Anti-CD94 antibodies and methods of use thereof

Abstract

The present disclosure relates to antibodies that bind to human CD94, as well as related methods, uses, polynucleotides, vectors, host cells, and pharmaceutical compositions. In some embodiments, the antibodies are human or humanized antibodies that bind to human CD94 and do not block the binding between CD94 and HLA-E. In some embodiments, the antibodies cross-react with cynomolgus monkey CD94. In some embodiments, the antibodies do not promote internalization of surface-expressed CD94 as well as existing antibodies. In some embodiments, the antibodies promote ADCC targeting cells that express human CD94, for example, on the cell surface.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 63 / 085,932, filed September 30, 2020, and U.S. Provisional Application No. 63 / 088,926, filed October 7, 2020, the disclosures of each of which are incorporated herein by reference in their entireties.

[0002] Submitting a sequence listing as an ASCII text file The contents of the following ASCII text file submission are incorporated herein by reference in their entirety: Sequence Listing in Computer Readable Form (CRF) (Filename: 186542000340SEQLIST.TXT, Recorded: September 28, 2021, Size: 52,165 bytes).

[0003] The present disclosure relates to antibodies that bind to CD94 and their uses for treating diseases and disorders associated with NK cells and / or T cells. [Background technology]

[0004] Natural killer (NK) / T-cell lymphomas and leukemias are characterized by the clonal expansion of NK cells and / or CD8+ and CD4+ T cells. NK / T-cell lymphomas account for a small proportion of non-Hodgkin's lymphomas (NHLs), with a 5-year survival rate of less than 50% (Kwong, 2012). Approximately 4,000 to 7,000 new cases occur annually in the United States alone, with a higher incidence in Asian populations (Bajaj, A. (2019) Int. J. Hemat. Ther. 5:1-7). NK / T-cell lymphomas can occur at any age, but more than half of NHL patients are 65 years of age or older (Bajaj, 2019). There are also NK cell- and T cell-based leukemias, such as LGL leukemia and aggressive NK leukemia. Other examples of diseases and disorders in which NK cells play a role include LGL leukemia (e.g., T-cell LGL leukemia), chronic NK-cell lymphoproliferative disorder (CLPD-NK, formerly NK-LGL), rheumatoid arthritis, Felty's syndrome, aggressive NK leukemia (e.g., aggressive natural killer leukemia (ANKL) and extranodal NKL, nasal type (ENKL)), IBM, and IBD.

[0005] There are 13 distinct diseases involving NK / T-cell lymphoma: extranodal NK / T-cell lymphoma, hepatosplenic T-cell lymphoma (TCL), enteropathy-associated TCL, cutaneous TCL, anaplastic large cell lymphoma (ALK+), anaplastic large cell lymphoma (ALK-), peripheral TCL (not otherwise specified), angioimmunoblastic TCL, adult TCL, monomorphic epitheliotropic intestinal TCL, epidermotropic CD8+ cutaneous TCL, primary cutaneous gamma / delta TCL, and subcutaneous panniculitis TCL (Bajaj, 2019). The major subtypes of NK / T-cell lymphoma, most of which are driven by cytotoxic cells (NK / CD8+ T cells), include extranodal NK / T-cell lymphoma, hepatosplenic TCL, enteropathy-associated TCL, monomorphic epitheliotropic intestinal TCL, epidermotropic CD8+ cutaneous TCL, primary cutaneous gamma / delta TCL, and subcutaneous panniculitis TCL. NK / T-cell lymphoma can affect various organs, including the skin, gastrointestinal (GI) tract, liver, spleen, and bone marrow. Symptoms include cervical lymphadenopathy. Most NK / T-cell lymphoma subtypes are driven by Epstein-Barr virus infection.

[0006] Current treatments include chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by stem cell transplantation, but progression-free survival rates remain at 40%–50%. Current treatments under investigation include alemtuzumab, carfilzomib (a proteasome inhibitor), romidepsin (an HDAC inhibitor), bevacizumab, brentuximab vedotin (an antibody-drug conjugate), bortezomib (a proteasome inhibitor), belinstat (an HDAC inhibitor), pralatrexate, vorinostat (an HDAC inhibitor), and avelumab. Despite the diversity of drugs in development, many of them are often used off-label and have produced mixed results.

[0007] Currently, there are no effective therapies for the treatment of NK / T-cell lymphoma, and no therapies that selectively target NK / T-cell lymphoma have been developed. Current therapies for NK / T-cell lymphoma may have off-target effects and are not completely effective. The high mortality rate of the disease combined with the lack of effective treatments highlights the need for therapeutic advances in NK / T-cell lymphoma.

[0008] Thus, there is a need in the art to develop safe and effective therapies for treating diseases mediated by NK cells and / or T cells that express CD94, such as NK / T cell lymphoma. Summary of the Invention [Means for solving the problem]

[0009] To meet these and other needs, the present disclosure provides, among other things, antibodies that specifically bind to CD94 (e.g., human CD94), methods of treating diseases or disorders associated with NK cells and / or T cells that express CD94, such as NK / T cell lymphomas and leukemias (e.g., LGL leukemia), and methods of depleting or reducing the number of NK cells and / or T cells that express CD94 in a subject upon administration of an antibody that specifically binds CD94. These antibodies of the present disclosure may have one or more of the following properties: high-affinity binding to human CD94 (e.g., cells expressing human CD94 on their surface), cross-reactivity to cynomolgus CD94 (useful for preclinical studies), the ability to bind human CD94 without blocking the interaction of human CD94 with HLA-E, minimal internalization following binding to CD94, and / or induction of ADCC against cells expressing CD94, such as leukemia cells. These properties are believed to be advantageous for testing, development, and use in treating NK / T cell-based diseases such as lymphoma and leukemia. For example, without wishing to be bound by theory, it is believed that targeting CD94 on NK cells by ADCC may induce cancer cells (e.g., LGL leukemia or lymphoma cells) to kill other cancer cells.

[0010] In some aspects, provided herein are human or humanized antibodies that bind to human CD94, wherein the binding of the antibody to human CD94 does not block the binding between human CD94 and human HLA-E. In some embodiments, the antibody binds to human CD94 expressed on the surface of a cell (e.g., a human natural killer (NK) cell). In some embodiments, the antibody binds to the extracellular domain of human CD94. In some embodiments, the antibody binds to cynomolgus monkey CD94 expressed on the surface of a cell. In some embodiments, the binding of the antibody to a cell expressing human CD94 blocks less than 20% of HLA-E binding to human CD94. In other aspects, provided herein are human or humanized antibodies that bind to human CD94 and cynomolgus monkey CD94 (e.g., can bind to human CD94 and cynomolgus monkey CD94 separately). In some embodiments, the antibody binds to human CD94 expressed on the surface of a cell (e.g., a human natural killer (NK) cell). In some embodiments, the antibody binds to cynomolgus CD94 expressed on the surface of a cell (e.g., a cell, such as a cynomolgus NK cell or a human cell overexpressing cynomolgus CD94). In some embodiments, binding of the antibody to human CD94 does not block binding between human CD94 and human HLA-E. In some embodiments, incubation of the antibody with cells expressing human CD94 on their surface at 37°C for 24 hours results in less than a 50% reduction in surface antibody staining due to internalization.

[0011] In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 1, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 2, and CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 3, and the VL domain comprises CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 4, CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 5, and CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 6. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3; and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6. In some embodiments, the VH domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 19, and the VL domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 20. In some embodiments, the VH domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 19, and the VL domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 20. In some embodiments, the VH domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 19, and the VL domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 20. In some embodiments, the VH domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 19, and the VL domain comprisesIn some embodiments, the antibody comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 20. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 19, and the VL domain comprises the amino acid sequence of SEQ ID NO: 20. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 7, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 8, and CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 9, and the VL domain comprises CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 10, CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 11, and CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 12. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO:7, CDR-H2 comprising the amino acid sequence of SEQ ID NO:8, and CDR-H3 comprising the amino acid sequence of SEQ ID NO:9, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO:10, CDR-L2 comprising the amino acid sequence of SEQ ID NO:11, and CDR-L3 comprising the amino acid sequence of SEQ ID NO:12. In some embodiments, the VH domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:21, and the VL domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:22. In some embodiments, the VH domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:21, and the VL domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:22. In some embodiments, the VH domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 21, and the VL domain comprisesIn some embodiments, the VH domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 22. In some embodiments, the VH domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 21, and the VL domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 22. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 21, and the VL domain comprises the amino acid sequence of SEQ ID NO: 22. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 13, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 14, and CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 15, and the VL domain comprises CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 16, CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 17, and CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 13, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 14, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 15, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 16, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 17, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 18. In some embodiments, the VH domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 23, and the VL domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 24. In some embodiments, the VH domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 23, and the VL domain comprisesIn some embodiments, the VH domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 24. In some embodiments, the VH domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 23, and the VL domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 24. In some embodiments, the VH domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 23, and the VL domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 24. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 23, and the VL domain comprises the amino acid sequence of SEQ ID NO: 24. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein (a) the VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 30, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 31, and CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 32; and the VL domain comprises CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 33, CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 34, and CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 35. (b) the VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 36, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 37, and CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 38, and the VL domain comprises CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 33 and CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 34;and CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 35; or (c) the VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 36, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 39, and CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 40, and the VL domain comprises CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 33, CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 35; or (d) the VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 41, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 42. (e) the VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 47, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 48, and CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 49, and the VL domain comprises CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 50;(f) a CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 51, and a CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 52, or (f) a CDR-H wherein the VH domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 53; 1. a CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 54, and a CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 55, wherein the VL domain comprises CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 50, CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 45, and CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 56; or (g) a VH domain comprising CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 57, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 58, and CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 59, wherein the VL domain comprises CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 50, CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 45, and CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 56. (h) the VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 83, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 84, and CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 61; or or (i) the VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 86, CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 61; or (i) the VH domain comprisesThe VL domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 47, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 48, and CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 63, CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 64. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein (a) the VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 87, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 88, and CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 89; and the VL domain comprises CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 90, CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 91, and CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 89. or (b) the VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 87, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 92, and CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 90 and CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 91;and CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 35; or (c) the VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 87, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 92, and CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 94, and the VL domain comprises CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 90, CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 91, and CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 35; or (d) the VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 95, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 96. and CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 97, and the VL domain comprises CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 98, CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 99, and CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 100. or (e) a CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 109, a CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 110, and a CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 114, and the VL domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 115;(f) the VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 116, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 117, and CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 52, or (g) the VH domain comprises a CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 115, a CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 99, and a CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 56; or and CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 102, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 102, and CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 103, wherein the VL domain comprises CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 104, CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 91, (h) the VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 105, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 106, and CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 107, and the VL domain comprisesor (i) the VH domain comprises CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 108, CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 91, and CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 61, or (ii) the VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 109, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 110, CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 111, and CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 111, and CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 111, and the VL domain comprises CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 112, CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 113, and CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 64. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein (a) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 30, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 31, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 32, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 33, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 35; or (b) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 36. (c) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 36, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 39, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 40, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 33, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 35, or(d) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 41, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 42, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 43, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 44, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 45, and CDR comprising the amino acid sequence of SEQ ID NO: 46; (e) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 47, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 48, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 49, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 50, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 51, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 52; or (f) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 53, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 54, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 55. (g) a VH domain comprising CDR-H1 comprising the amino acid sequence of SEQ ID NO: 57, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 58, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 59, wherein the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 50, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 45, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 56; or (h) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 83, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 84, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 86, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 61; or or (i) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 47, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 48, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 63, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 64. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, and (a) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 87, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 88, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises(b) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 87, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 92, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 90, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 91, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 350; or (c) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 87, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 92, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 94, and a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 90, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 91, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 35; or (d) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 95, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 96, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 97. 3, wherein the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 98, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 99, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 100, or (e) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 109, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 110, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 114, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 115, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 99, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 52. (f) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 116, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 117, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 118, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 115, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 99, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 56; or (g) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 101 and CDR-H2 comprising the amino acid sequence of SEQ ID NO: 102;and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 103, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 104, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 91, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 61, or (h) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 105, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 106, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 107, and the VL domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 108. -L1 comprising the amino acid sequence of SEQ ID NO: 91, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 61, or (i) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 109, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 110, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 111, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 112, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 113, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 64. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein (a) the VH domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 65 and the VL domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 66, or (b) the VH domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 67 and the VL domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 68. (c) the VH domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 69 and the VL domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 70; (d) the VH domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 71 and the VL domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 72; or (e) the VH domain comprises(f) the VH domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 73, and the VL domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 74; (f) the VH domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 75, and the VL domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 76; or (g) the VH domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 77, and the VL domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 78. (h) the VH domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 79 and the VL domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 80; or (i) the VH domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 81 and the VL domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 82. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein (a) the VH domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 65, and the VL domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 66; (b) the VH domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 67, and the VL domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 68; (c) the VH domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 69, and the VL domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 70; or (d) the VH domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 71, and the VL domain comprises(e) the VH domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 73 and the VL domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 74; (f) the VH domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 75 and the VL domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 76; or (g) the VH domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 77. 90% sequence identity to the amino acid sequence of SEQ ID NO: 78, wherein the VL domain comprises an amino acid sequence that has at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 78; (h) the VH domain comprises an amino acid sequence that has at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 79, and the VL domain comprises an amino acid sequence that has at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 80; or (i) the VH domain comprises an amino acid sequence that has at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 81, and the VL domain comprises an amino acid sequence that has at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 82. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein (a) the VH domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 65, and the VL domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 66; (b) the VH domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 67, and the VL domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 68; (c) the VH domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 69, and the VL domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 70; or (d) the VH domain(e) the VL domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 71, and the VL domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 72; or (e) the VH domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 73, and (f) the VH domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 75 and the VL domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 76; or (g) the VH domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 77 and the VL domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 78. (h) the VH domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 79 and the VL domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 80; or (i) the VH domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 81 and the VL domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 82. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein (a) the VH domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 65 and the VL domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 66, or (b) the VH domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 67 and the VL domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 68. (c) the VH domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 69 and the VL domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 70; (d) the VH domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 71 and the VL domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 72;(e) the VH domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 73 and the VL domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 74; (f) the VH domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 75 and the VL domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 76; or (g) the VH domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 77; (h) the VH domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 79 and the VL domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 80; or (i) the VH domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 81 and the VL domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 82. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein (a) the VH domain comprises the amino acid sequence of SEQ ID NO: 65 and the VL domain comprises the amino acid sequence of SEQ ID NO: 66; (b) the VH domain comprises the amino acid sequence of SEQ ID NO: 67 and the VL domain comprises the amino acid sequence of SEQ ID NO: 68; (c) the VH domain comprises the amino acid sequence of SEQ ID NO: 69 and the VL domain comprises the amino acid sequence of SEQ ID NO: 70; or (d) the V (e) the H domain comprises the amino acid sequence of SEQ ID NO: 71 and the VL domain comprises the amino acid sequence of SEQ ID NO: 72; (f) the VH domain comprises the amino acid sequence of SEQ ID NO: 75 and the VL domain comprises the amino acid sequence of SEQ ID NO: 76; (g) the VH domain comprises the amino acid sequence of SEQ ID NO: 77 and the VL domain comprises the amino acid sequence of SEQ ID NO: 78;(h) the VH domain comprises the amino acid sequence of SEQ ID NO: 79 and the VL domain comprises the amino acid sequence of SEQ ID NO: 80, or (i) the VH domain comprises the amino acid sequence of SEQ ID NO: 81 and the VL domain comprises the amino acid sequence of SEQ ID NO: 82.

[0012] In some aspects, provided herein is an antibody that binds to human CD94. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 1, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 2, and CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 3, and the VL domain comprises CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 4, CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 5, and CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 6. In some embodiments, the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6. In some embodiments, the VH domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 19, and the VL domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 20. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 19, and the VL domain comprises the amino acid sequence of SEQ ID NO: 20.In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 7, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 8, and CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 9, and the VL domain comprises CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 10, CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 11, and CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 12. In some embodiments, the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO:7, CDR-H2 comprising the amino acid sequence of SEQ ID NO:8, and CDR-H3 comprising the amino acid sequence of SEQ ID NO:9, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO:10, CDR-L2 comprising the amino acid sequence of SEQ ID NO:11, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 12. In some embodiments, the VH domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:21, and the VL domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:22. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:21, and the VL domain comprises the amino acid sequence of SEQ ID NO:22.In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 13, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 14, and CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 15, and the VL domain comprises CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 16, CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 17, and CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 13, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 14, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 15, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 16, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 17, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 18. In some embodiments, the VH domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 23, and the VL domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 24. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 23, and the VL domain comprises the amino acid sequence of SEQ ID NO: 24. In some embodiments, the antibody is a human antibody.

[0013] In some aspects, provided herein are antibodies that bind to human CD94. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein (a) the VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 30, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 31, and CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 32, and the VL domain comprises CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 33, CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 35; or (b) the VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 36 and CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 37. (c) the VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 36, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 39, and CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 40, and the VL domain comprises CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 33, CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 35;(d) the VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 41, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 42, and CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 43, and the VL domain comprises CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 44, CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 45, and CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 46; or (e) the VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 47, (f) the VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 53, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 54, and CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 49, and the VL domain comprises CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 50, CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 51, and CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 52; or(g) the VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 57, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 58, and CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 59, and the VL domain comprises CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 60, CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 61. (h) the VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 83, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 84, and CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 86, CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 61; or (i) the VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 47 and CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 48;and CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 63, CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 64. In some embodiments, (a) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 30, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 31, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 32; and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 33, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 35; (b) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 36, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 37, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 38; and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 33, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 35; or (c) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 36, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 39. (d) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 41, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 42, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 43, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 44, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 45, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 46; or (e) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 47, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 48, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 49, and the VL domain comprises(f) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 53, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 54, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 55, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 50, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 45, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 56; or (g) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 57, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 58, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 59, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 60 and the amino acid sequence of SEQ ID NO: 34. (h) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 83, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 84, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 86, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 61; or (i) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 47, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 48, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 63, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 64. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein (a) the VH domain comprises a CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 87, a CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 88, and a CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises(b) the VH domain comprises a CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 90, a CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 91, and a CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 35, or (b) the VH domain comprises a CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 87, an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 92; a CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 93, and a CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises a CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 90, a CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 91, and a CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 35; or (c) the VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 87, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 92, and CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 94; and the VL domain comprises CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 90, and CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 91. (d) the VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 95, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 96, and an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 97; (e) a CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 109, wherein the VL domain comprises a CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 98, a CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 99, and a CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 100;and a CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 110, and a CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 114, wherein the VL domain comprises a CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 115, a CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 99, and a CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 52. or (f) the VH domain comprises a CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 116, a CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 117, and a CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 118, and the VL domain comprises a CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 115. (g) the VH domain comprises CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 99, CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 56, or (g) the VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 101, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 102, (h) the VH domain comprises CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 104, CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 91, and CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 61; or (h) the VH domain comprisesor (i) the VL domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 105, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 106, and CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 107, and the VL domain comprises CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 108, CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 91, and CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 61; The VH domain comprises CDR-H1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 109, CDR-H2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 110, and CDR-H3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 111, and the VL domain comprises CDR-L1 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 112, CDR-L2 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 113, and CDR-L3 comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 64. In some embodiments, (a) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 87, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 88, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 89; and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 90, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 91, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 35; or (b) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 87, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 92, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 93; and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 90, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 91;and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 350; (c) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 87, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 92, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 94, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 90, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 91, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 35; or (d) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 95, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 96 (e) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 109, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 110, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 114, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 115, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 116, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 117; (f) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 116, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 117, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 118, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 115, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 99, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 56; or (g) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 101. (h) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 105, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 106, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 107, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 104, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 91, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 61; oror (i) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 109, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 110, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 111, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 112, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 113, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 64. In some embodiments, (a) the VH domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 65, and the VL domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 66; (b) the VH domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 67, and the VL domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 68; (c) the VH domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 69, and the VL domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 70; or (d) the VH domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 71. (e) the VH domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 73 and the VL domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 74; (f) the VH domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 75 and the VL domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 76; or (g) the VH domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 77 and the VL domain comprises(h) the VH domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 79 and the VL domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 80; or (i) the VH domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 81; and the VL domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:82. In some embodiments, (a) the VH domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 65, and the VL domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 66; (b) the VH domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 67, and the VL domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 68; (c) the VH domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 69, and the VL domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 70; (d) the VH domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 71, and the VL domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 72; a) the VH domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 73, and the VL domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 74; (f) the VH domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 75, and the VL domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 76; (g) the VH domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 77, and the VL domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 78; (h) the VH domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 79, and the VL domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 80; or (i) the VH domainThe VL domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:81, and the VL domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:82. In some embodiments, (a) the VH domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 65, and the VL domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 66; (b) the VH domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 67, and the VL domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 68; (c) the VH domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 69, and the VL domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 70; or (d) the VH domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 71, and the VL domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 72. or (e) the VH domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 73 and the VL domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 74; (f) the VH domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 75 and the VL domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 76; (g) the VH domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 77 and the VL domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 78; or (h) the VH domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 79 and the VL domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 80;or (i) the VH domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 81, and the VL domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 82. In some embodiments, (a) the VH domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 65, and the VL domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 66; (b) the VH domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 67, and the VL domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 68; (c) the VH domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 69, and the VL domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 70; or (d) the VH domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 71, and the VL domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 72. (e) the VH domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 73 and the VL domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 74; (f) the VH domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 75 and the VL domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 76; (g) the VH domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 77 and the VL domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 78; or (h) the VH domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 79 and the VL domain comprisesor (i) the VH domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 81 and the VL domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 82. In some embodiments, (a) the VH domain comprises the amino acid sequence of SEQ ID NO: 65 and the VL domain comprises the amino acid sequence of SEQ ID NO: 66, (b) the VH domain comprises the amino acid sequence of SEQ ID NO: 67 and the VL domain comprises the amino acid sequence of SEQ ID NO: 68, (c) the VH domain comprises the amino acid sequence of SEQ ID NO: 69 and the VL domain comprises the amino acid sequence of SEQ ID NO: 70, (d) the VH domain comprises the amino acid sequence of SEQ ID NO: 71 and the VL domain comprises the amino acid sequence of SEQ ID NO: 72, or (e) the VH domain comprises the amino acid sequence of SEQ ID NO: 73. (f) the VH domain comprises the amino acid sequence of SEQ ID NO: 75 and the VL domain comprises the amino acid sequence of SEQ ID NO: 76; (g) the VH domain comprises the amino acid sequence of SEQ ID NO: 77 and the VL domain comprises the amino acid sequence of SEQ ID NO: 78; (h) the VH domain comprises the amino acid sequence of SEQ ID NO: 79 and the VL domain comprises the amino acid sequence of SEQ ID NO: 80; or (i) the VH domain comprises the amino acid sequence of SEQ ID NO: 81 and the VL domain comprises the amino acid sequence of SEQ ID NO: 82.

[0014] In a further aspect, provided herein is an antibody that binds to the same epitope as an antibody according to any one of the above embodiments. In some embodiments, an antibody of the present disclosure binds to the same epitope as a reference antibody. In some embodiments, the reference antibody comprises a VH domain comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3, and a VL domain comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6. In some embodiments, the reference antibody comprises a VH domain comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 7, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 8, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 9, and a VL domain comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 10, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 11, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 12. In some embodiments, the reference antibody comprises a VH domain comprising CDR-H1 comprising the amino acid sequence of SEQ ID NO: 13, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 14, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 15, and a VL domain comprising CDR-L1 comprising the amino acid sequence of SEQ ID NO: 16, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 17, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 18. In some embodiments, the reference antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein (a) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 30, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 31, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 32, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 33, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 35; or (b) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 36, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 37, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 38, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 33, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34,and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 35; (c) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 36, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 39, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 40, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 33, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 35; or (d) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 41 and the amino acid sequence of SEQ ID NO: 42. (e) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 47, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 48, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 49, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 50, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 51, (f) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 53, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 54, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 55, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 50, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 45, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 56; or (g) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 57, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 58, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 59. (h) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 83, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 84, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 86;or (i) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 47, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 48, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 63, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 64.

[0015] In a further aspect, provided herein is an antibody that competes with an antibody according to any one of the above embodiments for binding to human CD94. In some embodiments, an antibody of the present disclosure competes with a reference antibody for binding to human CD94. In some embodiments, the reference antibody comprises a VH domain comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3, and a VL domain comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6. In some embodiments, the reference antibody comprises a VH domain comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 7, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 8, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 9, and a VL domain comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 10, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 11, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 12. In some embodiments, the reference antibody comprises a VH domain comprising CDR-H1 comprising the amino acid sequence of SEQ ID NO: 13, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 14, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 15, and a VL domain comprising CDR-L1 comprising the amino acid sequence of SEQ ID NO: 16, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 17, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 18. In some embodiments, the reference antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein (a) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 30, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 31, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 32, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 33, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 35; or (b) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 36, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 37, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 38, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 33, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34,and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 35; (c) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 36, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 39, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 40, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 33, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 35; or (d) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 41 and the amino acid sequence of SEQ ID NO: 42. (e) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 47, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 48, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 49, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 50, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 51, (f) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 53, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 54, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 55, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 50, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 45, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 56; or (g) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 57, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 58, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 59. (h) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 83, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 84, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 86;or (i) the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 47, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 48, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 63, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 64.

[0016] In some embodiments according to any of the embodiments described herein, the antibody is an antigen-binding antibody fragment or a single-chain antibody. In some embodiments, the antibody further comprises an Fc region, e.g., a human IgG1 Fc region. In some embodiments, the antibody comprises a non-fucosylated human Fc region. In some embodiments, the antibody is produced in a cell line (e.g., a CHO cell line) lacking an alpha-1,6-fucosyltransferase gene, such as FUT8. In some embodiments, the antibody binds to human cell Fc gamma receptor IIIA to a greater extent than antibodies comprising a wild-type human IgG1 Fc region. In some embodiments, the antibody is capable of inducing antibody-dependent cellular cytotoxicity (ADCC) against cells expressing human CD94 on their surface.

[0017] In a further aspect, provided herein is a polynucleotide(s) encoding an antibody according to any one of the above embodiments. Further provided herein is a vector (e.g., an expression vector) comprising a polynucleotide(s) according to any one of the above embodiments. Further provided herein is a host cell (e.g., an isolated host cell or cell line) comprising a polynucleotide(s) or vector according to any one of the above embodiments. Further provided herein is a method for producing an antibody, comprising culturing a host cell according to any one of the above embodiments under conditions suitable for producing the antibody. In some embodiments, the method further comprises recovering the antibody from the host cell.

[0018] Further provided herein is a composition (eg, a pharmaceutical composition) comprising an antibody according to any one of the above embodiments and a pharmaceutically acceptable carrier.

[0019] In a further aspect, provided herein is a method for treating a disease or disorder in a subject, the method comprising administering to the subject an effective amount of an antibody or composition according to any one of the above embodiments. In some embodiments, administering the antibody results in a reduction in the number of peripheral blood LGL cells or NK cells in the subject. In some embodiments, the disease or disorder is Felty syndrome, and administering the antibody to a subject results in a reduction of one or more symptoms of Felty syndrome in the subject. In some embodiments, the disease or disorder is inclusion body myositis, and administering the antibody to a subject results in a reduction of one or more symptoms of inclusion body myositis in the subject. In some embodiments, the disease or disorder is aggressive NK leukemia, and administering the antibody to a subject results in a reduction of one or more symptoms of aggressive NK leukemia in the subject. In some embodiments, the disease or disorder is rheumatoid arthritis, and administering the antibody to a subject results in a reduction of one or more symptoms of rheumatoid arthritis in the subject. In some embodiments, the disease or disorder is LGL leukemia, and administering the antibody to a subject results in a reduction of one or more symptoms of LGL leukemia in the subject. In some embodiments, the disease or disorder is CLPD-NK, and administering the antibody to a subject results in a reduction of one or more symptoms of CLPD-NK in the subject. In some embodiments, the disease or disorder is natural killer (NK) cell lymphoma or T-cell lymphoma, and administering the antibody to a subject results in a reduction of one or more symptoms of lymphoma in the subject. In some embodiments, the NK cell lymphoma or T cell lymphoma is extranodal NK / T cell lymphoma, hepatosplenic T cell lymphoma (TCL), enteropathy-associated TCL, cutaneous TCL, anaplastic large cell lymphoma (ALK+), anaplastic large cell lymphoma (ALK-), peripheral TCL, angioimmunoblastic TCL, adult TCL, monomorphic epitheliotropic enteric TCL, epidermotropic CD8+ cutaneous TCL, primary cutaneous gamma / delta TCL, or subcutaneous panniculitis TCL. In some embodiments, the NK cell lymphoma or T cell lymphoma is extranodal NK / T cell lymphoma, hepatosplenic TCL, or enteropathy-associated TCL.In some embodiments, the disease or disorder is microscopic colitis, and administration of the antibody to a subject results in a reduction of one or more symptoms of microscopic colitis in the subject.

[0020] In a further aspect, provided herein is a method for reducing the number of peripheral blood LGL cells and / or NK cells in a subject, the method comprising administering to the subject an effective amount of an antibody or composition according to any one of the above embodiments. In a further aspect, provided herein is a method for inducing ADCC activity in a subject, the method comprising administering to the subject an effective amount of an antibody or composition according to any one of the above embodiments. In a further aspect, provided herein is a method for treating CLPD-NK in a human subject in need of CLPD-NK treatment, the method comprising administering to the subject an effective amount of an antibody or composition according to any one of the above embodiments. In some embodiments, administration of the antibody results in improvement of one or more symptoms of CLPD-NK in the subject.

[0021] In a further aspect, provided herein are methods of treating natural killer (NK) cell lymphoma or T cell lymphoma, the methods comprising administering to a subject in need thereof an effective amount of an antibody or composition according to any one of the above embodiments. In some embodiments, the antibody does not bind to the same epitope on human CD94 as the anti-CD94 antibody clones HP-3D9, HP-3B1, DX22, 131412, or 12K45. In some embodiments, the antibody binds to human CD94 with higher affinity than the anti-CD94 antibody clones HP-3D9, HP-3B1, DX22, 131412, and 12K45. In some embodiments, the NK cell lymphoma or T cell lymphoma is extranodal NK / T cell lymphoma, hepatosplenic T cell lymphoma (TCL), enteropathy-associated TCL, cutaneous TCL, anaplastic large cell lymphoma (ALK+), anaplastic large cell lymphoma (ALK-), peripheral TCL, angioimmunoblastic TCL, or adult TCL. In some embodiments, the NK cell lymphoma or T cell lymphoma is extranodal NK / T cell lymphoma, hepatosplenic TCL, or enteropathy-associated TCL.

[0022] In a further aspect, provided herein are methods of enhancing chimeric antigen receptor T-cell (CAR-T) therapy in a human subject in need thereof, the method comprising administering to the subject an effective amount of an antibody or composition according to any one of the above embodiments prior to administering CAR-T treatment to the subject. In some embodiments, administration of the antibody or composition results in depletion of NK cells in the subject prior to administering CAR-T treatment.

[0023] In a further aspect, provided herein is a method of depleting CD8+ CD94+ T cells in a human subject in need thereof, the method comprising administering to the subject an effective amount of an antibody or composition according to any one of the above embodiments. In some embodiments, administration of the antibody or composition results in depletion of CD8+ CD94+ T cells in the subject.

[0024] In some embodiments according to any of the embodiments described herein, the method further comprises administering an IL-2 polypeptide to the subject.

[0025] In some embodiments according to any of the embodiments described herein, the subject is a human.

[0026] In a further aspect, provided herein is an antibody or composition according to any one of the above embodiments for use in treating a disease or disorder in a subject, reducing the number of peripheral blood LGL cells and / or NK cells in a subject, treating CLPD-NK in a human subject in need thereof, treating natural killer (NK) cell lymphoma or T-cell lymphoma, treating microscopic colitis in a subject, or augmenting CAR-T therapy in a subject in need thereof. In some embodiments, the NK cell lymphoma or T cell lymphoma is extranodal NK / T cell lymphoma, hepatosplenic T cell lymphoma (TCL), enteropathy-associated TCL, cutaneous TCL, anaplastic large cell lymphoma (ALK+), anaplastic large cell lymphoma (ALK-), peripheral TCL, angioimmunoblastic TCL, adult TCL, monomorphic epitheliotropic enteric TCL, epidermotropic CD8+ cutaneous TCL, primary cutaneous gamma / delta TCL, or subcutaneous panniculitis TCL. In some embodiments, the NK cell lymphoma or T cell lymphoma is extranodal NK / T cell lymphoma, hepatosplenic TCL, or enteropathy-associated TCL.

[0027] In a further aspect, provided herein is the use of an antibody or composition according to any one of the above embodiments for the manufacture of a medicament for use in, e.g., treating a disease or disorder in a subject, reducing the number of peripheral blood LGL cells and / or NK cells in a subject, treating CLPD-NK in a human subject in need thereof, treating natural killer (NK) cell lymphoma or T cell lymphoma, treating microscopic colitis in a subject, or augmenting CAR-T therapy in a subject in need thereof. In some embodiments, the NK cell lymphoma or T cell lymphoma is extranodal NK / T cell lymphoma, hepatosplenic T cell lymphoma (TCL), enteropathy-associated TCL, cutaneous TCL, anaplastic large cell lymphoma (ALK+), anaplastic large cell lymphoma (ALK-), peripheral TCL, angioimmunoblastic TCL, or adult TCL. In some embodiments, the NK cell lymphoma or T cell lymphoma is extranodal NK / T cell lymphoma, hepatosplenic TCL, or enteropathy-associated TCL.

[0028] In a further aspect, provided herein is a kit or article of manufacture comprising an antibody or composition according to any one of the above embodiments. In some embodiments, the kit further comprises instructions for use of the kit, e.g., in treating a disease or disorder in a subject, reducing the number of peripheral blood LGL cells and / or NK cells in a subject, treating CLPD-NK in a human subject in need thereof, treating natural killer (NK) cell lymphoma or T-cell lymphoma, treating microscopic colitis in a subject, or augmenting CAR-T therapy in a subject in need thereof. In some embodiments, the NK cell lymphoma or T cell lymphoma is extranodal NK / T cell lymphoma, hepatosplenic T cell lymphoma (TCL), enteropathy-associated TCL, cutaneous TCL, anaplastic large cell lymphoma (ALK+), anaplastic large cell lymphoma (ALK-), peripheral TCL, angioimmunoblastic TCL, adult TCL, monomorphic epitheliotropic enteric TCL, epidermotropic CD8+ cutaneous TCL, primary cutaneous gamma / delta TCL, or subcutaneous panniculitis TCL. In some embodiments, the NK cell lymphoma or T cell lymphoma is extranodal NK / T cell lymphoma, hepatosplenic TCL, or enteropathy-associated TCL.

[0029] In some embodiments that may be combined with any of the preceding embodiments, an antibody of the present disclosure comprises six CDRs from a single antibody listed in Table 1 (e.g., antibody 18H3, 1M4, 1E4, ATX-122, ATX-123, ATX-124, ATX-125, ATX-126, ATX-127, ATX-128, ATX-129, or ATX-130). In some embodiments that may be combined with any of the preceding embodiments, an antibody of the present disclosure comprises a VH and VL domain from a single antibody listed in Table 2 (e.g., antibody 18H3, 1M4, 1E4, ATX-122, ATX-123, ATX-124, ATX-125, ATX-126, ATX-127, ATX-128, ATX-129, or ATX-130).

[0030] All references cited herein, including patent applications and publications, are incorporated by reference in their entirety.

[0031] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings. [Brief explanation of the drawings]

[0032] [Figure 1] This figure shows the affinity of the anti-CD94 antibody 18H3 for human primary natural killer (NK) cells, as measured by flow cytometry. Peripheral blood mononuclear cells (PBMCs) from healthy donor HD-40 were used for antibody staining. The 18H3 antibody was titrated from 100 nM to 0.046 nM at a 1:3 dilution and incubated with PBMCs. NK cells were identified based on flow scatter using CD3 and CD56 antibodies. The affinity of 18H3 was assessed using the binding of the 18H3 antibody to CD3+ and CD56 bright NK cells. Titration curves and EC50s were generated using Graphpad Prism. 18H3 bound to CD3+CD56 bright NK cells with an affinity of 2.6 nM. A human IgG1 isotype control (hIgG1) with a secondary antibody and the goat (Fab)2 fragment anti-human Fcy-specific secondary antibody AF647 alone (secondary Ab) were used as controls. [Figure 2] Figure 1 shows the binding of anti-CD94 antibodies to human primary NK cells as measured by flow cytometry. Anti-CD94 hybridoma supernatants were screened on human primary NK cells by flow cytometry. HP-3D9 is a commercial anti-CD94 antibody used as a positive control. Mouse IgG1, IgG2a, IgG2b, and IgG3 were used as negative controls. The anti-CD94 antibodies 18H3, 1M4, and 1E4 bound to CD94 expressed on human primary NK cells. [Figure 3]Figures A-B show the cross-reactivity of anti-CD94 antibodies to cynomolgus monkey CD94. Figure A shows the cross-reactivity of hybridoma antibodies to cynomolgus monkey CD94. Anti-CD94 hybridoma supernatants were screened for cross-reactivity to cynomolgus monkey CD94 by flow cytometry in cynomolgus monkey CD94-expressing HEK293 cells. HP-3D9 is a commercial anti-CD94 antibody used as a negative control. Mouse IgG1, IgG2a, IgG2b, and IgG3 were used as negative controls. 18H3, 1M4, and 1E4 cross-reacted with cynomolgus monkey CD94, while 20F2 is an example of another CD94 antibody clone that reacts with human CD94 but not with cynomolgus monkey CD94. Figure B shows the cross-reactivity of commercial antibodies to cynomolgus monkey CD94. Cynomolgus monkey cross-reactivity was tested using commercially available anti-CD94 antibodies. 18H3 was used as a positive control. The MFI of each antibody was normalized to the MFI of its respective isotype. Unlike 18H3, HP-3B1, 131412, 12K45, DX22, and HP-3D9 did not cross-react with cynomolgus monkey CD94. [Figure 4] This figure shows the results of an HLA-E tetramer blocking assay performed using anti-CD94 and a commercially available anti-CD94 antibody using flow cytometry. PBMCs from a healthy donor were incubated with anti-CD94 antibody. PE-labeled HLA-E tetramers were then incubated with the cell and antibody mixture and detected using flow cytometry. For HP-3B1, 131412, 12K45, DX22, 1M4, and 1E4, 2.5 μl of HLA-E tetramer reagent was used, while 5 μl was used for 18H3 and HP-3D9. Saturating concentrations of each antibody were used in the assay. Percent blocking was calculated as 100 - ((percent HLA-E positive for anti-CD94 antibody) / (percent HLA-E positive for isotype) × 100). The 18H3 and 1E4 antibodies did not block HLA-E binding to CD94. [Figure 5A]Figure 1 shows the results of competition assays performed to evaluate the 18H3 anti-CD94 antibody. For all competition assays, 18H3 was incubated with PBMCs at a concentration of 1.3 μg / ml. Figure 2 shows competition assays between 18H3 and commercially available anti-CD94 antibodies. Commercial anti-CD94 antibodies were titrated and incubated with PBMCs in parallel with 18H3. 18H3 was fluorescently tagged with AF647 and incubated with cells in parallel with 18H3-AF647. 18H3 only partially competed with HP-3D9 and did not compete with DX22, HP-3B1, 131412, and 12K45. These results suggest that the 18H3 antibody binds to an epitope not shared with the commercially available antibodies. [Figure 5B] Figure 1 shows the results of competition assays performed to evaluate the 18H3 anti-CD94 antibody. For all competition assays, 18H3 was incubated with PBMCs at a concentration of 1.3 μg / ml. Competition assays using 18H3 and other hybridoma anti-CD94 antibodies disclosed herein (1M4 and 1E4) are shown. To test competition between 18H3 and 1M4 / 1E4, 1M4 and 1E4 were incubated with cells at concentrations of 8.5 μg / ml and 11 μg / ml, respectively. 18H3 was fluorescently tagged with AF647 and incubated with cells in parallel with 18H3-AF647. 18H3 did not compete with 1E4 and 1M4. These results suggest that the 18H3 antibody binds to an epitope not shared with commercially available antibodies. [Figure 6A]

[0033] Figure 1 shows the results of a competition assay performed to evaluate the 1M4 anti-CD94 antibody. For all competition assays, 1M4 was incubated with PBMCs at a concentration of 8.5 μg / ml.

[0034] Figure 2 shows a competition assay between 1M4 and a commercially available anti-CD94 antibody. The commercially available anti-CD94 antibody was titrated and incubated with PBMCs in parallel with 1M4. The 1M4 antibody did not compete with the commercially available antibody. [Figure 6B]Figure 1 shows the results of a competition assay performed to evaluate the 1M4 anti-CD94 antibody. For all competition assays, 1M4 was incubated with PBMCs at a concentration of 8.5 μg / ml. Competition assays using 1M4 and 1E4 antibodies are shown. To test competition between 1M4 and 1E4, 1E4 was incubated with cells at a concentration of 11 μg / ml. 1M4 with an anti-mouse secondary antibody was incubated with cells in parallel with 1E4. The 1M4 antibody competed with 1E4. [Figure 7] The results of competition assays performed to evaluate the 1E4 anti-CD94 antibody are shown. For all competition assays, 1E4 was incubated with PBMCs at a concentration of 11 μg / ml. Commercially available anti-CD94 antibodies were titrated and incubated with PBMCs in parallel with 1E4. The 1E4 antibody did not compete with four of the five commercially available anti-CD94 antibodies tested, but partially competed with 12K45. [Figure 8A] Figure 1 shows the results of an anti-CD94 antibody internalization assay. Peripheral blood mononuclear cells (PBMCs) from healthy donors were incubated with unconjugated anti-CD94 antibodies for multiple time points ranging from 30 minutes to 24 hours. Cells were maintained at either 4°C to prevent internalization or 37°C to induce internalization. Results are shown for the commercially available antibodies HP-3D9 and DX22. The commercially available anti-CD94 antibodies were internalized in a time-dependent manner. [Figure 8B] Figure 1 shows the results of an anti-CD94 antibody internalization assay. Peripheral blood mononuclear cells (PBMCs) from healthy donors were incubated with unconjugated anti-CD94 antibodies for multiple time points ranging from 30 minutes to 24 hours. Cells were maintained at either 4°C to prevent internalization or 37°C to induce internalization. Results are shown for the 18H3, 1M4, and 1E4 antibodies. The 18H3, 1M4, and 1E4 antibodies were not significantly internalized upon binding to CD94. [Figure 9A]Figure 1 shows the results of an antibody-dependent cellular cytotoxicity (ADCC) assay using anti-CD94 antibodies from healthy donors. The 18H3 antibody was produced in Expi-CHO cells cultured in the presence of kifunensine, a potent inhibitor of the mannosidase I enzyme, and used to generate 18H3-KIF, which mimics nonfucosylated antibodies. PBMCs were plated in 96-well plates and incubated overnight in the presence of anti-CD94 antibodies at 10-fold dilutions ranging from 1 x 10 to 10 μg / ml. NK cell numbers were quantified by flow cytometry. NK cell numbers in the human IgG1 and anti-CD94 antibody treatment conditions were normalized to the number of NK cells from human IgG1-treated wells. Results are shown for an ADCC assay using the human IgG1 18H3 antibody. Human IgG1 18H3 depleted human primary NK cells in a concentration-dependent manner. [Figure 9B] Figure 1 shows the results of an antibody-dependent cellular cytotoxicity (ADCC) assay for anti-CD94 antibodies using PBMCs from healthy donors. Fucosylated 1E4 antibody was used in the ADCC assay. PBMCs were plated in a 96-well plate and incubated overnight in the presence of anti-CD94 antibodies at 10-fold dilutions ranging from 1 x 10-6 to 10 μg / ml. The number of NK cells was quantified by flow cytometry. The number of NK cells in the human IgG1 and anti-CD94 antibody treatment conditions was normalized to the number of NK cells from human IgG1-treated wells. The results of an ADCC assay using fucosylated 1E4 antibody are shown. Fucosylated 1E4 depleted human primary NK cells in a concentration-dependent manner. [Figure 10]This figure shows the results of an ADCC assay of anti-CD94 antibodies using PBMCs from a CLPD-NK patient. 18H3 was produced in Expi-CHO cells cultured in the presence of kifunensine, a potent inhibitor of the mannosidase I enzyme, to generate 18H3-KIF, a nonfucosylated antibody mimic. PBMCs were plated in 96-well plates and incubated overnight in the presence of anti-CD94 antibodies at 10-fold dilutions ranging from 1 x 10-6 to 10 µg / ml. The number of CD3-CD16+ leukemia cells was quantified by flow cytometry. The number of leukemia cells in the human IgG1 and anti-CD94 antibody treatment conditions was normalized to the number of leukemia cells from the human IgG1-treated wells. Partially nonfucosylated human IgG1 18H3 depleted human CLPD-NK leukemia cells in a concentration-dependent manner. [Figure 11] A summary of the properties and functional assessment of anti-CD94 antibodies compared to commercially available anti-CD94 antibodies is shown. [Figure 12]This figure shows the affinity of the anti-CD94 antibody ATX-130 for human primary natural killer (NK) cells, as well as the anti-CD94 antibody ATX-130-KIF for cynomolgus monkey primary natural killer (NK) cells, chronic NK cell lymphoproliferative disorder (CLPD-NK), and T-cell large granular lymphocytic leukemia (T-LGLL) cells, as measured by flow cytometry. The ATX-130 antibody was produced in Expi-CHO cells cultured in the presence of kifunensine, a potent inhibitor of the mannosidase I enzyme, and used to generate ATX-130-KIF, which mimics nonfucosylated antibodies. PBMCs from healthy donors were used for antibody staining. The ATX-130 antibody was titrated from 50 nM to 0.02 nM. A secondary anti-human antibody labeled with Alexa Fluor 647 was used to detect binding on CD3-CD56 bright NK cells. ATX-130-KIF antibody conjugated with Alexa Fluor 647 was titrated from 50 nM to 0.02 nM. T-LGLL cells were identified using CD3+CD16+ gating, while CLPD-NK cells were identified using a CD3-CD16+ gating strategy. Titration curves and EC50s were generated using Graphpad Prism. ATX-130 bound to CD3-CD56 bright NK cells with an affinity of 0.6 nM. ATX-130-KIF showed affinities of 1 nM on primary cynomolgus monkey NK cells, 1.4 nM on CLPD-NK cells, and 3 nM on T-LGLL cells. Fluorescently labeled human IgG1-KIF isotype-KIF antibody was used as a control. Arrows indicate the data points for ATX-130 and human IgG1-KIF. [Figure 13]Figure 1 shows the affinity of the anti-CD94 antibody ATX-130 for CD94 homodimers or heterodimers. BaF3 cells overexpressing CD94 homodimers (upper panel), CD94 / NKG2A heterodimers (lower left panel), and CD94 / NKG2C heterodimers (lower right panel) were incubated with unconjugated ATX-130 antibody at dilutions ranging from 50 nM to 0.02 nM. ATX-130 binding on the cells was detected using a secondary anti-human antibody labeled with Alexa Fluor 647. ATX-130 binds to CD94 homodimers, CD94 / NKG2A, and CD94 / NKG2C heterodimer BaF3 cells with affinities of 0.3, 0.8, and 1.8 nM, respectively. [Figure 14] Figure 1 shows IFN-gamma secretion on human NK cells in the presence of ATX-130 antibody, as assessed by ELISA. NK cells were isolated from PBMCs of healthy donors and cultured in the presence of ATX-130 with mouse IgG1 inactive Fc (mATX-130), human IgG1-KIF isotype control, ATX-130 (hATX-130), or vehicle alone. After 24 hours of incubation, cell culture supernatants were collected and ELISA was performed to detect secreted IFN-gamma. The ATX-130 concentration (10 μg / mL, 5 μg / mL, 1 μg / mL, or vehicle) is indicated above each bar and corresponds to the concentration indicated in the figure legend. [Figure 15] Figure 1 shows the results of competition assays performed to evaluate the ATX-130 anti-CD94 antibody. For all competition assays, ATX-130 was incubated with PBMCs at a concentration of 7.5 μg / ml. Commercially available anti-CD94 antibodies (clones HP-3D9, DX22, 131412, 12K45, and HP-3B1) were titrated and incubated with PBMCs in parallel with ATX-130. Competition was assessed by plotting the MFI of the titrated commercial anti-CD94 antibodies. ATX-130 does not compete with HP-3D9, DX22, 131412, 12K45, or HP-3B1. [Figure 16]Figure 1 shows the results of an HLA-E tetramer blocking assay performed using ATX-130-KIF and an isotype control antibody using flow cytometry. PBMCs from a healthy donor were incubated with ATX-130-KIF. PE-labeled HLA-E tetramers were then incubated with the cell and antibody mixture and detected by flow cytometry. A saturating concentration of ATX-130-KIF was used in the assay. Percent blocking was calculated as 100 - ((percent HLA-E positive for anti-CD94 antibody) / (percent HLA-E positive for isotype) x 100). Arrows indicate histograms of ATX-130-KIF and isotype. ATX-130-KIF did not block HLA-E binding to CD94. [Figure 17]

[0033] Figure 1 shows the results of an anti-CD94 antibody internalization assay. PBMCs from healthy donors were incubated with unconjugated ATX-130 for multiple time points ranging from 30 minutes to 24 hours. Cells were maintained at either 4°C to prevent internalization or 37°C to induce internalization. ATX-130 was not significantly internalized within 24 hours. [Figure 18] Figure 1 shows the binding of ATX-130-KIF to immune cell types as measured by flow cytometry. Immune cell types (monocytes, CD4 T cells, B cells, CD8 T cells, and NK cells) from PBMCs derived from normal human, cynomolgus monkey, and LGL leukemia patient samples were stained with ATX-130-KIF Alexa Fluor 647 (50 nM) and assessed for binding. ATX-130-KIF selectively binds to NK cells (CD3-CD56+ / CD16+), a subset of normal CD8 T cells (CD3+CD8+), and all LGL cells (CD3-CD16+). Arrows indicate histograms of ATX-130-KIF and isotypes. [Figure 19]Figure 1 shows the results of an ADCC assay for ATX-130-KIF using PBMCs from healthy donors. PBMCs from healthy donors were plated in 96-well plates and incubated with ATX-130 (titrated at 1:10 dilutions) for 24 hours. Depletion of different immune cell types was assessed by quantifying the number of remaining cells by flow cytometry. Arrows indicate ATX-130-KIF and isotype curves. ATX-130 depletes human NK cells with a potency of 0.8 ng / ml while sparing other immune cell types. [Figure 20] Figure 1 shows the results of an ADCC assay of anti-CD94 antibodies using cynomolgus monkey PBMCs. Cynomolgus monkey PBMCs were plated in a 96-well plate and incubated with ATX-130-KIF (titrated at 1:10 dilutions) for 24 hours. Depletion of different immune cell types (NK cells, CD8 T cells, CD4 T cells, and B cells) was assessed by quantitating the number of remaining cells by flow cytometry. Arrows indicate ATX-130-KIF and isotype curves. ATX-130-KIF depletes cynomolgus monkey NK cells with a potency of 0.3 ng / ml while sparing other immune cell types. [Figure 21] This figure shows the results of an ADCC assay of anti-CD94 antibodies using PBMCs from T-LGLL and CLPD-NK. PBMCs from T-LGLL and CLPD-NK were plated in a 96-well plate and incubated with ATX-130-KIF (titrated at 1:10 dilutions) for 24 hours. Depletion of different immune cell types was assessed by quantitating the number of remaining cells by flow cytometry. Arrows indicate the ATX-130-KIF and isotype curves. ATX-130-KIF depletes T-LGLL and CLPD-NK cells with potencies of 0.2 and 0.6 ng / ml, respectively, while sparing other immune cell types. [Figure 22A] 1 shows the study design examining the effect of ATK-130 or isotype control on humanized IL-15 transgenic mice engrafted with PBMCs from healthy human donors. [Figure 22B]Figure 1 shows depletion of normal human NK cells and CD8 T cells in IL-15 transgenic mice. Mice were transplanted with PBMCs from healthy donors for 3 days. Mice (5 mice per group) were injected with a single dose of human IgG1 isotype control or ATX-130 (5 mg / kg), and NK cell (upper panel) and CD8 T cell (lower panel) depletion in blood, spleen, and bone marrow was assessed by flow cytometry 48 hours post-dose. Depletion was quantified by the number of NK cells and CD8 T cells remaining in each sample. [Figure 23] Figure 1 shows depletion of LGLL cells in the blood, spleen, bone marrow, and liver in IL-15 transgenic mice. Mice were transplanted with LGLL PBMCs for 28 days. Mice (5 mice per group) were injected with a single dose of human IgG1 isotype control or ATX-130 (5 mg / kg), and LGLL cell depletion in the blood, spleen, bone marrow, and liver was assessed by flow cytometry 48 hours after dosing. Depletion was quantified by the number of CD94+ LGLL cells remaining in each sample. [Figure 24A] 1 shows the design of an exploratory pharmacodynamic (PD) study in non-human primates to evaluate the efficacy of ATK-130 in vivo. [Figure 24B] Figure 1 shows the in vivo depletion of cynomolgus monkey NK cells by dosing with ATX-130-KIF at 2 mg / kg, as assessed by flow cytometry. Two naive cynomolgus monkeys (cynomolgus monkey #1 and cynomolgus monkey #2) were administered ATX-130-KIF (2 mg / kg) via intravenous (IV) infusion over 60 minutes. Cynomolgus monkey #1 received an additional 2 mg / kg ATX-130-KIF at week 8 and week 16, respectively. Body weight and clinical observations were recorded periodically. PBMCs were isolated from 5 mL of blood drawn per animal per time point. 0.3 x 106 cells were plated per well in technical triplicates and stained with a panel of antibodies. A CD3-CD8+ gating strategy was used to identify cynomolgus monkey NK cells. NK cells were quantified by calculating the percentage of this cell population among total PBMCs. Arrows indicate the time points at which doses were administered. [Figure 25A] Figure 1 shows the assessment of depletion of cynomolgus monkey CD4 T cells, CD8 T cells, and B cells. PBMCs were isolated from 5 mL of blood drawn per time point from cynomolgus monkey #1. 0.3 x 10 cells were plated per well in technical triplicates and stained with a panel of antibodies. CD3+CD4+, CD3+CD8+, and CD3-CD20+ gating strategies were used to identify CD4+ T cells, CD8+ T cells, and B cells, respectively, from cynomolgus monkey #1. Cells were quantified by calculating the percentage of the cell populations among total PBMCs. [Figure 25B] Figure 1 shows the assessment of depletion of cynomolgus monkey CD4 T cells, CD8 T cells, and B cells. PBMCs were isolated from 5 mL of blood drawn per time point from cynomolgus monkey #2. 0.3 x 10 cells were plated per well in technical triplicates and stained with a panel of antibodies. CD3+CD4+, CD3+CD8+, and CD3-CD20+ gating strategies were used to identify CD4+ T cells, CD8+ T cells, and B cells, respectively, from cynomolgus monkey #2. Cells were quantified by calculating the percentage of the cell populations among total PBMCs. [Figure 26] Results of monocyte depletion assessment by flow cytometry are shown. PBMCs were isolated from 5 mL of blood drawn per time point from cynomolgus monkey #1 (left panel) and cynomolgus monkey #2 (right panel). 0.3 x 10 cells were plated per well in technical triplicates and stained with a panel of antibodies. A CD3-CD14+ gating strategy was used to identify monocytes. Cells were quantified by calculating the percentage of the cell population among all PBMCs. [Figure 27] Figure 1 shows the results of assessing CD16 expression on monocytes by flow cytometry. PBMCs were isolated from 5 mL blood draws per time point for cynomolgus monkey #1 (left panel) and cynomolgus monkey #2 (right panel). 0.3 x 106 cells were plated per well in technical triplicates and stained with a panel of antibodies. A CD3-CD14+ gating strategy was used to identify monocytes. CD16 MFI was assessed in monocytes. [Figure 28A] 1 shows the design of a non-GLP PD study in non-human primates to evaluate the efficacy of ATK-130 in vivo. [Figure 28B] Figure 1 shows the in vivo depletion of cynomolgus monkey NK cells by dosing with ATX-130 at 5, 50, and 100 mg / kg. PBMCs were isolated from 0.5 mL of blood drawn per animal per time point. 0.3 x 10 cells were plated per well in technical triplicates and stained with a panel of antibodies. A CD3-CD16+ gating strategy was used to identify cynomolgus monkey NK cells. NK cells were quantified by calculating the percentage of the cell population among total PBMCs. [Figure 29] Figure 1 shows in vivo depletion of cynomolgus monkey CD94+CD8+NKG2A+ cells by dosing with ATX-130 at 5, 50, and 100 mg / kg. PBMCs were isolated from 0.5 mL of blood drawn per animal per time point. 0.3 x 106 cells were plated per well in technical triplicates and stained with a panel of antibodies. A CD3+CD8+NKG2A+ gating strategy was used to identify cynomolgus monkey CD8+ T cells. CD8 T cells were quantified by calculating the percentage of this cell population among total PBMCs. The identifiers above each bar indicate the time point at which PBMCs were isolated and correspond to the time points depicted in the figure legend. [Figure 30] Figure 1 shows the in vivo depletion of cynomolgus monkey NK cells and CD94+CD8+NKG2A+ T cells by dosing with ATX-130 at 5, 50, and 100 mg / kg or vehicle control at 0 mg / kg in Dulbecco's phosphate-buffered saline (PBS). At study endpoint, duodenum, liver, spleen, and bone marrow were harvested. Tissues were dissociated into single-cell suspensions, and 0.3 x 106 cells were plated per well in technical triplicates and stained with a panel of antibodies. A CD3+CD8+NKG2A+ gating strategy was used to identify cynomolgus monkey CD8+ T cells. The CD45+CD3-NKG2A+ marker was used to identify cynomolgus monkey NK cells. The identifiers above each boxplot indicate the antibodies used in the experiment. [Figure 31A]Figure 1 shows the binding of the indicated anti-CD94 antibodies to normal human NK cells. Antibodies are indicated by ATX numbers. The results showed that the ATX-numbered anti-CD94 antibodies bound to human NK cells. [Figure 31B] Figure 1 shows binding of the indicated anti-CD94 antibodies to HEK293 cells expressing cynomolgus monkey CD94. Antibodies are indicated by ATX numbers. The results showed that the ATX-numbered anti-CD94 antibodies bound to cells expressing cynomolgus monkey CD94. [Figure 32A] This figure shows the results of an HLA-E tetramer-blocking assay to determine whether the indicated anti-CD94 antibodies block HLA-E binding. PBMCs from a healthy donor were incubated with the anti-CD94 antibodies. PE-labeled HLA-E tetramers were then incubated with the cell and antibody mixture and detected by flow cytometry. [Figure 32B] This figure shows the results of an HLA-E tetramer-blocking assay to determine whether the indicated anti-CD94 antibodies block HLA-E binding. PBMCs from a healthy donor were incubated with the anti-CD94 antibodies. PE-labeled HLA-E tetramers were then incubated with the cell and antibody mixture and detected by flow cytometry. [Figure 32C] This figure shows the results of an HLA-E tetramer-blocking assay to determine whether the indicated anti-CD94 antibodies block HLA-E binding. PBMCs from a healthy donor were incubated with the anti-CD94 antibodies. PE-labeled HLA-E tetramers were then incubated with the cell and antibody mixture and detected by flow cytometry. [Figure 32D] This figure shows the results of an HLA-E tetramer-blocking assay to determine whether the indicated anti-CD94 antibodies block HLA-E binding. PBMCs from a healthy donor were incubated with the anti-CD94 antibodies. PE-labeled HLA-E tetramers were then incubated with the cell and antibody mixture and detected by flow cytometry. [Figure 32E]This figure shows the results of an HLA-E tetramer-blocking assay to determine whether the indicated anti-CD94 antibodies block HLA-E binding. PBMCs from a healthy donor were incubated with the anti-CD94 antibodies. PE-labeled HLA-E tetramers were then incubated with the cell and antibody mixture and detected by flow cytometry. [Figure 32F] This figure shows the results of an HLA-E tetramer-blocking assay to determine whether the indicated anti-CD94 antibodies block HLA-E binding. PBMCs from a healthy donor were incubated with the anti-CD94 antibodies. PE-labeled HLA-E tetramers were then incubated with the cell and antibody mixture and detected by flow cytometry. [Figure 32G] This figure shows the results of an HLA-E tetramer-blocking assay to determine whether the indicated anti-CD94 antibodies block HLA-E binding. PBMCs from a healthy donor were incubated with the anti-CD94 antibodies. PE-labeled HLA-E tetramers were then incubated with the cell and antibody mixture and detected by flow cytometry. [Figure 32H] This figure shows the results of an HLA-E tetramer-blocking assay to determine whether the indicated anti-CD94 antibodies block HLA-E binding. PBMCs from a healthy donor were incubated with the anti-CD94 antibodies. PE-labeled HLA-E tetramers were then incubated with the cell and antibody mixture and detected by flow cytometry. [Figure 32I] This figure shows the results of an HLA-E tetramer-blocking assay to determine whether the indicated anti-CD94 antibodies block HLA-E binding. PBMCs from a healthy donor were incubated with the anti-CD94 antibodies. PE-labeled HLA-E tetramers were then incubated with the cell and antibody mixture and detected by flow cytometry. DETAILED DESCRIPTION OF THE INVENTION

[0033] For illustrative purposes, several aspects are described below with reference to example applications. It should be understood that numerous specific details, relationships, and methods are described to provide a thorough understanding of the features described herein. However, one skilled in the art will readily recognize that the features described herein can be implemented without one or more of the specific details or using other methods. The features described herein are not limited by the order of the illustrated acts or events, as some acts can occur in different orders and / or simultaneously with other acts or events. Furthermore, not all illustrated acts or events are required to implement a methodology in accordance with the features described herein.

[0034] As used herein, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly dictates otherwise. Furthermore, to the extent the terms "including," "includes," "having," "has," "with," or variations thereof are used in either the detailed description and / or claims, such terms are intended to be inclusive in a manner similar to the term "comprising." As used herein, the term "comprising" is synonymous with "including" or "containing," and is inclusive or open-ended.

[0035] Any reference to "or" herein is intended to include "and / or" unless otherwise specified. As used herein, the term "about" in reference to a number refers to that number plus or minus 10% of that number. The term "about" in reference to a range refers to that range plus or minus 10% of its lower limit and plus 10% of its upper limit.

[0036] I. Antibodies In some embodiments, provided herein are antibodies that bind to CD94, e.g., human CD94 expressed on the surface of NK cells or T cells. Also provided herein are antibodies that bind to CD94 and have an immunoglobulin Fc portion with modifications, including reduced fucosylation, afucosylation, or mutations that enhance ADCC activity and / or improve affinity of the Fc region for an Fc receptor, such as CD16 (e.g., CD16a). Also provided herein are antibodies that bind to CD94 and have one or more of the following properties: bind to human CD94 and cynomolgus CD94, do not block HLA-E binding to the CD94 / NKG2A heterodimer, have low target (e.g., CD94) internalization, are afucosylated or have reduced fucosylation, and / or induce or promote ADCC activity.

[0037] A. Antibody Targets and Affinity In some embodiments, the antibodies provided herein bind to CD94. In some embodiments, the antibodies provided herein bind to human CD94 (e.g., the extracellular domain of human CD94). In some embodiments, the antibodies provided herein bind to cynomolgus CD94 (e.g., the extracellular domain of cynomolgus CD94). In some embodiments, the antibodies provided herein bind to human CD94 and cynomolgus CD94. In some embodiments, the antibodies of the present disclosure bind to CD94 on the surface of NK cells and / or T cells.

[0038] In some embodiments, antibodies of the present disclosure bind to human CD94 protein or a portion thereof, or a protein having at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) homology to human CD94 protein or a portion thereof. The amino acid sequences of representative human CD94 proteins are provided as SEQ ID NOs:25-27. [ka]

[0039] In some embodiments, the terms bind, specifically bind to, or specific for refer to a measurable and reproducible interaction, such as binding between a target and an antibody, that determines the presence of the target in the presence of a heterogeneous population of molecules, including biomolecules. For example, an antibody that binds to or specifically binds to a target (which may be an epitope) is an antibody that binds to this target with higher affinity, avidity, more readily, and / or with longer duration than it binds to other targets. In one embodiment, the extent of binding of an antibody to an unrelated target is less than about 10% of the binding of the antibody to the target, as measured, for example, by radioimmunoassay (RIA). In certain embodiments, an antibody that specifically binds to a target has a dissociation constant (K) of <1 μM, <100 nM, <10 nM, <1 nM, or <0.1 nM. D ) In certain embodiments, the antibody specifically binds to an epitope on a protein that is conserved among proteins of different species. In another embodiment, specific binding can include, but does not require, exclusive binding.

[0040] In some embodiments, the antibodies provided herein bind to human CD94 (natural killer cell antigen CD94; CD94 Entrez Gene ID: 3824; KLRD1 (HGNC symbol); UniProtKB identifier: Q13241; HGNC: 6378; Ensembl: ENSG00000134539 OMIM: 602894; KP43).

[0041] In some embodiments, an antibody of the present disclosure binds to a cynomolgus monkey CD94 protein or a portion thereof, or a protein having at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) homology to a cynomolgus monkey CD94 protein or a portion thereof. The amino acid sequence of the cynomolgus monkey CD94 protein is known in the art (e.g., UniProtKB identifier: Q68VD4).

[0042] In certain embodiments, the affinity of an antibody for its target (e.g., CD94) can be determined by the dissociation constant (K D Affinity can be measured using assays described herein (e.g., in the Examples) by common methods known in the art, such as flow cytometry or Western blotting. In some embodiments, K D is measured using a radiolabeled antigen binding assay (RIA) performed with the Fab version of an antibody of the disclosure and its target (e.g., CD94). In some embodiments, K D is measured using a surface plasmon resonance assay. A representative assay is described, for example, in Drake, A W and Klakamp, ​​S L (2007) J. Immunol. Methods 318:147-152.

[0043] In some embodiments, the binding of an antibody of the present disclosure to CD94, e.g., human CD94 and / or cynomolgus CD94, may be assessed using any method known in the art. For example, the binding of an antibody of the present disclosure to human CD94 may be assessed in an ex vivo flow cytometry-based assay using peripheral blood mononuclear cells (PMBCs) and / or NK cells, e.g., as described in the Examples. Titration curves and EC50s may be generated and evaluated using methods known in the art, such as using Graphpad Prism. In another example, the binding of an antibody of the present disclosure to cynomolgus CD94 may be assessed in an ex vivo or in vitro flow cytometry-based assay using cynomolgus CD94-expressing cells, e.g., cynomolgus CD94-expressing HEK293 cells, e.g., as described in the Examples.

[0044] In certain embodiments, an antibody of the disclosure has a K of less than about 10 μM for binding to its target (e.g., human and / or cynomolgus CD94). D In certain embodiments, an antibody of the disclosure has a K of less than about 1 μM for binding to its target (e.g., human and / or cynomolgus CD94). D In certain embodiments, an antibody of the disclosure has a binding affinity to its target (e.g., human and / or cynomolgus monkey CD94) of less than about 1000 nM, less than about 900 nM, less than about 800 nM, less than about 700 nM, less than about 600 nM, less than about 500 nM, less than about 400 nM, less than about 300 nM, less than about 200 nM, less than about 100 nM, less than about 90 nM, a K of less than about 80 nM, less than about 70 nM, less than about 60 nM, less than about 50 nM, less than about 40 nM, less than about 30 nM, less than about 20 nM, less than about 10 nM, less than about 9 nM, less than about 8 nM, less than about 7 nM, less than about 6 nM, less than about 5 nM, less than about 4 nM, less than about 3 nM, less than about 2 nM, less than about 1 nM, less than about 0.5 nM, or less than about 0.1 nM DIn some embodiments, an antibody of the disclosure has a K of less than about 100 pM, less than about 75 pM, less than about 50 pM, less than about 25 pM, less than about 10 pM, less than about 5 pM, less than about 1 pM, less than about 0.5 pM, or less than about 0.1 pM for binding to its target (e.g., human and / or cynomolgus CD94). D It has.

[0045] In certain embodiments, an antibody of the disclosure has a K of less than about 100 nM, less than about 90 nM, less than about 80 nM, less than about 70 nM, less than about 60 nM, less than about 50 nM, less than about 40 nM, less than about 30 nM, less than about 20 nM, less than about 10 nM, less than about 9 nM, less than about 8 nM, less than about 7 nM, less than about 6 nM, less than about 5 nM, less than about 4 nM, less than about 3 nM, less than about 2 nM, less than about 1 nM, less than about 0.5 nM, or less than about 0.1 nM for binding to human CD94 on human NK cells or T cells. D In certain embodiments, an antibody of the disclosure has a K of less than about 75 nM, less than about 80 nM, less than about 70 nM, less than about 60 nM, less than about 50 nM, less than about 40 nM, less than about 30 nM, less than about 20 nM, less than about 10 nM, less than about 9 nM, less than about 8 nM, less than about 7 nM, less than about 6 nM, less than about 5 nM, less than about 4 nM, less than about 3 nM, less than about 2 nM, less than about 1 nM, less than about 0.5 nM, or less than about 0.1 nM with respect to binding to human CD94 on human NK cells or T cells. D In certain embodiments, the antibodies of the disclosure have a K of about 2 nM to about 80 nM for binding to human CD94 on human NK cells or T cells. D It has.

[0046] In certain embodiments, an antibody of the disclosure has a K of less than about 100 nM, less than about 90 nM, less than about 80 nM, less than about 70 nM, less than about 60 nM, less than about 50 nM, less than about 40 nM, less than about 30 nM, less than about 20 nM, less than about 10 nM, less than about 9 nM, less than about 8 nM, less than about 7 nM, less than about 6 nM, less than about 5 nM, less than about 4 nM, less than about 3 nM, less than about 2 nM, less than about 1 nM, less than about 0.5 nM, or less than about 0.1 nM for binding to cynomolgus CD94 on cells expressing cynomolgus CD94. D In certain embodiments, antibodies of the disclosure have a K of less than about 75 nM, less than about 80 nM, less than about 70 nM, less than about 60 nM, less than about 50 nM, less than about 40 nM, less than about 30 nM, less than about 20 nM, less than about 10 nM, less than about 9 nM, less than about 8 nM, less than about 7 nM, less than about 6 nM, less than about 5 nM, less than about 4 nM, less than about 3 nM, less than about 2 nM, less than about 1 nM, less than about 0.5 nM, or less than about 0.1 nM for binding to cynomolgus CD94 on cells expressing cynomolgus CD94. D In certain embodiments, antibodies of the disclosure have a K of about 2 nM to about 80 nM for binding to cynomolgus monkey CD94 on cells expressing cynomolgus monkey CD94. D It has.

[0047] In some embodiments, an antibody of the present disclosure binds to its target (e.g., CD94) at the same or a different epitope as an antibody known in the art for that target. In some embodiments, an antibody of the present disclosure binds to a different epitope than an antibody known in the art. In some embodiments, an antibody of the present disclosure specifically binds to human CD94, and the antibody does not bind to the same epitope on human CD94 as anti-CD94 antibody clones HP-3D9, DX22, HP-3B1, 131412, or 12K45. In some embodiments, an antibody of the present disclosure specifically binds to human CD94, and the antibody does not bind to the same epitope on human CD94 as anti-CD94 antibody clones DX22, HP-3B1, or 131412. In some embodiments, an antibody of the present disclosure specifically binds to human CD94, and the antibody binds to the same epitope on human CD94 as anti-CD94 antibody clone HP-3D9, DX22, HP-3B1, 131412, or 12K45. In some embodiments, an antibody of the present disclosure specifically binds to human CD94, and the antibody binds to the same epitope on human CD94 as anti-CD94 antibody clone HP-3D9. In some embodiments, an antibody of the present disclosure specifically binds to human CD94, and the antibody binds to the same epitope on human CD94 as anti-CD94 antibody clone 12K45.

[0048] In some embodiments, if an antibody of the present disclosure does not bind to a target (e.g., CD94) at the same epitope as another antibody to that target, e.g., a commercially available antibody or an antibody known in the art for that target, the antibody of the present disclosure does not block binding of the other antibody to the target in a competition assay (e.g., as described in the Examples), e.g., by 50% or more.

[0049] In some embodiments, an antibody of the present disclosure binds to its target (e.g., CD94) with higher affinity than antibodies known in the art for that target. In some embodiments, an antibody of the present disclosure binds to its target (e.g., CD94) with higher affinity than anti-CD94 antibody clones HP-3D9, DX22, HP-3B1, 131412, or 12K45. In some embodiments, an antibody of the present disclosure binds to its target (e.g., CD94) with higher affinity than anti-CD94 antibody clones HP-3B1, 131412, or 12K45.

[0050] In some embodiments, an antibody of the present disclosure specifically binds to human CD94, wherein the antibody binds to human CD94 with greater affinity than the anti-CD94 antibody clones HP-3D9, DX22, HP-3B1, 131412, or 12K45. In some embodiments, an antibody of the present disclosure specifically binds to human CD94, wherein the antibody binds to human CD94 with greater affinity than the anti-CD94 antibody clones HP-3B1, 131412, or 12K45.

[0051] In some embodiments, an antibody of the disclosure binds to its target (e.g., CD94) with an affinity that is at least 1.5 times, at least 2 times, at least 2.5 times, at least 3 times, at least 3.5 times, at least 4 times, at least 4.5 times, at least 5 times, at least 5.5 times, at least 6 times, at least 6.5 times, at least 7 times, at least 7.5 times, at least 8 times, at least 8.5 times, at least 9 times, at least 9.5 times, at least 10 times, or more, higher than another antibody known in the art for that target.

[0052] B. Representative anti-CD94 antibodies In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain has an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 100%, at least 101%, at least 102%, at least 103%, at least 104%, at least 105%, at least 106%, at least 107%, at least 108%, at least 109%, at least 110%, at least 111%, at least 112%, at least 113%, at least 114%, at least 115%, at least 116%, at least 117%, at least 118%, at least 119%, at least 119%, at least 120%, at least 121%, at least 122%, at least 123%, at least 124%, at least 125%, at least 126%, at least 127%, at least 128%, at least 129%, at least 129%. CDR-H1 comprising an amino acid sequence having at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:2, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:2. and CDR-H2 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:3. a CDR-L1 comprising a DR-H3, wherein the VL domain comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:4;a CDR-L2 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:5; and and a CDR-L3 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:6.

[0053] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 1, CDR-H2 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 2, and CDR-H3 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 3, and the VL domain comprises CDR-L1 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 4, CDR-L2 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 5, and CDR-L3 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 6.

[0054] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0055] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain has a sequence identity that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or similar to the amino acid sequence of SEQ ID NO: 19. and the VL domain comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:20.

[0056] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 19 and the VL domain comprises the amino acid sequence of SEQ ID NO: 20.

[0057] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain has a sequence identity at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least CDR-H1 comprising an amino acid sequence having 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO:8, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:8. and CDR-H2 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 9. R-H3, wherein the VL domain comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 10;a CDR-L2 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 11; and and a CDR-L3 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 12.

[0058] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 7, CDR-H2 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 8, and CDR-H3 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 9, and the VL domain comprises CDR-L1 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 10, CDR-L2 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 11, and CDR-L3 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 12.

[0059] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 7, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 8, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 9, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 10, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 11, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 12.

[0060] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain has a sequence identity that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or similar to the amino acid sequence of SEQ ID NO: 21. and the VL domain comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:22.

[0061] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 21 and the VL domain comprises the amino acid sequence of SEQ ID NO: 22.

[0062] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain has an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 100%, at least 101%, at least 102%, at least 103%, at least 104%, at least 105%, at least 106%, at least 107%, at least 108%, at least 109%, at least 110%, at least 111%, at least 112%, at least 113%, at least 114%, at least 115%, at least 116%, at least 117%, at least 118%, at least 119%, at least 119%, at least 120%, at least 121%, at least 122%, at least 123%, at least 124%, at least 125%, at least 126%, at least 127%, at least 128%, at least 129%, at least 129%. CDR-H1 comprising an amino acid sequence having at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 14, CDR-H1 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 14. and CDR-H2 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 15. a CDR-L1 comprising a DR-H3, wherein the VL domain comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 16;a CDR-L2 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 17; and and a CDR-L3 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 18.

[0063] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 13, CDR-H2 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 14, and CDR-H3 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 15, and the VL domain comprises CDR-L1 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 16, CDR-L2 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 17, and CDR-L3 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 18.

[0064] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 13, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 14, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 15, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 16, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 17, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 18.

[0065] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain has a sequence identity that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or similar to the amino acid sequence of SEQ ID NO: 23. and the VL domain comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:24.

[0066] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 23 and the VL domain comprises the amino acid sequence of SEQ ID NO: 24.

[0067] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain has an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 100%, at least 101%, at least 102%, at least 103%, at least 104%, at least 105%, at least 106%, at least 107%, at least 108%, at least 109%, at least 110%, at least 111%, at least 112%, at least 113%, at least 114%, at least 115%, at least 116%, at least 117%, at least 118%, at least 119%, at least 119%, at least 120%, at least 121%, at least 122%, at least 123%, at least 124%, at least 125%, at least 126%, at least 127%, at least 128%, at least 129%, at least 129%. CDR-H1 comprising an amino acid sequence having at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 31, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 31. and CDR-H2 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 32. a CDR-L1 comprising a DR-H3, wherein the VL domain comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 33;a CDR-L2 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 34; and and a CDR-L3 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 35.

[0068] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 30, CDR-H2 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 31, and CDR-H3 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 32, and the VL domain comprises CDR-L1 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 33, CDR-L2 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 35.

[0069] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 30, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 31, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 32, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 33, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 35.

[0070] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain has a sequence identity that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or similar to the amino acid sequence of SEQ ID NO: 65. and the VL domain comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:66.

[0071] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 65 and the VL domain comprises the amino acid sequence of SEQ ID NO: 66.

[0072] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain has an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 100%, at least 101%, at least 102%, at least 103%, at least 104%, at least 105%, at least 106%, at least 107%, at least 108%, at least 109%, at least 110%, at least 111%, at least 112%, at least 113%, at least 114%, at least 115%, at least 116%, at least 117%, at least 118%, at least 119%, at least 119%, at least 119%, at least 120%, at least 121%, at least 122%, at least 123%, at least 124%, at least 125%, at least 126%, at least 127%, at least 128%, at least 129%, at least 129%. CDR-H1 comprising an amino acid sequence having at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 37, CDR-H1 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 37. and CDR-H2 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 38. a CDR-L1 comprising a DR-H3, wherein the VL domain comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 33;a CDR-L2 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 34; and and a CDR-L3 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 35.

[0073] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 36, CDR-H2 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 37, and CDR-H3 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 38, and the VL domain comprises CDR-L1 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 33, CDR-L2 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 35.

[0074] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 36, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 37, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 38, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 33, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 35.

[0075] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain has a sequence identity that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or similar to the amino acid sequence of SEQ ID NO: 67. and the VL domain comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:68.

[0076] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 67 and the VL domain comprises the amino acid sequence of SEQ ID NO: 68.

[0077] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain has an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 100%, at least 101%, at least 102%, at least 103%, at least 104%, at least 105%, at least 106%, at least 107%, at least 108%, at least 109%, at least 110%, at least 111%, at least 112%, at least 113%, at least 114%, at least 115%, at least 116%, at least 117%, at least 118%, at least 119%, at least 119%, at least 119%, at least 120%, at least 121%, at least 122%, at least 123%, at least 124%, at least 125%, at least 126%, at least 127%, at least 128%, at least 129%, at least 129%. CDR-H1 comprising an amino acid sequence having at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 39, CDR-H1 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 39. and CDR-H2 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 40. a CDR-L1 comprising a DR-H3, wherein the VL domain comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 33;a CDR-L2 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 34; and and a CDR-L3 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 35.

[0078] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 36, CDR-H2 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 39, and CDR-H3 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 40, and the VL domain comprises CDR-L1 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 33, CDR-L2 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 35.

[0079] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 36, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 39, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 40, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 33, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 35.

[0080] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain has a sequence identity that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or similar to the amino acid sequence of SEQ ID NO: 69. and wherein the VL domain comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:70.

[0081] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 69 and the VL domain comprises the amino acid sequence of SEQ ID NO: 70.

[0082] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain has an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 100%, at least 101%, at least 102%, at least 103%, at least 104%, at least 105%, at least 106%, at least 107%, at least 108%, at least 109%, at least 110%, at least 111%, at least 112%, at least 113%, at least 114%, at least 115%, at least 116%, at least 117%, at least 118%, at least 119%, at least 119%, at least 120%, at least 121%, at least 122%, at least 123%, at least 124%, at least 125%, at least 126%, at least 127%, at least 128%, at least 129%, at least 129%. CDR-H1 comprising an amino acid sequence having at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:42, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:42. and CDR-H2 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 43. a CDR-L1 comprising a DR-H3, wherein the VL domain comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:44;a CDR-L2 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 45; and and a CDR-L3 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:46.

[0083] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 41, CDR-H2 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 42, and CDR-H3 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 43; and the VL domain comprises CDR-L1 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 44, CDR-L2 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 45, and CDR-L3 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 46.

[0084] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 41, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 42, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 43, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 44, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 45, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 46.

[0085] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain has a sequence identity that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or similar to the amino acid sequence of SEQ ID NO: 71. and wherein the VL domain comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:72.

[0086] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 71 and the VL domain comprises the amino acid sequence of SEQ ID NO: 72.

[0087] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain has an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 100%, at least 101%, at least 102%, at least 103%, at least 104%, at least 105%, at least 106%, at least 107%, at least 108%, at least 109%, at least 110%, at least 111%, at least 112%, at least 113%, at least 114%, at least 115%, at least 116%, at least 117%, at least 118%, at least 119%, at least 119%, at least 120%, at least 121%, at least 122%, at least 123%, at least 124%, at least 125%, at least 126%, at least 127%, at least 128%, at least 129%, at least 129%. CDR-H1 comprising an amino acid sequence having at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:48, CDR-H1 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:48. and CDR-H2 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:49. a CDR-L1 comprising a DR-H3, wherein the VL domain comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 50;a CDR-L2 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 51; and and a CDR-L3 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 52.

[0088] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 47, CDR-H2 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 48, and CDR-H3 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 49, and the VL domain comprises CDR-L1 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 50, CDR-L2 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 51, and CDR-L3 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 52.

[0089] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 47, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 48, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 49, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 50, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 51, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 52.

[0090] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain has a sequence identity that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or similar to the amino acid sequence of SEQ ID NO: 73. and wherein the VL domain comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:74.

[0091] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 73 and the VL domain comprises the amino acid sequence of SEQ ID NO: 74.

[0092] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain has an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 100%, at least 101%, at least 102%, at least 103%, at least 104%, at least 105%, at least 106%, at least 107%, at least 108%, at least 109%, at least 110%, at least 111%, at least 112%, at least 113%, at least 114%, at least 115%, at least 116%, at least 117%, at least 118%, at least 119%, at least 119%, at least 120%, at least 121%, at least 122%, at least 123%, at least 124%, at least 125%, at least 126%, at least 127%, at least 128%, at least 129%, at least 129%. CDR-H1 comprising an amino acid sequence having at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:54, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:54. and CDR-H2 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 55. a CDR-L1 comprising a DR-H3, wherein the VL domain comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 50;a CDR-L2 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 45; and and a CDR-L3 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 56.

[0093] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 53, CDR-H2 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 54, and CDR-H3 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 55, and the VL domain comprises CDR-L1 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 50, CDR-L2 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 45, and CDR-L3 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 56.

[0094] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 53, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 54, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 55, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 50, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 45, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 56.

[0095] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain has a sequence identity that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or similar to the amino acid sequence of SEQ ID NO: 75. and wherein the VL domain comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:76.

[0096] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 75 and the VL domain comprises the amino acid sequence of SEQ ID NO: 76.

[0097] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain has an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 100%, at least 101%, at least 102%, at least 103%, at least 104%, at least 105%, at least 106%, at least 107%, at least 108%, at least 109%, at least 110%, at least 111%, at least 112%, at least 113%, at least 114%, at least 115%, at least 116%, at least 117%, at least 118%, at least 119%, at least 119%, at least 120%, at least 121%, at least 122%, at least 123%, at least 124%, at least 125%, at least 126%, at least 127%, at least 128%, at least 129%, at least 129%. CDR-H1 comprising an amino acid sequence having at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:58, CDR-H1 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:58. and CDR-H2 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 59. a CDR-L1 comprising a DR-H3, wherein the VL domain comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 60;a CDR-L2 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 34; and and a CDR-L3 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 61.

[0098] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 57, CDR-H2 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 58, and CDR-H3 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 59, and the VL domain comprises CDR-L1 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 60, CDR-L2 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 61.

[0099] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 57, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 58, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 59, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 60, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 61.

[0100] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain has a sequence identity that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or similar to the amino acid sequence of SEQ ID NO: 77. and wherein the VL domain comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:78.

[0101] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 77 and the VL domain comprises the amino acid sequence of SEQ ID NO: 78.

[0102] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain has an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 100%, at least 101%, at least 102%, at least 103%, at least 104%, at least 105%, at least 106%, at least 107%, at least 108%, at least 109%, at least 110%, at least 111%, at least 112%, at least 113%, at least 114%, at least 115%, at least 116%, at least 117%, at least 118%, at least 119%, at least 119%, at least 120%, at least 121%, at least 122%, at least 123%, at least 124%, at least 125%, at least 126%, at least 127%, at least 128%, at least 129%, at least 129%. CDR-H1 comprising an amino acid sequence having at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 84, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 84. and CDR-H2 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 85. a CDR-L1 comprising a DR-H3, wherein the VL domain comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 86;a CDR-L2 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 34; and and a CDR-L3 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 61.

[0103] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 83, CDR-H2 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 84, and CDR-H3 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises CDR-L1 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 86, CDR-L2 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 61.

[0104] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 83, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 84, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 86, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 61.

[0105] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain has a sequence identity that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or similar to the amino acid sequence of SEQ ID NO: 79. and the VL domain comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:80.

[0106] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 79 and the VL domain comprises the amino acid sequence of SEQ ID NO: 80.

[0107] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain has an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 100%, at least 101%, at least 102%, at least 103%, at least 104%, at least 105%, at least 106%, at least 107%, at least 108%, at least 109%, at least 110%, at least 111%, at least 112%, at least 113%, at least 114%, at least 115%, at least 116%, at least 117%, at least 118%, at least 119%, at least 119%, at least 120%, at least 121%, at least 122%, at least 123%, at least 124%, at least 125%, at least 126%, at least 127%, at least 128%, at least 129%, at least 129%. CDR-H1 comprising an amino acid sequence having at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:48, CDR-H1 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:48. and CDR-H2 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 62. a CDR-L1 comprising a DR-H3, wherein the VL domain comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 63;a CDR-L2 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 34; and and a CDR-L3 comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:64.

[0108] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 47, CDR-H2 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 48, and CDR-H3 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises CDR-L1 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 63, CDR-L2 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising an amino acid sequence comprising one, two, or three amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 64.

[0109] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 47, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 48, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 63, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 64.

[0110] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain has a sequence identity that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or similar to the amino acid sequence of SEQ ID NO: 81. and the VL domain comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:82.

[0111] In some embodiments, an antibody of the disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 81 and the VL domain comprises the amino acid sequence of SEQ ID NO: 82.

[0112] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 87, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 88, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 90, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 91, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 35.

[0113] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 87, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 92, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 90, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 91, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 35.

[0114] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 87, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 92, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 94, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 90, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 91, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 35.

[0115] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 95, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 96, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 97, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 98, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 99, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 100.

[0116] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 109, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 110, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 114, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 115, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 99, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 52.

[0117] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 116, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 117, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 118, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 115, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 99, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 56.

[0118] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 101, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 102, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 103, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 104, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 91, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 61.

[0119] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 105, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 106, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 107, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 108, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 91, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 61.

[0120] In some embodiments, an antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 109, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 110, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 111, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 112, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 113, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 64.

[0121] In some embodiments, an antibody of the disclosure comprises a VH domain comprising one, two, or three CDRs from a single antibody listed in Table 1, and / or a VL domain comprising one, two, or three CDRs from a single antibody listed in Table 1. In some embodiments, an antibody of the disclosure comprises a VH and / or VL domain from a single antibody listed in Table 2. [Table 1-1] [Table 1-2] [Table 1-3] [Table 2-1] [Table 2-2]

[0122] Numerous definitions of CDR sequences of antibody variable domains are known in the art and can be used to describe the antibodies of the present disclosure, for example, by their CDR sequences. In some embodiments, antibody CDR sequences are defined as in Kabat (see, e.g., Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md., 1991). In some embodiments, antibody CDR sequences are defined as in Chothia (see, e.g., Chothia and Lesk J. Mol. Biol. 196:901-917 (1987)). In some embodiments, antibody CDR sequences are defined as in IMGT (see, e.g., Lefranc, MP (1999) The Immunologist 7:132-136). In some embodiments, the CDR sequences of a single antibody are defined by combining two or more definitions, e.g., Kabat, Chothia, and / or IMGT. In some embodiments, an antibody of the present disclosure comprises a VH domain comprising one, two, or all three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO: 65, and / or a VL domain comprising one, two, or all three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO: 66. In some embodiments, an antibody of the present disclosure comprises a VH domain comprising one, two, or all three CDR or HVR sequences present in the VH domain sequence of ATX-122 described herein (see, e.g., Table 2), and / or a VL domain comprising one, two, or all three CDR or HVR sequences present in the VL domain sequence of ATX-122 described herein (see, e.g., Table 2). In some embodiments, an antibody of the disclosure comprises a VH domain comprising one, two, or all three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO: 67, and / or a VL domain comprising one, two, or all three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO: 68.In some embodiments, an antibody of the disclosure comprises a VH domain comprising one, two, or all three CDR or HVR sequences present in the VH domain sequences of ATX-123 described herein (see, e.g., Table 2), and / or a VL domain comprising one, two, or all three CDR or HVR sequences present in the VL domain sequences of ATX-123 described herein (see, e.g., Table 2). In some embodiments, an antibody of the disclosure comprises a VH domain comprising one, two, or all three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO:69, and / or a VL domain comprising one, two, or all three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO:70. In some embodiments, an antibody of the disclosure comprises a VH domain that comprises one, two, or all three CDR or HVR sequences present in the VH domain sequences of ATX-124 described herein (see, e.g., Table 2), and / or a VL domain that comprises one, two, or all three CDR or HVR sequences present in the VL domain sequences of ATX-124 described herein (see, e.g., Table 2). In some embodiments, an antibody of the disclosure comprises a VH domain that comprises one, two, or all three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO:71, and / or a VL domain that comprises one, two, or all three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO:72. In some embodiments, an antibody of the disclosure comprises a VH domain comprising one, two, or all three CDR or HVR sequences present in the VH domain sequences of ATX-125 described herein (see, e.g., Table 2), and / or a VL domain comprising one, two, or all three CDR or HVR sequences present in the VL domain sequences of ATX-125 described herein (see, e.g., Table 2). In some embodiments, an antibody of the disclosure comprises a VH domain comprising one, two, or all three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO:73, and / or a VL domain comprising one, two, or all three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO:74.In some embodiments, an antibody of the disclosure comprises a VH domain comprising one, two, or all three CDR or HVR sequences present in the VH domain sequences of ATX-126 described herein (see, e.g., Table 2), and / or a VL domain comprising one, two, or all three CDR or HVR sequences present in the VL domain sequences of ATX-126 described herein (see, e.g., Table 2). In some embodiments, an antibody of the disclosure comprises a VH domain comprising one, two, or all three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO:75, and / or a VL domain comprising one, two, or all three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO:76. In some embodiments, an antibody of the disclosure comprises a VH domain comprising one, two, or all three CDR or HVR sequences present in the VH domain sequence of ATX-127 described herein (see, e.g., Table 2), and / or a VL domain comprising one, two, or all three CDR or HVR sequences present in the VL domain sequence of ATX-127 described herein (see, e.g., Table 2). In some embodiments, an antibody of the disclosure comprises a VH domain comprising one, two, or all three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO:77, and / or a VL domain comprising one, two, or all three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO:78. In some embodiments, an antibody of the disclosure comprises a VH domain comprising one, two, or all three CDR or HVR sequences present in the VH domain sequences of ATX-128 described herein (see, e.g., Table 2), and / or a VL domain comprising one, two, or all three CDR or HVR sequences present in the VL domain sequences of ATX-128 described herein (see, e.g., Table 2). In some embodiments, an antibody of the disclosure comprises a VH domain comprising one, two, or all three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO:79, and / or a VL domain comprising one, two, or all three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO:80.In some embodiments, an antibody of the disclosure comprises a VH domain that comprises one, two, or all three CDR or HVR sequences present in the VH domain sequences of ATX-129 described herein (see, e.g., Table 2), and / or a VL domain that comprises one, two, or all three CDR or HVR sequences present in the VL domain sequences of ATX-129 described herein (see, e.g., Table 2). In some embodiments, an antibody of the disclosure comprises a VH domain that comprises one, two, or all three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO: 81, and / or a VL domain that comprises one, two, or all three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO: 82. In some embodiments, an antibody of the present disclosure comprises a VH domain that comprises one, two, or all three CDR or HVR sequences present in the VH domain sequences of ATX-130 described herein (see, e.g., Table 2), and / or a VL domain that comprises one, two, or all three CDR or HVR sequences present in the VL domain sequences of ATX-130 described herein (see, e.g., Table 2).

[0123] In some embodiments, an antibody of the present disclosure binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope bound by an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0124] In some embodiments, an antibody of the disclosure binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope bound by an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 19 and the VL domain comprises the amino acid sequence of SEQ ID NO: 20.

[0125] In some embodiments, an antibody of the present disclosure binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope bound by an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 7, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 8, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 9, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 10, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 11, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 12.

[0126] In some embodiments, an antibody of the disclosure binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope bound by an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 21 and the VL domain comprises the amino acid sequence of SEQ ID NO: 22.

[0127] In some embodiments, an antibody of the present disclosure binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope bound by an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 13, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 14, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 15, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 16, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 17, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 18.

[0128] In some embodiments, an antibody of the disclosure binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope bound by an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 23 and the VL domain comprises the amino acid sequence of SEQ ID NO: 24.

[0129] In some embodiments, an antibody of the present disclosure binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope bound by an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 30, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 31, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 32, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 33, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 35.

[0130] In some embodiments, an antibody of the disclosure binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope bound by an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 65 and the VL domain comprises the amino acid sequence of SEQ ID NO: 66.

[0131] In some embodiments, an antibody of the present disclosure binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope bound by an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 36, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 37, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 38, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 33, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 35.

[0132] In some embodiments, an antibody of the disclosure binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope bound by an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 67 and the VL domain comprises the amino acid sequence of SEQ ID NO: 68.

[0133] In some embodiments, an antibody of the present disclosure binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope bound by an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 36, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 39, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 40, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 33, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 35.

[0134] In some embodiments, an antibody of the disclosure binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope bound by an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 69 and the VL domain comprises the amino acid sequence of SEQ ID NO: 70.

[0135] In some embodiments, an antibody of the present disclosure binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope bound by an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 41, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 42, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 43, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 44, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 45, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 46.

[0136] In some embodiments, an antibody of the disclosure binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope bound by an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 71 and the VL domain comprises the amino acid sequence of SEQ ID NO: 72.

[0137] In some embodiments, an antibody of the present disclosure binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope bound by an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 47, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 48, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 49, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 50, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 51, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 52.

[0138] In some embodiments, an antibody of the disclosure binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope bound by an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 73 and the VL domain comprises the amino acid sequence of SEQ ID NO: 74.

[0139] In some embodiments, an antibody of the present disclosure binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope bound by an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 53, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 54, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 55, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 50, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 45, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 56.

[0140] In some embodiments, an antibody of the disclosure binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope bound by an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 75 and the VL domain comprises the amino acid sequence of SEQ ID NO: 76.

[0141] In some embodiments, an antibody of the present disclosure binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope bound by an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 57, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 58, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 59, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 60, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 61.

[0142] In some embodiments, an antibody of the disclosure binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope bound by an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 77 and the VL domain comprises the amino acid sequence of SEQ ID NO: 78.

[0143] In some embodiments, an antibody of the present disclosure binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope bound by an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 83, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 84, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 86, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 61.

[0144] In some embodiments, an antibody of the disclosure binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope bound by an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 79 and the VL domain comprises the amino acid sequence of SEQ ID NO: 80.

[0145] In some embodiments, an antibody of the present disclosure binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope bound by an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 47, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 48, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 63, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 64.

[0146] In some embodiments, an antibody of the disclosure binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope bound by an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 81 and the VL domain comprises the amino acid sequence of SEQ ID NO: 82.

[0147] In some embodiments, an antibody of the present disclosure competes for binding to human or cynomolgus monkey CD94 with an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0148] In some embodiments, an antibody of the disclosure competes for binding to human or cynomolgus monkey CD94 with an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 19 and the VL domain comprises the amino acid sequence of SEQ ID NO: 20.

[0149] In some embodiments, an antibody of the present disclosure competes for binding to human or cynomolgus monkey CD94 with an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 7, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 8, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 9, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 10, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 11, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 12.

[0150] In some embodiments, an antibody of the disclosure competes for binding to human or cynomolgus monkey CD94 with an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 21 and the VL domain comprises the amino acid sequence of SEQ ID NO: 22.

[0151] In some embodiments, an antibody of the present disclosure competes for binding to human or cynomolgus monkey CD94 with an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 13, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 14, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 15, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 16, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 17, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 18.

[0152] In some embodiments, an antibody of the disclosure competes for binding to human or cynomolgus monkey CD94 with an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 23 and the VL domain comprises the amino acid sequence of SEQ ID NO: 24.

[0153] In some embodiments, an antibody of the disclosure competes for binding to human or cynomolgus monkey CD94 with an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 30, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 31, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 32, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 33, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 35.

[0154] In some embodiments, an antibody of the disclosure competes for binding to human or cynomolgus monkey CD94 with an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 65 and the VL domain comprises the amino acid sequence of SEQ ID NO: 66.

[0155] In some embodiments, an antibody of the disclosure competes for binding to human or cynomolgus monkey CD94 with an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 36, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 37, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 38, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 33, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 35.

[0156] In some embodiments, an antibody of the disclosure competes for binding to human or cynomolgus monkey CD94 with an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 67 and the VL domain comprises the amino acid sequence of SEQ ID NO: 68.

[0157] In some embodiments, an antibody of the disclosure competes for binding to human or cynomolgus monkey CD94 with an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 36, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 39, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 40, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 33, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 35.

[0158] In some embodiments, an antibody of the disclosure competes for binding to human or cynomolgus monkey CD94 with an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 69 and the VL domain comprises the amino acid sequence of SEQ ID NO: 70.

[0159] In some embodiments, an antibody of the disclosure competes for binding to human or cynomolgus monkey CD94 with an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 41, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 42, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 43, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 44, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 45, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 46.

[0160] In some embodiments, an antibody of the disclosure competes for binding to human or cynomolgus monkey CD94 with an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 71 and the VL domain comprises the amino acid sequence of SEQ ID NO: 72.

[0161] In some embodiments, an antibody of the disclosure competes for binding to human or cynomolgus monkey CD94 with an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 47, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 48, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 49, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 50, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 51, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 52.

[0162] In some embodiments, an antibody of the disclosure competes for binding to human or cynomolgus monkey CD94 with an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 73 and the VL domain comprises the amino acid sequence of SEQ ID NO: 74.

[0163] In some embodiments, an antibody of the disclosure competes for binding to human or cynomolgus monkey CD94 with an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 53, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 54, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 55, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 50, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 45, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 56.

[0164] In some embodiments, an antibody of the disclosure competes for binding to human or cynomolgus monkey CD94 with an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 75 and the VL domain comprises the amino acid sequence of SEQ ID NO: 76.

[0165] In some embodiments, an antibody of the disclosure competes for binding to human or cynomolgus monkey CD94 with an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 57, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 58, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 59, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 60, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 61.

[0166] In some embodiments, an antibody of the disclosure competes for binding to human or cynomolgus monkey CD94 with an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 77 and the VL domain comprises the amino acid sequence of SEQ ID NO: 78.

[0167] In some embodiments, an antibody of the disclosure competes for binding to human or cynomolgus monkey CD94 with an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 83, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 84, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 86, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 61.

[0168] In some embodiments, an antibody of the disclosure competes for binding to human or cynomolgus monkey CD94 with an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 79 and the VL domain comprises the amino acid sequence of SEQ ID NO: 80.

[0169] In some embodiments, an antibody of the disclosure competes for binding to human or cynomolgus monkey CD94 with an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 47, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 48, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 63, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 64.

[0170] In some embodiments, an antibody of the disclosure competes for binding to human or cynomolgus monkey CD94 with an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 81 and the VL domain comprises the amino acid sequence of SEQ ID NO: 82.

[0171] In some embodiments, the antibody of the present disclosure comprises an Fc region. In some embodiments, the Fc region is a human IgG1 Fc region. In some embodiments, the antibody comprises a non-fucosylated human Fc region. In some embodiments, the antibody binds to human cell Fc gamma receptor IIIA to a greater extent than an antibody comprising a wild-type human IgG1 Fc region. In some embodiments, the antibody can induce antibody-dependent cellular cytotoxicity (ADCC) against cells expressing human CD94 on their surface.

[0172] In some embodiments, the term antibody is used in the broadest sense to encompass a variety of antibody structures, including, but not limited to, monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), and antibody fragments, so long as they exhibit the desired antigen-binding activity. In some embodiments, the antibodies of the present disclosure are isolated antibodies. An "isolated" antibody is one that has been identified and separated and / or recovered from components of its natural environment. Contaminant components of its natural environment are materials that would interfere with research, diagnostic, and / or therapeutic uses of the antibody, and may include enzymes, hormones, and other proteinaceous or non-proteinaceous solutes. In some embodiments, antibodies are purified (1) to greater than 95% by weight, and in some embodiments, greater than 99% by weight, as determined, for example, by the Lowry method; (2) to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence, for example, by use of a spinning cup sequenator; or (3) to homogeneity by SDS-PAGE under reducing or non-reducing conditions, for example, using 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.

[0173] In some embodiments, a monoclonal antibody is an antibody obtained from a substantially homogeneous population of antibodies, i.e., the individual antibodies comprising the population are identical and / or bind to the same epitope, with the exception of possible variant antibodies that contain, for example, naturally occurring mutations or arise during the generation of the monoclonal antibody preparation, and such variants are generally present in minor amounts. In contrast to polyclonal antibody preparations, which typically contain different antibodies directed against different determinants (epitopes), each monoclonal antibody of a monoclonal antibody preparation is directed against a single determinant on an antigen. Thus, in some embodiments, a monoclonal antibody is obtained from a substantially homogeneous population of antibodies. Monoclonal antibodies may be produced using any method known in the art. For example, monoclonal antibodies used in accordance with the present disclosure may be produced by a variety of techniques, including, but not limited to, hybridoma methods, recombinant DNA methods, phage display methods, and methods utilizing transgenic animals containing all or part of the human immunoglobulin loci.

[0174] C. Blockade of HLA-E binding Major histocompatibility complex class I, E (HLA-E) is a ligand for the CD94 / NKG2A heterodimer and plays an essential role in inhibiting NK cell and CD8+ T cell activity when bound to the CD94 / NKG2A heterodimer. Therefore, without wishing to be bound by theory, blocking the interaction between HLA-E and CD94 / NKG2A can result in the activation and proliferation of target cells, e.g., cells expressing CD94. Therefore, for example, in a subject with NK / T cell lymphoma who has been administered an anti-CD94 antibody, it may be beneficial for the anti-CD94 antibody not to block the interaction of HLA-E with the CD94 / NKG2A heterodimer. In some embodiments, the HLA-E is human HLA-E, also known as QA1 and HLA-6.2. For a representative HLA-E gene, see, e.g., NCBI gene ID number 3133, and for a representative HLA-E polypeptide, see, e.g., NP_005507.3.

[0175] In some embodiments, blocking HLA-E binding to the CD94 / NKG2A heterodimer refers to blocking HLA-E binding to the CD94 / NKG2A heterodimer, blocking HLA-E binding to CD94, and / or blocking HLA-E binding to NKG2A.

[0176] Blockade of HLA-E binding to CD94 / NKG2A heterodimers by antibodies of the present disclosure may be assessed using any method known in the art. For example, blockade of HLA-E binding to CD94 / NKG2A heterodimers by antibodies of the present disclosure may be assessed using an ex vivo assay using PBMCs and / or NK cells, e.g., as described in the Examples. In a typical assay, PBMCs obtained from, for example, a healthy donor are incubated with human Fc block (Biolegend, San Diego, CA) and a cell viability dye (Thermo Fisher, Carlsbad, CA) on ice for 30 minutes protected from light. The cells are then washed once with FACS buffer (PBS containing 2% low IgG FBS). A saturating concentration of anti-CD94 antibody or isotype control antibody is incubated with the cells on ice for 30 minutes protected from light. The cells are then washed and incubated with HLA-E tetramer PE (Creative Biolabs, Shirley, NY), CD3 Pacific Blue antibody, and CD56 FITC antibody (Biolegend, San Diego, CA) on ice for 30 minutes, protected from light. The cells are then given a final wash in FACS buffer before quantification on a flow cytometer. Data acquisition and fluorescence compensation may be performed using methods known in the art, such as using a CytoFlex flow cytometer (Beckman Coulter, Chaska, MN). Data analysis may be performed using any method known in the art, such as using FlowJo software. NK cells are identified by gating lymphocytes based on forward and side scatter, subsequently excluding doublets and dead cells, and gating on the CD3-CD56+ population. HLA-E is then quantified in the CD3-CD56+ NK cell population. The percent blockage of HLA-E binding to CD94 / NKG2A heterodimers by an anti-CD94 antibody compared to a control antibody, e.g., an isotype control antibody, is calculated as 100 - ((percent HLA-E positive for anti-CD94 antibody) / (percent HLA-E positive for isotype) x 100).

[0177] In some embodiments, an antibody blocks HLA-E binding to the CD94 / NKG2A heterodimer if it blocks more than about 20% of HLA-E binding to the CD94 / NKG2A heterodimer, e.g., compared to an isotype control antibody. In some embodiments, an antibody blocks HLA-E binding to the CD94 / NKG2A heterodimer if it blocks about 21%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, about 99%, or 100% of HLA-E binding to the CD94 / NKG2A heterodimer, e.g., compared to a control antibody, e.g., an isotype control antibody.

[0178] In some embodiments, an antibody does not block HLA-E binding to the CD94 / NKG2A heterodimer if it blocks about 20% or less of HLA-E binding to the CD94 / NKG2A heterodimer, e.g., compared to an isotype control antibody. In some embodiments, an antibody does not block HLA-E binding to the CD94 / NKG2A heterodimer if it blocks about 20%, about 18%, about 16%, about 14%, about 12%, about 10%, about 8%, about 6%, about 4%, about 2%, about 1%, about 0.5%, or 0% of HLA-E binding to the CD94 / NKG2A heterodimer, e.g., compared to a control antibody, e.g., an isotype control antibody.

[0179] In some embodiments, the antibodies provided herein do not block HLA-E binding to CD94 / NKG2A heterodimers. In some embodiments, the antibodies provided herein block about 20% or less, about 19% or less, about 18% or less, about 17% or less, about 16% or less, about 15% or less, about 14% or less, about 13% or less, about 12% or less, about 11% or less, about 10% or less, about 9% or less, about 8% or less, about 6% or less, about 5% or less, about 4% or less, about 3% or less, about 2% or less, about 1% or less, about 0.5% or less, or 0% of HLA-E binding to CD94 / NKG2A heterodimers compared to a control antibody, e.g., an isotype control antibody. In some embodiments, the antibodies provided herein block 0% of HLA-E binding to CD94 / NKG2A heterodimers compared to a control antibody, e.g., an isotype control antibody.

[0180] D. Enhanced ADCC Activity In some embodiments, antibody-dependent cell-mediated cytotoxicity, antibody-dependent cellular cytotoxicity, antibody-directed cytotoxicity, or ADCC refers to a cell-mediated reaction in which nonspecific cytotoxic cells bearing Fc receptors, such as natural killer cells (NK cells), neutrophils, and macrophages, recognize antibodies bound to target cells and subsequently cause lysis of the target cells. The primary mediator cells are natural killer (NK) cells. NK cells express FcγRIII (Ravetch et al. (1991) Annu. Rev. Immunol., 9:457-92). In some embodiments, ADCC activity refers to the ability of an antibody or Fc fusion protein to induce an ADCC response.

[0181] In some embodiments, the antibodies provided herein have enhanced antibody-dependent cellular cytotoxicity (ADCC) activity. In some embodiments, enhanced ADCC activity refers to an antibody or the Fc region of an antibody more efficiently and / or more effectively mediating or inducing ADCC in vitro or in vivo in the presence of effector cells than a native or wild-type antibody and / or native or wild-type Fc region of the antibody, which can be determined, for example, using an ADCC assay described herein or known in the art. In some embodiments, the effector cells are leukocytes that bear one or more Fc receptors and perform effector function. In some embodiments, such cells bear at least FcγRIII and perform ADCC effector function. Examples of human leukocytes that mediate ADCC include peripheral blood mononuclear cells (PBMCs), natural killer cells (NK), monocytes, cytotoxic T cells, and neutrophils.

[0182] In some embodiments, ADCC activity was measured using peripheral blood mononuclear cells (PBMCs) and / or NK effector cells. 51ADCC activity can be assessed directly using an in vitro assay, such as a Cr release assay (see, e.g., Shields et al. (2001) J. Biol. Chem., 276:6591-6604), or another suitable method. ADCC activity can be expressed as the number of cells remaining following an ADCC assay, or the concentration of antibody or Fc fusion protein at which half-maximal target cell lysis occurs (e.g., EC50 or IC50). In some embodiments, ADCC activity is determined using an ex vivo assay using PBMCs, LGL cells, and / or NK cells, e.g., as described in the Examples, and the ADCC activity of an antibody of the present disclosure is described as the percent of target cells remaining following an ADCC assay and / or the antibody's IC50 or EC50 (i.e., the concentration of an antibody of the present disclosure at which half-maximal target cell depletion or cell lysis is achieved). The antibody's IC50 or EC50 may be determined using any method known in the art, e.g., using a dose-response curve and GraphPad Prism.

[0183] In some embodiments, the antibodies provided herein induce ADCC activity with an IC50 or EC50 of about 1 ng / ml to about 100 ng / ml (e.g., any of about 1 ng / ml, about 2 ng / ml, about 3 ng / ml, about 4 ng / ml, about 5 ng / ml, about 10 ng / ml, about 15 ng / ml, about 20 ng / ml, about 25 ng / ml, about 30 ng / ml, about 35 ng / ml, about 40 ng / ml, about 45 ng / ml, about 50 ng / ml, about 55 ng / ml, about 60 ng / ml, about 65 ng / ml, about 70 ng / ml, about 75 ng / ml, about 80 ng / ml, about 85 ng / ml, about 90 ng / ml, about 95 ng / ml, or about 100 ng / ml), as measured using an ex vivo assay. In some embodiments, the antibodies provided herein induce ADCC activity with an IC50 or EC50 of about 20 ng / ml or less, as measured using an ex vivo assay. In some embodiments, the antibodies provided herein induce ADCC activity with an IC50 or EC50 of about 60 ng / ml or less, as measured using an ex vivo assay. In some embodiments, the antibodies of the present disclosure exhibit an IC50 or EC50 that is at least 1%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, 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%, or at least 95% lower than the IC50 or EC50 of a control antibody (e.g., a wild-type control antibody or an art-known or commercially available antibody against the same target).

[0184] In some embodiments, IC50 or EC50 refers to the concentration of a compound (e.g., an antibody) that induces a response halfway between baseline and maximum after a specified exposure time. For example, IC50 or EC50 may be used to measure the potency of an antibody in mediating and / or inducing effector function, e.g., ADCC activity. In some embodiments, the IC50 or EC50 of a dose-response curve represents the concentration of a compound (e.g., an antibody) at which 50% of its maximum effect is observed.

[0185] In some embodiments, antibodies of the present disclosure have a higher maximum target cell lysis compared to a control antibody (e.g., a wild-type control antibody, or an art-known or commercially available antibody against the same target). For example, antibodies of the present disclosure may exhibit a target cell lysis maximum that is at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, 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 100% higher than the target cell lysis maximum of a control antibody (e.g., a wild-type control antibody, or an art-known or commercially available antibody against the same target).

[0186] (i) Enhanced binding to Fc receptors In some embodiments, the antibodies provided herein comprise a human immunoglobulin Fc region that has enhanced ADCC activity compared to a wild-type Fc region. In some embodiments, the antibodies provided herein bind to human cell Fc receptors to a greater extent than antibodies comprising a wild-type Fc region. In some embodiments, the Fc receptor (FcR) is a receptor that can bind to the Fc region of an antibody. Certain Fc receptors can bind to IgG (i.e., γ-receptors), and such receptors include the FcyRI, FcyRII, and FcyRIII subclasses, as well as their allelic variants and alternative splicing events. For a general overview of Fc receptors, see Ravetch and China: Annu. Port. Immunol. 9, 457 (1991); Capel et al., Immunomethods, 4, 25 (1994); and de Haas et al., J. Leg. Clin. Med. 126, 330 (1995).

[0187] In some embodiments, the antibodies provided herein bind to human cellular Fc gamma receptor IIIA to a greater extent than antibodies comprising wild-type Fc regions. In some embodiments, the human cellular Fc gamma receptor IIIA comprises a valine or phenylalanine residue at amino acid residue 158. See, for example, UniProt accession numbers P08637 or VAR_003960. In some embodiments, the human cellular Fc gamma receptor IIIA comprises the sequence of SEQ ID NO: 28 or 29. Human Cellular Fc Gamma Receptor IIIA 158F [ka] Human cell Fc gamma receptor IIIA 158V [ka]

[0188] In some embodiments, the antibodies provided herein are of the IgG (e.g., IgG1, IgG2, IgG3, or IgG4), IgA (IgA1 or IgA2), IgD, IgM, or IgE isotype. In some embodiments, the antibodies provided herein are of the IgG isotype. In some embodiments, the antibodies provided herein are of the IgG1 isotype. In some embodiments, the antibodies provided herein bind to human cellular Fc gamma receptor IIIA (FcγRIIIA) to a greater extent than antibodies comprising a wild-type human IgG1 Fc region. In some embodiments, the human cellular Fc gamma receptor IIIA comprises a valine or phenylalanine residue at amino acid residue 158. Representative assays for determining binding to human cell Fc gamma receptor IIIA are known in the art, see, e.g., Lazar, GA et al. (2006) Proc. Natl. Acad. Sci. 103:4005-1010, and Ferrara, C. et al. (2011) Proc. Natl. Acad. Sci. 108:12669-12674.

[0189] In some embodiments, the Fc region is the C-terminal region of an immunoglobulin heavy chain containing at least a portion of the constant region. In some embodiments, the Fc region includes a native Fc region or a variant Fc region. In one embodiment, a human IgG heavy chain Fc region extends from Cys226 or from Pro230 to the carboxyl terminus of the heavy chain. However, the C-terminal lysine (Lys447) of the Fc region may or may not be present. In some embodiments, the numbering of amino acid residues in the Fc region or constant region follows the EU numbering system, also known as the EU index, as described in Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md., 1991. In some embodiments, a wild-type or native Fc region is an Fc region comprising an amino acid sequence identical to that of an Fc region found in nature. In some embodiments, a variant Fc region is an Fc region comprising an amino acid sequence that differs by at least one amino acid from the native or wild-type sequence of the Fc region. In some embodiments, the variant Fc region has at least one amino acid substitution, e.g., approximately 1-10 or 1-5 amino acid substitutions. In some embodiments, the Fc region variant is at least approximately 80% (e.g., at least about 90%, or at least about 95%) homologous to the native or wild-type sequence Fc region and / or the Fc region of the original polypeptide. In some embodiments, the at least one amino acid substitution in the variant Fc region enhances the effector function of the variant Fc region compared to the native or wild-type Fc region. In some embodiments, effector function is a biological activity attributable to the Fc region of an antibody, which varies depending on the antibody isotype.Examples of antibody effector functions include Clq binding and complement-dependent cytotoxicity (CDC), Fc receptor binding, antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP), down-regulation of cell surface receptors (e.g., B cell receptors), and B cell activation.

[0190] The binding affinity of an antibody to an Fc receptor may be assessed using any method known in the art, such as, for example, using surface plasmon resonance and / or ELISA, as described in Shields et al. (2001) J. Biol. Chem., 276:6591-6604. In some embodiments, the affinity of an antibody of the disclosure for FcγRIIIA may exceed that of a wild-type control by any of the following: at least about 1.5-fold, at least about 2-fold, at least about 3-fold, at least about 4-fold, at least about 5-fold, at least about 6-fold, at least about 7-fold, at least about 8-fold, at least about 9-fold, at least about 10-fold, at least about 20-fold, at least about 30-fold, at least about 40-fold, at least about 50-fold, or more.

[0191] In some embodiments, affinity refers to the strength of the sum of non-covalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen or target). For example, the affinity of a molecule X for its partner Y is generally determined by the dissociation constant (K D Affinity can be measured by common methods known in the art, including those described herein.

[0192] In some embodiments, a statement that one molecule (e.g., an antibody and / or Fc region) binds to a greater extent than another molecule (e.g., an antibody and / or Fc region), or that one molecule (e.g., an antibody and / or Fc region) binds with higher affinity than another molecule (e.g., an antibody and / or Fc region), or other grammatical equivalents, refers to one molecule (e.g., an antibody and / or Fc region) binding more tightly (e.g., having a lower dissociation constant) to a target (e.g., an Fc receptor, a cell surface protein) than another molecule (e.g., an antibody and / or Fc region) under substantially the same conditions in a binding assay (e.g., as described herein and / or known in the art). For example, a statement that antibody "X" binds to an Fc receptor to a greater extent than antibody "Y" indicates that antibody "X" binds more tightly (e.g., has a lower dissociation constant) to an Fc receptor than antibody "Y" under substantially the same conditions in a binding assay (e.g., as described herein and / or known in the art). In another example, a statement that antibody "X" binds to a target (e.g., a cell surface protein such as CD94) with higher affinity than antibody "Y" indicates that antibody "X" binds more tightly (e.g., has a lower dissociation constant) to the target (e.g., a cell surface protein such as CD94) than antibody "Y" under substantially the same conditions in a binding assay (e.g., as described herein and / or known in the art).

[0193] (ii) Reduced fucosylation In some embodiments, the antibodies of the present disclosure are non-fucosylated or fucose-deficient, e.g., glycosylated antibody variants comprising an Fc region in which the carbohydrate structures attached to the Fc region have reduced fucose or lack fucose. In some embodiments, antibodies with reduced fucose or lacking fucose have improved ADCC function. Non-fucosylated or fucose-deficient antibodies have reduced fucose compared to the amount of fucose on the same antibody produced in a cell line. In some embodiments, the non-fucosylated or fucose-deficient antibody composition of the present disclosure is a composition in which less than about 50% of the N-linked glycans attached to the Fc region of the antibody in the composition contain fucose.

[0194] In some embodiments, fucosylation or fucosylated refers to fucose residues within the oligosaccharides attached to the peptide backbone of an antibody of the present disclosure. Specifically, a fucosylated antibody contains an α(1,6)-linked fucose at the innermost N-acetylglucosamine (GlcNAc) residue in one or both N-linked oligosaccharides attached to an antibody Fc region, e.g., at position Asn297 (EU numbering of Fc region residues) of a human IgG1 Fc domain. Asn297 may also be located approximately +3 amino acids upstream or downstream from position 297, i.e., between positions 294 and 300, due to minor sequence variability in immunoglobulins.

[0195] In some embodiments, the degree of fucosylation is the percentage of fucosylated oligosaccharides relative to all oligosaccharides, as determined by methods known in the art, such as, for example, in an antibody composition treated with N-glycosidase F as assessed by matrix-assisted laser desorption / ionization time-of-flight mass spectrometry (MALDI-TOF MS). In a composition of fully fucosylated antibodies, at least 90% or essentially all of the oligosaccharides contain a fucose residue, i.e., are fucosylated. Thus, individual antibodies in such compositions typically contain a fucose residue on each of the two N-linked oligosaccharides in the Fc region. In some embodiments, in a composition of fully nonfucosylated antibodies, less than about 10% of the oligosaccharides are fucosylated or essentially none of the oligosaccharides are fucosylated, and individual antibodies in such compositions do not contain a fucose residue on either of the two N-linked oligosaccharides in the Fc region. In a composition of partially fucosylated antibodies, only a portion of the oligosaccharides contain fucose. The individual antibodies in such compositions can contain no fucose residues in any of the N-linked oligosaccharides in their Fc regions, or can contain fucose residues in one or both of the N-linked oligosaccharides in their Fc regions, so long as essentially all of the individual antibodies in the composition lack fucose residues in the N-linked oligosaccharides in their Fc regions or contain fucose residues in both of the N-linked oligosaccharides in their Fc regions. In one embodiment, a composition of partially fucosylated antibodies has a degree of fucosylation of about 10% to about 80% (e.g., about 50% to about 80%, about 60% to about 80%, or about 70% to about 80%).

[0196] In some embodiments, glycosylated antibody variants comprise an Fc region in which the carbohydrate structures attached to the Fc region lack fucose, and such variants have improved ADCC function. Examples of defucosylated or fucose-deficient antibodies are described in US2003 / 0157108, WO2000 / 61739, WO2001 / 29246, US2003 / 0115614, US2002 / 0164328, US2004 / 0093621, US2004 / 0132140, US2004 / 0110704, US2004 / 0110282, US2004 / 0109865, WO2003 / 085119, WO2003 / 084570, WO2005 / 035586, WO2005 / 035778, WO2005 / 053742, Okazaki et al. al. J. Mol. Biol. 336:1239-1249 (2004), Yamane-Ohnuki et al. Biotech. Bioeng. 87:614 (2004).

[0197] Antibodies with reduced fucosylation or afucosylated antibodies may be produced using any method known in the art. In some embodiments of the antibodies of the present disclosure, at least one or two of the heavy chains of the antibody may be afucosylated. For example, antibodies of the present disclosure with reduced fucosylation or afucosylated antibodies may be produced in cell lines with an alpha 1,6-fucosyltransferase (Fut8) knockout and / or overexpressing β1,4-N-acetylglucosaminyltransferase III (GnT-III) and / or overexpressing Golgi μ-mannosidase II (ManII). Antibodies with reduced fucosylation or no fucosylated antibodies may also be produced using cell lines deficient in "FUT8," i.e., alpha-1,6 fucosyltransferase, which catalyzes the transfer of fucose; for example, using Chinese hamster ovary (CHO) cells deficient in FUT8 (Yamane-Ohnuki et al., 2004); or using small interfering RNA (siRNA) to block expression of the FUT8 gene (Mori et al., 2004). Other cell lines that can be used to generate non-fucosylated or defucosylated antibodies or antibodies with reduced fucosylation are known in the art, such as Lec13 CHO cells, which are deficient in protein fucosylation (Ripka et al. Arch. Biochem. Biophys. 249:533-545 (1986); US Patent Application No. US2003 / 0157108A1 (Presta, L); and WO2004 / 056312A1 (Adams et al., especially in Example 11)), and knockout cell lines, such as alpha-1,6-fucosyltransferase gene (FUT8) knockout CHO cells (Yamane-Ohnuki et al. al. Biotech. Bioeng. 87:614 (2004)), as well as cells overexpressing β1,4-N-acetylglucosaminyltransferase III (GnT-III) and Golgi μ-mannosidase II (ManII).

[0198] In some embodiments, the antibodies of the present disclosure have reduced fucose compared to the amount of fucose on the same antibody produced in wild-type CHO cells. For example, the antibody may have a lower amount of fucose than it would otherwise have if produced by a native CHO cell (e.g., a CHO cell that produces a native glycosylation pattern, such as a CHO cell containing a native FUT8 gene). In some embodiments, the antibodies provided herein are antibodies in which less than about 50%, 40%, 30%, 20%, 10%, 5%, or 1% of the N-linked glycans thereon contain fucose. In certain embodiments, the antibodies provided herein are antibodies in which none of the N-linked glycans thereon contain fucose, i.e., the antibody does not contain any fucose, does not have fucose, is non-fucosylated, or is defucosylated. The amount of fucose can be determined by one skilled in the art by, for example, calculating the average amount of fucose in the glycan at Asn297 relative to the sum of all glycostructures (e.g., complex, hybrid, and high-mannose structures) attached to Asn297, as measured by MALDI-TOF mass spectrometry, e.g., as described in WO2008 / 077546. Asn297 refers to an asparagine residue located at about position 297 (Eu numbering of Fc region residues) in the Fc region; however, Asn297 may also be located approximately ±3 amino acids upstream or downstream from position 297, i.e., between positions 294 and 300, due to minor sequence variability in antibodies. In some embodiments, at least one or two of the heavy chains of the antibody are nonfucosylated.

[0199] Antibodies lacking 1,6-fucose in their heavy chain glycosylation may have enhanced binding affinity to the FcγRIII receptor and increased ADCC activity (see, e.g., Shields et al., 2002; Shinkawa et al., 2002; Okazaki, 2004; Dall'Ozzo, 2004). In some embodiments, the antibodies provided herein comprise an Fc region with modifications, including reduced fucosylation, afucosylation, and / or mutations that enhance ADCC activity and / or improve the affinity of the Fc region for Fc receptors, such as FcγRIII and CD16 (e.g., CD16a). In some embodiments, the molecules (e.g., antibodies provided herein) induce antibody-directed cytotoxicity (ADCC) and deplete or reduce the number of CD94-expressing NK cells and / or T cells to a greater extent than fucosylated or wild-type antibodies.

[0200] In some embodiments, antibodies of the present disclosure are engineered to improve ADCC activity by reducing fucosylation. In some embodiments, molecules provided herein (e.g., antibodies provided herein) induce antibody-directed cytotoxicity (ADCC) to a greater extent than fucosylated or wild-type antibodies and can deplete or reduce the number of CD94-expressing NK cells and / or T cells. In some embodiments, at least one or two heavy chains of an antibody of the present disclosure are afucosylated. In some embodiments, antibodies of the present disclosure are modified so that the carbohydrates of the antibody are afucosylated. In some embodiments, antibodies of the present disclosure are modified so that less than about 90% of the carbohydrates of the antibody contain fucose, e.g., less than any of about 90%, about 80%, about 70%, about 60%, about 50%, about 40%, about 30%, about 20%, about 10%, about 5%, or about 1%. In some embodiments, the antibodies of the present disclosure are modified so that less than about 40% of the carbohydrates of the antibody contain fucose. In some embodiments, the antibodies provided herein are non-fucosylated.

[0201] In some embodiments, the molecules (e.g., antibodies) provided herein induce antibody-directed cytotoxicity (ADCC) and deplete or reduce the numbers of CD94-expressing NK cells and / or T cells to a greater extent than fucosylated or wild-type antibodies.

[0202] (iii) Mutations that enhance ADCC activity Antibodies of the present disclosure may comprise a variant Fc region. In some embodiments, the variant Fc region comprises at least one amino acid substitution in the Fc region that improves ADCC activity. For example, an antibody of the present disclosure may have a variant IgG1 Fc region comprising one or more Fc mutations selected from S239D, A330L, I332E, F243L, and G236A. In another example, an antibody of the present disclosure may have a human IgG1 Fc variant region comprising one or more Fc mutations selected from S239D, A330L, I332E, F243L, and G236A. Other amino acid substitutions known to enhance ADCC activity may also be used, for example, as described in Lazar et al., PNAS 103, 4005-4010 (2006), Shields et al., J. Biol. Chem. 276, 6591-6604 (2001), Stewart et al., Protein Engineering, Design and Selection 24, 671-678 (2011), and Richards et al., Mol Cancer Ther 7, 2517-2527 (2008).

[0203] (iv) reduced internalization In some embodiments, antibodies of the present disclosure have a lower degree of internalization, e.g., receptor-induced internalization or target internalization (i.e., internalization of surface-expressed CD94), compared to, for example, a wild-type control antibody or an art-known or commercially available antibody against the same target. Antibodies with lower internalization have higher receptor (e.g., CD94) occupancy on the cell surface and higher levels of receptor-antibody complexes on the cell surface, which may enhance ADCC activity. Antibodies of the present disclosure may be tested for their internalization ability in vitro. Antibodies of the present disclosure may be tested for their internalization ability in ex vivo assays, e.g., using PBMCs and / or NK cells, e.g., as described in the Examples. Target (e.g., CD94) internalization may be expressed as a percentage decrease in mean fluorescence intensity (MFI) over a period of time, e.g., using a flow cytometry-based assay, e.g., as described in the Examples. For example, target internalization (i.e., the internalization ability of an antibody of the present disclosure) can be expressed as a percentage reduction in MFI, calculated by calculating the difference in MFI over a 24 hour period (e.g., between 0.5 hours and 24 hours) in cells incubated with the antibody at 37°C, e.g., as described in the Examples, and multiplying by 100.

[0204] In some embodiments, an antibody has a high degree of internalization if the antibody results in a greater than 50% reduction in MFI, as measured, for example, by an ex vivo assay using PBMCs and / or NK cells as described in the Examples, calculated by calculating the difference in MFI over a 24 hour period (e.g., between 0.5 hours and 24 hours) in cells incubated with the antibody at 37°C and multiplying by 100. In some embodiments, an antibody has a high degree of internalization if incubation of the antibody with cells expressing human CD94 on their surface at 37°C for 24 hours results in a greater than 50% reduction in surface antibody staining due to internalization, as assessed using methods known in the art and / or as described above.

[0205] In some embodiments, an antibody has a low degree of internalization if the antibody causes a decrease in MFI of less than 50% (e.g., about any of 50% or less, 45% or less, 40% or less, 35% or less, 30% or less, 25% or less, 20% or less, 15% or less, 10% or less, 5% or less, 1% or less, or 0%), as measured by an ex vivo assay using PBMCs and / or NK cells, e.g., as described in the Examples, by calculating the difference in MFI over a 24 hour period (e.g., between 0.5 hours and 24 hours) in cells incubated with the antibody at 37°C and multiplying by 100. In some embodiments, antibodies of the disclosure have a low degree of internalization, resulting in about 50% or less, about 40% or less, about 35% or less, about 30% or less, about 25% or less, about 20% or less, about 15% or less, about 10% or less, about 5% or less, about 2.5% or less, about 1% or less, or about 0% reduction in MFI, calculated as described above. In some embodiments, an antibody has a low degree of internalization if incubation of the antibody with cells expressing human CD94 on their surface at 37°C for 24 hours results in less than a 50% reduction in surface antibody staining due to internalization, as assessed using methods known in the art and / or as described above.

[0206] In some embodiments, antibodies of the present disclosure have or result in an internalization activity that is at least about 5%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 99%, or about 100% less than the internalization of a control antibody, e.g., a commercial or wild-type control antibody, or an isotype control antibody, where internalization is assessed as described above and / or using any suitable method known in the art.

[0207] Antibody candidates with no or low internalization activity may be further tested for binding to cynomolgus monkey-derived and / or human-derived targets (e.g., cynomolgus monkey and / or human CD94). Antibodies that bind to cynomolgus monkey and / or human targets may be used in in vitro and in vivo cell killing assays (e.g., ADCC assays). The cell killing activity (e.g., ADCC activity) of selected antibodies may be compared with commercially available antibodies or antibodies known in the art.

[0208] E. Antibody Generation The antibodies of the present disclosure may be produced using any technique and / or method known in the art. Techniques for preparing antibodies, e.g., monoclonal antibodies (mAbs), against virtually any target antigen are well known in the art. See, for example, Kohler and Milstein, Nature 256:495 (1975), and Coligan et al. (eds.), CURRENT PROTOCOLS IN IMMUNOLOGY, VOL. 1, pages 2.5.1-2.6.7 (John Wiley & Sons 1991). Briefly, monoclonal antibodies can be obtained by injecting a composition containing an antigen (e.g., CD94, or a portion thereof) into a mouse, removing the spleen to obtain B lymphocytes, fusing the B lymphocytes with myeloma cells to produce hybridomas, cloning the hybridomas, selecting positive clones that produce antibodies against the antigen, culturing the clones that produce antibodies against the antigen, and isolating the antibodies from the hybridoma culture. One of skill in the art will recognize that if the antibody is to be administered to a human subject, the antibody will bind to a human antigen (eg, human CD94, or a portion thereof).

[0209] MAbs can be isolated and purified from hybridoma cultures by a variety of well-established techniques, including affinity chromatography with Protein-A or Protein-G Sepharose, size-exclusion chromatography, and ion-exchange chromatography. See, e.g., Coligan at pages 2.7.1-2.7.12 and pages 2.9.1-2.9.3. See also, Baines et al., "Purification of Immunoglobulin G (IgG)," in METHODS IN MOLECULAR BIOLOGY, VOL. 10, pages 79-104 (The Humana Press, Inc. 1992).

[0210] After initial generation of antibodies against an immunogen (e.g., CD94, or a portion thereof), the antibodies can be sequenced and then prepared by recombinant techniques. Humanization and chimerization of murine antibodies and antibody fragments are well known to those skilled in the art, as discussed below.

[0211] In an exemplary method for generating antibodies of the present disclosure, a recombinant target (e.g., CD94) may be used to immunize mice. Following immunization of mice, for example, as described above, the generated antibodies may be analyzed for specific or selective binding to their target (e.g., CD94) by ELISA and flow cytometry. Antibodies may be selected based on their ability to bind to the target (e.g., CD94).

[0212] In some embodiments, non-human primate antibodies may be generated. General techniques for raising therapeutically useful antibodies in baboons can be found, for example, in Goldenberg et al., WO91 / 11465 (1991), and Losman et al., Int. J. Cancer 46:310 (1990).

[0213] In some embodiments, the antibody may be a human antibody. In some embodiments, the antibody may be a monoclonal human antibody. In some embodiments, a human antibody has an amino acid sequence that corresponds to that of an antibody produced by a human or human cell, or an antibody derived from a non-human source that utilizes the human antibody repertoire or other human antibody coding sequence. Such antibodies may be obtained from transgenic mice engineered to produce specific human antibodies in response to antigenic stimulation, e.g., CD94, or a portion thereof. Methods for generating fully human antibodies using either combinatorial approaches or transgenic animals transformed with human immunoglobulin loci are known in the art (e.g., Mancini et al., 2004, New Microbiol. 27:315-28; Conrad and Scheller, 2005, Comb. Chem. High Throughput Screen. 8:117-26; Brekke and Loset, 2003, Curr. Opin. Pharmacol. 3:544-50). In certain embodiments, the claimed methods and procedures may utilize human antibodies produced by such techniques. Other methods for producing fully human antibodies include phage display, e.g., as described in Dantas-Barbosa et al., 2005, Genet. Mol. Res. 4:126-40; generation of antibodies in normal humans or from humans exhibiting a particular disease state, e.g., as described in Dantas-Barbosa et al., 2005; or the use of transgenic animals (e.g., mice) that have been genetically engineered to produce human antibodies using standard immunization protocols discussed above, such as those described in Green et al., 1999, J. Immunol. Methods 231:11-23; Green et al., Nature Genet. 7:13 (1994); Lonberg et al., Nature 368:856 (1994); and Taylor et al., Int. Immun. 6:579 (1994).

[0214] (i) In vitro cell killing assay Generation of antibodies of the present disclosure may involve testing the antibody's in vitro ADCC activity. The improved cell-killing or ADCC activity of antibodies of the present disclosure may be tested as described above, in the Examples, and / or using methods known in the art. The improved cell-killing or ADCC activity of antibodies of the present disclosure may be tested for depletion of CD94-expressing NK cells and / or T cells. Depletion of CD94-expressing NK cells and / or T cells may be tested using representative in vitro models that recapitulate activity in humans (Tomasevic, et al., Growth Factors, 2014, 32(6):223-235; Huang, et al., JCI insight, 2016;1(7):e86689). Peripheral blood lymphocytes (PBLs) isolated from the blood of normal (i.e., healthy) donors are incubated with antibodies with human Fc regions with and without fucose and / or with and without Fc region mutations. The killing level of CD94-expressing NK cells and / or T cells in PBLs (e.g., in a PBL sample) is measured using any method known in the art, such as flow cytometry (e.g., as described in the Examples). The cell killing activity (e.g., ADCC activity) of the antibodies may be tested using the above-described assays using a variety of biological samples, such as blood, synovial fluid, bone marrow, and intact splenocyte homogenates fr...

Claims

1. An antibody that binds to human CD94, the antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain; The antibody, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 47, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 48, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 63, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO:

64.

2. An antibody that binds to human CD94, the antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain; the antibody, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 109, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 110, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 111, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 112, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 113, and CDR-L3 comprising the amino acid sequence of SEQ ID NO:

64.

3. The antibody of claim 1 or claim 2, wherein the VH domain comprises an amino acid sequence having at least 90%, or at least 95%, sequence identity to the amino acid sequence of SEQ ID NO: 81, and the VL domain comprises an amino acid sequence having at least 90%, or at least 95% sequence identity to the amino acid sequence of SEQ ID NO:

82.

4. The antibody of claim 3, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 81 and the VL domain comprises the amino acid sequence of SEQ ID NO:

82.

5. The antibody according to any one of claims 1 to 4, wherein the antibody is a human antibody.

6. The antibody of any one of claims 1 to 5, wherein the antibody is an antigen-binding antibody fragment or a single-chain antibody.

7. The antibody of any one of claims 1 to 5, wherein the antibody further comprises an Fc region.

8. The antibody of claim 7 , wherein the Fc region is a human IgG1 Fc region.

9. The antibody of claim 7 or claim 8, wherein the antibody comprises a non-fucosylated human Fc region.

10. The antibody of any one of claims 7 to 9, wherein the antibody binds to human cellular Fc gamma receptor IIIA to a greater extent than an antibody comprising a wild-type human IgG1 Fc region.

11. The antibody according to any one of claims 7 to 10, which is capable of inducing antibody-dependent cellular cytotoxicity (ADCC) against cells expressing human CD94 on their surface.

12. A polynucleotide encoding the antibody of any one of claims 1 to 11.

13. A vector comprising the polynucleotide of claim 12, optionally wherein the vector is an expression vector.

14. 14. An isolated host cell comprising the polynucleotide of claim 12 or the vector of claim 13.

15. 15. A method for producing an antibody, the method comprising culturing a host cell according to claim 14 under conditions suitable for producing the antibody, and optionally, the method further comprising recovering the antibody from the host cell.

16. A pharmaceutical composition comprising the antibody of any one of claims 1 to 11 and a pharmaceutically acceptable carrier.

17. (c) inducing ADCC activity in a subject; (d) treating CLPD-NK in a subject in need thereof; (e) treating natural killer (NK) cell lymphoma or T-cell lymphoma in a subject; (f) enhancing chimeric antigen receptor T-cell (CAR-T) therapy in a subject; (g) depleting CD8+ CD94+ T cells in a subject; or (h) depleting NK cells in a subject. A pharmaceutical comprising the antibody of any one of claims 1 to 11 for use in a method for: (a) treating a disease or disorder in a subject; (b) reducing the number of peripheral blood LGL cells and / or NK cells in a subject; (c) inducing ADCC activity in a subject; (d) treating CLPD-NK in a subject in need thereof; (e) treating natural killer (NK) cell lymphoma or T-cell lymphoma in a subject; (f) enhancing chimeric antigen receptor T-cell (CAR-T) therapy in a subject; (g) depleting CD8+ CD94+ T cells in a subject; or (h) depleting NK cells in a subject.

18. 18. The medicament of claim 17, wherein the medicament is for use in a method for treating a disease or disorder in a subject, wherein the disease or disorder is Felty's syndrome, inclusion body myositis, aggressive NK leukemia, rheumatoid arthritis, LGL leukemia, CLPD-NK, NK cell lymphoma, T cell lymphoma, or microscopic colitis.

19. 18. The medicament of claim 17, wherein the medicament is for use in a method for treating NK cell lymphoma or T cell lymphoma in a subject, wherein the NK cell lymphoma or T cell lymphoma is extranodal NK / T cell lymphoma, hepatosplenic T cell lymphoma (TCL), enteropathy-associated TCL, cutaneous TCL, anaplastic large cell lymphoma (ALK+), anaplastic large cell lymphoma (ALK-), peripheral TCL, angioimmunoblastic TCL, adult TCL, monomorphic epitheliotropic intestinal TCL, epidermotropic CD8+ cutaneous TCL, primary cutaneous gamma / delta TCL, or subcutaneous panniculitis TCL, and optionally the NK cell lymphoma or T cell lymphoma is extranodal NK / T cell lymphoma, hepatosplenic TCL, or enteropathy-associated TCL.

20. The medicament according to any one of claims 17 to 19, further comprising an IL-2 polypeptide.

21. The pharmaceutical composition according to any one of claims 17 to 20, wherein the subject is a human.

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