaneously engaging both targets, TCEs promote formation of an immunological synapse, leading to T cell activation and tumor cell lysis in a manner that is independent of MHC presentation. CD3-targeted bispecific antibodies have demonstrated potent anti-tumor activity in both hematologic and solid tumors, underscoring their potential in cancer immunotherapy .

[0004] Despite the growing clinical relevance of TCEs, their development remains technically challenging. While many candidate TCEs display high selectivity and potency in preclinical experiments, they often suffer from problems in downstream development and clinical efficiency studies, including polyspecific, nonspecific and / or off-target binding; poor expression levels or profiles in eukaryotic host cells, such as mammalian host cells and yeast cells; poor chemical and physical properties, such as poor stability during storage (e.g., poor / low “shelf-life” stability), poor (low) solubility, poor (high) viscosity, propensity to aggregate; and poor clinical and biophysical profiles, such as poor pharmacokinetic profiles,poor pharmacodynamic profiles, fast or poor in vivo clearance rates , short circulation halflife, some of which result in termination of their development.

[0005] One frequently used CD3-binding scaffold is SP34, a murine monoclonal antibody that binds human CD3s with high affinity, demonstrates robust T cell activation, and exhibits cross-reactivity with non-human primate CD3, thereby facilitating preclinical studies in relevant animal models. However, like those described above, TCEs and monoclonal antibodies derived from SP34 often display unfavorable biophysical characteristics and their translation into commercial therapeutics is often hampered by persistent developability challenges.

[0006] While recent efforts have focused on the de novo discovery of CD3-binding domains with improved biophysical properties, such approaches often require significant optimization and lack extensive clinical validation. By contrast, scaffolds like SP34 benefit from well-characterized pharmacology, high potency, and cross-reactivity with non-human primates. Accordingly, there remains a need for CD3-binding antibody domains that preserve the potent T cell activation and non-human primate cross -reactivity of established and validated binders, such as SP34, while exhibiting improved physicochemical and manufacturing properties.SUMMARY

[0007] The present disclosure, at least in part, provides engineered humanized SP34 antibodies that specifically recognize and bind CD3 and display improved biophysical and developability properties (e.g., improved binding affinity, and / or reduced polyreactivity as compared to existing humanized anti-CD3 antibodies or the murine parental antibody). For example, in one aspect, the disclosure features an isolated antibody or antigen-binding fragment thereof that binds to CD3 (e.g., human CD3). In some embodiments, an anti-CD3 antibody can be used to activate T cells, such as to induce their proliferation or differentiation. In some embodiments, an anti-CD3 antibody can be used to deplete T cells, such as to treat a T cell-mediated autoimmune condition or to ameliorate the symptoms of a T cell-mediated autoimmune condition. In other aspects, the present disclosure provides T-cell engaging bispecific antibodies targeting CD3, which comprise a first antigen binding site that specifically binds a cancer antigen or a pathogen-derived antigen, and a second antigen binding site that specifically binds CD3 (e.g., an antigen binding sites derived from any of the anti-CD3 antibodies described here). In some embodiments, a bispecific antibody described herein recruits a T cell (e.g., cytotoxic T cell) to a cancer cell or an infected cell. In some embodiments, a bispecific antibody described herein elicits T cell mediated immune response(e.g., cytotoxic T cell mediated immune response) against a cancer cell or an infected cell. In some embodiments, a bispecific antibody described herein induces T cell mediated killing (e.g., cytotoxic T cell mediated immune response) of a cancer cell or an infected cell. In some embodiments, a bispecific antibody described herein is useful for treating cancer or infection.

[0008] In some embodiments, the present disclosure provides means for engaging a T cell to a cancer cell or an infected cell. In some embodiments, the means for engaging a T cell to a cancer cell or an infected cell is a bispecific antibody described herein. In some embodiments, the present disclosure provides means for eliciting cytotoxic T cell immunity against cancer cells or infected cells. In some embodiments, the means for eliciting cytotoxic T cell immunity against cancer cells or infected cells is a bispecific antibody described herein.

[0009] In some embodiments, the present disclosure provides an antibody that specifically binds CD3, wherein the improvement comprises one or more of the HC CDR (e.g., HC CDR1, HC CDR2, or HC CDR3) amino acid sequences from any one of an anti-CD3 antibodies selected from Table 1. In some embodiments, the present disclosure provides an antibody that specifically binds CD3, wherein the improvement comprises the HC CDR1, HC CDR2, and HC CDR3 as provided for any one of the antibodies elected from Table 1. In some embodiments, the present disclosure provides an antibody that specifically binds CD3, wherein the improvement comprises one or more of the LC CDRs (e.g., LC CDR1, LC CDR2, or LC CDR3) amino acid sequences from any one of an anti-CD3 antibody selected from Table 1. In some embodiments, the present disclosure provides an antibody that specifically binds CD3, wherein the improvement comprises the LC CDR1, LC CDR2, and LC CDR3 s provided for any one of an anti-CD3 antibody selected from Table 1. In some embodiments, the present disclosure provides an antibody that specifically binds CD3, wherein the improvement comprises HC CDR1, HC CDR2, and HC CDR3, LC CDR1, LC CDR2, and LC CDR3 as provided for any one of an anti-CD3 antibody selected from Table 1.

[0010] In some embodiments, the present disclosure provides anti-CD3 antibodies having one or more amino acid change (e.g., substitution) in one or more of the framework regions as compared to the parental murine anti-CD3 antibody and / or a pre-existing humanized anti- CD3 antibody of the same parental murine antibody. In some embodiments, the present disclosure provides an antibody that specifically binds CD3, wherein the improvement comprises one or more of the framework sequences from any one of an anti-CD3 antibodies selected from Table 5.

[0011] In some embodiments, a bispecific antibody comprises a second antigen binding site that specifically binds to a cancer antigen or a pathogen-derived antigen, wherein the improvement comprises a first antigen binding site that specifically binds to CD3 that comprises any one of the anti-CD3 binding sites derived from an anti-CD3 antibody described herein (e.g., any one of the anti-CD3 binders described in Table 1).

[0012] Accordingly, in some aspects, provided herein is an antibody that specifically binds CD3 comprising (a) a heavy chain complementarity determining region 1 (HC CDR1), a heavy chain complementarity determining region 2 (HC CDR2), and a heavy chain complementarity determining region 3 (HC CDR3) of a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 7; and a light chain complementarity determining region 1 (LC CDR1), a light chain complementarity determining region 2 (LC CDR2), and a light chain complementarity determining region 3 (LC CDR3) of a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 8; or (b) a HC CDR1, HC CDR2, and a HC CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 11; and a LC CDR1, LC CDR2, and a LC CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 8.

[0013] In some aspects, an antibody that specifically binds CD3 comprises (a) a HC CDR1 comprising the amino acid sequence of SEQ ID NO: 1, a HC CDR2 comprising the amino acid sequence of SEQ ID NO: 2, a HC CDR3 comprising the amino acid sequence of SEQ ID NO: 3, a LC CDR1 comprising the amino acid sequence of SEQ ID NO: 4, a LC CDR2 comprising the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 comprising the amino acid sequence of SEQ ID NO: 6; or (b) a HC CDR1 comprising the amino acid sequence of SEQ ID NO: 1, a HC CDR2 comprising the amino acid sequence of SEQ ID NO: 9, a HC CDR3 comprising the amino acid sequence of SEQ ID NO: 10, a LC CDR1 comprising the amino acid sequence of SEQ ID NO: 4, a LC CDR2 comprising the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 comprising the amino acid sequence of SEQ ID NO: 6.

[0014] In some embodiments, the antibody comprises (a) a VH comprising the amino acid of SEQ ID NO: 7, and / or a VL comprising the amino acid sequence of SEQ ID NO: 8; or (b) a VH comprising the amino acid of SEQ ID NO: 1, and / or a VL comprising the amino acid sequence of SEQ ID NO: 8.

[0015] In some embodiments, the antibody is a full-length IgG, a Fab fragment, a F(ab') fragment, a F(ab’)2 fragment, a scFv, or a Fv. In some embodiments, the antibody comprises a heavy chain constant region of the isotype IgGl, IgG2, IgG3, or IgG4.

[0016] In some embodiments, the disclosure provides an isolated nucleic acid encoding the VH and / or VL of an antibody provided herein. In some embodiments, the isolated nucleic acid comprises (a) the nucleic acid sequence of SEQ ID NO: 12, and / or the nucleic acid sequence of SEQ ID NO: 13; or (b) the nucleic acid sequence of SEQ ID NO: 14, and / or the nucleic acid sequence of SEQ ID NO: 13.

[0017] In some embodiments, the disclosure provides an expression vector comprising an isolated nucleic acid provided herein. In some embodiments, the disclosure provides a hist cell comprising an antibody, an isolated nucleic, or a vector provided herein.

[0018] In some embodiments, the disclosure provides a composition comprising an antibody, an isolated nucleic acid, a vector, a history cell, or an engineered cell provided herein. In some embodiments, the composition further comprises a pharmaceutically acceptable carrier.

[0019] In some embodiments, the disclosure provides a bispecific antibody comprising a first antigen binding site and a second antigen binding site, wherein the second antigen binding site comprises the antibody of any one of claims 1-5. In some embodiments, the first antigen binding site specifically binds to a cancer antigen, a pathogen-derived antigen, or a B cell antigen.

[0020] In some embodiments, the first antigen binding site specifically binds to a cancer antigen. In some embodiments, the cancer antigen is selected from WT1, PRAME, DLL3, CD70, Claudinl8.2, MSLN, MAGE-A1, MAGE-A3, MAGE-A4, MAGE-A8, and CD38. In some embodiments, the cancer antigen is WT1. In some embodiments, the cancer antigen is PRAME. In some embodiments, the cancer antigen is DLL3. In some embodiments, the cancer antigen is CD70. In some embodiments, the cancer antigen is Claudinl8.2. In some embodiments, the cancer antigen is MSLN. In some embodiments, the cancer antigen is MAGE-A4. In some embodiments, the cancer antigen is MAGE-A8. In some embodiments, the cancer antigen is CD38. In some embodiments, the cancer antigen is BCMA.

[0021] In some embodiments, the first antigen binding site specifically binds a pathogen- derived antigen. In some embodiments, the pathogen-derived antigen is a viral antigen. In some embodiments, the viral antigen is an HIV antigen, an influenza antigen, an HPV antigen, or a Zika virus antigen. In some embodiments, the pathogen-derived antigen is a bacterial antigen. In some embodiments, the bacterial antigen is a Staphylococcus species antigen or a Pseudomonas species antigen. In some embodiments, the pathogen-derived antigen is a parasitic antigen. In some embodiments, the parasitic antigen is a Plasmodium species antigen, a Trypanosoma species antigen, or a Schistosoma species antigen.

[0022] In some embodiments, the first antigen binding site specifically binds a B cell antigen. In some embodiments, the B cell antigen is CD19, CD22, or CD79.

[0023] In some embodiments, the bispecific antibody comprises a first arm that is configured as a Fab, a Fab’, or a scFv and that comprises the first antigen binding site. In some embodiments, the bispecific antibody comprises a second arm that is configured as a Fab, a Fab’, or a scFv and that comprises the first antigen binding site. In some embodiments, the bispecific antibody comprises a first arm that is configured as a Fab and a second arm that is configured as a scFv. In some embodiments, the bispecific antibody comprises a first arm that is configured as a scFv and a second arm that is configured as a Fab. In some embodiments, the ratio between the first antigen binding site and the second antigen binding site is 1:1, 1:2, 1:3, 2:1 or 3:1.

[0024] In some embodiments, the disclosure provides a host cell comprising a bispecific antibody provided herein. In some embodiments, the disclosure provides a composition comprising a bispecific antibody provided herein. In some embodiments, the composition further comprises a pharmaceutically acceptable carrier.

[0025] In some embodiments, the disclosure provides a method of treating cancer, the method comprising administering to a subject in need an antibody, an engineered cell, a composition, or a bispecific antibody provided herein.

[0026] In some embodiments, the disclosure provides a method of treating infection, the method comprising administering to a subject in need an antibody, an engineered cell, a composition, or a bispecific antibody provided herein.

[0027] In some embodiments, the disclosure provides a method of treating an autoimmune disorder, the method comprising administering to a subject in need an antibody, an engineered cell, a composition, or a bispecific antibody provided herein.

[0028] The foregoing and other aspects, implementations, acts, functionalities, features and embodiments of the present teachings can be more fully understood from the following description.DETAILED DESCRIPTION

[0029] The present disclosure, at least in part, relates to the development of humanized antibodies that specifically recognize and bind CD3 that has improved properties (e.g., improved binding affinity, and / or reduced polyreactivity as compared to existing humanized anti-CD3 antibodies). In some embodiments, methods and related compositions are providedthat are useful for targeting cells (e.g., T cells) that express CD3. Aspects of the disclosure provide anti-CD3 antibodies with high binding affinity and specificity to CD3.

[0030] CD3 (cluster of differentiation 3) is a multimeric complex expressed by T cells (also called T lymphocytes). CD3 is composed of multiple subunits, including CD3y, CD35, CD3s, and CD3^, and is a part of the T cell receptor (TCR) complex. Binding of CD3 via anti-CD3 antibodies can activate T cells, resulting in their proliferation, or deplete T cells by inducing apoptosis. In the case of bispecific antibodies comprising one binding site that targets CD3, binding of CD3 can redirect T cells to localize them to a cell expressing the antigen targeted by the other binding site of the bispecific antibody.

[0031] Also provided is the use of an anti-CD3 antibody and its variants in research, diagnostic / detection, and therapeutic applications In some embodiments, an anti-CD3 antibody is a bispecific antibody and comprises a first binding site that specifically binds a cancer antigen or a pathogen-derived antigen and a second binding site that specifically binds CD3. In some embodiments, the first binding site specifically binds a cancer antigen. In some embodiments, the first binding site specifically binds a pathogen-derived antigen. By having a binding site specific for CD3 and a binding site specific for a cancer antigen or a pathogen- derived antigen, the bispecific antibody can act as a scaffold, bringing a T cell to a cancer cell or an infected cell to induce an immune response against the cancer cell or infected cell.

[0032] The foregoing and other aspects, implementations, acts, functionalities, features and embodiments of the present teachings can be more fully understood from the following description in conjunction with the accompanying drawings.I. Definitions

[0033] AC-SINS: Affinity-Capture Self-Interaction Nanoparticle Spectroscopy (AC-SINS) is a biophysical assay used to evaluate antibody self-interaction. The assay measures changes in plasmon resonance (AXmax), which correlates with the degree of self-association. Lower AZmax values indicate lower self-interaction and improved developability.

[0034] Administering: As used herein, the terms “administering” or “administration” means to provide an antibody or a composition thereof to a subject in a manner that is physiologically and / or pharmacologically useful (e.g., to treat a condition in the subject).

[0035] Affinity Matured Antibody: “Affinity Matured Antibody” is used herein to refer to an antibody with one or more alterations in one or more CDRs, which result in an improvement in the affinity (e.g., KD, kd or ka) of the antibody for a target antigen comparedto a parent antibody, which does not possess the alteration(s). Exemplary affinity matured antibodies will have nanomolar or even picomolar affinities for the target antigen. A variety of procedures for producing affinity matured antibodies are known in the art, including the screening of a combinatory antibody library that has been prepared using bio-display. For example, Marks et al., BioTechnology, 10: 779-783 (1992) describes affinity maturation by VH and VL domain shuffling. Random mutagenesis of CDR and / or framework residues is described by Barbas et al., Proc. Nat. Acad. Sci. USA, 91: 3809-3813 (1994); Schier et al., Gene, 169: 147-155 (1995); Yelton et al., J. Immunol., 155: 1994-2004 (1995); Jackson et al., J. Immunol., 154(7): 3310-3319 (1995); and Hawkins et al, J. Mol. Biol., 226: 889-896 (1992). Selective mutation at selective mutagenesis positions and at contact or hypermutation positions with an activity-enhancing amino acid residue is described in U.S. Pat. No. 6,914,128 Bl.

[0036] Antibody: As used herein, the term “antibody” refers to a polypeptide that includes at least one immunoglobulin variable domain or at least one site, e.g., paratope, that specifically binds to an antigen. In some embodiments, an antibody comprises a paratope. In some embodiments, a paratope comprises one or more complementarity determining regions (CDRs). In some embodiments, an antibody is a full-length antibody. In some embodiments, an antibody is a chimeric antibody. In some embodiments, an antibody is a humanized antibody. However, in some embodiments, an antibody is a Fab fragment, a F(ab’)2 fragment, a Fv fragment or a scFv fragment. In some embodiments, an antibody is a nanobody derived from a camelid antibody or a nanobody derived from shark antibody. In some embodiments, an antibody is a diabody. In some embodiments, an antibody comprises a framework having a human germline sequence. In another embodiment, an antibody comprises a heavy chain constant domain selected from the group consisting of IgG, IgGl, IgG2, IgG2A, IgG2B, IgG2C, IgG3, IgG4, IgAl, IgA2, IgD, IgM, and IgE constant domains. In some embodiments, an antibody comprises a heavy (H) chain variable region (abbreviated herein as VH), and / or a light (E) chain variable region (abbreviated herein as VE). In some embodiments, an antibody comprises a constant domain, e.g., an Fc region. An immunoglobulin constant domain refers to a heavy or light chain constant domain. Human IgG heavy chain and light chain constant domain amino acid sequences and their functional variations are known. With respect to the heavy chain, in some embodiments, the heavy chain of an antibody described herein can be an alpha (a), delta (5), epsilon (e), gamma (y) or mu (p) heavy chain. In some embodiments, the heavy chain of an antibody described hereincan comprise a human alpha (a), delta (5), epsilon (e), gamma (y) or mu (p) heavy chain. In a particular embodiment, an antibody described herein comprises a human gamma 1 CHI, CH2, and / or CH3 domain. In some embodiments, the amino acid sequence of the VH domain comprises the amino acid sequence of a human gamma (y) heavy chain constant region, such as any known in the art. Non-limiting examples of human constant region sequences have been described in the art, e.g., see U.S. Pat. No. 5,693,780 and Kabat E A et al., (1991) supra. In some embodiments, the VH domain comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, or at least 99% identical to any of the variable chain constant regions provided herein. In some embodiments, an antibody is modified, e.g., modified via glycosylation, phosphorylation, sumoylation, and / or methylation. In some embodiments, an antibody is a glycosylated antibody, which is conjugated to one or more sugar or carbohydrate molecules. In some embodiments, the one or more sugar or carbohydrate molecule are conjugated to the antibody via N-glycosylation, O-glycosylation, C-glycosylation, glypiation (GPI anchor attachment), and / or phosphoglycosylation. In some embodiments, the one or more sugar or carbohydrate molecule are monosaccharides, disaccharides, oligosaccharides, or glycans. In some embodiments, the one or more sugar or carbohydrate molecule is a branched oligosaccharide or a branched glycan. In some embodiments, the one or more sugar or carbohydrate molecule includes a mannose unit, a glucose unit, an N-acetylglucosamine unit, or a phospholipid unit. In some embodiments, an antibody is a construct that comprises a polypeptide comprising one or more antigen binding fragments of the disclosure linked to a linker polypeptide or an immunoglobulin constant domain. Linker polypeptides comprise two or more amino acid residues joined by peptide bonds and are used to link one or more antigen binding portions. Examples of linker polypeptides have been reported (see e.g., Holliger, P, et al. (1993) Proc. Natl. Acad. Sci. USA 90:6444-6448; Poljak, R. J., et al. (1994) Structure 2:1121-1123). Still further, an antibody may be part of a larger immunoadhesion molecule, formed by covalent or noncovalent association of the antibody or antibody portion with one or more other proteins or peptides. Examples of such immunoadhesion molecules include use of the streptavidin core region to make a tetrameric scFv molecule (Kipriyanov, S. M., et al. (1995) Human Antibodies and Hybridomas 6:93-101) and use of a cysteine residue, a marker peptide and a C-terminal polyhistidine tag to make bivalent and biotinylated scFv molecules (Kipriyanov, S. M., et al. (1994) Mol. Immunol. 31:1047-1058).

[0037] Approximately: As used herein, the term “approximately” or “about,” as applied toone or more values of interest, refers to a value that is similar to a stated reference value. In certain embodiments, the term “approximately” or “about” refers to a range of values that fall within 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or less in either direction (greater than or less than) of the stated reference value unless otherwise stated or otherwise evident from the context (except where such number would exceed 100% of a possible value).

[0038] Bispecific Antibody: As used herein, the term “bispecific antibody” refers to a polypeptide or a complex (e.g., two covalently linked polypeptides) that includes two different antigen binding, e.g., paratopes, that have different antigen binding specificities. For example, in one embodiment, a bispecific antibody is a polypeptide that includes two different antigen binding sites in which each antigen binding site binds to a different epitope of the same antigen. In other embodiments, a bispecific antibody is a polypeptide that includes two different antigen binding sites in which each site binds to a different antigen. In some embodiments, a bispecific antibody comprises two different sets of immunoglobulin variable domains, each of which set binds to a different epitope or group of epitopes.

[0039] Typically, each of the two antigen binding sites is present within an “arm” of a bispecific antibody. In some embodiments, an arm of a bispecific antibody is configured as a monospecific antibody, e.g., a full-length IgG or a fragment thereof. In some embodiments, a bispecific antibody comprises two arms, one or each of which is configured as an Fv region that confers specificity to distinct antigen residues. In some embodiments, a bispecific antibody comprises two arms of the same configuration, e.g., a Fab, a Fab’, a svFc, or any other suitable format. In some embodiments, a bispecific antibody comprises two arms of two different configurations, e.g., a Fab on one arm and a scFv on the other arm. In some embodiments, a bispecific antibody does not comprise an Fc region. In some embodiments, the two arms of a bispecific antibody are linked directly. In some embodiments, the two arms of a bispecific antibody are linked by a linker. In some embodiments, a bispecific antibody comprises an Fc region, e.g., a dimeric Fc or a monomeric Fc. In some embodiments, a bispecific antibody comprises a monomeric Fc. In some embodiments, a bispecific antibody comprises one arm linked to one end (e.g., the N terminal) of a monomeric Fc and a second arm linked to the other end (e.g., the C terminal) of the monomeric Fc (see, e.g., Shan el al., “In vivo pharmacokinetic enhancement of monomeric Fc and monovalent bispecific designs through structural guidance”, Communications Biology, Vol. 4, Article No. 1048 (2021)). In some embodiments, a bispecific antibody comprises a dimeric Fc region. In some embodiments, a bispecific antibody comprises two arms that are oriented symmetricallyaround an Fc region (e.g., each Fc monomer of a dimeric Fc region is linked to one arm). In some embodiments, a bispecific antibody comprises two distinct heavy chains and two distinct light chains, with each heavy chain / light chain pair having different antigen binding specificity. In some embodiments, a bispecific antibody comprises two arms that are oriented asymmetrically around an Fc (e.g., the two arms of the bispecific antibody are linked to one of the monomers of a dimeric Fc region). In some embodiments, because bispecific antibodies are capable of binding two different targets, they can be used as scaffolds to recruit or redirect cells to antigenic targets, e.g., to recruit immune cells to cancer cells. In some embodiments, a bispecific antibody contains a first antigen binding and a second antigen binding site that specifically binds CD3 or a portion thereof, e.g., CD3e, a CD3E / 8 heterodimer, or a CD3e / y heterodimer.

[0040] CDR: As used herein, the term “CDR” refers to the complementarity determining region within antibody variable sequences. A typical antibody molecule comprises a heavy chain variable region (VH) and a light chain variable region (VL), which are usually involved in antigen binding. The VH and VL regions can be further subdivided into regions of hypervariability, also known as “complementarity determining regions” (“CDR”), interspersed with regions that are more conserved, which are known as “framework regions” (“FR”). Each VH and VL is typically composed of three CDRs and four FRs, arranged from amino-terminus to carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The extent of the framework region and CDRs can be precisely identified using methodology known in the art, for example, by the Kabat definition, the IMGT definition, the Chothia definition, the AbM definition, and / or the contact definition, all of which are well known in the art. See, e.g., Kabat, E.A., et al. (1991) Sequences of Proteins of Immunological Interest, Fifth Edition, U.S. Department of Health and Human Services, NIH Publication No. 91-3242; IMGT®, the international ImMunoGeneTics information system® http: / / www.imgt.org, Lefranc, M.-P. et al., Nucleic Acids Res., 27:209-212 (1999); Ruiz, M. et al., Nucleic Acids Res., 28:219-221 (2000); Lefranc, M.-P, Nucleic Acids Res., 29:207- 209 (2001); Lefranc, M.-P, Nucleic Acids Res., 31:307-310 (2003); Lefranc, M.-P. et al., In Silico Biol., 5, 0006 (2004) [[Epub]], 5:45-60 (2005); Lefranc, M.-P. et al., Nucleic Acids Res., 33:D593-597 (2005); Lefranc, M.-P. et al., Nucleic Acids Res., 37:D1006-1012 (2009); Lefranc, M.-P. et al., Nucleic Acids Res., 43:D413-422 (2015); Chothia et al., (1989) Nature 342:877; Chothia, C. et al. (1987) J. Mol. Biol. 196:901-917, Al-lazikani et al (1997) J.Molec. Biol. 273:927-948; and Almagro, J. Mol. Recognit. 17: 132-143 (2004). See alsohgmp.mrc.ac.uk and bioinf.org.uk / abs. As used herein, a CDR may refer to the CDR defined by any method known in the art. Two antibodies having the same CDR means that the two antibodies have the same amino acid sequence of that CDR as determined by the same method, for example, the IMGT definition.

[0041] In certain embodiments, there are three CDRs in each of the variable regions of a heavy chain and a light chain, which are designated CDR1, CDR2 and CDR3, for each of the variable regions. The term “CDR set” as used herein refers to a group of three CDRs that occur in a single variable region capable of binding the antigen. The exact boundaries of these CDRs have been defined differently according to different systems. The system described by Kabat (Kabat et al., Sequences of Proteins of Immunological Interest (National Institutes of Health, Bethesda, Md. (1987) and (1991)) not only provides an unambiguous residue numbering system applicable to any variable region of an antibody, but also provides precise residue boundaries defining the three CDRs. These CDRs may be referred to as Kabat CDRs. Sub-portions of CDRs may be designated as LC CDR1, LC CDR2 and LC CDR3 or HC CDR1, HC CDR2 and HC CDR3 where the “LC” and the “HC” designate the light chain and the heavy chains regions, respectively. These regions may be referred to as Chothia CDRs, which have boundaries that overlap with Kabat CDRs. Other boundaries defining CDRs overlapping with the Kabat CDRs have been described by Padlan (FASEB J. 9:133- 139 (1995)) and MacCallum (J Mol Biol 262(5) :732-45 (1996)). Still other CDR boundary definitions may not strictly follow one of the above systems, but will nonetheless overlap with the Kabat CDRs, although they may be shortened or lengthened in light of prediction or experimental findings that particular residues or groups of residues or even entire CDRs do not significantly impact antigen binding. The methods used herein may utilize CDRs defined according to any of these systems, although preferred embodiments use Kabat or Chothia defined CDRs.

[0042] In certain embodiments, the CDRs of an antibody may have different amino acid sequences when different definition systems are used (e.g., the IMGT definition, the Kabat definition, or the Chothia definition). A definition system annotates each amino acid in a given antibody sequence (e.g., VH or VL sequence) with a number, and numbers corresponding to the heavy chain and light chain CDRs are provided in Table 2. The CDRs listed in Table 1 are defined in accordance with the Kabat definition. One skilled in the art is able to derive the CDR sequences using the different numbering systems for the anti- CD3 antibodies provided in Table 1.Table 2. CDR Definitions1IMGT®, the international ImMunoGeneTics information system®, imgt.org, Lefranc, M.-P. et al., Nucleic Acids Res., 27:209-212 (1999)2Kabat et al. (1991) Sequences of Proteins of Immunological Interest, Fifth Edition, U.S. Department of Health and Human Services, NIH Publication No. 91-32423Chothia et al., J. Mol. Biol. 196:901-917 (1987))

[0043] CDR-grafted antibody: The term “CDR-grafted antibody” refers to antibodies which comprise heavy and light chain variable region sequences from one species but in which the sequences of one or more of the CDR regions of VH and / or VL are replaced with CDR sequences of another species, such as antibodies having murine heavy and light chain variable regions in which one or more of the murine CDRs (e.g., CDR3) has been replaced with human CDR sequences.

[0044] Chemotherapeutic agent: As used herein, a “chemotherapeutic agent” refers to a chemical compound useful in the treatment of proliferative disorders, such as cancers. These agents can be, e.g., alkylating agents, such as thiotepa and cyclophosphamide (CYTOXAN®); alkylsulfonates such as busulfan, improsulfan and piposulfane; aziridines such as benzodopa, carbocuone, meturedopa and uredopa; ethylene imines and methylamelamines, including altretamine, triethylene methamine, triethylene phosphoramide, triethylene-thiophosphoramide and trimethylolomelamine; acetogenins (especially bulatacin and bulatacinone); delta-9-tetrahydrocannabinol (dronabinol, MARINOL); beta-lapacona; lapacol; Colchicines; betulinic acid; a camptothecin (which includes the synthetic analog topotecan (HYCAMTIN®), CPT-11 (irinotecan, CAMPTOSAR), acetylcamptothecin, scopolectin and 9-aminocamptothecin); Bryostatin; Callistatin; CC-1065 (including its synthetic analogs of adozelesin, carzelesin and bizelesin); podophyllo toxin; podophyllinic acid; teniposide; cryptophycins (particularly cryptophycin 1 and cryptophycin 8); dolastatin; duocarmycin (which include the synthetic analogs, KW-2189 and CB1-TM1); eleutherobin; pancratistatin; a sarcodictiina, -pongistatin; nitrogen mustards such as chlorambucil, chlomaphazine, colofosfamide, estramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, novembichin, phenesterin, prednimustine, trofosfamidea, uracil mustard; nitrosureas such as carmustine, chlorozotocin, fotemustine, lomustine, nimustine and ranimnustine; antibiotics, such as enediin antibiotics (e.g., calicheamicin, especially gammall calicheamicin and omegall calicheamicin (see, for example, Agnew,Chem Inti. Ed. Engl., 33: 183-186 (1994)); dynemycin, including dynemycin A; a esperamycin; as well as neocarzinostatin chromophore and chromophores of related chromoprotein antibiotics), aclacinomisins, actinomycin, autramycin, azaserin, bleomycin, cactinomycin, carabicin, carminomycin, carzinophilin, chromomycins, dactinomycin, daunorubicin, detorrubicin, 6-diazo-5-oxo- L-norleucine, doxorubicin (including morpholinodoxorubicin, cyanomorpholino-doxorubicin, 2-pyrrolino-doxorubicin and deoxy doxorubicin), epirubicin, esorubicin, idarubicin, marcellomycin, mitomycins such as mitomycin C, mycophenolic acid, nogalamycin, olivomycins, peplomycin, porfiromycin, puromycin , chelamicin, rodrububicin, streptonigrin, streptozocin, tubercidin, ubenimex, zinostatin, zorubicin; anti-metabolites such as methotrexate and 5 -fluorouracil (5-FU); folic acid analogues such as denopterin, methotrexate, pteropterin, trimetrexate; purine analogues such as fludarabine, 6-mercaptopurine, tiamiprin, thioguanine; analogues of pyrimidine such as ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, enocythabin, floxuridine; androgens such as calusterone, dromostanolone propionate, epithiostanol, mepitiostane, testolactone; antisuprenal drugs such as aminoglutethimide, mitotane, trilostane; folic acid enhancer such as frolinic acid; aceglatone; aldophosphamide glycoside; aminolevulinic acid; eniluracil; amsacrine; bestrabuchil; bisantrene; driamycin; defofamin; demecolcine; diazicuone; elfornitin; eliptinium acetate; an epothilone; etoglucid; gallium nitrate; hydroxyurea; lentinan; lonidainin; maytansinoids such as maytansine and ansamitocins; mitoguazone; mitoxantrone; mopidanmol; nitraerine; pentostatin; fenamet; pirarubicin; losoxantrone; 2-ethylhydrazide; procarbazine; PSK® polysaccharide complex (JHS Natural Products, Eugene, OR); razoxane; rhizoxin; sizofirano; spirogermanium; tenuazonic acid; triazicuone; 2,2 ‘, 2”-trichlorotriethylamine, trichothecenes (especially T-2 toxin, verracurin A, roridin A and anguidine), urethane, vindesine (ELDISINE, FILDESIN), dacarbazine, manomustine, mitobronitol, mitolactol, pipobroman, gacitosin, arabinoside (“Ara-C”), thiotepa, taxoids, for example, paclitaxel (TAXOL, Bristol-Myers Squibb Oncology, Princeton, NJ), Cremophor-free ABRAXANE ™, nanoparticle formulation modified with paclitaxel albumin (American Pharmaceutical Partners, Schaumberg, Illinois), and docetaxel (TAXOTERE®; Rhone-Poulenc Rorer, Antony, France); chloranbuchil; gemcitabine (GEMZAR); 6-thioguanine; mercaptopurine; methotrexate; platinum analogues such as cisplatin and carboplatin; vinblastine (VELBAN®); platinum; etoposide (VP- 16); ifosfamide; mitoxantrone; vincristine (ONCOVIN®); oxaliplatin; leucovovina; vinorrelbine (NAVELBINE®); novantrone; edatrexate; Daunomycin; aminopterin; ibandronate;Topoisomerase inhibitor RFS 2000; difluoromethylornithine (DMFO); retinoids such asretinoic acid; capecitabine (XELODA®); pharmaceutically acceptable salts, acids or derivatives of any of the foregoing; as well as combinations of two or more of the foregoing such as CHOP, an abbreviation for a combination therapy of cyclophosphamide, doxorubicin, vincristine and prednisolone; CVP, an abbreviation for a combination therapy of cyclophosphamide, vincristine and prednisolone; and FOLFOX, an abbreviation for an oxaliplatin treatment regimen (ELOXATIN ™) combined with 5-FU and leucovorin.

[0045] Chimeric antibody: The term “chimeric antibody” refers to antibodies which comprise heavy and light chain variable region sequences from one species and constant region sequences from another species, such as antibodies having murine heavy and light chain variable regions linked to human constant regions.

[0046] Compete: The term “compete”, as used herein with regard to an antibody, means that a first antibody binds to an epitope of a protein (e.g., CD3) in a manner sufficiently similar to the binding of a second antibody, such that the result of binding of the first antibody with its epitope is detectably decreased in the presence of the second antibody compared to the binding of the first antibody in the absence of the second antibody. The alternative, where the binding of the second antibody to its epitope is also detectably decreased in the presence of the first antibody, can, but need not be the case. That is, a first antibody can inhibit the binding of a second antibody to its epitope without that second antibody inhibiting the binding of the first antibody to its respective epitope. However, where each antibody detectably inhibits the binding of the other antibody with its epitope or ligand, whether to the same, greater, or lesser extent, the antibodies are said to “Cross-compete” with each other for binding of their respective epitope(s). In some embodiments, antibodies that compete or cross-compete bind to the same or overlapping epitopes. Regardless of the mechanism by which such competition or cross-competition occurs (e.g., steric hindrance, conformational change, or binding to a common epitope, or portion thereof), the skilled artisan would appreciate that such competing and / or cross-competing antibodies are encompassed and can be useful for the methods and / or compositions provided herein.

[0047] Complementary: As used herein, the term “complementary” refers to the capacity for precise pairing between two nucleotides or two sets of nucleotides. In particular, complementary is a term that characterizes an extent of hydrogen bond pairing that brings about binding between two nucleotides or two sets of nucleotides. For example, if a base at one position of an oligonucleotide is capable of hydrogen bonding with a base at the corresponding position of a target nucleic acid (e.g., an mRNA), then the bases are considered to be complementary to each other at that position. Base pairings may includeboth canonical Watson-Crick base pairing and non- Watson-Crick base pairing (e.g., Wobble base pairing and Hoogsteen base pairing). For example, in some embodiments, for complementary base pairings, adenosine-type bases (A) are complementary to thymidine- type bases (T) or uracil-type bases (U), that cytosine-type bases (C) are complementary to guanosine-type bases (G), and that universal bases such as 3-nitropyrrole or 5-nitroindole can hybridize to and are considered complementary to any A, C, U, or T. Inosine (I) has also been considered in the art to be a universal base and is considered complementary to any A, C, U or T.

[0048] Conjugated: As used herein, “conjugated” means two entities are associated, preferably with sufficient affinity that a therapeutic / diagnostic benefit of the association between the two entities is realized. The association between the two entities can be either direct or via a linker, such as a polymer linker. Conjugated can include covalent or noncovalent bonding as well as other forms of association, such as entrapment, e.g., of one entity on or within the other, or of either or both entities on or within a third entity, such as a micelle.

[0049] Conservative amino acid substitution: As used herein, a “conservative amino acid substitution” refers to an amino acid substitution that does not alter the relative charge or size characteristics of the protein in which the amino acid substitution is made. Variants can be prepared according to methods for altering polypeptide sequence known to one of ordinary skill in the art such as are found in references which compile such methods, e.g. Molecular Cloning: A Laboratory Manual, J. Sambrook, et al., eds., Fourth Edition, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 2012, or Current Protocols in Molecular Biology, F.M. Ausubel, et al., eds., John Wiley & Sons, Inc., New York. Conservative substitutions of amino acids include substitutions made amongst amino acids within the following groups: (a) M, I, L, V; (b) F, Y, W; (c) K, R, H; (d) A, G; (e) S, T; (f) Q, N; and (g) E, D.

[0050] Cross-reactive: As used herein and in the context of a targeting agent (e.g., antibody), the term “cross-reactive,” refers to a property of the agent being capable of specifically binding to more than one antigen of a similar type or class (e.g., antigens of multiple homologs, paralogs, or orthologs) with similar affinity or avidity.

[0051] Cytotoxic agent: As used herein, the term “cytotoxic agent” refers to a substance that inhibits or prevents a cellular function and / or causes cell death or destruction. Such agents are well known in the art, and include, e.g., radioactive isotopes (e.g., At211, 1131, 1125, Y90, Re186, Re188, Sm153, Bi212, P32, Pb212and radioactive isotopes of Lu); chemotherapeuticagents or drugs (e.g., methotrexate, adriamycin, vinca alkaloids (vincristine, vinblastine, etoposide), doxorubicin, melphalan, mitomycin C, chlorambucil, daunorubicin, or other intercalating agents); growth inhibitory agents; enzymes and fragments thereof, such as nucleolytic enzymes; antibiotics; toxins such as small molecule toxins or enzymatically active toxins of bacterial, fungal, plant or animal origin, including fragments and / or variants thereof; and the various anti-tumor or anti-cancer agents described below.

[0052] Developability: As used herein, the term “developability” refers to the extent to which a polypeptide, such as an antibody or antibody fragment, possesses characteristics favorable for its manufacture, formulation, storage, and clinical use. Attributes of developability include, but are not limited to: high expression in eukaryotic cells, solubility, low viscosity, resistance to aggregation, high chemical and thermal stability, long serum halflife, low clearance rate, and minimal nonspecific or polyspecific binding. Developability may be assessed using a suite of biophysical and biochemical assays including, but not limited to, PSR (poly specificity reagent) binding, AC-SINS (affinity-capture self-interaction nanoparticle spectroscopy), HIC (hydrophobic interaction chromatography), SEC (sizeexclusion chromatography), DLS (dynamic light scattering), DSF (differential scanning fluorimetry), CIC (cross-interaction chromatography), and others. A developability profile may refer to the composite score or assessment derived from these assays and can be used to compare or rank antibody candidates.

[0053] Effective Amount: As used herein, “an effective amount” refers to the amount of each active agent (e.g., anti-CD3 antibody) required to confer a desired effect (e.g., a therapeutic effect on the subject), either alone or in combination with one or more other active agents. In some embodiments, the therapeutic effect is reduced depleted T cells or activity and / or alleviated disease conditions (e.g., treatment of cancer, infection, or an autoimmune disorder).

[0054] Framework: As used herein, the term “framework” or “framework sequence” refers to the remaining sequences of a variable region minus the CDRs. Because the exact definition of a CDR sequence can be determined by different systems, the meaning of a framework sequence is subject to correspondingly different interpretations. The six CDRs (LC CDR1, LC CDR2, and LC CDR3 of light chain and HC CDR1, HC CDR2, and HC CDR3 of heavy chain) also divide the framework regions on the light chain and the heavy chain into four sub-regions (FR1, FR2, FR3 and FR4) on each chain, in which CDR1 is positioned between FR1 and FR2, CDR2 between FR2 and FR3, and CDR3 between FR3 and FR4. Without specifying the particular sub-regions as FR1, FR2, FR3 or FR4, aframework region, as referred to by others, represents the combined FRs within the variable region of a single, naturally occurring immunoglobulin chain. As used herein, a FR represents one of the four sub-regions, and FRs represents two or more of the four sub-regions constituting a framework region. Human heavy chain and light chain acceptor sequences are known in the art. In one embodiment, the acceptor sequences known in the art may be used in the antibodies disclosed herein.

[0055] HIC Retention Time: As used herein, the term “Hydrophobic Interaction Chromatography (HIC)” refers to a technique used to assess hydrophobicity of antibodies. Retention time on a HIC column is used as a proxy for hydrophobicity. Lower retention times are generally indicative of more favorable developability profiles.

[0056] Human antibody: The term “human antibody”, as used herein, is intended to include antibodies having variable and constant regions derived from human germline immunoglobulin sequences. The human antibodies of the disclosure may include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-specific mutagenesis in vitro or by somatic mutation in vivo), for example in the CDRs and in particular CDR3. However, the term “human antibody”, as used herein, is not intended to include antibodies in which CDR sequences derived from the germline of another mammalian species, such as a mouse, have been grafted onto human framework sequences.

[0057] Humanized antibody: The term “humanized antibody” refers to antibodies which comprise heavy and light chain variable region sequences from a non-human species (e.g., a mouse) but in which at least a portion of the VH and / or VL sequence has been altered to be more “human-like”, i.e., more similar to human germline variable sequences. One type of humanized antibody is a CDR-grafted antibody, in which non-human CDR sequences are introduced into human VH and VL sequences to replace the corresponding human germline CDR sequences. In one embodiment, humanized anti-CD3 antibodies and antigen binding portions are provided. Such antibodies may be generated by obtaining murine anti-CD3 monoclonal antibodies using traditional hybridoma technology followed by humanization using in vitro genetic engineering, such those disclosed in Kasaian el al. PCT publication No. WO 2005 / 123126 A2. In some embodiments, humanization involves switching light chain isotypes. In some embodiments, during humanization, a lambda light chain is changed to a kappa light chain. In some embodiments, during humanization, a kappa light chain is changed to a lambda light chain. In some embodiments, humanization may be guided by machine learning using a deep learning model trained , e.g., Hu-mAb (Oxford Protein InformaticsGroup), or BioPhi (Prihoda et al. A platform for antibody design, humanization, and humanness evaluation based on natural antibody repertoires and deep learning. 2022. mAbs, 14:1). In some embodiments, humanization may also be guided by heuristic rules used in the art (Honegger, A. Engineering antibodies for stability and efficient folding. 2008. Therapeutic Antibodies, 47-68). In some embodiments, humanization may also be guided by matching the non-human CDRs against a large database of known human CDRs using machine learning or heuristic rules, thereby identifying suitable human VH and VL acceptor frameworks. Any of the suitable humanization methods can be used alone or in combination.

[0058] Humanized antibodies are human immunoglobulins (recipient antibody) in which residues from a complementary determining region (CDR) of the recipient are replaced by residues from a CDR of a non-human species (donor antibody) such as mouse, rat, or rabbit having the desired specificity, affinity, and capacity. In some embodiments, Fv framework region (FR) residues of the human immunoglobulin are replaced by corresponding non- human residues. Furthermore, the humanized antibody may comprise residues that are found neither in the recipient antibody nor in the imported CDR or framework sequences, but are included to further refine and optimize antibody performance. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the FR regions are those of a human immunoglobulin consensus sequence. The humanized antibody optimally also will comprise at least a portion of an immunoglobulin constant region or domain (Fc), typically that of a human immunoglobulin. Antibodies may have Fc regions modified as described in WO 99 / 58572. Other forms of humanized antibodies have one or more CDRs (one, two, three, four, five, six) which are altered with respect to the original antibody, which are also termed one or more CDRs derived from one or more CDRs from the original antibody. Humanized antibodies may also involve affinity maturation.

[0059] In some embodiments, humanization is achieved by grafting the CDRs (e.g., as shown in Table 1) into the human variable domains (e.g., IGHV3-23, IGHV3-72, IGHV3- 73, IGKV3-20, IGKV1-16, IGEV1-40, IGEV1-44, IGEV1-47, and IGKV4-1 human variable domains). In some embodiments, the anti-CD3 antibody of the present disclosure is a humanized variant comprising one or more amino acid substitutions (e.g., in the VH framework region) as compared with any one of the VHs listed in Table 1, and / or one or more amino acid substitutions (e.g., in the VE framework region) as compared with any one of the VEs listed in Table 1.

[0060] Framework regions provide the structural support for antibodies. Alterations in the framework sequences of an antibody can affect the structural stability, antibody conformation, solubility, effector functions (e.g., antibody-dependent cellular cytotoxicity), and immunogenicity of an antibody. Humanization of a framework region or regions can increase stability, reduce immunogenicity, and increase specificity and affinity of an antibody for a human antigen compared to antibodies that have not been humanized.

[0061] Methods of antibody humanization can also affect the properties of the humanized antibody. Humanizing antibodies can include altering the framework regions of an antibody (e.g., to replace them with human framework sequences), grafting CDRs into a human variable domain (as described above), optimizing the residues in the framework and CDR regions to improve binding to human antigen and / or reduce immunogenicity, or a combination of any of the aforementioned. Machine learning algorithms and heuristic rules known in the art may be used to humanize an antibody.

[0062] Isolated antibody: An “isolated antibody”, as used herein, is intended to refer to an antibody that is substantially free of other antibodies having different antigenic specificities (e.g., an isolated antibody that specifically binds CD3 is substantially free of antibodies that specifically bind antigens other than CD3. An isolated antibody that specifically binds CD3 may, however, have cross -reactivity to other antigens. Moreover, an isolated antibody may be substantially free of other cellular material and / or chemicals.

[0063] Kabat numbering: The terms “Kabat numbering”, “Kabat definitions” and “Kabat labeling” are used interchangeably herein. These terms, which are recognized in the art, refer to a system of numbering amino acid residues which are more variable (i.e. hypervariable) than other amino acid residues in the heavy and light chain variable regions of an antibody, or an antigen binding portion thereof (Kabat et al. (1971) Ann. NY Acad, Sci. 190:382-391 and, Kabat, E. A., et al. (1991) Sequences of Proteins of Immunological Interest, Fifth Edition, U.S. Department of Health and Human Services, NIH Publication No. 91-3242). For the heavy chain variable region, the hypervariable region ranges from amino acid positions 31 to 35 for CDR1, amino acid positions 50 to 65 for CDR2, and amino acid positions 95 to 102 for CDR3. For the light chain variable region, the hypervariable region ranges from amino acid positions 24 to 34 for CDR1, amino acid positions 50 to 56 for CDR2, and amino acid positions 89 to 97 for CDR3.

[0064] Multispecific Antibody: As used herein, the term “multispecific antibody” refers to a polypeptide or a complex (e.g., two or more covalently linked polypeptides) that includes at least two different immunoglobulin variable domains or at least two different sites, e.g.,paratopes, that specifically bind to one or more antigens. For example, in one embodiment, a multispecific antibody is a polypeptide that includes at least two different sites in which each site binds to a different epitope of the same antigen. In other embodiments, a multispecific antibody is a polypeptide that includes at least two different sites in which each site binds to a different antigen. In some embodiments, a multispecific antibody is a trispecific antibody comprises three different sites in which each site binds to a different antigen. In some embodiments, a trispecific antibody comprises a site comprising an anti-CD3 antibody provided herein, a site that specifically binds a tumor antigen, and a site that specifically binds a T cell co-stimulatory antigen (e.g., that specifically binds CD28 or CD137 (4-1BB)) or a cytokine (e.g., that specifically binds interleukin (IL)-2, IL12, IL15, or IL-21).

[0065] Polyspecificity: As used herein, the term “polyspecificity” refers to the unintended binding of an antibody to multiple non-target antigens, often as a result of hydrophobic or electrostatic interactions. High poly specificity is generally undesirable in therapeutic antibodies due to increased risk of off-target effects, altered pharmacokinetics, and increased immunogenicity. Poly specificity can be assessed using PSR assays, CIC, SIC, and other binding or chromatography -based techniques.

[0066] PSR Score: As used herein, a “PSR score (Poly specificity Reagent score)” is a quantitative measure of an antibody's propensity for nonspecific binding. It is typically derived from flow cytometry assays using labeled polyreactive reagents, ELISA assays, or other binding assays using polyreactive reagents. Scores may generally be interpreted as follows:0.1: Clean0.33: Low0.33^ PSR < 0.66: Medium0.661.0: High

[0067] A lower PSR score is generally associated with improved developability. A PSR experiment to produce a PSR score may be run with control antibodies have low, medium and high polyreactivity to establish cutoffs for nonspecific binding for a given experiment.

[0068] Recombinant antibody: The term “recombinant antibody”, as used herein, is intended to include all antibodies that are prepared, expressed, created or isolated by recombinant means, such as antibodies expressed using a recombinant expression vector transfected into a host cell (described in more details in this disclosure), including, for example, antibodies isolated from a recombinant, combinatorial human antibody library(Hoogenboom H. R., (1997) TIB Tech. 15:62-70; Azzazy H., and Highsmith W. E., (2002) Clin. Biochem. 35:425-445; Gavilondo J. V., and Larrick J. W. (2002) BioTechniques 29: 128- 145; Hoogenboom H., and Chames P. (2000) Immunology Today 21 :371-378), antibodies isolated from an animal (e.g., a mouse) that is transgenic for human immunoglobulin genes (see e.g., Taylor, L. D., et al. (1992) Nucl. Acids Res. 20:6287-6295; Kellermann S-A., and Green L. L. (2002) Current Opinion in Biotechnology 13:593-597; Little M. et al (2000) Immunology Today 21:364-370) or antibodies prepared, expressed, created or isolated by any other means that involves splicing of human immunoglobulin gene sequences to other DNA sequences. In some embodiments, recombinant human antibodies are provided herein. In certain embodiments, such recombinant human antibodies have variable and constant regions derived from human germline immunoglobulin sequences. In certain embodiments, however, such recombinant human antibodies are subjected to in vitro mutagenesis (or, when an animal transgenic for human Ig sequences is used, in vivo somatic mutagenesis) and thus the amino acid sequences of the VH and VL regions of the recombinant antibodies are sequences that, while derived from and related to human germline VH and VL sequences, may not naturally exist within the human antibody germline repertoire in vivo. One embodiment of the disclosure provides fully human antibodies capable of binding human CD3 which can be generated using techniques well known in the art, such as, but not limited to, using human Ig phage libraries such as those disclosed in Jermutus et al., PCT publication No. WO 2005 / 007699 A2.

[0069] Selective: As used herein, the term “selective” or “selectively” refers to the ability of a molecule to produce an effect (e.g., inhibit, antagonize, agonize, etc.) in relation to its target molecule compared to a reference molecule. For example, a molecule that selectively inhibits its target molecule means that this molecule is capable of inhibiting its target molecule to a degree that is distinguishable from a reference molecule in an inhibition assay or other inhibitory context. For example, with respect to an inhibitor, the term, “selectively inhibits”, refers to the ability of the inhibitor to inhibit its target molecule with a degree that is distinguishable from a reference molecule that is not substantially inhibited in an inhibition assay, e.g., to an extent that permit selective inhibition of the target molecule, as described herein. Once the reaction is terminated, the signal produced by inhibiting the target molecule can be measured. The half maximal inhibitor concentration for the target molecule and the reference molecule can be calculated. In some embodiments, a molecule described herein selectively binds to a target molecule. In some embodiments, a molecule described herein selectively binds CD3. In some embodiments, a molecule described herein directs a CD3-expressign cell (e.g., a T cell) to target a cancer cell or an infected cell. In some embodiments, a molecule described herein binds to CD3 to induce apoptosis of a CD3- expressing cell (e.g., a T cell). In some embodiments, a molecule described herein binds to CD3 to induce activation and proliferation of a CD3-expressing cell (e.g., a T cell).

[0070] SP34: As used herein, “SP34” refers to a murine monoclonal antibody that binds to the epsilon (CEp) subunit of the CD3 complex. It is widely used in immunological studies as a benchmark anti-CD3 antibody. The murine SP34 variable region sequences are provided below:• SP34 VH(EVQLVESGGGLVQPKGSLKLSCAASGFTFNTYAMNWVRQAPGKGLEWVAR IRSKYNNYATYYADSVKDRFTISRDDSQSILYLQMNNLKTEDTAMYYCVRHG NFGNSYVSWFAYWGQGTLVTVSA): [SEQ ID NO: 33]• SP34 VL(QAVVTQESALTTSPGETVTLTCRSSTGAVTTSNYANWVQEKPDHLFTGLIGG TNKRAPGVPARFSGSLIGDKAALTITGAQTEDEAIYFCALWYSNLWVFGGGT KLTVL): [SEQ ID NO: 34]

[0071] SP34 is known for its high affinity to human CD3CEp and its ability to activate T cells. It also demonstrates cross-reactivity to CD3 from non-human primates, including cynomolgus monkeys.

[0072] Specifically binds: As used herein, the term “specifically binds” refers to the ability of a molecule to bind to a binding partner with a degree of affinity or avidity that enables the molecule to be used to distinguish the binding partner from an appropriate control in a binding assay or other binding context. With respect to an antibody, the term, “specifically binds”, refers to the ability of the antibody to bind to a specific antigen with a degree of affinity or avidity, compared with an appropriate reference antigen or antigens, which enables the antibody to be used to distinguish the specific antigen from others, as described herein. In some embodiments, an antibody specifically binds to a target if the antibody has a KD for binding the target of at least about 10'4M, 10'5M, 10'6M, 10'7M, 10'8M, 10'9M, IO'10M, 10'11M, 10'12M, 10'13M, or less. In some embodiments, an antibody specifically binds CD3.

[0073] Subject: As used herein, the term “subject” refers to a mammal. In some embodiments, a subject is a human. In some embodiments, a subject is a patient, e.g., a human patient that has or is suspected of having a disease. In some embodiments, the subject is a human patient who has or is suspected of having cancer and / or one or more conditions arising as a result of a cancer.

[0074] Treatment: As used herein, the term “treating” or “treatment” refers to the application or administration of a composition including one or more active agents (e.g., anti- CD3 antibodies) to a subject, who has a target disease or disorder (e.g., cancer, infection, or an autoimmune disorder), a symptom of the disease / disorder, or a predisposition toward the disease / disorder, with the purpose to cure, heal, alleviate, relieve, alter, remedy, ameliorate, improve, or affect the disorder, the symptom of the disease, or the predisposition toward the disease or disorder. Alleviating a target disease / disorder includes delaying or preventing the development or progression of the disease, or reducing disease severity.II. Developability of Anti-CD3 antibodies

[0075] The present disclosure, at least in part, provides engineered humanized SP34 (hSP34) antibodies that specifically recognize and bind CD3 and display improved developability properties (e.g., improved binding affinity, and / or reduced polyreactivity) as compared to existing humanized anti-CD3 antibodies or the murine parental antibody. Improved properties may be improved binding affinity, reduced polyreactivity, expression in eukaryotic cells, solubility, low viscosity, resistance aggregation, high chemical and thermal stability, long serum half-life, low clearance rate, minimal non-specific or polyspecific binding, or some combination thereof.

[0076] In some embodiments, an improved developability property of an antibody provided herein is improved binding affinity relative to an existing anti-CD3 antibody or a murine parental antibody. Improved binding affinity may be binding affinity that is increased by 50% to 1,000%, 100% to 950%, 150% to 900%, 200% to 850%, 250% to 800%, 300% to 750%, 350% to 700%, 400% to 650%, 450% to 600%, or 500% to 550% relative to an existing anti-CD3 antibody or a murine parental antibody. In some embodiments, improved binding affinity is increased by 50%, 75%, 100%, 125%, 150%, 175%, 200%, 225%, 250%, 275%, 300%, 325%, 350%, 375%, 400%, 425%, 450%, 475%, 500%, 525%, 550%, 575%, 600%, 625%, 650%, 675%, 700%, 725%, 750%, 775%, 800%, 825%, 850%, 875%, 900%, 925%, 950%, 975%, or 1,000% or more relative to an existing anti-CD3 antibody or a murine parental antibody.

[0077] In some embodiments, an improved developability property of an antibody provided herein is reduced polyreactivity relative to an existing anti-CD3 antibody or a murine parental antibody. Polyreactivity, as used herein, refers to cross -reactivity to off- target antigens (e.g., antigens other than CD3). Reduced polyreactivity is an improved developability property of an antibody because an antibody that has reduced cross -reactivity to off-target antigens is more likely to bind to its target antigen more consistently, requiring lower and / or less consistent antibody administration. In some embodiments, an antibody provided herein has polyreactivity that is reduced by 10% to 100%, 20% to 90%, 30% to 80%, 40% to 70%, or 50% to 60% relative to an existing anti-CD3 antibody or a murine parental antibody. In some embodiments, an antibody provided herein has polyreactivity that is reduced by 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% or more relative to an existing anti-CD3 antibody or a murine parental antibody.

[0078] In some embodiments, an improved developability property of an antibody provided herein is expression in eukaryotic cells. Expression in eukaryotic cells is a developability advantage (e.g., an improved property) relative to an antibody that is not expressed in eukaryotic cells because: antibodies expressed in eukaryotic cells are subject to increased expression regulation (e.g., transcriptional, post-transcription, translational, post- translational), antibodies expressed in eukaryotic cells have increased complexity compared to prokaryotic cells (e.g., post-translational modifications), have higher levels of antibody production, or some combination thereof. It is to be understood that each of these properties are relative to expression in prokaryotic cells. Non-limiting examples of eukaryotic cells that may express an antibody provided herein are: mammalian cells, yeast cells, plant cells, fungal cells, and protozoan cells. In some embodiments, an improved biophysical and / or developability property of an antibody provided herein is expression in mammalian cells.

[0079] In some embodiments, an improved developability property of an antibody provided herein is increased solubility relative to an existing anti-CD3 antibody or murine parental antibody. Solubility means that an antibody retains its proper, folded antibody conformation in solution (e.g., buffer, serum, etc). Increased solubility may be increased by 10% to 100%, 20% to 90%, 30% to 80%, 40% to 70%, or 50% to 60% relative to an existing anti-CD3 antibody or a murine parental antibody. In some embodiments, an antibody provided herein has solubility that is increased by 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% or more relative to an existing anti-CD3 antibody or a murine parental antibody.

[0080] In some embodiments, an improved developability property of an antibody provided herein is low viscosity relative to an existing anti-CD3 antibody or murine parental antibody. Low viscosity means that the thickness (also known as resistance to flow) of a solution comprising an antibody provided herein is lower for an antibody provided herein relative to an existing anti-CD3 antibody or murine parental antibody. Lower viscosity provides increased administration routes and may improve drug delivery. Lower viscosity may be decreased by 10% to 100%, 20% to 90%, 30% to 80%, 40% to 70%, or 50% to 60% relative to an existing anti-CD3 antibody or a murine parental antibody. In some embodiments, an antibody provided herein has solubility that is decreased by 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% or more relative to an existing anti-CD3 antibody or a murine parental antibody.

[0081] In some embodiments, an improved developability property of an antibody provided herein is increased resistance to aggregation relative to an existing anti-CD3 antibody or a murine parental antibody. Resistance to aggregation means that an antibody provided herein retains its proper, folded antibody conformation as opposed to mis-folded, higher order aggregates comprising an antibody provided herein. In some embodiments, an antibody provided herein has resistance to aggregation that is increased by 10% to 100%, 20% to 90%, 30% to 80%, 40% to 70%, or 50% to 60% relative to an existing anti-CD3 antibody or a murine parental antibody. In some embodiments, an antibody provided herein has resistance to aggregation that is increased by 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% or more relative to an existing anti-CD3 antibody or a murine parental antibody.

[0082] In some embodiments, an improved developability property of an antibody provided herein is high chemical and thermal stability relative to an existing anti-CD3 antibody or a murine parental antibody. High chemical stability may be improved tolerance to an acidic environment or acidic stress, such as a pH of about 6 or below, about 5 or below, about 4 or below, about 3 or below, or about 2 or below. High thermal stability by a melting temperature of about 55°C, about 56°C, about 57°C, about 58°C, about 59°C, about 60°C, about 61°C, about 62°C, about 63°C, 64°C, or about 65°C, or higher.

[0083] In some embodiments, an improved developability property of an antibody provided herein is long serum half-life relative to an existing anti-CD3 antibody or a murine parental antibody. Long serum half-life is increased concentration of an anti-CD3 in the serum of a subject administered the antibody. Long serum half-life is a half-life of 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 15 days, 16 days, 17 days, 18 days,19 days, 20 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, 28 days, 29 days, or 29 days or more.

[0084] In some embodiments, an improved developability property of an antibody provided herein is low clearance rate relative to an existing anti-CD3 antibody or a murine parental antibody. Low clearance rate is reduced clearance of an antibody (e.g., relative to an existing anti-CD3 antibody) from a subject. Clearance may clearance by liver, clearance by kidney, or any other antibody clearance route known in the art.

[0085] Developability may be assessed using a suite of biophysical and biochemical assays including, but not limited to, PSR (poly specificity reagent) binding, AC-SINS (affinitycapture self-interaction nanoparticle spectroscopy), HIC (hydrophobic interaction chromatography), SEC (size-exclusion chromatography), DLS (dynamic light scattering), DSF (differential scanning fluorimetry), CIC (cross -interaction chromatography), enzyme linked immunosorbent assay (ELISA), measuring antibody concentration in body fluid (e.g., blood, plasma, serum, urine, etc).III. Antibodies and Related Compositions(a) Anti-CD3 Antibodies

[0086] In some embodiments, a humanized anti-CD3 antibody provided herein has enhanced affinity for human CD3 relative to anti-CD3 antibodies known in the art. In some embodiments, a humanized anti-CD3 antibody provided herein has increased specificity for human CD3 relative to anti-CD3 antibodies in the art. In some embodiments, a humanized anti-CD3 antibody provided herein has reduced polyreactivity (e.g., cross -reactivity to off- target antigens) relative to anti-CD3 antibodies known in the art. In some embodiments, a humanized anti-CD3 antibody provided herein has increased stability relative to anti-CD3 antibodies known in the art. In some embodiments, a humanized anti-CD3 antibody provided herein has reduced immunogenicity relative to anti-CD3 antibodies known in the art. In some embodiments, a humanized anti-CD3 antibody provided herein has a reduced aggregation propensity or self-association propensity (e.g., as measured by affinity-capture selfinteraction nanoparticle spectroscopy, AC-SINS).

[0087] In some aspects, the disclosure provides a humanized anti-CD3 antibody. Anti-CD3 antibodies provided herein are humanized murine antibodies that demonstrate improved properties compared to non-humanized antibodies. For example, in some embodiments, a humanized anti-CD3 antibody provided herein exhibits enhanced affinity and / or specificityfor human CD3 compared to an anti-CD3 antibody that has not been humanized or humanized anti-CD3 antibodies known in the art. In some embodiments, a humanized anti- CD3 antibody provided herein exhibits decreased polyreactivity (e.g., cross -reactivity with off-target antigens) compared to an anti-CD3 antibody that has not been humanized or humanized anti-CD3 antibodies known in the art.

[0088] In some embodiments, the anti-CD3 antibody is an antibody specific for CD3 (e.g., CD3e). Anti-CD3 antibodies can be useful for targeting T cells to induce their activation and / or proliferation, or to deplete them. Anti-CD3 antibodies can induce T cell activation and expansion via cross-linking and clustering of CD3 on the surface of T cells, mimicking signaling via the T cell receptor (TCR). Such activation and expansion can be helpful to generate a more robust T cell response, for example by increasing the population of de novo effector T cells responding to infection or cancer or by reactivating memory T cells to enhance the immune response against rechallenge by a pathogen or cancer. Conversely, depletion of T cells with anti-CD3 antibodies may be helpful where aberrant T cell responses drive pathology, such as in graft-versus-host disease (GVHD), organ transplantation, autoimmune disorders, or allergy. Additionally, depletion of endogenous T cells with anti- CD3 antibodies can improve the outcome of adoptive cell transfer, such as in the context of CAR-T cell therapy to treat cancer, by creating empty niches in lymphoid organs that can be engrafted by adoptively-transferred cells.

[0089] The present disclosure, at least in part, provides engineered humanized SP34 (hSP34) antibodies that specifically recognizes and binds CD3. SP34 is a murine monoclonal antibody that binds human CD3s with high affinity, demonstrates robust T cell activation, and exhibits cross-reactivity with non-human primate CD3, thereby facilitating preclinical studies in relevant animal models. SP34 is known for its high affinity to human CD3s and its ability to activate T cells. It also demonstrates cross-reactivity to CD3 from non-human primates, including cynomolgus monkeys. In some embodiments, a comparator (e.g., control) anti-CD3 antibody provided herein is a SP34 antibody.

[0090] In some embodiments, an antibody provided herein is a humanized SP34 antibody that specifically recognizes and binds CD3. In some embodiments, an antibody provided herein comprises a SP34 sequence that is humanized to reduce immunogenicity compared with a non-humanized sequence.

[0091] Provided herein, in some aspects, are humanized antibodies that bind to human CD3 with high specificity and affinity. In some embodiments, the anti-CD3 antibodydescribed herein specifically binds to any extracellular epitope of a CD3 or an epitope that becomes exposed to an antibody. In some embodiments, anti-CD3 antibodies provided herein bind to human CD3. In some embodiments, the anti-CD3 antibody described herein binds to an amino acid segment of a human CD3. CD3 is a multimeric protein expressed by T cells. CD3 is part of the T cell receptor (TCR) complex. Binding to CD3 can thus, in some instances, activate T cells. In some other instances, binding to CD3 can deplete T cells by inducing their apoptosis. In some instances, binding to CD3 is useful for redirecting T cells or detecting T cells.

[0092] In some embodiments, the anti-CD3 antibody described herein specifically binds to human CD3. Human CD3 is made up of four subunits: CD3y, CD35, CD3s, and CD3(^. An exemplary amino acid sequence of human CD3y is set forth in NCBI Accession Number NP_000064.1 (SEQ ID NO: 15).

[0093] Human CD3y amino acid sequence (SEQ ID NO: 15):

[0094] MEQGKGLAVLILAI ILLQGTLAQSIKGNHLVKVYDYQEDGSVLLTCDAEAKNITWFKDGKM IGFLTEDKKKWNLGSNAKDPRGMYQCKGSQNKSKPLQVYYRMCQNCIELNAATISGFLFAEIVSIFVL AVGVYFIAGQDGVRQSRASDKQTLLPNDQLYQPLKDREDDQYSHLQGNQLRRN .

[0095] An exemplary amino acid sequence of human CD35 is set forth in NCBI Accession Number ACA05962.1 (SEQ ID NO: 16).

[0096] Human CD35 amino acid sequence (SEQ ID NO: 16):

[0097] MEHSTFLSGLVLATLLSQVSPFKIPIEELEDRVFVNCNTSITWVEGTVGTLLSDITRLDLG KRILDPRGIYRCNGTDIYKDKESTVQVHYRMCQSCVELDPATVAGI IVTDVIATLLLALGVFCFAGHE TGRLSGAADTQALLRNDQVYQPLRDRDDAQYSHLGGNWARNK

[0098] An exemplary amino acid sequence of human CD3s is set forth in NCBI Accession Number NP_000724.1 (SEQ ID NO: 17).

[0099] Human CD3s amino acid sequence (SEQ ID NO: 17):[000100] MQSGTHWRVLGLCLLSVGVWGQDGNEEMGGITQTPYKVSISGTTVILTCPQYPGSEILWQH NDKNIGGDEDDKNIGSDEDHLSLKEFSELEQSGYYVCYPRGSKPEDANFYLYLRARVCENCMEMDVMS VATIVIVDICITGGLLLLVYYWSKNRKAKAKPVTRGAGAGGRQRGQNKERPPPVPNPDYEPIRKGQRD LYSGLNQRRI[000101] Exemplary amino acid sequences of human CD3(^ are set forth in NCBI Accession Numbers NP_932170.1, NP_000725.1, NP_001365444.1, and NP_001365445.1. An exemplary amino acid sequence of human CD3(^ is set forth in SEQ ID NO: 18.[000102] Human CD3(^ amino acid sequence (SEQ ID NO: 18):[000103] MKWKALFTAAILQAQLPITEAQSFGLLDPKLCYLLDGILFIYGVILTALFLRVKFSRSADA PAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPQRRKNPQEGLYNELQKDKMAEAYSEIGMK GERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR[000104] In some embodiments, an anti-CD3 antibody is an antibody specific for CD3.Provided herein, in some aspects, are antibodies that bind to human CD3 with high specificity and affinity. In some embodiments, the anti-CD3 antibody described herein specifically binds to any extracellular epitope of a CD3 or an epitope that becomes exposed to an antibody.[000105] In some embodiments, the anti-CD3 antibody described herein may bind to a fragment of a human CD3. The fragment of CD3 may be between about 5 and about 425 amino acids, between about 10 and about 400 amino acids, between about 50 and about 350 amino acids, between about 100 and about 300 amino acids, between about 150 and about 250 amino acids, between about 200 and about 300 amino acids, or between about 75 and about 150 amino acids in length. The fragment may comprise a contiguous number of amino acids from CD3. In some embodiments, the anti-CD3 antibody described herein binds a fragment of CD3 comprising the amino acid sequence of QDGNE (SEQ ID NO: 32).[000106] In some embodiments, an anti-CD3 antibody described herein are affinity matured clones. In some embodiments, an anti-CD3 antibody specifically binds a CD3 (e.g., a human CD3) with binding affinity (e.g., as indicated by KD) of at least about 10'4M, 10'5M, 10'6M, IO’7M, 10'8M, 10'9M, 100M, 1041M, 102M, 103M, or less. For example, an anti-CD3 antibody of the present disclosure can bind to a CD3 protein (e.g., human CD3) with an affinity between 5 pM and 500 nM, between 50 pM and 100 nM, between 500 pM and 50 nM, between 1 nM and 50 nM, between 2 nM and 20 nM, between 1 nM and 10 nM, between 1 nM and 3 nM, or between 2 nM and 5 nM. In some embodiments, an anti-CD3 antibody specifically binds a CD3 (e.g., a human CD3s) with a binding affinity in the range of 10 nM to 1000 nM, 10 nM to 900 nM, 10 nM to 800 nM, 10 nM to 700 nM, 10 nM to 600 nM, 10 nM to 500 nM, 10 nM to 400 nM, 10 nM to 300 nM, 10 nM to 200 nM, 10 nM to 100 nM, 10 nM to 90 nM, 10 nM to 80 nM, 10 nM to 70 nM, 10 nM to 60 nM, 10 nM to 50 nM, 10 nM to 40 nM, 10 nM to 30 nM, 10 nM to 20 nM, 10 nM to 15 nM, 20 nM to 1000 nM, 20 nM to 900 nM, 20 nM to 800 nM, 20 nM to 700 nM, 20 nM to 600 nM, 20 nM to 500 nM, 20 nM to 400 nM, 20 nM to 300 nM, 20 nM to 200 nM, 20 nM to 150 nM, 20 nM to 120 nM, 20 nM to 100 nM, 20 nM to 90 nM, 20 nM to 80 nM, 20 nM to 70 nM, 20 nM to 60 nM, 20 nM to 50 nM, 20 nM to 40 nM, 20 nM to 30 nM, 50 nM to 1000 nM, 50 nM to 900 nM, 50 nM to 800 nM, 50 nM to 700 nM, 50 nM to 600 nM, 50 nM to 500 nM, 50 nM to 400 nM, 50 nM to300 nM, 50 nM to 250 nM, 50 nM to 200 nM, 50 nM to 150 nM, 50 nM to 120 nM, 50 nM to 100 nM, 50 nM to 80 nM, 50 nM to 75 nM, 50 nM to 60 nM, 75 nM to 1000 nM, 75 nM to 900 nM, 75 nM to 800 nM, 75 nM to 700 nM, 75 nM to 600 nM, 75 nM to 500 nM, 75 nM to 400 nM, 75 nM to 300 nM, 75 nM to 250 nM, 75 nM to 200 nM, 75 nM to 150 nM, 75 nM to 120 nM, 75 nM to 100 nM, 75 nM to 80 nM, 100 nM to 1000 nM, 100 nM to 900 nM, 100 nM to 800 nM, 100 nM to 700 nM, 100 nM to 600 nM, 100 nM to 500 nM, 100 nM to 400 nM, 100 nM to 300 nM, 100 nM to 250 nM, 100 nM to 200 nM, 100 nM to 150 nM, 100 nM to 120 nM, 200 nM to 1000 nM, 200 nM to 900 nM, 200 nM to 800 nM, 200 nM to 700 nM, 200 nM to 600 nM, 200 nM to 500 nM, 200 nM to 400 nM, 200 nM to 300 nM, 200 nM to 250 nM, 300 nM to 1000 nM, 300 nM to 900 nM, 300 nM to 800 nM, 300 nM to 700 nM, 300 nM to 600 nM, 300 nM to 500 nM, 300 nM to 400 nM, 400 nM to 1000 nM, 400 nM to 900 nM, 400 nM to 800 nM, 400 nM to 750 nM, 400 nM to 700 nM, 400 nM to 650 nM, 400 nM to 600 nM, 400 nM to 550 nM, 400 nM to 500 nM, 500 nM to 1000 nM, 500 nM to 900 nM, 500 nM to 800 nM, 500 nM to 750 nM, 500 nM to 700 nM, 500 nM to 650 nM, 500 nM to 600 nM, 500 nM to 550 nM,750 nM to 1000 nM, 750 nM to 900 nM, or 750 nM to 800 nM .[000107] The disclosure also includes antibodies that compete with any of the antibodies described herein for binding to a CD3 protein (e.g., human CD3) and that have an affinity of 100 nM or lower (e.g., 80 nM or lower, 50 nM or lower, 20 nM or lower, 10 nM or lower, 5 nM or lower, 500 pM or lower, 50 pM or lower, or 5 pM or lower). In some embodiments, an anti-CD3 antibody specifically binds a CD3 (e.g., a human CD3) with a binding affinity between 4 x 10'11and 3 x 10’11.[000108] In some embodiments, an anti-CD3 antibody specifically binds a CD3 (e.g., a human CD3) with a binding affinity (e.g., as indicated by EC50 in cell binding measured by a bivalent CD3 antibody) of between 0.1 and 2.5 nM. In some embodiments, an anti-CD3 antibody specifically binds a CD3 (e.g., a human CD3) with a binding affinity (e.g., as indicated by EC50 in cell binding) of between 0.25 and 2.0 nM. In some embodiments, an anti-CD3 antibody specifically binds a CD3 (e.g., a human CD3) with a binding affinity (e.g., as indicated by EC50 in cell binding) of between 0.5 and 1.5 nM. In some embodiments, an anti-CD3 antibody specifically binds a CD3 (e.g., a human CD3) with a binding affinity (e.g., as indicated by EC50 in cell binding) of between 0.75 and 1.0 nM. In some embodiments, an anti-CD3 antibody specifically binds a CD3 (e.g., a human CD3) with a binding affinity (e.g., as indicated by EC50 in cell binding) of between 0.75 and 0.9 nM. In some embodiments, it is understood that if the EC50 values was measured using monovalent anti-CD3 antibody, theEC50 value should be lower than the EC50 value measured using bivalent anti-CD3 antibody comprising the same antibody binding domain.[000109] The affinity and binding kinetics of the anti-CD3 antibody can be tested using any suitable method including but not limited to biosensor technology (e.g., OCTET or BIACORE). In some embodiments, an anti-CD3 antibody described herein binds to CD3 with a KD of sub-nanomolar range, single-digit nanomolar range, double-digit nanomolar range, or triple-digit nanomolar range.[000110] Binding affinity (or binding specificity) can be determined by a variety of methods including equilibrium dialysis, equilibrium binding, gel filtration, ELISA, surface plasmon resonance (SPR), florescent activated cell sorting (FACS) or spectroscopy (e.g., using a fluorescence assay). Exemplary conditions for evaluating binding affinity are in HBS-P buffer (10 mM HEPES pH7.4, 150 mM NaCl, 0.005% (v / v) surfactant P20) and PBS buffer (lOmM PO4-3, 137mM NaCl, and 2.7mM KC1). These techniques can be used to measure the concentration of bound proteins as a function of target protein concentration. The concentration of bound protein ([[Bound]]) is generally related to the concentration of free target protein ([[Free]]) by the following equation:[[Bound]] = [[Free]] / (Kd+[[Free]])[000111] It is not always necessary to make an exact determination of KA, though, since sometimes it is sufficient to obtain a quantitative measurement of affinity, e.g., determined using a method such as ELISA or FACS analysis, is proportional to KA, and thus can be used for comparisons, such as determining whether a higher affinity is, e.g., 2-fold higher, to obtain a qualitative measurement of affinity, or to obtain an inference of affinity, e.g., by activity in a functional assay, e.g., an in vitro or in vivo assay.[000112] In some embodiments, an anti-CD3 antibody herein exhibits reduced polyreactivity compared to anti-CD3 antibodies known in the art. Reduced polyreactivity in antibodies refers to a decreased ability to bind to multiple different antigens (e.g., reduced crossreactivity with an off-target antigen or antigens). Reducing polyreactivity of an antibody minimizes risk of off-target binding or immunogenicity. Polyreactivity can be measured using a baculovirus particle (BVP) enzyme-linked immunosorbent assay (ELISA), a multiantigen binding ELISA. Lower normalized BVP scores indicate decreased polyreactivity. In some embodiments, an anti-CD3 antibody provided herein has a normalized BVP score of between 0.01 and 0.2. In some embodiments, an anti-CD3 antibody provided herein has a normalized BVP score of between 0.05 and 0.15. In some embodiments, an anti-CD3 antibody provided herein has a normalized BVP score of between 0.07 and 0.12.[000113] In some embodiments, an anti-CD3 antibody provided herein exhibits reduced aggregation or self-association propensity. Self-association propensity can be measured using an affinity-capture self-interaction nanoparticle spectroscopy (AC-SINS) assay. Lower normalized AC-SINS values indicate decreased aggregation or self-association propensity. In some embodiments, an anti-CD3 antibody provided herein has a normalized AC-SINS value of between 0.01 and 0.2, 0.01 and 0.195, 0.01 and 0.19, 0.01 and 0.185, 0.01 and 0.18, 0.01 and 0.175, 0.01 and 0.17, 0.01 and 0.165, 0.01 and 0.16, 0.01 and 0.155, 0.01 and 0.15, 0.01 and 0.145, 0.01 and 0.14, 0.01 and 0.135, 0.01 and 0.13, 0.01 and 0.125, 0.01 and 0.12, 0.01 and 0.115, 0.01 and 0.11, 0.01 and 0.105, 0.01 and 0.10, 0.01 and 0.095, 0.01 and 0.09, 0.01 and 0.085, 0.01 and 0.08, 0.01 and 0.075, 0.01 and 0.07, 0.01 and 0.065, 0.01 and 0.06, 0.01 and 0.055, 0.01 and 0.05, 0.01 and 0.045, 0.01 and 0.040, 0.01 and 0.035, 0.01 and 0.03, 0.01 and 0.025, 0.01 and 0.020, 0.01 and 0.15, 0.02 and 0.2, 0.02 and 0.195, 0.02 and 0.19, 0.02 and 0.185, 0.02 and 0.18, 0.02 and 0.175, 0.02 and 0.17, 0.02 and 0.165, 0.02 and 0.16, 0.02 and 0.155, 0.02 and 0.15, 0.02 and 0.145, 0.02 and 0.14, 0.02 and 0.135, 0.02 and 0.13, 0.02 and 0.125, 0.02 and 0.12, 0.02 and 0.115, 0.02 and 0.11, 0.02 and 0.105, 0.02 and 0.10, 0.02 and 0.095, 0.02 and 0.09, 0.02 and 0.085, 0.02 and 0.08, 0.02 and 0.075, 0.02 and 0.07, 0.02 and 0.065, 0.02 and 0.06, 0.02 and 0.055, 0.02 and 0.05, 0.02 and 0.045, 0.02 and 0.040, 0.02 and 0.035, 0.02 and 0.03, 0.02 and 0.025, 0.05 and 0.2, 0.05 and 0.195, 0.05 and 0.19, 0.05 and 0.185, 0.05 and 0.18, 0.05 and 0.175, 0.05 and 0.17, 0.05 and 0.165, 0.05 and 0.16, 0.05 and 0.155, 0.05 and 0.15, 0.05 and 0.145, 0.05 and 0.14, 0.05 and 0.135, 0.05 and 0.13, 0.05 and 0.125, 0.05 and 0.12, 0.05 and 0.115, 0.05 and 0.11, 0.05 and 0.105, 0.05 and 0.10, 0.05 and 0.095, 0.05 and 0.09, 0.05 and 0.085, 0.05 and 0.08, 0.05 and 0.075, 0.05 and 0.07, 0.05 and 0.065, 0.05 and 0.06, 0.05 and 0.055, 0.07 and 0.2, 0.07 and 0.195, 0.07 and 0.19, 0.07 and 0.185, 0.07 and 0.18, 0.07 and 0.175, 0.07 and 0.17, 0.07 and 0.165, 0.07 and 0.16, 0.07 and 0.155, 0.07 and 0.15, 0.07 and 0.145, 0.07 and 0.14, 0.07 and 0.135, 0.07 and 0.13, 0.07 and 0.125, 0.07 and 0.12, 0.07 and 0.115, 0.07 and 0.11, 0.07 and 0.105, 0.07 and 0.10, 0.07 and 0.095, 0.07 and 0.09, 0.07 and 0.085, 0.07 and 0.08, 0.07 and 0.075, 0.10 and 0.2, 0.10 and 0.195, 0.10 and 0.19, 0.10 and 0.185, 0.10 and 0.18, 0.10 and 0.175, 0.10 and 0.17, 0.10 and 0.165, 0.10 and 0.16, 0.10 and 0.155, 0.10 and 0.15, 0.10 and 0.145, 0.10 and 0.14, 0.10 and 0.135, 0.10 and 0.13, 0.10 and 0.125, 0.10 and 0.12, 0.10 and 0.115, 0.10 and 0.11, 0.10 and 0.105, 0.12 and 0.2, 0.12 and 0.195, 0.12 and 0.19, 0.12 and 0.185, 0.12 and 0.18, 0.12 and 0.175, 0.12 and 0.17, 0.12 and 0.165, 0.12 and 0.16, 0.12 and 0.155, 0.12 and 0.15, 0.12 and 0.145, 0.12 and 0.14, 0.12 and 0.135, 0.12 and 0.13, 0.12 and 0.125, 0.15 and 0.2, 0.15 and 0.195, 0.15 and 0.19, 0.15 and 0.185, 0.15 and 0.18, 0.15 and 0.175, 0.15 and 0.17, 0.15and 0.165, 0.15 and 0.16, 0.15 and 0.155, 0.16 and 0.2, 0.16 and 0.195, 0.16 and 0.19, 0.16 and 0.185, 0.16 and 0.18, 0.16 and 0.175, 0.16 and 0.17, 0.16 and 0.165, 0.17 and 0.2, 0.17 and 0.195, 0.17 and 0.19, 0.17 and 0.185, 0.17 and 0.18, 0.17 and 0.175, 0.18 and 0.2, 0.18 and 0.195, 0.18 and 0.19, 0.18 and 0.185, 0.19 and 0.2, 0.19 and 0.195, or 0.195 and 0.2. [000114] In some embodiments, the antibody is a full-length IgG, a Fab fragment, a F(ab’) fragment, a scFv, or a Fv. In some embodiments, the antibody comprises a heavy chain constant region of the isotype IgGl, IgG2, IgG3, or IgG4.[000115] The heavy chain variable domain (VH) and light chain variable domain (VL), CDR sequences, and heavy chain and light chain constant region sequences of non-limiting examples of anti-CD3 antibodies are provided in Table 1.Table 1. Examples of anti-CD3 binders (CDRs according to the Kabat definition)Table 5. Examples of anti-CD3 binder framework sequences[000116] In some embodiments, an anti-CD3 antibody of the present disclosure comprises one or more of the HC CDRs (e.g., HC CDR1, HC CDR2, or HC CDR3) amino acid sequences from any one of an anti-CD3 antibody selected from Table 1. In some embodiments, an anti-CD3 antibody of the present disclosure comprise the HC CDR1, HC CDR2, and HC CDR3 as provided for any one of the antibodies elected from Table 1. In some embodiments, the present disclosure provides an antibody that specifically binds CD3 complex, wherein the improvement comprises the HC CDR1, HC CDR2, and HC CDR3 as provided for any one of the antibodies elected from Table 1. In some embodiments, the present disclosure provides an antibody that specifically binds CD3 complex, wherein the improvement comprises one or more of the LC CDRs (e.g., LC CDR1, LC CDR2, or LC CDR3) amino acid sequences from any one of an anti-CD3 antibody selected from Table 1. In some embodiments, the present disclosure provides an antibody that specifically binds CD3 complex, wherein the improvement comprises the LC CDR1, LC CDR2, and LC CDR3 s provided for any one of an anti-CD3 antibody selected from Table 1. In some embodiments, the present disclosure provides an antibody that specifically binds CD3 complex, wherein the improvement comprises HC CDR1, HC CDR2, and HC CDR3, LC CDR1, LC CDR2, and LC CDR3 as provided for any one of an anti-CD3 antibody selected from Table 1.[000117] In some embodiments, an anti-CD3 antibody of the present disclosure comprises one or more of the LC CDRs (e.g., LC CDR1, LC CDR2, or LC CDR3) amino acid sequences from any one of an anti-CD3 antibody selected from Table 1. In some embodiments, an anti-CD3 antibody of the present disclosure comprise the LC CDR1, LC CDR2, and LC CDR3s provided for any one of the anti-CD3 antibodies selected from Table 1. In some embodiments, the present disclosure provides an antibody that specifically binds a CD3 complex, wherein the improvement comprises the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3 as provided for any one of an anti-CD3 antibody selected from Table 1.[000118] In some embodiments, an anti-CD3 antibody of the present disclosure comprises the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3 as provided for any one of an anti-CD3 antibody selected from Table 1. In some embodiments, antibody heavy and light chain CDR3 domains may play a particularly important role in the binding specificity / affinity of an antibody for an antigen. Accordingly, an anti-CD3 antibody of the disclosure may include at least the heavy and / or light chain CDR3s of any one of an anti-CD3 antibody selected from Table 1.[000119] In some embodiments, an anti-CD3 antibody of the present disclosure comprises the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 of the antibody anti-CD3 Abl.[000120] In some embodiments, an anti-CD3 antibody of the present disclosure comprises the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 of the antibody anti-CD3 Ab2.[000121] In some embodiments, the isolated anti-CD3 antibody comprises a heavy chain variable region that comprises a heavy chain CDR1 (HC CDR1), a heavy chain CDR2 (HC CDR2), and a heavy chain CDR3 (HC CDR3).[000122] Also within the scope of the present disclosure are functional variants of any of the exemplary anti-CD3 antibodies as disclosed herein. A functional variant may contain one or more amino acid residue variations in the VH and / or VL, or in one or more of the HC CDRs and / or one or more of the LC CDRs as relative to the reference antibody, while retaining substantially similar binding and biological activities (e.g., substantially similar binding affinity, binding specificity, inhibitory activity, anti-inflammatory activity, or a combination thereof) as the reference antibody.[000123] In some embodiments, an anti-CD3 antibody of the disclosure have one or more CDRs (e.g., HC CDR or LC CDR) sequences substantially similar to any of the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 sequences from one of an anti-CD3 antibody selected from Table 1. In some embodiments, the position of one or more CDRs along the VH (e.g., HC CDR1, HC CDR2, or HC CDR3) and / or VL (e.g., LC CDR1, LC CDR2, or LC CDR3) region of an antibody described herein can vary by one, two, three, four, five, or six amino acid positions so long as immuno specific binding to CD3 (e.g., human CD3) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% of the binding of the original antibody from which it is derived). For example, in some embodiments, the position defining a CDR of any antibody described herein can vary by shifting the N-terminal and / or C-terminal boundary of the CDR by one, two, three, four, five, or six amino acids, relative to the CDR position of any one of the antibodies described herein, so long as immuno specific binding to CD3 (e.g., human CD3) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% of the binding of the original antibody from which it is derived). In another embodiment, the length of one or more CDRs along the VH (e.g., HC CDR1, HC CDR2, or HC CDR3) and / or VL (e.g., LC CDR1, LC CDR2, or LC CDR3) region of an antibody described herein can vary (e.g., be shorter or longer) by one, two, three, four, five, or more amino acids, so long as immuno specific binding to CD3 (e.g., human CD3) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% of the binding of the original antibody from which it is derived).[000124] Accordingly, in some embodiments, a HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein may be one, two, three, four, five or more amino acids shorter than one or more of the CDRs described herein (e.g., CDRS from an anti-CD3 antibody selected from Table 1) so long as immuno specific binding to CD3 (e.g., human CD3) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% relative to the binding of the original antibody from which it is derived). In some embodiments, a HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein may be one, two, three, four, five or more amino acids longer than one or more of the CDRs described herein (e.g., CDRS from an anti-CD3 antibody selected from Table 1) so long as immuno specific binding to CD3 (e.g., human CD3) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% relative to the binding of the original antibody from which it is derived). In some embodiments, the amino portion of a HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein can be extended by one, two, three, four, five or more amino acids compared to one or more of the CDRs described herein (e.g., CDRS from an anti-CD3 antibody selected from Table 1) so long as immuno specific binding to CD3 (e.g., human CD3) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% relative to the binding of the original antibody from which it is derived). In some embodiments, the carboxy portion of a HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein can be extended by one, two, three, four, five or more amino acids compared to one or more of the CDRs described herein (e.g., CDRS from an anti-CD3 antibody selected from Table 1) so long asimmuno specific binding to CD3 (e.g., human CD3) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% relative to the binding of the original antibody from which it is derived). In some embodiments, the amino portion of a HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein can be shortened by one, two, three, four, five or more amino acids compared to one or more of the CDRs described herein (e.g., CDRS from any of the anti- CD3 antibodies selected from Table 1) so long as immuno specific binding to CD3 (e.g., human CD3) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% relative to the binding of the original antibody from which it is derived). In some embodiments, the carboxy portion of a HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein can be shortened by one, two, three, four, five or more amino acids compared to one or more of the CDRs described herein (e.g., CDRS from an anti-CD3 antibody selected from Table 1) so long as immuno specific binding to CD3 (e.g., human CD3) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% relative to the binding of the original antibody from which it is derived). Any method can be used to ascertain whether immuno specific binding to CD3 (e.g., human CD3) is maintained, for example, using binding assays and conditions described in the art.[000125] In some examples, an anti-CD3 antibody of the disclosure has one or more CDR (e.g., HC CDR or LC CDR) sequences substantially similar to any one of an anti-CD3 antibody selected from Table 1. For example, the antibodies may include one or more CDR sequence(s) from an anti-CD3 antibody selected from Table 1 containing up to 5, 4, 3, 2, or 1 amino acid residue variations as compared to the corresponding CDR region in any one of the CDRs provided herein (e.g., CDRs from an anti-CD3 antibody selected from Table 1) so long as immuno specific binding to CD3 (e.g., human CD3) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% relative to the binding of the original antibody from which it is derived). In some embodiments, any of the amino acid variations in any of the CDRs provided herein may be conservative variations. Conservative variations can be introduced into the CDRs at positions where the residues are not likely to be involved in interacting with a CD3 protein (e.g., a human CD3 protein), for example, as determined based on a crystal structure. Some aspects of the disclosure provide anti-CD3 antibodies that comprise one or more of the heavy chain variable (VH) and / or light chain variable (VL) domains provided herein. In someembodiments, any of the VH domains provided herein include one or more of the HC CDR sequences (e.g., HC CDR1, HC CDR2, and HC CDR3) provided herein, for example, any of the CDR-H sequences provided in any one of the anti-CD3 selected from Table 1. In some embodiments, any of the VL domains provided herein include one or more of the CDR-L sequences (e.g., LC CDR1, LC CDR2, and LC CDR3) provided herein, for example, any of the LC CDR sequences provided in any one of an anti-CD3 antibody selected from Table 1. [000126] In some embodiments, an anti-CD3 antibody of the disclosure includes any antibody that includes a heavy chain variable domain and / or a light chain variable domain of any one of an anti-CD3 antibody selected from Table 1, and variants thereof. In some embodiments, anti-CD3 antibodies of the disclosure include any antibody that includes the heavy chain variable and light chain variable pairs of any anti-CD3 antibodies selected from Table 1.[000127] Aspects of the disclosure provide anti-CD3 antibodies having a heavy chain variable (VH) and / or a light chain variable (VL) domain amino acid sequence homologous to any of those described herein. In some embodiments, the anti-CD3 antibody comprises a heavy chain variable sequence or a light chain variable sequence that is at least 75% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the heavy chain variable sequence and / or any light chain variable sequence of any one of an anti-CD3 antibody selected from Table 1. In some embodiments, the homologous heavy chain variable and / or a light chain variable amino acid sequences do not vary within any of the CDR sequences provided herein. For example, in some embodiments, the degree of sequence variation (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) may occur within a heavy chain variable and / or a light chain variable sequence excluding any of the CDR sequences provided herein. In some embodiments, an anti-CD3 antibody provided herein comprise a heavy chain variable sequence and a light chain variable sequence that comprises a framework sequence that is at least 75%, (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) to the framework sequence of any anti-CD3 antibodies selected from Table 1.[000128] In some embodiments, an anti-CD3 antibody of the present disclosure comprises one or more of the framework (FW) amino acid sequences of a heavy chain variable region (VH) (e.g., VH FW1, VH FW2, VH FW3, or VH FW4) from any one of the frameworkregions selected from Table 5. In some embodiments, an anti-CD3 antibody of the present disclosure comprises one or more FW amino acid sequences of a light chain variable region (VL) (e.g., VL FW1, VL FW2, VL FW3, or VL FW4) from any one of the framework regions selected from Table 5.[000129] In some embodiments, the present disclosure provides an antibody that specifically binds CD3, wherein the improvement comprises one or more of the VH FWs (e.g., VH FW1, VH FW2, VH FW3, or VH FW4) amino acid sequences from any one of framework regions selected from Table 5. In some embodiments, the present disclosure provides an antibody that specifically binds CD3, wherein the improvement comprises the VH FW1, VH FW2, VH FW3, or VH FW4 as provided for any one of the antibodies elected from Table 5. Alternatively or in addition, in some embodiments, the present disclosure provides an antibody that specifically binds CD3, wherein the improvement comprises one or more of the VL FWs (e.g., VL FW1, VL FW2, VL FW3, or VL FW4) amino acid sequences from any one of the framework regions selected from Table 5. In some embodiments, the present disclosure provides an antibody that specifically binds CD3, wherein the improvement comprises the VL FW1, VL FW2, VL FW3, or VL FW4 provided for any one of an anti-CD3 antibodies selected from Table 5. In some embodiments, the present disclosure provides an antibody that specifically binds CD3, wherein the improvement comprises VH FW1, VH FW2, VH FW3, VH FW4, and VL FW1, VL FW2, VL FW3, and VL FW4 as provided for any one of an anti-CD3 antibodies selected from Table 5.[000130] In some embodiments, an anti-CD3 antibody of the present disclosure comprises the VH FW1, VH FW2, VH FW3, VH FW4, VL FW1, VL FW2, VL FW3, and VL FW4 as provided for any one of an anti-CD3 antibody selected from Table 5. Alternative or in addition, in some embodiments, an anti-CD3 antibody of the present disclosure comprises one or more of the VL FWs (e.g., VL FW1, VL FW2, VL FW3, or VL FW4) amino acid sequences from any one of an anti-CD3 antibodies selected from Table 5. In some embodiments, an anti-CD3 antibody of the present disclosure comprises the VL FW1, VL FW2, VL FW3, and VL FW4s provided for any one of the anti-CD3 antibodies selected from Table 5. In some embodiments, the present disclosure provides an antibody that specifically binds CD3, wherein the improvement comprises the VH FW1, VH FW2, VH FW3, VH FW4, VL FW1, VL FW2, VL FW3, and VL FW4 as provided for any one of an anti-CD3 antibodies selected from Table 5. In some embodiments, antibody heavy and light chain framework regions may play a particularly important role in the binding of an antibody to an antigen. Accordingly, an anti-CD3 antibody of the disclosure may include at least the heavyand / or light chain framework regions of any one of an anti-CD3 antibody selected from Table 5.[000131] In some embodiments, an anti-CD3 antibody of the present disclosure comprises the VH FW1, VH FW2, VH FW3, VH FW4, VL FW1, VL FW2, VL FW3, and / or VL FW4of the antibody anti-CD3 Abl. In some embodiments, an anti-CD3 antibody of the present disclosure comprises the VH FW1, VH FW2, VH FW3, VH FW4, VL FW1, VL FW2, VL FW3, and / or VL FW4 comprising the amino acid sequence as set forth in SEQ ID NOs: 19-26, respectively.[000132] In some embodiments, an anti-CD3 antibody of the present disclosure comprises the VH FW1, VH FW2, VH FW3, VH FW4, VL FW1, VL FW2, VL FW3, and / or VL FW4 of the antibody anti-CD3 Ab2. In some embodiments, an anti-CD3 antibody of the present disclosure comprises the VH FW1, VH FW2, VH FW3, VH FW4, VL FW1, VL FW2, VL FW3, and / or VL FW4 comprising the amino acid sequence set forth in SEQ ID NOs: 27, 28, 29, 22, 23, 24, 25, and 26, respectively.[000133] In some embodiments, an anti-CD3 antibody of the present disclosure is a humanized antibody (e.g., a humanized variant containing one or more CDRs of Table 1). In some embodiments, the anti-CD3 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, a HC CDR3, a LC CDR1, a LC CDR2, and a LC CDR3 that are the same as the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3 shown in Table 1, and comprises a humanized heavy chain variable region and / or a humanized light chain variable region.[000134] In some embodiments, an anti-CD3 antibody of the present disclosure is a humanized antibody comprising a VH containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VH of an anti-CD3 antibody listed in Table 1. Alternatively or in addition, the anti-CD3 antibody of the present disclosure is a humanized antibody comprising a VL containing no more than 20 amino acid variations e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VL of any one of an anti-CD3 antibody listed in Table 1.[000135] In some embodiments, an anti-CD3 antibody of the present disclosure comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 7. Alternatively or in addition, the anti-CD3 antibody of the present disclosure comprises a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 8.[000136] In some embodiments, an anti-CD3 antibody of the present disclosure comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 7. Alternatively or in addition, the anti-CD3 antibody of the present disclosure comprises a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 8.[000137] In some embodiments, according to the Kabat definition, an anti-CD3 antibody of the present disclosure comprises a HC CDR3 having the amino acid sequence of SEQ ID NO: 3. In some embodiments, an anti-CD3 antibody of the present disclosure comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 1, a HC CDR2 having the amino acid sequence of SEQ ID NO: 2, a HC CDR3 having the amino acid sequence of SEQ ID NO: 3, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 6.[000138] In some embodiments, an anti-CD3 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 1, HC CDR2 having the amino acid sequence of SEQ ID NO: 2, and HC CDR3 having the amino acid sequence of SEQ ID NO: 3. “Collectively,” as used anywhere in the present disclosure, means that the total number of amino acid variations in all of the three heavy chain CDRs is within the defined range. Alternatively or in addition, the anti-CD3 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2 or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 4, LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 6.[000139] In some embodiments, an anti-CD3 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 1, HC CDR2 having the amino acid sequence of SEQ ID NO: 2, and HC CDR3 having the amino acid sequence of SEQ ID NO: 3. Alternatively or in addition, the anti-CD3 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3 that collectively are at least 80% (e.g., at least 80%,at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the to the LC CDR1 having the amino acid sequence of SEQ ID NO: 4, LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 6.[000140] In some embodiments, an anti-CD3 antibody of the present disclosure comprises: a HC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 1; a HC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR2 having the amino acid sequence of SEQ ID NO: 2; and / or a HC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR3 having the amino acid sequence of SEQ ID NO: 3. Alternatively or in addition, the anti-CD3 antibody of the present disclosure comprises: a LC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 4; a LC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or a LC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR3 having the amino acid sequence of SEQ ID NO: 6.[000141] In some embodiments, an anti-CD3 antibody of the present disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 7. Alternatively or in addition, the anti-CD3 antibody of the present disclosure comprises a VL comprising the amino acid sequence of SEQ ID NO: 8.[000142] In some embodiments, an anti-CD3 antibody of the present disclosure comprises a VH containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VH as set forth in SEQ ID NO: 7. Alternatively or in addition, the anti-CD3 antibody of the present disclosure comprises a VL containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VL as set forth in SEQ ID NO: 8. In some embodiments, the number of amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) may occur within a VH of SEQ ID NO: 7 and / or a VL of SEQ ID NO: 8 excluding any of the CDR sequences therein. In someembodiments, an anti-CD3 antibodies provided herein comprise a heavy chain variable sequence that comprises a framework sequence that that contains no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation to the framework sequence of a VH of SEQ ID NO: 7, and / or a light chain variable sequence that comprises a framework sequence that that contains no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation to the framework sequence of a VL of SEQ ID NO: 8.[000143] In some embodiments, an anti-CD3 antibody of the present disclosure comprises a VH comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the VH as set forth in SEQ ID NO: 7. Alternatively or in addition, the anti-CD3 antibody of the present disclosure comprises a VL comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the VL as set forth in SEQ ID NO: 8. In some embodiments, the degree of sequence variation (e e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) may occur within a VH of SEQ ID NO: 7, and / or a VL of SEQ ID NO: 8 excluding any of the CDR sequences therein. In some embodiments, an anti-CD3 antibody provided herein comprise a heavy chain variable sequence that is at least 75%, (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the framework sequence of a VH of SEQ ID NO: 7, and / or a light chain variable sequence that comprises a framework sequence that is at least 75%, (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the framework sequence of a VL of SEQ ID NO: 8.[000144] In some embodiments, an anti-CD3 antibody of the present disclosure comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 11. Alternatively or in addition, the anti-CD3 antibody of the present disclosure comprises a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 8.[000145] In some embodiments, an anti-CD3 antibody of the present disclosure comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the aminoacid sequence of SEQ ID NO: 11. Alternatively or in addition, the anti-CD3 antibody of the present disclosure comprises a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 8.[000146] In some embodiments, according to the Kabat definition system, the anti-CD3 antibody of the present disclosure comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 1, a HC CDR2 having the amino acid sequence of SEQ ID NO: 9, a HC CDR3 having the amino acid sequence of SEQ ID NO: 10, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 6.[000147] In some embodiments, an anti-CD3 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 1, HC CDR2 having the amino acid sequence of SEQ ID NO: 9, and HC CDR3 having the amino acid sequence of SEQ ID NO: 10. “Collectively,” as used anywhere in the present disclosure, means that the total number of amino acid variations in all of the three heavy chain CDRs is within the defined range. Alternatively or in addition, the anti-CD3 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2 or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 4, LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 6.[000148] In some embodiments, an anti-CD3 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 1, HC CDR2 having the amino acid sequence of SEQ ID NO: 9, and HC CDR3 having the amino acid sequence of SEQ ID NO: 10. Alternatively or in addition, the anti-CD3 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the to the LC CDR1 having the amino acid sequence of SEQ ID NO: 4, LC CDR2 having the amino acidsequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 6.[000149] In some embodiments, an anti-CD3 antibody of the present disclosure comprises: a HC CDR1 having no more than 3 amino acid variations e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 1; a HC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR2 having the amino acid sequence of SEQ ID NO: 9; and / or a HC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR3 having the amino acid sequence of SEQ ID NO: 10. Alternatively or in addition, the anti-CD3 antibody of the present disclosure comprises: a LC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 4; a LC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or a LC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR3 having the amino acid sequence of SEQ ID NO: 6.[000150] An anti-CD3 antibody described herein can be in any antibody form, including, but not limited to, intact (i.e., full-length) antibodies, antigen-binding fragments thereof (such as Fab, F(ab'), F(ab')2, Fv), single chain antibodies, bi-specific antibodies, or nanobodies. In some embodiments, the anti-CD3 antibody described herein is a scFv. In some embodiments, the anti-CD3 antibody described herein is a scFv-Fab (e.g., scFv fused to a portion of a constant region). Provided herein, in some embodiments, is a bispecific antibody. In some embodiments, the first antigen binding site of the bispecific antibody specifically binds CD3. In some embodiments, the second antigen binding site specifically binds a T cell antigen. In some antibodies, the T cell antigen is a CD3 complex or a portion thereof.[000151] In some embodiments, conservative mutations can be introduced into antibody sequences (e.g., CDRs or framework sequences) at positions where the residues are not likely to be involved in interacting with a target antigen (e.g., CD3), for example, as determined based on a crystal structure. In some embodiments, one, two or more mutations (e.g., amino acid substitutions) are introduced into the Fc region of an anti-CD3 antibody described herein (e.g., in a CH2 domain (residues 231-340 of human IgGl) and / or CH3 domain (residues 341- 447 of human IgGl) and / or the hinge region, with numbering according to the Kabat numbering system (e.g., the EU index in Kabat)) to alter one or more functional properties ofthe antibody, such as serum half-life, complement fixation, Fc receptor binding and / or antigen-dependent cellular cytotoxicity.[000152] In some embodiments, one, two or more mutations (e.g., amino acid substitutions) are introduced into the hinge region of the Fc region (CHI domain) such that the number of cysteine residues in the hinge region are altered (e.g., increased or decreased) as described in, e.g., U.S. Pat. No. 5,677,425. The number of cysteine residues in the hinge region of the CHI domain can be altered to, e.g., facilitate assembly of the light and heavy chains, or to alter (e.g., increase or decrease) the stability of the antibody or to facilitate linker conjugation. [000153] In some embodiments, one, two or more mutations (e.g., amino acid substitutions) are introduced into the Fc region of an antibody described herein (e.g., in a CH2 domain (residues 231-340 of human IgGl) and / or CH3 domain (residues 341-447 of human IgGl) and / or the hinge region, with numbering according to the Kabat numbering system (e.g., the EU index in Kabat)) to increase or decrease the affinity of the antibody for an Fc receptor (e.g., an activated Fc receptor) on the surface of an effector cell. Mutations in the Fc region of an antibody that decrease or increase the affinity of an antibody for an Fc receptor and techniques for introducing such mutations into the Fc receptor or fragment thereof are known to one of skill in the art. Examples of mutations in the Fc receptor of an antibody that can be made to alter the affinity of the antibody for an Fc receptor are described in, e.g., Smith P el al., (2012) PNAS 109: 6181-6186, U.S. Pat. No. 6,737,056, and International Publication Nos. WO 02 / 060919; WO 98 / 23289; and WO 97 / 34631, which are incorporated herein by reference.[000154] In some embodiments, one, two or more amino acid mutations (i.e., substitutions, insertions or deletions) are introduced into an IgG constant domain, or FcRn-binding fragment thereof (preferably an Fc or hinge-Fc domain fragment) to alter (e.g., decrease or increase) half-life of the antibody in vivo. See, e.g., International Publication Nos. WO 02 / 060919; WO 98 / 23289; and WO 97 / 34631; and U.S. Pat. Nos. 5,869,046, 6,121,022, 6,277,375 and 6,165,745 for examples of mutations that will alter (e.g., decrease or increase) the half-life of an antibody in vivo.[000155] In some embodiments, one, two or more amino acid mutations (i.e., substitutions, insertions, or deletions) are introduced into an IgG constant domain, or FcRn-binding fragment thereof (preferably an Fc or hinge-Fc domain fragment) to decrease the half-life of the anti-CD3 antibody in vivo.[000156] In some embodiments, one, two or more amino acid mutations (i.e., substitutions, insertions or deletions) are introduced into an IgG constant domain, or FcRn-bindingfragment thereof (preferably an Fc or hinge-Fc domain fragment) to increase the half-life of the antibody in vivo. In some embodiments, the antibodies can have one or more amino acid mutations (e.g., substitutions) in the second constant (CH2) domain (residues 231-340 of human IgGl) and / or the third constant (CH3) domain (residues 341-447 of human IgGl), with numbering according to the EU index in Kabat (Kabat E A et al., (1991) supra). In some embodiments, the constant region of the IgGl of an antibody described herein comprises a methionine (M) to tyrosine (Y) substitution in position 252, a serine (S) to threonine (T) substitution in position 254, and a threonine (T) to glutamic acid (E) substitution in position 256, numbered according to the EU index as in Kabat. See U.S. Pat. No. 7,658,921, which is incorporated herein by reference. This type of mutant IgG, referred to as "YTE mutant" has been shown to display fourfold increased half-life as compared to wild-type versions of the same antibody (see Dall'Acqua W F et al., (2006) J Biol Chem 281: 23514-24). In some embodiments, an antibody comprises an IgG constant domain comprising one, two, three or more amino acid substitutions of amino acid residues at positions 251-257, 285-290, 308- 314, 385-389, and 428-436, numbered according to the EU index as in Kabat.[000157] In some embodiments, one, two or more amino acid substitutions are introduced into an IgG constant domain Fc region to alter the effector function(s) of the anti-CD3 antibody. The effector ligand to which affinity is altered can be, for example, an Fc receptor or the Cl component of complement. This approach is described in further detail in U.S. Pat. Nos. 5,624,821 and 5,648,260 (e.g., a L234A and L235A mutation). In some embodiments, the deletion or inactivation (through point mutations or other means) of a constant region domain can reduce Fc receptor binding of the circulating antibody thereby increasing tumor localization. See, e.g., U.S. Pat. Nos. 5,585,097 and 8,591,886 for a description of mutations that delete or inactivate the constant domain and thereby increase tumor localization. In some embodiments, one or more amino acid substitutions may be introduced into the Fc region of an antibody described herein to remove potential glycosylation sites on Fc region, which may reduce Fc receptor binding (see, e.g., Shields R L et al., (2001) J Biol Chem 276: 6591-604). [000158] In some embodiments, one or more amino in the constant region of an anti-CD3 antibody described herein can be replaced with a different amino acid residue such that the antibody has altered Clq binding and / or reduced or abolished complement dependent cytotoxicity (CDC). This approach is described in further detail in U.S. Pat. No. 6,194,551 (Idusogie et al). In some embodiments, one or more amino acid residues in the N-terminal region of the CH2 domain of an antibody described herein are altered to thereby alter the ability of the antibody to fix complement. This approach is described further in InternationalPublication No. WO 94 / 29351. In some embodiments, the Fc region of an antibody described herein is modified to increase the ability of the antibody to mediate antibody dependent cellular cytotoxicity (ADCC) and / or to increase the affinity of the antibody for an Fey receptor. This approach is described further in International Publication No. WO 00 / 42072. [000159] In some embodiments, the heavy and / or light chain variable domain(s) sequence(s) of the antibodies provided herein can be used to generate, for example, CDR-grafted, chimeric, humanized, or composite human antibodies or antigen-binding fragments, as described elsewhere herein. As understood by one of ordinary skill in the art, any variant, CDR-grafted, chimeric, humanized, or composite antibodies derived from any of the antibodies provided herein may be useful in the compositions and methods described herein and will maintain the ability to specifically bind CD3, such that the variant, CDR-grafted, chimeric, humanized, or composite antibody has at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% or more binding to CD3 relative to the original antibody from which it is derived.[000160] In some embodiments, the antibodies provided herein comprise mutations that confer desirable properties to the antibodies. For example, to avoid potential complications due to Fab-arm exchange, which is known to occur with native IgG4 mAbs, the antibodies provided herein may comprise a stabilizing ‘Adair’ mutation (Angal S., et al., “A single amino acid substitution abolishes the heterogeneity of chimeric mouse / human (IgG4) antibody,” Mol Immunol 30, 105-108; 1993), where serine 228 (EU numbering; residue 241 Kabat numbering) is converted to proline resulting in an IgGl-like hinge sequence. Accordingly, any of the antibodies may include a stabilizing ‘Adair’ mutation.[000161] In some embodiments, an antibody is modified, e.g., modified via glycosylation, phosphorylation, sumoylation, and / or methylation. In some embodiments, an antibody is a glycosylated antibody, which is conjugated to one or more sugar or carbohydrate molecules. In some embodiments, the one or more sugar or carbohydrate molecule are conjugated to the antibody via N-glycosylation, O-glycosylation, C-glycosylation, glypiation (GPI anchor attachment), and / or phosphoglycosylation. In some embodiments, the one or more sugar or carbohydrate molecules are monosaccharides, disaccharides, oligosaccharides, or glycans. In some embodiments, the one or more sugar or carbohydrate molecule is a branched oligosaccharide or a branched glycan. In some embodiments, the one or more sugar or carbohydrate molecule includes a mannose unit, a glucose unit, an N-acetylglucosamine unit, an N-acetylgalactosamine unit, a galactose unit, a fucose unit, or a phospholipid unit. In some embodiments, there are about 1-10, about 1-5, about 5-10, about 1-4, about 1-3, orabout 2 sugar molecules. In some embodiments, a glycosylated antibody is fully or partially glycosylated. In some embodiments, an antibody is glycosylated by chemical reactions or by enzymatic means. In some embodiments, an antibody is glycosylated in vitro or inside a cell, which may optionally be deficient in an enzyme in the N- or O- glycosylation pathway, e.g., a glycosyltransferase. In some embodiments, an antibody is functionalized with sugar or carbohydrate molecules as described in International Patent Application Publication WO2014065661, published on May 1, 2014, entitled, “Modified antibody, antibodyconjugate and process for the preparation thereof ’ .[000162] In some embodiments, any one of an anti-CD3 antibody described herein may comprise a signal peptide in the heavy and / or light chain sequence (e.g., a N-terminal signal peptide). In some embodiments, the anti-CD3 antibody described herein comprises any one of the VH and VL sequences, any one of the IgG heavy chain and light chain sequences, or any one of the F(ab’) heavy chain and light chain sequences described herein, and further comprises a signal peptide (e.g., a N-terminal signal peptide).[000163] In some embodiments, any one of the antibodies described herein is a multispecific antibody that specifically binds CD3 and one or more additional target antigens. In some embodiments, the antibody is a bispecific antibody that specifically binds to CD3 and one additional target antigen. In some embodiments, the multispecific antibody or bispecific antibody can be obtained by known technology in the art. In some embodiments, the one or more additional target antigens include are not limited to CD3, CD4, CD8, CD20, CD19, CD21, CD23, CD46, CD80, HLA-DR, CD74, CD22, CD14, CD15, CD16, CD123, CD28, CD137 (4-1BB), interleukin (IL)-2, IL-12, IL-15, IL-21, TCR gamma / delta, NKp46, or KIR. In some embodiments, the one or more additional target antigens comprise a cancer antigen or a pathogen-derived antigen.[000164] In some embodiments, the antibodies described herein are conjugated directly or indirectly to one or more molecular pay loads or labels. For example, in some embodiments, antibodies described herein are conjugated to molecular payload, e.g., a molecular payload providing a therapeutic benefit for a subject, e.g., an antibody-drug conjugate (ADC). In some embodiments, a molecular payload may be a small molecule, protein, nucleic acid, oligonucleotide, or any molecular entity capable of modulating the activity or function of a gene, protein, and / or nucleic acid, e.g., in a cell. In some embodiments, the molecular pay load is a cytotoxic agent or a chemotherapeutic agent. In some embodiments, antibodies described herein are conjugated directly or indirectly to a detectable label, e.g., for diagnostic purposes.[000165] In some embodiments, the present disclosure also provides fusion proteins comprising an anti-CD3 antibody described herein fused directly or indirectly (e.g., via a linker) to one or more polypeptide or protein.(b) T cell engaging bispecific antibodies targeting a CD3 complex[000166] In some aspects, the present disclosure provides a multispecific (e.g., a bispecific) antibody comprising one or more first antigen binding sites targeting one or more different epitopes of a cancer antigen or a pathogen-derived antigen, and one or more second binding sites targeting CD3. In some aspects, the present disclosure provides a multispecific (e.g., a bispecific) antibody comprising one or more first antigen binding sites targeting one or more different epitopes of a cancer antigen or a pathogen-derived antigen and one or more second antigen binding sites targeting CD3. Such multispecific (e.g., bispecific) antibodies can redirect T cells (e.g., cytotoxic T cells) to cancer cells, or infected cells that are displaying pathogen-derived antigens on the cell surface, by binding CD3 on T cells with one binding site and binding one or more cancer or pathogen-derived antigens with another binding site. This dual-binding activity spatially reorients T cells to directly kill the target cells, thereby enhancing the cytolytic immune response.[000167] In some embodiments, the present disclosure provides a bispecific antibody comprising a first antigen binding site targeting a cancer antigen or a pathogen-derived antigen, and a second binding site targeting CD3. In some embodiments, the present disclosure provides a bispecific antibody comprising a first antigen binding site targeting a cancer antigen or a pathogen-derived antigen, and a second antigen binding site that specifically binds CD3. In some embodiments, the present disclosure provides a bispecific antibody comprising a first antigen binding site targeting one or more epitopes of a cancer antigen or a pathogen-derived antigen, and a second antigen binding site that specifically binds CD3. In some embodiments, a bispecific antibody described herein comprises a second antigen binding site comprising an antigen binding site of any one of the CD3 antibodies described in Table 1. In some embodiments, a bispecific antibody described herein comprises a second antigen binding site comprising a HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 of any one of the anti-CD3 antibodies described in Table 1. In some embodiments, a bispecific antibody described herein comprises a second antigen binding site comprising a VH and / or VL of any one of the anti-CD3 antibodies described in Table 1.[000168] In some embodiments, a bispecific antibody described herein is a T cell engaging antibody that targets CD3 and also targets a cancer antigen or a pathogen-derived antigen. In some embodiments, a bispecific antibody described herein comprises a second antigen binding site that specifically binds CD3 and a first antigen binding site that specifically binds a cancer antigen or a pathogen-derived antigen (referred to as a bispecific antibody). In some embodiments, the first antigen binding site specifically binds to a cancer antigen. In some embodiments, the cancer antigen includes but is not limited to CD13, CD14, CD15, CD19, CD20, CD22, CD30, CD33, CD38, CD41, CD61, CD64, CD68, CD117, CD123, CD138, CD267, CD269, Claudinl8.2, DLL3, HER2 / neu, PSA (pro state- specific antigen), PSMA, CEA (carcinoembryonic antigen), NY-ESO-1, glypican-3, EGFR, EGFRvIII, MAGE (melanoma antigens), MAGE-A1, MAGE-A3, MAGE-A4, MAGE-A8, MSLN (mesothelin), BCMA, TACI, alpha-fetoprotein, BAFF, FET3, CA 9-19, CA 72-4, FAP, MART-1, F77, GD2, CT83, HORMAD1, glycoprotein (gp) 100, HPV16, WT1, or PRAME. In some embodiments, the cancer antigen is WT1. In some embodiments, the cancer antigen is PRAME. In some embodiments, the cancer antigen is DEE3. In some embodiments, the cancer antigen is CD70. In some embodiments, the cancer antigen is Claudinl8.2. In some embodiments, the cancer antigen is MSEN. In some embodiments, the cancer antigen is MAGE-A4. In some embodiments, the cancer antigen is CD38. In some embodiments, the cancer antigen is BCMA.[000169] In some embodiments, first antigen binding site specifically binds a pathogen- derived antigen. In some embodiments, the pathogen-derived antigen is derived from pathogens that include but are not limited to HIV, HPV, RSV, influenza, Epstein-Barr virus (EBV), cytomegalovirus (CMV), Dengue virus (DNV), Zika virus (ZIKV), SARS-CoV-2, Staphyloccocus species (e.g., S. aureus, S. pneumoniae, and others), Enterococcus spp. (e.g., E. faecium and others), Klebsiella spp. (e.g., K. pneumoniae and others), Acinetobacter spp. (e.g., A. baumannii and others), Pseudomonas spp. (e.g., P. aeruginosa and others, Enterobacter spp. (e.g., E. cloacae, E. aerogenes, and others), Plasmodium spp. (e.g., P. falciparum, P. vivax, and others), Trypanosoma spp. (e.g., T. brucei gambiense, T. brucei rhodesiense, and others), Schistosoma spp. (e.g., .S'. mansoni, S. haematobium, S. japonicum), T. solium, and E. histolytica.[000170] In some embodiments, a need for recruiting a T cell to a cancer cell to kill the cancer cell exists. In some embodiments, the present disclosure provides means for engaging a T cell to a cancer cell. In some embodiments, the means for engaging a T cell to a cancercell is a bispecific antibody described herein. In some embodiments, the present disclosure provides means for eliciting cytotoxic T cell immunity against cancer cells. In some embodiments, the means for eliciting cytotoxic T cell immunity against cancer cells is a bispecific antibody described herein.[000171] In some embodiments, a need for recruiting a T cell to an infected cell to kill the infected cell exists. In some embodiments, the present disclosure provides means for engaging a T cell to an infected cell. In some embodiments, the means for engaging a T cell to an infected cell is a bispecific antibody described herein. In some embodiments, the present disclosure provides means for eliciting cytotoxic T cell immunity against infected cells. In some embodiments, the means for eliciting cytotoxic T cell immunity against infected cells is a bispecific antibody described herein.[000172] In some embodiments, a bispecific antibody comprises a second antigen binding site that specifically binds to CD3, wherein the improvement comprises a second antigen binding site that specifically binds to a CD3 complex that comprises any one of the anti-CD3 binding site derived from an anti-CD3 antibody described herein (e.g., any one of the anti- CD3 antibody described in Table 1).[000173] In some embodiments, a bispecific antibody provided herein comprises an antigen binding site that binds to B-cell maturation antigen (BCMA) and an antigen binding site that specifically binds to CD3. BCMA is a tumor necrosis factor receptor (TNFR) superfamily member that helps to coordinate B cell proliferation maturation and survival, as well as differentiation into plasma cells. BCMA is expressed almost exclusively on plasmablasts and plasma cells and is weakly detectable on some memory B cells committed to plasma cell differentiation and on plasmacytoid dendritic cells.[000174] In some embodiments, a bispecific antibody described herein comprises a second antigen binding site that specifically binds to CD3. In some embodiments, a bispecific antibody described herein comprises a second antigen binding site comprising a HC CDR1, a HC CDR2 and a HC CDR3 of a heavy chain variable domain (VH) having the amino acid sequence of SEQ ID NO: 7. Alternatively or in addition, a bispecific antibody described herein comprises a second antigen binding site comprising a LC CDR1, a LC CDR2 and a LC CDR3 of a light chain variable domain (VL) having the amino acid sequence of SEQ ID NO: 8.[000175] In some embodiments, a bispecific antibody described herein comprises a second antigen binding site comprising a HC CDR3 having the amino acid sequence of SEQ ID NO: 3. In some embodiments, a bispecific antibody described herein comprises a second antigenbinding site comprising a HC CDR1 having the amino acid sequence of SEQ ID NO: 1, a HC CDR2 having the amino acid sequence of SEQ ID NO: 2, and a HC CDR3 having the amino acid sequence of SEQ ID NO: 3. Alternatively or in addition, in some embodiments, a bispecific antibody described herein comprises a second antigen binding site comprising a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 6. In some embodiments, a bispecific antibody described herein comprises a second antigen binding site comprising a HC CDR1 having the amino acid sequence of SEQ ID NO: 1, a HC CDR2 having the amino acid sequence of SEQ ID NO: 2, a HC CDR3 having the amino acid sequence of SEQ ID NO: 3, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 6.[000176] In some embodiments, a bispecific antibody described herein comprises a second antigen binding site comprising a HC CDR1, a HC CDR2, and a HC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 1, HC CDR2 having the amino acid sequence of SEQ ID NO: 2, and HC CDR3 having the amino acid sequence of SEQ ID NO: 3. Alternatively or in addition, a bispecific antibody described herein comprises a second antigen binding site comprising a LC CDR1, a LC CDR2, and a LC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2 or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 4, LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 6.[000177] In some embodiments, a bispecific antibody described herein comprises a second antigen binding site comprising a HC CDR1, a HC CDR2, and a HC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 1, HC CDR2 having the amino acid sequence of SEQ ID NO: 2, and HC CDR3 having the amino acid sequence of SEQ ID NO: 3. Alternatively or in addition, a bispecific antibody described herein comprises a second antigen binding site comprising a LC CDR1, a LC CDR2, and a LC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99%, or 100%) identical to the to the LC CDR1 having the amino acid sequence of SEQ ID NO: 4, LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 6.[000178] In some embodiments, a bispecific antibody described herein comprises a second antigen binding site comprising a HC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 1; a HC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR2 having the amino acid sequence of SEQ ID NO: 2; and / or a HC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR3 having the amino acid sequence of SEQ ID NO: 3. Alternatively or in addition, a bispecific antibody described herein comprises a second antigen binding site comprising a LC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 4; a LC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR2 having the amino acid sequence of SEQ ID NO: ; and / or a LC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR3 having the amino acid sequence of SEQ ID NO: 6.[000179] In some embodiments, a bispecific antibody described herein comprises a second antigen binding site comprising a HC CDR1 at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 1; a HC at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the HC CDR2 having the amino acid sequence of SEQ ID NO: 2; and / or a HC CDR3 at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the HC CDR3 having the amino acid sequence of SEQ ID NO: 3. Alternatively or in addition, a bispecific antibody described herein comprises a second antigen binding site comprising a LC CDR1 at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the LC CDR1 having the amino acid sequence of SEQ ID NO: 4; a LC CDR2 atleast 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or a LC CDR3 at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the LC CDR3 having the amino acid sequence of SEQ ID NO: 6. [000180] In some embodiments, a bispecific antibody described herein comprises a second antigen binding site comprising a VH comprising the amino acid sequence of SEQ ID NO: 7. Alternatively or in addition a bispecific antibody described herein comprises a second antigen binding site comprising a VL comprising the amino acid sequence of SEQ ID NO: 8. In some embodiments, a bispecific antibody described herein comprises a second antigen binding site comprising a VH comprising the amino acid sequence of SEQ ID NO: 7, and a VL comprising the amino acid sequence of SEQ ID NO: 8.[000181] In some embodiments, a bispecific antibody described herein comprises a second antigen binding site comprising a VH containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VH as set forth in SEQ ID NO: 7. Alternatively or in addition, a bispecific antibody described herein comprises a second antigen binding site comprising a VL containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VL as set forth in SEQ ID NO: 8.[000182] In some embodiments, a bispecific antibody described herein comprises a second antigen binding site comprising a VH comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the VH as set forth in SEQ ID NO: 7. Alternatively or in addition, a bispecific antibody described herein comprises a second antigen binding site comprising a VL comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the VL as set forth in SEQ ID NO: 8.[000183] In some embodiments, a bispecific antibody described herein comprises a second antigen binding site comprising a comprises a VH containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VH as set forth in SEQ ID NO: 7.Alternatively or in addition, a bispecific antibody described herein comprises a second antigen binding site comprising a VL containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VL as set forth in SEQ ID NO: 8. In some embodiments, the number of amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) may occur within a VH of SEQ ID NO: 7 and / or a VL of SEQ ID NO: 8 excluding any of the CDR sequences therein. In some embodiments, a bispecific antibody described herein comprises a second antigen binding site comprising a heavy chain variable sequence that comprises a framework sequence that that contains no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation to the framework sequence of a VH of SEQ ID NO: 7, and / or a light chain variable sequence that comprises a framework sequence that that contains no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation to the framework sequence of a VL of SEQ ID NO: 8.[000184] In some embodiments, a bispecific antibody described herein comprises a second antigen binding site comprising a VH comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the VH as set forth in SEQ ID NO: 7. Alternatively or in addition, a bispecific antibody described herein comprises a second antigen binding site comprising a VL comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the VL as set forth in SEQ ID NO: 8. In some embodiments, the degree of sequence variation (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) may occur within a VH of SEQ ID NO: 7, and / or a VL of SEQ ID NO: 8 excluding any of the CDR sequences therein. In some embodiments, a bispecific antibody described herein comprises a second antigen binding site comprising a heavy chain variable sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the framework sequence of a VH of SEQ ID NO: 7, and / or a light chain variable sequence that comprises a framework sequence that at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the framework sequence of a VL of SEQ ID NO: 8.[000185] In some embodiments, a bispecific antibody described herein comprises a second antigen binding site comprising a HC CDR1, a HC CDR2 and a HC CDR3 of a heavy chain variable domain (VH) having the amino acid sequence of SEQ ID NO: 11. Alternatively or in addition, a bispecific antibody described herein comprises a second antigen binding site comprising a LC CDR1, a LC CDR2 and a LC CDR3 of a light chain variable domain (VL) having the amino acid sequence of SEQ ID NO: 8.[000186] In some embodiments, a bispecific antibody described herein comprises a second antigen binding site comprising a HC CDR3 having the amino acid sequence of SEQ ID NO: 10. In some embodiments, a bispecific antibody described herein comprises a second antigen binding site comprising a HC CDR1 having the amino acid sequence of SEQ ID NO: 1, a HC CDR2 having the amino acid sequence of SEQ ID NO: 9, and a HC CDR3 having the amino acid sequence of SEQ ID NO: 10. Alternatively or in addition, in some embodiments, a bispecific antibody described herein comprises a second antigen binding site comprising a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 6. In some embodiments, a bispecific antibody described herein comprises a second antigen binding site comprising a HC CDR1 having the amino acid sequence of SEQ ID NO: 1, a HC CDR2 having the amino acid sequence of SEQ ID NO: 9, a HC CDR3 having the amino acid sequence of SEQ ID NO: 10, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 6.[000187] In some embodiments, a bispecific antibody described herein comprises a second antigen binding site comprising a HC CDR1, a HC CDR2, and a HC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 1, HC CDR2 having the amino acid sequence of SEQ ID NO: 9, and HC CDR3 having the amino acid sequence of SEQ ID NO: 10. Alternatively or in addition, a bispecific antibody described herein comprises a second antigen binding site comprising a LC CDR1, a LC CDR2, and a LC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2 or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 4, LC CDR2 having the amino acidsequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 6.[000188] In some embodiments, a bispecific antibody described herein comprises a second antigen binding site comprising a HC CDR1, a HC CDR2, and a HC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 1, HC CDR2 having the amino acid sequence of SEQ ID NO: 9, and HC CDR3 having the amino acid sequence of SEQ ID NO: 10. Alternatively or in addition, a bispecific antibody described herein comprises a second antigen binding site comprising a LC CDR1, a LC CDR2, and a LC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the to the LC CDR1 having the amino acid sequence of SEQ ID NO: 4, LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 6.[000189] In some embodiments, a bispecific antibody described herein comprises a second antigen binding site comprising a HC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 1; a HC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR2 having the amino acid sequence of SEQ ID NO: 9; and / or a HC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR3 having the amino acid sequence of SEQ ID NO: 10. Alternatively or in addition, a bispecific antibody described herein comprises a second antigen binding site comprising a LC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 4; a LC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or a LC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR3 having the amino acid sequence of SEQ ID NO: 6.[000190] In some embodiments, a bispecific antibody described herein comprises a second antigen binding site comprising a HC CDR1 at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, atleast 97%, at least 98%, at least 99%, or 100%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 1; a HC at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the HC CDR2 having the amino acid sequence of SEQ ID NO: 9; and / or a HC CDR3 at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the HC CDR3 having the amino acid sequence of SEQ ID NO: 10. Alternatively or in addition, a bispecific antibody described herein comprises a second antigen binding site comprising a LC CDR1 at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the LC CDR1 having the amino acid sequence of SEQ ID NO: 4; a LC CDR2 at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or a LC CDR3 at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the LC CDR3 having the amino acid sequence of SEQ ID NO: 6. [000191] Typically, each of the two antigen binding sites is present within an “arm” of a bispecific antibody. In some embodiments, an arm of a bispecific antibody is configured as a monospecific antibody, e.g., a full-length IgG or a fragment thereof. In some embodiments, a bispecific antibody comprises two arms, one or each of which is configured as an Fv region that confers specificity to distinct antigen residues. In some embodiments, a bispecific antibody comprises two arms of the same configuration in any other suitable format. In some embodiments, a bispecific antibody comprises two arms of two different configurations. In some embodiments, a bispecific antibody comprises a first arm that is configured as a Fab, a Fab’, or a scFv and that comprises the first antigen binding site (e.g., a first antigen binding site that specifically binds a cancer antigen or a pathogen-derived antigen). In some embodiments, a bispecific antibody comprises a second arm that is configured as a Fab, a Fab’, or a scFv and that comprises the second antigen binding site (e.g., a second antigen binding site that specifically binds CD3). In some embodiments, a bispecific antibody comprises a first arm that is configured as an scFv that comprises a first antigen binding site (e.g., a first antigen binding site that specifically binds a cancer antigen or a pathogen-derived antigen). In some embodiments, a bispecific antibody comprises a first arm that is configuredas a Fab that comprises a first antigen binding site (e.g., a first antigen binding site that specifically binds a cancer antigen or a pathogen-derived antigen). In some embodiments, a bispecific antibody comprises a first arm that is configured as a Fab’ that comprises a first antigen binding site (e.g., a first antigen binding site that specifically binds a cancer antigen or a pathogen-derived antigen). In some embodiments, a bispecific antibody comprises a second arm that is configured as an scFv that comprises a second antigen binding site (e.g., a second antigen binding site that specifically binds CD3). In some embodiments, a bispecific antibody comprises a second arm that is configured as a Fab that comprises a second antigen binding site (e.g., a second antigen binding site that specifically binds CD3). In some embodiments, a bispecific antibody comprises a second arm that is configured as a Fab’ that comprises a second antigen binding site (e.g., a second antigen binding site that specifically binds CD3).[000192] In some embodiments, a bispecific antibody comprises a first arm that is configured as an scFv that comprises a first antigen binding site (e.g., a first antigen binding site that specifically binds a cancer antigen or a pathogen-derived antigen) and a second arm that is configured as an scFv that comprises a second antigen binding site (e.g., a second antigen binding site that specifically binds CD3). In some embodiments, a bispecific antibody comprises a first arm that is configured as an scFv that comprises a first antigen binding site (e.g., a first antigen binding site that specifically binds a cancer antigen or a pathogen-derived antigen), and a second arm that is configured as a Fab that comprises a second antigen binding site (e.g., a second antigen binding site that specifically binds CD3). In some embodiments, a bispecific antibody comprises a first arm that is configured as an scFv that comprises a first antigen binding site (e.g., a first antigen binding site that specifically binds a cancer antigen or a pathogen-derived antigen), and a second arm that is configured as a Fab’ that comprises a second antigen binding site (e.g., a second antigen binding site that specifically binds CD3). In some embodiments, a bispecific antibody comprises a first arm that is configured as a Fab that comprises a first antigen binding site (e.g., a first antigen binding site that specifically binds a cancer antigen or a pathogen-derived antigen), and a second arm that is configured as a Fab’ that comprises a second antigen binding site (e.g., a second antigen binding site that specifically binds CD3). In some embodiments, a bispecific antibody comprises a first arm that is configured as a Fab that comprises a first antigen binding site (e.g., a first antigen binding site that specifically binds a cancer antigen or a pathogen-derived antigen), and a second arm that is configured as an scFv that comprises a second antigen binding site (e.g., a second antigen binding site that specifically binds CD3).In some embodiments, a bispecific antibody comprises a first arm that is configured as a Fab that comprises a first antigen binding site (e.g., a first antigen binding site that specifically binds a cancer antigen or a pathogen-derived antigen), and a second arm that is configured as a Fab that comprises a second antigen binding site (e.g., a second antigen binding site that specifically binds CD3). In some embodiments, a bispecific antibody comprises a first arm that is configured as a Fab’ that comprises a first antigen binding site (e.g., a first antigen binding site that specifically binds a cancer antigen or a pathogen-derived antigen), and a second arm that is configured as a Fab’ that comprises a second antigen binding site (e.g., a second antigen binding site that specifically binds CD3) that is a Fab’. In some embodiments, a bispecific antibody comprises a first arm that is configured as a Fab’ that comprises a first antigen binding site (e.g., a first antigen binding site that specifically binds a cancer antigen or a pathogen-derived antigen), and a second arm that is configured as a Fab that comprises a second antigen binding site (e.g., a second antigen binding site that specifically binds CD3). In some embodiments, a bispecific antibody comprises a first arm that is configured as a Fab’ that comprises a first antigen binding site (e.g., a first antigen binding site that specifically binds a cancer antigen or a pathogen-derived antigen), and a second arm that is configured as an scFv that comprises a second antigen binding site (e.g., a second antigen binding site that specifically binds CD3).[000193] In some embodiments, a bispecific antibody does not comprise an Fc region. In some embodiments, the two arms of a bispecific antibody are linked directly. In some embodiments, the two arms of a bispecific antibody are linked by a linker. In some embodiments, a bispecific antibody comprises an Fc region, e.g., a dimeric Fc or a monomeric Fc. In some embodiments, a bispecific antibody comprises a monomeric Fc. In some embodiments, a bispecific antibody comprises one arm linked to one end (e.g., the N terminal) of a monomeric Fc and a second arm linked to the other end (e.g., the C terminal) of the monomeric Fc. In some embodiments, a bispecific antibody comprises a dimeric Fc region. In some embodiments, a bispecific antibody comprises two arms that are oriented symmetrically around an Fc region (e.g., each Fc monomer of a dimeric Fc region is linked to one arm). In some embodiments, a bispecific antibody comprises two distinct heavy chains and two distinct light chains, with each heavy chain / light chain pair having different antigen binding specificity. In some embodiments, a bispecific antibody comprises two arms that are oriented asymmetrically around an Fc (e.g., the two arms of the bispecific antibody are linked to one of the monomers of a dimeric Fc region).[000194] In some embodiments, a bispecific antibody comprises a monomeric Fc region containing mutations which abolish Fc gamma receptor (FcyR) binding, resulting in loss of effector functions in immune cells that would typically bind FcyRs, such as phagocytosis and cytokine release. In some embodiments, a bispecific antibody comprises a monomeric human serum albumin (HSA). In some embodiments, a bispecific antibody comprises an anti-HSA domain. In some embodiments, a bispecific antibody comprises an anti-HSA domain configured as a VHH antibody.[000195] In some embodiments, the ratio of the first antigen binding site (e.g., a first antigen binding site that specifically binds a cancer antigen or a pathogen-derived antigen) and a second antigen binding site (e.g., a second antigen binding site that specifically binds CD3) of a bispecific antibody is 1:1, 1:2, 1:3, 1:4, 1:5, 2:3, 2:5, 3:4, 3:5, 4:5, 5:4, 5:3, 5:2, 3:2, 5:1, 4:1, 3:1, or 2:1. In some embodiments, a bispecific antibody comprises a first Fc region and a second Fc region. In some embodiments, a bispecific antibody does not include a Fc region. In some embodiments, a bispecific antibody can be constructed and assembled using any suitable methods into any suitable configurations, e.g., methods and configurations described by Ma et al., Bispecific Antibodies: From Research to Clinical Application, Front. Immunol., 05 May 2021, Sec. Cancer Immunity and Immunotherapy, Volume 12 - 2021, the entire contents are incorporated herein by reference.III. Preparation of an anti-CD3 antibody[000196] Antibodies capable of binding CD3 as described herein can be made by any method known in the art. See, for example, Harlow and Lane, (1998) Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, New York.[000197] In some embodiments, antibodies specific to a target antigen (e.g., CD3) can be made by the conventional hybridoma technology. The full-length target antigen or a fragment thereof, optionally coupled to a carrier protein such as KLH, can be used to immunize a host animal for generating antibodies binding to that antigen. The route and schedule of immunization of the host animal are generally in keeping with established and conventional techniques for antibody stimulation and production, as further described herein. General techniques for production of mouse, humanized, and human antibodies are known in the art and are described herein. It is contemplated that any mammalian subject including humans or antibody producing cells therefrom can be manipulated to serve as the basis for production of mammalian, including human hybridoma cell lines. Typically, the host animal is inoculatedintraperitoneally, intramuscularly, orally, subcutaneously, intraplantar, and / or intradermally with an amount of immunogen, including as described herein.[000198] If desired, an antibody (monoclonal or polyclonal) of interest (e.g., produced by a hybridoma) may be sequenced and the polynucleotide sequence may then be cloned into a vector for expression or propagation. The sequence encoding the antibody of interest may be maintained in vector in a host cell and the host cell can then be expanded and frozen for future use. In an alternative, the polynucleotide sequence may be used for genetic manipulation to "humanize" the antibody or to improve the affinity (affinity maturation), or other characteristics of the antibody. For example, the constant region may be engineered to more resemble human constant regions to avoid immune response if the antibody is used in clinical trials and treatments in humans. It may be desirable to genetically manipulate the antibody sequence to obtain greater affinity to the target antigen and greater efficacy. It will be apparent to one of skill in the art that one or more polynucleotide changes can be made to the antibody and still maintain its binding specificity to the target antigen.[000199] In other embodiments, fully human antibodies can be obtained by using commercially available mice that have been engineered to express specific human immunoglobulin proteins. Transgenic animals that are designed to produce a more desirable (e.g., fully human antibodies) or more robust immune response may also be used for generation of humanized or human antibodies. Examples of such technology are XenomouseRTM from Amgen, Inc. (Fremont, CA) and HuMAb-MouseRTM and TC MouseTM from Medarex, Inc. (Princeton, NJ) or H2L2 mice from Harbour Antibodies BV (Holland). In another alternative, antibodies may be made recombinantly by phage display or yeast technology. See, for example, U.S. Pat. Nos. 5,565,332; 5,580,717; 5,733,743; and 6,265,150; and Winter et al., (1994) Annu. Rev. Immunol. 12:433-455. Alternatively, the phage display technology (McCafferty et al., (1990) Nature 348:552-553) can be used to produce human antibodies and antibody fragments in vitro, from immunoglobulin variable (V) domain gene repertoires from unimmunized donors.[000200] Antigen-binding fragments of an intact antibody (full-length antibody) can be prepared via routine methods. For example, F(ab')2 fragments can be produced by pepsin digestion of an antibody molecule, and Fab fragments that can be generated by reducing the disulfide bridges of F(ab')2 fragments. Genetically engineered antibodies, such as humanized antibodies, chimeric antibodies, single-chain antibodies, and bi-specific antibodies, can be produced via, e.g., conventional recombinant technology. In one example, DNA encoding a monoclonal antibodies specific to a target antigen can be readily isolated and sequencedusing conventional procedures e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of the monoclonal antibodies). The hybridoma cells serve as a preferred source of such DNA. Once isolated, the DNA may be placed into one or more expression vectors, which are then transfected into host cells such as E. coli cells, simian COS cells, Chinese hamster ovary (CHO) cells, human HEK293 cells, or myeloma cells that do not otherwise produce immunoglobulin protein, to obtain the synthesis of monoclonal antibodies in the recombinant host cells. See, e.g., PCT Publication No. WO 87 / 04462. The DNA can then be modified, for example, by substituting the coding sequence for human heavy and light chain constant domains in place of the homologous murine sequences, Morrison et al., (1984) Proc. Nat. Acad. Sci. 81:6851, or by covalently joining to the immunoglobulin coding sequence all or part of the coding sequence for a non-immunoglobulin polypeptide. In that manner, genetically engineered antibodies, such as “chimeric” or “hybrid” antibodies; can be prepared that have the binding specificity of a target antigen.[000201] A single-chain antibody can be prepared via recombinant technology by linking a nucleotide sequence coding for a heavy chain variable region and a nucleotide sequence coding for a light chain variable region. Preferably, a flexible linker is incorporated between the two variable regions.[000202] Alternatively, techniques described for the production of single chain antibodies (U.S. Patent Nos. 4,946,778 and 4,704,692) can be adapted to produce a phage or yeast scFv library and scFv clones specific to CD3 can be identified from the library following routine procedures. Positive clones can be subjected to further screening to identify those that have high CD3 binding affinity.[000203] Antibodies obtained following a method known in the art and described herein can be characterized using methods well known in the art. For example, one method is to identify the epitope to which the antigen binds, or “epitope mapping.” There are many methods known in the art for mapping and characterizing the location of epitopes on proteins, including solving the crystal structure of an antibody-antigen complex, competition assays, gene fragment expression assays, and synthetic peptide-based assays, as described, for example, in Chapter 11 of Harlow and Lane, Using Antibodies, a Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1999. In one example, epitope mapping can be accomplished using H / D-Ex (hydrogen deuterium exchange) coupled with proteolysis and mass spectrometry. In an additional example, epitope mapping can be used to determine the sequence to which an antibody binds. The epitope can be a linear epitope, i.e.,contained in a single stretch of amino acids, or a conformational epitope formed by a three- dimensional interaction of amino acids that may not necessarily be contained in a single stretch (primary structure linear sequence). Peptides of varying lengths (e.g., at least 4-6 amino acids long) can be isolated or synthesized (e.g., recombinantly) and used for binding assays with an antibody. In another example, the epitope to which the antibody binds can be determined in a systematic screening by using overlapping peptides derived from the target antigen sequence and determining binding by the antibody. According to the gene fragment expression assays, the open reading frame encoding the target antigen is fragmented either randomly or by specific genetic constructions and the reactivity of the expressed fragments of the antigen with the antibody to be tested is determined. The gene fragments may, for example, be produced by PCR and then transcribed and translated into protein in vitro, in the presence of radioactive amino acids. The binding of the antibody to the radioactively labeled antigen fragments is then determined by immunoprecipitation and gel electrophoresis.Certain epitopes can also be identified by using large libraries of random peptide sequences displayed on the surface of phage particles (phage libraries). Alternatively, a defined library of overlapping peptide fragments can be tested for binding to the test antibody in simple binding assays. In an additional example, mutagenesis of an antigen binding domain, domain swapping experiments and alanine scanning mutagenesis can be performed to identify residues required, sufficient, and / or necessary for epitope binding. Alternatively, competition assays can be performed using other antibodies known to bind to the same antigen to determine whether an antibody binds to the same epitope as the other antibodies. Competition assays are well known to those of skill in the art.[000204] In some examples, an anti-CD3 antibody is prepared by recombinant technology as exemplified below. Nucleic acids encoding the heavy and light chain of an anti-CD3 antibody as described herein can be cloned into one expression vector, each nucleotide sequence being in operable linkage to a suitable promoter. In one example, each of the nucleotide sequences encoding the heavy chain and light chain is in operable linkage to a distinct promoter. Alternatively, the nucleotide sequences encoding the heavy chain and the light chain can be in operable linkage with a single promoter, such that both heavy and light chains are expressed from the same promoter. When necessary, an internal ribosomal entry site (IRES) can be inserted between the heavy chain and light chain encoding sequences.[000205] In some examples, the nucleotide sequences encoding the two chains of the antibody are cloned into two vectors, which can be introduced into the same or different cells. When the two chains are expressed in different cells, each of them can be isolated from thehost cells expressing such and the isolated heavy chains and light chains can be mixed and incubated under suitable conditions allowing for the formation of the antibody.[000206] Generally, a nucleic acid sequence encoding one or all chains of an antibody can be cloned into a suitable expression vector in operable linkage with a suitable promoter using methods known in the art. For example, the nucleotide sequence and vector can be contacted, under suitable conditions, with a restriction enzyme to create complementary ends on each molecule that can pair with each other and be joined together with a ligase. Alternatively, synthetic nucleic acid linkers can be ligated to the termini of a gene. These synthetic linkers contain nucleic acid sequences that correspond to a particular restriction site in the vector. The selection of expression vectors / promoter would depend on the type of host cells for use in producing the antibodies.[000207] A variety of promoters can be used for expression of the antibodies described herein, including, but not limited to, cytomegalovirus (CMV) intermediate early promoter, a viral LTR such as the Rous sarcoma virus LTR, HIV-LTR, HTLV-1 LTR, the simian virus 40 (SV40) early promoter, E. coli lac UV promoter, and the herpes simplex tk virus promoter.[000208] Regulatable promoters can also be used. Such regulatable promoters include those using the lac repressor from E. coli as a transcription modulator to regulate transcription from lac operator bearing mammalian cell promoters [[Brown, M. et al., Cell, 49:603-612 (1987)]], those using the tetracycline repressor (tetR) [[Gossen, M., and Bujard, H., Proc. Natl. Acad. Sci. USA 89:5547-555115 (1992); Yao, F. et al., Human Gene Therapy, 9:1939-1950 (1998); Shockelt, P., et al., Proc. Natl. Acad. Sci. USA, 92:6522-6526 (1995)]]. Other systems include FK506 dimer, VP 16 or p65 using astradiol, RU486, diphenol murislerone, or rapamycin. Inducible systems are available from Invitrogen, Clontech and Ariad, among others.[000209] Regulatable promoters that include a repressor with the operon can be used. In one embodiment, the lac repressor from E. coli can function as a transcriptional modulator to regulate transcription from lac operator-bearing mammalian cell promoters [[M. Brown et al., Cell, 49:603-612 (1987)]]; Gossen and Bujard (1992); [[M. Gossen et al., Natl. Acad. Sci. USA, 89:5547-5551(1992)]] combined the tetracycline repressor (tetR) with the transcription activator (VP 16) to create a tetR-mammalian cell transcription activator fusion protein, tTa (tetR- VP 16), with the tetO bearing minimal promoter derived from the human cytomegalovirus (hCMV) promoter to create a tetR-tet operator system to control gene expression in mammalian cells. In one embodiment, a tetracycline inducible switch is used.The tetracycline repressor (tetR) alone, rather than the tetR-mammalian cell transcription factor fusion derivatives can function as potent trans-modulator to regulate gene expression in mammalian cells when the tetracycline operator is properly positioned downstream for the TATA element of the CMVIE promoter (Yao et al., Human Gene Therapy). One particular advantage of this tetracycline inducible switch is that it does not require the use of a tetracycline repressor-mammalian cells transactivator or repressor fusion protein, which in some instances can be toxic to cells (Gossen et al., Natl. Acad. Sci. USA, 89:5547-5551 (1992); Shockett et al., Proc. Natl. Acad. Sci. USA, 92:6522-6526 (1995)), to achieve its regulatable effects.[000210] Additionally, the vector can contain, for example, some or all of the following: a selectable marker gene, such as the neomycin gene for selection of stable or transient transfectants in mammalian cells; enhancer / promoter sequences from the immediate early gene of human CMV for high levels of transcription; transcription termination and RNA processing signals from SV40 for mRNA stability; SV40 polyoma origins of replication and ColEl for proper episomal replication; internal ribosome binding sites (IRESes), versatile multiple cloning sites; and T7 and SP6 RNA promoters for in vitro transcription of sense and antisense RNA. Suitable vectors and methods for producing vectors containing transgenes are well known and available in the art. Examples of polyadenylation signals useful to practice the methods described herein include, but are not limited to, human collagen I poly adenylation signal, human collagen II poly adenylation signal, and SV40 poly adenylation signal.[000211] One or more vectors (e.g., expression vectors) comprising nucleic acids encoding any of the antibodies (e.g.. the nucleic acid coding sequence listed in Table 3) may be introduced into suitable host cells for producing the antibodies. Non-limiting examples of the host cells include Chinese hamster ovary (CHO) cells, dhfr- CHO cell, human embryonic kidney (HEK)-293 cells, verda reno (VERO) cells, nonsecreting null (NS0) cells, human embryonic retinal (PER.C6) cells, Sp2 / 0 cells, baby hamster kidney (BHK) cells, Madin- Darby Canine Kidney (MDCK) cells, Madin-Darby Bovine Kidney (MDBK) cells, and monkey kidney CV1 line transformed by SV40 (COS) cells. In some embodiments, the host cell expressing an anti-CD3 antibody are CHO cells. The host cells can be cultured under suitable conditions for expression of the antibody or any polypeptide chain thereof. Such antibodies or polypeptide chains thereof can be recovered by the cultured cells (e.g.. from the cells or the culture supernatant) via a conventional method, e.g., affinity purification. If necessary, polypeptide chains of the antibody can be incubated under suitable conditions for asuitable period of time allowing for production of the antibody. In some embodiments, the host cell comprises the nucleic acid encoding the heavy chain of the anti-CD3 antibody. In some embodiments, the host cell comprises the nucleic acid encoding the light chain of the anti-CD3 antibody. In some embodiments, the host cell comprises the nucleic acid encoding the heavy chain and the nucleic acid encoding the light chain.[000212] In some embodiments, methods for preparing an antibody described herein involve a recombinant expression vector that encodes both the heavy chain and the light chain of an anti-CD3 antibody, as also described herein. The recombinant expression vector can be introduced into a suitable host cell (e.g., a dhfr- CHO cell) by a conventional method, e.g., calcium phosphate mediated transfection. Positive transformant host cells can be selected and cultured under suitable conditions allowing for the expression of the two polypeptide chains that form the antibody, which can be recovered from the cells or from the culture medium. When necessary, the two chains recovered from the host cells can be incubated under suitable conditions allowing for the formation of the antibody.[000213] In one example, two recombinant expression vectors are provided, one encoding the heavy chain of the anti-CD3 antibody and the other encoding the light chain of the anti-CD3 antibody. Both of the two recombinant expression vectors can be introduced into a suitable host cell e.g., dhfr- CHO cell) by a conventional method, e.g., calcium phosphate-mediated transfection.[000214] Alternatively, each of the expression vectors can be introduced into a suitable host cells. Positive transformants can be selected and cultured under suitable conditions allowing for the expression of the polypeptide chains of the antibody. When the two expression vectors are introduced into the same host cells, the antibody produced therein can be recovered from the host cells or from the culture medium. If necessary, the polypeptide chains can be recovered from the host cells or from the culture medium and then incubated under suitable conditions allowing for formation of the antibody. When the two expression vectors are introduced into different host cells, each of them can be recovered from the corresponding host cells or from the corresponding culture media. The two polypeptide chains can then be incubated under suitable conditions for formation of the antibody.[000215] Standard molecular biology techniques are used to prepare the recombinant expression vector, transfect the host cells, select for transformants, culture the host cells and recovery of the antibodies from the culture medium. For example, some antibodies can be isolated by affinity chromatography with a Protein A or Protein G coupled matrix.[000216] Any of the nucleic acids encoding the heavy chain, the light chain, or both of an anti-CD3 antibody as described herein (e.g., as provided in Table 3), vectors (e.g., expression vectors) containing such; and host cells comprising the vectors are within the scope of the present disclosure.[000217] Table 3: Nucleic acids sequences encoding the VH / VL of anti-CD3 binders listed in Table.[000218] In some embodiments, the present disclosure provides an isolated nucleic acid comprising a sequence at least 60% (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) identical to SEQ ID NO: 12. In some embodiments, the present disclosure provides an isolated nucleic acid comprising a sequenceat least 60% (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) identical to SEQ ID NO: 13.[000219] In some embodiments, the present disclosure provides an isolated nucleic acid comprising a sequence at least 60% (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) identical to SEQ ID NO: 14. In some embodiments, the present disclosure provides an isolated nucleic acid comprising a sequence at least 60% (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) identical to SEQ ID NO: 13.[000220] It should be understood that an antibody provided herein may be produced by expressing a polypeptide comprising the heavy chain and light chain CDRs of any antibody provided herein. In some embodiments, a single polypeptide comprises a HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3 of any antibody provided herein. In some embodiments, a polypeptide (e.g., a first polypeptide) comprises a HC CDR1, HC CDR2, and HC CDR3 of any antibody provided herein and a polypeptide (e.g., a second polypeptide) comprises a LC CDR1, LC CDR2, and LC CDR3 of any antibody provided herein. In some embodiments, the first polypeptide and the second polypeptide form a polypeptide complex. A polypeptide complex may be further modified (e.g., by protein folding, by post-translational modifications, or any other modification either singly or in combination). In some embodiments, a polypeptide complex is any antibody provided herein.[000221] In some embodiments, the present disclosure provides an expression vector encoding an anti-CD3 antibody described herein. In some embodiments, the expression vector comprises an isolated nucleic acid at least 60% (e.g., at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 12. In some embodiments, the expression vector comprises an isolated nucleic acid at least 60% (e.g., at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 13. In some embodiments, the expression vector comprises an isolated nucleic acid at least 60% (e.g., at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 12, and an isolated nucleic acid at least 60% (e.g., at least 60%, at least 65%, at least10%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 13.[000222] In some embodiments, the present disclosure provides an expression vector encoding an anti-CD3 antibody described herein. In some embodiments, the expression vector comprises an isolated nucleic acid at least 60% (e.g., at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 14. In some embodiments, the expression vector comprises an isolated nucleic acid at least 60% (e.g., at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 13. In some embodiments, the expression vector comprises an isolated nucleic acid at least 60% (e.g., at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 14, and an isolated nucleic acid at least 60% (e.g., at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 13.[000223] In some embodiments, an anti-CD3 antibody described herein is produced by expressing in a recombinant cell: (i) an isolated nucleic acid at least 60% (e.g., at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 12, and / or (ii) an isolated nucleic acid at least 60% (e.g., at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 13.[000224] In some embodiments, the anti-CD3 antibody described herein is produced by expressing in a recombinant cell an expression vector comprising: (i) an isolated nucleic acid at least 60% (e.g., at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 14, and / or (ii) an isolated nucleic acid at least 60% (e.g., at least 60%, at least 65%, at least 70%, at least75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 13.[000225] In some embodiments, the present disclosure provides a recombinant cell (e.g., a recombinant cell for producing the antibody) expressing the anti-CD3 antibody described herein.[000226] Accordingly, the present disclosure provides methods for producing the antibody, the methods comprising culturing the recombinant cells under conditions suitable for expression of the antibody from the expression vector by the recombinant cell. Recombinant cells expressing the antibody can be cultured in any suitable condition known in the art. In some embodiments, the method further comprises isolating the antibody from the culture media in which the cell or cells were cultured using any suitable known methods in the art.IV. Pharmaceutical Composition[000227] The antibodies, as well as the encoding nucleic acids or nucleic acid sets, vectors comprising such, or host cells comprising the vectors, as described herein can be mixed with a pharmaceutically acceptable carrier (excipient) to form a pharmaceutical composition for use in treating a target disease. “Acceptable” means that the carrier must be compatible with the active ingredient of the composition (and preferably, capable of stabilizing the active ingredient) and not deleterious to the subject to be treated. Pharmaceutically acceptable excipients (carriers) including buffers, which are well known in the art. See, e.g., Remington: The Science and Practice of Pharmacy 20th Ed. (2000) Lippincott Williams and Wilkins, Ed. K. E. Hoover.[000228] The anti-CD3 antibody containing pharmaceutical composition disclosed herein may further comprise a suitable buffer agent. A buffer agent is a weak acid or base used to maintain the pH of a solution near a chosen value after the addition of another acid or base. In some examples, the buffer agent disclosed herein can be a buffer agent capable of maintaining physiological pH despite changes in carbon dioxide concentration (produced by cellular respiration). Exemplary buffer agents include, but are not limited to, a HEPES (4-(2- hydroxyethyl)-l -piperazineethanesulfonic acid) buffer, Dulbecco's phosphate-buffered saline (DPBS) buffer, or Phosphate-buffered Saline (PBS) buffer. Such buffers may comprise disodium hydrogen phosphate and sodium chloride, or potassium dihydrogen phosphate and potassium chloride.[000229] In some embodiments, the buffer agent in the pharmaceutical composition described herein may maintain a pH value of about 5-8. For example, the pH of the pharmaceutical composition can be about 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, or 8.0. In other examples, the pharmaceutical composition may have a pH value lower than 7, for example, about 7, 6.8, 6.5, 6.3, 6, 5.8, 5.5, 5.3, or 5.[000230] The pharmaceutical composition described herein comprises one or more suitable salts. A salt is an ionic compound that can be formed by the neutralization reaction of an acid and a base. (Skoog, D.A; West, D.M.; Holler, J.F.; Crouch, S.R. (2004). “Chapters 14-16”. Fundamentals of Analytical Chemistry (8th ed.)). Salts are composed of related numbers of cations (positively charged ions) and anions (negative ions) so that the product is electrically neutral (without a net charge).[000231] In some embodiments, the pharmaceutical compositions can comprise pharmaceutically acceptable carriers, excipients, or stabilizers in the form of lyophilized formulations or aqueous solutions. (Remington: The Science and Practice of Pharmacy 20th Ed. (2000) Lippincott Williams and Wilkins, Ed. K. E. Hoover). In some embodiments, the pharmaceutical composition can be formulated for intravenous injection. In some embodiments, the pharmaceutical composition can be formulated for subcutaneous injection. The pharmaceutical compositions to be used for in vivo administration must be sterile. This is readily accomplished by, for example, filtration through sterile filtration membranes. Therapeutic antibody compositions are generally placed into a container having a sterile access port, for example, an intravenous or subcutaneous solution bag or vial having a stopper pierceable by a hypodermic injection needle.V. Methods of Use[000232] Aspects of the disclosure relate to compositions and methods for treating autoimmune disorders. Many autoimmune disorders are mediated by T cells bearing T cell receptors (TCRs) that recognize antigen similar to or the same as endogenously-expressed proteins. Upon recognition of endogenous cognate antigen, such T cells become aberrantly activated and mount a response against host cells, resulting in tissue degeneration and disease. T cell-mediated autoimmune diseases include rheumatoid arthritis, type-1 diabetes, systemic lupus erythematosus, atherosclerotic cardiovascular disease, myositis, psoriasis / psoriatic arthritis, vasculitis, and others. Graft-versus-host-disease (GVHD), initiated following transplant of cells or tissue from a donor into a recipient, is also mediatedby T cells. Thus, depletion of T cells via administration of anti-CD3 antibodies provided herein may be useful for treating autoimmune disorders or ameliorating the associated symptoms, or for depleting endogenous recipient T cells that would otherwise mount an attack against donor cells or tissue ahead of allogeneic cell or tissue transplant.[000233] Other aspects of the disclosure relate to compositions and methods for treating cancer or infection. In the context of chronic exposure of T cells to antigen, such as in cancer or chronic (long-term) infection, T cells can become exhausted or fail to mount a persistently robust response. Administration of anti-CD3 therapy (e.g., administration of anti-CD3 antibodies provided herein) can rescue the function of exhausted T cells by reactivating them to restore cytolytic activity or by inducing their proliferation, thereby increasing the pool of responding T cells.[000234] Additionally, an anti-CD3 antibody may comprise two binding sites, a second site which specifically binds to CD3 and first binding site which binds to a cancer antigen or a pathogen-derived antigen. In some embodiments, the second binding site specifically binds to a cancer antigen. In some embodiments, the cancer antigens include but are not limited to CD13, CD14, CD15, CD19, CD20, CD22, CD30, CD33, CD38, CD41, CD61, CD64, CD68, CD70, CD117, CD123, CD138, CD267, CD269, Claudinl8.2, DLL3, HER2 / neu, PSA (pro state- specific antigen), PSMA, CEA (carcinoembryonic antigen), NY-ESO-1, glypican-3, EGFR, EGFRvIII, MAGE (melanoma antigens), MAGE -Al, MAGE-A3, MAGE-A4, MAGE-A8, MSLN (mesothelin), BCMA, TACI, alpha-fetoprotein, BAFF, FLT3, CA 9-19, CA 72-4, FAP, MART-1, F77, GD2, CT83, H0RMAD1, glycoprotein (gp) 100, HPV16, WT1, or PRAME. In some embodiments, the cancer antigen is WT1. In some embodiments, the cancer antigen is PRAME. In some embodiments, the cancer antigen is BCMA.[000235] In some embodiments, the second binding site specifically binds to a pathogen- derived antigen. In some embodiments, the pathogen-derived antigens are derived from pathogens that include but are not limited to HIV, HPV, RSV, influenza, Epstein-Barr virus (EBV), cytomegalovirus (CMV), Dengue virus (DNV), Zika virus (ZIKV), SARS-CoV-2, Staphyloccocus species (e.g., S. aureus, S. pneumoniae, and others), Enterococcus spp. (e.g., E. faecium and others), Klebsiella spp. (e.g., K. pneumoniae and others), Acinetobacter spp. (e.g., A. baumannii and others), Pseudomonas spp. (e.g., P. aeruginosa and others, Enterobacter spp. (e.g., E. cloacae, E. aerogenes, and others), Plasmodium spp. (e.g., P. falciparum, P. vivax, and others), Trypanosoma spp. (e.g., T. brucei gambiense, T. bruceirhodesiense, and others), Schistosoma spp. (e.g., S. mansoni, S. haematobium, S. japonicum), T. solium, and E. histolytica.[000236] By binding CD3 with a second binding site and a cancer antigen or a pathogen- derived antigen with a first binding site, an anti-CD3 antibody direct cytotoxic T cells against CD3 expressing cancer cells, inducing death in those cancer cells.[000237] In some aspects, the disclosure features a method for treating cancer or infection (e.g., by redirected CD3 -expressing cells, T cells, to a cancer cell to kill it or an infected cell to kill it), the method comprising administering to a subject in need an effective amount of a therapeutic agent, wherein the therapeutic agent is or comprises: (i) any one or more of the antibodies or antigen-binding fragments thereof described herein (including conjugates), (ii) any one or more of the fusion proteins described herein, (iii) any one or more of the bispecific or multispecific polypeptides described herein; (iv) any one or more of the nucleic acids described herein; (v) any one or more of the expression vectors described herein; (vi) any one or more of the recombinant cells described herein; (vii) any one or more of the isolated polypeptides described herein; and / or (viii) any one or more of the pharmaceutical compositions described herein.[000238] In certain embodiments, the therapeutic agent can be administered through injection by intravenous, intraperitoneal, intracerebral (intra-parenchymal), intracerebroventricular, intramuscular, subcutaneously, intra-ocular, intraarterial, intraportal, or intralesional routes; by sustained release systems or by implantation devices. In certain embodiments, the compositions can be administered by bolus injection or continuously by infusion, or by implantation device.[000239] Determination of whether an amount of the antibody (e.g., anti-CD3 antibody) achieved the therapeutic effect would be evident to one of skill in the art based on the teachings provided herein. Effective amounts vary, as recognized by those skilled in the art, depending on the particular condition being treated, the severity of the condition, the individual patient parameters including age, physical condition, size, gender and weight, the duration of the treatment, the nature of concurrent therapy (if any), the specific route of administration and like factors within the knowledge and expertise of the health practitioner. The particular dosage regimen, i.e., dose, timing and repetition, used in the method described herein will depend on the particular subject and that subject's medical history, as discussed herein.[000240] Empirical considerations, such as time to maximum effect, the half-life, and / or time above a specific concentration generally will contribute to the determination of the dosage.For example, antibodies that are compatible with the human immune system, such as humanized antibodies or fully human antibodies, may be used to prolong half-life of the antibody and to prevent the antibody being attacked by the host's immune system. Other reasons for dose-adjusting include differences in pharmacokinetics or pharmacodynamic response driven by sex, age, individual response, polymorphisms on the antibody target and / or receptors involved in antibody clearance. Frequency of administration may be determined and adjusted over the course of therapy, and is generally, but not necessarily, based on treatment and / or suppression and / or amelioration and / or delay of a target disease / disorder. Alternatively, sustained continuous release formulations of an antibody may be appropriate. Various formulations and devices for achieving sustained release are known in the art.[000241] Dosing frequencies may vary in accordance with the claimed methods. In some embodiments, a composition may be administered once. In some embodiments, a composition will be administered on multiple occasions. In some embodiments, dosing frequency is every week, every 2 weeks, every 3 weeks, every 4 weeks, every 5 weeks, every 6 weeks, every 7 weeks, every 8 weeks, every 9 weeks, or every 10 weeks; or once every month, every 2 months, or every 3 months, or longer. In some embodiments, a composition will be administered daily, biweekly, weekly, bimonthly, monthly, or at any time interval that provides suitable (e.g., maximal) efficacy while minimizing safety risks to the subject. Generally, the efficacy and the treatment and safety risks may be monitored throughout the course of treatment.[000242] In some embodiments, a subject may be administered a composition provided herein (e.g., an anti-CD3 antibody) at one or more intervals during a set period of time. In some cases, periods of time during which a subject is administered a composition at one or more intervals may be separated by periods of time in which the subject is not administered the composition. In some embodiments, the relative durations of respective periods of time may depend on the subject’s response to treatment or severity of disease or both and / or may be determined based on the judgment of a treating physician.[000243] In some embodiments, an antibody can be administered parenterally. For example, a parenterally administered composition may be administered by subcutaneous, intracutaneous, intravenous, intraperitoneal, intratumor, intramuscular, intraarticular, intraarterial, or infusion techniques. In addition, it can be administered to the subject via injectable depot routes of administration such as using 1-, 3-, or 6-month depot injectable or biodegradable materials and methods.[000244] In some embodiments, an antibody (e.g., an anti-CD3 antibody) is administered intravenously. In some embodiments, an antibody (e.g., an anti-CD3 antibody) is administered subcutaneously.[000245] For intravenous injection, water soluble antibodies can be administered by the drip method, whereby a pharmaceutical formulation containing the antibody and a physiologically acceptable excipient is infused. Physiologically acceptable excipients may include, for example, 5% dextrose, 0.9% saline. Ringer’s solution or other suitable excipients. Other injectable compositions may contain various carriers such as vegetable oils, dimethylactamide, dimethyformamide, ethyl lactate, ethyl carbonate, isopropyl myristate, ethanol, and polyols (glycerol, propylene glycol, liquid polyethylene glycol, and the like). In some cases, preparations, e.g., a sterile formulation of a suitable soluble salt form of the antibody, can be dissolved and administered in a pharmaceutical excipient such as Water-for- Injection, 0.9% saline, or 5% glucose solution.[000246] In one embodiment, an antibody is administered via site- specific or targeted local delivery techniques. Examples of site- specific or targeted local delivery techniques include various implantable depot sources of the antibody or local delivery catheters, such as infusion catheters, an indwelling catheter, or a needle catheter, synthetic grafts, adventitial wraps, shunts and stents or other implantable devices, site specific carriers, direct injection, or direct application. See, e.g., PCT Publication No. WO 00 / 53211 and U.S. Pat. No. 5,981,568.[000247] In some embodiments, more than one antibody, or a combination of an antibody and another suitable therapeutic agent, may be administered to a subject in need of the treatment. The antibody can also be used in conjunction with other agents that serve to enhance and / or complement the effectiveness of the agents. Treatment efficacy for a target disease / disorder can be assessed by methods well-known in the art.[000248] The anti-CD3 antibody and treatment methods involving such as described in the present disclosure may be utilized in combination with other types of therapy for the target disease or disorder disclosed herein. In this context, an antibody composition and a therapeutic agent may be given either simultaneously or sequentially. Examples include chemotherapy, immune therapy, surgery, radiation, gene therapy, and so forth, or antiinfection therapy. Such therapies can be administered simultaneously or sequentially (in any order) with the treatment according to the present disclosure.[000249] For example, the combination therapy can include the anti-CD3 antibody and pharmaceutical composition described herein, co-formulated with and / or co-administered with, at least one additional therapeutic agent. Such combination therapies mayadvantageously utilize lower dosages of the administered therapeutic agents, thus preventing possible toxicities or complications associated with the various monotherapies.[000250] In some embodiments, the antibodies described herein are conjugated directly or indirectly to one or more molecular pay loads or labels. For example, in some embodiments, antibodies described herein are conjugated to molecular payload, e.g., a molecular payload providing a therapeutic benefit for a subject, e.g., an antibody-drug conjugate (ADC). Accordingly, in some embodiments, methods are provided for delivering a molecular payloads to a subject for therapeutic purposes. In such embodiments, the molecular payload may be a small molecule, protein, nucleic acid, oligonucleotide, or any molecular entity capable of modulating the activity or function of a gene, protein, and / or nucleic acid, e.g., in a cell. In some embodiments, the molecular payload is a cytotoxic agent or a chemotherapeutic agent.[000251] An anti-CD3 antibody disclosed herein can also be used for detecting presence of CD3 in vitro or in vivo. Results obtained from such detection methods can be used for diagnostic purposes (e.g., diagnosing diseases associated with CD3) or for scientific research purposes (e.g., studying bioactivity and / or regulation of CD3). For assay uses such as diagnostic uses, an anti-CD3 antibody as described herein may be conjugated with a detectable label (e.g., an imaging agent such as a contrast agent) for detecting presence of CD3 complexes, either in vivo or in vitro.[000252] In other embodiments, an anti-CD3 antibody as described herein can be attached to a detectable label, which is a compound that is capable of releasing a detectable signal, either directly or indirectly, such that the aptamer can be detected, measured, and / or qualified, in vitro or in vivo. Examples of such “detectable labels" are intended to include, but are not limited to, fluorescent labels, chemiluminescent labels, colorimetric labels, enzymatic markers, radioactive isotopes, and affinity tags such as biotin. Such labels can be conjugated to the aptamer, directly or indirectly, by conventional methods.[000253] In some embodiments, the detectable label is an agent suitable for detecting CD3- expressing cells (e.g., T cells) in vitro, which can be a radioactive molecule, a radiopharmaceutical, or an iron oxide particle. Radioactive molecules suitable for in vivo imaging include, but are not limited to,122I,123I,124I,125I,131I,18F,75Br,76Br,77Br,211At,225Ac,177LU,153Sm,186Re,188Re,67Cu,213Bi,212Bi,212Pb, and67Ga. Exemplary radiopharmaceuticals suitable for in vivo imaging includeinIn Oxyquinoline,131I Sodium iodide, "mTc Mebrofenin, and "mTc Red Blood Cells,123I Sodium iodide, "mTc Exametazime, "mTc Macroaggregate Albumin, "mTc Medronate, "mTc Mertiatide, "mTcOxidronate, "mTc Pentetate, "mTc Pertechnetate, "mTc Sestamibi, "mTc Sulfur Colloid, "mTc Tetrofosmin, Thallium-201, or Xenon- 133. The reporting agent can also be a dye, e.g., a fluorophore, which is useful in detecting a disease mediated by CD3-expressing cells in tissue samples.[000254] To perform a diagnostic assay in vitro, an anti-CD3 antibody can be brought in contact with a sample suspected of containing CD3, e.g., CD3 expressing cells or soluble CD3 in disease microenvironment. The antibody and the sample may be incubated under suitable conditions for a suitable period to allow for binding of the antibody to the CD3 antigen. Such an interaction can then be detected via routine methods, e.g., ELISA, histological staining or FACS. To perform a diagnostic assay in vivo, a suitable amount of anti-CD3 antibodies, conjugated with a label (e.g., an imaging agent or a contrast agent), can be administered to a subject in need of the examination. Presence of the labeled antibody can be detected based on the signal released from the label by routine methods.[000255] To perform scientific research assays, an anti-CD3 antibody can be used to study bioactivity of CD3, detect the presence of CD3 intracellularly, and or regulate the effect of CD3. For example, a suitable amount of anti-CD3 can be brought in contact with a sample (e.g., a new cell type that is not previously identified as CD3 producing cells) suspected of producing CD3. The cells are permeabilized prior to contacting the anti-CD3 antibody. The antibody and the sample may be incubated under suitable conditions for a suitable period to allow for binding of the antibody to the CD3 antigen. Such an interaction can then be detected via routine methods, e.g., EEISA, histological staining or FACS.VI. Kits for Therapeutic and Diagnostic Applications[000256] The present disclosure also provides kits for the therapeutic or diagnostic applications as disclosed herein. Such kits can include one or more containers comprising an anti-CD3 antibody, e.g., any of those described herein.[000257] In some embodiments, the kit can comprise instructions for use in accordance with any of the methods described herein. The included instructions can comprise a description of administration of the anti-CD3 antibody to treat, delay the onset, or alleviate a target disease as those described herein. The kit may further comprise a description of selecting an individual suitable for treatment based on identifying whether that individual has the target disease. In still other embodiments, the instructions comprise a description of administering an antibody to an individual at risk of the target disease.[000258] The instructions relating to the use of an anti-CD3 antibody generally include information as to dosage, dosing schedule, and route of administration for the intended treatment. The containers may be unit doses, bulk packages (e.g., multi-dose packages) or sub-unit doses. Instructions supplied in the kits of the invention are typically written instructions on a label or package insert (e.g., a paper sheet included in the kit), but machine- readable instructions (e.g., instructions carried on a magnetic or optical storage disk) are also acceptable.[000259] The label or package insert indicates that the composition is used for treating, delaying the onset and / or alleviating a disease or disorder. Instructions may be provided for practicing any of the methods described herein.[000260] The kits of this invention are in suitable packaging. Suitable packaging includes, but is not limited to, vials, bottles, jars, flexible packaging (e.g., sealed Mylar or plastic bags), and the like.[000261] Also contemplated are packages for use in combination with a specific device, such as an infusion device, such as a minipump. A kit may have a sterile access port (for example the container may be an intravenous solution bag or a vial having a stopper pierceable by a hypodermic injection needle). The container may also have a sterile access port (for example the container may be an intravenous solution bag or a vial having a stopper pierceable by a hypodermic injection needle). At least one active agent in the composition is an anti-CD3 antibody as those described herein.[000262] Kits may optionally provide additional components such as buffers and interpretive information. Normally, the kit comprises a container and a label or package insert(s) on or associated with the container. In some embodiments, the invention provides articles of manufacture comprising contents of the kits described above.[000263] Also provided herein are kits for use in detecting CD3 in a sample. Such a kit may comprise an anti-CD3 antibody described herein. In some instances, the anti-CD3 antibody can be conjugated with a detectable label as those described herein. As used herein, “conjugated” or “attached” means two entities are associated, preferably with sufficient affinity that the therapeutic / diagnostic benefit of the association between the two entities is realized. The association between the two entities can be either direct or via a linker, such as a polymer linker. Conjugated or attached can include covalent or noncovalent bonding as well as other forms of association, such as entrapment, e.g., of one entity on or within the other, or of either or both entities on or within a third entity, such as a micelle.[000264] Alternatively or in addition, the kit may comprise a secondary antibody capable ofbinding to anti-CD3 antibody. The kit may further comprise instructions for using the anti- CD3 antibody for detecting CD3.EXAMPLESExample 1. Testing of anti-CD3 candidates.A deep humanization campaign using computational tools to forecast alterations, modify the anti-CD3 sequence, and confirm changes through experimental validation was performed on a murine antibody against CD3 to obtain improved humanized antibody (Terhorst et al. , EMBO J. 4(2):337-344 (1985)). Resulting candidate humanized antibodies were then tested for kinetic s / affinity, polyreactivity, and colloidal stability relevant to an existing humanized version of the murine antibody (referred to as “Comparator humanized antibody”). Amino acid sequences of the Comparator humanized antibody are set forth below:VH: VQLVESGGGLVQPGGSLRLSCAASGFTFSTYAMNWVRQAPGKGLWVGRIRSKYN NYATYYADSVKDRFTISRDDSKNSLYLQMNSLKTEDTAVYYCVRHGNFGNSYVSYFA YWGQGTLVTVSS (SEQ ID NO: 30) and VL:DIQMTQSPSSLSASVGDRVTITCRSSTGAVTTSNYANWVQQKPGKAPKALIGGT NKRAPGVPSRFSGSLIGDKATLTISSLQPEDFATYYCALWYSNLWVFGQGTKVEIK (SEQ ID NO: 31).[000265] Kinetic experiments were performed on Carterra LSA with a running buffer HBSTE, lOmM HEPES pH7.4, 150mM NaCl, 3mM EDTA, 0.05% Tween 20. Antibodies were captured on an anti-human Fc capture chip prepared with a HC30M chip. For kinetics analysis, human CD3 was injected sequentially at analyte in the binding kinetics experiment. For each concentration, there was 5 minute association followed by 15 minute dissociation. Results were processed and analyzed in Carterra LSA Kinetics Software. The kinetic data was referenced with the interstitial reference spots and double-referenced to a buffer cycle, and then fit globally to a 1:1 binding model to determine their apparent association and dissociation kinetic rate constants (Ka and Kd values). The ratio of Kd / Ka was used to derive the KD value of each antigen / mAb interaction, i.e. KD=Kd / Ka, shown in Table 4 below.[000266] To measure cell binding, T2 cells at a concentration of 106cells / mL were incubated with 50 pM peptide of interest or control peptide overnight in serum-free RPMI medium supplemented with 5 mg / mL human b2-microglobulin (Sigma, St. Louis, MO, USA). After incubation, T2 cell was washed with PBS. In the antibody-cell binding experiment, the antibodies were tested at a concentration from 100 nM to 0.6 pM (a serial 3-fold dilution) forbinding on the prepared T2 cells for 45 min at 4°C. Cells were then incubated with the secondary antibody R-Phycoerythrin AffiniPure Goat Anti-Human IgG (Jackson Immunoresearch 109-115-098). The data was acquired on FACSCanto II (BD) or on Intellicyt iQue3. Median fluorescence intensities (MFI) were plotted against the concentrations of the antibodies. EC50 was derived from fitting to 4 parameter dose-response curve. Values are shown in Table 4 below.Table 4. Polyreactivity, binding affinity, and colloidal stability of anti-CD3 candidates in IgGl format.[000267] Cell-binding and affinity, as measured by EC50 and KD in Table El, were markedly better for the candidate anti-CD3 Abl and anti-CD3 Ab2 compared to Comparator humanized antibody. Additionally, polyreactivity, as measured by BVP (baculovirus viral particle ELISA), and colloidal stability, as measured by affinity-capture self-interaction nanoparticle spectroscopy (AC-SINS), were also improved for candidate anti-CD3 antibodies compared to Comparator humanized Antibody.[000268] Polyreactivity and aggregation propensity of the antibodies were further evaluated by BVP ELISA and AC-SINS assays, respectively.[000269] Functional activity of candidate anti-CD3 antibodies in solution and after crosslinking was further evaluated. A commercially available and stably-engineered Jurkat cell line (human CD4+ T cells) that express the luciferase gene under the control of NFAT (nuclear factor of activated T cells), which allows a bioluminescent readout of T cell activation, were plated at 100,000 cells / mL. Candidate anti-CD3 antibodies were added at 3pg / mL. Antibody activity in the present of crosslinkers was compared to activity in the absence of crosslinkers. When used, crosslinkers (Jackson ImmunoResearch Laboratories, Inc., West Grove, PA) were added at lOnM for a crosslinkerantibody ratio of 1:2. Anti-CD3 candidate antibodies Abl and Ab2 showed robust activity only in the presence of crosslinking, indicating strong, specific binding to anti-CD3 and very low background binding activity.OTHER EMBODIMENTS[000270] All of the features disclosed in this specification may be combined in any combination. Each feature disclosed in this specification may be replaced by an alternative feature serving the same, equivalent, or similar purpose. Thus, unless expressly stated otherwise, each feature disclosed is only an example of a generic series of equivalent or similar features.[000271] From the above description, one skilled in the art can easily ascertain the essential characteristics of the present invention, and without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions. Thus, other embodiments are also set forth as follows:EQUIVALENTS AND SCOPE[000272] In the claims, articles such as “a,” “an,” and “the” may mean one or more than one unless indicated to the contrary or otherwise evident from the context. Claims or descriptions that include “or” between one or more members of a group are considered satisfied if one, more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process unless indicated to the contrary or otherwise evident from the context. The invention includes embodiments in which exactly one member of the group is present in, employed in, or otherwise relevant to a given product or process. The invention includes embodiments in which more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process.[000273] Furthermore, the invention encompasses all variations, combinations, and permutations in which one or more limitations, elements, clauses, and descriptive terms from one or more of the listed claims is introduced into another claim. For example, any claim that is dependent on another claim can be modified to include one or more limitations found in any other claim that is dependent on the same base claim. Where elements are presented as lists, e.g., in Markush group format, each subgroup of the elements is also disclosed, and any element(s) can be removed from the group. It should it be understood that, in general, where the invention, or aspects of the invention, is / are referred to as comprising particular elements and / or features, certain embodiments of the invention or aspects of the invention consist, orconsist essentially of, such elements and / or features. For purposes of simplicity, those embodiments have not been specifically set forth in haec verba herein.[000274] The phrase “and / or,” as used herein in the specification and in the claims, should be understood to mean “either or both” of the elements so conjoined, i.e., elements that are conjunctively present in some cases and disjunctively present in other cases. Multiple elements listed with “and / or” should be construed in the same fashion, i.e., “one or more” of the elements so conjoined. Other elements may optionally be present other than the elements specifically identified by the “and / or” clause, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, a reference to “A and / or B”, when used in conjunction with open-ended language such as “comprising” can refer, in one embodiment, to A only (optionally including elements other than B); in another embodiment, to B only (optionally including elements other than A); in yet another embodiment, to both A and B (optionally including other elements); etc.[000275] As used herein in the specification and in the claims, “or” should be understood to have the same meaning as “and / or” as defined above. For example, when separating items in a list, “or” or “and / or” shall be interpreted as being inclusive, i.e., the inclusion of at least one, but also including more than one, of a number or list of elements, and, optionally, additional unlisted items. Only terms clearly indicated to the contrary, such as “only one of’ or “exactly one of,” or, when used in the claims, “consisting of,” will refer to the inclusion of exactly one element of a number or list of elements. In general, the term “or” as used herein shall only be interpreted as indicating exclusive alternatives (i.e. “one or the other but not both”) when preceded by terms of exclusivity, such as “either,” “one of,” “only one of,” or “exactly one of.” “Consisting essentially of,” when used in the claims, shall have its ordinary meaning as used in the field of patent law.[000276] As used herein in the specification and in the claims, the phrase “at least one,” in reference to a list of one or more elements, should be understood to mean at least one element selected from any one or more of the elements in the list of elements, but not necessarily including at least one of each and every element specifically listed within the list of elements and not excluding any combinations of elements in the list of elements. This definition also allows that elements may optionally be present other than the elements specifically identified within the list of elements to which the phrase “at least one” refers, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, “at least one of A and B” (or, equivalently, “at least one of A or B,” or, equivalently “at least one of A and / or B”) can refer, in one embodiment, to at least one, optionally including more than one,A, with no B present (and optionally including elements other than B); in another embodiment, to at least one, optionally including more than one, B, with no A present (and optionally including elements other than A); in yet another embodiment, to at least one, optionally including more than one, A, and at least one, optionally including more than one, B (and optionally including other elements); etc.[000277] It should also be understood that, unless clearly indicated to the contrary, in any methods claimed herein that include more than one step or act, the order of the steps or acts of the method is not necessarily limited to the order in which the steps or acts of the method are recited.[000278] In the claims, as well as in the specification above, all transitional phrases such as “comprising,” “including,” “carrying,” “having,” “containing,” “involving,” “holding,” “composed of,” and the like are to be understood to be open-ended, i.e., to mean including but not limited to. Only the transitional phrases “consisting of’ and “consisting essentially of’ shall be closed or semi-closed transitional phrases, respectively, as set forth in the United States Patent Office Manual of Patent Examining Procedures, Section 2111.03. It should be appreciated that embodiments described in this document using an open-ended transitional phrase (e.g., “comprising”) are also contemplated, in alternative embodiments, as “consisting of’ and “consisting essentially of’ the feature described by the open-ended transitional phrase. For example, if the application describes “a composition comprising A and B,” the application also contemplates the alternative embodiments “a composition consisting of A and B” and “a composition consisting essentially of A and B.”[000279] Where ranges are given, endpoints are included. Furthermore, unless otherwise indicated or otherwise evident from the context and understanding of one of ordinary skill in the art, values that are expressed as ranges can assume any specific value or sub-range within the stated ranges in different embodiments of the invention, to the tenth of the unit of the lower limit of the range, unless the context clearly dictates otherwise.[000280] This application refers to various issued patents, published patent applications, journal articles, and other publications, all of which are incorporated herein by reference. If there is a conflict between any of the incorporated references and the instant specification, the specification shall control. In addition, any particular embodiment of the present invention that falls within the prior art may be explicitly excluded from any one or more of the claims. Because such embodiments are deemed to be known to one of ordinary skill in the art, they may be excluded even if the exclusion is not set forth explicitly herein. Any particularembodiment of the invention can be excluded from any claim, for any reason, whether or not related to the existence of prior art.[000281] Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation many equivalents to the specific embodiments described herein. The scope of the present embodiments described herein is not intended to be limited to the above Description, but rather is as set forth in the appended claims. Those of ordinary skill in the art will appreciate that various changes and modifications to this description may be made without departing from the spirit or scope of the present invention, as defined in the following claims.[000282] The recitation of a listing of chemical groups in any definition of a variable herein includes definitions of that variable as any single group or combination of listed groups. The recitation of an embodiment for a variable herein includes that embodiment as any single embodiment or in combination with any other embodiments or portions thereof. The recitation of an embodiment herein includes that embodiment as any single embodiment or in combination with any other embodiments or portions thereof.

Claims

1. CLAIMSWhat is claimed is:

1. An antibody that specifically binds CD3 comprising:(a) a heavy chain complementarity determining region 1 (HC CDR1), a heavy chain complementarity determining region 2 (HC CDR2), and a heavy chain complementarity determining region 3 (HC CDR3) of a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 7; and a light chain complementarity determining region 1 (LC CDR1), a light chain complementarity determining region 2 (LC CDR2), and a light chain complementarity determining region 3 (LC CDR3) of a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 8; or(b) a HC CDR1, HC CDR2, and a HC CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 11; and a LC CDR1, LC CDR2, and a LC CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 8.

2. An antibody that specifically binds CD3 comprising:(a) a HC CDR1 comprising the amino acid sequence of SEQ ID NO: 1, a HC CDR2 comprising the amino acid sequence of SEQ ID NO: 2, a HC CDR3 comprising the amino acid sequence of SEQ ID NO: 3, a LC CDR1 comprising the amino acid sequence of SEQ ID NO: 4, a LC CDR2 comprising the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 comprising the amino acid sequence of SEQ ID NO: 6; or(b) a HC CDR1 comprising the amino acid sequence of SEQ ID NO: 1, a HC CDR2 comprising the amino acid sequence of SEQ ID NO: 9, a HC CDR3 comprising the amino acid sequence of SEQ ID NO: 10, a LC CDR1 comprising the amino acid sequence of SEQ ID NO: 4, a LC CDR2 comprising the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 comprising the amino acid sequence of SEQ ID NO: 6.

3. The antibody of claim 1 or 2, wherein the antibody comprises:(a) a VH comprising the amino acid of SEQ ID NO: 7, and / or a VL comprising the amino acid sequence of SEQ ID NO: 8; or(b) a VH comprising the amino acid of SEQ ID NO: 1, and / or a VL comprising the amino acid sequence of SEQ ID NO: 8.

4. The antibody of any one of claims 1-3, wherein the antibody is a full-length IgG, a Fab fragment, a F(ab') fragment, a F(ab’)2 fragment, a scFv, or a Fv.

5. The antibody of any one of claims 1-4, wherein the antibody comprises a heavy chain constant region of the isotype IgGl, IgG2, IgG3, or IgG4.

6. An isolated nucleic acid encoding the VH and / or VL of the antibody of any one of claims 1-57. The isolated nucleic acid of claim 6, wherein the isolated nucleic acid comprises:(a) the nucleic acid sequence of SEQ ID NO: 12, and / or the nucleic acid sequence of SEQ ID NO: 13; or(b) the nucleic acid sequence of SEQ ID NO: 14, and / or the nucleic acid sequence of SEQ ID NO: 13.

8. An expression vector comprising the isolated nucleic acid of any claim 6 or 7.

9. A host cell comprising the antibody of any one of claims 1-5, the isolated nucleic acid of claim 6 or 7, or the vector of claim 8.

10. An engineered cell expressing the antibody of any one of claims 1-5.

11. The engineered cell of claim 10, wherein the engineered cell is a T cell, a NK cell, or a NKT cell.

12. A composition comprising the antibody of any one of claims 1-5, the isolated nucleic acid of claim 6 or 7, the vector of claim 8, the host cell of claim 9, or the engineered cell of claim 10 or 11.

13. The composition of claim 12, further comprising a pharmaceutically acceptable carrier.

14. A bispecific antibody comprising a first antigen binding site and a second antigen binding site, wherein the second antigen binding site comprises the antibody of any one of claims 1-5.15 The bispecific antibody of claim 14, wherein the first antigen binding site specifically binds to a cancer antigen, a pathogen-derived antigen, or a B cell antigen.16 The bispecific antibody of claim 15, wherein the first antigen binding site specifically binds to a cancer antigen.17 The bispecific antibody of claim 16, wherein the cancer antigen is selected from WT1, PRAME, DLL3, CD70, Claudinl8.2, MSLN, MAGE-A1, MAGE-A3, MAGE-A4, MAGE- A8, CD38, and BCMA.

18. The bispecific antibody of claim 17, wherein the cancer antigen is WT1.

19. The bispecific antibody of claim 17, wherein the cancer antigen is PRAME.

20. The bispecific antibody of claim 17, wherein the cancer antigen is DLL3.

21. The bispecific antibody of claim 17, wherein the cancer antigen is CD70.

22. The bispecific antibody of claim 17, wherein the cancer antigen is Claudinl8.2.

23. The bispecific antibody of claim 17, wherein the cancer antigen is MSLN.

24. The bispecific antibody of claim 17, wherein the cancer antigen is MAGE-A425. The bispecific antibody of claim 17, wherein the cancer antigen is MAGE-A8.

26. The bispecific antibody of claim 17, wherein the cancer antigen is CD38.

27. The bispecific antibody of claim 17, wherein the cancer antigen is BCMA.

28. The bispecific antibody of claim 15, wherein the first antigen binding site specifically binds a pathogen-derived antigen.

29. The bispecific antibody of claim 28, wherein the pathogen-derived antigen is a viral antigen.

30. The bispecific antibody of claim 29, wherein the viral antigen is an HIV antigen, an influenza antigen, an HPV antigen, or a Zika virus antigen.

31. The bispecific antibody of claim 28, wherein the pathogen-derived antigen is a bacterial antigen.

32. The bispecific antibody of claim 31, wherein the bacterial antigen is a Staphylococcus species antigen or a Pseudomonas species antigen.

33. The bispecific antibody of claim 28, wherein the pathogen-derived antigen is a parasitic antigen.

34. The bispecific antibody of claim 33, wherein the parasitic antigen is a Plasmodium species antigen, a Trypanosoma species antigen, or a Schistosoma species antigen.

35. The bispecific antibody of claim 15, wherein the first antigen binding site specifically binds a B cell antigen.

36. The bispecific antibody of claim 35, wherein the B cell antigen is CD19, CD22, or CD79.

37. The bispecific antibody of any one of claims 14-36, wherein the bispecific antibody comprises a first arm that is configured as a Fab, a Fab’, or a scFv and that comprises the first antigen binding site.

38. The bispecific antibody of any one of claims 14-36, wherein the bispecific antibody comprises a second arm that is configured as a Fab, a Fab’, or a scFv and that comprises the first antigen binding site.

39. The bispecific antibody of any one of claims 14-36, wherein the bispecific antibody comprises a first arm that is configured as a Fab and a second arm that is configured as a scFv.

40. The bispecific antibody of any one of claims 14-36, wherein the bispecific antibody comprises a first arm that is configured as a scFv and a second arm that is configured as a Fab.

41. The bispecific antibody of any one of claims 14-40, wherein the ratio between the first antigen binding site and the second antigen binding site is 1:1, 1:2, 1:3, 2:1 or 3:1.

42. A host cell comprising the bispecific antibody of any one of claims 14-41.

43. A composition comprising the bispecific antibody of any one of claims 14-41.

44. The composition of claim 43, further comprising a pharmaceutically acceptable carrier.

45. A method of treating cancer, the method comprising administering to a subject in need thereof an effective amount of the antibody of any one of claims 1-5, the engineered cell of claim 10 or 11, the composition of any one of claims 12, 13, 43, or 44, or the bispecific antibody of any one of claims 14-26 or 38-41.

46. A method of treating infection, the method comprising administering to a subject in need thereof an effective amount of the antibody of any one of claims 1-5, the engineered cell of claim 10 or 11, the composition of any one of claims 12, 13, 43, or 44, or the bispecific antibody of any one of claims 14, 15, 28-34, or 38-41.

47. A method of treating an autoimmune disorder, the method comprising administering to a subject in need thereof an effective amount of the antibody of anyone one of claims 1-5, the engineered cell of claim 10 or 11, the composition of any one of claims 12, 13, 43, or 44, or the bispecific antibody of any one of claims 14, 15, or 35-41.

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