BTN1A1 binding proteins and methods of use thereof

Abstract

Provided herein are molecules having an antigen-binding fragment that immunospecifically binds to BTN1A1, e.g., anti-BTN1A1 antibodies. These molecules include those having an antigen-binding fragment that immunospecifically binds to BTN1A1. Methods of making and using these molecules are also provided, including methods of using these molecules in detecting the presence of BTN1A1 in a sample, e.g., a patient's bodily fluid or tissue, for the diagnosis and treatment of a BTN1A1-mediated disease or condition.

Description

[Technical field]

[0001] (CROSS REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of priority to U.S. Patent Application No. 63 / 320,646, filed March 16, 2022, the contents of which are incorporated by reference in their entirety herein.

[0002] (Reference to electronically submitted sequence listing) This application contains a computer readable sequence listing that has been submitted herewith in XML file format, the entire contents of which are incorporated herein by reference in their entirety. The sequence listing XML file submitted herewith is entitled "13532-025-228_SEQLIST.xml", was created on Mar. 15, 2023, and is 156,059 bytes in size. [Background technology]

[0003] (1. Field) The present invention relates generally to the fields of cancer immunology and molecular biology. Provided herein are anti-BTN1A1 antibodies or other molecules having antigen-binding fragments that immunospecifically bind to BTN1A1, and uses thereof. Summary of the Invention

[0004] (2. Overview) The present disclosure provides proteins that bind to BTN1A1 (e.g., human BTN1A1, SEQ ID NO:1), including binding proteins such as antibodies that bind to BTN1A1. Such binding proteins, including antibodies, can bind to a BTN1A1 polypeptide, a BTN1A1 fragment, and / or a BTN1A1 epitope. Such binding proteins, including antibodies, can be agonistic (e.g., induce BTN1A1 ligand-like signaling). In some embodiments, the binding protein does not compete with a BTN1A1 ligand for interaction with BTN1A1 (e.g., a non-blocking antibody).

[0005] Also provided herein are polynucleotides and vectors comprising sequences encoding such antibodies, cells (e.g., host cells) comprising such polynucleotides or vectors, and compositions, reagents, and kits comprising such antibodies. In another aspect, provided herein are methods for detecting BTN1A1 from a sample, methods for evaluating a subject for treatment, diagnostic methods, and other uses of such anti-BTN1A1 antibodies.

[0006] In some embodiments, the binding protein (e.g., an anti-BTN1A1 antibody) comprises six complementarity determining regions (CDRs) or fewer than six CDRs. In other embodiments, the binding protein (e.g., an anti-BTN1A1 antibody) comprises one, two, three, four, five, or six CDRs selected from heavy chain variable region (VH) CDR1, VH CDR2, VH CDR3, light chain variable region (VL) CDR1, VL CDR2, and / or VL CDR3. In certain embodiments, the binding protein (e.g., an anti-BTN1A1 antibody) comprises one, two, three, four, five, or six CDRs selected from VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 of the monoclonal antibody designated STC43H11-1 described herein or a humanized variant thereof. In some embodiments, the binding protein (e.g., an anti-BTN1A1 antibody) further comprises a scaffold or framework region (FR) comprising VH FR1, VH FR2, VH FR3, VH FR4, VL FR1, VL FR2, VL FR3, and / or VL FR4 of a human immunoglobulin amino acid sequence or a variant thereof.

[0007] In one aspect, provided herein is an antibody or antigen-binding fragment thereof that (a) binds to an epitope of BTN1A1 recognized by an antibody comprising a light chain variable region having the amino acid sequence of SEQ ID NO: 19 and a heavy chain variable region having the amino acid sequence of SEQ ID NO: 20; or (b) competes for binding to BTN1A1 with an antibody comprising a light chain variable region having the amino acid sequence of SEQ ID NO: 19 and a heavy chain variable region having the amino acid sequence of SEQ ID NO: 20.

[0008] In one aspect, provided herein is an antibody or antigen-binding fragment thereof that (a) binds to an epitope of BTN1A1 recognized by an antibody comprising a light chain variable region having the amino acid sequence of SEQ ID NO:66 and a heavy chain variable region having the amino acid sequence of SEQ ID NO:68; or (b) competes for binding to BTN1A1 with an antibody comprising a light chain variable region having the amino acid sequence of SEQ ID NO:66 and a heavy chain variable region having the amino acid sequence of SEQ ID NO:68.

[0009] In one aspect, provided herein is an antibody or antigen-binding fragment thereof that (a) binds to an epitope of BTN1A1 recognized by an antibody comprising a light chain variable region having the amino acid sequence of SEQ ID NO:67 and a heavy chain variable region having the amino acid sequence of SEQ ID NO:69; or (b) competes for binding to BTN1A1 with an antibody comprising a light chain variable region having the amino acid sequence of SEQ ID NO:67 and a heavy chain variable region having the amino acid sequence of SEQ ID NO:69.

[0010] In one aspect, provided herein is an antibody or antigen-binding fragment thereof that binds to BTN1A1, wherein the antibody or antigen-binding fragment thereof comprises: (a) a light chain variable region (VL) comprising VL complementarity determining region 1 (CDR1), VL CDR2, and VL CDR3 of antibody STC43H11-1 as shown in Table 1; and / or a heavy chain variable region (VH) comprising VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3 of antibody STC43H11-1 as shown in Table 2; (b) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 19; and / or a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 20. VH: comprising CDR2, and VH CDR3.

[0011] In one aspect, provided herein is an antibody or antigen-binding fragment thereof that binds to BTN1A1, wherein the antibody or antigen-binding fragment thereof comprises: (a) a light chain variable region (VL) comprising the VL complementarity determining region 1 (CDR1), VL CDR2, and VL CDR3 of antibody STC43G3-1 shown in Table 3; and / or a heavy chain variable region (VH) comprising the VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3 of antibody STC43G3-1 shown in Table 4; (b) a VL comprising the VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 66; and / or a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 68. VH: comprising CDR2, and VH CDR3.

[0012] In one aspect, provided herein is an antibody or antigen-binding fragment thereof that binds to BTN1A1, wherein the antibody or antigen-binding fragment thereof comprises: (a) a light chain variable region (VL) comprising the VL complementarity determining region 1 (CDR1), VL CDR2, and VL CDR3 of antibody STC85F1-1 shown in Table 5; and / or a heavy chain variable region (VH) comprising the VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3 of antibody STC85F1-1 shown in Table 6; (b) a VL comprising the VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 67; and / or a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 69. VH: comprising CDR2, and VH CDR3.

[0013] In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the Kabat numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the Chothia numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the ABM numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the Contact numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the IMGT numbering system.

[0014] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a light chain variable region (VL) further comprising a VL framework 1 (FR1), a VL FR2, a VL FR3, and a VL FR4 of any one of antibodies STC43H11-1 shown in Table 7; and / or (b) a heavy chain variable region (VH) further comprising a VH framework 1 (FR1), a VH FR2, a VH FR3, and a VH FR4 of any one of antibodies STC43H11-1 shown in Table 8.

[0015] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a light chain variable region (VL) further comprising a VL framework 1 (FR1), a VL FR2, a VL FR3, and a VL FR4 of any one of antibodies STC43G3-1 shown in Table 7; and / or (b) a heavy chain variable region (VH) further comprising a VH framework 1 (FR1), a VH FR2, a VH FR3, and a VH FR4 of any one of antibodies STC43G3-1 shown in Table 8.

[0016] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a light chain variable region (VL) further comprising a VL framework 1 (FR1), a VL FR2, a VL FR3, and a VL FR4 of any one of antibodies STC85F1-1 shown in Table 7; and / or (b) a heavy chain variable region (VH) further comprising a VH framework 1 (FR1), a VH FR2, a VH FR3, and a VH FR4 of any one of antibodies STC85F1-1 shown in Table 8.

[0017] In some embodiments, the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOs: 5, 6, and 7, respectively, and the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOs: 8, 9, and 10, respectively.

[0018] In some embodiments, the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOs: 74, 75, and 76, respectively, and the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOs: 71, 72, and 73, respectively.

[0019] In some embodiments, the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOs: 80, 81, and 82, respectively, and the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOs: 77, 78, and 79, respectively.

[0020] In some embodiments, the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOs: 86, 87, and 88, respectively, and the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOs: 83, 84, and 85, respectively.

[0021] In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 19. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 19.

[0022] In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 20. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH comprising the amino acid sequence of SEQ ID NO: 20. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 19 and a VH comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 20.

[0023] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VL comprising the amino acid sequence of SEQ ID NO: 19; and (b) a VH comprising the amino acid sequence of SEQ ID NO: 20.

[0024] In some embodiments, the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOs: 38, 39, and 40, respectively, and the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOs: 44, 45, and 46, respectively.

[0025] In some embodiments, the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOs: 94, 95, and 96, respectively, and the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOs: 91, 92, and 93, respectively.

[0026] In some embodiments, the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOs: 100, 101, and 102, respectively, and the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOs: 97, 98, and 99, respectively.

[0027] In some embodiments, the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOs: 106, 107, and 108, respectively, and the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOs: 103, 104, and 105, respectively.

[0028] In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 66. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 66.

[0029] In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 68. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH comprising the amino acid sequence of SEQ ID NO: 68.

[0030] In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 66, and a VH comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 68. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VL comprising the amino acid sequence of SEQ ID NO: 66; and (b) a VH comprising the amino acid sequence of SEQ ID NO: 68.

[0031] In some embodiments, the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOs: 41, 42, and 43, respectively, and the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOs: 47, 48, and 49, respectively.

[0032] In some embodiments, the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOs: 114, 115, and 116, respectively, and the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOs: 111, 112, and 113, respectively.

[0033] In some embodiments, the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOs: 120, 121, and 122, respectively, and the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOs: 117, 118, and 119, respectively.

[0034] In some embodiments, the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOs: 126, 127, and 128, respectively, and the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOs: 123, 124, and 125, respectively.

[0035] In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 67. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 67.

[0036] In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 69. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH comprising the amino acid sequence of SEQ ID NO: 69.

[0037] In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 67, and a VH comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 69. In some embodiments, the antibody or antigen-binding fragment thereof comprises: (a) a VL comprising the amino acid sequence of SEQ ID NO: 67; and (b) a VH comprising the amino acid sequence of SEQ ID NO: 69.

[0038] In some embodiments, the antibody or antigen-binding fragment thereof binds to human BTN1A1. In some embodiments, the antibody or antigen-binding fragment thereof binds to mouse BTN1A1.

[0039] In some embodiments, when binding to BTN1A1, the antibody or antigen-binding fragment binds to at least one of residues 361-375 within the amino acid sequence of SEQ ID NO: 1. In some embodiments, when binding to BTN1A1, the antibody or antigen-binding fragment binds to at least one of residues 365-372 within the amino acid sequence of SEQ ID NO: 1. In some embodiments, when binding to BTN1A1, the antibody or antigen-binding fragment binds to at least one of residues 366-372 within the amino acid sequence of SEQ ID NO: 1.

[0040] In some embodiments, when binding to BTN1A1, the antibody or antigen-binding fragment binds to at least one residue selected from the group consisting of G365, D366, T368, D369, W370, A371, I372, and G373 in the amino acid sequence of SEQ ID NO:1. In some embodiments, when binding to BTN1A1, the antibody or antigen-binding fragment binds to G365 in the amino acid sequence of SEQ ID NO:1. In some embodiments, when binding to BTN1A1, the antibody or antigen-binding fragment binds to D366 in the amino acid sequence of SEQ ID NO:1. In some embodiments, when binding to BTN1A1, the antibody or antigen-binding fragment binds to T368 in the amino acid sequence of SEQ ID NO:1. In some embodiments, when binding to BTN1A1, the antibody or antigen-binding fragment binds to D369 in the amino acid sequence of SEQ ID NO:1. In some embodiments, when binding to BTN1A1, the antibody or antigen-binding fragment binds to W370 in the amino acid sequence of SEQ ID NO:1. In some embodiments, when bound to BTN1A1, the antibody or antigen-binding fragment binds to A371 in the amino acid sequence of SEQ ID NO: 1. In some embodiments, when bound to BTN1A1, the antibody or antigen-binding fragment binds to I372 in the amino acid sequence of SEQ ID NO: 1. In some embodiments, when bound to BTN1A1, the antibody or antigen-binding fragment binds to G373 in the amino acid sequence of SEQ ID NO: 1.

[0041] In some embodiments, when binding to BTN1A1, the antibody or antigen-binding fragment binds to D366, D369, and I372 within the amino acid sequence of SEQ ID NO: 1. In some embodiments, when binding to BTN1A1, the antibody or antigen-binding fragment binds to G365, T368, D369, A371, and I372 within the amino acid sequence of SEQ ID NO: 1. In some embodiments, when binding to BTN1A1, the antibody or antigen-binding fragment binds to D366, T368, D369, W370, A371, I372, and G373 within the amino acid sequence of SEQ ID NO: 1.

[0042] In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody is a humanized, human, or chimeric antibody. In some embodiments, the humanized antibody is a deimmunized antibody or a synthetic human antibody. In some embodiments, the antibody or antigen-binding fragment thereof is a Fab, Fab', F(ab')2, Fv, scFv, dsFv, diabody, triabody, tetrabody, or a multispecific antibody formed from antibody fragments.

[0043] In some embodiments, the antibody or antigen-binding fragment thereof is conjugated to an agent, hi some embodiments, the agent is selected from the group consisting of a radioisotope, a metal chelator, an enzyme, a fluorescent compound, a bioluminescent compound, and a chemiluminescent compound.

[0044] In one aspect, provided herein is a composition comprising an antibody or antigen-binding fragment thereof provided herein and a pharma- ceutically acceptable carrier.

[0045] In one aspect, provided herein is a polynucleotide comprising a nucleotide sequence encoding the VH, the VL, or both the VH and VL of an antibody provided herein.

[0046] In one aspect, provided herein is a polynucleotide comprising a nucleotide sequence encoding the heavy chain, the light chain, or both the heavy and light chains of an antibody provided herein. In some embodiments, the polynucleotide is operably linked to a promoter.

[0047] In one aspect, provided herein is a vector comprising a polynucleotide provided herein.

[0048] In one aspect, provided herein is a cell comprising a polynucleotide provided herein. In one aspect, provided herein is a cell comprising a vector provided herein. In one aspect, provided herein is an isolated cell that produces an antibody or antigen-binding fragment thereof provided herein.

[0049] In one aspect, provided herein is a kit comprising an antibody or antigen-binding fragment thereof provided herein.

[0050] In one aspect, provided herein is a method of making an antibody or antigen-binding fragment thereof that specifically binds to an epitope of BTN1A1, comprising culturing a cell provided herein to express the antibody or antigen-binding fragment thereof.In one aspect, provided herein is a method of making an antibody or antigen-binding fragment thereof that specifically binds to an epitope of BTN1A1, comprising expressing a polynucleotide provided herein.

[0051] In one aspect, provided herein is a method for detecting BTN1A1 in a sample, comprising contacting the sample with an anti-BTN1A1 antibody or antigen-binding fragment thereof provided herein, and detecting the presence of the anti-BTN1A1 antibody or antigen-binding fragment thereof bound to the sample, wherein detection of the amount of anti-BTN1A1 antibody or antigen-binding fragment thereof bound to the sample above background indicates the presence of BTN1A1 in the sample. In some embodiments, the method further comprises quantifying the amount of BTN1A1 detected in the sample.

[0052] In some embodiments, the anti-BTN1A1 antibody or antigen-binding fragment thereof is conjugated to a detectable agent that produces a signal, and detecting comprises detecting the signal from the sample. In some embodiments, the anti-BTN1A1 antibody or antigen-binding fragment thereof is contacted with a secondary binding molecule that specifically binds to the anti-BTN1A1 antibody or antigen-binding fragment thereof in the sample, and detecting comprises detecting the secondary binding molecule from the sample.

[0053] In some embodiments, the sample is a cell-containing sample. In some embodiments, the cells in the sample are fixed in situ before being contacted with the anti-BTN1A1 antibody or antigen-binding fragment thereof. In some embodiments, the sample is a formalin-fixed paraffin-embedded (FFPE) tissue sample. In some embodiments, the sample is a cancer tissue; optionally, wherein the cancer is selected from skin cancer, pancreatic cancer, breast cancer, esophageal cancer, and endometrial cancer. In some embodiments, the sample is a body fluid sample; optionally, wherein the body fluid sample is blood, serum, or plasma.

[0054] In some embodiments, a sample is obtained from a subject and the method includes diagnosing the subject as having or at risk of developing a BTN1A1-mediated disease or condition when an amount of BTN1A1 in the sample is detected above a threshold amount. In some embodiments, the BTN1A1-mediated disease or condition is cancer.

[0055] In some embodiments, the subject is a mammal, hi some embodiments, the subject is a human.

[0056] In one aspect, provided herein is a kit for carrying out any one of the methods provided herein.

[0057] In one aspect, provided herein is a method of treating a subject with a BTN1A1 targeting agent, comprising detecting BTN1A1 in a sample from the subject. In some embodiments, detecting BTN1A1 in a sample comprises any one of the methods provided herein. In some embodiments, the targeting agent is an antagonistic polypeptide that binds to BTN1A1. In some embodiments, the targeting agent is an agonistic polypeptide that binds to BTN1A1. In some embodiments, the polypeptide that binds to BTN1A1 is an antibody or an antigen-binding fragment thereof. In some embodiments, the targeting agent is a small molecule compound that inhibits BTN1A1. In some embodiments, the subject has a disease or condition mediated by BTN1A1. In some embodiments, the method eliminates a population of diseased cells that express BTN1A1. In some embodiments, the subject has cancer. [Brief description of the drawings]

[0058] (3. BRIEF DESCRIPTION OF THE DRAWINGS) [Figure 1] FIG. 1 shows the overall workflow for generating anti-BTN1A1 antibodies.

[0059] [Diagram 2] FIG. 2 shows the ICD domains of human BTN1A1 (SEQ ID NO: 3) and mouse BTN1A1 (SEQ ID NO: 4) and an alignment of the peptide (peptide 4 of SEQ ID NO: 23) used to immunize animals in the BTN1A1 ICD.

[0060] [Diagram 3] 3A-3C show the binding of diluted serum samples taken from immunized rabbits to BTN1A1 peptide 4, hBTN1A1-ICD, and denatured hBTN1A1-ICD, respectively, by ELISA.

[0061] [Figure 4] 4A-4C show screening of antibodies produced by different hybridoma clones against peptide 4, hBTN1A1-ICD, and denatured hBTN1A1-ICD, respectively, by ELISA.

[0062] [Diagram 5] 5A and 5B show binding of purified antibody STC43H11-1 to peptide 4 or hBTN1A1-ICD, respectively, by ELISA.

[0063] [Figure 6] 6A-6C show the sequencing and isotyping characterization of STC43H11-1.

[0064] [Figure 7] 7A-7F show detection of BTN1A1 protein expressed by HEK293T cells by Western blotting using STC43H11-1 at a concentration of (1 μg / ml). Western blotting detection of Flag peptide and β-actin expressed by the cells is also shown as a control.

[0065] [Figure 8] Figure 8 shows detection of BTN1A1 protein expressed by HEK293T cells stained with STC43H11-1 or control IgG (top panel) in an immunohistochemistry assay. HEK293T cells that do not express BTN1A1 were included as a negative control (left column).

[0066] [Figure 9]Figures 9A-9C show immunostaining of various tissue samples (histologically normal (HN), bladder, NSCLC, ovary, colon, pancreas) with STC43H11-1 or anti-PD-L1 antibody.

[0067] [Figure 10] Figures 10A-10E show immunostaining of tissue microarrays ("TMAs") with STC43H11-1 at concentrations of 2 μg / mL (Figure 10C), 5 μg / mL (Figure 10D), and 10 μg / mL (Figure 10E). A negative control using staining with rabbit IgG at a concentration of 2 μg / mL was included (Figure 10A).

[0068] [Figure 11] Figure 11 shows detection of BTN1A1 protein by immunohistochemistry in formalin-fixed paraffin-embedded (FFPE) cells expressing BTN1A1. STC43H11-1 was used for immunostaining at a concentration of 2 μg / mL.

[0069] [Figure 12] Figure 12 shows immunohistochemistry assay of tissue samples (LC-642b TMA) using IgG (negative control), rabbit polyclonal antibody R4-17 (control), STC43H11-1, and E1L3N (PD-L1) antibody, respectively. STC43H11-1 was used for immunostaining at a concentration of 2 μg / mL.

[0070] [Figure 13] Figure 13 shows immunohistochemistry assays of tissue samples (LC-642b: 6F) using IgG (negative control), rabbit polyclonal antibody R4-17 (control), STC43H11-1, and E1L3N antibodies, respectively. STC43H11-1 was used for immunostaining at a concentration of 2 μg / mL.

[0071] [Figure 14]FIG. 14 shows immunohistochemistry assays for tissue samples (LC-642b: 6G) using immunostaining of tissue samples with IgG (negative control), rabbit polyclonal antibody R4-17 (control), STC43H11-1, and E1L3N antibodies, respectively.

[0072] [Figure 15] Figure 15 shows immunohistochemistry assay of tissue sample (HN TMA: E6) using IgG (negative control), rabbit polyclonal antibody R4-17 (control), STC43H11-1, and E1L3N antibody, respectively. STC43H11-1 was used for immunostaining at a concentration of 2 μg / mL.

[0073] [Figure 16] Figure 16 shows immunohistochemistry assay of tissue sample (HN TMA: B3) using IgG (negative control), rabbit polyclonal antibody R4-17 (control), STC43H11-1, and E1L3N antibody, respectively. STC43H11-1 was used for immunostaining at a concentration of 2 μg / mL.

[0074] [Figure 17] Figure 17 shows immunostaining of multiple skin tumor tissues, pancreatic cancer tissues, and breast cancer tissues using STC43H11-1 in an immunohistochemistry assay. STC43H11-1 was used for immunostaining at a concentration of 2 μg / mL.

[0075] [Figure 18] FIG. 18 shows immunostaining of esophageal and endometrial cancer tissues with STC43H11-1 in an immunohistochemistry assay.

[0076] [Figure 19]Figures 19A-19D show immunostaining of mouse 4T1 breast cancer cells expressing mBTN1A1 (lower panel) or not expressing mBTN1A1 (upper panel) in an immunohistochemistry assay. STC43H11-1 was used for immunostaining at a concentration of 2 μg / mL (Figure 19B), 5 μg / mL (Figure 19C), or 10 μg / mL (Figure 19D). Rabbit IgG was used for immunostaining at a concentration of 10 μg / mL as a negative control (Figure 19A).

[0077] [Figure 20] Figure 20 shows detection of BTN1A1 protein by immunohistochemistry in snap-frozen mouse mammary fat pads. Mice were either mBTN1A1 heterologous (heterologous) or BTN1A1 knockout (KO). STC43H11-1 was used for immunostaining at a concentration of 10 μg / mL.

[0078] [Figure 21] FIG. 21 shows sensorgrams illustrating the steps of the interaction between STC43H11-1 and variants of peptide 4 containing mutated alanine (or glycine) residues at specific positions as shown in Table 14.

[0079] [Figure 22] 22 shows sensorgrams illustrating the interaction between STC43H11-1 and mutants of peptide 4 containing alanine mutations. STC43H11-1 was found to bind to peptide 4 and mutant peptides #6 and #10 of peptide 4.

[0080] [Figure 23] FIG. 23 shows sensorgrams illustrating the interaction between STC43H11-1 and peptide 4 or various mutant variants of peptide 4.

[0081] [Figure 24]FIG. 24 shows a sensorgram illustrating the interaction between STC43H11-1 and a peptide containing an amino acid sequence that is homologous to the amino acid sequence of peptide 4.

[0082] [Diagram 25] Figure 25 shows the detection of mutant variants of peptide 4 expressed by HEK293T cells by Western blot using STC43H11-1 at a concentration of (1 μg / ml). Western blotting detection of Flag peptide and β-actin expressed by the cells is also shown as a control.

[0083] [Figure 26] FIG. 26 shows the quantified percentage of relative binding between STC43H11-1 and the mutant variants of peptide 4 as measured by the Western blotting assay shown in FIG.

[0084] [Figure 27] FIG. 27 shows an alignment of the ECD domains of mouse BTN1A1 (SEQ ID NO: 131), human BTN1A1 (SEQ ID NO: 132), and rabbit BTN1A1 (SEQ ID NO: 133).

[0085] [Figure 28] Figure 28 shows both N-terminal signal peptides. [ka] 1 shows the alignment of the heavy chain between STC43G3-1 (SEQ ID NO: 134) and STC85F1-1 (SEQ ID NO: 136), having the following structure:

[0086] [Figure 29] Figure 29 shows both N-terminal signal peptides. [ka] 1 shows the alignment of the light chain between STC43G3-1 (SEQ ID NO: 135) and STC85F1-1 (SEQ ID NO: 137), having the following structure:

[0087] [Diagram 30] Figures 30A and 30B show binding of several purified antibodies to ECD1 or hBTN1A1-His by ELISA.

[0088] [Diagram 31] Figures 31A and 31B show the binding of purified STC43G3-1 and STC85F1-1, respectively, to monomeric forms of BTN1A1 (denatured hBTN1A1-His and hBTN1A1-His), and to the ECD1 peptide by ELISA.

[0089] [Figure 32A] Figure 32A shows detection of BTN1A1 protein expressed on HEK293T cells by immunohistochemistry using the STC43G3-1 antibody, in which HEK293T cells overexpressing BTN1A1 (bottom row) are compared to HEK293T cells not overexpressing BTN1A1 (top row).

[0090] [Figure 32B] Figure 32B shows a magnified image of Figure 32A. The STC43G3-1 antibody shows strong membrane staining of BTN1A1 on the membrane of HEK293T cells.

[0091] [Figure 33A] Figure 33A shows detection of BTN1A1 protein expressed on HEK293T cells by immunohistochemistry using STC85F1-1 antibody. HEK293T cells overexpressing BTN1A1 (bottom row) compared to HEK293T cells not overexpressing BTN1A1 (top row).

[0092] [Figure 33B] Figure 33B shows a magnified image of Figure 33A. The STC85F1-1 antibody shows strong membrane staining of BTN1A1 on the membrane of HEK293T cells.

[0093] [Diagram 34] FIG. 34 shows a map of the human BTN1A1 amino acid sequence (SEQ ID NO:1). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0094] (4. Detailed Description) Costimulatory molecules of the B7 family can promote immune cell activation and inhibition. A related family of molecules - butyrophilins - also have similar immunoregulatory functions as B7 family members. Butyrophilin, subfamily 1, member A1 ("BTN1A1") is a type I membrane glycoprotein and a major component of the milk fat globule membrane, and has structural similarity to the B7 family. BTN1A1 is known to be the main protein regulating lipid droplet formation in milk (Ogg et al., PNAS, 101(27):10084-10089 (2004)). BTN1A1 is also expressed in immune cells, including T cells. Treatment with recombinant BTN1A1 was found to inhibit T cell activation and protect against animal models of EAE (Stefferl et al., J. Immunol. 165(5):2859-65 (2000)).

[0095] BTN1A1 is also specifically and highly expressed in cancer cells, and its expression can be used to aid in the diagnosis of cancer as well as the evaluation of the efficacy of cancer treatments.

[0096] Provided herein are anti-BTN1A1 antibodies and other molecules that immunospecifically bind to BTN1A1 and methods of their use in providing cancer diagnosis, evaluating cancer treatments, or modulating immune cell activity, and treating cancer.

[0097] (4.1 General Technology) The techniques or procedures described or referred to herein include those that are generally well understood by those of skill in the art and / or commonly employed using conventional methods, such as the widely employed methods described in, for example, Sambrook et al., Molecular Cloning: A Laboratory Manual (3rd ed., 2001); Current Protocols in Molecular Biology (Ausubel et al., eds., 2003); Therapeutic Monoclonal Antibodies: From Bench to Clinic (An, eds., 2009); Monoclonal Antibodies: Methods and Protocols (Albitar, eds., 2010); and Antibody Engineering, vols. 1 and 2 (Kontermann and Dubel, eds., 2010).

[0098] (4.2 Terminology) Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art. For the purposes of interpreting this specification, the following explanations of terms are applied, and whenever appropriate, terms used in the singular form also include the plural form and vice versa. All patents, applications, published applications, and other publications are incorporated by reference in their entirety. If any explanation of the terms described contradicts any document incorporated by reference herein, the explanation set forth below shall prevail.

[0099] As used herein, and unless otherwise specified, the term "butyrophilin, subfamily 1, member A1" or "BTN1A1" refers to BTN1A1 from any vertebrate source, including mammals, e.g., primates (e.g., humans, cynos), dogs, and rodents (e.g., mice and rats). Unless otherwise specified, BTN1A1 also includes various BTN1A1 isoforms, related BTN1A1 polypeptides, including SNP variants thereof, and various modified forms of BTN1A1, including, but not limited to, phosphorylated BTN1A1, glycosylated BTN1A1, and ubiquitinated BTN1A1. As used herein, glycosylated BTN1A1 includes BTN1A1 having N55, N215, and / or N449 glycosylation.

[0100] An exemplary amino acid sequence of human BTN1A1 (BC096314.1 GI: 64654887) is provided below: [ka]

[0101] An exemplary coding nucleic acid sequence for human BTN1A1 (BC096314.1 GI: 64654887) is provided below: [ka]

[0102] A signal peptide is a short amino acid sequence that can control protein secretion and translocation in living cells. In some embodiments, the signal peptide can be fused to an antibody sequence, for example, to the heavy chain (e.g., VH) or light chain (e.g., VL) of an antibody. In some embodiments, the signal peptide is fused to the N-terminus of the antibody sequence. In some embodiments, the signal peptide is fused to the N-terminus of an antibody VH sequence described herein. In some embodiments, the signal peptide is fused to the N-terminus of an antibody VL sequence described herein. In some embodiments, the signal peptide is fused to the N-terminus of an antibody VH region. In a specific embodiment, the signal peptide is [ka] and is fused to the N-terminus of an antibody VH sequence described herein. In a specific embodiment, the signal peptide has the sequence: [ka] and is fused to an antibody VL sequence described herein.

[0103] BTN1A1 polypeptide "intracellular domain" or "ICD" refers to a form of a BTN1A1 polypeptide that is essentially free of transmembrane and extracellular domains. For example, a BTN1A1 polypeptide ICD may have less than 1% of such transmembrane and / or extracellular domains, and may have less than 0.5% of such domains. Figure 2 shows an alignment of two example BTN1A1 ICD amino acid sequences from human and mouse, respectively. The ICD domains include [ka] A peptide having the sequence: (peptide 4) was used as an immunogen to produce anti-BTN1A1 antibodies, such as STC43H11-1.

[0104] BTN1A1 polypeptide "extracellular domain" or "ECD" refers to a form of the BTN1A1 polypeptide that is essentially free of transmembrane and intracellular domains. For example, a BTN1A1 polypeptide extracellular domain may have less than 1% of such transmembrane and / or intracellular domains, and may have less than 0.5% of such domains. Two regions in the BTN1A1 ECD (sometimes referred to herein as "ECD1" and "ECD2") were selected for animal immunization. Figure 27 shows an alignment of the ECD amino acid sequences between mouse, human, and rabbit. The ECD domain (ECD1) [ka] was used as an immunogen to produce anti-BTN1A1 antibodies, such as STC43G3-1 and STC85F1-1.

[0105] "Related BTN1A1 polypeptides" include allelic variants (e.g., SNP variants); splice variants; fragments; derivatives; substitution, deletion, and insertion variants; fusion polypeptides; and interspecies homologs, which may retain BTN1A1 activity. As will be appreciated by those skilled in the art, the anti-BTN1A1 antibodies provided herein may bind to a BTN1A1 polypeptide, a BTN1A1 polypeptide fragment, a BTN1A1 antigen, and / or a BTN1A1 epitope. An "epitope" may be a portion of a larger BTN1A1 antigen, which may be a portion of a larger BTN1A1 polypeptide fragment, which may in turn be a portion of a larger BTN1A1 polypeptide. BTN1A1 may be present in native or denatured form. The BTN1A1 polypeptides described herein may be isolated from a variety of sources, such as from human tissue types or from another source, or may be prepared by recombinant or synthetic methods. Orthologs of BTN1A1 polypeptides are also well known in the art.

[0106] The terms "BTN1A1 activity," "BTN1A1 signaling," and "BTN1A1 ligand-like signaling" as applied to a binding protein, such as an antibody that binds to BTN1A1 of the present disclosure, mean that the binding protein (e.g., an antibody) mimics or modulates the biological effect induced by binding of a BTN1A1 ligand, or induces a biological response that would otherwise result from the binding of a BTN1A1 ligand to BTN1A1, e.g., in vivo or in vitro. When assessing the binding specificity of an anti-BTN1A1 antibody, e.g., an antibody or fragment thereof that binds to BTN1A1 (e.g., human BTN1A1), the antibody is considered to induce a biological response if the response is 5% or more, e.g., 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 125%, 150%, 175%, or 200% or more, of the activity of a wild-type BTN1A1 ligand standard. In one embodiment, the anti-BTN1A1 antibody or BTN1A1 ligand is immobilized (e.g., on a plastic surface or bead). In certain embodiments, the antibody has the following properties: (1) an EC of 100 nM or less, e.g., 90 nM, 80 nM, 70 nM, 60 nM, 50 nM, 40 nM, 30 nM, 20 nM, 10 nM, 5 nM, 2 nM, 1 nM, 0.5 nM, 0.2 nM, or 0.1 nM, in a human or cynomolgus monkey PBMC assay (see, e.g., Examples 4.2.1 and 4.2.2); or (2) a human whole blood sample assay (see, e.g., Example 4.2.1). 50 , showing potency levels of 5% or greater than that of the BTN1A1 ligand standard.

[0107] The term "binding protein" refers to a protein that includes a portion that binds to BTN1A1, including human, mouse, and / or cynomolgus BTN1A1 (e.g., one or more binding regions, e.g., CDRs), and, optionally, a scaffold or framework portion (e.g., one or more scaffold or framework regions) that enables the binding portion to adopt a conformation that promotes binding of the binding protein to a BTN1A1 polypeptide, fragment, or epitope. Examples of such binding proteins include human antibodies, humanized antibodies, chimeric antibodies, recombinant antibodies, single chain antibodies, diabodies, triabodies, tetrabodies, Fab fragments, F(ab')2 antibodies, and the like. 2 The binding proteins may include antibodies, such as IgD, IgE, IgM, IgG1, IgG2, IgG3, or IgG4 antibodies, and fragments thereof. The binding proteins may include, for example, another protein scaffold or an artificial scaffold onto which CDRs or CDR derivatives have been grafted. Such scaffolds include, but are not limited to, antibody-derived scaffolds, including mutations introduced to stabilize the three-dimensional structure of the binding protein, and fully synthetic scaffolds, including, for example, biocompatible polymers. See, for example, Korndorfer et al., 2003, Proteins: Structure, Function, and Bioinformatics 53(1):121-29; and Roque et al., 2004, Biotechnol. Prog. 20:639-54. Additionally, peptide antibody mimetics ("PAMs") and scaffolds based on antibody mimetics utilizing fibronectin components as scaffolds may be used. In the context of the present disclosure, a binding protein can be, for example, a protein having a dissociation constant (K D ) is ≦10 -7 M. In some embodiments, a binding protein (e.g., an antibody) is said to specifically or selectively bind to BTN1A1 when the binding protein has a molecular weight of about 10 -7 M ~ about 10 -12 K of M DIn some embodiments, the binding protein (e.g., an antibody) can specifically bind to BTN1A1 at K D is ≦ 10 -8 M or K D is ≦ 10 -9 When it is M, it can specifically bind to BTN1A1 with high affinity.

[0108] In one embodiment, the binding protein (e.g., an antibody) has a binding affinity of 1×10 as measured by Biacore®. -9 M~10×10 -9 K of M D In another embodiment, the binding protein (e.g., antibody) can specifically bind to purified human BTN1A1 at a concentration of 0.1×10 as measured by KinExA™ (Sapidyne, Boise, ID). -9 M~1×10 -9 K of M D In yet another embodiment, the binding protein (e.g., antibody) can specifically bind to purified human BTN1A1 at a concentration of 0.1×10 -9 M~10×10 -9 K of M D In one embodiment, the binding protein (e.g., antibody) specifically binds to human BTN1A1 expressed on cells at a concentration of 0.1×10 -9 M~1×10 -9 K of M D In some embodiments, the binding protein (e.g., antibody) specifically binds to human BTN1A1 expressed on cells at a concentration of 1×10 -9 M~10×10 -9 K of M D In one embodiment, the binding protein (e.g., antibody) specifically binds to human BTN1A1 expressed on cells at a concentration of about 0.1×10 -9 M, approx. 0.5×10 -9 M, about 1 x 10 -9 M, about 5 x 10 -9 M, about 10 x 10 -9 M, or any range or interval of K DIn yet another embodiment, the binding protein (e.g., antibody) specifically binds to human BTN1A1 expressed on cells at a concentration of 0.1×10 -9 M~10×10 -9 K of M D In one embodiment, the binding protein (e.g., antibody) can specifically bind to cynomolgus BTN1A1 expressed on cells at a concentration of 0.1×10 -9 M~1×10 -9 K of M D In some embodiments, the binding protein (e.g., antibody) specifically binds to cynomolgus BTN1A1 expressed on cells at a concentration of 1×10 -9 M~10×10 -9 K of M D In one embodiment, the binding protein (e.g., antibody) specifically binds to cynomolgus BTN1A1 expressed on cells at a concentration of about 0.1 x 10 -9 M, approx. 0.5×10 -9 M, about 1 x 10 -9 M, about 5 x 10 -9 M, about 10 x 10 -9 M, or any range or interval of K D In yet another embodiment, the binding protein (e.g., antibody) specifically binds to cynomolgus BTN1A1 expressed on cells at a concentration of 0.1 x 10 -9 M~10×10 -9 K of M D In one embodiment, the binding protein (e.g., antibody) can specifically bind to mouse BTN1A1 expressed on cells at a concentration of 0.1×10 -9 M~1×10 -9 K of M D In some embodiments, the binding protein (e.g., antibody) specifically binds to mouse BTN1A1 expressed on cells at a concentration of 1×10 -9 M~10×10 -9 K of M D In one embodiment, the binding protein (e.g., antibody) specifically binds to mouse BTN1A1 expressed on cells at a concentration of about 0.1 x 10 -9 M, approx. 0.5×10 -9M, about 1 x 10 -9 M, about 5 x 10 -9 M, about 10 x 10 -9 M, or any range or interval of K D and specifically binds to mouse BTN1A1 expressed on cells.

[0109] The terms "antibody," "immunoglobulin," or "Ig" are used interchangeably herein and in the broadest sense, specifically including, for example, individual anti-BTN1A1 monoclonal antibodies (including agonist, antagonist, neutralizing, full-length or intact monoclonal antibodies), anti-BTN1A1 antibody compositions having multi-epitope or single-epitope specificity, polyclonal or monovalent antibodies, multivalent antibodies, multispecific antibodies formed from at least two intact antibodies (e.g., bispecific antibodies, so long as they exhibit the desired biological activity), single-chain anti-BTN1A1 antibodies, and fragments of anti-BTN1A1 antibodies, as described below. Antibodies can be human, humanized, chimeric, and / or affinity matured, as well as antibodies from other species, such as mouse and rabbit. The term "antibody" is intended to include polypeptide products of B cells within the immunoglobulin class of polypeptides that are capable of binding to a specific molecular antigen and are composed of two identical pairs of polypeptide chains, each pair having one heavy chain (about 50-70 kDa) and one light chain (about 25 kDa), each amino-terminal portion of each chain comprising a variable region of about 100 to about 130 or more amino acids, and each carboxy-terminal portion of each chain comprising a constant region. See, e.g., Antibody Engineering (Borrebaeck, ed., 2nd ed., 1995); and Kuby, Immunology (3rd ed., 1997). In a specific embodiment, a specific molecular antigen can be bound by an antibody provided herein, e.g., a BTN1A1 polypeptide, a BTN1A1 fragment, or a BTN1A1 epitope. Antibodies include, but are not limited to, synthetic antibodies, recombinantly produced antibodies, camelized antibodies, intrabodies, anti-idiotypic (anti-Id) antibodies, and functional fragments of any of the above (e.g., antigen-binding fragments such as BTN1A1-binding fragments), where a functional fragment refers to a portion of an antibody heavy or light chain polypeptide that retains some or all of the binding activity of the antibody from which the fragment is derived.Non-limiting examples of functional fragments (e.g., antigen-binding fragments such as BTN1A1-binding fragments) include single chain Fvs (scFvs) (e.g., monospecific, bispecific, etc.), Fab fragments, F(ab') fragments, and F(ab). 2 Fragment, F(ab') 2 These include Fv fragments, disulfide-linked Fv (dsFv), Fd fragments, Fv fragments, diabodies, triabodies, tetrabodies, and minibodies. In particular, the antibodies provided herein include immunoglobulin molecules and immunologically active portions of immunoglobulin molecules, such as antigen binding domains or molecules that contain an antigen binding site that binds the BTN1A1 antigen (e.g., one or more CDRs of an anti-BTN1A1 antibody). Such antibody fragments can be found, for example, in Harlow and Lane, Antibodies: A Laboratory Manual (1989); Mol. Biology and Biotechnology: A Comprehensive Desk Reference (Myers, ed., 1995); Huston et al., 1993, Cell Biophysics 22:189-224; Pluckthun and Skerra, 1989, Meth. Enzymol. 178:497-515; and Day, Advanced Immunochemistry (2nd ed., 1990). The antibodies provided herein can be of any class (e.g., IgG, IgE, IgM, IgD, and IgA) or any subclass (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2) of immunoglobulin molecules. Anti-BTN1A1 antibodies can be agonistic or antagonistic antibodies. Provided herein are agonistic antibodies to BTN1A1, including antibodies that induce BTN1A1 signaling.

[0110] The term "monoclonal antibody" as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, e.g., the individual antibodies comprising the population are identical except for possible minor natural mutations, and each monoclonal antibody usually recognizes a single epitope on an antigen. In a specific embodiment, a "monoclonal antibody" as used herein is an antibody produced by a single hybridoma or other cell, where the antibody binds only to a BTN1A1 epitope, e.g., as determined by ELISA or other antigen-binding or competitive binding assays known in the art. The term "monoclonal" is not limited to any particular antibody production method. For example, the monoclonal antibodies useful in the present disclosure can be prepared by the hybridoma method first described by Kohler et al., 1975, Nature 256:495, or can be produced in bacterial cells or eukaryotic animal cells or plant cells using recombinant DNA methods (see, e.g., U.S. Pat. No. 4,816,567). "Monoclonal antibodies" can also be isolated from phage antibody libraries using the techniques described, for example, in Clackson et al., 1991, Nature 352:624-28 and Marks et al., 1991, J. Mol. Biol. 222:581-97. Other methods for preparing clonal cell lines and the monoclonal antibodies expressed thereby are well known in the art. See, for example, Short Protocols in Molecular Biology (Ausubel et al., eds., 5th ed., 2002). Exemplary methods for producing monoclonal antibodies are provided in the Examples herein.

[0111] As used herein, "polyclonal antibodies" refers to an antibody population generated in an immunogenic response to a protein with many epitopes, and thus includes a variety of different antibodies to the same or different epitopes within the protein. Methods for producing polyclonal antibodies are known in the art (see, for example, Short Protocols in Molecular Biology (Ausubel et al., eds., 5th ed., 2002)).

[0112] The term "fragment" as used herein in the context of a peptide or polypeptide refers to a peptide or polypeptide that comprises less than the full length amino acid sequence. Such fragments can result, for example, from truncations at the amino terminus, truncations at the carboxy terminus, and / or internal deletion of residues from the amino acid sequence. Fragments can result, for example, from alternative RNA splicing or from in vivo protease activity. In certain embodiments, a BTN1A1 fragment or anti-BTN1A1 antibody fragment comprises at least 5 contiguous amino acid residues, at least 10 contiguous amino acid residues, at least 15 contiguous amino acid residues, at least 20 contiguous amino acid residues, at least 25 contiguous amino acid residues, at least 30 contiguous amino acid residues, at least 40 contiguous amino acid residues, at least 50 contiguous amino acid residues, at least 60 contiguous amino acid residues, at least 70 contiguous amino acid residues, at least 80 contiguous amino acid residues, at least 90 ...0 contiguous amino acid residues, at least 10 contiguous amino acid residues, at least 10 contiguous amino acid residues, at least 10 contig In certain embodiments, a fragment of a BTN1A1 polypeptide or anti-BTN1A1 antibody comprises an amino acid sequence of at least one, at least two, at least three, or more of the amino acid residues of the polypeptide or antibody.

[0113] An "antigen" is a predetermined antigen to which an antibody can selectively bind. A target antigen can be a polypeptide, carbohydrate, nucleic acid, lipid, hapten, or other natural or synthetic compound. In some embodiments, the target antigen is a polypeptide.

[0114] The terms "antigen-binding fragment," "antigen-binding domain," "antigen-binding region," and similar terms refer to the portion of an antibody (e.g., the CDRs) that contains the amino acid residues that interact with an antigen and confer on the binding agent its specificity and affinity for the antigen.

[0115] An "epitope" is a site on the surface of an antigen molecule to which a single antibody molecule binds, e.g., a localized region on the surface of an antigen, such as a BTN1A1 polypeptide or BTN1A1 polypeptide fragment, that can bind to one or more antigen-binding regions of an antibody and has antigenic or immunogenic activity, i.e., can elicit an immune response in an animal, e.g., a mammal (e.g., a human). An epitope with immunogenic activity is a portion of a polypeptide that elicits an antibody response in an animal. An epitope with antigenic activity is a portion of a polypeptide to which an antibody binds, as determined by any method known in the art, including, e.g., by immunoassay. An antigenic epitope is not necessarily immunogenic. Epitopes often consist of chemically active surface groupings of molecules, such as amino acids or sugar side chains, and have specific three-dimensional structural characteristics and specific charge characteristics. Antibody epitopes can be linear or conformational epitopes. Linear epitopes are formed by consecutive sequences of amino acids in a protein. Conformational epitopes are formed from amino acids that are discontinuous in the protein sequence but come together by folding of the protein into its three-dimensional structure. Derived epitopes are formed when the three-dimensional structure of a protein assumes an altered conformation, for example, after activation or binding of another protein or ligand. In one embodiment, the BTN1A1 epitope is a three-dimensional surface feature of the BTN1A1 polypeptide. In another embodiment, the BTN1A1 epitope is a linear feature of the BTN1A1 polypeptide. Usually, an antigen has several or many different epitopes and can react with many different antibodies.

[0116] An antibody binds to an "epitope", "essentially the same epitope" as a reference antibody, or "the same epitope" as a reference antibody if the two antibodies recognize the same, overlapping, or adjacent epitopes in three-dimensional space. The most widely used rapid method for determining whether two antibodies bind to the same, overlapping, or adjacent epitopes in three-dimensional space is a competition assay, which can be configured in several different formats, for example, using either labeled antigen or labeled antibody. In some assays, the antigen is immobilized on a 96-well plate or expressed on a cell surface, and the ability of an unlabeled antibody to block the binding of the labeled antibody is measured using a radioactive, fluorescent, or enzymatic label.

[0117] "Epitope mapping" is the process of identifying the binding site, or epitope, of an antibody on its target antigen. "Epitope binning" is the process of classifying antibodies based on the epitopes they recognize. More specifically, epitope binning includes methods and systems that use competitive assays combined with computational processes to distinguish the epitope recognition characteristics of different antibodies and cluster antibodies based on their epitope recognition characteristics, and to identify antibodies with different binding specificities.

[0118] The term "bind" or "binding" refers to interactions between molecules, including, for example, forming a complex. The interactions can be non-covalent interactions, including, for example, hydrogen bonds, ionic bonds, hydrophobic interactions, and / or van der Waals interactions. A complex can also include the association of two or more molecules joined by covalent or non-covalent bonds, interactions, or forces. The strength of the overall non-covalent interactions between a single antigen binding site on an antibody and a single epitope on a target molecule, such as BTN1A1, is the affinity of the antibody or functional fragment for that epitope. The dissociation rate (k off ) and association rate (k on ) ratio (k off / k on ) is the dissociation constant K, which is inversely related to affinity D It is. DThe lower the value, the higher the affinity of the antibody. D The value of k varies depending on the antibody-antigen complex. on and k off The dissociation constant K of the antibodies provided herein depends on both D can be determined using any of the methods provided herein or any other methods known to those skilled in the art. The affinity at one binding site does not necessarily reflect the true strength of the antibody-antigen interaction. When a composite antigen containing multiple repeating antigenic determinants, such as multivalent BTN1A1, contacts an antibody containing multiple binding sites, the interaction of the antibody with the antigen at one site increases the probability of a reaction at a second site. The strength of such multiple interactions between a multivalent antibody and an antigen is called avidity. The avidity of an antibody can be a better measure of its binding ability than the affinity of its individual binding sites. For example, high avidity can compensate for the low affinity sometimes seen with pentameric IgM antibodies, which may have a lower affinity than IgG but can effectively bind to antigens due to the high avidity of IgM resulting from its multivalency.

[0119] The terms "antibody that specifically binds to BTN1A1", "antibody that specifically binds to a BTN1A1 epitope", and similar terms are also used interchangeably herein and refer to an antibody that specifically binds to a BTN1A1 polypeptide, e.g., a BTN1A1 antigen or fragment or epitope (e.g., human BTN1A1, e.g., a human BTN1A1 polypeptide, antigen, or epitope). An antibody that specifically binds to BTN1A1 (e.g., human BTN1A1) can bind to the extracellular domain of BTN1A1 or a peptide derived from the extracellular domain. An antibody that specifically binds to a BTN1A1 antigen (e.g., human BTN1A1) can cross-react with related antigens (e.g., cynomolgus monkey BTN1A1). In certain embodiments, an antibody that specifically binds to a BTN1A1 antigen does not cross-react with other antigens. An antibody that specifically binds to a BTN1A1 antigen can be identified, for example, by immunoassays, Biacore®, or other techniques known to those of skill in the art. An antibody specifically binds to the BTN1A1 antigen if it binds to the BTN1A1 antigen with higher affinity than to any cross-reactive antigen, as determined using experimental techniques such as radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA). Typically, a specific or selective response is at least twice the background signal or noise, and may be more than 10 times the background. For example, see Fundamental Immunology 332-36 (Paul, ed., 2nd ed., 1989) for a discussion of antibody specificity. An antibody that "binds to an antigen of interest (e.g., a target antigen such as BTN1A1)" is an antibody that binds to the antigen with sufficient affinity to be useful as a therapeutic agent in targeting cells or tissues expressing the antigen, and does not significantly cross-react with other proteins. In such an embodiment, the extent of binding of the antibody to a "non-target" protein is less than about 10% of the binding of the antibody to its particular target protein, as determined, for example, by fluorescence-activated cell sorting (FACS) analysis or RIA.With respect to the binding of an antibody to a target molecule, the terms "specific binding", "specifically binds to" an epitope on a particular polypeptide or a particular polypeptide target, or "is specific for" an epitope on a particular polypeptide or a particular polypeptide target, refer to binding that is measurably different from non-specific interactions. Specific binding can be measured, for example, by determining the binding of a molecule compared to the binding of a control molecule, which is usually a molecule of similar structure that has no binding activity. For example, specific binding can be determined by competition with a control molecule that is similar to the target, for example, an excess of unlabeled target. In this case, specific binding is indicated when the binding of the labeled target to the probe is competitively inhibited by an excess of unlabeled target. The terms "anti-BTN1A1 antibody" or "antibody that binds to BTN1A1" include antibodies that can bind to BTN1A1 with sufficiently high affinity that the antibody is useful, for example, as a diagnostic agent in targeting BTN1A1. As used herein, the terms "specific binding," "specifically binds to" an epitope on a particular polypeptide or a particular polypeptide target, or "is specific for" an epitope on a particular polypeptide or a particular polypeptide target, refer to binding where a molecule binds to a particular polypeptide or an epitope on a particular polypeptide without substantially binding to any other polypeptides or polypeptide epitopes. In certain embodiments, an antibody that binds to BTN1A1 has a dissociation constant (K) of 10 nM, 5 nM, 4 nM, 3 nM, 2 nM, 1 nM, 0.9 nM, 0.8 nM, 0.7 nM, 0.6 nM, 0.5 nM, 0.4 nM, 0.3 nM, 0.2 nM, or 0.1 nM or less. D In certain embodiments, the anti-BTN1A1 antibody binds to an epitope of BTN1A1 that is conserved between BTN1A1 from different species (e.g., between human BTN1A1 and cynomolgus monkey BTN1A1).

[0120] The term "compete" when used in the context of anti-BTN1A1 antibodies (e.g., agonist antibodies and binding proteins that bind to BTN1A1 and compete for the same epitope or binding site on a target) means competition as determined by an assay in which the antibody (or binding fragment) under test interferes with or inhibits specific binding of a reference molecule (e.g., a reference ligand or reference antigen binding protein, e.g., a reference antibody) to a common antigen (e.g., BTN1A1 or a fragment thereof). Many types of competitive binding assays can be used to determine whether a test antibody competes with a reference antibody for binding to BTN1A1 (e.g., human BTN1A1). Examples of assays that can be utilized include solid-phase direct or indirect RIA, solid-phase direct or indirect enzyme immunoassays (EIA), sandwich competition assays (see, e.g., Stahli et al., 1983, Methods in Enzymology 9:242-53), solid-phase direct biotin-avidin EIA (see, e.g., Kirkland et al., 1986, J. Immunol. 137:3614-19), solid-phase direct label assays, solid-phase direct label sandwich assays (see, e.g., Harlow and Lane, Antibodies, A Laboratory Manual (1988)), solid-phase direct label RIA using an I-125 label (see, e.g., Morel et al., 1988, Mol. Immunol. 25:7-15), and direct label RIA (Moldenhauer et al., 1990, Scand. J. Immunol. 32:77-82). Typically, such assays involve the use of purified antigen (e.g., BTN1A1, e.g., human BTN1A1) bound to a solid surface, or cells bearing either an unlabeled test antigen binding protein (e.g., a test anti-BTN1A1 antibody) or a labeled reference antigen binding protein (e.g., a reference anti-BTN1A1 antibody). Competitive inhibition can be measured by determining the amount of label bound to the solid surface or cells in the presence of the test antigen binding protein. Typically, the test antigen binding protein is present in excess.Antibodies identified by competitive assays (competing antibodies) include antibodies that bind to the same epitope as the reference antibody and / or antibodies that bind to adjacent epitopes close enough to the epitope bound by the reference for steric hindrance of the antibodies to occur. Further details regarding methods for determining competitive binding are described herein. Usually, when a competing antibody protein is present in excess, it inhibits the specific binding of the reference antibody to a common antigen by at least 30%, for example, 40%, 45%, 50%, 55%, 60%, 65%, 70%, or 75%. In some cases, binding is inhibited by at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more.

[0121] An "isolated" antibody is substantially free of cellular material or other contaminating proteins from the cell or tissue source and / or other contaminating components from which the antibody is derived, or, if chemically synthesized, is substantially free of chemical precursors or other chemicals. The phrase "substantially free of cellular material" includes preparations of an antibody in which the antibody is separated from cellular components of the cells from which the antibody is isolated or recombinantly produced. Thus, an antibody that is substantially free of cellular material includes preparations of an antibody having less than about 30%, 25%, 20%, 15%, 10%, 5%, or 1% (by dry weight) of heterologous proteins (also referred to herein as "contaminating proteins"). In certain embodiments, when an antibody is recombinantly produced, it is substantially free of culture medium, e.g., culture medium represents less than about 20%, 15%, 10%, 5%, or 1% of the volume of the protein preparation. In certain embodiments, when an antibody is produced by chemical synthesis, it is substantially free of chemical precursors or other chemicals, e.g., it is separated from chemical precursors or other chemicals involved in the synthesis of the protein. Thus, such preparations of antibodies have less than about 30%, 25%, 20%, 15%, 10%, 5%, or 1% (by dry weight) of chemical precursors or compounds other than the antibody of interest. Contaminating components may include, but are not limited to, substances that interfere with therapeutic use of the antibody, and may include enzymes, hormones, and other proteinaceous or non-proteinaceous solutes. In certain embodiments, the antibody is purified (1) to greater than 95%, e.g., 96%, 97%, 98%, or 99%, by weight of the antibody, as measured by the Lowry method (Lowry et al., 1951, J. Bio. Chem. 193: 265-75), (2) to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence by use of a spinning cup sequenator, or (3) to homogeneity by SDS-PAGE under reducing or non-reducing conditions with Coomassie blue or silver staining. Isolated antibody includes the antibody in situ within recombinant cells since at least one component of the antibody's natural environment will not be present. Ordinarily, however, isolated antibody will be prepared by at least one purification step.In a specific embodiment, the antibodies provided herein are isolated.

[0122] The four-chain antibody unit is a heterotetrameric glycoprotein composed of two identical light (L) chains and two identical heavy (H) chains. For IgG, the four-chain unit is usually about 150,000 daltons. Each L chain is linked to the H chain by one covalent disulfide bond, while the two H chains are linked to each other by one or more disulfide bonds depending on the H chain isotype. Each H and L chain also has regularly spaced intrachain disulfide bridges. Each H chain has a variable domain (VH) at the N-terminus, followed by three constant domains (CH) for each of the α and γ chains, and four CH domains for the μ and ε isotypes. Each L chain has a variable domain (VL) at the N-terminus, followed by a constant domain (CL) at its other end. The VL is aligned with the VH, and the CL is aligned with the first constant domain (CH1) of the heavy chain. It is believed that certain amino acid residues form an interface between the light chain variable domain and the heavy chain variable domain. When VH and VL are paired together, a single antigen-binding site is formed. For the structure and properties of different classes of antibodies, see, for example, Basic and Clinical Immunology 71 (Stites et al., eds., 8th ed., 1994).

[0123] The term "heavy chain" when used with respect to an antibody refers to a polypeptide chain of about 50-70 kDa, the amino-terminal portion of which contains a variable region of about 120-130 or more amino acids, and the carboxy-terminal portion of which contains a constant region. The constant region can be one of five different types (e.g., isotypes), called alpha (α), delta (δ), epsilon (ε), gamma (γ), and mu (μ), based on the amino acid sequence of the heavy chain constant region. The different heavy chains vary in size: α, δ, and γ contain about 450 amino acids, while μ and ε contain about 550 amino acids. When combined with light chains, these different types of heavy chains give rise to the five well-known classes (e.g., isotypes) of antibodies: IgA, IgD, IgE, IgG, and IgM, respectively, including the four subclasses of IgG, namely IgG1, IgG2, IgG3, and IgG4. The heavy chain can be a human heavy chain.

[0124] The term "light chain" when used in reference to an antibody refers to a polypeptide chain of about 25 kDa, the amino-terminal portion of which contains a variable region of about 100 to about 110 or more amino acids and the carboxy-terminal portion of which contains a constant region. The approximate length of a light chain is 211 to 217 amino acids. There are two different types, called kappa (κ) or lambda (λ), based on the amino acid sequence of the constant domain. Light chain amino acid sequences are well known in the art. The light chain can be a human light chain.

[0125] The terms "variable region", "variable domain", "V region", or "V domain" refer to the portion of an antibody light or heavy chain that is typically located at the amino terminus of the light or heavy chain, has a length of about 120-130 amino acids in the heavy chain and about 100-110 amino acids in the light chain, and is used in the context of the binding and specificity of each particular antibody to its particular antigen. The variable region of the heavy chain is sometimes referred to as "VH". The variable region of the light chain is sometimes referred to as "VL". The term "variable" refers to the fact that certain segments of the variable region vary widely in sequence between antibodies. The V region mediates antigen binding and defines the specificity of a particular antibody to its particular antigen. However, the variability is not evenly distributed across the 110 amino acid span of the variable region. Instead, the V region consists of less variable (e.g., relatively invariant) stretches called framework regions (FR) of about 15-30 amino acids separated by shorter regions of greater variability (e.g., extremely variable) called "hypervariable regions", each about 9-12 amino acids long. Each of the variable regions of the heavy and light chains comprises four FRs, which are mainly in the shape of a β-sheet, connected by three hypervariable regions, which form loops that connect and sometimes form part of the β-sheet structure. The hypervariable regions in each chain are held in close proximity to each other by the FRs, and together with the hypervariable regions from other chains, contribute to the formation of the antigen-binding site of the antibody (see, for example, Kabat et al., Sequences of Proteins of Immunological Interest (5th ed., 1991)). The constant region is not directly involved in binding the antibody to the antigen, but shows various effector functions, such as participating in antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) of the antibody. The variable region is highly variable in sequence between different antibodies. In a specific embodiment, the variable region is a human variable region.

[0126] The terms "variable region residue numbering as in Kabat" or "amino acid position numbering as in Kabat" and variations thereof refer to the numbering system used for the heavy or light chain variable regions of the compilation of antibodies in Kabat et al., supra. Using this numbering system, the actual linear amino acid sequence may contain fewer or additional amino acids corresponding to a shortening of, or an insertion into, a FR or CDR of the variable domain. For example, a heavy chain variable domain may contain a single amino acid insertion after residue 52 (residue 52a according to Kabat) as well as three inserted residues after residue 82 (e.g., residues 82a, 82b, and 82c, etc., according to Kabat). The Kabat numbering of residues can be determined for a given antibody by alignment of the antibody's sequence in the regions of homology with the "standard" Kabat numbered sequence. The Kabat numbering system is typically used when referring to residues in the variable domain (approximately residues 1-107 of the light chain and residues 1-113 of the heavy chain) (e.g., Kabat et al., supra). The "EU numbering system" or "EU index" is typically used when referring to residues in the immunoglobulin heavy chain constant region (e.g., the EU index as reported in Kabat et al., supra). "EU index as per Kabat" refers to the residue numbering of the human IgG1 EU antibody. Other numbering systems have been described, for example, by AbM, Chothia, Contact, IMGT, and AHon, and are encompassed herein.

[0127] "CDR" refers to one of the three hypervariable regions (H1, H2, or H3) in the non-framework region of an immunoglobulin (Ig or antibody) VH β-sheet framework, or one of the three hypervariable regions (L1, L2, or L3) in the non-framework region of an antibody VL β-sheet framework. Thus, CDRs are variable region sequences interspersed within framework region sequences. CDR regions are well known to those skilled in the art and have been defined, for example, by Kabat as the most hypervariable regions within antibody variable (V) domains (Kabat et al., 1997, J. Biol. Chem. 252:6609-16; Kabat, 1978, Adv. Prot. Chem. 32:1-75). CDR region sequences have also been structurally defined by Chothia as residues that are not part of a conserved β-sheet framework and therefore can adopt various conformations (Chothia and Lesk, 1987, J. Mol. Biol. 196:901-17). Both terminologies are well recognized in the art. CDR region sequences have also been defined by AbM, contact, and IMGT. The positions of CDRs within standard antibody variable regions have been determined by comparison of multiple structures (Al-Lazikani et al., 1997, J. Mol. Biol. 273:927-48; Morea et al., 2000, Methods 20:267-79). Because the number of residues within hypervariable regions varies among different antibodies, additional residues relative to the standard positions are conventionally numbered with a, b, c, etc. next to the residue number in the standard variable region numbering system (Al-Lazikani et al., supra). Such nomenclature is similarly well known to those of skill in the art.

[0128] The term "hypervariable region", "HVR" or "HV" as used herein refers to the region of an antibody variable region that is hypervariable in sequence and / or forms structurally defined loops. Typically, an antibody contains six hypervariable regions, three in VH (H1, H2, H3) and three in VL (L1, L2, L3). Several delineations of hypervariable regions are in use and are encompassed herein. The Kabat complementarity determining regions (CDRs) are based on sequence variability and are the most commonly used (see, e.g., Kabat et al., supra). Chothia instead refers to the location of structural loops (see, e.g., Chothia and Lesk, 1987, J. Mol. Biol. 196:901-17). The ends of the Chothia CDR-H1 loops, when numbered using the Kabat numbering convention, vary between H32 and H34 depending on the length of the loop (this is because the Kabat numbering system places insertions at H35A and H35B; if neither 35A nor 35B are present, the loop ends at 32; if only 35A is present, the loop ends at 33; if both 35A and 35B are present, the loop ends at 34). The AbM hypervariable regions represent a compromise of the Kabat CDRs and Chothia structural loops and are used by Oxford Molecular's AbM antibody modeling software (see, for example, Antibody Engineering, Vol. 2 (Kontermann and Dubel, eds., 2nd ed., 2010)). The "contact" hypervariable regions are based on an analysis of available complex crystal structures. Residues from each of these hypervariable regions or CDRs are listed below.

[0129] Recently, a universal numbering system, the ImMunoGeneTics (IMGT) Information System®, has been developed and widely adopted (Lafranc et al., 2003, Dev. Comp. Immunol. 27(1):55-77). IMGT is a comprehensive information system dedicated to immunoglobulins (IG), T cell receptors (TCR), and major histocompatibility complexes (MHC) of humans and other vertebrates. In this specification, CDRs are referred to with respect to both amino acid sequence and location within a light or heavy chain. Because the "location" of CDRs within the structure of immunoglobulin variable domains is conserved across species and occurs in structures called loops, by using a numbering system that aligns variable domain sequences according to structural features, CDR and framework residues are easily identified. This information can be used in the grafting and replacement of CDR residues from one type of immunoglobulin into an acceptor framework, typically from a human antibody. An additional numbering system (AHon) has been developed by Honegger and Pluckthun (2001, J. Mol. Biol. 309: 657-70). Correspondence between numbering systems is well known to those skilled in the art, including, for example, the Kabat numbering system and the IMGT unique numbering system (see, for example, Kabat, supra; Chothia and Lesk, supra; Martin, supra; Lefranc et al., supra). In some embodiments, the CDRs are as defined by the IMGT numbering system. In other embodiments, the CDRs are as defined by the Kabat numbering system. In some embodiments, the CDRs are as defined by the AbM numbering system. In other embodiments, the CDRs are as defined by the Chothia system. In yet other embodiments, the CDRs are as defined by the contact numbering system. [Table 1] The hypervariable regions may include "extended hypervariable regions" as follows: 24-36 or 24-34 (L1), 46-56 or 50-56 (L2), and 89-97 or 89-96 (L3) of VL, and 26-35 or 26-35A (H1), 50-65 or 49-65 (H2), and 93-102, 94-102 or 95-102 (H3) of VH. As used herein, the terms "HVR" and "CDR" are used interchangeably.

[0130] The term "constant region" or "constant domain" refers to the carboxy-terminal portions of the light and heavy chains that are not directly involved in binding the antibody to an antigen, but exhibit various effector functions, such as interaction with Fc receptors. This term refers to the portion of the immunoglobulin molecule that has a more conserved amino acid sequence than the other part of the immunoglobulin, the variable region, which contains the antigen-binding site. The constant region may contain the CH1, CH2, and CH3 regions of the heavy chain and the CL region of the light chain.

[0131] The term "framework" or "FR" refers to variable region residues that flank the CDRs. FR residues are present, for example, in chimeric, humanized, human, domain antibodies, diabodies, linear antibodies, and bispecific antibodies. FR residues are variable domain residues other than the hypervariable region or CDR residues.

[0132] The term "Fc region" herein is used to define the C-terminal region of an immunoglobulin heavy chain, including, for example, native sequence Fc regions, recombinant Fc regions, and variant Fc regions. Although the boundaries of an immunoglobulin heavy chain Fc region can vary, the human IgG heavy chain Fc region is often defined as extending from an amino acid residue at position Cys226 or from Pro230 to its carboxyl terminus. The C-terminal lysine of the Fc region (residue 447 according to the EU numbering system) can be removed, for example, during production or purification of the antibody, or by recombinantly engineering the nucleic acid encoding the antibody heavy chain. Thus, a composition of intact antibodies can include an antibody population with all K447 residues removed, an antibody population with no K447 residues removed, and an antibody population having a mixture of antibodies with and without the K447 residue.

[0133] A "functional Fc region" possesses an "effector function" of a native sequence Fc region. Exemplary "effector functions" include C1q binding; CDC; Fc receptor binding; ADCC; phagocytosis; down-regulation of cell surface receptors (e.g., B cell receptors); and the like. Such effector functions typically require that the Fc region be combined with a binding region or domain (e.g., an antibody variable region or domain), and can be assessed using a variety of assays, as disclosed.

[0134] A "native sequence Fc region" comprises an amino acid sequence identical to that of an Fc region found in nature and that has not been engineered, modified, and / or altered by man (e.g., not isolated, purified, selected, not containing or combined with other sequences, such as variable region sequences). Native sequence human Fc regions include native sequence human IgG1 Fc regions (non-A and A allotypes); native sequence human IgG2 Fc regions; native sequence human IgG3 Fc regions; and native sequence human IgG4 Fc regions, as well as naturally occurring variants thereof.

[0135] A "variant Fc region" comprises an amino acid sequence that differs from the amino acid sequence of a native sequence Fc region by virtue of at least one amino acid modification (e.g., substitution, addition, or deletion). In certain embodiments, the variant Fc region has at least one amino acid substitution, e.g., about 1 to about 10 amino acid substitutions, or about 1 to about 5 amino acid substitutions, in the native sequence Fc region or in the Fc region of the parent polypeptide, compared to the native sequence Fc region or the Fc region of the parent polypeptide. A variant Fc region herein can retain at least about 80% homology with the native sequence Fc region and / or the Fc region of the parent polypeptide, or at least about 90% homology therewith, e.g., at least about 95% homology therewith.

[0136] The term "variant" when used in the context of BTN1A1 or anti-BTN1A1 antibodies can refer to a peptide or polypeptide that contains one or more (e.g., about 1 to about 25, about 1 to about 20, about 1 to about 15, about 1 to about 10, or about 1 to about 5, etc.) amino acid sequence substitutions, deletions, and / or additions compared to the native or unmodified sequence. For example, a BTN1A1 variant can result from one or more (e.g., about 1 to about 25, about 1 to about 20, about 1 to about 15, about 1 to about 10, or about 1 to about 5, etc.) changes to the amino acid sequence of native BTN1A1. Also by way of example, variants of anti-BTN1A1 antibodies can arise by one or more (e.g., about 1 to about 25, about 1 to about 20, about 1 to about 15, about 1 to about 10, or about 1 to about 5, etc.) changes to the amino acid sequence of a native or previously unmodified anti-BTN1A1 antibody. Variants may be naturally occurring, such as allelic or splice variants, or may be artificially constructed. Polypeptide variants may be prepared from the corresponding nucleic acid molecule encoding the variant. In specific embodiments, the BTN1A1 variant or anti-BTN1A1 antibody variant retains at least the functional activity of BTN1A1 or anti-BTN1A1 antibody, respectively. In specific embodiments, the anti-BTN1A1 antibody variant binds to BTN1A1 and / or is antagonistic to BTN1A1 activity. In specific embodiments, the anti-BTN1A1 antibody variant binds to BTN1A1 and / or is agonistic to BTN1A1 activity. In certain embodiments, the variants are encoded by single nucleotide polymorphism (SNP) variants of a nucleic acid molecule encoding a VH or VL region or subregion, eg, one or more CDRs, of BTN1A1 or an anti-BTN1A1 antibody.

[0137] An "intact" antibody is an antibody that comprises an antigen-binding site and a CL and at least a heavy chain constant region CH1, CH2, and CH3. The constant region may comprise a human constant region or an amino acid sequence variant thereof. In some embodiments, an intact antibody has one or more effector functions.

[0138] An "antibody fragment" includes a portion of an intact antibody, such as the antigen binding or variable region of the intact antibody. Examples of antibody fragments include, but are not limited to, Fab, Fab', F(ab') 2 and Fv fragments; diabodies and di-diabodies (e.g., Holliger et al., 1993, Proc. Natl. Acad. Sci. 90:6444-48; Lu et al., 2005, J. Biol. Chem. 280:19665-72; Hudson et al., 2003, Nat. Med. 9:129-34; WO 02 / 063636; WO 02 / 063636; WO 02 / 063636). 93 / 11161; and U.S. Pat. Nos. 5,837,242 and 6,492,123); single chain antibody molecules (see, e.g., U.S. Pat. Nos. 4,946,778; 5,260,203; 5,482,858; and 5,476,786); dual variable domain antibodies (see, e.g., U.S. Pat. No. 7,612,181); single variable domain antibodies (sdAbs) (see, e.g., Woolven et al., 1999, Immunogenetics 50: 98-101; and Streltsov et al., 2004, Proc Natl Acad Sci USA. 101:12444-49); and multispecific antibodies formed from antibody fragments.

[0139] A "functional fragment," "binding fragment," or "antigen-binding fragment" of a diagnostic antibody exhibits at least one, if not some or all, of the biological functions attributable to an intact antibody, which function includes at least binding to a target antigen (e.g., a BTN1A1-binding fragment or a fragment that binds to BTN1A1).

[0140] The term "fusion protein" as used herein refers to a polypeptide that comprises the amino acid sequence of an antibody and the amino acid sequence of a heterologous polypeptide or protein (e.g., a polypeptide or protein that is not normally a part of an antibody (e.g., a non-anti-BTN1A1 antigen-binding antibody)). The term "fusion" when used in the context of BTN1A1 or an anti-BTN1A1 antibody refers to the association of a peptide or polypeptide, or a fragment, variant, and / or derivative thereof, with a heterologous peptide or polypeptide. In certain embodiments, a fusion protein retains the biological activity of BTN1A1 or an anti-BTN1A1 antibody. In certain embodiments, a fusion protein comprises the VH region, VL region, VH CDRs (one, two, or three VH CDRs), and / or VL CDRs (one, two, or three VL CDRs) of a BTN1A1 antibody, where the fusion protein binds a BTN1A1 epitope, a BTN1A1 fragment, and / or a BTN1A1 polypeptide.

[0141] The term "native" when used in reference to biological material, e.g., nucleic acid molecules, polypeptides, host cells, etc., refers to that which is found in nature and has not been manipulated, modified, and / or altered (e.g., isolated, purified, selected) by man.

[0142] The antibodies provided herein can include "chimeric" antibodies in which a portion of the heavy and / or light chains are identical to or homologous to corresponding sequences in antibodies from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chains are identical to or homologous to corresponding sequences in antibodies from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies, so long as they exhibit the desired biological activity (see U.S. Pat. No. 4,816,567; and Morrison et al., 1984, Proc. Natl. Acad. Sci. USA 81:6851-55).

[0143] "Humanized" forms of non-human (e.g., murine) antibodies are chimeric antibodies comprising a human immunoglobulin (e.g., recipient antibody) in which native CDR residues are replaced by residues from a corresponding CDR (e.g., donor antibody) of a non-human species, such as mouse, rat, rabbit, or non-human primate, having the desired specificity, affinity, and capacity. In some cases, one or more FR region residues of the human immunoglobulin are replaced by corresponding non-human residues. Furthermore, humanized antibodies can contain residues that are not found in either the recipient antibody or the donor antibody. These modifications are made to further refine antibody performance. The heavy or light chain of a humanized antibody can comprise substantially all of at least one or more variable regions, in which all or substantially all of the CDRs correspond to those of a non-human immunoglobulin and all or substantially all of the FRs are those of a human immunoglobulin sequence. In certain embodiments, a humanized antibody comprises at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin. For further details, see Jones et al., 1986, Nature 321:522-25; Riechmann et al., 1988, Nature 332:323-29; Presta, 1992, Curr. Op. Struct. Biol. 2:593-96; Carter et al., 1992, Proc. Natl. Acad. Sci. USA 89:4285-89; U.S. Patent Nos. 6,800,738; 6,719,971; 6,639,055; 6,407,213; and 6,054,297.

[0144] A "human antibody" is one that possesses an amino acid sequence that corresponds to that of an antibody produced by a human and / or that has been produced using any of the human antibody production techniques disclosed herein. This definition of a human antibody specifically excludes humanized antibodies that contain non-human antigen-binding residues. Human antibodies can be produced using a variety of techniques known in the art, including phage display libraries (Hoogenboom and Winter, 1991, J. Mol. Biol. 227:381; Marks et al., 1991, J. Mol. Biol. 222:581) and yeast display libraries (Chao et al., 2006, Nature Protocols 1: 755-68). The methods described in Cole et al., Monoclonal Antibodies and Cancer Therapy, 77 (1985); Boerner et al., 1991, J. Immunol. 147(1):86-95; and van Dijk and van de Winkel, 2001, Curr. Opin. Pharmacol. 5: 368-74 can also be used for preparing human monoclonal antibodies. Human antibodies can be prepared by administering antigen to transgenic animals, e.g., mice, that have been modified to produce such antibodies in response to antigenic stimulation, but whose endogenous loci have been disabled (see, e.g., Jakobovits, 1995, Curr. Opin. Biotechnol. 6(5):561-66; Bruggemann and Taussing, 1997, Curr. Opin. Biotechnol. 8(4):455-58; and U.S. Pat. Nos. 6,075,181 and 6,150,584 regarding XENOMOUSE™ technology). See also, e.g., Li et al., 2006, Proc. Natl. Acad. Sci. USA 103:3557-62 regarding human antibodies generated by human B cell hybridoma technology.

[0145] An "affinity matured" antibody is an antibody that has one or more changes (e.g., amino acid sequence variations, including modifications, additions, and / or deletions) in one or more of its HVRs that result in an improvement in the affinity of the antibody for an antigen compared to a parent antibody that does not possess these changes. Affinity matured antibodies can have nanomolar or even picomolar affinities for the target antigen. Affinity matured antibodies are produced by procedures known in the art. For reviews, see Hudson and Souriau, 2003, Nature Medicine 9:129-34; Hoogenboom, 2005, Nature Biotechnol. 23:1105-16; Quiroz and Sinclair, 2010, Revista Ingeneria Biomedia 4:39-51.

[0146] A "blocking" or "antagonist" antibody is an antibody that inhibits or reduces the biological activity of the antigen to which it binds. For example, a blocking or antagonist antibody can substantially or completely inhibit the biological activity of the antigen.

[0147] An "agonist antibody" is an antibody that elicits a response, e.g., an antibody that mimics at least one of the functional activities of a polypeptide of interest. Agonist antibodies include antibodies that are ligand mimetics, e.g., where a ligand binds to a cell surface receptor, binding induces cell signaling or activity through a cell signaling pathway within the cell, and where the antibody induces similar cell signaling or activation. An "agonist" of BTN1A1 refers to a molecule that can activate or otherwise increase one or more of the biological activities of BTN1A1, e.g., in a cell that expresses BTN1A1. In some embodiments, an agonist of BTN1A1 (e.g., an agonistic antibody described herein) can act, e.g., by activating or otherwise increasing the activation and / or cell signaling pathway of a cell that expresses a BTN1A1 protein, thereby increasing the BTN1A1-mediated biological activity of the cell compared to the BTN1A1-mediated biological activity in the absence of the agonist. In some embodiments, the antibodies provided herein are agonistic anti-BTN1A1 antibodies, including antibodies that induce BTN1A1 signaling.

[0148] "Binding affinity" typically refers to the strength of the sum of non-covalent interactions between a single binding site of a molecule (e.g., a binding protein, e.g., an antibody) and its binding partner (e.g., an antigen). As used herein, unless otherwise indicated, "binding affinity" refers to the intrinsic binding affinity that reflects a 1:1 interaction between members of a binding pair (e.g., an antibody and an antigen). The affinity of a binding molecule X for its binding partner Y is typically measured by the dissociation constant (K D) Affinity can be measured by common methods known in the art, including those described herein. Low affinity antibodies usually bind antigens slowly and tend to dissociate quickly, whereas high affinity antibodies usually bind antigens faster and tend to remain bound longer. Various methods of measuring binding affinity are known in the art, any of which can be used for the purposes of the present disclosure. Specific illustrative embodiments include the following. In one embodiment, "K D " or "K D The "K value" can be measured by assays known in the art, for example, by binding assays. D can be measured, for example, by RIA performed using the Fab form of the antibody of interest and its antigen (Chen et al., 1999, J. Mol Biol 293:865-81). D Or K D Values ​​can also be measured by using surface plasmon resonance assays by Biacore®, for example using a Biacore® TM-2000 or Biacore® TM-3000, or by biolayer interferometry, for example using an Octet® QK384 system. "Binding rate" or "rate of association" or "association rate" or "k on " can also be determined by the same surface plasmon resonance or biolayer interferometry methods described above, for example, using a Biacore® TM-2000 or Biacore® TM-3000, or an Octet® QK384 system.

[0149] The terms "inhibition" or "inhibit" as used herein refer to partial (e.g., 1%, 2%, 5%, 10%, 20%, 25%, 50%, 75%, 90%, 95%, 99%) or complete (i.e., 100%) inhibition.

[0150] The terms "attenuate," "attenuate," or "attenuated" as used herein refer to a partial (e.g., 1%, 2%, 5%, 10%, 20%, 25%, 50%, 75%, 90%, 95%, 99%) or complete (i.e., 100%) reduction in a property, activity, effect, or value.

[0151] "Antibody effector functions" refer to the biological activities attributable to the Fc region of an antibody (e.g., a native sequence Fc region or an amino acid sequence variant Fc region) and vary with the antibody isotype. Examples of antibody effector functions include: C1q binding; CDC; Fc receptor binding; ADCC; phagocytosis; down-regulation of cell surface receptors (e.g., B cell receptor); and B cell activation.

[0152] "T cell effector functions" refer to biological activities attributable to various types of T cells, including, but not limited to, cytotoxic T cells, T helper cells, and memory T cells. Examples of T cell effector functions include: increased T cell proliferation, secretion of cytokines, release of cytotoxins, expression of membrane-associated molecules, killing of target cells, activation of macrophages, and activation of B cells.

[0153] "Antibody-dependent cell-mediated cytotoxicity" or "ADCC" refers to a form of cytotoxicity in which secreted immunoglobulins bound to Fc receptors (FcRs) present on certain cytotoxic cells (e.g., natural killer (NK) cells, neutrophils, and macrophages) enable these cytotoxic effector cells to specifically bind to antigen-bearing target cells and subsequently kill the target cells with cytotoxins. Antibodies "arm" the cytotoxic cells and are absolutely required for such killing. NK cells, the primary cells mediating ADCC, express only FcγRIII, whereas monocytes express FcγRI, FcγRII, and FcγRIII. FcR expression on hematopoietic cells is known (see, e.g., Ravetch and Kinet, 1991, Annu. Rev. Immunol. 9:457-92). To assess the ADCC activity of a molecule of interest, an in vitro ADCC assay (see, e.g., U.S. Patent Nos. 5,500,362 and 5,821,337) can be performed. Useful effector cells for such assays include peripheral blood mononuclear cells (PBMC) and natural killer (NK) cells. Alternatively or additionally, the ADCC activity of a molecule of interest can be assessed in vivo, for example, in an animal model (see, e.g., Clynes et al., 1998, Proc. Natl. Acad. Sci. USA 95:652-56). Antibodies with little or no ADCC activity can be selected for use.

[0154] "Antibody-dependent cellular phagocytosis" or "ADCP" refers to the destruction of target cells by monocyte- or macrophage-mediated phagocytosis when immunoglobulins bound to Fc receptors (FcRs) present on certain phagocytes (e.g., neutrophils, monocytes, and macrophages) enable these phagocytes to specifically bind to antigen-bearing target cells and subsequently kill the target cells with cytotoxins. To assess the ADCP activity of a molecule of interest, an in vitro ADCP assay (see, e.g., Bracher et al., 2007, J. Immunol. Methods 323:160-71) can be performed. Useful phagocytes for such assays include peripheral blood mononuclear cells (PBMCs), purified monocytes derived from PBMCs, or U937 cells differentiated into mononuclear forms. Alternatively, or in addition, the ADCP activity of the molecule of interest can be assessed in vivo, for example, in an animal model (see, e.g., Wallace et al., 2001, J. Immunol. Methods 248:167-82). Antibodies with little or no ADCP activity can be selected for use.

[0155] "Fc receptor" or "FcR" refers to a receptor that binds to the Fc region of an antibody. An exemplary FcR is a native sequence human FcR. Further exemplary FcRs are those that bind IgG antibodies (e.g., gamma receptors) and include receptors of the FcγRI, FcγRII, and FcγRIII subclasses, including allelic variants and alternatively spliced ​​forms of these receptors. FcγRII receptors include FcγRIIA (an "activating receptor") and FcγRIIB (an "inhibiting receptor"), which have similar amino acid sequences that differ primarily in their cytoplasmic domains (see, e.g., Daeron, 1997, Annu. Rev. Immunol. 15:203-34). A variety of FcRs are known (see, e.g., Ravetch and Kinet, 1991, Annu. Rev. Immunol. 9:457-92; Capel et al., 1994, Immunomethods 4:25-34; and de Haas et al., 1995, J. Lab. Clin. Med. 126:330-41). Other FcRs, including those to be identified in the future, are encompassed by the term "FcR" herein. The term also includes FcRn, the neonatal receptor involved in the transfer of maternal IgG to the fetus (see, e.g., Guyer et al., 1976, J. Immunol. 117:587-93; and Kim et al., 1994, Eu. J. Immunol. 24:2429-34). Antibody variants with improved or diminished binding to FcRs have been described (see, e.g., WO 2000 / 42072; U.S. Pat. Nos. 7,183,387; 7,332,581; and 7,335,742; Shields et al., 2001, J. Biol. Chem. 9(2):6591-604).

[0156] "Complement-dependent cytotoxicity" or "CDC" refers to the lysis of target cells in the presence of complement. Activation of the classical complement pathway is initiated by the binding of the first component of the complement system (C1q) to an antibody (of the appropriate subclass) that is bound to its cognate antigen. To assess complement activation, a CDC assay (see, e.g., Gazzano-Santoro et al., 1996, J. Immunol. Methods 202:163) can be performed. Polypeptide variants with altered Fc region amino acid sequences (polypeptides with variant Fc regions) and with increased or decreased C1q binding ability have been described (see, e.g., U.S. Pat. No. 6,194,551; WO 1999 / 51642; Idusogie et al., 2000, J. Immunol. 164: 4178-84). Antibodies with little or no CDC activity can be selected for use.

[0157] The term "identity" refers to the relationship between sequences of two or more polypeptide molecules or two or more nucleic acid molecules, determined by aligning and comparing the sequences. "Percent (%) amino acid sequence identity" with respect to a reference polypeptide sequence is defined as the percentage of amino acid residues in a candidate sequence that are identical to the amino acid residues in the reference polypeptide sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, without taking into account any conservative substitutions as part of the sequence identity. Alignment to determine percent amino acid sequence identity can be achieved in a variety of ways that are within the capabilities of those skilled in the art, for example, using publicly available computer software, such as BLAST, BLAST-2, ALIGN, or MEGALIGN (DNAStar, Inc.) software. Those skilled in the art can determine appropriate parameters for aligning sequences, including any algorithms required to achieve maximum alignment over the entire length of the sequences being compared.

[0158] A "modification" of an amino acid residue / position refers to a change in the primary amino acid sequence as compared to a starting amino acid sequence, where the change occurs by alteration of the sequence containing that amino acid residue / position. For example, typical modifications include substitution of the residue with another amino acid (e.g., a conservative or non-conservative substitution), insertion of one or more (e.g., usually less than 5, 4, or 3) amino acids adjacent to that residue / position, and / or deletion of that residue / position.

[0159] The term "analog" as used herein in reference to a polypeptide refers to a polypeptide that possesses a similar or identical function as a BTN1A1 polypeptide, a fragment of a BTN1A1 polypeptide, or an anti-BTN1A1 antibody, but does not necessarily contain a similar or identical amino acid sequence of a BTN1A1 polypeptide, a fragment of a BTN1A1 polypeptide, or an anti-BTN1A1 antibody, nor does it possess a similar or identical structure of a BTN1A1 polypeptide, a fragment of a BTN1A1 polypeptide, or an anti-BTN1A1 antibody. Polypeptides having a similar amino acid sequence include: (a) polypeptides having an amino acid sequence that is at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identical to the amino acid sequence of a BTN1A1 polypeptide, a fragment of a BTN1A1 polypeptide, or an anti-BTN1A1 antibody provided herein; (b) polypeptides having at least 5 amino acid residues, at least 10 amino acid residues, at least 15 amino acid residues, at least 20 amino acid residues, at least a polypeptide encoded by a nucleotide sequence that hybridizes under stringent conditions to a nucleotide sequence encoding a BTN1A1 polypeptide described herein, a fragment of a BTN1A1 polypeptide, or an anti-BTN1A1 antibody (or a VH or VL region thereof) of 25 amino acid residues, at least 40 amino acid residues, at least 50 amino acid residues, at least 60 amino acid residues, at least 70 amino acid residues, at least 80 amino acid residues, at least 90 amino acid residues, at least 100 amino acid residues, at least 125 amino acid residues, or at least 150 amino acid residues (see, e.g., Sambrook et al., Molecular Cloning: A Laboratory Manual (2001); and Maniatis et al., Molecular Cloning: A Laboratory Manual (1982));or (c) a polypeptide encoded by a nucleotide sequence that is at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identical to a nucleotide sequence encoding a BTN1A1 polypeptide, a fragment of a BTN1A1 polypeptide, or an anti-BTN1A1 antibody (or a VH or VL region thereof) described herein. A polypeptide having a similar structure to a BTN1A1 polypeptide, a fragment of a BTN1A1 polypeptide, or an anti-BTN1A1 antibody provided herein refers to a polypeptide having a similar secondary, tertiary, or quaternary structure to a BTN1A1 polypeptide, a fragment of BTN1A1, or a BTN1A1 antibody provided herein. The structure of a polypeptide can be determined by methods known to those skilled in the art, including, but not limited to, X-ray crystallography, nuclear magnetic resonance, and crystallographic electron microscopy;

[0160] The term "derivative" as used herein in the context of a polypeptide refers to a polypeptide comprising the amino acid sequence of a BTN1A1 polypeptide, a fragment of a BTN1A1 polypeptide, or an antibody that binds to a BTN1A1 polypeptide, that has been altered by the introduction of substitutions, deletions, or additions of amino acid residues. The term "derivative" as used herein also refers to a BTN1A1 polypeptide, a fragment of a BTN1A1 polypeptide, or an antibody that binds to a BTN1A1 polypeptide, that has been chemically modified, for example, by the covalent attachment of any type of molecule to the polypeptide. For example, but not limited to, a BTN1A1 polypeptide, a fragment of a BTN1A1 polypeptide, or a BTN1A1 antibody may be chemically modified, for example, by increasing or decreasing glycosylation, acetylation, pegylation, phosphorylation, amidation, derivatization with known protecting / blocking groups, proteolytic cleavage, chemical cleavage, attachment to cellular ligands or other proteins, and the like. A derivative is modified such that either the type or location of the attached molecule is different from the naturally occurring peptide or polypeptide or the starting peptide or polypeptide. Derivatives further include deletion of one or more chemical groups naturally occurring on the peptide or polypeptide. Additionally, derivatives of a BTN1A1 polypeptide, a fragment of a BTN1A1 polypeptide, or a BTN1A1 antibody may contain one or more non-classical amino acids. Polypeptide derivatives retain a similar or identical function as a BTN1A1 polypeptide, a fragment of a BTN1A1 polypeptide, or a BTN1A1 antibody provided herein.

[0161] As used herein, the term "host" refers to an animal, for example, a mammal (eg, a human).

[0162] The term "host cell," as used herein, refers to a particular subject cell that can be transfected with a nucleic acid molecule and the progeny or potential progeny of such a cell. The progeny of such a cell may not be identical to the parent cell transfected with the nucleic acid molecule due to mutations or environmental influences that may occur in subsequent generations or integration of the nucleic acid molecule into the host cell genome.

[0163] The term "vector" refers to a material used to carry or contain a nucleic acid sequence, including, for example, a nucleic acid sequence encoding an anti-BTN1A1 antibody described herein, for introducing a nucleic acid sequence into a host cell. Vectors applicable for use include, for example, expression vectors, plasmids, phage vectors, viral vectors, episomes, and artificial chromosomes, which can include a selection sequence or marker operable for stable integration into a host cell chromosome. In addition, the vector can include one or more selectable marker genes and appropriate expression control sequences. Selectable marker genes that can be included provide, for example, resistance to antibiotics or toxins, complement autotrophic deficiencies, or provide critical nutrients not present in the culture medium. Expression control sequences can include constitutive and inducible promoters, transcription enhancers, transcription terminators, and the like, which are well known in the art. When two or more nucleic acid molecules (e.g., both heavy and light chains of an antibody or both VH and VL of an antibody) are to be co-expressed, both nucleic acid molecules can be inserted, for example, into a single expression vector or into separate expression vectors. For single vector expression, the encoding nucleic acids can be operably linked to one common expression control sequence or to different expression control sequences, for example, one inducible promoter and one constitutive promoter. The introduction of the nucleic acid molecule into the host cell can be confirmed using methods well known in the art. Such methods include, for example, nucleic acid analysis, such as Northern blot or polymerase chain reaction (PCR) amplification of mRNA, or immunoblotting for expression of gene products, or other suitable analytical methods to test the expression of the introduced nucleic acid sequence or its corresponding gene product. It will be understood by those skilled in the art that the nucleic acid molecule will be expressed in sufficient amounts to produce the desired product (e.g., anti-BTN1A1 antibody described herein), and it will be further understood that the expression level can be optimized using methods well known in the art to obtain sufficient expression.

[0164] An "isolated nucleic acid" is a nucleic acid, e.g., RNA, DNA, or mixed nucleic acid, that is substantially separated from other genomic DNA sequences, and proteins or complexes that naturally accompany the native sequence, e.g., ribosomes and polymerases. An "isolated" nucleic acid molecule is a nucleic acid molecule that is separated from other nucleic acid molecules that are present in the natural source of the nucleic acid molecule. Furthermore, an "isolated" nucleic acid molecule, e.g., a cDNA molecule, can be substantially free of other cellular material, or culture medium if produced by recombinant techniques, or substantially free of chemical precursors or other chemicals if chemically synthesized. In a specific embodiment, one or more nucleic acid molecules encoding the antibodies described herein are isolated or purified. This term includes a nucleic acid sequence that has been removed from its natural environment, including recombinant or cloned DNA isolates and chemically synthesized analogs or analogs biosynthesized by heterologous systems. A substantially pure molecule can include an isolated form of the molecule.

[0165] "Polynucleotide" or "nucleic acid" as used interchangeably herein refers to a polymer of nucleotides of any length, including DNA and RNA. The nucleotides can be deoxyribonucleotides, ribonucleotides, modified nucleotides or bases, and / or their analogs, or any substrate that can be incorporated into a polymer by DNA or RNA polymerase or by a synthetic reaction. Polynucleotides can include modified nucleotides, such as methylated nucleotides and their analogs. "Oligonucleotides" as used herein refer to short, usually single-stranded, synthetic polynucleotides that are usually, but not necessarily, less than about 200 nucleotides in length. The terms "oligonucleotide" and "polynucleotide" are not mutually exclusive. The above description of polynucleotides is equally and fully applicable to oligonucleotides. Cells producing the anti-BTN1A1 antibodies of the present disclosure can include parent hybridoma cells, as well as bacterial and eukaryotic host cells into which nucleic acid encoding the antibody has been introduced. Suitable host cells are disclosed below.

[0166] Unless otherwise specified, the left-hand end of any single-stranded polynucleotide sequence disclosed herein is the 5' end; the left-hand direction of a double-stranded polynucleotide sequence is referred to as the 5' direction. The direction of 5' to 3' addition of the nascent RNA transcript is referred to as the transcription direction; the region of sequence on the DNA strand that has the same sequence as the RNA transcript that is 5' to the 5' end of the RNA transcript is referred to as the "upstream sequence"; the region of sequence on the DNA strand that has the same sequence as the RNA transcript that is 3' to the 3' end of the RNA transcript is referred to as the "downstream sequence".

[0167] The term "encoding nucleic acid" or its grammatical equivalents, when used in reference to a nucleic acid molecule, refers to a nucleic acid molecule in its native state or a nucleic acid molecule that, when manipulated by methods well known to those of skill in the art, can be transcribed to produce an mRNA that is subsequently translated into a polypeptide and / or fragment thereof. The antisense strand is the complement of such a nucleic acid molecule, and the coding sequence can be deduced therefrom.

[0168] The term "recombinant antibody" refers to an antibody prepared, expressed, created, or isolated by recombinant means. A recombinant antibody can be an antibody expressed using a recombinant expression vector transfected into a host cell, an antibody isolated from a recombinant combinatorial antibody library, an antibody isolated from an animal (e.g., mouse or cow) that is transgenic and / or transchromosomal for human immunoglobulin genes (see, e.g., Taylor et al., 1992, Nucl. Acids Res. 20:6287-95), or an antibody prepared, expressed, created, or isolated by any other means involving splicing of immunoglobulin gene sequences to other DNA sequences. Such recombinant antibodies can have variable and constant regions, including those derived from human germline immunoglobulin sequences (Kabat et al., supra). In certain embodiments, however, such recombinant antibodies may be subjected to in vitro mutagenesis (or in vivo somatic mutagenesis, when animals transgenic for human Ig sequences are used) such that the amino acid sequences of the VH and VL regions of the recombinant antibodies are derived from and related to human germline VH and VL sequences, but are sequences that may not naturally exist in the human antibody germline repertoire in vivo.

[0169] The term "detectable probe" refers to a composition that provides a detectable signal. This term includes, but is not limited to, any fluorophore, chromophore, radiolabel, enzyme, antibody, or antibody fragment, etc. that provides a detectable signal through its activity.

[0170] The term "detectable agent" refers to a substance that can be used to confirm the existence or presence of a desired molecule, such as an anti-BTN1A1 antibody described herein, in a sample or subject. A detectable agent can be a substance that can be visualized or otherwise determined and / or measured (e.g., by quantification).

[0171] The term "diagnostic agent" refers to a substance administered to a subject that aids in the diagnosis of a disease, disorder, or condition. Such substances can be used to localize, pinpoint, and / or define a disease-inducing process. In certain embodiments, a diagnostic agent comprises a substance conjugated to an anti-BTN1A1 antibody described herein that aids in the diagnosis of a BTN1A1-mediated disease when administered to a subject or contacted with a sample from a subject.

[0172] The term "composition" is intended to encompass products that contain specified ingredients (eg, an antibody provided herein), optionally in specified amounts.

[0173] As used herein, "carrier" includes pharma- ceutically acceptable carriers, excipients, or stabilizers that are non-toxic to cells or mammals exposed thereto at the dosages and concentrations employed. In many cases, the physiologically acceptable carrier is an aqueous pH buffered solution. Examples of physiologically acceptable carriers include buffers such as phosphates, citrates, and other organic acids; antioxidants, including ascorbic acid; low molecular weight (e.g., less than about 10 amino acid residues) polypeptides; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers, such as polyvinylpyrrolidone; amino acids, such as glycine, glutamine, asparagine, arginine, or lysine; monosaccharides, disaccharides, and other carbohydrates, including glucose, mannose, or dextrin; chelating agents, such as EDTA; sugar alcohols, such as mannitol or sorbitol; salt-forming counterions, such as sodium; and / or non-ionic surfactants, such as TWEEN™, polyethylene glycol (PEG), and PLURONICS™. The term "carrier" can also refer to a diluent, adjuvant (e.g., Freund's adjuvant (complete or incomplete)), excipient, or vehicle. Such carriers, including pharmaceutical carriers, can be sterile liquids, such as water and oils, including those of petroleum, animal, vegetable, or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil, and the like. Water is an exemplary carrier when the composition (e.g., pharmaceutical composition) is administered intravenously. Saline solutions and aqueous dextrose and glycerol solutions can also be employed as liquid carriers, particularly for injectable solutions. Suitable excipients (e.g., pharmaceutical excipients) include starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, nonfat dry milk, glycerol, propylene, glycol, water, ethanol, and the like. The compositions can also contain minor amounts of wetting or emulsifying agents, or pH buffering agents, if desired.The compositions can take the form of solutions, suspensions, emulsions, tablets, pills, capsules, powders, sustained-release formulations, and the like.Oral compositions, including formulations, can contain standard carriers, such as pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharin, cellulose, magnesium carbonate, etc. Examples of suitable pharmaceutical carriers are described in Remington and Gennaro, Remington's Pharmaceutical Sciences (18th ed., 1990). Compositions containing pharmaceutical compounds can contain anti-BTN1A1 antibodies, for example, in isolated or purified form, together with a suitable amount of carrier.

[0174] As used herein, the term "pharmaceutical acceptable" means approved by a regulatory agency of the Federal or state government, or listed in the United States Pharmacopoeia, the European Pharmacopoeia, or other generally recognized pharmacopoeias, for use in animals, and more particularly in humans.

[0175] The term "excipient" refers to an inert substance commonly used as a diluent, vehicle, preservative, binder, or stabilizer, and includes, but is not limited to, proteins (e.g., serum albumin, etc.), amino acids (e.g., aspartic acid, glutamic acid, lysine, arginine, glycine, histidine, etc.), fatty acids and phospholipids (e.g., alkylsulfonates, caprylates, etc.), surfactants (e.g., SDS, polysorbates, non-ionic surfactants, etc.), sugars (e.g., sucrose, maltose, trehalose, etc.), and polyols (e.g., mannitol, sorbitol, etc.). See also Remington and Gennaro, Remington's Pharmaceutical Sciences (18th ed., 1990), which is incorporated herein by reference in its entirety.

[0176] The terms "subject" and "patient" can be used interchangeably. As used herein, in some embodiments, a subject is a mammal, such as a non-primate (e.g., cows, pigs, horses, cats, dogs, rats, etc.) or a primate (e.g., monkeys and humans). In a specific embodiment, a subject is a human.

[0177] "Administering" or "administration" refers to the act of injecting or otherwise physically delivering an agent in its exogenous state (e.g., an anti-BTN1A1 antibody described herein) to a patient, for example, by mucosal, intradermal, intravenous, intramuscular delivery, and / or any other physical delivery method described herein or known in the art.

[0178] As used herein, the term "effective amount" refers to an amount of an antibody or pharmaceutical composition provided herein that is sufficient to effect a desired outcome.

[0179] The term "about" or "approximately" means within 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% or less of a given value or range.

[0180] "Substantially all" refers to at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99%, or about 100%.

[0181] The phrases "substantially similar" or "substantially the same" are used by those of ordinary skill in the art to describe the difference between two values ​​(e.g., K DBy "similarities" is meant a degree of similarity between two numerical values ​​(e.g., one numerical value associated with an antibody of the present disclosure and another numerical value associated with a reference antibody) that is sufficiently high to be considered to be of little or no biological and / or statistical significance in the context of a biological characteristic measured by the antibody's value (i.e., the difference between the two values ​​can be less than about 50%, less than about 40%, less than about 30%, less than about 20%, less than about 10%, or less than about 5% as a function of the value for the reference antibody.

[0182] The phrases "substantially increased," "substantially decreased," or "substantially different" as used herein refer to a degree of dissimilarity between two numerical values ​​(e.g., one numerical value associated with an antibody of the present disclosure and another numerical value associated with a reference antibody) that is high enough that one of ordinary skill in the art would consider the difference between the two values ​​to be statistically significant in relation to the biological characteristic measured by the values. For example, the difference between the two values ​​can be more than about 10%, more than about 20%, more than about 30%, more than about 40%, or more than about 50% as a function of the value for the reference antibody.

[0183] 4.3 Composition and method for preparing same Provided herein are antibodies that bind to a BTN1A1 polypeptide, a BTN1A1 polypeptide fragment, a BTN1A1 peptide, or a BTN1A1 epitope.

[0184] In certain embodiments, the antibodies provided herein bind to human and / or cynomolgus BTN1A1. In one embodiment, the BTN1A1 antibody binds to human BTN1A1. In one embodiment, the BTN1A1 antibody binds to cynomolgus BTN1A1. In one embodiment, the BTN1A1 antibody binds to both human BTN1A1 and cynomolgus BTN1A1. In other embodiments, the antibodies provided herein bind to rodent BTN1A1. In other embodiments, the antibodies provided herein bind to both human BTN1A1 and rodent BTN1A1. In other embodiments, the antibodies provided herein bind to human, cynomolgus, and rodent BTN1A1.

[0185] In some embodiments, the anti-BTN1A1 antibody binds to the intracellular domain (ICD) of BTN1A1.

[0186] In some embodiments, the anti-BTN1A1 antibody binds to the extracellular domain of BTN1A1. In some embodiments, the anti-BTN1A1 antibody binds to a region of the extracellular domain identified as ECD1 (amino acid residues 67-86) of BTN1A1. In some embodiments, the anti-BTN1A1 antibody binds to a region of the extracellular domain identified as ECD2 (amino acid residues 179-197) of BTN1A1.

[0187] Also provided are antibodies that competitively block the binding of the anti-BTN1A1 antibodies provided herein to a BTN1A1 polypeptide.

[0188] Also provided are antibodies that compete with the anti-BTN1A1 antibodies provided herein for binding to a BTN1A1 polypeptide.

[0189] The anti-BTN1A1 antibodies provided herein can also be conjugated or recombinantly fused to, for example, a diagnostic or detectable agent. Also provided are compositions comprising anti-BTN1A1 antibodies.

[0190] Also provided herein are isolated nucleic acid molecules encoding an immunoglobulin heavy chain, light chain, VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 of a BTN1A1 polypeptide, a BTN1A1 polypeptide fragment, a BTN1A1 peptide, or an anti-BTN1A1 antibody that binds to a BTN1A1 epitope.

[0191] Further provided are vectors and host cells comprising the nucleic acid molecules encoding a BTN1A1 polypeptide, a BTN1A1 polypeptide fragment, a BTN1A1 peptide, or an anti-BTN1A1 antibody that binds a BTN1A1 epitope. Also provided are methods of making a BTN1A1 polypeptide, a BTN1A1 polypeptide fragment, a BTN1A1 peptide, or an antibody that binds a BTN1A1 epitope.

[0192] (4.3.1 Anti-BTN1A1 antibody) In one embodiment, the present disclosure provides anti-BTN1A1 antibodies that may find use herein as diagnostic agents. Exemplary antibodies include polyclonal, monoclonal, humanized, human, bispecific, and heteroconjugate antibodies, as well as variants thereof that have improved affinity or other properties.

[0193] In some embodiments, provided herein are antibodies that bind to BTN1A1, including BTN1A1 polypeptides, BTN1A1 polypeptide fragments, BTN1A1 peptides, or BTN1A1 epitopes. In certain embodiments, the antibodies provided herein bind to human and / or cynomolgus BTN1A1. In other embodiments, the antibodies provided herein bind to rodent BTN1A1 (e.g., mouse BTN1A1). In one embodiment, the antibodies provided herein bind to human BTN1A1. In another embodiment, the antibodies provided herein bind to cynomolgus BTN1A1. In another embodiment, the antibodies provided herein bind to human BTN1A1 and cynomolgus BTN1A1. In some embodiments, the antibodies provided herein bind to both human BTN1A1 and rodent BTN1A1 (e.g., mouse BTN1A1). In some embodiments, the antibodies provided herein bind to both cynomolgus monkey BTN1A1 and rodent BTN1A1 (e.g., mouse BTN1A1). In some embodiments, the antibodies provided herein bind to human BTN1A1, bind to cynomolgus monkey BTN1A1, and bind to rodent BTN1A1 (e.g., mouse BTN1A1). In other embodiments, the anti-BTN1A1 antibody is a humanized antibody that binds to BTN1A1 (e.g., comprising a human constant region), comprising a BTN1A1 polypeptide, a BTN1A1 polypeptide fragment, a BTN1A1 peptide, or a BTN1A1 epitope.

[0194] In certain embodiments, an anti-BTN1A1 antibody comprises the VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 of any one of the murine monoclonal antibodies provided herein, e.g., the amino acid sequences set out in Tables 1-6. Thus, in some embodiments, an isolated antibody or functional fragment thereof provided herein comprises one, two, and / or three heavy chain CDRs and / or one, two, and / or three light chain CDRs from antibody STC43H11-1, STC43G3-1, or STC85F1-1 set out in Tables 1-6. Table 1. VL CDR sequences of anti-BTN1A1 antibody STC43H11-1 [Table 2] Table 2. VH CDR sequences of anti-BTN1A1 antibody STC43H11-1 [Table 3]

[0195] In some embodiments, the antibodies provided herein comprise or consist of six CDRs, e.g., VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3, as identified in Tables 1 and 2. In some embodiments, the antibodies provided herein can comprise fewer than six CDRs. In some embodiments, the antibodies comprise or consist of one, two, three, four, or five CDRs selected from the group consisting of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3, as identified in Tables 1 and 2. In some embodiments, the antibodies comprise or consist of one, two, three, four, or five CDRs selected from the group consisting of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 of the monoclonals described herein. Thus, in some embodiments, the antibody comprises or consists of one, two, three, four, or five CDRs of any one of the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 identified in Tables 1 and 2.

[0196] In some embodiments, the antibodies provided herein comprise one or more (e.g., one, two, or three) VH CDRs set forth in Table 2. In other embodiments, the antibodies provided herein comprise one or more (e.g., one, two, or three) VL CDRs set forth in Table 1. In yet other embodiments, the antibodies provided herein comprise one or more (e.g., one, two, or three) VH CDRs set forth in Table 2 and one or more VL CDRs set forth in Table 1.

[0197] In some embodiments, the antibody comprises a VH CDR1, a VH CDR1, a VH CDR3, a VL CDR1, a VL CDR2, a VL CDR3 according to the Kabat numbering system. Thus, in some embodiments, the antibody comprises a VH CDR1 having the amino acid sequence of SEQ ID NO:8. In some embodiments, the antibody comprises a VH CDR2 having the amino acid sequence of SEQ ID NO:9. In some embodiments, the antibody comprises a VH CDR3 having the amino acid sequence of SEQ ID NO:10. In some embodiments, the antibody comprises a VH CDR1 and / or a VH CDR2 and / or a VH CDR3 independently selected from any one of the VH CDR1, VH CDR2, VH CDR3 amino acid sequences shown in Table 2. In some embodiments, the antibody comprises a VL CDR1 having the amino acid sequence of any one of SEQ ID NO:5. In another embodiment, the antibody comprises a VL CDR2 having the amino acid sequence of SEQ ID NO:6. In some embodiments, the antibody comprises a VL CDR3 having the amino acid sequence of SEQ ID NO:7. In some embodiments, the antibody comprises a VL CDR1 and / or a VL CDR2 and / or a VL CDR3 independently selected from any one of the VL CDR1, VL CDR2, VL CDR3 amino acid sequences shown in Table 1.

[0198] In one embodiment, the antibody provided herein comprises a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:8; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:9; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:10; and a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:5; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:6; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:7.

[0199] In some embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:8; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:9; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:10.

[0200] In other embodiments, the antibodies provided herein comprise a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:5; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:6; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:7.

[0201] Also provided herein are antibodies that comprise one or more (e.g., one, two, or three) VH CDRs and one or more (e.g., one, two, or three) VL CDRs as set forth in Tables 1 and 2. In particular, provided herein are antibodies that comprise a VH CDR1 (SEQ ID NO:8) and a VL CDR1 (SEQ ID NO:5). In one embodiment, the antibody comprises a VH CDR1 (SEQ ID NO:8) and a VL CDR2 (SEQ ID NO:6). In other embodiments, the antibody comprises a VH CDR1 (SEQ ID NO:8) and a VL CDR3 (SEQ ID NO:7). In another embodiment, the antibody comprises a VH CDR2 (SEQ ID NO:9) and a VL CDR1 (SEQ ID NO:5). In some embodiments, the antibody comprises a VH CDR2 (SEQ ID NO:9) and a VL CDR2 (SEQ ID NO:6). In one embodiment, the antibody comprises a VH CDR2 (SEQ ID NO:9) and a VL CDR3 (SEQ ID NO:7). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 10) and a VL CDR1 (SEQ ID NO: 5). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 10) and a VL CDR2 (SEQ ID NO: 6). In some embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 10) and a VL CDR3 (SEQ ID NO: 7). In another embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 8), a VH CDR2 (SEQ ID NO: 9), and a VL CDR1 (SEQ ID NO: 5). In one embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 8), a VH CDR2 (SEQ ID NO: 9), and a VL CDR2 (SEQ ID NO: 6). In another embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 8), a VH CDR2 (SEQ ID NO: 9), and a VL CDR3 (SEQ ID NO: 7). In another embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 9), a VH CDR3 (SEQ ID NO: 10), and a VL CDR1 (SEQ ID NO: 5). In some embodiments, the antibody comprises a VH CDR2 (SEQ ID NO: 9), a VH CDR3 (SEQ ID NO: 10), and a VL CDR2 (SEQ ID NO: 6). In one embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 9), a VH CDR3 (SEQ ID NO: 10), and a VL CDR3 (SEQ ID NO: 7).In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO:8), VH CDR3 (SEQ ID NO:10), and VL CDR1 (SEQ ID NO:5). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO:8), VH CDR3 (SEQ ID NO:10), and VL CDR2 (SEQ ID NO:6). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO:8), VH CDR3 (SEQ ID NO:10), and VL CDR3 (SEQ ID NO:7). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO:8), VL CDR1 (SEQ ID NO:5), and VL CDR2 (SEQ ID NO:6). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO:8), VL CDR1 (SEQ ID NO:5), and VL CDR3 (SEQ ID NO:7). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO:8), VL CDR2 (SEQ ID NO:6), and VL CDR3 (SEQ ID NO:7). In another embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 9), a VL CDR1 (SEQ ID NO: 5), and a VL CDR2 (SEQ ID NO: 6). In some embodiments, the antibody comprises a VH CDR2 (SEQ ID NO: 9), a VL CDR1 (SEQ ID NO: 5), and a VL CDR3 (SEQ ID NO: 7). In one embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 9), a VL CDR2 (SEQ ID NO: 6), and a VL CDR3 (SEQ ID NO: 7). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 10), a VL CDR1 (SEQ ID NO: 5), and a VL CDR2 (SEQ ID NO: 6). In other embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 10), a VL CDR1 (SEQ ID NO: 5), and a VL CDR3 (SEQ ID NO: 7). In some embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 10), a VL CDR2 (SEQ ID NO: 6), and a VL CDR3 (SEQ ID NO: 7). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 8), VH CDR2 (SEQ ID NO: 9), VH CDR3 (SEQ ID NO: 10), and VL CDR1 (SEQ ID NO: 5). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 8), VH CDR2 (SEQ ID NO: 9), VH CDR3 (SEQ ID NO: 10), and VL CDR2 (SEQ ID NO: 6).In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO:8), VH CDR2 (SEQ ID NO:9), VH CDR3 (SEQ ID NO:10), and VL CDR3 (SEQ ID NO:7). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO:8), VH CDR2 (SEQ ID NO:9), VL CDR1 (SEQ ID NO:5), and VL CDR2 (SEQ ID NO:6). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO:8), VH CDR2 (SEQ ID NO:9), VL CDR1 (SEQ ID NO:5), and VL CDR3 (SEQ ID NO:7). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO:8), VH CDR2 (SEQ ID NO:9), VL CDR2 (SEQ ID NO:6), and VL CDR3 (SEQ ID NO:7). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO:8), VH CDR3 (SEQ ID NO:10), VL CDR1 (SEQ ID NO:5), and VL CDR2 (SEQ ID NO:6). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO:8), VH CDR3 (SEQ ID NO:10), VL CDR1 (SEQ ID NO:5), and VL CDR3 (SEQ ID NO:7). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO:8), VH CDR3 (SEQ ID NO:10), VL CDR2 (SEQ ID NO:6), and VL CDR3 (SEQ ID NO:7). In another embodiment, the antibody comprises VH CDR2 (SEQ ID NO:9), VH CDR3 (SEQ ID NO:10), VL CDR1 (SEQ ID NO:5), and VL CDR2 (SEQ ID NO:6). In one embodiment, the antibody comprises VH CDR2 (SEQ ID NO:9), VH CDR3 (SEQ ID NO:10), VL CDR1 (SEQ ID NO:5), and VL CDR3 (SEQ ID NO:7). In other embodiments, the antibody comprises VH CDR2 (SEQ ID NO:9), VH CDR3 (SEQ ID NO:10), VL CDR2 (SEQ ID NO:6), and VL CDR3 (SEQ ID NO:7). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 8), VH CDR2 (SEQ ID NO: 9), VH CDR3 (SEQ ID NO: 10), VL CDR1 (SEQ ID NO: 5), and VL CDR2 (SEQ ID NO: 6).In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO:8), VH CDR2 (SEQ ID NO:9), VH CDR3 (SEQ ID NO:10), VL CDR1 (SEQ ID NO:5), and VL CDR3 (SEQ ID NO:7). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO:8), VH CDR2 (SEQ ID NO:9), VH CDR3 (SEQ ID NO:10), VL CDR2 (SEQ ID NO:6), and VL CDR3 (SEQ ID NO:7). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO:8), VH CDR2 (SEQ ID NO:9), VL CDR1 (SEQ ID NO:5), VL CDR2 (SEQ ID NO:6), and VL CDR3 (SEQ ID NO:7). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO:8), VH CDR3 (SEQ ID NO:10), VL CDR1 (SEQ ID NO:5), VL CDR2 (SEQ ID NO:6), and VL CDR3 (SEQ ID NO:7). In some embodiments, the antibody comprises VH CDR2 (SEQ ID NO: 9), VH CDR3 (SEQ ID NO: 10), VL CDR1 (SEQ ID NO: 5), VL CDR2 (SEQ ID NO: 6), and VL CDR3 (SEQ ID NO: 7). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 8), VL CDR1 (SEQ ID NO: 5), VL CDR2 (SEQ ID NO: 6), and VL CDR3 (SEQ ID NO: 7). In one embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 9), VL CDR1 (SEQ ID NO: 5), VL CDR2 (SEQ ID NO: 6), and VL CDR3 (SEQ ID NO: 7). In another embodiment, the antibody comprises any combination thereof of the VH CDRs and VL CDRs set forth in Tables 1 and 2.

[0202] In some embodiments, the antibody comprises a VH CDR1, a VH CDR1, a VH CDR3, a VL CDR1, a VL CDR2, a VL CDR3 according to the Chothia numbering system. Thus, in some embodiments, the antibody comprises a VH CDR1 having the amino acid sequence of SEQ ID NO: 71. In some embodiments, the antibody comprises a VH CDR2 having the amino acid sequence of SEQ ID NO: 72. In some embodiments, the antibody comprises a VH CDR3 having the amino acid sequence of SEQ ID NO: 73. In some embodiments, the antibody comprises a VH CDR1 and / or a VH CDR2 and / or a VH CDR3 independently selected from any one of the VH CDR1, VH CDR2, VH CDR3 amino acid sequences shown in Table 2. In some embodiments, the antibody comprises a VL CDR1 having the amino acid sequence of any one of SEQ ID NO: 74. In another embodiment, the antibody comprises a VL CDR2 having the amino acid sequence of SEQ ID NO: 6. In some embodiments, the antibody comprises a VL CDR3 having the amino acid sequence of SEQ ID NO: 76. In some embodiments, the antibody comprises a VL CDR1 and / or a VL CDR2 and / or a VL CDR3 independently selected from any one of the VL CDR1, VL CDR2, VL CDR3 amino acid sequences shown in Table 1.

[0203] In one embodiment, the antibody provided herein comprises a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 71; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 72; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 73; and a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 74; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 6; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 76.

[0204] In some embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 71; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 72; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 73.

[0205] In other embodiments, the antibodies provided herein comprise a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 74; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 6; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 76.

[0206] Also provided herein are antibodies comprising one or more (e.g., one, two, or three) VH CDRs and one or more (e.g., one, two, or three) VL CDRs as set forth in Tables 1 and 2. In particular, provided herein are antibodies comprising a VH CDR1 (SEQ ID NO: 71) and a VL CDR1 (SEQ ID NO: 74). In one embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 71) and a VL CDR2 (SEQ ID NO: 6). In other embodiments, the antibody comprises a VH CDR1 (SEQ ID NO: 71) and a VL CDR3 (SEQ ID NO: 76). In another embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 72) and a VL CDR1 (SEQ ID NO: 74). In some embodiments, the antibody comprises a VH CDR2 (SEQ ID NO: 72) and a VL CDR2 (SEQ ID NO: 6). In one embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 72) and a VL CDR3 (SEQ ID NO: 76). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 73) and a VL CDR1 (SEQ ID NO: 74). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 73) and a VL CDR2 (SEQ ID NO: 6). In some embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 73) and a VL CDR3 (SEQ ID NO: 76). In another embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 71), a VH CDR2 (SEQ ID NO: 72), and a VL CDR1 (SEQ ID NO: 74). In one embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 71), a VH CDR2 (SEQ ID NO: 72), and a VL CDR2 (SEQ ID NO: 6). In another embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 71), a VH CDR2 (SEQ ID NO: 72), and a VL CDR3 (SEQ ID NO: 76). In another embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 72), a VH CDR3 (SEQ ID NO: 73), and a VL CDR1 (SEQ ID NO: 74). In some embodiments, the antibody comprises a VH CDR2 (SEQ ID NO: 72), a VH CDR3 (SEQ ID NO: 73), and a VL CDR2 (SEQ ID NO: 6). In one embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 72), a VH CDR3 (SEQ ID NO: 73), and a VL CDR3 (SEQ ID NO: 76).In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 71), VH CDR3 (SEQ ID NO: 73), and VL CDR1 (SEQ ID NO: 74). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 71), VH CDR3 (SEQ ID NO: 73), and VL CDR2 (SEQ ID NO: 6). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 71), VH CDR3 (SEQ ID NO: 73), and VL CDR3 (SEQ ID NO: 76). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 71), VL CDR1 (SEQ ID NO: 74), and VL CDR2 (SEQ ID NO: 6). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 71), VL CDR1 (SEQ ID NO: 74), and VL CDR3 (SEQ ID NO: 76). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 71), VL CDR2 (SEQ ID NO: 6), and VL CDR3 (SEQ ID NO: 76). In another embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 72), a VL CDR1 (SEQ ID NO: 74), and a VL CDR2 (SEQ ID NO: 6). In some embodiments, the antibody comprises a VH CDR2 (SEQ ID NO: 72), a VL CDR1 (SEQ ID NO: 74), and a VL CDR3 (SEQ ID NO: 76). In one embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 72), a VL CDR2 (SEQ ID NO: 6), and a VL CDR3 (SEQ ID NO: 76). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 73), a VL CDR1 (SEQ ID NO: 74), and a VL CDR2 (SEQ ID NO: 6). In other embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 73), a VL CDR1 (SEQ ID NO: 74), and a VL CDR3 (SEQ ID NO: 76). In some embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 73), a VL CDR2 (SEQ ID NO: 6), and a VL CDR3 (SEQ ID NO: 76). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 71), VH CDR2 (SEQ ID NO: 72), VH CDR3 (SEQ ID NO: 73), and VL CDR1 (SEQ ID NO: 74). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 71), VH CDR2 (SEQ ID NO: 72), VH CDR3 (SEQ ID NO: 73), and VL CDR2 (SEQ ID NO: 6).In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO:71), VH CDR2 (SEQ ID NO:72), VH CDR3 (SEQ ID NO:73), and VL CDR3 (SEQ ID NO:76). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO:71), VH CDR2 (SEQ ID NO:72), VL CDR1 (SEQ ID NO:74), and VL CDR2 (SEQ ID NO:6). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO:71), VH CDR2 (SEQ ID NO:72), VL CDR1 (SEQ ID NO:74), and VL CDR3 (SEQ ID NO:76). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO:71), VH CDR2 (SEQ ID NO:72), VL CDR2 (SEQ ID NO:6), and VL CDR3 (SEQ ID NO:76). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO:71), VH CDR3 (SEQ ID NO:73), VL CDR1 (SEQ ID NO:74), and VL CDR2 (SEQ ID NO:6). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO:71), VH CDR3 (SEQ ID NO:73), VL CDR1 (SEQ ID NO:74), and VL CDR3 (SEQ ID NO:76). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO:71), VH CDR3 (SEQ ID NO:73), VL CDR2 (SEQ ID NO:6), and VL CDR3 (SEQ ID NO:76). In another embodiment, the antibody comprises VH CDR2 (SEQ ID NO:72), VH CDR3 (SEQ ID NO:73), VL CDR1 (SEQ ID NO:74), and VL CDR2 (SEQ ID NO:6). In one embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 72), VH CDR3 (SEQ ID NO: 73), VL CDR1 (SEQ ID NO: 74), and VL CDR3 (SEQ ID NO: 76). In other embodiments, the antibody comprises VH CDR2 (SEQ ID NO: 72), VH CDR3 (SEQ ID NO: 73), VL CDR2 (SEQ ID NO: 6), and VL CDR3 (SEQ ID NO: 76). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 71), VH CDR2 (SEQ ID NO: 72), VH CDR3 (SEQ ID NO: 73), VL CDR1 (SEQ ID NO: 74), and VL CDR2 (SEQ ID NO: 6).In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO:71), VH CDR2 (SEQ ID NO:72), VH CDR3 (SEQ ID NO:73), VL CDR1 (SEQ ID NO:74), and VL CDR3 (SEQ ID NO:76). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO:71), VH CDR2 (SEQ ID NO:72), VH CDR3 (SEQ ID NO:73), VL CDR2 (SEQ ID NO:6), and VL CDR3 (SEQ ID NO:76). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO:71), VH CDR2 (SEQ ID NO:72), VL CDR1 (SEQ ID NO:74), VL CDR2 (SEQ ID NO:6), and VL CDR3 (SEQ ID NO:76). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO:71), VH CDR3 (SEQ ID NO:73), VL CDR1 (SEQ ID NO:74), VL CDR2 (SEQ ID NO:6), and VL CDR3 (SEQ ID NO:76). In some embodiments, the antibody comprises VH CDR2 (SEQ ID NO:72), VH CDR3 (SEQ ID NO:73), VL CDR1 (SEQ ID NO:74), VL CDR2 (SEQ ID NO:6), and VL CDR3 (SEQ ID NO:76). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO:71), VL CDR1 (SEQ ID NO:74), VL CDR2 (SEQ ID NO:6), and VL CDR3 (SEQ ID NO:76). In one embodiment, the antibody comprises VH CDR2 (SEQ ID NO:72), VL CDR1 (SEQ ID NO:74), VL CDR2 (SEQ ID NO:6), and VL CDR3 (SEQ ID NO:76). In other embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 73), a VL CDR1 (SEQ ID NO: 74), a VL CDR2 (SEQ ID NO: 6), and a VL CDR3 (SEQ ID NO: 76). In another embodiment, the antibody comprises any combination of the VH and VL CDRs set forth in Tables 1 and 2.

[0207] In some embodiments, the antibody comprises a VH CDR1, a VH CDR1, a VH CDR3, a VL CDR1, a VL CDR2, a VL CDR3 according to the IMGT numbering system. In some embodiments, the antibody comprises a VH CDR1 having the amino acid sequence of SEQ ID NO: 77. In some embodiments, the antibody comprises a VH CDR2 having the amino acid sequence of SEQ ID NO: 78. In some embodiments, the antibody comprises a VH CDR3 having the amino acid sequence of SEQ ID NO: 79. In some embodiments, the antibody comprises a VH CDR1 and / or a VH CDR2 and / or a VH CDR3 independently selected from any one of the VH CDR1, VH CDR2, VH CDR3 amino acid sequences shown in Table 2. In some embodiments, the antibody comprises a VL CDR1 having the amino acid sequence of any one of SEQ ID NO: 80. In another embodiment, the antibody comprises a VL CDR2 having the amino acid sequence of SEQ ID NO: 81. In some embodiments, the antibody comprises a VL CDR3 having the amino acid sequence of SEQ ID NO: 82. In some embodiments, the antibody comprises a VL CDR1 and / or a VL CDR2 and / or a VL CDR3 independently selected from any one of the VL CDR1, VL CDR2, VL CDR3 amino acid sequences shown in Table 1.

[0208] In one embodiment, the antibody provided herein comprises a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 77; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 78; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 79; and a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 80; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 81; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 82.

[0209] In some embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 77; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 78; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 79.

[0210] In other embodiments, the antibodies provided herein comprise a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 80; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 81; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 82.

[0211] Also provided herein are antibodies that comprise one or more (e.g., one, two, or three) VH CDRs and one or more (e.g., one, two, or three) VL CDRs as set forth in Tables 1 and 2. In particular, provided herein are antibodies that comprise a VH CDR1 (SEQ ID NO: 77) and a VL CDR1 (SEQ ID NO: 80). In one embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 77) and a VL CDR2 (SEQ ID NO: 81). In other embodiments, the antibody comprises a VH CDR1 (SEQ ID NO: 77) and a VL CDR3 (SEQ ID NO: 82). In another embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 78) and a VL CDR1 (SEQ ID NO: 80). In some embodiments, the antibody comprises a VH CDR2 (SEQ ID NO: 78) and a VL CDR2 (SEQ ID NO: 81). In one embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 78) and a VL CDR3 (SEQ ID NO: 82). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 79) and a VL CDR1 (SEQ ID NO: 80). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 79) and a VL CDR2 (SEQ ID NO: 81). In some embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 79) and a VL CDR3 (SEQ ID NO: 82). In another embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 77), a VH CDR2 (SEQ ID NO: 78), and a VL CDR1 (SEQ ID NO: 80). In one embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 77), a VH CDR2 (SEQ ID NO: 78), and a VL CDR2 (SEQ ID NO: 81). In other embodiments, the antibody comprises a VH CDR1 (SEQ ID NO: 77), a VH CDR2 (SEQ ID NO: 78), and a VL CDR3 (SEQ ID NO: 82). In another embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 78), a VH CDR3 (SEQ ID NO: 79), and a VL CDR1 (SEQ ID NO: 80). In some embodiments, the antibody comprises a VH CDR2 (SEQ ID NO: 78), a VH CDR3 (SEQ ID NO: 79), and a VL CDR2 (SEQ ID NO: 81). In one embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 78), a VH CDR3 (SEQ ID NO: 79), and a VL CDR3 (SEQ ID NO: 82).In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 77), VH CDR3 (SEQ ID NO: 79), and VL CDR1 (SEQ ID NO: 80). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 77), VH CDR3 (SEQ ID NO: 79), and VL CDR2 (SEQ ID NO: 81). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 77), VH CDR3 (SEQ ID NO: 79), and VL CDR3 (SEQ ID NO: 82). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 77), VL CDR1 (SEQ ID NO: 80), and VL CDR2 (SEQ ID NO: 81). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 77), VL CDR1 (SEQ ID NO: 80), and VL CDR3 (SEQ ID NO: 82). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 77), VL CDR2 (SEQ ID NO: 81), and VL CDR3 (SEQ ID NO: 82). In another embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 78), a VL CDR1 (SEQ ID NO: 80), and a VL CDR2 (SEQ ID NO: 81). In some embodiments, the antibody comprises a VH CDR2 (SEQ ID NO: 78), a VL CDR1 (SEQ ID NO: 80), and a VL CDR3 (SEQ ID NO: 82). In one embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 78), a VL CDR2 (SEQ ID NO: 81), and a VL CDR3 (SEQ ID NO: 82). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 79), a VL CDR1 (SEQ ID NO: 80), and a VL CDR2 (SEQ ID NO: 81). In other embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 79), a VL CDR1 (SEQ ID NO: 80), and a VL CDR3 (SEQ ID NO: 82). In some embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 79), a VL CDR2 (SEQ ID NO: 81), and a VL CDR3 (SEQ ID NO: 82). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 77), VH CDR2 (SEQ ID NO: 78), VH CDR3 (SEQ ID NO: 79), and VL CDR1 (SEQ ID NO: 80). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 77), VH CDR2 (SEQ ID NO: 78), VH CDR3 (SEQ ID NO: 79), and VL CDR2 (SEQ ID NO: 81).In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 77), VH CDR2 (SEQ ID NO: 78), VH CDR3 (SEQ ID NO: 79), and VL CDR3 (SEQ ID NO: 82). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 77), VH CDR2 (SEQ ID NO: 78), VL CDR1 (SEQ ID NO: 80), and VL CDR2 (SEQ ID NO: 81). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 77), VH CDR2 (SEQ ID NO: 78), VL CDR1 (SEQ ID NO: 80), and VL CDR3 (SEQ ID NO: 82). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 77), VH CDR2 (SEQ ID NO: 78), VL CDR2 (SEQ ID NO: 81), and VL CDR3 (SEQ ID NO: 82). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 77), VH CDR3 (SEQ ID NO: 79), VL CDR1 (SEQ ID NO: 80), and VL CDR2 (SEQ ID NO: 81). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 77), VH CDR3 (SEQ ID NO: 79), VL CDR1 (SEQ ID NO: 80), and VL CDR3 (SEQ ID NO: 82). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 77), VH CDR3 (SEQ ID NO: 79), VL CDR2 (SEQ ID NO: 81), and VL CDR3 (SEQ ID NO: 82). In another embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 78), VH CDR3 (SEQ ID NO: 79), VL CDR1 (SEQ ID NO: 80), and VL CDR2 (SEQ ID NO: 81). In one embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 78), VH CDR3 (SEQ ID NO: 79), VL CDR1 (SEQ ID NO: 80), and VL CDR3 (SEQ ID NO: 82). In other embodiments, the antibody comprises VH CDR2 (SEQ ID NO: 78), VH CDR3 (SEQ ID NO: 79), VL CDR2 (SEQ ID NO: 81), and VL CDR3 (SEQ ID NO: 82). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 77), VH CDR2 (SEQ ID NO: 78), VH CDR3 (SEQ ID NO: 79), VL CDR1 (SEQ ID NO: 80), and VL CDR2 (SEQ ID NO: 81).In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO:77), VH CDR2 (SEQ ID NO:78), VH CDR3 (SEQ ID NO:79), VL CDR1 (SEQ ID NO:80), and VL CDR3 (SEQ ID NO:82). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO:77), VH CDR2 (SEQ ID NO:78), VH CDR3 (SEQ ID NO:79), VL CDR2 (SEQ ID NO:81), and VL CDR3 (SEQ ID NO:82). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO:77), VH CDR2 (SEQ ID NO:78), VL CDR1 (SEQ ID NO:80), VL CDR2 (SEQ ID NO:81), and VL CDR3 (SEQ ID NO:82). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 77), VH CDR3 (SEQ ID NO: 79), VL CDR1 (SEQ ID NO: 80), VL CDR2 (SEQ ID NO: 81), and VL CDR3 (SEQ ID NO: 82). In some embodiments, the antibody comprises VH CDR2 (SEQ ID NO: 78), VH CDR3 (SEQ ID NO: 79), VL CDR1 (SEQ ID NO: 80), VL CDR2 (SEQ ID NO: 81), and VL CDR3 (SEQ ID NO: 82). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 77), VL CDR1 (SEQ ID NO: 80), VL CDR2 (SEQ ID NO: 81), and VL CDR3 (SEQ ID NO: 82). In one embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 78), VL CDR1 (SEQ ID NO: 80), VL CDR2 (SEQ ID NO: 81), and VL CDR3 (SEQ ID NO: 82). In other embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 79), a VL CDR1 (SEQ ID NO: 80), a VL CDR2 (SEQ ID NO: 81), and a VL CDR3 (SEQ ID NO: 82). In another embodiment, the antibody comprises any combination of the VH and VL CDRs set forth in Tables 1 and 2.

[0212] In some embodiments, the antibody comprises a VH CDR1, a VH CDR1, a VH CDR3, a VL CDR1, a VL CDR2, a VL CDR3 according to the contact numbering system. In some embodiments, the antibody comprises a VH CDR1, a VH CDR1, a VH CDR3, a VL CDR1, a VL CDR2, a VL CDR3 according to the contact numbering system. In some embodiments, the antibody comprises a VH CDR1 having the amino acid sequence of SEQ ID NO: 83. In some embodiments, the antibody comprises a VH CDR2 having the amino acid sequence of SEQ ID NO: 84. In some embodiments, the antibody comprises a VH CDR3 having the amino acid sequence of SEQ ID NO: 85. In some embodiments, the antibody comprises a VH CDR1 and / or a VH CDR2 and / or a VH CDR3 independently selected from any one of the VH CDR1, VH CDR2, VH CDR3 amino acid sequences shown in Table 2. In some embodiments, the antibody comprises a VL CDR1 having the amino acid sequence of any one of SEQ ID NO: 86. In another embodiment, the antibody comprises a VL CDR2 having the amino acid sequence of SEQ ID NO: 87. In some embodiments, the antibody comprises a VL CDR3 having the amino acid sequence of SEQ ID NO: 88. In some embodiments, the antibody comprises a VL CDR1 and / or a VL CDR2 and / or a VL CDR3 independently selected from any one of the VL CDR1, VL CDR2, VL CDR3 amino acid sequences shown in Table 1.

[0213] In one embodiment, the antibody provided herein comprises a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 83; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 84; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 85; and a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 86; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 87; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 88.

[0214] In some embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 83; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 84; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 85.

[0215] In other embodiments, the antibodies provided herein comprise a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 86; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 87; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 88.

[0216] Also provided herein are antibodies comprising one or more (e.g., one, two, or three) VH CDRs and one or more (e.g., one, two, or three) VL CDRs as set forth in Tables 1 and 2. In particular, provided herein are antibodies comprising a VH CDR1 (SEQ ID NO: 83) and a VL CDR1 (SEQ ID NO: 86). In one embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 83) and a VL CDR2 (SEQ ID NO: 87). In other embodiments, the antibody comprises a VH CDR1 (SEQ ID NO: 83) and a VL CDR3 (SEQ ID NO: 88). In another embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 84) and a VL CDR1 (SEQ ID NO: 86). In some embodiments, the antibody comprises a VH CDR2 (SEQ ID NO: 84) and a VL CDR2 (SEQ ID NO: 87). In one embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 84) and a VL CDR3 (SEQ ID NO: 88). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 85) and a VL CDR1 (SEQ ID NO: 86). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 85) and a VL CDR2 (SEQ ID NO: 87). In some embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 85) and a VL CDR3 (SEQ ID NO: 88). In another embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 83), a VH CDR2 (SEQ ID NO: 84), and a VL CDR1 (SEQ ID NO: 86). In one embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 83), a VH CDR2 (SEQ ID NO: 84), and a VL CDR2 (SEQ ID NO: 87). In other embodiments, the antibody comprises a VH CDR1 (SEQ ID NO: 83), a VH CDR2 (SEQ ID NO: 84), and a VL CDR3 (SEQ ID NO: 88). In another embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 84), a VH CDR3 (SEQ ID NO: 85), and a VL CDR1 (SEQ ID NO: 86). In some embodiments, the antibody comprises a VH CDR2 (SEQ ID NO: 84), a VH CDR3 (SEQ ID NO: 85), and a VL CDR2 (SEQ ID NO: 87). In one embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 84), a VH CDR3 (SEQ ID NO: 85), and a VL CDR3 (SEQ ID NO: 88).In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 83), VH CDR3 (SEQ ID NO: 85), and VL CDR1 (SEQ ID NO: 86). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 83), VH CDR3 (SEQ ID NO: 85), and VL CDR2 (SEQ ID NO: 87). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 83), VH CDR3 (SEQ ID NO: 85), and VL CDR3 (SEQ ID NO: 88). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 83), VL CDR1 (SEQ ID NO: 86), and VL CDR2 (SEQ ID NO: 87). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 83), VL CDR1 (SEQ ID NO: 86), and VL CDR3 (SEQ ID NO: 88). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 83), VL CDR2 (SEQ ID NO: 87), and VL CDR3 (SEQ ID NO: 88). In another embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 84), a VL CDR1 (SEQ ID NO: 86), and a VL CDR2 (SEQ ID NO: 87). In some embodiments, the antibody comprises a VH CDR2 (SEQ ID NO: 84), a VL CDR1 (SEQ ID NO: 86), and a VL CDR3 (SEQ ID NO: 88). In one embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 84), a VL CDR2 (SEQ ID NO: 87), and a VL CDR3 (SEQ ID NO: 88). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 85), a VL CDR1 (SEQ ID NO: 86), and a VL CDR2 (SEQ ID NO: 87). In other embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 85), a VL CDR1 (SEQ ID NO: 86), and a VL CDR3 (SEQ ID NO: 88). In some embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 85), a VL CDR2 (SEQ ID NO: 87), and a VL CDR3 (SEQ ID NO: 88). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 83), VH CDR2 (SEQ ID NO: 84), VH CDR3 (SEQ ID NO: 85), and VL CDR1 (SEQ ID NO: 86). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 83), VH CDR2 (SEQ ID NO: 84), VH CDR3 (SEQ ID NO: 85), and VL CDR2 (SEQ ID NO: 87).In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 83), VH CDR2 (SEQ ID NO: 84), VH CDR3 (SEQ ID NO: 85), and VL CDR3 (SEQ ID NO: 88). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 83), VH CDR2 (SEQ ID NO: 84), VL CDR1 (SEQ ID NO: 86), and VL CDR2 (SEQ ID NO: 87). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 83), VH CDR2 (SEQ ID NO: 84), VL CDR1 (SEQ ID NO: 86), and VL CDR3 (SEQ ID NO: 88). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 83), VH CDR2 (SEQ ID NO: 84), VL CDR2 (SEQ ID NO: 87), and VL CDR3 (SEQ ID NO: 88). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 83), VH CDR3 (SEQ ID NO: 85), VL CDR1 (SEQ ID NO: 86), and VL CDR2 (SEQ ID NO: 87). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 83), VH CDR3 (SEQ ID NO: 85), VL CDR1 (SEQ ID NO: 86), and VL CDR3 (SEQ ID NO: 88). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 83), VH CDR3 (SEQ ID NO: 85), VL CDR2 (SEQ ID NO: 87), and VL CDR3 (SEQ ID NO: 88). In another embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 84), VH CDR3 (SEQ ID NO: 85), VL CDR1 (SEQ ID NO: 86), and VL CDR2 (SEQ ID NO: 87). In one embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 84), VH CDR3 (SEQ ID NO: 85), VL CDR1 (SEQ ID NO: 86), and VL CDR3 (SEQ ID NO: 88). In other embodiments, the antibody comprises VH CDR2 (SEQ ID NO: 84), VH CDR3 (SEQ ID NO: 85), VL CDR2 (SEQ ID NO: 87), and VL CDR3 (SEQ ID NO: 88). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 83), VH CDR2 (SEQ ID NO: 84), VH CDR3 (SEQ ID NO: 85), VL CDR1 (SEQ ID NO: 86), and VL CDR2 (SEQ ID NO: 87).In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 83), VH CDR2 (SEQ ID NO: 84), VH CDR3 (SEQ ID NO: 85), VL CDR1 (SEQ ID NO: 86), and VL CDR3 (SEQ ID NO: 88). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 83), VH CDR2 (SEQ ID NO: 84), VH CDR3 (SEQ ID NO: 85), VL CDR2 (SEQ ID NO: 87), and VL CDR3 (SEQ ID NO: 88). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 83), VH CDR2 (SEQ ID NO: 84), VL CDR1 (SEQ ID NO: 86), VL CDR2 (SEQ ID NO: 87), and VL CDR3 (SEQ ID NO: 88). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 83), VH CDR3 (SEQ ID NO: 85), VL CDR1 (SEQ ID NO: 86), VL CDR2 (SEQ ID NO: 87), and VL CDR3 (SEQ ID NO: 88). In some embodiments, the antibody comprises VH CDR2 (SEQ ID NO: 84), VH CDR3 (SEQ ID NO: 85), VL CDR1 (SEQ ID NO: 86), VL CDR2 (SEQ ID NO: 87), and VL CDR3 (SEQ ID NO: 88). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 83), VL CDR1 (SEQ ID NO: 86), VL CDR2 (SEQ ID NO: 87), and VL CDR3 (SEQ ID NO: 88). In one embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 84), VL CDR1 (SEQ ID NO: 86), VL CDR2 (SEQ ID NO: 87), and VL CDR3 (SEQ ID NO: 88). In other embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 85), a VL CDR1 (SEQ ID NO: 86), a VL CDR2 (SEQ ID NO: 87), and a VL CDR3 (SEQ ID NO: 88). In another embodiment, the antibody comprises any combination of the VH and VL CDRs set forth in Tables 1 and 2. Table 3. VL CDR sequences of anti-BTN1A1 antibody STC43G3-1 [Table 4] Table 4. VH CDR sequences of anti-BTN1A1 antibody STC43G3-1 [Table 5]

[0217] In some embodiments, the antibodies provided herein comprise or consist of six CDRs, e.g., VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3, identified in Tables 3 and 4. In some embodiments, the antibodies provided herein can comprise fewer than six CDRs. In some embodiments, the antibodies comprise or consist of one, two, three, four, or five CDRs selected from the group consisting of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3, identified in Tables 3 and 4. In some embodiments, the antibodies comprise or consist of one, two, three, four, or five CDRs selected from the group consisting of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 of the monoclonals described herein. Thus, in some embodiments, the antibody comprises or consists of one, two, three, four, or five CDRs of any one of the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 identified in Tables 3 and 4.

[0218] In some embodiments, the antibodies provided herein comprise one or more (e.g., one, two, or three) VH CDRs set forth in Table 4. In other embodiments, the antibodies provided herein comprise one or more (e.g., one, two, or three) VL CDRs set forth in Table 3. In yet other embodiments, the antibodies provided herein comprise one or more (e.g., one, two, or three) VH CDRs set forth in Table 4 and one or more VL CDRs set forth in Table 3.

[0219] In some embodiments, the antibody comprises a VH CDR1, a VH CDR1, a VH CDR3, a VL CDR1, a VL CDR2, a VL CDR3 according to the contact numbering system. In some embodiments, the antibody comprises a VH CDR1, a VH CDR1, a VH CDR3, a VL CDR1, a VL CDR2, a VL CDR3 according to the Kabat numbering system. Thus, in some embodiments, the antibody comprises a VH CDR1 having the amino acid sequence of SEQ ID NO: 44. In some embodiments, the antibody comprises a VH CDR2 having the amino acid sequence of SEQ ID NO: 45. In some embodiments, the antibody comprises a VH CDR3 having the amino acid sequence of SEQ ID NO: 46. In some embodiments, the antibody comprises a VH CDR1 and / or a VH CDR2 and / or a VH CDR3 independently selected from any one of the VH CDR1, VH CDR2, VH CDR3 amino acid sequences shown in Table 4. In some embodiments, the antibody comprises a VL CDR1 having the amino acid sequence of any one of SEQ ID NO: 38. In another embodiment, the antibody comprises a VL CDR2 having the amino acid sequence of SEQ ID NO: 39. In some embodiments, the antibody comprises a VL CDR3 having the amino acid sequence of SEQ ID NO: 40. In some embodiments, the antibody comprises a VL CDR1 and / or a VL CDR2 and / or a VL CDR3 independently selected from any one of the VL CDR1, VL CDR2, VL CDR3 amino acid sequences shown in Table 3.

[0220] In one embodiment, the antibody provided herein comprises a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 44; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 45; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 46; and a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 38; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 39; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 40.

[0221] In some embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 44; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 45; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 46.

[0222] In other embodiments, the antibodies provided herein comprise a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 38; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 39; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 40.

[0223] Also provided herein are antibodies comprising one or more (e.g., one, two, or three) VH CDRs and one or more (e.g., one, two, or three) VL CDRs as set forth in Tables 3 and 4. In particular, provided herein are antibodies comprising a VH CDR1 (SEQ ID NO: 44) and a VL CDR1 (SEQ ID NO: 38). In one embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 44) and a VL CDR2 (SEQ ID NO: 39). In other embodiments, the antibody comprises a VH CDR1 (SEQ ID NO: 44) and a VL CDR3 (SEQ ID NO: 40). In another embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 45) and a VL CDR1 (SEQ ID NO: 38). In some embodiments, the antibody comprises a VH CDR2 (SEQ ID NO: 45) and a VL CDR2 (SEQ ID NO: 39). In one embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 45) and a VL CDR3 (SEQ ID NO: 40). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 46) and a VL CDR1 (SEQ ID NO: 38). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 46) and a VL CDR2 (SEQ ID NO: 39). In some embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 46) and a VL CDR3 (SEQ ID NO: 40). In another embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 44), a VH CDR2 (SEQ ID NO: 45), and a VL CDR1 (SEQ ID NO: 38). In one embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 44), a VH CDR2 (SEQ ID NO: 45), and a VL CDR2 (SEQ ID NO: 39). In other embodiments, the antibody comprises a VH CDR1 (SEQ ID NO: 44), a VH CDR2 (SEQ ID NO: 45), and a VL CDR3 (SEQ ID NO: 40). In another embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 45), a VH CDR3 (SEQ ID NO: 46), and a VL CDR1 (SEQ ID NO: 38). In some embodiments, the antibody comprises a VH CDR2 (SEQ ID NO: 45), a VH CDR3 (SEQ ID NO: 46), and a VL CDR2 (SEQ ID NO: 39). In one embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 45), a VH CDR3 (SEQ ID NO: 46), and a VL CDR3 (SEQ ID NO: 40).In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 44), VH CDR3 (SEQ ID NO: 46), and VL CDR1 (SEQ ID NO: 38). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 44), VH CDR3 (SEQ ID NO: 46), and VL CDR2 (SEQ ID NO: 39). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 44), VH CDR3 (SEQ ID NO: 46), and VL CDR3 (SEQ ID NO: 40). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 44), VL CDR1 (SEQ ID NO: 38), and VL CDR2 (SEQ ID NO: 39). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 44), VL CDR1 (SEQ ID NO: 38), and VL CDR3 (SEQ ID NO: 40). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 44), VL CDR2 (SEQ ID NO: 39), and VL CDR3 (SEQ ID NO: 40). In another embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 45), a VL CDR1 (SEQ ID NO: 38), and a VL CDR2 (SEQ ID NO: 39). In some embodiments, the antibody comprises a VH CDR2 (SEQ ID NO: 45), a VL CDR1 (SEQ ID NO: 38), and a VL CDR3 (SEQ ID NO: 40). In one embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 45), a VL CDR2 (SEQ ID NO: 39), and a VL CDR3 (SEQ ID NO: 40). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 46), a VL CDR1 (SEQ ID NO: 38), and a VL CDR2 (SEQ ID NO: 39). In other embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 46), a VL CDR1 (SEQ ID NO: 38), and a VL CDR3 (SEQ ID NO: 40). In some embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 46), a VL CDR2 (SEQ ID NO: 39), and a VL CDR3 (SEQ ID NO: 40). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 44), VH CDR2 (SEQ ID NO: 45), VH CDR3 (SEQ ID NO: 46), and VL CDR1 (SEQ ID NO: 38). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 44), VH CDR2 (SEQ ID NO: 45), VH CDR3 (SEQ ID NO: 46), and VL CDR2 (SEQ ID NO: 39).In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 44), VH CDR2 (SEQ ID NO: 45), VH CDR3 (SEQ ID NO: 46), and VL CDR3 (SEQ ID NO: 40). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 44), VH CDR2 (SEQ ID NO: 45), VL CDR1 (SEQ ID NO: 38), and VL CDR2 (SEQ ID NO: 39). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 44), VH CDR2 (SEQ ID NO: 45), VL CDR1 (SEQ ID NO: 38), and VL CDR3 (SEQ ID NO: 40). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 44), VH CDR2 (SEQ ID NO: 45), VL CDR2 (SEQ ID NO: 39), and VL CDR3 (SEQ ID NO: 40). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 44), VH CDR3 (SEQ ID NO: 46), VL CDR1 (SEQ ID NO: 38), and VL CDR2 (SEQ ID NO: 39). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 44), VH CDR3 (SEQ ID NO: 46), VL CDR1 (SEQ ID NO: 38), and VL CDR3 (SEQ ID NO: 40). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 44), VH CDR3 (SEQ ID NO: 46), VL CDR2 (SEQ ID NO: 39), and VL CDR3 (SEQ ID NO: 40). In another embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 45), VH CDR3 (SEQ ID NO: 46), VL CDR1 (SEQ ID NO: 38), and VL CDR2 (SEQ ID NO: 39). In one embodiment, the antibody comprises VH CDR2 (SEQ ID NO:45), VH CDR3 (SEQ ID NO:46), VL CDR1 (SEQ ID NO:38), and VL CDR3 (SEQ ID NO:40). In other embodiments, the antibody comprises VH CDR2 (SEQ ID NO:45), VH CDR3 (SEQ ID NO:46), VL CDR2 (SEQ ID NO:39), and VL CDR3 (SEQ ID NO:40). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO:44), VH CDR2 (SEQ ID NO:45), VH CDR3 (SEQ ID NO:46), VL CDR1 (SEQ ID NO:38), and VL CDR2 (SEQ ID NO:39).In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO:44), VH CDR2 (SEQ ID NO:45), VH CDR3 (SEQ ID NO:46), VL CDR1 (SEQ ID NO:38), and VL CDR3 (SEQ ID NO:40). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO:44), VH CDR2 (SEQ ID NO:45), VH CDR3 (SEQ ID NO:46), VL CDR2 (SEQ ID NO:39), and VL CDR3 (SEQ ID NO:40). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO:44), VH CDR2 (SEQ ID NO:45), VL CDR1 (SEQ ID NO:38), VL CDR2 (SEQ ID NO:39), and VL CDR3 (SEQ ID NO:40). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 44), VH CDR3 (SEQ ID NO: 46), VL CDR1 (SEQ ID NO: 38), VL CDR2 (SEQ ID NO: 39), and VL CDR3 (SEQ ID NO: 40). In some embodiments, the antibody comprises VH CDR2 (SEQ ID NO: 45), VH CDR3 (SEQ ID NO: 46), VL CDR1 (SEQ ID NO: 38), VL CDR2 (SEQ ID NO: 39), and VL CDR3 (SEQ ID NO: 40). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 44), VL CDR1 (SEQ ID NO: 38), VL CDR2 (SEQ ID NO: 39), and VL CDR3 (SEQ ID NO: 40). In one embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 45), VL CDR1 (SEQ ID NO: 38), VL CDR2 (SEQ ID NO: 39), and VL CDR3 (SEQ ID NO: 40). In other embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 46), a VL CDR1 (SEQ ID NO: 38), a VL CDR2 (SEQ ID NO: 39), and a VL CDR3 (SEQ ID NO: 40). In another embodiment, the antibody comprises any combination of the VH and VL CDRs set forth in Tables 3 and 4.

[0224] In some embodiments, the antibody comprises a VH CDR1, a VH CDR1, a VH CDR3, a VL CDR1, a VL CDR2, a VL CDR3 according to the Chothia numbering system. Thus, in some embodiments, the antibody comprises a VH CDR1 having the amino acid sequence of SEQ ID NO: 91. In some embodiments, the antibody comprises a VH CDR2 having the amino acid sequence of SEQ ID NO: 92. In some embodiments, the antibody comprises a VH CDR3 having the amino acid sequence of SEQ ID NO: 93. In some embodiments, the antibody comprises a VH CDR1 and / or a VH CDR2 and / or a VH CDR3 independently selected from any one of the VH CDR1, VH CDR2, VH CDR3 amino acid sequences shown in Table 4. In some embodiments, the antibody comprises a VL CDR1 having the amino acid sequence of any one of SEQ ID NO: 94. In another embodiment, the antibody comprises a VL CDR2 having the amino acid sequence of SEQ ID NO: 95. In some embodiments, the antibody comprises a VL CDR3 having the amino acid sequence of SEQ ID NO: 96. In some embodiments, the antibody comprises a VL CDR1 and / or a VL CDR2 and / or a VL CDR3 independently selected from any one of the VL CDR1, VL CDR2, VL CDR3 amino acid sequences shown in Table 3.

[0225] In one embodiment, the antibody provided herein comprises a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 91; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 92; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 93; and a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 94; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 95; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 96.

[0226] In some embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 91; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 92; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 93.

[0227] In other embodiments, the antibodies provided herein comprise a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 94; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 95; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 96.

[0228] Also provided herein are antibodies that comprise one or more (e.g., one, two, or three) VH CDRs and one or more (e.g., one, two, or three) VL CDRs as set forth in Tables 3 and 4. In particular, provided herein are antibodies that comprise a VH CDR1 (SEQ ID NO: 91) and a VL CDR1 (SEQ ID NO: 94). In one embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 91) and a VL CDR2 (SEQ ID NO: 95). In other embodiments, the antibody comprises a VH CDR1 (SEQ ID NO: 91) and a VL CDR3 (SEQ ID NO: 96). In another embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 92) and a VL CDR1 (SEQ ID NO: 94). In some embodiments, the antibody comprises a VH CDR2 (SEQ ID NO: 92) and a VL CDR2 (SEQ ID NO: 95). In one embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 92) and a VL CDR3 (SEQ ID NO: 96). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 93) and a VL CDR1 (SEQ ID NO: 94). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 93) and a VL CDR2 (SEQ ID NO: 95). In some embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 93) and a VL CDR3 (SEQ ID NO: 96). In another embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 91), a VH CDR2 (SEQ ID NO: 92), and a VL CDR1 (SEQ ID NO: 94). In one embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 91), a VH CDR2 (SEQ ID NO: 92), and a VL CDR2 (SEQ ID NO: 95). In other embodiments, the antibody comprises a VH CDR1 (SEQ ID NO: 91), a VH CDR2 (SEQ ID NO: 92), and a VL CDR3 (SEQ ID NO: 96). In another embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 92), a VH CDR3 (SEQ ID NO: 93), and a VL CDR1 (SEQ ID NO: 94). In some embodiments, the antibody comprises a VH CDR2 (SEQ ID NO: 92), a VH CDR3 (SEQ ID NO: 93), and a VL CDR2 (SEQ ID NO: 95). In one embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 92), a VH CDR3 (SEQ ID NO: 93), and a VL CDR3 (SEQ ID NO: 96).In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 91), VH CDR3 (SEQ ID NO: 93), and VL CDR1 (SEQ ID NO: 94). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 91), VH CDR3 (SEQ ID NO: 93), and VL CDR2 (SEQ ID NO: 95). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 91), VH CDR3 (SEQ ID NO: 93), and VL CDR3 (SEQ ID NO: 96). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 91), VL CDR1 (SEQ ID NO: 94), and VL CDR2 (SEQ ID NO: 95). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 91), VL CDR1 (SEQ ID NO: 94), and VL CDR3 (SEQ ID NO: 96). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 91), VL CDR2 (SEQ ID NO: 95), and VL CDR3 (SEQ ID NO: 96). In another embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 92), a VL CDR1 (SEQ ID NO: 94), and a VL CDR2 (SEQ ID NO: 95). In some embodiments, the antibody comprises a VH CDR2 (SEQ ID NO: 92), a VL CDR1 (SEQ ID NO: 94), and a VL CDR3 (SEQ ID NO: 96). In one embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 92), a VL CDR2 (SEQ ID NO: 95), and a VL CDR3 (SEQ ID NO: 96). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 93), a VL CDR1 (SEQ ID NO: 94), and a VL CDR2 (SEQ ID NO: 95). In other embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 93), a VL CDR1 (SEQ ID NO: 94), and a VL CDR3 (SEQ ID NO: 96). In some embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 93), a VL CDR2 (SEQ ID NO: 95), and a VL CDR3 (SEQ ID NO: 96). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 91), VH CDR2 (SEQ ID NO: 92), VH CDR3 (SEQ ID NO: 93), and VL CDR1 (SEQ ID NO: 94). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 91), VH CDR2 (SEQ ID NO: 92), VH CDR3 (SEQ ID NO: 93), and VL CDR2 (SEQ ID NO: 95).In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 91), VH CDR2 (SEQ ID NO: 92), VH CDR3 (SEQ ID NO: 93), and VL CDR3 (SEQ ID NO: 96). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 91), VH CDR2 (SEQ ID NO: 92), VL CDR1 (SEQ ID NO: 94), and VL CDR2 (SEQ ID NO: 95). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 91), VH CDR2 (SEQ ID NO: 92), VL CDR1 (SEQ ID NO: 94), and VL CDR3 (SEQ ID NO: 96). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 91), VH CDR2 (SEQ ID NO: 92), VL CDR2 (SEQ ID NO: 95), and VL CDR3 (SEQ ID NO: 96). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 91), VH CDR3 (SEQ ID NO: 93), VL CDR1 (SEQ ID NO: 94), and VL CDR2 (SEQ ID NO: 95). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 91), VH CDR3 (SEQ ID NO: 93), VL CDR1 (SEQ ID NO: 94), and VL CDR3 (SEQ ID NO: 96). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 91), VH CDR3 (SEQ ID NO: 93), VL CDR2 (SEQ ID NO: 95), and VL CDR3 (SEQ ID NO: 96). In another embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 92), VH CDR3 (SEQ ID NO: 93), VL CDR1 (SEQ ID NO: 94), and VL CDR2 (SEQ ID NO: 95). In one embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 92), VH CDR3 (SEQ ID NO: 93), VL CDR1 (SEQ ID NO: 94), and VL CDR3 (SEQ ID NO: 96). In other embodiments, the antibody comprises VH CDR2 (SEQ ID NO: 92), VH CDR3 (SEQ ID NO: 93), VL CDR2 (SEQ ID NO: 95), and VL CDR3 (SEQ ID NO: 96). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 91), VH CDR2 (SEQ ID NO: 92), VH CDR3 (SEQ ID NO: 93), VL CDR1 (SEQ ID NO: 94), and VL CDR2 (SEQ ID NO: 95).In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 91), VH CDR2 (SEQ ID NO: 92), VH CDR3 (SEQ ID NO: 93), VL CDR1 (SEQ ID NO: 94), and VL CDR3 (SEQ ID NO: 96). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 91), VH CDR2 (SEQ ID NO: 92), VH CDR3 (SEQ ID NO: 93), VL CDR2 (SEQ ID NO: 95), and VL CDR3 (SEQ ID NO: 96). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 91), VH CDR2 (SEQ ID NO: 92), VL CDR1 (SEQ ID NO: 94), VL CDR2 (SEQ ID NO: 95), and VL CDR3 (SEQ ID NO: 96). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 91), VH CDR3 (SEQ ID NO: 93), VL CDR1 (SEQ ID NO: 94), VL CDR2 (SEQ ID NO: 95), and VL CDR3 (SEQ ID NO: 96). In some embodiments, the antibody comprises VH CDR2 (SEQ ID NO: 92), VH CDR3 (SEQ ID NO: 93), VL CDR1 (SEQ ID NO: 94), VL CDR2 (SEQ ID NO: 95), and VL CDR3 (SEQ ID NO: 96). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 91), VL CDR1 (SEQ ID NO: 94), VL CDR2 (SEQ ID NO: 95), and VL CDR3 (SEQ ID NO: 96). In one embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 92), VL CDR1 (SEQ ID NO: 94), VL CDR2 (SEQ ID NO: 95), and VL CDR3 (SEQ ID NO: 96). In other embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 93), a VL CDR1 (SEQ ID NO: 94), a VL CDR2 (SEQ ID NO: 95), and a VL CDR3 (SEQ ID NO: 96). In another embodiment, the antibody comprises any combination of the VH and VL CDRs set forth in Tables 3 and 4.

[0229] In some embodiments, the antibody comprises a VH CDR1, a VH CDR1, a VH CDR3, a VL CDR1, a VL CDR2, a VL CDR3 according to the IMGT numbering system. Thus, in some embodiments, the antibody comprises a VH CDR1 having the amino acid sequence of SEQ ID NO: 97. In some embodiments, the antibody comprises a VH CDR2 having the amino acid sequence of SEQ ID NO: 98. In some embodiments, the antibody comprises a VH CDR3 having the amino acid sequence of SEQ ID NO: 99. In some embodiments, the antibody comprises a VH CDR1 and / or a VH CDR2 and / or a VH CDR3 independently selected from any one of the VH CDR1, VH CDR2, VH CDR3 amino acid sequences shown in Table 4. In some embodiments, the antibody comprises a VL CDR1 having the amino acid sequence of any one of SEQ ID NO: 100. In another embodiment, the antibody comprises a VL CDR2 having the amino acid sequence of SEQ ID NO: 101. In some embodiments, the antibody comprises a VL CDR3 having the amino acid sequence of SEQ ID NO: 102. In some embodiments, the antibody comprises a VL CDR1 and / or a VL CDR2 and / or a VL CDR3 independently selected from any one of the VL CDR1, VL CDR2, VL CDR3 amino acid sequences shown in Table 3.

[0230] In one embodiment, the antibody provided herein comprises a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 97; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 98; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 99; and a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 100; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 101; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 102.

[0231] In some embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 97; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 98; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 99.

[0232] In other embodiments, the antibodies provided herein comprise a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 100; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 101; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 102.

[0233] Also provided herein are antibodies that comprise one or more (e.g., one, two, or three) VH CDRs and one or more (e.g., one, two, or three) VL CDRs as set forth in Tables 3 and 4. In particular, provided herein are antibodies that comprise a VH CDR1 (SEQ ID NO: 97) and a VL CDR1 (SEQ ID NO: 100). In one embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 97) and a VL CDR2 (SEQ ID NO: 101). In other embodiments, the antibody comprises a VH CDR1 (SEQ ID NO: 97) and a VL CDR3 (SEQ ID NO: 102). In another embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 98 and a VL CDR1 (SEQ ID NO: 100). In some embodiments, the antibody comprises a VH CDR2 (SEQ ID NO: 98 and a VL CDR2 (SEQ ID NO: 101). In one embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 98 and a VL CDR3 (SEQ ID NO: 102). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 99) and a VL CDR1 (SEQ ID NO: 100). In other embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 99) and a VL CDR2 (SEQ ID NO: 101). In some embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 99) and a VL CDR3 (SEQ ID NO: 102). In another embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 97), a VH CDR2 (SEQ ID NO: 98, and a VL CDR1 (SEQ ID NO: 100). In one embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 97), a VH In another embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 98, a VH CDR3 (SEQ ID NO: 102). In another embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 98, a VH CDR3 (SEQ ID NO: 99), and a VL CDR1 (SEQ ID NO: 100). In some embodiments, the antibody comprises a VH CDR2 (SEQ ID NO: 98, a VH CDR3 (SEQ ID NO: 99), and a VL CDR2 (SEQ ID NO: 101). In one embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 98, a VH CDR3 (SEQ ID NO: 99), and a VL CDR3 (SEQ ID NO: 102).In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 97), VH CDR3 (SEQ ID NO: 99), and VL CDR1 (SEQ ID NO: 100). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 97), VH CDR3 (SEQ ID NO: 99), and VL CDR2 (SEQ ID NO: 101). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 97), VH CDR3 (SEQ ID NO: 99), and VL CDR3 (SEQ ID NO: 102). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 97), VL CDR1 (SEQ ID NO: 100), and VL CDR2 (SEQ ID NO: 101). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 97), VL CDR1 (SEQ ID NO: 100), and VL CDR3 (SEQ ID NO: 102). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 97), VL CDR2 (SEQ ID NO: 101), and VL CDR3 (SEQ ID NO: 102). In another embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 98, a VL CDR1 (SEQ ID NO: 100), and a VL CDR2 (SEQ ID NO: 101). In some embodiments, the antibody comprises a VH CDR2 (SEQ ID NO: 98, a VL CDR1 (SEQ ID NO: 100), and a VL CDR3 (SEQ ID NO: 102). In one embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 98, a VL CDR2 (SEQ ID NO: 101), and a VL CDR3 (SEQ ID NO: 102). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 99), a VL CDR1 (SEQ ID NO: 100), and a VL CDR2 (SEQ ID NO: 101). In other embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 99), a VL CDR1 (SEQ ID NO: 100), and a VL CDR3 (SEQ ID NO: 102). In some embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 99), a VL CDR2 (SEQ ID NO: 101), and a VL CDR3 (SEQ ID NO: 102). In another embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 97), a VH CDR2 (SEQ ID NO: 98, a VH CDR3 (SEQ ID NO: 99), and a VL CDR1 (SEQ ID NO: 100).In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 97), VH CDR2 (SEQ ID NO: 98, VH CDR3 (SEQ ID NO: 99), and VL CDR2 (SEQ ID NO: 101). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 97), VH CDR2 (SEQ ID NO: 98, VH CDR3 (SEQ ID NO: 99), and VL CDR3 (SEQ ID NO: 102). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 97), VH CDR2 (SEQ ID NO: 98, VL CDR1 (SEQ ID NO: 100), and VL CDR2 (SEQ ID NO: 101). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 97), VH CDR2 (SEQ ID NO: 98, VL CDR1 (SEQ ID NO: 100), and VL CDR3 (SEQ ID NO: 102). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 97), VH CDR2 (SEQ ID NO: 98, VL CDR1 (SEQ ID NO: 100), and VL CDR3 (SEQ ID NO: 102). In another embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 97), a VH CDR3 (SEQ ID NO: 99), a VL CDR1 (SEQ ID NO: 100), and a VL CDR2 (SEQ ID NO: 101). In other embodiments, the antibody comprises a VH CDR1 (SEQ ID NO: 97), a VH CDR3 (SEQ ID NO: 99), a VL CDR1 (SEQ ID NO: 100), and a VL CDR3 (SEQ ID NO: 102). In some embodiments, the antibody comprises a VH CDR1 (SEQ ID NO: 97), a VH CDR3 (SEQ ID NO: 99), a VL CDR2 (SEQ ID NO: 101), and a VL CDR3 (SEQ ID NO: 102). In another embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 98, a VH CDR3 (SEQ ID NO: 99), a VL CDR1 (SEQ ID NO: 100), and a VL CDR2 (SEQ ID NO: 101). In one embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 98, a VH CDR3 (SEQ ID NO: 99), a VL CDR1 (SEQ ID NO: 100), and a VL CDR3 (SEQ ID NO: 102). In another embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 98, a VH CDR3 (SEQ ID NO: 99), a VL CDR2 (SEQ ID NO: 101), and a VL CDR3 (SEQ ID NO: 102).In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 97), VH CDR2 (SEQ ID NO: 98, VH CDR3 (SEQ ID NO: 99), VL CDR1 (SEQ ID NO: 100), and VL CDR2 (SEQ ID NO: 101). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 97), VH CDR2 (SEQ ID NO: 98, VH CDR3 (SEQ ID NO: 99), VL CDR1 (SEQ ID NO: 100), and VL CDR3 (SEQ ID NO: 102). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 97), VH CDR2 (SEQ ID NO: 98, VH CDR3 (SEQ ID NO: 99), VL CDR2 (SEQ ID NO: 101), and VL CDR3 (SEQ ID NO: 102). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 97), VH CDR2 (SEQ ID NO: 98, VL CDR1 (SEQ ID NO: 100), VL CDR2 (SEQ ID NO: 101), and VL CDR3 (SEQ ID NO: 102). In another embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 97), a VH CDR3 (SEQ ID NO: 99), a VL CDR1 (SEQ ID NO: 100), a VL CDR2 (SEQ ID NO: 101), and a VL CDR3 (SEQ ID NO: 102). In some embodiments, the antibody comprises a VH CDR2 (SEQ ID NO: 98, a VH CDR3 (SEQ ID NO: 99), a VL CDR1 (SEQ ID NO: 100), a VL CDR2 (SEQ ID NO: 101), and a VL CDR3 (SEQ ID NO: 102). In another embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 97), a VL CDR1 (SEQ ID NO: 100), a VL CDR2 (SEQ ID NO: 101), and a VL CDR3 (SEQ ID NO: 102). In one embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 98, a VL CDR1 (SEQ ID NO: 100), a VL CDR2 (SEQ ID NO: 101), and a VL CDR3 (SEQ ID NO: 102). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 99), a VL CDR1 (SEQ ID NO: 100), a VL CDR2 (SEQ ID NO: 101), and a VL CDR3 (SEQ ID NO: 102). In another embodiment, the antibody comprises any combination of the VH and VL CDRs set forth in Tables 3 and 4.

[0234] In some embodiments, the antibody comprises a VH CDR1, a VH CDR1, a VH CDR3, a VL CDR1, a VL CDR2, a VL CDR3 according to the contact numbering system. Thus, in some embodiments, the antibody comprises a VH CDR1 having the amino acid sequence of SEQ ID NO: 103. In some embodiments, the antibody comprises a VH CDR2 having the amino acid sequence of SEQ ID NO: 104. In some embodiments, the antibody comprises a VH CDR3 having the amino acid sequence of SEQ ID NO: 105. In some embodiments, the antibody comprises a VH CDR1 and / or a VH CDR2 and / or a VH CDR3 independently selected from any one of the VH CDR1, VH CDR2, VH CDR3 amino acid sequences shown in Table 4. In some embodiments, the antibody comprises a VL CDR1 having the amino acid sequence of any one of SEQ ID NO: 106. In another embodiment, the antibody comprises a VL CDR2 having the amino acid sequence of SEQ ID NO: 107. In some embodiments, the antibody comprises a VL CDR3 having the amino acid sequence of SEQ ID NO: 108. In some embodiments, the antibody comprises a VL CDR1 and / or a VL CDR2 and / or a VL CDR3 independently selected from any one of the VL CDR1, VL CDR2, VL CDR3 amino acid sequences shown in Table 3.

[0235] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 103; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 104; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 105; and a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 106; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 107; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 108. In some embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 103; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 104; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 105.

[0236] In other embodiments, the antibodies provided herein comprise a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 106; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 107; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 108.

[0237] Also provided herein are antibodies comprising one or more (e.g., one, two, or three) VH CDRs and one or more (e.g., one, two, or three) VL CDRs as set forth in Tables 3 and 4. In particular, provided herein are antibodies comprising a VH CDR1 (SEQ ID NO: 103) and a VL CDR1 (SEQ ID NO: 106). In one embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 103) and a VL CDR2 (SEQ ID NO: 107). In other embodiments, the antibody comprises a VH CDR1 (SEQ ID NO: 103) and a VL CDR3 (SEQ ID NO: 108). In another embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 104) and a VL CDR1 (SEQ ID NO: 106). In some embodiments, the antibody comprises a VH CDR2 (SEQ ID NO: 104) and a VL CDR2 (SEQ ID NO: 107). In one embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 104) and a VL CDR3 (SEQ ID NO: 108). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 105) and a VL CDR1 (SEQ ID NO: 106). In other embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 105) and a VL CDR2 (SEQ ID NO: 107). In some embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 105) and a VL CDR3 (SEQ ID NO: 108). In another embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 103), a VH CDR2 (SEQ ID NO: 104), and a VL CDR1 (SEQ ID NO: 106). In one embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 103), a VH CDR2 (SEQ ID NO: 104), and a VL CDR2 (SEQ ID NO: 107). In other embodiments, the antibody comprises a VH CDR1 (SEQ ID NO: 103), a VH CDR2 (SEQ ID NO: 104), and a VL CDR3 (SEQ ID NO: 108). In another embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 104), VH CDR3 (SEQ ID NO: 105), and VL CDR1 (SEQ ID NO: 106). In some embodiments, the antibody comprises VH CDR2 (SEQ ID NO: 104), VH CDR3 (SEQ ID NO: 105), and VL CDR2 (SEQ ID NO: 107).In one embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 104), VH CDR3 (SEQ ID NO: 105), and VL CDR3 (SEQ ID NO: 108). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 103), VH CDR3 (SEQ ID NO: 105), and VL CDR1 (SEQ ID NO: 106). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 103), VH CDR3 (SEQ ID NO: 105), and VL CDR2 (SEQ ID NO: 107). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 103), VH CDR3 (SEQ ID NO: 105), and VL CDR3 (SEQ ID NO: 108). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 103), VL CDR1 (SEQ ID NO: 106), and VL CDR2 (SEQ ID NO: 107). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 103), VL CDR1 (SEQ ID NO: 106), and VL CDR3 (SEQ ID NO: 108). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 103), VL CDR2 (SEQ ID NO: 107), and VL CDR3 (SEQ ID NO: 108). In another embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 104), VL CDR1 (SEQ ID NO: 106), and VL CDR2 (SEQ ID NO: 107). In some embodiments, the antibody comprises VH CDR2 (SEQ ID NO: 104), VL CDR1 (SEQ ID NO: 106), and VL CDR3 (SEQ ID NO: 108). In one embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 104), VL CDR2 (SEQ ID NO: 107), and VL CDR3 (SEQ ID NO: 108). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 105), a VL CDR1 (SEQ ID NO: 106), and a VL CDR2 (SEQ ID NO: 107). In other embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 105), a VL CDR1 (SEQ ID NO: 106), and a VL CDR3 (SEQ ID NO: 108). In some embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 105), a VL CDR2 (SEQ ID NO: 107), and a VL CDR3 (SEQ ID NO: 108).In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 103), VH CDR2 (SEQ ID NO: 104), VH CDR3 (SEQ ID NO: 105), and VL CDR1 (SEQ ID NO: 106). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 103), VH CDR2 (SEQ ID NO: 104), VH CDR3 (SEQ ID NO: 105), and VL CDR2 (SEQ ID NO: 107). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 103), VH CDR2 (SEQ ID NO: 104), VH CDR3 (SEQ ID NO: 105), and VL CDR3 (SEQ ID NO: 108). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 103), VH CDR2 (SEQ ID NO: 104), VL CDR1 (SEQ ID NO: 106), and VL CDR2 (SEQ ID NO: 107). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 103), VH CDR2 (SEQ ID NO: 104), VL CDR1 (SEQ ID NO: 106), and VL CDR3 (SEQ ID NO: 108). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 103), VH CDR2 (SEQ ID NO: 104), VL CDR2 (SEQ ID NO: 107), and VL CDR3 (SEQ ID NO: 108). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 103), VH CDR3 (SEQ ID NO: 105), VL CDR1 (SEQ ID NO: 106), and VL CDR2 (SEQ ID NO: 107). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 103), VH CDR3 (SEQ ID NO: 105), VL CDR1 (SEQ ID NO: 106), and VL CDR3 (SEQ ID NO: 108). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 103), VH CDR3 (SEQ ID NO: 105), VL CDR2 (SEQ ID NO: 107), and VL CDR3 (SEQ ID NO: 108). In another embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 104), VH CDR3 (SEQ ID NO: 105), VL CDR1 (SEQ ID NO: 106), and VL CDR2 (SEQ ID NO: 107). In one embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 104), VH CDR3 (SEQ ID NO: 105), VL CDR1 (SEQ ID NO: 106), and VL CDR3 (SEQ ID NO: 108).In other embodiments, the antibody comprises VH CDR2 (SEQ ID NO: 104), VH CDR3 (SEQ ID NO: 105), VL CDR2 (SEQ ID NO: 107), and VL CDR3 (SEQ ID NO: 108). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 103), VH CDR2 (SEQ ID NO: 104), VH CDR3 (SEQ ID NO: 105), VL CDR1 (SEQ ID NO: 106), and VL CDR2 (SEQ ID NO: 107). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 103), VH CDR2 (SEQ ID NO: 104), VH CDR3 (SEQ ID NO: 105), VL CDR1 (SEQ ID NO: 106), and VL CDR3 (SEQ ID NO: 108). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 103), VH CDR2 (SEQ ID NO: 104), VH CDR3 (SEQ ID NO: 105), VL CDR2 (SEQ ID NO: 107), and VL CDR3 (SEQ ID NO: 108). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 103), VH CDR2 (SEQ ID NO: 104), VL CDR1 (SEQ ID NO: 106), VL CDR2 (SEQ ID NO: 107), and VL CDR3 (SEQ ID NO: 108). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 103), VH CDR3 (SEQ ID NO: 105), VL CDR1 (SEQ ID NO: 106), VL CDR2 (SEQ ID NO: 107), and VL CDR3 (SEQ ID NO: 108). In some embodiments, the antibody comprises VH CDR2 (SEQ ID NO: 104), VH CDR3 (SEQ ID NO: 105), VL CDR1 (SEQ ID NO: 106), VL CDR2 (SEQ ID NO: 107), and VL CDR3 (SEQ ID NO: 108). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 103), VL CDR1 (SEQ ID NO: 106), VL CDR2 (SEQ ID NO: 107), and VL CDR3 (SEQ ID NO: 108). In one embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 104), VL CDR1 (SEQ ID NO: 106), VL CDR2 (SEQ ID NO: 107), and VL CDR3 (SEQ ID NO: 108). In other embodiments, the antibody comprises VH CDR3 (SEQ ID NO: 105), VL CDR1 (SEQ ID NO: 106), VL CDR2 (SEQ ID NO: 107), and VL CDR3 (SEQ ID NO: 108).In another embodiment, the antibody comprises any combination of the VH and VL CDRs set forth in Tables 3 and 4. Table 5. VL CDR sequences of anti-BTN1A1 antibody STC85F1-1 [Table 6] Table 6. VH CDR sequences of anti-BTN1A1 antibody STC85F1-1 [Table 7]

[0238] In some embodiments, the antibodies provided herein comprise or consist of six CDRs, e.g., VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3, identified in Tables 5 and 6. In some embodiments, the antibodies provided herein can comprise fewer than six CDRs. In some embodiments, the antibodies comprise or consist of one, two, three, four, or five CDRs selected from the group consisting of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3, identified in Tables 5 and 6. In some embodiments, the antibodies comprise or consist of one, two, three, four, or five CDRs selected from the group consisting of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 of the monoclonals described herein. Thus, in some embodiments, the antibody comprises or consists of one, two, three, four, or five CDRs of any one of the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 identified in Tables 5 and 6.

[0239] In some embodiments, the antibodies provided herein comprise one or more (e.g., one, two, or three) VH CDRs set forth in Table 6. In other embodiments, the antibodies provided herein comprise one or more (e.g., one, two, or three) VL CDRs set forth in Table 5. In yet other embodiments, the antibodies provided herein comprise one or more (e.g., one, two, or three) VH CDRs set forth in Table 6 and one or more VL CDRs set forth in Table 5.

[0240] In some embodiments, the antibody comprises a VH CDR1, a VH CDR1, a VH CDR3, a VL CDR1, a VL CDR2, a VL CDR3 according to the Kabat numbering system. Thus, in some embodiments, the antibody comprises a VH CDR1 having the amino acid sequence of SEQ ID NO: 47. In some embodiments, the antibody comprises a VH CDR2 having the amino acid sequence of SEQ ID NO: 48. In some embodiments, the antibody comprises a VH CDR3 having the amino acid sequence of SEQ ID NO: 49. In some embodiments, the antibody comprises a VH CDR1 and / or a VH CDR2 and / or a VH CDR3 independently selected from any one of the VH CDR1, VH CDR2, VH CDR3 amino acid sequences shown in Table 6. In some embodiments, the antibody comprises a VL CDR1 having the amino acid sequence of any one of SEQ ID NO: 41. In another embodiment, the antibody comprises a VL CDR2 having the amino acid sequence of SEQ ID NO: 42. In some embodiments, the antibody comprises a VL CDR3 having the amino acid sequence of SEQ ID NO: 43. In some embodiments, the antibody comprises a VL CDR1 and / or a VL CDR2 and / or a VL CDR3 independently selected from any one of the VL CDR1, VL CDR2, VL CDR3 amino acid sequences shown in Table 5.

[0241] In one embodiment, the antibody provided herein comprises a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 47; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 48; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 49; and a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 41; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 42; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 43.

[0242] In some embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 47; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 48; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 49.

[0243] In other embodiments, the antibodies provided herein comprise a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 41; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 42; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 43.

[0244] Also provided herein are antibodies comprising one or more (e.g., one, two, or three) VH CDRs and one or more (e.g., one, two, or three) VL CDRs as set forth in Tables 5 and 6. In particular, provided herein are antibodies comprising a VH CDR1 (SEQ ID NO: 47) and a VL CDR1 (SEQ ID NO: 41). In one embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 47) and a VL CDR2 (SEQ ID NO: 42). In other embodiments, the antibody comprises a VH CDR1 (SEQ ID NO: 47) and a VL CDR3 (SEQ ID NO: 43). In another embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 48) and a VL CDR1 (SEQ ID NO: 41). In some embodiments, the antibody comprises a VH CDR2 (SEQ ID NO: 48) and a VL CDR2 (SEQ ID NO: 42). In one embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 48) and a VL CDR3 (SEQ ID NO: 43). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 49) and a VL CDR1 (SEQ ID NO: 41). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 49) and a VL CDR2 (SEQ ID NO: 42). In some embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 49) and a VL CDR3 (SEQ ID NO: 43). In another embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 47), a VH CDR2 (SEQ ID NO: 48), and a VL CDR1 (SEQ ID NO: 41). In one embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 47), a VH CDR2 (SEQ ID NO: 48), and a VL CDR2 (SEQ ID NO: 42). In other embodiments, the antibody comprises a VH CDR1 (SEQ ID NO: 47), a VH CDR2 (SEQ ID NO: 48), and a VL CDR3 (SEQ ID NO: 43). In another embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 48), a VH CDR3 (SEQ ID NO: 49), and a VL CDR1 (SEQ ID NO: 41). In some embodiments, the antibody comprises a VH CDR2 (SEQ ID NO: 48), a VH CDR3 (SEQ ID NO: 49), and a VL CDR2 (SEQ ID NO: 42). In one embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 48), a VH CDR3 (SEQ ID NO: 49), and a VL CDR3 (SEQ ID NO: 43).In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 47), VH CDR3 (SEQ ID NO: 49), and VL CDR1 (SEQ ID NO: 41). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 47), VH CDR3 (SEQ ID NO: 49), and VL CDR2 (SEQ ID NO: 42). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 47), VH CDR3 (SEQ ID NO: 49), and VL CDR3 (SEQ ID NO: 43). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 47), VL CDR1 (SEQ ID NO: 41), and VL CDR2 (SEQ ID NO: 42). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 47), VL CDR1 (SEQ ID NO: 41), and VL CDR3 (SEQ ID NO: 43). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 47), VL CDR2 (SEQ ID NO: 42), and VL CDR3 (SEQ ID NO: 43). In another embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 48), a VL CDR1 (SEQ ID NO: 41), and a VL CDR2 (SEQ ID NO: 42). In some embodiments, the antibody comprises a VH CDR2 (SEQ ID NO: 48), a VL CDR1 (SEQ ID NO: 41), and a VL CDR3 (SEQ ID NO: 43). In one embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 48), a VL CDR2 (SEQ ID NO: 42), and a VL CDR3 (SEQ ID NO: 43). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 49), a VL CDR1 (SEQ ID NO: 41), and a VL CDR2 (SEQ ID NO: 42). In other embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 49), a VL CDR1 (SEQ ID NO: 41), and a VL CDR3 (SEQ ID NO: 43). In some embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 49), a VL CDR2 (SEQ ID NO: 42), and a VL CDR3 (SEQ ID NO: 43). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 47), VH CDR2 (SEQ ID NO: 48), VH CDR3 (SEQ ID NO: 49), and VL CDR1 (SEQ ID NO: 41). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 47), VH CDR2 (SEQ ID NO: 48), VH CDR3 (SEQ ID NO: 49), and VL CDR2 (SEQ ID NO: 42).In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 47), VH CDR2 (SEQ ID NO: 48), VH CDR3 (SEQ ID NO: 49), and VL CDR3 (SEQ ID NO: 43). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 47), VH CDR2 (SEQ ID NO: 48), VL CDR1 (SEQ ID NO: 41), and VL CDR2 (SEQ ID NO: 42). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 47), VH CDR2 (SEQ ID NO: 48), VL CDR1 (SEQ ID NO: 41), and VL CDR3 (SEQ ID NO: 43). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 47), VH CDR2 (SEQ ID NO: 48), VL CDR2 (SEQ ID NO: 42), and VL CDR3 (SEQ ID NO: 43). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO:47), VH CDR3 (SEQ ID NO:49), VL CDR1 (SEQ ID NO:41), and VL CDR2 (SEQ ID NO:42). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO:47), VH CDR3 (SEQ ID NO:49), VL CDR1 (SEQ ID NO:41), and VL CDR3 (SEQ ID NO:43). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO:47), VH CDR3 (SEQ ID NO:49), VL CDR2 (SEQ ID NO:42), and VL CDR3 (SEQ ID NO:43). In another embodiment, the antibody comprises VH CDR2 (SEQ ID NO:48), VH CDR3 (SEQ ID NO:49), VL CDR1 (SEQ ID NO:41), and VL CDR2 (SEQ ID NO:42). In one embodiment, the antibody comprises VH CDR2 (SEQ ID NO:48), VH CDR3 (SEQ ID NO:49), VL CDR1 (SEQ ID NO:41), and VL CDR3 (SEQ ID NO:43). In other embodiments, the antibody comprises VH CDR2 (SEQ ID NO:48), VH CDR3 (SEQ ID NO:49), VL CDR2 (SEQ ID NO:42), and VL CDR3 (SEQ ID NO:43). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO:47), VH CDR2 (SEQ ID NO:48), VH CDR3 (SEQ ID NO:49), VL CDR1 (SEQ ID NO:41), and VL CDR2 (SEQ ID NO:42).In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO:47), VH CDR2 (SEQ ID NO:48), VH CDR3 (SEQ ID NO:49), VL CDR1 (SEQ ID NO:41), and VL CDR3 (SEQ ID NO:43). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO:47), VH CDR2 (SEQ ID NO:48), VH CDR3 (SEQ ID NO:49), VL CDR2 (SEQ ID NO:42), and VL CDR3 (SEQ ID NO:43). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO:47), VH CDR2 (SEQ ID NO:48), VL CDR1 (SEQ ID NO:41), VL CDR2 (SEQ ID NO:42), and VL CDR3 (SEQ ID NO:43). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO:47), VH CDR3 (SEQ ID NO:49), VL CDR1 (SEQ ID NO:41), VL CDR2 (SEQ ID NO:42), and VL CDR3 (SEQ ID NO:43). In some embodiments, the antibody comprises VH CDR2 (SEQ ID NO:48), VH CDR3 (SEQ ID NO:49), VL CDR1 (SEQ ID NO:41), VL CDR2 (SEQ ID NO:42), and VL CDR3 (SEQ ID NO:43). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO:47), VL CDR1 (SEQ ID NO:41), VL CDR2 (SEQ ID NO:42), and VL CDR3 (SEQ ID NO:43). In one embodiment, the antibody comprises VH CDR2 (SEQ ID NO:48), VL CDR1 (SEQ ID NO:41), VL CDR2 (SEQ ID NO:42), and VL CDR3 (SEQ ID NO:43). In other embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 49), a VL CDR1 (SEQ ID NO: 41), a VL CDR2 (SEQ ID NO: 42), and a VL CDR3 (SEQ ID NO: 43). In another embodiment, the antibody comprises any combination of the VH and VL CDRs set forth in Tables 5 and 6.

[0245] In some embodiments, the antibody comprises a VH CDR1, a VH CDR1, a VH CDR3, a VL CDR1, a VL CDR2, a VL CDR3 according to the Chothia numbering system. Thus, in some embodiments, the antibody comprises a VH CDR1 having the amino acid sequence of SEQ ID NO: 111. In some embodiments, the antibody comprises a VH CDR2 having the amino acid sequence of SEQ ID NO: 112. In some embodiments, the antibody comprises a VH CDR3 having the amino acid sequence of SEQ ID NO: 113. In some embodiments, the antibody comprises a VH CDR1 and / or a VH CDR2 and / or a VH CDR3 independently selected from any one of the VH CDR1, VH CDR2, VH CDR3 amino acid sequences shown in Table 6. In some embodiments, the antibody comprises a VL CDR1 having the amino acid sequence of any one of SEQ ID NO: 114. In another embodiment, the antibody comprises a VL CDR2 having the amino acid sequence of SEQ ID NO: 115. In some embodiments, the antibody comprises a VL CDR3 having the amino acid sequence of SEQ ID NO: 116. In some embodiments, the antibody comprises a VL CDR1 and / or a VL CDR2 and / or a VL CDR3 independently selected from any one of the VL CDR1, VL CDR2, VL CDR3 amino acid sequences shown in Table 5.

[0246] In one embodiment, the antibody provided herein comprises a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 111; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 112; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 113; and a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 114; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 115; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 116.

[0247] In some embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 111; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 112; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 113.

[0248] In other embodiments, the antibodies provided herein comprise a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 114; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 115; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 116.

[0249] Also provided herein are antibodies comprising one or more (e.g., one, two, or three) VH CDRs and one or more (e.g., one, two, or three) VL CDRs as set forth in Tables 5 and 6. In particular, provided herein are antibodies comprising VH CDR1 (SEQ ID NO:111) and VL CDR1 (SEQ ID NO:114). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO:111) and VL CDR2 (SEQ ID NO:115). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO:111) and VL CDR3 (SEQ ID NO:116). In another embodiment, the antibody comprises VH CDR2 (SEQ ID NO:112) and VL CDR1 (SEQ ID NO:114). In some embodiments, the antibody comprises VH CDR2 (SEQ ID NO:112) and VL CDR2 (SEQ ID NO:115). In one embodiment, the antibody comprises VH CDR2 (SEQ ID NO:112) and VL CDR3 (SEQ ID NO:116). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO:113) and a VL CDR1 (SEQ ID NO:114). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO:113) and a VL CDR2 (SEQ ID NO:115). In some embodiments, the antibody comprises a VH CDR3 (SEQ ID NO:113) and a VL CDR3 (SEQ ID NO:116). In another embodiment, the antibody comprises a VH CDR1 (SEQ ID NO:111), a VH CDR2 (SEQ ID NO:112), and a VL CDR1 (SEQ ID NO:114). In one embodiment, the antibody comprises a VH CDR1 (SEQ ID NO:111), a VH CDR2 (SEQ ID NO:112), and a VL CDR2 (SEQ ID NO:115). In other embodiments, the antibody comprises a VH CDR1 (SEQ ID NO:111), a VH CDR2 (SEQ ID NO:112), and a VL CDR3 (SEQ ID NO:116). In another embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 112), VH CDR3 (SEQ ID NO: 113), and VL CDR1 (SEQ ID NO: 114). In some embodiments, the antibody comprises VH CDR2 (SEQ ID NO: 112), VH CDR3 (SEQ ID NO: 113), and VL CDR2 (SEQ ID NO: 115).In one embodiment, the antibody comprises VH CDR2 (SEQ ID NO:112), VH CDR3 (SEQ ID NO:113), and VL CDR3 (SEQ ID NO:116). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO:111), VH CDR3 (SEQ ID NO:113), and VL CDR1 (SEQ ID NO:114). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO:111), VH CDR3 (SEQ ID NO:113), and VL CDR2 (SEQ ID NO:115). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO:111), VH CDR3 (SEQ ID NO:113), and VL CDR3 (SEQ ID NO:116). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO:111), VL CDR1 (SEQ ID NO:114), and VL CDR2 (SEQ ID NO:115). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO:111), VL CDR1 (SEQ ID NO:114), and VL CDR3 (SEQ ID NO:116). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO:111), VL CDR2 (SEQ ID NO:115), and VL CDR3 (SEQ ID NO:116). In another embodiment, the antibody comprises VH CDR2 (SEQ ID NO:112), VL CDR1 (SEQ ID NO:114), and VL CDR2 (SEQ ID NO:115). In some embodiments, the antibody comprises VH CDR2 (SEQ ID NO:112), VL CDR1 (SEQ ID NO:114), and VL CDR3 (SEQ ID NO:116). In one embodiment, the antibody comprises VH CDR2 (SEQ ID NO:112), VL CDR2 (SEQ ID NO:115), and VL CDR3 (SEQ ID NO:116). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 113), a VL CDR1 (SEQ ID NO: 114), and a VL CDR2 (SEQ ID NO: 115). In other embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 113), a VL CDR1 (SEQ ID NO: 114), and a VL CDR3 (SEQ ID NO: 116). In some embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 113), a VL CDR2 (SEQ ID NO: 115), and a VL CDR3 (SEQ ID NO: 116).In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO:111), VH CDR2 (SEQ ID NO:112), VH CDR3 (SEQ ID NO:113), and VL CDR1 (SEQ ID NO:114). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO:111), VH CDR2 (SEQ ID NO:112), VH CDR3 (SEQ ID NO:113), and VL CDR2 (SEQ ID NO:115). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO:111), VH CDR2 (SEQ ID NO:112), VH CDR3 (SEQ ID NO:113), and VL CDR3 (SEQ ID NO:116). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO:111), VH CDR2 (SEQ ID NO:112), VL CDR1 (SEQ ID NO:114), and VL CDR2 (SEQ ID NO:115). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO:111), VH CDR2 (SEQ ID NO:112), VL CDR1 (SEQ ID NO:114), and VL CDR3 (SEQ ID NO:116). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO:111), VH CDR2 (SEQ ID NO:112), VL CDR2 (SEQ ID NO:115), and VL CDR3 (SEQ ID NO:116). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO:111), VH CDR3 (SEQ ID NO:113), VL CDR1 (SEQ ID NO:114), and VL CDR2 (SEQ ID NO:115). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO:111), VH CDR3 (SEQ ID NO:113), VL CDR1 (SEQ ID NO:114), and VL CDR3 (SEQ ID NO:116). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO:111), VH CDR3 (SEQ ID NO:113), VL CDR2 (SEQ ID NO:115), and VL CDR3 (SEQ ID NO:116). In another embodiment, the antibody comprises VH CDR2 (SEQ ID NO:112), VH CDR3 (SEQ ID NO:113), VL CDR1 (SEQ ID NO:114), and VL CDR2 (SEQ ID NO:115). In one embodiment, the antibody comprises VH CDR2 (SEQ ID NO:112), VH CDR3 (SEQ ID NO:113), VL CDR1 (SEQ ID NO:114), and VL CDR3 (SEQ ID NO:116).In other embodiments, the antibody comprises VH CDR2 (SEQ ID NO:112), VH CDR3 (SEQ ID NO:113), VL CDR2 (SEQ ID NO:115), and VL CDR3 (SEQ ID NO:116). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO:111), VH CDR2 (SEQ ID NO:112), VH CDR3 (SEQ ID NO:113), VL CDR1 (SEQ ID NO:114), and VL CDR2 (SEQ ID NO:115). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO:111), VH CDR2 (SEQ ID NO:112), VH CDR3 (SEQ ID NO:113), VL CDR1 (SEQ ID NO:114), and VL CDR3 (SEQ ID NO:116). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO:111), VH CDR2 (SEQ ID NO:112), VH CDR3 (SEQ ID NO:113), VL CDR2 (SEQ ID NO:115), and VL CDR3 (SEQ ID NO:116). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO:111), VH CDR2 (SEQ ID NO:112), VL CDR1 (SEQ ID NO:114), VL CDR2 (SEQ ID NO:115), and VL CDR3 (SEQ ID NO:116). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO:111), VH CDR3 (SEQ ID NO:113), VL CDR1 (SEQ ID NO:114), VL CDR2 (SEQ ID NO:115), and VL CDR3 (SEQ ID NO:116). In some embodiments, the antibody comprises VH CDR2 (SEQ ID NO:112), VH CDR3 (SEQ ID NO:113), VL CDR1 (SEQ ID NO:114), VL CDR2 (SEQ ID NO:115), and VL CDR3 (SEQ ID NO:116). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO:111), VL CDR1 (SEQ ID NO:114), VL CDR2 (SEQ ID NO:115), and VL CDR3 (SEQ ID NO:116). In one embodiment, the antibody comprises VH CDR2 (SEQ ID NO:112), VL CDR1 (SEQ ID NO:114), VL CDR2 (SEQ ID NO:115), and VL CDR3 (SEQ ID NO:116). In other embodiments, the antibody comprises VH CDR3 (SEQ ID NO:113), VL CDR1 (SEQ ID NO:114), VL CDR2 (SEQ ID NO:115), and VL CDR3 (SEQ ID NO:116).In another embodiment, the antibody comprises any combination of the VH and VL CDRs set forth in Tables 5 and 6.

[0250] In some embodiments, the antibody comprises a VH CDR1, a VH CDR1, a VH CDR3, a VL CDR1, a VL CDR2, a VL CDR3 according to the IMGT numbering system. Thus, in some embodiments, the antibody comprises a VH CDR1 having the amino acid sequence of SEQ ID NO: 117. In some embodiments, the antibody comprises a VH CDR2 having the amino acid sequence of SEQ ID NO: 118. In some embodiments, the antibody comprises a VH CDR3 having the amino acid sequence of SEQ ID NO: 119. In some embodiments, the antibody comprises a VH CDR1 and / or a VH CDR2 and / or a VH CDR3 independently selected from any one of the VH CDR1, VH CDR2, VH CDR3 amino acid sequences shown in Table 6. In some embodiments, the antibody comprises a VL CDR1 having the amino acid sequence of any one of SEQ ID NO: 120. In another embodiment, the antibody comprises a VL CDR2 having the amino acid sequence of SEQ ID NO: 121. In some embodiments, the antibody comprises a VL CDR3 having the amino acid sequence of SEQ ID NO: 122. In some embodiments, the antibody comprises a VL CDR1 and / or a VL CDR2 and / or a VL CDR3 independently selected from any one of the VL CDR1, VL CDR2, VL CDR3 amino acid sequences shown in Table 5.

[0251] In one embodiment, the antibody provided herein comprises a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 117; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 118; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 119; and a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 120; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 121; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 122.

[0252] In some embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 117; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 118; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 119.

[0253] In other embodiments, the antibodies provided herein comprise a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 120; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 121; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 122.

[0254] Also provided herein are antibodies comprising one or more (e.g., one, two, or three) VH CDRs and one or more (e.g., one, two, or three) VL CDRs as set forth in Tables 5 and 6. In particular, provided herein are antibodies comprising a VH CDR1 (SEQ ID NO: 117) and a VL CDR1 (SEQ ID NO: 120). In one embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 117) and a VL CDR2 (SEQ ID NO: 121). In other embodiments, the antibody comprises a VH CDR1 (SEQ ID NO: 117) and a VL CDR3 (SEQ ID NO: 122). In another embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 118) and a VL CDR1 (SEQ ID NO: 120). In some embodiments, the antibody comprises a VH CDR2 (SEQ ID NO: 118) and a VL CDR2 (SEQ ID NO: 121). In one embodiment, the antibody comprises a VH CDR2 (SEQ ID NO: 118) and a VL CDR3 (SEQ ID NO: 122). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 119) and a VL CDR1 (SEQ ID NO: 120). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 119) and a VL CDR2 (SEQ ID NO: 121). In some embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 119) and a VL CDR3 (SEQ ID NO: 122). In another embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 117), a VH CDR2 (SEQ ID NO: 118), and a VL CDR1 (SEQ ID NO: 120). In one embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 117), a VH CDR2 (SEQ ID NO: 118), and a VL CDR2 (SEQ ID NO: 121). In other embodiments, the antibody comprises a VH CDR1 (SEQ ID NO: 117), a VH CDR2 (SEQ ID NO: 118), and a VL CDR3 (SEQ ID NO: 122). In another embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 118), VH CDR3 (SEQ ID NO: 119), and VL CDR1 (SEQ ID NO: 120). In some embodiments, the antibody comprises VH CDR2 (SEQ ID NO: 118), VH CDR3 (SEQ ID NO: 119), and VL CDR2 (SEQ ID NO: 121).In one embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 118), VH CDR3 (SEQ ID NO: 119), and VL CDR3 (SEQ ID NO: 122). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 117), VH CDR3 (SEQ ID NO: 119), and VL CDR1 (SEQ ID NO: 120). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 117), VH CDR3 (SEQ ID NO: 119), and VL CDR2 (SEQ ID NO: 121). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 117), VH CDR3 (SEQ ID NO: 119), and VL CDR3 (SEQ ID NO: 122). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 117), VL CDR1 (SEQ ID NO: 120), and VL CDR2 (SEQ ID NO: 121). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 117), VL CDR1 (SEQ ID NO: 120), and VL CDR3 (SEQ ID NO: 122). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 117), VL CDR2 (SEQ ID NO: 121), and VL CDR3 (SEQ ID NO: 122). In another embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 118), VL CDR1 (SEQ ID NO: 120), and VL CDR2 (SEQ ID NO: 121). In some embodiments, the antibody comprises VH CDR2 (SEQ ID NO: 118), VL CDR1 (SEQ ID NO: 120), and VL CDR3 (SEQ ID NO: 122). In one embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 118), VL CDR2 (SEQ ID NO: 121), and VL CDR3 (SEQ ID NO: 122). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 119), a VL CDR1 (SEQ ID NO: 120), and a VL CDR2 (SEQ ID NO: 121). In other embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 119), a VL CDR1 (SEQ ID NO: 120), and a VL CDR3 (SEQ ID NO: 122). In some embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 119), a VL CDR2 (SEQ ID NO: 121), and a VL CDR3 (SEQ ID NO: 122).In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 117), VH CDR2 (SEQ ID NO: 118), VH CDR3 (SEQ ID NO: 119), and VL CDR1 (SEQ ID NO: 120). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 117), VH CDR2 (SEQ ID NO: 118), VH CDR3 (SEQ ID NO: 119), and VL CDR2 (SEQ ID NO: 121). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 117), VH CDR2 (SEQ ID NO: 118), VH CDR3 (SEQ ID NO: 119), and VL CDR3 (SEQ ID NO: 122). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 117), VH CDR2 (SEQ ID NO: 118), VL CDR1 (SEQ ID NO: 120), and VL CDR2 (SEQ ID NO: 121). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO:117), VH CDR2 (SEQ ID NO:118), VL CDR1 (SEQ ID NO:120), and VL CDR3 (SEQ ID NO:122). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO:117), VH CDR2 (SEQ ID NO:118), VL CDR2 (SEQ ID NO:121), and VL CDR3 (SEQ ID NO:122). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO:117), VH CDR3 (SEQ ID NO:119), VL CDR1 (SEQ ID NO:120), and VL CDR2 (SEQ ID NO:121). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO:117), VH CDR3 (SEQ ID NO:119), VL CDR1 (SEQ ID NO:120), and VL CDR3 (SEQ ID NO:122). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 117), VH CDR3 (SEQ ID NO: 119), VL CDR2 (SEQ ID NO: 121), and VL CDR3 (SEQ ID NO: 122). In another embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 118), VH CDR3 (SEQ ID NO: 119), VL CDR1 (SEQ ID NO: 120), and VL CDR2 (SEQ ID NO: 121). In one embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 118), VH CDR3 (SEQ ID NO: 119), VL CDR1 (SEQ ID NO: 120), and VL CDR3 (SEQ ID NO: 122).In other embodiments, the antibody comprises VH CDR2 (SEQ ID NO:118), VH CDR3 (SEQ ID NO:119), VL CDR2 (SEQ ID NO:121), and VL CDR3 (SEQ ID NO:122). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO:117), VH CDR2 (SEQ ID NO:118), VH CDR3 (SEQ ID NO:119), VL CDR1 (SEQ ID NO:120), and VL CDR2 (SEQ ID NO:121). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO:117), VH CDR2 (SEQ ID NO:118), VH CDR3 (SEQ ID NO:119), VL CDR1 (SEQ ID NO:120), and VL CDR3 (SEQ ID NO:122). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO:117), VH CDR2 (SEQ ID NO:118), VH CDR3 (SEQ ID NO:119), VL CDR2 (SEQ ID NO:121), and VL CDR3 (SEQ ID NO:122). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO:117), VH CDR2 (SEQ ID NO:118), VL CDR1 (SEQ ID NO:120), VL CDR2 (SEQ ID NO:121), and VL CDR3 (SEQ ID NO:122). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO:117), VH CDR3 (SEQ ID NO:119), VL CDR1 (SEQ ID NO:120), VL CDR2 (SEQ ID NO:121), and VL CDR3 (SEQ ID NO:122). In some embodiments, the antibody comprises VH CDR2 (SEQ ID NO:118), VH CDR3 (SEQ ID NO:119), VL CDR1 (SEQ ID NO:120), VL CDR2 (SEQ ID NO:121), and VL CDR3 (SEQ ID NO:122). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO:117), VL CDR1 (SEQ ID NO:120), VL CDR2 (SEQ ID NO:121), and VL CDR3 (SEQ ID NO:122). In one embodiment, the antibody comprises VH CDR2 (SEQ ID NO:118), VL CDR1 (SEQ ID NO:120), VL CDR2 (SEQ ID NO:121), and VL CDR3 (SEQ ID NO:122). In other embodiments, the antibody comprises VH CDR3 (SEQ ID NO:119), VL CDR1 (SEQ ID NO:120), VL CDR2 (SEQ ID NO:121), and VL CDR3 (SEQ ID NO:122).In another embodiment, the antibody comprises any combination of the VH and VL CDRs set forth in Tables 5 and 6.

[0255] In some embodiments, the antibody comprises a VH CDR1, a VH CDR1, a VH CDR3, a VL CDR1, a VL CDR2, a VL CDR3 according to the contact numbering system. Thus, in some embodiments, the antibody comprises a VH CDR1 having the amino acid sequence of SEQ ID NO: 123. In some embodiments, the antibody comprises a VH CDR2 having the amino acid sequence of SEQ ID NO: 124. In some embodiments, the antibody comprises a VH CDR3 having the amino acid sequence of SEQ ID NO: 125. In some embodiments, the antibody comprises a VH CDR1 and / or a VH CDR2 and / or a VH CDR3 independently selected from any one of the VH CDR1, VH CDR2, VH CDR3 amino acid sequences shown in Table 6. In some embodiments, the antibody comprises a VL CDR1 having the amino acid sequence of any one of SEQ ID NO: 126. In another embodiment, the antibody comprises a VL CDR2 having the amino acid sequence of SEQ ID NO: 127. In some embodiments, the antibody comprises a VL CDR3 having the amino acid sequence of SEQ ID NO: 128. In some embodiments, the antibody comprises a VL CDR1 and / or a VL CDR2 and / or a VL CDR3 independently selected from any one of the VL CDR1, VL CDR2, VL CDR3 amino acid sequences shown in Table 5.

[0256] In one embodiment, the antibody provided herein comprises a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 123; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 124; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 125; and a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 126; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 127; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 128.

[0257] In some embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 123; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 124; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 125.

[0258] In other embodiments, the antibodies provided herein comprise a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 126; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 127; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 128.

[0259] Also provided herein are antibodies comprising one or more (e.g., one, two, or three) VH CDRs and one or more (e.g., one, two, or three) VL CDRs as set forth in Tables 5 and 6. In particular, provided herein are antibodies comprising VH CDR1 (SEQ ID NO: 123) and VL CDR1 (SEQ ID NO: 126). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 123) and VL CDR2 (SEQ ID NO: 127). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 123) and VL CDR3 (SEQ ID NO: 128). In another embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 124) and VL CDR1 (SEQ ID NO: 126). In some embodiments, the antibody comprises VH CDR2 (SEQ ID NO: 124) and VL CDR2 (SEQ ID NO: 127). In one embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 124) and VL CDR3 (SEQ ID NO: 128). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 125) and a VL CDR1 (SEQ ID NO: 126). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 125) and a VL CDR2 (SEQ ID NO: 127). In some embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 125) and a VL CDR3 (SEQ ID NO: 128). In another embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 123), a VH CDR2 (SEQ ID NO: 124), and a VL CDR1 (SEQ ID NO: 126). In one embodiment, the antibody comprises a VH CDR1 (SEQ ID NO: 123), a VH CDR2 (SEQ ID NO: 124), and a VL CDR2 (SEQ ID NO: 127). In other embodiments, the antibody comprises a VH CDR1 (SEQ ID NO: 123), a VH CDR2 (SEQ ID NO: 124), and a VL CDR3 (SEQ ID NO: 128). In another embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 124), VH CDR3 (SEQ ID NO: 125), and VL CDR1 (SEQ ID NO: 126). In some embodiments, the antibody comprises VH CDR2 (SEQ ID NO: 124), VH CDR3 (SEQ ID NO: 125), and VL CDR2 (SEQ ID NO: 127).In one embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 124), VH CDR3 (SEQ ID NO: 125), and VL CDR3 (SEQ ID NO: 128). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 123), VH CDR3 (SEQ ID NO: 125), and VL CDR1 (SEQ ID NO: 126). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 123), VH CDR3 (SEQ ID NO: 125), and VL CDR2 (SEQ ID NO: 127). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 123), VH CDR3 (SEQ ID NO: 125), and VL CDR3 (SEQ ID NO: 128). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 123), VL CDR1 (SEQ ID NO: 126), and VL CDR2 (SEQ ID NO: 127). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 123), VL CDR1 (SEQ ID NO: 126), and VL CDR3 (SEQ ID NO: 128). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 123), VL CDR2 (SEQ ID NO: 127), and VL CDR3 (SEQ ID NO: 128). In another embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 124), VL CDR1 (SEQ ID NO: 126), and VL CDR2 (SEQ ID NO: 127). In some embodiments, the antibody comprises VH CDR2 (SEQ ID NO: 124), VL CDR1 (SEQ ID NO: 126), and VL CDR3 (SEQ ID NO: 128). In one embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 124), VL CDR2 (SEQ ID NO: 127), and VL CDR3 (SEQ ID NO: 128). In another embodiment, the antibody comprises a VH CDR3 (SEQ ID NO: 125), a VL CDR1 (SEQ ID NO: 126), and a VL CDR2 (SEQ ID NO: 127). In other embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 125), a VL CDR1 (SEQ ID NO: 126), and a VL CDR3 (SEQ ID NO: 128). In some embodiments, the antibody comprises a VH CDR3 (SEQ ID NO: 125), a VL CDR2 (SEQ ID NO: 127), and a VL CDR3 (SEQ ID NO: 128).In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 123), VH CDR2 (SEQ ID NO: 124), VH CDR3 (SEQ ID NO: 125), and VL CDR1 (SEQ ID NO: 126). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 123), VH CDR2 (SEQ ID NO: 124), VH CDR3 (SEQ ID NO: 125), and VL CDR2 (SEQ ID NO: 127). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 123), VH CDR2 (SEQ ID NO: 124), VH CDR3 (SEQ ID NO: 125), and VL CDR3 (SEQ ID NO: 128). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 123), VH CDR2 (SEQ ID NO: 124), VL CDR1 (SEQ ID NO: 126), and VL CDR2 (SEQ ID NO: 127). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 123), VH CDR2 (SEQ ID NO: 124), VL CDR1 (SEQ ID NO: 126), and VL CDR3 (SEQ ID NO: 128). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 123), VH CDR2 (SEQ ID NO: 124), VL CDR2 (SEQ ID NO: 127), and VL CDR3 (SEQ ID NO: 128). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 123), VH CDR3 (SEQ ID NO: 125), VL CDR1 (SEQ ID NO: 126), and VL CDR2 (SEQ ID NO: 127). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 123), VH CDR3 (SEQ ID NO: 125), VL CDR1 (SEQ ID NO: 126), and VL CDR3 (SEQ ID NO: 128). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 123), VH CDR3 (SEQ ID NO: 125), VL CDR2 (SEQ ID NO: 127), and VL CDR3 (SEQ ID NO: 128). In another embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 124), VH CDR3 (SEQ ID NO: 125), VL CDR1 (SEQ ID NO: 126), and VL CDR2 (SEQ ID NO: 127). In one embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 124), VH CDR3 (SEQ ID NO: 125), VL CDR1 (SEQ ID NO: 126), and VL CDR3 (SEQ ID NO: 128).In other embodiments, the antibody comprises VH CDR2 (SEQ ID NO: 124), VH CDR3 (SEQ ID NO: 125), VL CDR2 (SEQ ID NO: 127), and VL CDR3 (SEQ ID NO: 128). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 123), VH CDR2 (SEQ ID NO: 124), VH CDR3 (SEQ ID NO: 125), VL CDR1 (SEQ ID NO: 126), and VL CDR2 (SEQ ID NO: 127). In some embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 123), VH CDR2 (SEQ ID NO: 124), VH CDR3 (SEQ ID NO: 125), VL CDR1 (SEQ ID NO: 126), and VL CDR3 (SEQ ID NO: 128). In one embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 123), VH CDR2 (SEQ ID NO: 124), VH CDR3 (SEQ ID NO: 125), VL CDR2 (SEQ ID NO: 127), and VL CDR3 (SEQ ID NO: 128). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 123), VH CDR2 (SEQ ID NO: 124), VL CDR1 (SEQ ID NO: 126), VL CDR2 (SEQ ID NO: 127), and VL CDR3 (SEQ ID NO: 128). In other embodiments, the antibody comprises VH CDR1 (SEQ ID NO: 123), VH CDR3 (SEQ ID NO: 125), VL CDR1 (SEQ ID NO: 126), VL CDR2 (SEQ ID NO: 127), and VL CDR3 (SEQ ID NO: 128). In some embodiments, the antibody comprises VH CDR2 (SEQ ID NO: 124), VH CDR3 (SEQ ID NO: 125), VL CDR1 (SEQ ID NO: 126), VL CDR2 (SEQ ID NO: 127), and VL CDR3 (SEQ ID NO: 128). In another embodiment, the antibody comprises VH CDR1 (SEQ ID NO: 123), VL CDR1 (SEQ ID NO: 126), VL CDR2 (SEQ ID NO: 127), and VL CDR3 (SEQ ID NO: 128). In one embodiment, the antibody comprises VH CDR2 (SEQ ID NO: 124), VL CDR1 (SEQ ID NO: 126), VL CDR2 (SEQ ID NO: 127), and VL CDR3 (SEQ ID NO: 128). In other embodiments, the antibody comprises VH CDR3 (SEQ ID NO: 125), VL CDR1 (SEQ ID NO: 126), VL CDR2 (SEQ ID NO: 127), and VL CDR3 (SEQ ID NO: 128).In another embodiment, the antibody comprises any combination of the VH and VL CDRs set forth in Tables 5 and 6.

[0260] In some embodiments, the antibody provided herein comprises or consists of six CDRs, e.g., VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3, as identified in Tables 1-6. In some embodiments, the antibody provided herein can comprise fewer than six CDRs. In some embodiments, the antibody comprises or consists of one, two, three, four, or five CDRs selected from the group consisting of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3, as identified in Tables 1-6. In some embodiments, the antibody comprises or consists of one, two, three, four, or five CDRs selected from the group consisting of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 of the monoclonals described herein. Thus, in some embodiments, the antibody comprises or consists of one, two, three, four, or five CDRs of any one of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 identified in Tables 1-6.

[0261] In some embodiments, the antibodies provided herein comprise one or more (e.g., one, two, or three) VH CDRs set forth in Tables 2, 4, and 6. In other embodiments, the antibodies provided herein comprise one or more (e.g., one, two, or three) VL CDRs set forth in Tables 1, 3, and 5. In yet other embodiments, the antibodies provided herein comprise one or more (e.g., one, two, or three) VH CDRs set forth in Table 2 and one or more VL CDRs set forth in Table 1. In yet other embodiments, the antibodies provided herein comprise one or more (e.g., one, two, or three) VH CDRs set forth in Table 4 and one or more VL CDRs set forth in Table 3. In yet other embodiments, the antibodies provided herein comprise one or more (e.g., one, two, or three) VH CDRs set forth in Table 6 and one or more VL CDRs set forth in Table 5.

[0262] In some embodiments, the isolated antibodies or functional fragments thereof provided herein further comprise one, two, three, and / or four heavy chain FRs and / or one, two, three, and / or four light chain FRs from antibodies STC43H11-1, STC43G3-1, or STC85F1-1 shown in Tables 7 and 8. Table 7. VL FR amino acid sequences [Table 8] Table 8. VH FR amino acid sequences [Table 9]

[0263] In certain embodiments, the isolated antibodies or functional fragments thereof provided herein further comprise one, two, three, and / or four heavy chain FRs from STC43H11-1, STC43G3-1, or STC85F1-1 as shown in Table 8. In some embodiments, the antibody heavy chain FRs are from antibody STC43H11-1, STC43G3-1, or STC85F1-1.

[0264] In some embodiments, the isolated antibodies or functional fragments thereof provided herein further comprise one, two, three, and / or four light chain FRs from STC43H11-1, STC43G3-1, or STC85F1-1 as shown in Table 7. In some embodiments, the antibody light chain FRs are from antibody STC43H11-1, STC43G3-1, or STC85F1-1.

[0265] In one embodiment, the antibody or fragment thereof described herein comprises a VH region comprising: (1) a VH FR1 having the amino acid sequence of SEQ ID NO: 15; (2) a VH FR2 having the amino acid sequence of SEQ ID NO: 16; (3) a VH FR3 having the amino acid sequence of SEQ ID NO: 17; and / or (4) a VH FR4 having the amino acid sequence of SEQ ID NO: 18.

[0266] Thus, in one embodiment, the humanized antibody comprises a VH region comprising a VH FR1 having the amino acid sequence of SEQ ID NO: 15. In some embodiments, the humanized antibody comprises a VH region comprising a VH FR2 having the amino acid sequence of SEQ ID NO: 16. In one embodiment, the humanized antibody comprises a VH region comprising a VH FR3 having the amino acid sequence of SEQ ID NO: 17. In one embodiment, the humanized antibody comprises a VH region comprising a VH FR3 having the amino acid sequence of SEQ ID NO: 18.

[0267] In certain embodiments, the antibody or fragment thereof described herein comprises a VL region comprising: (1) a VL FR1 having the amino acid sequence of SEQ ID NO: 11; (2) a VL FR2 having the amino acid sequence of SEQ ID NO: 12; (3) a VL FR3 having the amino acid sequence of SEQ ID NO: 13; and / or (4) a VL FR4 having the amino acid sequence of SEQ ID NO: 14.

[0268] Thus, in some embodiments, the humanized antibody comprises a VL region comprising a VL FR1 having the amino acid sequence of SEQ ID NO: 11. In certain embodiments, the humanized antibody comprises a VL region comprising a VL FR2 having the amino acid sequence of SEQ ID NO: 12. In one embodiment, the humanized antibody comprises a VL region comprising a VL FR3 having the amino acid sequence of SEQ ID NO: 13. In other embodiments, the humanized antibody comprises a VL region comprising a VL FR4 having the amino acid sequence of SEQ ID NO: 14.

[0269] In some embodiments, the antibody or fragment thereof described herein comprises a VH region and a VL region, wherein the VH region comprises: (1) a VH FR1 having the amino acid sequence of SEQ ID NO: 15; (2) a VH FR2 having the amino acid sequence of SEQ ID NO: 16; (3) a VH FR3 having the amino acid sequence of SEQ ID NO: 17; and / or (4) a VH FR4 having the amino acid sequence of SEQ ID NO: 18; and wherein the VL region comprises: (1) a VL FR1 having the amino acid sequence of SEQ ID NO: 11; (2) a VL FR2 having the amino acid sequence of SEQ ID NO: 12; (3) a VL FR3 having the amino acid sequence of SEQ ID NO: 13; and / or (4) a VL FR4 having the amino acid sequence of SEQ ID NO: 14. In some embodiments, the antibody comprises a VH region comprising all four of the above-mentioned VH FR1, VH FR2, VH FR3, and VH FR4. In other embodiments, the antibody comprises a VL region comprising all four of the above-referenced VL FR1, VL FR2, VL FR3, and VL FR4. In yet other embodiments, the antibody comprises a VH region comprising all four of the above-referenced VH FR1, VH FR2, VH FR3, and VH FR4, and a VL region comprising all four of the above-referenced VL FR1, VL FR2, VL FR3, and VL FR4.

[0270] In some embodiments, the described antibodies or fragments thereof comprise a VH region comprising: (1) a VH FR1 having the amino acid sequence of SEQ ID NO:58; (2) a VH FR2 having the amino acid sequence of SEQ ID NO:59; (3) a VH FR3 having the amino acid sequence of SEQ ID NO:60; and / or (4) a VH FR4 having the amino acid sequence of SEQ ID NO:61.

[0271] In some embodiments, the humanized antibody comprises a VH region comprising a VH FR1 having the amino acid sequence of SEQ ID NO: 58. In some embodiments, the humanized antibody comprises a VH region comprising a VH FR1 having the amino acid sequence of SEQ ID NO: 59. In some embodiments, the humanized antibody comprises a VH region comprising a VH FR1 having the amino acid sequence of SEQ ID NO: 60. In some embodiments, the humanized antibody comprises a VH region comprising a VH FR1 having the amino acid sequence of SEQ ID NO: 61.

[0272] In certain embodiments, the antibody or fragment thereof described herein comprises a VL region comprising: (1) a VL FR1 having the amino acid sequence of SEQ ID NO: 50; (2) a VL FR2 having the amino acid sequence of SEQ ID NO: 51; (3) a VL FR3 having the amino acid sequence of SEQ ID NO: 52; and / or (4) a VL FR4 having the amino acid sequence of SEQ ID NO: 53.

[0273] In certain embodiments, the humanized antibody comprises a VL region comprising a VL FR1 having the amino acid sequence of SEQ ID NO: 50. In certain embodiments, the humanized antibody comprises a VL region comprising a VL FR1 having the amino acid sequence of SEQ ID NO: 51. In certain embodiments, the humanized antibody comprises a VL region comprising a VL FR1 having the amino acid sequence of SEQ ID NO: 52. In certain embodiments, the humanized antibody comprises a VL region comprising a VL FR1 having the amino acid sequence of SEQ ID NO: 53.

[0274] In some embodiments, the antibody or fragment thereof described herein comprises a VH region and a VL region, wherein the VH region comprises: (1) a VH FR1 having the amino acid sequence of SEQ ID NO: 58; (2) a VH FR2 having the amino acid sequence of SEQ ID NO: 59; (3) a VH FR3 having the amino acid sequence of SEQ ID NO: 60; and / or (4) a VH FR4 having the amino acid sequence of SEQ ID NO: 61; and wherein the VL region comprises: (1) a VL FR1 having the amino acid sequence of SEQ ID NO: 50; (2) a VL FR2 having the amino acid sequence of SEQ ID NO: 51; (3) a VL FR3 having the amino acid sequence of SEQ ID NO: 52; and / or (4) a VL FR4 having the amino acid sequence of SEQ ID NO: 53. In some embodiments, the antibody comprises a VH region comprising all four of the above-mentioned VH FR1, VH FR2, VH FR3, and VH FR4. In other embodiments, the antibody comprises a VL region comprising all four of the above-referenced VL FR1, VL FR2, VL FR3, and VL FR4. In yet other embodiments, the antibody comprises a VH region comprising all four of the above-referenced VH FR1, VH FR2, VH FR3, and VH FR4, and a VL region comprising all four of the above-referenced VL FR1, VL FR2, VL FR3, and VL FR4.

[0275] In some embodiments, the described antibodies or fragments thereof comprise a VH region comprising: (1) a VH FR1 having the amino acid sequence of SEQ ID NO: 62; (2) a VH FR2 having the amino acid sequence of SEQ ID NO: 63; (3) a VH FR3 having the amino acid sequence of SEQ ID NO: 64; and / or (4) a VH FR4 having the amino acid sequence of SEQ ID NO: 65.

[0276] In some embodiments, the humanized antibody comprises a VH region comprising a VH FR1 having the amino acid sequence of SEQ ID NO: 62. In some embodiments, the humanized antibody comprises a VH region comprising a VH FR1 having the amino acid sequence of SEQ ID NO: 63. In some embodiments, the humanized antibody comprises a VH region comprising a VH FR1 having the amino acid sequence of SEQ ID NO: 64. In some embodiments, the humanized antibody comprises a VH region comprising a VH FR1 having the amino acid sequence of SEQ ID NO: 65.

[0277] In certain embodiments, the antibody or fragment thereof described herein comprises a VL region comprising: (1) a VL FR1 having the amino acid sequence of SEQ ID NO: 54; (2) a VL FR2 having the amino acid sequence of SEQ ID NO: 55; (3) a VL FR3 having the amino acid sequence of SEQ ID NO: 56; and / or (4) a VL FR4 having the amino acid sequence of SEQ ID NO: 57.

[0278] In certain embodiments, the humanized antibody comprises a VL region comprising a VL FR1 having the amino acid sequence of SEQ ID NO: 54. In certain embodiments, the humanized antibody comprises a VL region comprising a VL FR1 having the amino acid sequence of SEQ ID NO: 55. In certain embodiments, the humanized antibody comprises a VL region comprising a VL FR1 having the amino acid sequence of SEQ ID NO: 56. In certain embodiments, the humanized antibody comprises a VL region comprising a VL FR1 having the amino acid sequence of SEQ ID NO: 57.

[0279] In some embodiments, the antibody or fragment thereof described herein comprises a VH region and a VL region, wherein the VH region comprises: (1) a VH FR1 having the amino acid sequence of SEQ ID NO: 62; (2) a VH FR2 having the amino acid sequence of SEQ ID NO: 63; (3) a VH FR3 having the amino acid sequence of SEQ ID NO: 64; and / or (4) a VH FR4 having the amino acid sequence of SEQ ID NO: 65; and wherein the VL region comprises: (1) a VL FR1 having the amino acid sequence of SEQ ID NO: 54; (2) a VL FR2 having the amino acid sequence of SEQ ID NO: 55; (3) a VL FR3 having the amino acid sequence of SEQ ID NO: 56; and / or (4) a VL FR4 having the amino acid sequence of SEQ ID NO: 57. In some embodiments, the antibody comprises a VH region comprising all four of the above-mentioned VH FR1, VH FR2, VH FR3, and VH FR4. In other embodiments, the antibody comprises a VL region comprising all four of the above-referenced VL FR1, VL FR2, VL FR3, and VL FR4. In yet other embodiments, the antibody comprises a VH region comprising all four of the above-referenced VH FR1, VH FR2, VH FR3, and VH FR4, and a VL region comprising all four of the above-referenced VL FR1, VL FR2, VL FR3, and VL FR4.

[0280] In some embodiments, the antibody comprises any combination of VH FRs (SEQ ID NOs: 15-18 and 58-65) and VL FRs (SEQ ID NOs: 11-14 and 50-57) listed in Tables 7 and 8. In some embodiments, the antibody comprises any combination of VH FRs (SEQ ID NOs: 15-18) and VL FRs (SEQ ID NOs: 11-14) listed in Table 7. In some embodiments, the antibody comprises any combination of VH FRs (SEQ ID NOs: 58-61) and VL FRs (SEQ ID NOs: 50-53) listed in Table 8. In some embodiments, the antibody comprises any combination of VH FRs (SEQ ID NOs: 62-65) and VL FRs (SEQ ID NOs: 54-57) listed in Table 7.

[0281] In some embodiments, the antibodies provided herein comprise a VH region or VH domain. In other embodiments, the antibodies provided herein comprise a VL region or VL domain. In certain embodiments, the antibodies provided herein comprise a combination of (i) a VH domain or VH region; and / or (ii) a VL domain or VL region. Exemplary amino acid sequences of the VL and VH regions of the BTN1A1 antibodies STCH11-1, STC43G3-1, and STC85F1-1 are shown in Tables 9 and 10. Table 9. VL domain amino acids and encoding nucleic acid sequences [Table 10] Table 10. VH domain amino acid sequences [Table 11]

[0282] In yet other embodiments, the antibodies provided herein have a combination of (i) a VH domain or VH region selected from the group consisting of SEQ ID NOs: 20, 68, 134, 69, and 136 as shown in Table 10; and / or (ii) a VL domain or VL region selected from the group consisting of SEQ ID NOs: 19, 66, 135, 67, and 137 as shown in Table 9.

[0283] In some embodiments, the antibodies provided herein comprise a VL region having an amino acid sequence that has at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 19. In some embodiments, the antibodies provided herein comprise a VL region having an amino acid sequence that has at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 66. In some embodiments, the antibodies provided herein comprise a VL region having an amino acid sequence that has at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 135. In some embodiments, the antibodies provided herein comprise a VL region having an amino acid sequence that has at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 67. In some embodiments, the antibodies provided herein comprise a VL region having an amino acid sequence that has at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 137. In some embodiments, the antibodies provided herein comprise a VH region having an amino acid sequence that has at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 20. In some embodiments, the antibodies provided herein comprise a VH region having an amino acid sequence having at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO:68.In some embodiments, the antibodies provided herein comprise a VH region having an amino acid sequence that has at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 134. In some embodiments, the antibodies provided herein comprise a VH region having an amino acid sequence that has at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 69. In some embodiments, the antibodies provided herein comprise a VH region having an amino acid sequence that has at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 136.

[0284] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:8; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:9; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:10; and a VL region as set forth in Table 9. In some embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:71; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:72; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:73; and a VL region as set forth in Table 9. In some embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:77; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:78; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:79; and a VL region as set forth in Table 9. In some embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 83; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 84; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 85; and a VL region as set forth in Table 9.

[0285] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:8; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:9; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:10; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 19. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:8; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:9; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:10; and a VL region having the amino acid sequence of SEQ ID NO:19.

[0286] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:8; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:9; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:10; and a VL region having an amino acid sequence having at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO:66. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:8; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:9; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:10; and a VL region having the amino acid sequence of SEQ ID NO:66.

[0287] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:8; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:9; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:10; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 135. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:8; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:9; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:10; and a VL region having the amino acid sequence of SEQ ID NO:135.

[0288] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:8; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:9; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:10; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO:67. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:8; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:9; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:10; and a VL region having the amino acid sequence of SEQ ID NO:67.

[0289] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:8; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:9; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:10; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 137. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:8; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:9; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:10; and a VL region having the amino acid sequence of SEQ ID NO:137.

[0290] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 71; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 72; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 73; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 19. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 71; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 72; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 73; and a VL region having the amino acid sequence of SEQ ID NO: 19.

[0291] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 71; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 72; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 73; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 66. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 71; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 72; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 73; and a VL region having the amino acid sequence of SEQ ID NO: 66.

[0292] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 71; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 72; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 73; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 135. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 71; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 72; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 73; and a VL region having the amino acid sequence of SEQ ID NO: 135.

[0293] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 71; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 72; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 73; and a VL region having an amino acid sequence having at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 67. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 71; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 72; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 73; and a VL region having the amino acid sequence of SEQ ID NO: 67.

[0294] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 71; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 72; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 73; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 137. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 71; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 72; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 73; and a VL region having the amino acid sequence of SEQ ID NO: 137.

[0295] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 77; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 78; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 79; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 19. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 77; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 78; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 79; and a VL region having the amino acid sequence of SEQ ID NO: 19.

[0296] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 77; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 78; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 79; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 66. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 77; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 78; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 79; and a VL region having the amino acid sequence of SEQ ID NO: 66.

[0297] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 77; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 78; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 79; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 135. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 77; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 78; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 79; and a VL region having the amino acid sequence of SEQ ID NO: 135.

[0298] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 77; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 78; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 79; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 67. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 77; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 78; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 79; and a VL region having the amino acid sequence of SEQ ID NO: 67.

[0299] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 77; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 78; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 79; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 137. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 77; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 78; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 79; and a VL region having the amino acid sequence of SEQ ID NO: 137.

[0300] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 83; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 84; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 85; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 19. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 83; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 84; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 85; and a VL region having the amino acid sequence of SEQ ID NO: 19.

[0301] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 83; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 84; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 85; and a VL region having an amino acid sequence having at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 66. In certain embodiments, the antibodies provided herein comprise: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 83; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 84; and a VL region having the amino acid sequence of SEQ ID NO: 66.

[0302] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 83; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 84; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 85; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 135. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 83; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 84; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 85; and a VL region having the amino acid sequence of SEQ ID NO: 135.

[0303] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 83; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 84; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 85; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 67. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 83; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 84; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 85; and a VL region having the amino acid sequence of SEQ ID NO: 67.

[0304] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 83; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 84; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 85; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 137. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 83; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 84; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 85; and a VL region having the amino acid sequence of SEQ ID NO: 137.

[0305] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 44; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 45; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 46; and a VL region as set forth in Table 9. In some embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 91; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 92; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 93; and a VL region as set forth in Table 9. In some embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 97; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 98; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 99; and a VL region as set forth in Table 9. In some embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 103; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 104; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 105; and a VL region as set forth in Table 9.

[0306] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 44; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 45; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 46; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 19. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 44; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 45; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 46; and a VL region having the amino acid sequence of SEQ ID NO: 19.

[0307] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 44; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 45; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 46; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 66. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 44; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 45; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 46; and a VL region having the amino acid sequence of SEQ ID NO: 66.

[0308] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 44; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 45; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 46; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 135. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 44; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 45; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 46; and a VL region having the amino acid sequence of SEQ ID NO: 135.

[0309] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 44; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 45; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 46; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 67. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 44; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 45; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 46; and a VL region having the amino acid sequence of SEQ ID NO: 67.

[0310] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 44; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 45; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 46; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 137. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 44; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 45; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 46; and a VL region having the amino acid sequence of SEQ ID NO: 137.

[0311] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 91; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 92; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 93; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 19. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 91; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 92; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 93; and a VL region having the amino acid sequence of SEQ ID NO: 19.

[0312] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 91; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 92; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 93; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 66. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 91; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 92; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 93; and a VL region having the amino acid sequence of SEQ ID NO: 66.

[0313] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 91; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 92; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 93; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 135. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 91; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 92; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 93; and a VL region having the amino acid sequence of SEQ ID NO: 135.

[0314] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 91; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 92; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 93; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 67. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 91; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 92; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 93; and a VL region having the amino acid sequence of SEQ ID NO: 67.

[0315] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 91; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 92; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 93; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 137. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 91; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 92; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 93; and a VL region having the amino acid sequence of SEQ ID NO: 137.

[0316] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 97; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 98; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 99; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 19. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 97; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 98; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 99; and a VL region having the amino acid sequence of SEQ ID NO: 19.

[0317] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 97; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 98; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 99; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 66. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 97; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 98; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 99; and a VL region having the amino acid sequence of SEQ ID NO: 66.

[0318] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 97; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 98; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 99; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 135. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 97; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 98; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 99; and a VL region having the amino acid sequence of SEQ ID NO: 135.

[0319] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 97; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 98; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 99; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 67. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 97; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 98; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 99; and a VL region having the amino acid sequence of SEQ ID NO: 67.

[0320] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 97; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 98; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 99; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 137. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 97; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 98; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 99; and a VL region having the amino acid sequence of SEQ ID NO: 137.

[0321] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 103; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 104; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 105; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 19. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 103; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 104; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 105; and a VL region having the amino acid sequence of SEQ ID NO: 19.

[0322] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 103; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 104; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 105; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 66. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 103; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 104; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 105; and a VL region having the amino acid sequence of SEQ ID NO:66.

[0323] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 103; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 104; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 105; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 135. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 103; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 104; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 105; and a VL region having the amino acid sequence of SEQ ID NO: 135.

[0324] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 103; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 104; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 105; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 67. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 103; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 104; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 105; and a VL region having the amino acid sequence of SEQ ID NO: 67.

[0325] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 103; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 104; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 105; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 137. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 103; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 104; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 105; and a VL region having the amino acid sequence of SEQ ID NO: 137.

[0326] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 47; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 48; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 49; and a VL region as set forth in Table 9. In some embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 111; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 112; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 113; and a VL region as set forth in Table 9. In some embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 117; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 118; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 119; and a VL region as set forth in Table 9. In some embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 123; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 124; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 125; and a VL region as set forth in Table 9.

[0327] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 47; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 48; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 49; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 19. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 47; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 48; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 49; and a VL region having the amino acid sequence of SEQ ID NO: 19.

[0328] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 47; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 48; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 49; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 66. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 47; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 48; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 49; and a VL region having the amino acid sequence of SEQ ID NO: 66.

[0329] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 47; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 48; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 49; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 135. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 47; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 48; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 49; and a VL region having the amino acid sequence of SEQ ID NO: 135.

[0330] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 47; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 48; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 49; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 67. In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 47; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 48; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 49; and a VL region having the amino acid sequence of SEQ ID NO: 67.

[0331] In certain embodiments, the antibodies provided herein comprise a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 47; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 48; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 49; and a VL region having an amino acid sequence with at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% sequence identity to SEQ ID NO: 137. In certain embodiments, the antibodies provided herein comprise a VH region comprising: ...

Claims

1. (a) (i) a light chain variable region having the amino acid sequence of SEQ ID NO: 19 and a heavy chain variable region having the amino acid sequence of SEQ ID NO: 20; (ii) a light chain variable region having the amino acid sequence of SEQ ID NO: 66 and a heavy chain variable region having the amino acid sequence of SEQ ID NO: 68; or (iii) a light chain variable region having the amino acid sequence of SEQ ID NO: 67 and a heavy chain variable region having the amino acid sequence of SEQ ID NO: 69; or (b) (i) a light chain variable region having the amino acid sequence of SEQ ID NO: 19 and a heavy chain variable region having the amino acid sequence of SEQ ID NO: 20; (ii) a light chain variable region having the amino acid sequence of SEQ ID NO: 66 and a heavy chain variable region having the amino acid sequence of SEQ ID NO: 68; or (iii) a light chain variable region having the amino acid sequence of SEQ ID NO: 67 and a heavy chain variable region having the amino acid sequence of SEQ ID NO: 69 competes for binding to BTN1A1 with an antibody comprising An antibody or an antigen-binding fragment thereof.

2. the antibody or antigen-binding fragment thereof (a) a light chain variable region (VL) comprising VL complementarity determining region 1 (CDR1), VL CDR2, and VL CDR3 of antibody STC43H11-1 shown in Table 1; and / or a heavy chain variable region (VH) comprising VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3 of antibody STC43H11-1 shown in Table 2; (b) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 19; and / or a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 20; (c) a VL comprising the VL CDR1, VL CDR2, and VL CDR3 of antibody STC43G3-1 shown in Table 3; and / or a VH comprising the VH CDR1, VH CDR2, and VH CDR3 of antibody STC43G3-1 shown in Table 4; (d) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 66; and / or a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 68; (e) a VL comprising the VL CDR1, VL CDR2, and VL CDR3 of antibody STC85F1-1 shown in Table 5; and / or a VH comprising the VH CDR1, VH CDR2, and VH CDR3 of antibody STC85F1-1 shown in Table 6; or (f) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 67; and / or a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO:

69. : An antibody or antigen-binding fragment thereof that binds to BTN1A1.

3. (a) the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the Kabat numbering system; (b) the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the Chothia numbering system; (c) whether the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the ABM numbering system; (d) the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the contact numbering system; or (e) the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the IMGT numbering system; The antibody or antigen-binding fragment thereof according to claim 2.

4. the antibody or antigen-binding fragment thereof (a) a VL further comprising a VL framework 1 (FR1), a VL FR2, a VL FR3, and a VL FR4 of any one of antibodies STC43H11-1 shown in Table 7; and / or a VH further comprising a VH framework 1 (FR1), a VH FR2, a VH FR3, and a VH FR4 of any one of antibodies STC43H11-1 shown in Table 8; (b) a VL further comprising the VL framework 1 (FR1), VL FR2, VL FR3, and VL FR4 of any one of antibodies STC43G3-1 shown in Table 7; and / or a VH further comprising the VH framework 1 (FR1), VH FR2, VH FR3, and VH FR4 of any one of antibodies STC43G3-1 shown in Table 8; or (c) a VL further comprising VL framework 1 (FR1), VL FR2, VL FR3, and VL FR4 of any one of antibodies STC85F1-1 shown in Table 7; and / or VH framework 1 (FR1), VH FR2, VH FR3, and VH FR4 of any one of antibodies STC85F1-1 shown in Table 8. VH further comprising 3. The antibody or antigen-binding fragment thereof of claim 2, comprising:

5. (a) the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOs: 5, 6, and 7, respectively, and the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOs: 8, 9, and 10, respectively; (b) the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOs: 74, 75, and 76, respectively, and the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOs: 71, 72, and 73, respectively; (c) the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOs: 80, 81, and 82, respectively, and the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOs: 77, 78, and 79, respectively; or (d) the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOs: 86, 87, and 88, respectively, and the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOs: 83, 84, and 85, respectively; The antibody or antigen-binding fragment thereof according to claim 2.

6. The antibody or antigen-binding fragment thereof of claim 2, wherein the antibody or antigen-binding fragment thereof comprises a VL comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO:

19.

7. The antibody or antigen-binding fragment thereof of claim 2, wherein the antibody or antigen-binding fragment thereof comprises a VL having the amino acid sequence of SEQ ID NO:

19.

8. The antibody or antigen-binding fragment thereof of claim 2, wherein the antibody or antigen-binding fragment thereof comprises a VH comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO:

20.

9. The antibody or antigen-binding fragment thereof of claim 2, wherein the antibody or antigen-binding fragment thereof comprises a VH having the amino acid sequence of SEQ ID NO:

20.

10. The antibody or antigen-binding fragment thereof of claim 2, wherein the antibody or antigen-binding fragment thereof comprises a VL comprising an amino acid sequence having at least 95% sequence identity with SEQ ID NO: 19 and a VH comprising an amino acid sequence having at least 95% sequence identity with SEQ ID NO:

20.

11. the antibody or antigen-binding fragment thereof (a) a VL comprising the amino acid sequence of SEQ ID NO: 19; and (b) a VH comprising the amino acid sequence of SEQ ID NO: 20 3. The antibody or antigen-binding fragment thereof of claim 2, comprising:

12. (a) the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOs: 38, 39, and 40, respectively, and the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOs: 44, 45, and 46, respectively; (b) the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOs: 94, 95, and 96, respectively, and the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOs: 91, 92, and 93, respectively; (c) the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOs: 100, 101, and 102, respectively, and the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOs: 97, 98, and 99, respectively; or (d) the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOs: 106, 107, and 108, respectively, and the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOs: 103, 104, and 105, respectively; The antibody or antigen-binding fragment thereof according to claim 2.

13. The antibody or antigen-binding fragment thereof of claim 2, wherein the antibody or antigen-binding fragment thereof comprises a VL comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO:

66.

14. The antibody or antigen-binding fragment thereof of claim 2, wherein the antibody or antigen-binding fragment thereof comprises a VL having the amino acid sequence of SEQ ID NO:

66.

15. The antibody or antigen-binding fragment thereof of claim 2, wherein the antibody or antigen-binding fragment thereof comprises a VH comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO:

68.

16. The antibody or antigen-binding fragment thereof of claim 2, wherein the antibody or antigen-binding fragment thereof comprises a VH having the amino acid sequence of SEQ ID NO:

68.

17. The antibody or antigen-binding fragment thereof of claim 2, wherein the antibody or antigen-binding fragment thereof comprises a VL comprising an amino acid sequence having at least 95% sequence identity with SEQ ID NO: 66 and a VH comprising an amino acid sequence having at least 95% sequence identity with SEQ ID NO:

68.

18. the antibody or antigen-binding fragment thereof (a) a VL comprising the amino acid sequence of SEQ ID NO: 66; and (b) VH comprising the amino acid sequence of SEQ ID NO: 68 3. The antibody or antigen-binding fragment thereof of claim 2, comprising:

19. (a) the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOs: 41, 42, and 43, respectively, and the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOs: 47, 48, and 49, respectively; (b) the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOs: 114, 115, and 116, respectively, and the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOs: 111, 112, and 113, respectively; (c) the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOs: 120, 121, and 122, respectively, and the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOs: 117, 118, and 119, respectively; or (d) the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOs: 126, 127, and 128, respectively, and the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOs: 123, 124, and 125, respectively; The antibody or antigen-binding fragment thereof according to claim 2.

20. The antibody or antigen-binding fragment thereof of claim 2, wherein the antibody or antigen-binding fragment thereof comprises a VL comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO:

67.

21. The antibody or antigen-binding fragment thereof of claim 2, wherein the antibody or antigen-binding fragment thereof comprises a VL having the amino acid sequence of SEQ ID NO:

67.

22. The antibody or antigen-binding fragment thereof of claim 2, wherein the antibody or antigen-binding fragment thereof comprises a VH comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO:

69.

23. The antibody or antigen-binding fragment thereof of claim 2, wherein the antibody or antigen-binding fragment thereof comprises a VH having the amino acid sequence of SEQ ID NO:

69.

24. The antibody or antigen-binding fragment thereof of claim 2, wherein the antibody or antigen-binding fragment thereof comprises a VL comprising an amino acid sequence having at least 95% sequence identity with SEQ ID NO: 67 and a VH comprising an amino acid sequence having at least 95% sequence identity with SEQ ID NO:

69.

25. the antibody or antigen-binding fragment thereof (a) a VL comprising the amino acid sequence of SEQ ID NO: 67; and (b) VH comprising the amino acid sequence of SEQ ID NO: 69 3. The antibody or antigen-binding fragment thereof of claim 2, comprising:

26. The antibody or antigen-binding fragment thereof of any one of claims 1 to 25, wherein the antibody or antigen-binding fragment thereof binds to human BTN1A1.

27. The antibody or antigen-binding fragment thereof of any one of claims 1 to 25, wherein the antibody or antigen-binding fragment thereof binds to mouse BTN1A1.

28. 28. The antibody or antigen-binding fragment thereof of any one of claims 1 to 27, wherein when bound to BTN1A1, the antibody or antigen-binding fragment binds to at least one of residues 361 to 375 within the amino acid sequence of SEQ ID NO:

1.

29. 28. The antibody or antigen-binding fragment thereof of any one of claims 1 to 27, wherein when bound to BTN1A1, the antibody or antigen-binding fragment binds to at least one of residues 365 to 372 within the amino acid sequence of SEQ ID NO:

1.

30. 28. The antibody or antigen-binding fragment thereof of any one of claims 1 to 27, wherein when bound to BTN1A1, the antibody or antigen-binding fragment binds to at least one of residues 366 to 372 within the amino acid sequence of SEQ ID NO:

1.

31. 28. The antibody or antigen-binding fragment thereof of any one of claims 1 to 27, wherein when bound to BTN1A1, the antibody or antigen-binding fragment binds to at least one residue selected from the group consisting of G365, D366, T368, D369, W370, A371, I372, and G373 in the amino acid sequence of SEQ ID NO:

1.

32. The antibody or antigen-binding fragment thereof of claim 31, wherein when bound to BTN1A1, the antibody or antigen-binding fragment binds to G365 in the amino acid sequence of SEQ ID NO:

1.

33. The antibody or antigen-binding fragment thereof of claim 31, wherein when bound to BTN1A1, the antibody or antigen-binding fragment binds to D366 within the amino acid sequence of SEQ ID NO:

1.

34. The antibody or antigen-binding fragment thereof of claim 31, wherein when bound to BTN1A1, the antibody or antigen-binding fragment binds to T368 within the amino acid sequence of SEQ ID NO:

1.

35. The antibody or antigen-binding fragment thereof of claim 31, wherein when bound to BTN1A1, the antibody or antigen-binding fragment binds to D369 within the amino acid sequence of SEQ ID NO:

1.

36. The antibody or antigen-binding fragment thereof of claim 31, wherein when bound to BTN1A1, the antibody or antigen-binding fragment binds to W370 within the amino acid sequence of SEQ ID NO:

1.

37. The antibody or antigen-binding fragment thereof of claim 31, wherein when bound to BTN1A1, the antibody or antigen-binding fragment binds to A371 within the amino acid sequence of SEQ ID NO:

1.

38. The antibody or antigen-binding fragment thereof of claim 31, wherein when bound to BTN1A1, the antibody or antigen-binding fragment binds to I372 within the amino acid sequence of SEQ ID NO:

1.

39. The antibody or antigen-binding fragment thereof of claim 31, wherein when bound to BTN1A1, the antibody or antigen-binding fragment binds to G373 within the amino acid sequence of SEQ ID NO:

1.

40. The antibody or antigen-binding fragment thereof of claim 31, wherein when bound to BTN1A1, the antibody or antigen-binding fragment binds to D366, D369, and I372 within the amino acid sequence of SEQ ID NO:

1.

41. The antibody or antigen-binding fragment thereof of claim 31, wherein when bound to BTN1A1, the antibody or antigen-binding fragment binds to G365, T368, D369, A371, and I372 within the amino acid sequence of SEQ ID NO:

1.

42. The antibody or antigen-binding fragment thereof of claim 31, wherein when bound to BTN1A1, the antibody or antigen-binding fragment binds to D366, T368, D369, W370, A371, I372, and G373 within the amino acid sequence of SEQ ID NO:

1.

43. The antibody or antigen-binding fragment thereof of any one of claims 1 to 42, wherein the antibody is a monoclonal antibody.

44. The antibody or antigen-binding fragment thereof of any one of claims 1 to 43, wherein the antibody is a humanized, human, or chimeric antibody.

45. 45. The antibody or antigen-binding fragment thereof of claim 44, wherein the humanized antibody is a deimmunized antibody or a synthetic human antibody.

46. The antibody or antigen-binding fragment thereof is Fab, Fab', F(ab') 2 46. ​​The antibody or antigen-binding fragment thereof of any one of claims 1 to 45, which is a multispecific antibody formed from an Fv, scFv, dsFv, diabody, triabody, tetrabody, or antibody fragment.

47. The antibody or antigen-binding fragment thereof of any one of claims 1 to 46, wherein the antibody or antigen-binding fragment thereof is conjugated to an agent.

48. 48. The antibody or antigen-binding fragment thereof of claim 47, wherein the agent is selected from the group consisting of a radioisotope, a metal chelator, an enzyme, a fluorescent compound, a bioluminescent compound, and a chemiluminescent compound.

49. A composition comprising the antibody or antigen-binding fragment thereof of any one of claims 1 to 48 and a pharma- ceutical acceptable carrier.

50. A polynucleotide comprising a nucleotide sequence encoding the VH, VL, or both the VH and VL of the antibody of any one of claims 1 to 48.

51. A polynucleotide comprising a nucleotide sequence encoding the heavy chain, the light chain, or both the heavy and light chains of the antibody of any one of claims 1 to 48.

52. 52. The polynucleotide of claim 50 or 51, wherein the polynucleotide is operably linked to a promoter.

53. A vector comprising the polynucleotide of any one of claims 50 to 52.

54. A cell comprising the polynucleotide of any one of claims 50 to 52.

55. 54. A cell comprising the vector of claim 53.

56. 49. An isolated cell producing the antibody or antigen-binding fragment thereof of any one of claims 1 to 48.

57. A kit comprising the antibody or antigen-binding fragment thereof of any one of claims 1 to 48.

58. 57. A method for producing an antibody or antigen-binding fragment thereof that specifically binds to an epitope of BTN1A1, the method comprising culturing a cell according to any one of claims 54 to 56 to express the antibody or antigen-binding fragment thereof.

59. 53. A method for producing an antibody or antigen-binding fragment thereof that specifically binds to an epitope of BTN1A1, the method comprising expressing a polynucleotide according to any one of claims 50 to 52.

60. 50. A method for detecting BTN1A1 in a sample, comprising contacting the sample with an anti-BTN1A1 antibody or antigen-binding fragment thereof of any one of claims 1 to 48 and detecting the presence of the anti-BTN1A1 antibody or antigen-binding fragment thereof bound to the sample, wherein detection of an amount of anti-BTN1A1 antibody or antigen-binding fragment thereof bound to the sample above background indicates the presence of BTN1A1 in the sample.

61. The method of claim 60, further comprising quantifying the amount of BTN1A1 detected in the sample.

62. 62. The method of claim 60 or 61, wherein the anti-BTN1A1 antibody or antigen-binding fragment thereof is conjugated to a detectable agent that produces a signal, and the detecting comprises detecting the signal from the sample.

63. The method of claim 60 or 61, wherein the anti-BTN1A1 antibody or antigen-binding fragment thereof is contacted with a secondary binding molecule that specifically binds to the anti-BTN1A1 antibody or antigen-binding fragment thereof in the sample, and the detecting comprises detecting the secondary binding molecule from the sample.

64. The method of any one of claims 60 to 63, wherein the sample is a cell-containing sample.

65. 65. The method of claim 64, wherein the cells in the sample are fixed in situ prior to contacting with the anti-BTN1A1 antibody or antigen-binding fragment thereof.

66. 66. The method of claim 64 or 65, wherein the sample is a formalin-fixed paraffin-embedded (FFPE) tissue sample.

67. 67. The method of any one of claims 60-66, wherein said sample is cancer tissue; optionally wherein said cancer is selected from skin cancer, pancreatic cancer, breast cancer, esophageal cancer, and endometrial cancer.

68. 67. The method of any one of claims 60-66, wherein the sample is a bodily fluid sample; optionally wherein the bodily fluid sample is blood, serum, or plasma.

69. The method of any one of claims 60 to 68, wherein the sample is obtained from a subject and the method further comprises diagnosing the subject as having or at risk of developing a BTN1A1-mediated disease or condition when an amount of BTN1A1 in the sample is detected above a threshold amount.

70. 70. The method of claim 69, wherein the BTN1A1-mediated disease or condition is cancer.

71. 71. The method of claim 69 or 70, wherein the subject is a mammal.

72. The method of any one of claims 69 to 71, wherein the subject is a human.

73. A kit for carrying out the method of any one of claims 60 to 72.

74. A method of treating a subject with a BTN1A1 targeting agent, comprising detecting BTN1A1 in a sample from the subject.

75. The method of claim 74, wherein detecting BTN1A1 in the sample comprises a method according to any one of claims 60 to 72.

76. The method of claim 74 or 75, wherein the targeting agent is an antagonistic polypeptide that binds to BTN1A1.

77. 76. The method of claim 74 or 75, wherein the targeting agent is an agonistic polypeptide that binds to BTN1A1.

78. The method of claim 76 or 77, wherein the polypeptide that binds to BTN1A1 is an antibody or an antigen-binding fragment thereof.

79. The method of claim 74 or 75, wherein the targeting agent is a small molecule compound that inhibits BTN1A1.

80. The method of any one of claims 74 to 79, wherein the subject has a disease or condition mediated by BTN1A1.

81. The method of any one of claims 74-80, wherein said method eliminates a population of diseased cells that express BTN1A1.

82. The method of any one of claims 74 to 81, wherein the subject has cancer.

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