CLEC2d binding proteins and related methods

Abstract

Provided herein are CLEC2D binding proteins (e.g., antibodies) and compositions (e.g., pharmaceutical compositions) comprising the same; as well as methods of making the CLEC2D binding proteins (e.g., antibodies) and compositions. The CLEC2D binding proteins provided herein are useful in e.g., pharmaceutical compositions and various methods, including methods of treating diseases (e.g., cancer (e.g., solid tumors)).

Description

CLEC2D BINDING PROTEINS AND RELATED METHODSRELATED APPLICATIONS

[0001] This application claims priority to U.S. Serial No.: 63 / 594,254, filed October 30, 2023, the entire contents of which is incorporated herein by reference.1. FIELD

[0002] This disclosure relates to CLEC2D binding proteins and nucleic acid molecules encoding the same. The disclosure further related to methods of manufacturing and utilizing the same, including, e.g., methods of treating cancer {e.g., a solid tumor).2. BACKGROUND

[0003] CLEC2D is a member of the C type lectin receptor superfamily. In humans, the protein is encoded by a single CLEC2D gene that is precent in the human natural killer gene complex. Multiple isoforms of human CLEC2D are known to be produced by alternative splicing, with isoform 1 being the only isoform predominantly expressed at the cell surface. CLEC2D is known to be expressed by e.g., myeloid cells, such as B cells, as well as on activated dendritic cells {e.g., plasmacytoid dendritic cells and classical dendritic cells). Surface CLEC2D is expressed as a disulfide-bonded homodimer and acts as a ligand for type II transmembrane C-type lectin-like receptor CD 161. CLEC2D / CD161 interactions play a role in regulating immune responses in various contexts, including, e.g., infectious diseases, autoimmunity, inflammatory conditions and cancer. CLEC2D is further known to, inter alia, bind histones released upon necrotic cell death that e.g., can stimulate inflammation and amplify tissue injury.3. SUMMARY

[0004] Provided herein are, inter alia, CLEC2D binding proteins and nucleic acid molecules encoding the same; fusions and conjugates comprising the CLEC2D binding proteins; methods of manufacturing; pharmaceutical compositions; and methods of use including e.g., methods of treating cancer, methods of inhibiting binding of CD161 to CLEC2D, and diagnostics.

[0005] Accordingly, in one aspect provided herein are CLEC2D binding proteins e.g., antibodies) comprising a binding domain that specifically binds CLEC2D {e.g., hCLEC2D), wherein the binding domain comprises: (a) a VH region comprising (i) a CDR-H1 comprising theamino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions); (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 4, or the amino acid sequence set forth in SEQ ID NO: 4 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions); and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 5, or the amino acid sequence set forth in SEQ ID NO: 5 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions); and (b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 6, or the amino acid sequence set forth in SEQ ID NO: 6 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions); (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7, or the amino acid sequence set forth in SEQ ID NO: 7 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions); and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 8, or the amino acid sequence set forth in SEQ ID NO: 8 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions).

[0006] In some embodiments, the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VH region set forth in Table 2. In some embodiments, the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VL region set forth in Table 2. In some embodiments, the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 9. In some embodiments, the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, (a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 9; and (b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 10.

[0007] In some embodiments, (a) the VH region comprises (i) a CDR-H1 comprising theamino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions); (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 4, or the amino acid sequence set forth in SEQ ID NO: 4 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions); and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 5, or the amino acid sequence set forth in SEQ ID NO: 5 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions) and the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 9; and (b) the VL region comprises (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 6, or the amino acid sequence set forth in SEQ ID NO: 6 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions); (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7, or the amino acid sequence set forth in SEQ ID NO: 7 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions); and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 8, or the amino acid sequence set forth in SEQ ID NO: 8 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions) and the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 10.

[0008] In some embodiments, the CLEC2D binding protein or domain comprises a heavy chain (HC). In some embodiments, the CLEC2D binding protein or domain comprises a light chain (LC). In some embodiments, the HC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a HC set forth in Table 2. In some embodiments, the LC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a LC set forth in Table 2. In some embodiments, the HC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 11. In some embodiments, the LC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 12. In someembodiments, (a) the HC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 11; and (b) the LC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 12.

[0009] In one aspect provided herein are CLEC2D binding proteins (e.g., antibodies) comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises: (a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 3; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 4; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 5; and a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 6; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 8.

[0010] In some embodiments, the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VH region set forth in Table 2. In some embodiments, the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VL region set forth in Table 2. In some embodiments, the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 9. In some embodiments, the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, (a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 9; and (b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 10.

[0011] In some embodiments, (a) the VH region comprises (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ IDNO: 3 comprising 1 , 2, or 3 amino acid variations (e.g., substitutions, deletions, additions); (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 4, or the amino acid sequence set forth in SEQ ID NO: 4 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions); and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 5, or the amino acid sequence set forth in SEQ ID NO: 5 comprising 1, 2, or 3 amino acid variations e.g., substitutions, deletions, additions) and the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 9; and (b) the VL region comprises (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 6, or the amino acid sequence set forth in SEQ ID NO: 6 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions); (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7, or the amino acid sequence set forth in SEQ ID NO: 7 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions); and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 8, or the amino acid sequence set forth in SEQ ID NO: 8 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions) and the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 10.

[0012] In some embodiments, the CLEC2D binding protein or domain comprises a heavy chain (HC). In some embodiments, the CLEC2D binding protein or domain comprises a light chain (LC). In some embodiments, the HC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a HC set forth in Table 2. In some embodiments, the LC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a LC set forth in Table 2. In some embodiments, the HC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 11. In some embodiments, the LC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 12. In some embodiments, (a) the HC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%,90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 11; and (b) the LC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 12.

[0013] In one aspect provided herein are CLEC2D binding proteins (e.g., antibodies) comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises: (a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence of a CDR-H1 set forth in Table 2, or the amino acid sequence of a CDR-H1 set forth in Table 2 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions); (ii) a CDR-H2 comprising the amino acid sequence of a CDR-H2 set forth in Table 2, or the amino acid sequence of a CDR-H2 set forth in Table 2 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions); and (iii) a CDR-H3 comprising the amino acid sequence of a CDR-H3 set forth in Table 2, or the amino acid sequence of a CDR-H3 set forth in Table 2 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions); and (b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence of a CDR-L1 set forth in Table 2, or the amino acid sequence of a CDR-L1 set forth in Table 2 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions); (ii) a CDR-L2 comprising the amino acid sequence of a CDR-L2 set forth in Table 2, or the amino acid sequence of a CDR-L2 set forth in Table 2 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions); and (iii) a CDR-L3 comprising the amino acid sequence of a CDR-L3 set forth in Table 2, or the amino acid sequence of a CDR-L3 set forth in Table 2 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions).

[0014] In some embodiments, the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VH region set forth in Table 2. In some embodiments, the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VL region set forth in Table 2. In some embodiments, the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 9. In some embodiments, the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%,95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, (a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 9; and (b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 10.

[0015] In some embodiments, (a) the VH region comprises (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions); (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 4, or the amino acid sequence set forth in SEQ ID NO: 4 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions); and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 5, or the amino acid sequence set forth in SEQ ID NO: 5 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions) and the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 9; and (b) the VL region comprises (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 6, or the amino acid sequence set forth in SEQ ID NO: 6 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions); (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7, or the amino acid sequence set forth in SEQ ID NO: 7 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions); and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 8, or the amino acid sequence set forth in SEQ ID NO: 8 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions) and the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 10.

[0016] In some embodiments, the CLEC2D binding protein or domain comprises a heavy chain (HC). In some embodiments, the CLEC2D binding protein or domain comprises a light chain (LC). In some embodiments, the HC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to theamino acid sequence of a HC set forth in Table 2. In some embodiments, the LC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a LC set forth in Table 2. In some embodiments, the HC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 11. In some embodiments, the LC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 12. In some embodiments, (a) the HC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 11; and (b) the LC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 12.

[0017] In one aspect provided herein are CLEC2D binding proteins (e.g., antibodies) comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises: (a) a VH region comprising a CDR-H1, CDR-H2, and CDR-H3 of SEQ ID NO: 9; and (b) a VL region comprising a CDR-L1, CDR-L2, and CDR-L3 of SEQ ID NO: 10.

[0018] In some embodiments, the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VH region set forth in Table 2. In some embodiments, the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VL region set forth in Table 2. In some embodiments, the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 9. In some embodiments, the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, (a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 9; and (b) the amino acid sequenceof the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 10.

[0019] In some embodiments, (a) the VH region comprises (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions); (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 4, or the amino acid sequence set forth in SEQ ID NO: 4 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions); and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 5, or the amino acid sequence set forth in SEQ ID NO: 5 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions) and the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 9; and (b) the VL region comprises (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 6, or the amino acid sequence set forth in SEQ ID NO: 6 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions); (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7, or the amino acid sequence set forth in SEQ ID NO: 7 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions); and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 8, or the amino acid sequence set forth in SEQ ID NO: 8 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions) and the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 10.

[0020] In some embodiments, the CLEC2D binding protein or domain comprises a heavy chain (HC). In some embodiments, the CLEC2D binding protein or domain comprises a light chain (LC). In some embodiments, the HC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a HC set forth in Table 2. In some embodiments, the LC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a LC set forth in Table 2. In some embodiments, the HC comprises an amino acid sequence at least 85%, 86%, 87%, 88%,89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 11. In some embodiments, the LC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 12. In some embodiments, (a) the HC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 11; and (b) the LC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 12.

[0021] In one aspect provided herein are CLEC2D binding proteins (e.g., antibodies) comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises: (a) a VH region comprising a CDR-H1, CDR-H2, and CDR-H3 of a VH region set forth in Table 2; and (b) a VL region comprising a CDR-L1, CDR-L2, and CDR- L3 of a VL region set forth in Table 2.

[0022] In some embodiments, the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VH region set forth in Table 2. In some embodiments, the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VL region set forth in Table 2. In some embodiments, the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 9. In some embodiments, the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, (a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 9; and (b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 10.

[0023] In some embodiments, (a) the VH region comprises (i) a CDR-H1 comprising theamino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions); (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 4, or the amino acid sequence set forth in SEQ ID NO: 4 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions); and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 5, or the amino acid sequence set forth in SEQ ID NO: 5 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions) and the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 9; and (b) the VL region comprises (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 6, or the amino acid sequence set forth in SEQ ID NO: 6 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions); (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7, or the amino acid sequence set forth in SEQ ID NO: 7 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions); and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 8, or the amino acid sequence set forth in SEQ ID NO: 8 comprising 1, 2, or 3 amino acid variations (e.g., substitutions, deletions, additions) and the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 10.

[0024] In some embodiments, the CLEC2D binding protein or domain comprises a heavy chain (HC). In some embodiments, the CLEC2D binding protein or domain comprises a light chain (LC). In some embodiments, the HC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a HC set forth in Table 2. In some embodiments, the LC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a LC set forth in Table 2. In some embodiments, the HC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 11. In some embodiments, the LC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 12. In someembodiments, (a) the HC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 11; and (b) the LC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 12.

[0025] In one aspect, provided herein are CLEC2D binding proteins (e.g., antibodies) comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises: (a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 3; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 4; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 5; and (b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 6; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 8.

[0026] In some embodiments, (a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 9; and (b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 10.

[0027] In one aspect, provided herein are CLEC2D binding proteins (e.g., antibodies) comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises: (a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 3; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 4; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 5; and (b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 66; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 67; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 68.

[0028] In some embodiments, (a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 9; and (b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%,97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 69.

[0029] In one aspect, provided herein are CLEC2D binding proteins (e.g., antibodies) comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises: (a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 3; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 4; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 5; and (b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 70; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 71; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 68.

[0030] In some embodiments, (a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 9; and (b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 72.

[0031] In one aspect, provided herein are CLEC2D binding proteins (e.g., antibodies) comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises: (a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 3; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 4; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 5; and (b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 73; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 74; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 75.

[0032] In some embodiments, (a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 9; and (b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 76.

[0033] In one aspect, provided herein are CLEC2D binding proteins (e.g., antibodies)comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises: (a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 3; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 77; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 78; and (b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 6; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 8.

[0034] In some embodiments, (a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 79; and (b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 10.

[0035] In one aspect, provided herein are CLEC2D binding proteins (e.g., antibodies) comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises: (a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 3; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 80; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 81; and (b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 6; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 8.

[0036] In some embodiments, (a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 82; and (b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 10.

[0037] In one aspect, provided herein are CLEC2D binding proteins (e.g., antibodies) comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises: (a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 3; (ii) a CDR-H2 comprising the amino acid sequence set forthin SEQ ID NO: 77; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 78; and (b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 6; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 8.

[0038] In some embodiments, (a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 83; and (b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 10.

[0039] In one aspect, provided herein are CLEC2D binding proteins (e.g., antibodies) comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises: (a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 3; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 77; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 78; and (b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 70; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 71; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 68.

[0040] In some embodiments, (a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 83; and (b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 72.

[0041] In one aspect, provided herein are CLEC2D binding proteins (e.g., antibodies) comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises: (a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 3; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 80; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 81; and (b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 73; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ IDNO: 74; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 75.

[0042] In some embodiments, (a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 82; and (b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 76.

[0043] In one aspect, provided herein are CLEC2D binding proteins (e.g., antibodies) comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises: (a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 3; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 80; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 81; and (b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 84; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 85; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 86.

[0044] In some embodiments, (a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 87 ; and (b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 88.

[0045] In one aspect, provided herein are CLEC2D binding proteins (e.g., antibodies) comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises: (a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 3; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 80; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 81; and (b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 89; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 74; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 68.

[0046] In some embodiments, (a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identicalto the amino acid sequence set forth in any one of SEQ ID NO: 87; and (b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 90.

[0047] In one aspect, provided herein are CLEC2D binding proteins (e.g., antibodies) comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises: (a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 91; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 92; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 93; and (b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 6; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 152.

[0048] In some embodiments, (a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 4; and (b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 95.

[0049] In one aspect, provided herein are CLEC2D binding proteins e.g., antibodies) comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises: (a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 91; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 92; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 96; and (b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 97; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 98.

[0050] In some embodiments, (a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 99; and (b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO:100.

[0051] In one aspect, provided herein arc CLEC2D binding proteins (e.g., antibodies) comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises: (a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 91; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 92; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 101; and (b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 97; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 102.

[0052] In some embodiments, (a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 103; and (b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 104.

[0053] In one aspect, provided herein are CLEC2D binding proteins (e.g., antibodies) comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises: (a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 105; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 106; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 107; and (b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 6; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 108.

[0054] In some embodiments, (a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 109; and (b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 110.

[0055] In one aspect, provided herein are CLEC2D binding proteins (e.g., antibodies)comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises: (a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 91; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 92; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 111; and (b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 97; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 112.

[0056] In some embodiments, (a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 113; and (b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 114.

[0057] In one aspect, provided herein are CLEC2D binding proteins (e.g., antibodies) comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises: (a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 3; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 4; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 115; and (b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 97; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 116.

[0058] In some embodiments, (a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 117; and (b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 118.

[0059] In one aspect, provided herein are CLEC2D binding proteins (e.g., antibodies) comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises: (a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 119; (ii) a CDR-H2 comprising the amino acid sequence setforth in SEQ TD NO: 120; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 121; and (b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 6; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 122.

[0060] In some embodiments, (a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 123; and (b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 124.

[0061] In one aspect, provided herein are CLEC2D binding proteins (e.g., antibodies) comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises: (a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 91; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 92; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 153; and (b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 97; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 125.

[0062] In some embodiments, (a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 126; and (b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 127.

[0063] In one aspect, provided herein are CLEC2D binding proteins e.g., antibodies) comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises: (a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 119; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 120; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 128; and (b) a VL region comprising (i) a CDR-L1 comprising the amino acidsequence set forth in SEQ TD NO: 6; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 129.

[0064] In some embodiments, (a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 130; and (b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 131.

[0065] In one aspect, provided herein are CLEC2D binding proteins (e.g., antibodies) comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises: (a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 91; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 92; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 132; and (b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 97; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 133.

[0066] In some embodiments, (a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 134; and (b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 135.

[0067] In one aspect, provided herein are CLEC2D binding proteins (e.g., antibodies) comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises: (a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 136; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 137; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 138; and (b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 97; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ IDNO: 139.

[0068] In some embodiments, (a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 140; and (b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 141.

[0069] In one aspect, provided herein are CLEC2D binding proteins (e.g., antibodies) comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises: (a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 136; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 137; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 142; and (b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 6; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 143.

[0070] In some embodiments, (a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 144; and (b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 145.

[0071] In one aspect, provided herein are CLEC2D binding proteins (e.g., antibodies) comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises: (a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 146; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 77; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 78; and (b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 147; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 74; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 75.

[0072] In some embodiments, (a) the amino acid sequence of the VH region is at least 85%,86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 148; and (b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 148.

[0073] In one aspect, provided herein are CLEC2D binding proteins (e.g., antibodies) comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises: (a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 146; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 77; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 78; and (b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 66; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 71; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 150.

[0074] In some embodiments, (a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 148; and (b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 151.

[0075] For the sake of clarity, it should be understood that any of the following embodiments are applicable to any of the foregoing aspects as if recited directly following each aspect.

[0076] In some embodiments, the CLEC2D binding protein (or the binding domain) comprises an antibody. In some embodiments, the CLEC2D binding protein (or the binding domain) comprises an IgG (e.g., IgGi, IgG2 (e.g., IgGia or IgGib), IgGa, IgG4), IgE, IgM, IgD, or IgA (e.g., IgAi or IgAo) antibody. In some embodiments, the CLEC2D binding protein (or the binding domain) comprises one or more of a monoclonal antibody, monospecific antibody, multispecific antibody, human antibody, humanized antibody, chimeric antibody, and / or murine antibody, or a functional fragment or functional variant of any of the foregoing. In some embodiments, the CLEC2D binding protein (or the binding domain) comprises one or more of a full-length antibody, scFv, Fab, F(ab')2, Fab', Fv, single domain antibody (e.g., a VHH), scFv-Fc, Fab-Fc, and / or single domain antibody-Fc (e.g., VHH-Fc).

[0077] In some embodiments, the CEEC2D binding protein comprises an Ig Fc (e.g., hlg Fc) region. In some embodiments, the Ig Fc (e.g., a hlg Fc) region comprises at least a portion of a hinge region, a CH2 region, and a CH3 region. In some embodiments, the Ig Fc (e.g., a hlg Fc) region comprises a hinge region, a CH2 region, and a CH3 region. In some embodiments, the Ig Fc (e.g., a hlg Fc) region is a hlgG (e.g., hlgGl, hIgG2, hIgG3, hIgG4). In some embodiments, the Ig Fc (e.g., a hlg Fc) region is part of a full-length antibody. In some embodiments, the CEEC2D binding protein comprises a first Ig Fc (e.g., a first hlg Fc) region and a second Ig Fc (e.g., a first hlg Fc) region. In some embodiments, the first Ig Fc (e.g., the first hlg Fc) region and the second Ig Fc (e.g., the second hlg Fc) each comprises at least a portion of a hinge region, a CH2 region, and a CH3 region. In some embodiments, the first Ig Fc (e.g., the first hlg Fc) region and the second Ig Fc (e.g., the second hlg Fc) each comprises a hinge region, a CH2 region, and a CH3 region. In some embodiments, the first Ig Fc (e.g., the first hlg Fc) region and the second Ig Fc (e.g., the second hlg Fc) each is a hlgG (e.g., hlgGl, hIgG2, hIgG3, hIgG4). In some embodiments, the first Ig Fc (e.g., the first hlg Fc) and the second Ig Fc (e.g., the second hlg Fc) regions are part of a full-length antibody.

[0078] In some embodiments, the Ig Fc (e.g., the hlg Fc), the first Ig Fc (e.g., the first hlg Fc), and / or the second Ig Fc (e.g., the second hlg Fc) comprises one or more amino acid variation and / or varied glycosylation relative to a reference Ig Fc region (e.g., a reference hlg Fc). In some embodiments, the Ig Fc (e.g., the hlg Fc), the first Ig Fc (e.g., the first hlg Fc), and / or the second Ig Fc (e.g., the second hlg Fc) comprises an amino acid variation at position N297, EU numbering according to Kabat.

[0079] In some embodiments, the Ig Fc (e.g., the hlg Fc), the first Ig Fc (e.g., the first hlg Fc), and / or the second Ig Fc (e.g., the second hlg Fc) exhibits an alteration in one or more effector function relative to a reference Ig Fc region (e.g., a reference hlg Fc). In some embodiments, the Ig Fc (e.g., the hlg Fc), the first Ig Fc (e.g., the first hlg Fc), and / or the second Ig Fc (e.g., the second hlg Fc) exhibits enhanced effector function relative to a reference Ig Fc region. In some embodiments, the Ig Fc (e.g., the hlg Fc), the first Ig Fc (e.g., the first hlg Fc), and / or the second Ig Fc (e.g., the second hlg Fc) exhibits reduced effector function relative to a reference Ig Fc region (e.g., a reference hlg Fc).

[0080] In some embodiments, the Ig Fc (e.g., the hlg Fc), the first Ig Fc (e.g., the first hlg Fc), and / or the second Ig Fc (e.g., the second hlg Fc) comprises one or more amino acid variationand / or varied glycosylation relative to a reference Ig Fc region (e.g., a reference hlg Fc), wherein the one or more amino acid variations and / or varied glycosylation alter one or more effector function. In some embodiments, the Ig Fc (e.g., the hlg Fc), the first Ig Fc (e.g., the first hlg Fc), and / or the second Ig Fc (e.g., the second hlg Fc) comprises one or more amino acid variation and / or varied glycosylation relative to a reference Ig Fc region (e.g., a reference hlg Fc), wherein the one or more amino acid variations and / or varied glycosylation enhance one or more effector function.

[0081] In some embodiments, the Ig Fc (e.g., the hlg Fc), the first Ig Fc (e.g., the first hlg Fc), and / or the second Ig Fc (e.g., the second hlg Fc) comprises one or more amino acid variation and / or varied glycosylation relative to a reference Ig Fc region (e.g., a reference hlg Fc), wherein the one or more amino acid variations and / or varied glycosylation reduce one or more effector function. In some embodiments, the effector comprises ADCC, CDC, and / or binding affinity to one or more Fc receptor (e.g., an Fey receptor (e.g., FcyRI, FcyRIIa, FcyRIIc, FcyRIIIa, and / or FcyRIIIb (e.g., FcyRI, Fcylla, and / or Fcyllla))).

[0082] In some embodiments, the antigen binding domain specifically binds CLEC2D (e.g., hCLEC2D) expressed on the surface of a cell (e.g., a target cell). In some embodiments, binding of the CLEC2D binding protein to CLEC2D inhibits (e.g., partially, substantially, fully) binding of CLEC2D to CD161.

[0083] In some embodiments, the CLEC2D binding protein further comprises a heterologous moiety (e.g., a heterologous protein). In some embodiments, the CLEC2D binding protein further comprises 2, 3, 4, or 5 or more heterologous moieties. In some embodiments, the heterologous moiety is attached to the N-terminus, C-terminus, and / or internally between the N- and C-terminus of the CLEC2D binding protein. In some embodiments, the heterologous moiety (e.g., heterologous polypeptide) is directly attached to the CLEC2D binding protein. In some embodiments, the heterologous moiety (e.g., heterologous polypeptide) is indirectly attached to the CLEC2D binding protein. In some embodiments, the heterologous moiety (e.g., heterologous polypeptide) is indirectly attached to the CLEC2D binding protein via a linker. In some embodiments, the heterologous moiety is a peptide, polypeptide, protein, nucleic acid molecule (e.g., DNA, RNA), carbohydrate, lipid, polymer, or small molecule. In some embodiments, the heterologous moiety is a detectable tag and / or a reporter gene. In some embodiments, the heterologous moiety is a therapeutic agent.

[0084] In some embodiments, the CLEC2D binding protein is isolated. In some embodiments, the CLEC2D binding protein is recombinant.

[0085] In one aspect, provided herein are conjugates comprising a CLEC2D binding protein described herein and a heterologous moiety. In some embodiments, the conjugate comprises 2, 3, 4, or 5 or more heterologous moieties. In some embodiments, the heterologous moiety is attached to the N-terminus, C-terminus, and / or internally between the N- and C-terminus of the CLEC2D binding protein. In some embodiments, the heterologous moiety (e.g., heterologous polypeptide) is directly attached to the CLEC2D binding protein, hi some embodiments, the heterologous moiety (e.g., heterologous polypeptide) is indirectly attached to the CLEC2D binding protein. In some embodiments, the heterologous moiety (e.g., heterologous polypeptide) is indirectly attached to the CLEC2D binding protein via a linker. In some embodiments, the heterologous moiety is a peptide, polypeptide, carbohydrate, lipid, polymer, or small molecule. In some embodiments, the heterologous moiety is a therapeutic agent. In some embodiments, the therapeutic agent is a small molecule.

[0086] In one aspect, provided herein are fusion proteins comprising a CLEC2D binding protein described herein and a heterologous protein. In some embodiments, the heterologous protein comprises a cytokine (or functional fragment or functional variant thereof), a chemokine (or a functional fragment or functional variant thereof), or an antibody (or a functional fragment or functional variant thereof). In some embodiments, the heterologous protein is fused to the N- terminus, C-terminus, and / or internally between the N- and C-terminus of the endonuclease. In some embodiments, the heterologous protein is fused directly to the endonuclease. In some embodiments, the heterologous protein is fused indirectly to the endonuclease. In some embodiments, the heterologous protein is fused indirectly to the endonuclease via a peptide linker.

[0087] In one aspect, provided herein are nucleic acid molecules encoding a CLEC2D binding protein described herein or a fusion protein described herein. In some embodiments, the nucleic acid molecule is a DNA or RNA (e.g., mRNA) molecule. In some embodiments, the nucleic acid molecule is codon optimized. In some embodiments, the nucleic acid molecule further comprises one or more transcription or translation regulatory elements (e.g., promoter, enhancer (e.g., cell or tissue specific transcription regulatory elements).

[0088] In one aspect, provided herein are vectors comprising a nucleic acid molecule described herein. In some embodiments, the vector is a viral vector or a non-viral vector (e.g., plasmid,minicircle). In some embodiments, the vector is a viral vector (e.g., an adeno associated viral (AAV) vector, a Icntiviral vector, an adenoviral vector).

[0089] In one aspect, provided herein are carriers comprising a CLEC2D binding protein described herein, a fusion protein described herein, a conjugate described herein, a nucleic acid molecule described herein, a vector described herein, a cell described herein, or a pharmaceutical composition described herein. In some embodiments, the carrier is a nanoparticle, polymer, virus (e.g., a recombinant virus), virus like particle, virosome, fusosome, vesicle, or lipid-based carrier (e.g., a lipid nanoparticle (LNP), liposome, lipoplex, nanoliposome, an exosome, or a micelle).

[0090] In one aspect, provided herein are cells comprising a CLEC2D binding protein described herein, a fusion protein described herein, a conjugate described herein, a nucleic acid molecule described herein, a vector described herein, a carrier described herein, or a pharmaceutical composition described herein.

[0091] In one aspect, provided herein are pharmaceutical compositions comprising a CLEC2D binding protein described herein, a fusion protein described herein, a conjugate described herein, a nucleic acid molecule described herein, a vector described herein, a cell described herein, or a carrier described herein, and a pharmaceutically acceptable excipient.

[0092] In one aspect, provided herein are kits comprising a CLEC2D binding protein described herein, a fusion protein described herein, a conjugate described herein, a nucleic acid molecule described herein, a vector described herein, a cell described herein, a carrier described herein, or a pharmaceutical composition described herein; and optionally instructions for using any one or more of the foregoing.

[0093] In one aspect, provided herein are kits comprising a CLEC2D binding protein described herein, a fusion protein described herein, or a conjugate described herein; and a labeled secondary antibody that specifically binds the CLEC2D binding protein, the fusion protein, or the conjugate.

[0094] In one aspect, provided herein are methods of manufacturing a CLEC2D binding protein described herein, a fusion protein described herein, a conjugate described herein, the method comprising: introducing into a cell a nucleic acid molecule described herein, a vector described herein, or a carrier described herein; culturing the cell under conditions that allow for expression of the CLEC2D binding protein, the conjugate, or the fusion protein; and optionally recovering the expressed the CLEC2D binding protein, the conjugate, or the fusion protein from the culture; and optionally purifying the expressed the CLEC2D binding protein, the conjugate, orthe fusion protein from the culture.

[0095] In one aspect, provided herein arc methods of delivering a CLEC2D binding protein, fusion protein, a conjugate, nucleic acid molecule, vector, carrier, cell, composition, pharmaceutical composition, or system to a cell, the method comprising, delivering to the cell a CLEC2D binding protein described herein, a fusion protein described herein, a conjugate described herein, a nucleic acid molecule described herein, a vector described herein, a cell described herein, a carrier described herein, or a pharmaceutical composition described herein, to thereby deliver the CLEC2D binding protein, the fusion protein, the conjugate protein, the nucleic acid molecule, the vector, the carrier, the cell, or the pharmaceutical composition to the cell.

[0096] In one aspect, provided herein are methods of delivering a CLEC2D binding protein, fusion protein, a conjugate, nucleic acid molecule, vector, carrier, cell, composition, pharmaceutical composition, or system to a subject, the method comprising, administering to the subject a CLEC2D binding protein described herein, a fusion protein described herein, a conjugate described herein, a nucleic acid molecule described herein, a vector described herein, a cell described herein, a carrier described herein, or a pharmaceutical composition described herein, to thereby deliver the CLEC2D binding protein, the fusion protein, the conjugate protein, the nucleic acid molecule, the vector, the carrier, the cell, or the pharmaceutical composition to the subject.

[0097] In one aspect, provided herein are methods of delivering a CLEC2D binding protein, fusion protein, a conjugate, nucleic acid molecule, vector, carrier, cell, composition, pharmaceutical composition, or system to a cell in a subject, the method comprising, administering to the subject a CLEC2D binding protein described herein, a fusion protein described herein, a conjugate described herein, a nucleic acid molecule described herein, a vector described herein, a cell described herein, a carrier described herein, or a pharmaceutical composition described herein, to thereby deliver the CLEC2D binding protein, the fusion protein, the conjugate protein, the nucleic acid molecule, the vector, the carrier, the cell, or the pharmaceutical composition to the cell in the subject.

[0098] In one aspect, provided herein are methods of inhibiting binding of CLEC2D to CD 161 in a subject, the method comprising administering to the subject a CLEC2D binding protein described herein, a fusion protein described herein, a conjugate described herein, a nucleic acid molecule described herein, a vector described herein, a cell described herein, a carrier described herein, or a pharmaceutical composition described herein, to thereby inhibit binding of CLEC2Dto CD161.

[0099] In one aspect, provided herein arc methods of treating, ameliorating, or preventing a disease in a subject in need thereof, the method comprising administering to the subject a CLEC2D binding protein described herein, a fusion protein described herein, a conjugate described herein, a nucleic acid molecule described herein, a vector described herein, a cell described herein, a carrier described herein, or a pharmaceutical composition described herein, to thereby treat, ameliorate, or prevent the CLEC2D associated disease in the subject.

[0100] In one aspect, provided herein are methods of treating, ameliorating, or preventing cancer in a subject in need thereof, the method comprising administering to the subject a CLEC2D binding protein described herein, a fusion protein described herein, a conjugate described herein, a nucleic acid molecule described herein, a vector described herein, a cell described herein, a carrier described herein, or a pharmaceutical composition described herein, to thereby treat, ameliorate, or prevent the cancer in the subject.

[0101] In one aspect, provided herein are in vitro methods for detecting a population of CLEC2D-expressing cells (e.g., a population of cells expressing CLEC2D on the cell surface) in a subject, the method comprising (a) contacting a sample comprising a population of cells from the subject with a CLEC2D binding protein described herein, a conjugate described herein, or a fusion protein described herein; and (b) detecting the binding of the CLEC2D binding protein, the conjugate, or the fusion protein to a population of cells in the sample; wherein the binding of the CLEC2D binding protein, the conjugate, or the fusion protein to a population of cells within the sample indicates the presence of a population of CLEC2D-expressing cells (e.g., a population of cells expressing CLEC2D on the cell surface).

[0102] In one aspect, provided herein are CLEC2D binding proteins, fusion proteins, conjugates, nucleic acid molecules, vectors, cells, or pharmaceutical compositions for use in the treatment of a disease e.g., cancer) in a subject in need thereof.

[0103] In one aspect, provided herein are CLEC2D binding proteins, fusion proteins, conjugates, nucleic acid molecules, vectors, cells, or pharmaceutical compositions for use as a medicament.

[0104] In one aspect, provided herein are use of a CLEC2D binding protein described herein, fusion protein described herein, conjugate described herein, nucleic acid molecule described herein, vector described herein, cell described herein, or pharmaceutical composition describedherein for the manufacture of a medicament for the treatment of a disease (e.g., cancer) in a subject in need thereof.4. BRIEF DESCRIPTION OF THE DRAWINGS

[0105] FIG. 1 is a line graph showing the normalized binding of a CLEC2D binding protein (SEQ ID NOS: 11-12) to CLEC2D expressed on the surface of an engineered cell line.

[0106] FIG. 2 is a line graph showing the normalized binding of CLEC2D to CD 161 in the presence of a CLEC2D binding protein (SEQ ID NOS: 11-12) or hlgG control.

[0107] FIG. 3 is a bar graph showing the internalization of a CLEC2D binding protein (SEQ ID NOS: 11-12) into CLEC2D expressing cells in vitro as compared to an isotype control antibody.

[0108] FIG. 4 is a graphical depiction of the relative level and percent of CLEC2D expressing cells within various tumor infiltrating immune cell subsets, including, T cells, B cells, NK cells, classical dendritic cells (eDCs), plasmacytoid dendritic cells (pDCs), and macrophages, in an ovarian tumor sample.

[0109] FIG. 5 is a bar graph showing the percent of tumor infiltrating CD11B+ myeloid cells expressing CLEC2D in various solid tumors, including head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and renal cell carcinoma (RCC).

[0110] FIG. 6A is a line graph showing the binding of the indicated anti-CLEC2D antibody (at the indicated concentration) to endogenous CLEC2D expressed on the surface of Nalm6 cells. FIG. 6B is a line graph showing the binding of the indicated anti-CLEC2D antibody (at the indicated concentration) to CLEC2D knockout Nalm6 cells (no binding observed).

[0111] FIG. 7 is a line graph showing the binding of the indicated anti-CLEC2D antibody (at the indicated concentration) to endogenous CLEC2D expressed on the surface of Nalm6 cells.

[0112] FIG. 8A is a line graph showing the binding of the indicated anti-CLEC2D antibody (at the indicated concentration) to endogenous CLEC2D expressed on the surface of Nalm6 cells. FIG. 8B is a line graph showing the binding of the indicated anti-CLEC2D antibody (at the indicated concentration) to CLEC2D knockout Nalm6 cells (no binding observed).

[0113] FIG. 9 is a line graph showing the blocking of human CD 161 binding to CD 161 expressed by HEK cells by the indicated anti-CLEC2D antibody (at the indicated concentration).

[0114] FIG. 10 is a line graph showing the blocking of signaling mediated throughCD161 / CLEC2D binding in a Jurkat-CD161 / Raji (CLEC2D+) signaling assay by the indicated anti-CLEC2D antibody (at the indicated concentration).

[0115] FIG. 11 is a bar graph showing the cellular internalization of the indicated anti- CLEC2D antibody (Ratio = MFI (Test Antibody ) / MFI (Ab-1)).

[0116] FIG. 12A is a graphical depiction of the key for each of FIGS. 12B-12F. FIG. 12B is a line graph showing the binding of each of the indicated anti-CLEC2D antibodies to fresh HEK cells not expressing CLEC2D (no binding observed). FIG. 12C is a line graph showing the binding of each of the indicated anti-CLEC2D antibodies to fixed HEK cells not expressing CLEC2D (no binding observed). FIG. 12D is a line graph showing the binding of each of the indicated anti- CLEC2D antibodies to fixed HEK expressing human CLEC2D. FIG. 12E is a line graph showing the binding of each of the indicated anti-CLEC2D antibodies to fresh HEK expressing human CLEC2D. FIG. 12F is a line graph showing the binding of each of the indicated anti-CLEC2D antibodies to fresh HEK expressing cyno CLEC2D.

[0117] FIG. 13A is an IHC image showing staining of human and cyno CLEC2D expressed by HEK cells by Ab-25. FIG. 13B is an IHC image showing staining of human and cyno CLEC2D expressed by HEK cells by Ab-8. FIG. 13C is an IHC image showing staining of human and cyno CLEC2D expressed by HEK cells by Ab- 14. FIG. 13D is an IHC image showing staining of human and cyno CLEC2D expressed by HEK cells by Ab-16.5. DETAILED DESCRIPTION

[0118] A limited number of antibodies that bind human CLEC2D (hCLEC2D) have been generated with varying degrees of binding specificity for hCLEC2D. The inventors have, inter alia, generated CLEC2D binding proteins that e.g., inter alia, exhibit one or more improved properties over current anti-CLEC2D antibodies. Accordingly, the novel CLEC2D binding proteins and polypeptides disclosed herein are good candidates for the treatment of diseases (e.g., cancer (e.g., solid tumors)). As such, the current disclosure provides, inter alia, novel CLEC2D binding proteins (e.g., antibodies) and methods of utilizing the same, including e.g., in pharmaceutical compositions for the treatment of diseases (e.g., cancer) and blocking CD161 binding to CLEC2D (e.g., in a subject).TABLE OF CONTENTS5.1 Definitions5.2 CLEC2D Binding Proteins5.3 Exemplary Properties of CLEC2D Binding Proteins5.3.1 Affinity of CLEC2D Binding Proteins5.3.2 Inhibition of CD161 Binding to CLEC2D5.4 Conjugates and Fusion Proteins5.4.1 Conjugates5.4.2 Fusion Proteins and Polypeptides5.4.3 Linkers5.4.3.1 Non-peptide Linkers5.4.3.2 Peptide Linkers5.4.4 Orientation5.5 Multimeric CLEC2D Binding Proteins5.6 Ig Constant Regions5.7 Ig Effector Function5.7.1 Reduced Ig Effector Function5.7.2 Enhanced Ig Effector Function5.8 Signal Peptides5.9 Nucleic Acid Molecules, Vectors, Cells, & Carriers5.10 Methods of Making Proteins5.11 Pharmaceutical Compositions5.12 Methods of Use5.12.1 Methods of Delivery5.12.2 Methods of Inhibiting Binding of CD161 to CLEC2D5.12.3 Methods of Treating a Disease5.12.4 Methods of Treating Cancer5.12.5 Detection Methods5.13 Kits5.1 Definitions

[0119] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0120] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the ail to which the claimed subject matter belongs. It is to be understood that the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of any subject matter claimed.

[0121] In this disclosure, the use of the singular includes the plural unless specifically stated otherwise. For example, as used in the specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Furthermore, use of the term “including” as well as other forms, such as “include,” “includes,” and “included,” is not limiting.

[0122] It is understood that wherever aspects are described herein with the language “comprising,” otherwise analogous aspects described in terms of “consisting of’ and “consisting essentially of’ are also provided herein.

[0123] The term “and / or” where used herein is to be taken as specific disclosure of each of the two specified features or components with or without the other. Thus, the term “and / or” as used in a phrase such as “A and / or B” herein is intended to include “A and B,” “A or B,” “A” (alone), and “B” (alone). Likewise, the term “and / or” as used in a phrase such as “A, B, and / or C” is intended to encompass each of the following aspects: A, B, and C; A, B, or C; A or C; A or B; B or C; A and C; A and B; B and C; A (alone); B (alone); and C (alone).

[0124] As described herein, any concentration range, percentage range, ratio range or integer range is to be understood to include the value of any integer within the recited range and, when appropriate, fractions thereof (such as one tenth and one hundredth of an integer), unless otherwise indicated.

[0125] The term “about” refers to a value or composition that is within an acceptable error range for the particular value or composition as determined by one of ordinary skill in the art, which will depend in part on how the value or composition is measured or determined, i.e., the limitations of the measurement system. When particular values or compositions are provided in the disclosure, unless otherwise stated, the meaning of “about” should be assumed to be within an acceptable error range for that particular value or composition.

[0126] Where proteins are described herein, it is understood that nucleic acid molecules (e.g., RNA (e.g., mRNA) or DNA nucleic acid molecules) encoding the protein are also provided herein.

[0127] Where proteins, nucleic acid molecules, vectors, carriers, etc. are described herein, it is understood that isolated forms of the proteins, nucleic acid molecules, vectors, carriers, etc. arc also provided herein.

[0128] Where proteins, nucleic acid molecules, etc. are described herein, it is understood that recombinant forms of the proteins, nucleic acid molecules, etc. are also provided herein.

[0129] Where polypeptides or sets of polypeptides are described herein, it is understood that proteins comprising the polypeptides or sets of polypeptides folded into their three-dimensional structure (i.e., tertiary or quaternary structure) are also provided herein and vice versa.

[0130] Where proteins are described herein, it is understood that polypeptides comprising the same amino acid sequence either linear or folded into their three-dimensional structure (i.e., tertiary or quaternary structure) are also provided herein.

[0131] As used herein, the term “administering” refers to the physical introduction of an agent (e.g., an antibody described herein) (e.g., a therapeutic agent) (or a precursor of an agent (e.g., a precursor of a therapeutic agent) that is metabolized or altered within the body of the subject to produce the agent (e.g., therapeutic agent) in vivo) to a subject, using any of the various methods and delivery systems known to those skilled in the art. Administering can also be performed, for example, once, a plurality of times, and / or over one or more extended periods. The term administering includes self-administration by a subject to the subject and administration to the subject by a third party.

[0132] The terms “agent” and “moiety” are used interchangeably herein and are used generically to describe any macro or micro molecule (and any combination thereof). Exemplary agents include, but are not limited proteins, peptides, nucleic acid molecules (e.g., DNA, RNA), small molecules, carbohydrates, lipids, synthetic polymers (e.g., polymers of PEG), conjugates (e.g., described herein), and any combination of the foregoing. Agents may contain more than one individual agent (wherein the individual agents are the same or different).

[0133] As used herein, the term “affinity” refers to the strength of the binding of one protein (e.g., an Antibody) to another protein (e.g., an Antigen). The affinity of a protein is measured by the dissociation constant Kd, defined as [Antibody] x [Antigen] / [Antibody-Antigen] where [Antibody-Antigen] is the molar concentration of the Antibody-Antigen complex, [Antibody] is the molar concentration of the unbound Antibody and [Ligand] is the molar concentration of the unbound Antigen. The affinity constant Ka is defined by 1 / Kd. Standard methods of measuringaffinity are known to the person of ordinary skill in the art. Exemplary methods of measuring affinity include, surface plasmon resonance (SPR) (e.g., BIAcorc®-bascd assay), a common method known in the ait (see, e.g., Wilson, Science 295:2103, 2002; Wolff et al., Cancer Res. 55:2560, 1993; and U.S. Patent Nos. 5,283,173, 5,468,614, the full contents of each of which are incorporated by reference herein for all purposes).

[0134] As used herein, the term “antibody” or “antibodies” is used in the broadest sense and encompasses various immunoglobulin (Ig) (e.g., human Ig (hlg), murine Ig (mlg)) structures, including, but not limited to monoclonal antibodies, polyclonal antibodies, multispecific (e.g., bispecific, trispecific) antibodies, and antibody fragments so long as they exhibit the desired antigen-binding activity (i.e., antigen binding fragments or variants). The term antibody thus includes, for example, full-length antibodies; antigen-binding fragments of full-length antibodies; molecules comprising antibody CDRs, VH regions, and / or VL regions; and antibody-like scaffolds (e.g., fibronectins). Examples of antibodies include, without limitation, monoclonal antibodies, polyclonal antibodies, monospecific antibodies, multispecific antibodies, human antibodies, humanized antibodies, chimeric antibodies, camelized antibodies, intrabodies, a variable domain of a new antigen receptor beta-lactamase (VNAR fragments), affybodies, diabodies, tribodies, heteroconjugate antibodies, antibody-drug conjugates, single domain antibodies (e.g.,VHH, (VHH)2), single chain antibodies, single-chain Fvs (scFv; (scFv) ), Fab fragments (e.g., Fab, single chain Fab (scFab), F(ab’)2 fragments, disulfide-linked Fvs (sdFv), Fc fusions (e.g., Fab-Fc, scFv- Fc, VHH-Fc, (SCFV)2-FC, (VHH)2-FC), and antigen-binding fragments of any of the above, and conjugates or fusion proteins comprising any of the above. Antibodies can be of Ig isotype (e.g., IgG, IgE, IgM, IgD, or IgA), any class (e.g., IgGi, IgG2, IgGa, IgG4, IgAi or IgAa), or any subclass (e.g., IgG2a or IgG2b) of Ig). In certain embodiments, antibodies described herein are IgG antibodies, or a class (e.g., human IgGi or IgG4) or subclass thereof. In certain embodiments, antibodies described herein are mlgG antibodies, or a class (e.g., mlgGl or mIgG2a) or subclass thereof. In some embodiments, the antibody is a human, humanized, or chimeric IgGi or IgG4 monoclonal antibody. In some embodiments, the term antibodies refers to a monoclonal or polyclonal antibody population. Antibodies described herein can be produced by any standard methods known in the art, e.g., recombinant production in host cells, see, e.g., § 5.10; or synthetic production.

[0135] As used herein, the term “antibody dependent cell mediated cytotoxicity” or “ADCC”refers to an immune mechanism leading to the lysis of antibody (or an Fc region containing protein) (e.g., an Ig Fc containing fusion protein described herein) -coated target cells by immune effector cells (e.g., NK cells). As used herein, the term “reduced ADCC” and the like refers to either a reduction in the number of target cells that are lysed in a given time, at a given concentration of antibody (or an Ig Fc region containing protein) (e.g., an Fc region containing fusion protein described herein) in the medium surrounding the target cells, by the mechanism of ADCC defined above, and / or an increase in the concentration of antibody (or an Fc region containing protein) (e.g., an Fc containing fusion protein described herein) in the medium surrounding the target cells, required to achieve the lysis of a given number of target cells in a given time, by the mechanism of ADCC defined above. The reduction in ADCC is relative to the ADCC mediated by the same antibody (or an Fc region containing protein) (e.g., an Fc containing fusion protein described herein) produced by the same type of host cells, using the same standard production, purification, formulation and storage methods (which are known to those skilled in the ail), but that has not been engineered (e.g., does not comprise one or more amino acid variation, e.g., amino acid substitution, that mediates a decrease in ADCC). For example the reduction in ADCC mediated by an antibody (or an Fc region containing protein) (e.g., an Fc containing fusion protein described herein) comprising in its Fc region an amino acid substitution that reduces ADCC, is relative to the ADCC mediated by the same antibody (or an Fc region containing protein) (e.g., an Fc containing fusion protein described herein) without said amino acid substitution in the Fc region.

[0136] The terms “cancer” and “tumor” are used interchangeably herein and refer to a broad group of various diseases characterized by the uncontrolled growth of abnormal cells in the body. Unregulated cell division and growth results in the formation of malignant tumors that can invade neighboring tissues and may also metastasize to distant parts of the body through, e.g., the lymphatic system or bloodstream.

[0137] As used herein, the term “CD 161” refers to the type II transmembrane C-type lectin- like receptor expressed, e.g., by natural killer cells. CD161 is also commonly referred to in the art as Killer cell lectin-like receptor subfamily B member 1 (KLRB1). The amino acid sequence of a reference human CD161 (hCD161) protein is set forth in SEQ ID NO: 2 (UniProt Ref.: Q12918- 1).

[0138] As used herein, the term “CDR” or “complementarity determining region” refers to the noncontiguous antigen combining sites found within the variable region of both heavy and lightchain polypeptides. These particular regions have been described by Kabat et al., J. Biol. Chem. 252, 6609-6616 (1977) and Kabat et al., Sequences of protein of immunological interest. (1991), the entire contents of each of which is incorporated herein by reference for all purposes. Unless otherwise specified, the term “CDR” is a CDR as defined by Kabat et al., J. Biol. Chem. 252, 6609-6616 (1977) and Kabat et al., Sequences of protein of immunological interest. (1991). A person of ordinary skill in the ail would be able to determine the CDRs as defined by another scheme, e.g., Chothia, IMGT, using ordinary methods known in the art.

[0139] The terms “CHI” and “CHI region” are used interchangeably herein and refer to the first constant region of an immunoglobulin heavy chain. The amino acid sequence of an exemplary reference hlgGl CHI region is set forth in SEQ ID NO: 33; and the amino acid sequence of an exemplary reference h!gG4 CHI region is set forth in SEQ ID NO: 46.

[0140] The terms “CH2” and “CH2 region” are used interchangeably herein and refer to the second constant region of an immunoglobulin heavy chain. The amino acid sequence of an exemplary reference hlgGl CH2 region is set forth in SEQ ID NO: 35; and the amino acid sequence of an exemplary reference hIgG4 CH2 region is set forth in SEQ ID NO: 48.

[0141] The terms “CH3” and “CH3 region” are used interchangeably herein and refer to the third constant region of an immunoglobulin heavy chain. The amino acid sequence of an exemplary reference hlgGl CH3 region is set forth in SEQ ID NO: 36; and the amino acid sequence of an exemplary reference hIgG4 CH3 region is set forth in SEQ ID NO: 49.

[0142] The terms “constant region” and “constant domain” are used interchangeably herein and refer to a carboxyl terminal portion of a light and / or heavy chain of a full-length antibody which is not directly involved in binding of an antibody to antigen, but which can exhibit various effector functions, such as interaction with an Ig Fc receptor (e.g., Fc gamma receptor). The constant region of an Ig molecule generally has a more conserved amino acid sequence relative to an Ig variable domain.

[0143] As used herein, the term “CLEC2D” or “C-type lectin domain family 2 member D” refers to the C type lectin receptor that, inter alia, has been reported to be capable of binding histones released upon necrotic cell death. The amino acid sequence of a reference huma CLEC2D (hCLEC2D) isoform is set forth in SEQ ID NO: 1 (UniProt Ref.: Q9UHP7-1). Multiple isoforms of hCLEC2D are known produced by alternative splicing.

[0144] As used herein, the term “conjugation” refers to chemical conjugation of a protein witha moiety (e.g., small molecule, polypeptide, nucleic acid molecule, carbohydrate, lipid, synthetic polymer (e.g., polymers of polyethylene glycol (PEG)), etc.). The moiety can be directly connected to the protein or indirectly connected through a linker, e.g., as described herein. Chemical conjugation methods are well known in the art, as are commercially available conjugation reagents and kits, with detailed instructions for their use readily available from the commercial suppliers.

[0145] As used herein, the term “derived from,” with reference to a nucleic acid molecule refers to a nucleic acid molecule that has at least 70% sequence identity to a reference nucleic acid molecule (e.g., a naturally occurring nucleic acid molecule) or a fragment thereof. The term “derived from,” with reference to a protein refers to a protein that comprises an amino acid sequence that has at least 70% sequence identity to the amino acid sequence of a reference protein (e.g., a naturally occurring protein). The term “derived from” as used herein does not denote any specific process or method for obtaining the nucleic acid molecule, polypeptide, or protein. For example, the nucleic acid molecule, polypeptide, or protein can be recombinantly produced or chemically synthesized.

[0146] As used herein, the term “diagnosing” or “diagnosis” refers to a determination of the presence, absence, severity, or course of treatment of a disease (e.g., cancer, pro-inflammatory disease, autoimmune disease). The term “diagnosing” encompasses an initial determination as well as subsequent determinations (e.g., monitoring) after the initial determination.

[0147] As used herein, the term “disease” refers to any abnormal condition that impairs physiological function. The term is used broadly to encompass any disorder, illness, abnormality, pathology, sickness, condition, or syndrome in which physiological function is impaired, irrespective of the nature of the etiology.

[0148] The terms “DNA” and “polydeoxyribonucleotide” are used interchangeably herein and refer to macromolecules that include multiple deoxyribonucleotides that are polymerized via phosphodiester bonds. Deoxyribonucleotides are nucleotides in which the sugar is deoxyribose.

[0149] The term “effector function” when used in reference to an Ig Fc region or a protein comprising an Ig Fc region (e.g., a full-length antibody) refers to those biological activities attributable to the Ig Fc region of a typical full-length antibody, which therefore vary with the antibody isotype. Antibody effector functions include, but are not limited to, antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), complement dependent cytotoxicity (CDC), Fc receptor binding (e.g., FcyRI, FcyRIIa, FcyRIIc,FcyRIIIa, and / or FcyRIIIb (e.g., FcyRI, Fcylla, and / or Fcyllla)), and Clq binding.

[0150] As used herein, the term “EU numbering system” refers to the EU numbering convention for the constant regions of an antibody, as described in Edelman, G.M. et al., Proc. Natl. Acad. USA, 63, 78-85 (1969) and Kabat et al, Sequences of Proteins of Immunological Interest, U.S. Dept. Health and Human Services, 5th edition, 1991, the entire contents of each of which is incorporated herein by reference for all purposes.

[0151] As used herein, the term “Fab” refers to an antigen binding domain that comprises a Fab heavy chain that comprises from N- to C-terminus a VH region and a CHI region; and a light chain comprising from N- to C-terminus a VL region and a CL region; and wherein the Fab heavy chain and the light chain associate to form an antigen binding domain.

[0152] The term “Fab-Fc” as used herein refers to an antibody that comprises a Fab operably linked to an Fc region.

[0153] As used herein, the term “Fc region” refers to the C-terminal region of a Ig (e.g., a human Ig) heavy chain that comprises from N- to C-terminus at least a CH2 region operably connected to a CH3 region. In some embodiments, the Fc region comprises an Ig hinge region or at least a portion of an Ig hinge region operably connected to the N-terminus of the CH2 region. In some embodiments, the Fc region is engineered relative to a reference Fc region (e.g., comprises one or more amino acid variation), see, e.g., § 5.7. Additional examples of proteins with engineered Fc regions can be found in Saunders 2019 (K. O. Saunders, “Conceptual Approaches to Modulating Antibody Effector Functions and Circulation Half-Life,” 2019, Frontiers in Immunology, V. 10, Art. 1296, pp. 1-20, the entire contents of which is incorporated herein by reference for all purposes).

[0154] As used herein, the terms “first” and “second” with respect to Fc regions etc., are used for convenience of distinguishing when there is more than one of each type of moiety. Use of these terms is not intended to confer a specific order or orientation in the protein unless explicitly so stated. For example, an antibody described herein (e.g., in the case of a full-length antibody) may contain two Fc regions that associate e.g., via one or more covalent (e.g., disulfide) bond.

[0155] As used herein, the term “framework region” or “FR region” refers to the amino acid residues that are part of the variable region of an antibody, but are not part of the CDRs (e.g., using the Kabat definition of CDRs).

[0156] As used herein, the term “full-length antibody” refers to an antibody having a structuresubstantially similar to a native antibody structure (i) a first Ig light chain comprising from N- to C-tcrminus a light chain variable region (VL) region and a light chain constant region (CL) region; (ii) a first Ig heavy chain comprising from N- to C-terminus a heavy chain variable region (VH) region, a CHI region, a hinge region, a CH2 region, and a CH3 region; (iii) a second Ig heavy chain comprising from N- to C-terminus a VH region, a CHI region, a hinge region, a CH2 region, and a CH3 region; (iv) a second Ig light chain comprising from N- to C-terminus a VL region and a VH region; wherein said first light chain and said first heavy chain associate to form a first antigen binding domain; wherein said second light chain and said second heavy chain associate to form a second antigen binding domain; and wherein said first heavy chain and said second heavy chain associate to form a dimer. In some embodiments, the two heavy chains comprise a substantially identical amino acid sequence; and the two light chains comprise a substantially identical amino acid sequence. In some embodiments, the two heavy chains comprise a substantially identical amino acid sequence except for one or more amino acid variations that promote heterodimerization of the correct heavy chains (e.g., as described herein); and the two light chains comprise a substantially identical amino acid sequence. Antibody chains may be substantially identical but not entirely identical if they differ due to post-translational modifications, such as C-terminal cleavage of lysine residues, alternative glycosylation patterns, etc.

[0157] The term “functional variant” as used herein in reference to a protein refers to a protein that comprises at least one but no more than 20%, not more than 15%, not more than 12%, no more than 10%, no more than 8% amino acid variation (e.g., substitution, deletion, addition) compared to the amino acid sequence of a reference protein, wherein the protein retains at least one particular function of the reference protein. Not all functions of the reference protein (e.g., wild type) need be retained by the functional variant of the protein. In some instances, one or more functions are selectively reduced or eliminated. In some embodiments, the reference protein is a wild type protein.

[0158] The term “functional fragment” as used herein in reference to a protein refers to a fragment of a reference protein that retains at least one particular function. Not all functions of the reference protein need be retained by a functional fragment of the protein. In some instances, one or more functions are selectively reduced or eliminated. In some embodiments, the reference protein is a wild type protein.

[0159] As used herein, the term “fuse” and grammatical equivalents thereof refer to the operable connection of at least a first polypeptide to a second polypeptide, wherein the first and second polypeptides are not naturally found operably connected together. For example, the first and second polypeptides are derived from different proteins. The term fuse encompasses both a direct connection of the at least two polypeptides through a peptide bond, and the indirect connection through a linker (e.g., a peptide linker).

[0160] As used herein, the term “fusion protein” and grammatical equivalents thereof refers to a protein that comprises at least one polypeptide operably connected to another polypeptide, wherein the first and second polypeptides are not naturally found operably connected together. For example, the first and second polypeptides of the fusion protein are each derived from different proteins. In some embodiments, the first and second polypeptide are different. The at least two polypeptides of the fusion protein can be directly operably connected through a peptide bond; or can be indirectly operably connected through a linker (e.g., a peptide linker). Therefore, for example, the term fusion polypeptide encompasses embodiments, wherein Polypeptide A is directly operably connected to Polypeptide B through a peptide bond (Polypeptide A - Polypeptide B), and embodiments, wherein Polypeptide A is operably connected to Polypeptide B through a peptide linker (Polypeptide A - peptide linker - Polypeptide B).

[0161] As used herein, the term “half-life extension moiety” refers to a moiety (e.g., small molecule, polypeptide, nucleic acid molecule, carbohydrate, lipid, synthetic polymer (e.g., polymers of PEG), etc.) that when conjugated or otherwise operably connected (e.g., fused) to a protein (the subject protein), increases the half-life of the subject protein in vivo when administered to a subject (e.g., a human subject). The pharmacokinetic properties of the protein can be evaluated utilizing in vivo models known in the art.

[0162] As used herein, the term “half-life extension polypeptide” or “half-life extension protein” refers to a protein that when operably connected to another protein (the subject protein), increases the half-life of the subject protein in vivo when administered to a subject (e.g., a human subject). The pharmacokinetic properties of the protein can be evaluated utilizing in vivo models known in the art.

[0163] As used herein, the term “heterologous”, when used to describe a first element in reference to a second element means that the first element and second element are different. For example, in some embodiments, a polypeptide operably connected to a “heterologous moiety”means a polypeptide that is operably connected to a moiety (e.g., small molecule, polypeptide, nucleic acid molecule, carbohydrate, lipid, synthetic polymer (e.g., polymers of PEG), etc.) that is not operably connected to the polypeptide in nature.

[0164] As used herein, the term “heavy chain” refers to the portion of an immunoglobulin (e.g., a human Ig) that typically comprises from N- to C-terminus a heavy chain variable region (VH), a CHI region, a hinge region, a CH2 region, and a CH3 region. The constant regions of the heavy chain (i.e., the CHI region, the hinge region, the CH2 region, and the CH3 region) can be any distinct isotype, for example, human alpha (a), delta (6), epsilon (e), gamma (y), and mu (p), based on the amino acid sequence of the constant domain, which give rise to the hlgA, hlgD, IgE, hlgG, and hlgM classes of human antibodies, respectively, including subclasses of hlgG, e.g., hlgGi, h!gG2, hlgG;, and h!gG4. As used herein, the term “heavy chain” when used in reference to a human antibody can refer to any distinct type, e.g., alpha (a), delta (5), epsilon (s), gamma (y), and mu (p), based on the amino acid sequence of the constant domain, which give rise to human IgA, IgD, IgE, IgG, and IgM classes of antibodies, respectively, including subclasses of human IgG, e.g., IgGi, IgG2, IgG3, and IgG4.

[0165] The terms “hinge” or “hinge region” are used interchangeably herein and refer to the hinge region of an immunoglobulin heavy chain. The amino acid sequence of an exemplary reference hlgGi hinge region is set forth in SEQ ID NO: 34; and the amino acid sequence of an exemplary reference h!gG4 hinge region is set forth in SEQ ID NO: 47.

[0166] As used herein, the term “isolated” with reference to an agent (e.g., a protein, nucleic acid molecule, etc.) refers to an agent (e.g., a protein, nucleic acid molecule, etc.) that is substantially free of other cellular components with which it is associated in the natural state.

[0167] The terms “nucleic acid molecule,” “polynucleotide,” and “oligonucleotide” are used interchangeably herein and refer to a polymer of DNA or RNA. The nucleic acid molecule can be single- stranded or double-stranded; contain natural, non-natural, or altered nucleotides; and contain a natural, non-natural, or altered internucleoside linkage, such as a phosphoroamidate linkage or a phosphorothioate linkage, instead of the phosphodiester found between the nucleotides of an unmodified nucleic acid molecule. Nucleic acid molecules include, but are not limited to, all nucleic acid molecules which are obtained by any means available in the art, including, without limitation, recombinant means, e.g., the cloning of nucleic acid molecules from a recombinant library or a cell genome, using ordinary cloning technology and polymerase chain reaction, andthe like, and by synthetic means. The skilled artisan will appreciate that, except where otherwise noted, nucleic acid sequences set forth in the instant application will recite thymidine (T) in a representative DNA sequence but where the sequence represents RNA (e.g., mRNA), the thymidines (Ts) would be substituted for uracils (Us). Thus, any of the RNA polynucleotides encoded by a DNA identified by a particular sequence identification number may also comprise the corresponding RNA (e.g., mRNA) sequence encoded by the DNA, where each thymidine (T) of the DNA sequence is substituted with uracil (U).

[0168] As used herein, the term “obtaining a sample” refers to the acquisition of a sample. The term includes the direct acquisition from a subject and the indirect acquisition through one or more third parties wherein one of the third parties directly acquired the sample from the subject.

[0169] As used herein, the term “operably connected” refers to the linkage of two agents in a functional relationship. For example, a polypeptide is operably connected to another polypeptide when they are linked (either directly or indirectly via a peptide linker) in frame such that both polypeptides are functional. Or for example, a transcription regulatory polynucleotide e.g., a promoter, enhancer, or other expression control element is operably linked to a polynucleotide that encodes a protein if it affects the transcription of the polynucleotide that encodes the protein. The term “operably connected” also refers for example to the conjugation of a first agent (e.g., an antibody (e.g., a CLEC2D binding protein))) to a second agent wherein the first and second agent are both capable of mediating their function.

[0170] The determination of “percent identity” between two sequences (e.g., protein (amino acid sequences) or oligonucleotide (nucleic acid sequences)) can be accomplished using a mathematical algorithm. Determinations of identity (as described herein) are independent of nucleotide chemical modifications (e.g., as described herein). For example, (mC) is identical to (C) for the purposes of determining identity. A specific, non-limiting example of a mathematical algorithm utilized for the comparison of two sequences is the algorithm of Karlin S & Altschul SF (1990) PNAS 87: 2264-2268, modified as in Karlin S & Altschul SF (1993) PNAS 90: 5873-5877, each of which is herein incorporated by reference in its entirety. Such an algorithm is incorporated into the NBLAST and XBLAST programs of Altschul SF et al., (1990) J Mol Biol 215: 403, which is herein incorporated by reference in its entirety. BLAST nucleotide searches can be performed with the NBLAST nucleotide program parameters set, e.g., for score=100, wordlength=12 to obtain nucleotide sequences homologous to a nucleic acid molecule described herein. BLASTprotein searches can be performed with the XBLAST program parameters set, e.g., to score 50, wordlcngth=3 to obtain amino acid sequences homologous to a protein molecule described herein. To obtain gapped alignments for comparison purposes, Gapped BLAST can be utilized as described in Altschul SF et al., (1997) Nuc Acids Res 25: 3389-3402, which is herein incorporated by reference in its entirety. Alternatively, PSI BLAST can be used to perform an iterated search which detects distant relationships between molecules (Id.). When utilizing BLAST, Gapped BLAST, and PSI Blast programs, the default parameters of the respective programs (e.g., of XBLAST and NBLAST) can be used (see, e.g., National Center for Biotechnology Information (NCBI) on the worldwide web, ncbi.nlm.nih.gov). Another specific, non-limiting example of a mathematical algorithm utilized for the comparison of sequences is the algorithm of Myers and Miller, 1988, CABIOS 4:11-17, which is herein incorporated by reference in its entirety. Such an algorithm is incorporated in the ALIGN program (version 2.0) which is part of the GCG sequence alignment software package. When utilizing the ALIGN program for comparing amino acid sequences, a PAM 120 weight residue table, a gap length penalty of 12, and a gap penalty of 4 can be used. The percent identity between two sequences can be determined using techniques similar to those described above, with or without allowing gaps. In calculating percent identity, typically only exact matches are counted.

[0171] As used herein, the term “pharmaceutical composition” means a composition that is suitable for administration to an animal, e.g., a human subject, and comprises a therapeutic agent (e.g., an antibody described herein) and a pharmaceutically acceptable carrier or diluent. A “pharmaceutically acceptable carrier or diluent” means a substance intended for use in contact with the tissues of human beings and / or non-human animals, and without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable therapeutic benefit / risk ratio.

[0172] As used herein, the term “plurality” means 2 or more (e.g., 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 9 or more, or 10 or more).

[0173] As used herein, the terms “protein”, “polypeptide”, and peptide refers to a polymer of at least 2 (e.g., at least 5) amino acids linked by a peptide bond. The term “polypeptide” does not denote a specific length of the polymer chain of amino acids. It is common in the art to refer to shorter polymers of amino acids (e.g., approximately 2-50 amino acids) as peptides; and to refer to longer polymers of amino acids (e.g., approximately over 50 amino acids) as polypeptides.However, the terms “peptide” and “polypeptide” and “protein” are used interchangeably herein. In some embodiments, the protein is folded into its three-dimensional structure. Where polypeptides (e.g., in a linear (i.e., primary) structure are contemplated herein, it should be understood that proteins folded into their three-dimensional structure (i.e., tertiary or quaternary structure) are also provided herein and vice versa. Proteins include e.g., naturally occurring proteins, variant (e.g., functional variants) of naturally occurring proteins, fragments (e.g., functional fragments) of naturally occurring proteins, and synthetic proteins (i.e., not naturally occurring proteins).

[0174] A “prophylactic” treatment is a treatment administered to a subject who does not exhibit signs of a disease or exhibits only early signs for the purpose of decreasing the risk of developing pathology.

[0175] The terms “RNA” and “polyribonucleotide” are used interchangeably herein and refer to macromolecules that include multiple ribonucleotides that are polymerized via phosphodiester bonds. Ribonucleotides are nucleotides in which the sugar is ribose. RNA may contain modified nucleotides; and contain natural, non-natural, or altered intemucleoside linkages, such as a phosphoroamidate linkage or a phosphorothioate linkage, instead of the phosphodiester found between the nucleotides of an unmodified nucleic acid molecule.

[0176] As used herein, the term “sample” encompass a variety of biological specimens obtained from a subject. Exemplary sample types include, e.g., blood and other liquid samples of biological origin (including, but not limited to, whole-blood, peripheral blood mononuclear cells (PBMCs), serum, plasma, urine, saliva, amniotic fluid, stool, synovial fluid, etc.), nasopharyngeal swabs, solid tissue samples such as biopsies (or cells derived therefrom and the progeny thereof), tissue cultures (or cells derived therefrom and the progeny thereof), and cell cultures (or cells derived therefrom and the progeny thereof). The term also includes samples that have been manipulated in any way after their procurement from a subject, such as by centrifugation, filtration, washing, precipitation, dialysis, chromatography, lysis, treatment with reagents, enriched for certain cell populations, refrigeration, freezing, staining, etc.

[0177] The term “scFv” or “single chain variable fragment” refers to an antibody that comprises a VH region operably connected via a peptide linker to a VL region, wherein the VH and VL regions associate to specifically bind an antigen (e.g., form an antigen binding domain). In some embodiments, the scFv comprises from N- to C-terminus an VH region, a peptide linker,and an VL region. In some embodiments, the scFv comprises from N- to C-terminus an VL region, a peptide linker, and an VH region.

[0178] The term “(scFv)2” as used herein refers to an antibody that comprises a first and a second scFv operably connected (e.g., via a peptide linker). The first and second scFv can specifically bind the same or different antigens. In some embodiments, the first and second scFv are operably connected by a peptide linker.

[0179] The term “scFv-Fc” as used herein refers to an antibody that comprises a scFv operably linked (e.g., via a peptide linker) to an Fc domain or subunit of an Fc domain. In some embodiments, a scFv is operably connected to only a first Fc domain of a first and a second Fc domain pair. In some embodiments, a first scFv is operably connected to a first Fc domain and a second scFv is operably connected to a second Fc domain of a first and second Fc domain pair.

[0180] The term “(scFv)2-Fc” as used herein refers to a (scFv)2 operably linked (e.g., via a peptide linker) to an Fc domain or a subunit of an Fc domain. In some embodiments, a (scFv)2 is operably connected to only a first Fc domain of a first and a second Fc domain pair. In some embodiments, a first (scFv is operably connected to a first Fc domain and a second (scFv)2 is operably connected to a second Fc domain of a first and second Fc domain pair.

[0181] As used herein, the term “single domain antibody” or “sdAb” refers to an antibody having a single monomeric variable antibody domain. A sdAb is able to specifically bind to a specific antigen. A VHH (as defined herein) is an example of a sdAb.

[0182] As used herein, the term “signal peptide” or “signal sequence” refers to a sequence (e.g., an amino acid sequence) that can direct the transport or localization of a protein to a certain organelle, cell compartment, or extracellular export. The term encompasses both the signal sequence peptide and the nucleic acid sequence encoding the signal peptide. Thus, references to a signal peptide in the context of a nucleic acid refers to the nucleic acid sequence encoding the signal peptide.

[0183] As used herein, the term “specifically binds” refers to preferential interaction, i.e., significantly higher binding affinity, between a first protein (e.g., an antibody) and a second protein (e.g., an antigen) relative to other amino acid sequences. Herein, when a first protein is said to “specifically bind” to a second protein, it is understood that the first protein specifically binds to an epitope of the second protein. The term “epitope” refers to the portion of the second protein that the first protein specifically recognizes. The term specifically binds includes molecules that arecross reactive with the same epitope of a different species. For example, an antibody that specifically binds huma CLEC2D may be cross reactive with CLEC2D of another species (e.g., cynomolgus, murine, etc.), and still be considered herein to specifically bind huma CLEC2D. A protein can specifically bind more than one different protein. Specific binding can be measured, e.g., through measuring binding affinity (e.g., using standard methods known in the art and described herein (e.g., surface plasmon resonance (SPR) (e.g., BIAcore®-based assay), a common method known in the art (see, e.g., Wilson, Science 295:2103, 2002; Wolff et al., Cancer Res. 55:2560, 1993; and U.S. Patent Nos. 5,283,173, 5,468,614, the full contents of each of which are incorporated by reference herein for all purposes).

[0184] As used herein, the term “subject” includes any animal, such as a human or other animal. In some embodiments, the subject is a vertebrate animal (e.g., mammal, bird, fish, reptile, or amphibian). In some embodiments, the subject is a human. In some embodiments, the method subject is a non-human mammal. In some embodiments, the subject is a non-human mammal is such as a non-human primate (e.g., monkeys, apes), ungulate (e.g., cattle, buffalo, sheep, goat, pig, camel, llama, alpaca, deer, horses, donkeys), carnivore (e.g., dog, cat), rodent (e.g., rat, mouse), or lagomorph (e.g., rabbit). In some embodiments, the subject is a bird, such as a member of the avian taxa Galliformes (e.g., chickens, turkeys, pheasants, quail), Anseriformes (e.g., ducks, geese), Paleaognathae (e.g., ostriches, emus), Columbiformes (e.g., pigeons, doves), or Psittaciformes (e.g., parrots).

[0185] As used herein, the term “therapeutic agent” refers to an agent (e.g., a conjugate described herein) capable of achieving a desired therapeutic (including prophylactic) result in a subject or ex vivo (e.g., capable of treating a disease as defined herein) when administered at a therapeutically effective amount.

[0186] As used herein, the term “therapeutically effective amount” of a therapeutic agent refers to any amount of the therapeutic agent that, when used alone or in combination with another therapeutic agent, improves a disease condition, e.g., protects a subject against the onset of a disease (or infection) (prophylaxis); improves a symptom of disease or infection, e.g., decreases severity of disease or infection symptoms, decreases frequency or duration of disease or infection symptoms, increases disease or infection symptom- free periods; prevents or reduces impairment or disability due to the disease or infection; or promotes disease (or infection) regression. The ability of a therapeutic agent to improve a disease condition can be evaluated using a variety ofmethods known to the skilled practitioner, such as in human subjects during clinical trials, in animal model systems predictive of efficacy in humans, or by assaying the activity of the agent in in vitro assays.

[0187] As used herein, the terms “treat,” treating,” “treatment,” and the like refer to reducing or ameliorating a disease and / or symptom(s) associated therewith or obtaining a desired pharmacologic and / or physiologic effect. It will be appreciated that, although not precluded, treating a disease does not require that the disease, or symptom(s) associated therewith be completely eliminated. In some embodiments, the effect is therapeutic, i.e., without limitation, the effect partially or completely reduces, diminishes, abrogates, abates, alleviates, decreases the intensity of, or cures a disease and / or adverse symptom attributable to the disease. In some embodiments, the effect is preventative (i.e., prophylactic), i.e., the effect protects or prevents an occurrence or reoccurrence of a disease. To this end, the presently disclosed methods comprise administering a therapeutically effective amount of e.g., a conjugate described herein (or a carrier, pharmaceutical composition, etc. comprising the same).

[0188] As used herein, the term “variation” or “variant” or use the like in reference to a nucleotide or nucleic acid sequence refers to a nucleic acid molecule that comprises at least one substitution, addition, deletion, or inversion of one or more nucleotide compared to a reference nucleic acid molecule. Likewise, as used herein, the term “variation” or “variant” or use the like with reference to a peptide or protein refers to a peptide or protein that comprises at least one substitution, addition, deletion, or inversion of an amino acid residue compared to a reference peptide or protein.

[0189] As used herein, the term “variable region” refers to a portion of an antibody, generally, a portion of a light or heavy chain, typically about the amino-terminal 110 to 120 amino acids or 110 to 125 amino acids in the mature heavy chain and about 90 to 115 amino acids in the mature light chain, which differ extensively in sequence among antibodies and are used in the binding and specificity of a particular antibody for its particular antigen. The variability in sequence is concentrated in those regions called complementarity determining regions (CDRs) while the more highly conserved regions in the variable domain are called framework regions (FR). Without wishing to be bound by any particular mechanism or theory, it is believed that the CDRs of the light and heavy chains are primarily responsible for the interaction and specificity of the antibody with antigen. In certain embodiments, the variable region is a human variable region. In certainembodiments, the variable region comprises rodent or murine CDRs and human framework regions (FRs). In particular embodiments, the variable region is a primate (e.g., non-human primate) variable region. In certain embodiments, the variable region comprises rodent or murine CDRs and primate (e.g., non-human primate) framework regions (FRs).

[0190] The terms “VL” and “VL region” are used interchangeably to refer to an immunoglobulin light chain variable region. A VL region can be incorporated into an antibody, e.g., a scFv, a Fab, a full-length antibody. For example, a scFv comprises a VL region operably connected via a peptide linker to a VH region.

[0191] The terms “VH” and “VH region” are used interchangeably to refer to an immunoglobulin heavy chain variable region. A VH region can be incorporated into an antibody, e.g., a scFv, a Fab, a full-length antibody. For example, a scFv comprises a VH region operably connected via a peptide linker to a VL region.

[0192] The term “VHH” as used herein refers to a type of single domain antibody (sdAb) that has a single monomeric heavy chain variable antibody domain (VH). Such antibodies can be found in or produced from camelid mammals (e.g., camels, llamas) which are naturally devoid of light chains or synthetically produced.

[0193] The term “(VHH ” as used herein refers to an antibody that comprises a first and a second VHH operably connected (e.g., via a peptide linker). The first and the second VHH can specifically bind the same or different antigens. In some embodiments, the first and second VHH are operably connected by a peptide linker.

[0194] The term “VHH-Fc” as used herein refers to an antibody that comprises a VHH operably linked (e.g., via a peptide linker) to an Fc domain or a subunit of an Fc domain. In some embodiments, a VHH is operably connected to only a first Fc domain of a first and a second Fc domain pair. In some embodiments, a first VHH is operably connected to a first Fc domain and a second VHH is operably connected to a second Fc domain of a first Fc and a second Fc pair.

[0195] The term “(VHH)2-Fc” as used herein refers to (VHH)2 operably linked (e.g., via a peptide linker) to an Fc domain or a subunit of an Fc domain. In some embodiments, a (VHH) is operably connected to only a first Fc domain of a first and a second Fc domain pair. In some embodiments, a first (VHH)2 is operably connected to a first Fc domain and a second (VHH)2 is operably connected to a second Fc domain of a first Fc and a second Fc pair.5.2 CLEC2D Binding Proteins

[0196] As described above, provided herein are, inter alia, proteins (e.g., antibodies (and functional fragments and functional variants thereof) that specifically bind CLEC2D (e.g., hCLEC2D).

[0197] CLEC2D is a C type lectin receptor that, inter alia, regulates immune responses through, e.g., binding to the type II transmembrane C-type lectin-like receptor, CD161 (known to be expressed by, e.g., natural killer (NK) cells). Multiple isoforms of hCLEC2D are known to be produced by alternative splicing, with isoform 1 being the only isoform predominantly expressed at the cell surface. The amino acid sequence of a reference hCLEC2D isoform 1 protein is set forth in SEQ ID NO: 1. The amino acid sequence of a reference hCD161 protein is set forth in SEQ ID NO: 2. See Table 1, herein.Table 1. The Amino Acid Sequence of a Reference hCLEC2D and hCD161 Protein.

[0198] In some embodiments, the CLEC2D binding protein comprises an antibody. In some embodiments, the CLEC2D binding protein comprises a full-length antibody, Fab, Fab', F(ab')2, Fab-Fc, scFv, scFv-Fc, (scFv)2-Fc, Fv, a single domain antibody (sdAb) (e.g., a VHH), a sdAb-Fc (e.g., a VHH-Fc), (sdAb)2 e.g., a (VHH)2, or a (sdAb)2-Fc (e.g., (VHH)2-Fc). In some embodiments, the CLEC2D binding protein comprises a full-length antibody, Fab, Fab', F(ab')2, Fab-Fc, scFv, scFv-Fc, (scFv)2-Fc, sdAb-Fc (e.g., a VHH-Fc), or (sdAb)2-Fc (e.g., (VHH)2-Fc). In some embodiments, the CLEC2D binding protein comprises a full-length antibody. In some embodiments, the CLEC2D binding protein comprises a Fab. In some embodiments, the antibody comprises a F(ab')2. In some embodiments, the CLEC2D binding protein comprises a Fab-Fc. In some embodiments, the antibody comprises a scFv-Fc. In some embodiments, the CLEC2D binding protein comprises a (scFv)2-Fc. In some embodiments, the CLEC2D binding protein comprises a sdAb-Fc (e.g., a VHH-Fc). In some embodiments, the CLEC2D binding protein comprises a (sdAb)2-Fc (e.g., (VHH)2-Fc)

[0199] In some embodiments, the CLEC2D binding protein comprises an antibody. In some embodiments, the antibody is an IgGl, IgG2, IgG3, or IgG4 antibody. In some embodiments, the antibody is an IgGl or IgG4 antibody. In some embodiments, the antibody is an IgGl antibody. In some embodiments, the antibody is an IgG4 antibody. In some embodiments, the antibody is a hlgGl, hIgG2, hIgG3, or hIgG4 antibody. In some embodiments, the antibody is ahlgGl or hIgG4 antibody. In some embodiments, the antibody is a hlgGl antibody. In some embodiments, the antibody is a hIgG4 antibody.

[0200] In some embodiments, the CLEC2D binding protein consists of an antibody. In some embodiments, the CLEC2D binding protein consists of a full-length antibody, Fab, Fab', F(ab')2, Fab-Fc, scFv, scFv-Fc, (scFv)2-Fc, Fv, a single domain antibody (sdAb) (e.g., a VHH), a sdAb-Fc (e.g., a VHH-Fc), (sdAb)2 (e.g., a (VHH)2, or a (sdAb)2-Fc (e.g., (VHH)2-Fc). In some embodiments, the CLEC2D binding protein consists of a full-length antibody, Fab, Fab', F(ab')2, Fab-Fc, scFv, scFv-Fc, (scFv)2-Fc, sdAb-Fc (e.g., a VHH-Fc), or (sdAb)2-Fc (e.g., (VHH)2-Fc). In some embodiments, the CLEC2D binding protein consists of a full-length antibody. In some embodiments, the CLEC2D binding protein consists of a Fab. In some embodiments, the antibody consists of a F(ab')2. In some embodiments, the CLEC2D binding protein consists of a Fab-Fc. Insome embodiments, the antibody consists of a scFv-Fc. Tn some embodiments, the CLEC2D binding protein consists of a (scFv)2-Fc. In some embodiments, the CLEC2D binding protein consists of a sdAb-Fc (e.g., a VHH-Fc). In some embodiments, the CLEC2D binding protein consists of a sdAb)2-Fc e.g., (VHH)2-Fc)

[0201] In some embodiments, the CLEC2D binding protein consists of an antibody. In some embodiments, the antibody is an IgGl, IgG2, IgG3, or IgG4 antibody. In some embodiments, the antibody is an IgGl or IgG4 antibody. In some embodiments, the antibody is an IgGl antibody. In some embodiments, the antibody is an IgG4 antibody. In some embodiments, the antibody is a hlgGl, hIgG2, hIgG3, or hIgG4 antibody. In some embodiments, the antibody is ahlgGl or hIgG4 antibody. In some embodiments, the antibody is a hlgGl antibody. In some embodiments, the antibody is a hIgG4 antibody.

[0202] The amino acid sequence of hCLEC2D binding proteins (e.g., anti-hCLEC2D antibodies) of the present disclosure is provided in Table 2. The CDRs of the antibodies in Table 2, are denoted according to Kabat. A person of ordinary skill in the art would be able to determine the CDRs as defined by another scheme, e.g., Chothia, IMGT, using ordinary methods known in the art.Table 2. The Amino Acid Sequence of hCLEC2D Binding Proteins.

[0001] In some embodiments, the CLEC2D binding protein comprises a VH that comprises: a VH CDR1, a VH CDR2, and a VH CDR3. In some embodiments, the CLEC2D binding protein comprises a VL that comprises: a VL CDR1 , a VL CDR2, and a VL CDR3.

[0002] In some embodiments, the CLEC2D binding protein comprises a VH that comprises: a VH CDR1, a VH CDR2, and a VH CDR3; and a VL that comprises: a VL CDR1, a VL CDR2, and a VL CDR3.

[0003] In some embodiments, the CLEC2D binding protein comprises a CLEC2D binding protein provided in Table 2.

[0004] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence of a VH CDR1 of a VH set forth in Table 2, or the amino acid of a VH CDR1 of a VH set forth in Table 2, comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence of a VH CDR2 of a VH set forth in Table 2, or the amino acid sequence of a VH CDR2 of a VH set forth in Table 2 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises of a VH CDR3 of a VH set forth in Table 2, or the amino acid sequence of a VH CDR3 of a VH set forth in Table 2 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence of a VL CDR1 of a VL set forth in Table 2, or the amino acid sequence of a VL CDR1 of a VL set forth in Table 2 comprising 1, 2, or 3 amino acid variations(e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence of a VL CDR2 of a VL set forth in Table 2, or the amino acid sequence of a VL CDR2 of a VL set forth in Table 2 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence of a VL CDR3 of a VL set forth in Table 2, or the amino acid sequence of a VL CDR3 of a VL set forth in Table 2 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0005] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence of a VH CDR1 of a VH set forth in Table 2, or the amino acid of a VH CDR1 of a VH set forth in Table 2, comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence of a VH CDR2 of a VH set forth in Table 2, or the amino acid sequence of a VH CDR2 of a VH set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises of a VH CDR3 of a VH set forth in Table 2, or the amino acid sequence of a VH CDR3 of a VH set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence of a VL CDR1 of a VL set forth in Table 2, or the amino acid sequence of a VL CDR1 of a VL set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence of a VL CDR2 of a VL set forth in Table 2, or the amino acid sequence of a VL CDR2 of a VL set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence of a VL CDR3 of a VL set forth in Table 2, or the amino acid sequence of a VL CDR3 of a VL set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0006] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence of a VH CDR1 of a VH set forth in Table 2; the amino acid sequence of VH CDR2 comprises the amino acid sequence of a VH CDR2 of a VH set forth in Table 2; the amino acid sequence of VH CDR3 comprises of a VH CDR3 of a VH set forth in Table 2; the amino acid sequence of VL CDR1 comprises the amino acid sequence of a VL CDR1 of a VL set forth inTable 2; the amino acid sequence of VL CDR2 comprises the amino acid sequence of a VL CDR2 of a VL set forth in Table 2; and the amino acid sequence of VL CDR3 comprises the amino acid sequence of a VL CDR3 of a VL set forth in Table 2.

[0007] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid of a VH CDR1 of a VH set forth in Table 2, comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of a VH CDR2 of a VH set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of a VH CDR3 of a VH set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of a VL CDR1 of a VL set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of a VL CDR2 of a VL set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of a VL CDR3 of a VL set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0008] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence of a VH CDR1 of a VH set forth in Table 2, or the amino acid of a VH CDR1 of a VH set forth in Table 2, comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence of a VH CDR2 of a VH set forth in Table 2, or the amino acid sequence of a VH CDR2 of a VH set forth in Table 2 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of a VH CDR3 of a VH set forth in Table 2, or the amino acid sequence of a VH CDR3 of a VH set forth in Table 2 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence of a VL CDR1 of a VL set forth in Table 2, or the amino acid sequence of a VL CDR1 of a VL set forth in Table 2 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence of a VL CDR2 of a VL set forth in Table 2, or the amino acid sequence of a VL CDR2 of a VL set forth in Table 2 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence of a VL CDR3 of a VL set forth in Table 2, or the amino acid sequence of aVL CDR3 of a VL set forth in Table 2 comprising 1 , 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0009] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence of a VH CDR1 of a VH set forth in Table 2, or the amino acid of a VH CDR1 of a VH set forth in Table 2, comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence of a VH CDR2 of a VH set forth in Table 2, or the amino acid sequence of a VH CDR2 of a VH set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of a VH CDR3 of a VH set forth in Table 2, or the amino acid sequence of a VH CDR3 of a VH set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence of a VL CDR1 of a VL set forth in Table 2, or the amino acid sequence of a VL CDR1 of a VL set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence of a VL CDR2 of a VL set forth in Table 2, or the amino acid sequence of a VL CDR2 of a VL set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence of a VL CDR3 of a VL set forth in Table 2, or the amino acid sequence of a VL CDR3 of a VL set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0010] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence of a VH CDR1 of a VH set forth in Table 2; the amino acid sequence of VH CDR2 consists of the amino acid sequence of a VH CDR2 of a VH set forth in Table 2; the amino acid sequence of VH CDR3 consists of a VH CDR3 of a VH set forth in Table 2; the amino acid sequence of VL CDR1 consists of the amino acid sequence of a VL CDR1 of a VL set forth in Table 2; the amino acid sequence of VL CDR2 consists of the amino acid sequence of a VL CDR2 of a VL set forth in Table 2; and the amino acid sequence of VL CDR3 consists of the amino acid sequence of a VL CDR3 of a VL set forth in Table 2.

[0011] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid of a VH CDR1 of a VH set forth in Table 2, comprising no more than 1, 2, or 3 amino acidvariations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of a VH CDR2 of a VH set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations e.g., substitution, deletion, addition, etc.); the amino acid sequence of a VH CDR3 of a VH set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of a VL CDR1 of a VL set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of a VL CDR2 of a VL set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of a VL CDR3 of a VL set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0012] In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VH set forth in Table 2; and the amino acid sequence of the VL comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VL set forth in Table 2. In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VH set forth in Table 2; and the amino acid sequence of the VL comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VL set forth in Table 2. In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VH set forth in Table 2; and the amino acid sequence of the VL comprises an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VL set forth in Table 2. In some embodiments, the amino acid sequence of the VH comprises the amino acid sequence of a VH set forth in Table 2; and the amino acid sequence of the VL comprises the amino acid sequence of a VL set forth in Table 2.

[0013] In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VH set forth in Table 2; and the amino acid sequence of the VL consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%,90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VL set forth in Table 2. In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VH set forth in Table 2; and the amino acid sequence of the VL consists of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VL set forth in Table 2. In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VH set forth in Table 2; and the amino acid sequence of the VL consists of an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VL set forth in Table 2. In some embodiments, the amino acid sequence of the VH consists of the amino acid sequence of a VH set forth in Table 2; and the amino acid sequence of the VL consists of the amino acid sequence of a VL set forth in Table 2.

[0014] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence of a VH CDR1 set forth in Table 2, or the amino acid of a VH CDR1 set forth in Table 2, comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence of a VH CDR2 set forth in Table 2, or the amino acid sequence of a VH CDR2 set forth in Table 2 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises of a VH CDR3 set forth in Table 2, or the amino acid sequence of a VH CDR3 set forth in Table 2 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence of a VL CDR1 set forth in Table 2, or the amino acid sequence of a VL CDR1 set forth in Table 2 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence of a VL CDR2 set forth in Table 2, or the amino acid sequence of a VL CDR2 set forth in Table 2 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence of a VL CDR3 set forth in Table 2, or the amino acid sequence of a VL CDR3 set forth in Table 2 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0015] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acidsequence of a VH CDR1 set forth in Table 2, or the amino acid of a VH CDR1 set forth in Table 2, comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence of a VH CDR2 set forth in Table 2, or the amino acid sequence of a VH CDR2 set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises of a VH CDR3 set forth in Table 2, or the amino acid sequence of a VH CDR3 set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence of a VL CDR1 set forth in Table 2, or the amino acid sequence of a VL CDR1 set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence of a VL CDR2 set forth in Table 2, or the amino acid sequence of a VL CDR2 set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence of a VL CDR3 set forth in Table 2, or the amino acid sequence of a VL CDR3 set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0016] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence of a VH CDR1 set forth in Table 2; the amino acid sequence of VH CDR2 comprises the amino acid sequence of a VH CDR2 set forth in Table 2; the amino acid sequence of VH CDR3 comprises of a VH CDR3 set forth in Table 2; the amino acid sequence of VL CDR1 comprises the amino acid sequence of a VL CDR1 set forth in Table 2; the amino acid sequence of VL CDR2 comprises the amino acid sequence of a VL CDR2 set forth in Table 2; and the amino acid sequence of VL CDR3 comprises the amino acid sequence of a VL CDR3 set forth in Table 2.

[0017] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid of a VH CDR1 set forth in Table 2, comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of a VH CDR2 set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of a VH CDR3 set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of a VL CDR1 set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g.,substitution, deletion, addition, etc.); the amino acid sequence of a VL CDR2 set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations {e.g., substitution, deletion, addition, etc.); and the amino acid sequence of a VL CDR3 set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations {e.g., substitution, deletion, addition, etc.).

[0018] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence of a VH CDR1 set forth in Table 2, or the amino acid of a VH CDR1 set forth in Table 2, comprising 1, 2, or 3 amino acid variations {e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence of a VH CDR2 set forth in Table 2, or the amino acid sequence of a VH CDR2 set forth in Table 2 comprising 1, 2, or 3 amino acid variations {e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of a VH CDR3 set forth in Table 2, or the amino acid sequence of a VH CDR3 set forth in Table 2 comprising 1, 2, or 3 amino acid variations {e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence of a VL CDR1 set forth in Table 2, or the amino acid sequence of a VL CDR1 set forth in Table 2 comprising 1, 2, or 3 amino acid variations {e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence of a VL CDR2 set forth in Table 2, or the amino acid sequence of a VL CDR2 set forth in Table 2 comprising 1, 2, or 3 amino acid variations {e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence of a VL CDR3 set forth in Table 2, or the amino acid sequence of a VL CDR3 set forth in Table 2 comprising 1, 2, or 3 amino acid variations {e.g., substitution, deletion, addition, etc.).

[0019] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence of a VH CDR1 set forth in Table 2, or the amino acid of a VH CDR1 set forth in Table 2, comprising no more than 1, 2, or 3 amino acid variations {e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence of a VH CDR2 set forth in Table 2, or the amino acid sequence of a VH CDR2 set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations {e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of a VH CDR3 set forth in Table 2, or the amino acid sequence of a VH CDR3 set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence of a VL CDR1 set forth in Table 2, or the amino acid sequenceof a VL CDR1 set forth in Table 2 comprising no more than 1 , 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence of a VL CDR2 set forth in Table 2, or the amino acid sequence of a VL CDR2 set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence of a VL CDR3 set forth in Table 2, or the amino acid sequence of a VL CDR3 set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0020] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence of a VH CDR1 set forth in Table 2; the amino acid sequence of VH CDR2 consists of the amino acid sequence of a VH CDR2 set forth in Table 2; the amino acid sequence of VH CDR3 consists of a VH CDR3 set forth in Table 2; the amino acid sequence of VL CDR1 consists of the amino acid sequence of a VL CDR1 set forth in Table 2; the amino acid sequence of VL CDR2 consists of the amino acid sequence of a VL CDR2 set forth in Table 2; and the amino acid sequence of VL CDR3 consists of the amino acid sequence of a VL CDR3 set forth in Table 2.

[0021] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid of a VH CDR1 set forth in Table 2, comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of a VH CDR2 set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of a VH CDR3 set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of a VL CDR1 set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of a VL CDR2 set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of a VL CDR3 set forth in Table 2 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0022] In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VH set forth in Table 2; and the amino acid sequence of the VL comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acidsequence of a VL set forth in Table 2. In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VH set forth in Table 2; and the amino acid sequence of the VL comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VL set forth in Table 2. In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VH set forth in Table 2; and the amino acid sequence of the VL comprises an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VL set forth in Table 2. In some embodiments, the amino acid sequence of the VH comprises the amino acid sequence of a VH set forth in Table 2; and the amino acid sequence of the VL comprises the amino acid sequence of a VL set forth in Table 2.

[0023] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 4, or the amino acid sequence set forth in SEQ ID NO: 4 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 5, or the amino acid sequence set forth in SEQ ID NO: 5 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 6, or the amino acid sequence set forth in SEQ ID NO: 6 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 7, or the amino acid sequence set forth in SEQ ID NO: 7 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 8, or the amino acid sequence set forth in SEQ ID NO: 8 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0024] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition,etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 4, or the amino acid sequence set forth in SEQ ID NO: 4 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 5, or the amino acid sequence set forth in SEQ ID NO: 5 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 6, or the amino acid sequence set forth in SEQ ID NO: 6 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 7, or the amino acid sequence set forth in SEQ ID NO: 7 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 8, or the amino acid sequence set forth in SEQ ID NO: 8 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0025] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3; the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 4; the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 5; the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 6; the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 7; and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 8.

[0026] In some embodiments, the amino acid sequence of VH CDR1 the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 4 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 5 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 6 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 7 comprising no more than 1,2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 8 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0027] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 4, or the amino acid sequence set forth in SEQ ID NO: 4 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 5, or the amino acid sequence set forth in SEQ ID NO: 5 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 6, or the amino acid sequence set forth in SEQ ID NO: 6 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 7, or the amino acid sequence set forth in SEQ ID NO: 7 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 8, or the amino acid sequence set forth in SEQ ID NO: 8 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0028] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 4, or the amino acid sequence set forth in SEQ ID NO: 4 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 5, or the amino acid sequence set forth in SEQ ID NO: 5 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 6, or the amino acid sequence set forth in SEQ ID NO: 6 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQID NO: 7, or the amino acid sequence set forth in SEQ ID NO: 7 comprising no more than 1 , 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 8, or the amino acid sequence set forth in SEQ ID NO: 8 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0029] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3; the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 4; the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 5; the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 6; the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 7; and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 8.

[0030] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations {e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 4 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 5 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 6 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 7 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 8 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0031] In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 9; and the amino acid sequence of the VL comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, the amino acid sequence of the VH comprisesan amino acid sequence at least 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 9; and the amino acid sequence of the VL comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 9; and the amino acid sequence of the VL comprises an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, the amino acid sequence of the VH comprises the amino acid sequence set forth in SEQ ID NO: 9; and the amino acid sequence of the VL comprises the amino acid sequence set forth in SEQ ID NO: 10.

[0032] In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 9; and the amino acid sequence of the VL consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 9; and the amino acid sequence of the VL consists of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 9; and the amino acid sequence of the VL consists of an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, the amino acid sequence of the VH consists of the amino acid sequence set forth in SEQ ID NO: 9; and the amino acid sequence of the VL consists of the amino acid sequence set forth in SEQ ID NO: 10.

[0033] In some embodiments, the amino acid sequence of the heavy chain comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 11; and theamino acid sequence of the light chain comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 12. In some embodiments, the amino acid sequence of the heavy chain comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 11; and the amino acid sequence of the light chain comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 12. In some embodiments, the amino acid sequence of the heavy chain comprises an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 11; and the amino acid sequence of the light chain comprises an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 12. In some embodiments, the amino acid sequence of the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 11; and the amino acid sequence of the light chain comprises the amino acid sequence set forth in SEQ ID NO: 12.

[0034] In some embodiments, the amino acid sequence of the heavy chain consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 11; and the amino acid sequence of the light chain consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 12. In some embodiments, the amino acid sequence of the heavy chain consists of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 11; and the amino acid sequence of the light chain consists of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 12. In some embodiments, the amino acid sequence of the heavy chain consists of an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 11; and the amino acid sequence of the light chain consists of an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 12. In some embodiments, the amino acid sequence of the heavy chain consists of the amino acid sequence set forth in SEQ ID NO: 11; and the amino acid sequence of the light chain consists of the amino acid sequence set forth in SEQ ID NO: 12.

[0035] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 4, or the amino acid sequence set forth in SEQ ID NO: 4 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 5, or the amino acid sequence set forth in SEQ ID NO: 5 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 66, or the amino acid sequence set forth in SEQ ID NO: 66 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 67, or the amino acid sequence set forth in SEQ ID NO: 67 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 68, or the amino acid sequence set forth in SEQ ID NO: 68 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0036] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 4, or the amino acid sequence set forth in SEQ ID NO: 4 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 5, or the amino acid sequence set forth in SEQ ID NO: 5 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 66, or the amino acid sequence set forth in SEQ ID NO: 66 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 67, or the amino acid sequence set forth in SEQ ID NO: 67 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 68, or the amino acidsequence set forth in SEQ ID NO: 68 comprising no more than 1 , 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0037] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3; the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 4; the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 5; the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 66; the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 67; and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 68.

[0038] In some embodiments, the amino acid sequence of VH CDR1 the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 4 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 5 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 66 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 67 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 68 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0039] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 4, or the amino acid sequence set forth in SEQ ID NO: 4 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 5, or the amino acid sequence set forth in SEQ ID NO: 5 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 66, orthe amino acid sequence set forth in SEQ ID NO: 66 comprising 1 , 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 67, or the amino acid sequence set forth in SEQ ID NO: 67 comprising 1, 2, or 3 amino acid variations e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 68, or the amino acid sequence set forth in SEQ ID NO: 68 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0040] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 4, or the amino acid sequence set forth in SEQ ID NO: 4 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 5, or the amino acid sequence set forth in SEQ ID NO: 5 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 66, or the amino acid sequence set forth in SEQ ID NO: 66 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 67, or the amino acid sequence set forth in SEQ ID NO: 67 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 68, or the amino acid sequence set forth in SEQ ID NO: 68 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0041] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3; the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 4; the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 5; the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 66; the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 67; and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 68.

[0042] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 4 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 5 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 66 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 67 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 68 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0043] In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 9; and the amino acid sequence of the VL comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 69. In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 9; and the amino acid sequence of the VL comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 69. In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 9; and the amino acid sequence of the VL comprises an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 69. In some embodiments, the amino acid sequence of the VH comprises the amino acid sequence set forth in SEQ ID NO: 9; and the amino acid sequence of the VL comprises the amino acid sequence set forth in SEQ ID NO: 69.

[0044] In some embodiments, the amino acid sequence of the VH consists of an amino acidsequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 9; and the amino acid sequence of the VL consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 69. In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 9; and the amino acid sequence of the VL consists of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 69. In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 9; and the amino acid sequence of the VL consists of an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 69. In some embodiments, the amino acid sequence of the VH consists of the amino acid sequence set forth in SEQ ID NO: 9; and the amino acid sequence of the VL consists of the amino acid sequence set forth in SEQ ID NO: 69.

[0045] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 4, or the amino acid sequence set forth in SEQ ID NO: 4 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 5, or the amino acid sequence set forth in SEQ ID NO: 5 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 70, or the amino acid sequence set forth in SEQ ID NO: 70 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 71, or the amino acid sequence set forth in SEQ ID NO: 71 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 68, or the amino acid sequence set forth in SEQ ID NO: 68 comprising 1, 2, or 3 amino acidvariations {e.g., substitution, deletion, addition, etc.).

[0046] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations {e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 4, or the amino acid sequence set forth in SEQ ID NO: 4 comprising no more than 1, 2, or 3 amino acid variations {e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 5, or the amino acid sequence set forth in SEQ ID NO: 5 comprising no more than 1, 2, or 3 amino acid variations {e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 70, or the amino acid sequence set forth in SEQ ID NO: 70 comprising no more than 1, 2, or 3 amino acid variations {e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 71, or the amino acid sequence set forth in SEQ ID NO: 71 comprising no more than 1, 2, or 3 amino acid variations e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 68, or the amino acid sequence set forth in SEQ ID NO: 68 comprising no more than 1, 2, or 3 amino acid variations {e.g., substitution, deletion, addition, etc.).

[0047] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3; the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 4; the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 5; the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 70; the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 71; and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 68.

[0048] In some embodiments, the amino acid sequence of VH CDR1 the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations {e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 4 comprising no more than 1, 2, or 3 amino acid variations {e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 5 comprising no more than 1, 2, or 3 amino acidvariations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 70 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 71 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 68 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0049] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 4, or the amino acid sequence set forth in SEQ ID NO: 4 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 5, or the amino acid sequence set forth in SEQ ID NO: 5 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 70, or the amino acid sequence set forth in SEQ ID NO: 70 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 71, or the amino acid sequence set forth in SEQ ID NO: 71 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 68, or the amino acid sequence set forth in SEQ ID NO: 68 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0050] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 4, or the amino acid sequence set forth in SEQ ID NO: 4 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 5, or the amino acid sequence set forth in SEQ ID NO: 5 comprising no more than 1, 2, or 3 amino acid variations (e.g.,substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 70, or the amino acid sequence set forth in SEQ ID NO: 70 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 71, or the amino acid sequence set forth in SEQ ID NO: 71 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 68, or the amino acid sequence set forth in SEQ ID NO: 68 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0051] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3; the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 4; the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 5; the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 70; the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 71; and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 68.

[0052] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 4 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 5 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 70 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 71 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 68 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0053] In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 9; and the amino acid sequence of the VL comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 72. In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 9; and the amino acid sequence of the VL comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 72. In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 9; and the amino acid sequence of the VL comprises an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 72. In some embodiments, the amino acid sequence of the VH comprises the amino acid sequence set forth in SEQ ID NO: 9; and the amino acid sequence of the VL comprises the amino acid sequence set forth in SEQ ID NO: 72.

[0054] In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 9; and the amino acid sequence of the VL consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 72. In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 9; and the amino acid sequence of the VL consists of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 72. In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 9; and the amino acid sequence of the VL consists of an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 72. In some embodiments, the amino acid sequence of the VH consists of the amino acid sequence set forth in SEQ ID NO: 9; and the amino acid sequence of the VL consists of the amino acid sequenceset forth in SEQ ID NO: 72.

[0055] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 4, or the amino acid sequence set forth in SEQ ID NO: 4 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 5, or the amino acid sequence set forth in SEQ ID NO: 5 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 73, or the amino acid sequence set forth in SEQ ID NO: 73 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 74, or the amino acid sequence set forth in SEQ ID NO: 74 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 75, or the amino acid sequence set forth in SEQ ID NO: 75 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0056] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 4, or the amino acid sequence set forth in SEQ ID NO: 4 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 5, or the amino acid sequence set forth in SEQ ID NO: 5 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 73, or the amino acid sequence set forth in SEQ ID NO: 73 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 74, or the amino acid sequence set forth in SEQ ID NO: 74 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequenceof VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 75, or the amino acid sequence set forth in SEQ ID NO: 75 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0057] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3; the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 4; the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 5; the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 73; the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 74; and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 75.

[0058] In some embodiments, the amino acid sequence of VH CDR1 the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 4 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 5 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 73 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 74 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 75 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0059] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 4, or the amino acid sequence set forth in SEQ ID NO: 4 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 5, or the amino acid sequence set forth in SEQ ID NO: 5 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the aminoacid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 73, or the amino acid sequence set forth in SEQ ID NO: 73 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 74, or the amino acid sequence set forth in SEQ ID NO: 74 comprising 1, 2, or 3 amino acid variations e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 75, or the amino acid sequence set forth in SEQ ID NO: 75 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0060] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 4, or the amino acid sequence set forth in SEQ ID NO: 4 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 5, or the amino acid sequence set forth in SEQ ID NO: 5 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 73, or the amino acid sequence set forth in SEQ ID NO: 73 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 74, or the amino acid sequence set forth in SEQ ID NO: 74 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 75, or the amino acid sequence set forth in SEQ ID NO: 75 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0061] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3; the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 4; the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 5; the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 73; the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 74; and the amino acidsequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 75.

[0062] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 4 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 5 comprising no more than 1, 2, or 3 amino acid variations e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 73 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 74 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 75 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0063] In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 9; and the amino acid sequence of the VL comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 76. In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 9; and the amino acid sequence of the VL comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 76. In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 9; and the amino acid sequence of the VL comprises an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 76. In some embodiments, the amino acid sequence of the VH comprises the amino acid sequence set forth in SEQ ID NO: 9; and the amino acid sequence of the VL comprises the amino acid sequence set forth in SEQ ID NO: 76.

[0064] In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 9; and the amino acid sequence of the VL consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 76. In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 9; and the amino acid sequence of the VL consists of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 76. In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 9; and the amino acid sequence of the VL consists of an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 76. In some embodiments, the amino acid sequence of the VH consists of the amino acid sequence set forth in SEQ ID NO: 9; and the amino acid sequence of the VL consists of the amino acid sequence set forth in SEQ ID NO: 76.

[0065] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 77, or the amino acid sequence set forth in SEQ ID NO: 77 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 78, or the amino acid sequence set forth in SEQ ID NO: 78 comprising 1, 2, or 3 amino acid variations e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 6, or the amino acid sequence set forth in SEQ ID NO: 6 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 7, or the amino acid sequence set forth in SEQ ID NO: 7 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO:8, or the amino acid sequence set forth in SEQ ID NO: 8 comprising 1 , 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0066] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 77, or the amino acid sequence set forth in SEQ ID NO: 77 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 78, or the amino acid sequence set forth in SEQ ID NO: 78 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 6, or the amino acid sequence set forth in SEQ ID NO: 6 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 7, or the amino acid sequence set forth in SEQ ID NO: 7 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 8, or the amino acid sequence set forth in SEQ ID NO: 8 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0067] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3; the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 77; the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 78; the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 6; the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 7; and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 8.

[0068] In some embodiments, the amino acid sequence of VH CDR1 the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 77 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises theamino acid sequence set forth in SEQ ID NO: 78 comprising no more than 1 , 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 6 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 7 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 8 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0069] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 77, or the amino acid sequence set forth in SEQ ID NO: 77 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 78, or the amino acid sequence set forth in SEQ ID NO: 78 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 6, or the amino acid sequence set forth in SEQ ID NO: 6 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 7, or the amino acid sequence set forth in SEQ ID NO: 7 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 8, or the amino acid sequence set forth in SEQ ID NO: 8 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0070] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 77, or the amino acid sequence set forth in SEQ ID NO: 77 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 78, or the amino acidsequence set forth in SEQ ID NO: 78 comprising no more than 1 , 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 6, or the amino acid sequence set forth in SEQ ID NO: 6 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 7, or the amino acid sequence set forth in SEQ ID NO: 7 comprising no more than1, 2, or 3 amino acid variations e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 8, or the amino acid sequence set forth in SEQ ID NO: 8 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0071] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3; the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 77; the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 78; the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 6; the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 7; and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 8.

[0072] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations {e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 77 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 78 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 6 comprising no more than 1,2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 7 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 8 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0073] In some embodiments, the amino acid sequence of the VH comprises an amino acidsequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 79; and the amino acid sequence of the VL comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 79; and the amino acid sequence of the VL comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 79; and the amino acid sequence of the VL comprises an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, the amino acid sequence of the VH comprises the amino acid sequence set forth in SEQ ID NO: 79; and the amino acid sequence of the VL comprises the amino acid sequence set forth in SEQ ID NO: 10.

[0074] In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 79; and the amino acid sequence of the VL consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 79; and the amino acid sequence of the VL consists of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 79; and the amino acid sequence of the VL consists of an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, the amino acid sequence of the VH consists of the amino acidsequence set forth in SEQ ID NO: 79; and the amino acid sequence of the VL consists of the amino acid sequence set forth in SEQ ID NO: 10.

[0075] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 80, or the amino acid sequence set forth in SEQ ID NO: 80 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 81, or the amino acid sequence set forth in SEQ ID NO: 81 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 6, or the amino acid sequence set forth in SEQ ID NO: 6 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 7, or the amino acid sequence set forth in SEQ ID NO: 7 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 8, or the amino acid sequence set forth in SEQ ID NO: 8 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0076] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 80, or the amino acid sequence set forth in SEQ ID NO: 80 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 81, or the amino acid sequence set forth in SEQ ID NO: 81 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 6, or the amino acid sequence set forth in SEQ ID NO: 6 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 7, or the amino acid sequence set forth in SEQ ID NO: 7 comprising no more than1 , 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 8, or the amino acid sequence set forth in SEQ ID NO: 8 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0077] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3; the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 80; the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 81 ; the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 6; the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 7 ; and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 8.

[0078] In some embodiments, the amino acid sequence of VH CDR1 the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 80 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 81 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 6 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 7 comprising no more than 1,2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 8 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0079] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 80, or the amino acid sequence set forth in SEQ ID NO: 80 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 81, or the amino acid sequence set forth in SEQ IDNO: 81 comprising 1 , 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 6, or the amino acid sequence set forth in SEQ ID NO: 6 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 7, or the amino acid sequence set forth in SEQ ID NO: 7 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 8, or the amino acid sequence set forth in SEQ ID NO: 8 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0080] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 80, or the amino acid sequence set forth in SEQ ID NO: 80 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 81, or the amino acid sequence set forth in SEQ ID NO: 81 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 6, or the amino acid sequence set forth in SEQ ID NO: 6 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 7, or the amino acid sequence set forth in SEQ ID NO: 7 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 8, or the amino acid sequence set forth in SEQ ID NO: 8 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0081] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3; the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 80; the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 81; the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 6; the amino acid sequence of VLCDR2 consists of the amino acid sequence set forth in SEQ ID NO: 7; and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 8.

[0082] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 80 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 81 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 6 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 7 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 8 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0083] In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 82; and the amino acid sequence of the VL comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 82; and the amino acid sequence of the VL comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 82; and the amino acid sequence of the VL comprises an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, the amino acid sequence of the VH comprises the amino acid sequence set forth in SEQ ID NO: 82; and the amino acid sequence of the VL comprises the aminoacid sequence set forth in SEQ ID NO: 10.

[0084] In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 82; and the amino acid sequence of the VL consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 82; and the amino acid sequence of the VL consists of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 82; and the amino acid sequence of the VL consists of an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, the amino acid sequence of the VH consists of the amino acid sequence set forth in SEQ ID NO: 82; and the amino acid sequence of the VL consists of the amino acid sequence set forth in SEQ ID NO: 10.

[0085] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 77, or the amino acid sequence set forth in SEQ ID NO: 77 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 78, or the amino acid sequence set forth in SEQ ID NO: 78 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 6, or the amino acid sequence set forth in SEQ ID NO: 6 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 7, or the amino acid sequence set forth in SEQ ID NO: 7 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); andthe amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 8, or the amino acid sequence set forth in SEQ ID NO: 8 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0086] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 77, or the amino acid sequence set forth in SEQ ID NO: 77 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 78, or the amino acid sequence set forth in SEQ ID NO: 78 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 6, or the amino acid sequence set forth in SEQ ID NO: 6 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 7, or the amino acid sequence set forth in SEQ ID NO: 7 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 8, or the amino acid sequence set forth in SEQ ID NO: 8 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0087] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3; the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 77; the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 78; the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 6; the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 7 ; and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 8.

[0088] In some embodiments, the amino acid sequence of VH CDR1 the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid valuations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 77 comprising no more than 1, 2, or 3 amino acid variations(e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 78 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 6 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 7 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 8 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0089] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 77, or the amino acid sequence set forth in SEQ ID NO: 77 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 78, or the amino acid sequence set forth in SEQ ID NO: 78 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 6, or the amino acid sequence set forth in SEQ ID NO: 6 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 7, or the amino acid sequence set forth in SEQ ID NO: 7 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 8, or the amino acid sequence set forth in SEQ ID NO: 8 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0090] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 77, or the amino acid sequence set forth in SEQ ID NO: 77 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence ofVH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 78, or the amino acid sequence set forth in SEQ ID NO: 78 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 6, or the amino acid sequence set forth in SEQ ID NO: 6 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 7, or the amino acid sequence set forth in SEQ ID NO: 7 comprising no more than1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 8, or the amino acid sequence set forth in SEQ ID NO: 8 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0091] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3; the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 77; the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 78; the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 6; the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 7; and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 8.

[0092] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 77 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 78 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 6 comprising no more than 1,2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 7 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 8 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0093] In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 83; and the amino acid sequence of the VL comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 83; and the amino acid sequence of the VL comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 83; and the amino acid sequence of the VL comprises an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, the amino acid sequence of the VH comprises the amino acid sequence set forth in SEQ ID NO: 83; and the amino acid sequence of the VL comprises the amino acid sequence set forth in SEQ ID NO: 10.

[0094] In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 83; and the amino acid sequence of the VL consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 83; and the amino acid sequence of the VL consists of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 83; and the amino acid sequence of the VL consists of an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQID NO: 10. In some embodiments, the amino acid sequence of the VH consists of the amino acid sequence set forth in SEQ ID NO: 83; and the amino acid sequence of the VL consists of the amino acid sequence set forth in SEQ ID NO: 10.

[0095] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 77, or the amino acid sequence set forth in SEQ ID NO: 77 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 78, or the amino acid sequence set forth in SEQ ID NO: 78 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 70, or the amino acid sequence set forth in SEQ ID NO: 70 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 71, or the amino acid sequence set forth in SEQ ID NO: 71 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 68, or the amino acid sequence set forth in SEQ ID NO: 68 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0096] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 77, or the amino acid sequence set forth in SEQ ID NO: 77 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 78, or the amino acid sequence set forth in SEQ ID NO: 78 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 70, or the amino acid sequence set forth in SEQ ID NO: 70 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence set forthin SEQ ID NO: 71 , or the amino acid sequence set forth in SEQ ID NO: 71 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 68, or the amino acid sequence set forth in SEQ ID NO: 68 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0097] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3; the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 77; the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 78; the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 70; the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 71; and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 68.

[0098] In some embodiments, the amino acid sequence of VH CDR1 the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 77 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 78 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 70 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 71 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 68 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0099] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 77, or the amino acid sequence set forth in SEQ ID NO: 77 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of theamino acid sequence set forth in SEQ ID NO: 78, or the amino acid sequence set forth in SEQ ID NO: 78 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 70, or the amino acid sequence set forth in SEQ ID NO: 70 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 71, or the amino acid sequence set forth in SEQ ID NO: 71 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 68, or the amino acid sequence set forth in SEQ ID NO: 68 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0100] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 77, or the amino acid sequence set forth in SEQ ID NO: 77 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 78, or the amino acid sequence set forth in SEQ ID NO: 78 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 70, or the amino acid sequence set forth in SEQ ID NO: 70 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 71, or the amino acid sequence set forth in SEQ ID NO: 71 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 68, or the amino acid sequence set forth in SEQ ID NO: 68 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0101] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3; the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 77; the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 78; the amino acid sequence of VL CDR1consists of the amino acid sequence set forth in SEQ ID NO: 70; the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 71; and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 68.

[0102] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 77 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 78 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 70 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 71 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 68 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0103] In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 83; and the amino acid sequence of the VL comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 72. In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 83; and the amino acid sequence of the VL comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 72. In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 83; and the amino acid sequence of the VL comprises an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 72. In some embodiments, the amino acid sequence of the VH comprises the amino acidsequence set forth in SEQ ID NO: 83; and the amino acid sequence of the VL comprises the amino acid sequence set forth in SEQ ID NO: 72.

[0104] In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 83; and the amino acid sequence of the VL consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 72. In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 83; and the amino acid sequence of the VL consists of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 72. In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 83; and the amino acid sequence of the VL consists of an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 72. In some embodiments, the amino acid sequence of the VH consists of the amino acid sequence set forth in SEQ ID NO: 83; and the amino acid sequence of the VL consists of the amino acid sequence set forth in SEQ ID NO: 72.

[0105] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 80, or the amino acid sequence set forth in SEQ ID NO: 80 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 81, or the amino acid sequence set forth in SEQ ID NO: 81 comprising 1, 2, or 3 amino acid variations e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 73, or the amino acid sequence set forth in SEQ ID NO: 73 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 74, or the amino acid sequence setforth in SEQ TD NO: 74 comprising 1 , 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 75, or the amino acid sequence set forth in SEQ ID NO: 75 comprising 1, 2, or 3 amino acid variations e.g., substitution, deletion, addition, etc.).

[0106] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 80, or the amino acid sequence set forth in SEQ ID NO: 80 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 81, or the amino acid sequence set forth in SEQ ID NO: 81 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 73, or the amino acid sequence set forth in SEQ ID NO: 73 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 74, or the amino acid sequence set forth in SEQ ID NO: 74 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 75, or the amino acid sequence set forth in SEQ ID NO: 75 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0107] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3; the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 80; the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 81; the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 73; the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 74; and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 75.

[0108] In some embodiments, the amino acid sequence of VH CDR1 the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the aminoacid sequence set forth in SEQ ID NO: 80 comprising no more than 1 , 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 81 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 73 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 74 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 75 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0109] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 80, or the amino acid sequence set forth in SEQ ID NO: 80 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 81, or the amino acid sequence set forth in SEQ ID NO: 81 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 73, or the amino acid sequence set forth in SEQ ID NO: 73 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 74, or the amino acid sequence set forth in SEQ ID NO: 74 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 75, or the amino acid sequence set forth in SEQ ID NO: 75 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0110] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 80, or the amino acid sequence set forth in SEQ ID NO: 80 comprising no more than 1, 2,or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 81, or the amino acid sequence set forth in SEQ ID NO: 81 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 73, or the amino acid sequence set forth in SEQ ID NO: 73 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 74, or the amino acid sequence set forth in SEQ ID NO: 74 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 75, or the amino acid sequence set forth in SEQ ID NO: 75 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0111] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3; the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 80; the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 81; the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 73; the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 74; and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 75.

[0112] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 80 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 81 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 73 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 74 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 75 comprisingno more than 1 , 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0113] In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 82; and the amino acid sequence of the VL comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 76. In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 82; and the amino acid sequence of the VL comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 76. In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 82; and the amino acid sequence of the VL comprises an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 76. In some embodiments, the amino acid sequence of the VH comprises the amino acid sequence set forth in SEQ ID NO: 82; and the amino acid sequence of the VL comprises the amino acid sequence set forth in SEQ ID NO: 76.

[0114] In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 82; and the amino acid sequence of the VL consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 76. In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 82; and the amino acid sequence of the VL consists of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 76. In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 82; and the amino acid sequence of the VL consists of an amino acid sequenceat least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 76. In some embodiments, the amino acid sequence of the VH consists of the amino acid sequence set forth in SEQ ID NO: 82; and the amino acid sequence of the VL consists of the amino acid sequence set forth in SEQ ID NO: 76.

[0115] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 80, or the amino acid sequence set forth in SEQ ID NO: 80 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 81, or the amino acid sequence set forth in SEQ ID NO: 81 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 84, or the amino acid sequence set forth in SEQ ID NO: 84 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 85; or the amino acid sequence set forth in SEQ ID NO: 85 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 86, or the amino acid sequence set forth in SEQ ID NO: 86 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0116] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 80, or the amino acid sequence set forth in SEQ ID NO: 80 comprising no more than I, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 81, or the amino acid sequence set forth in SEQ ID NO: 81 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 84, or the amino acid sequence set forth in SEQ ID NO: 84 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion,addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 85; or the amino acid sequence set forth in SEQ ID NO: 85 comprising no more than 1, 2, or 3 amino acid variations (e. ., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 86, or the amino acid sequence set forth in SEQ ID NO: 86 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0117] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3; the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 80; the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 81; the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 84; the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 85; and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 86.

[0118] In some embodiments, the amino acid sequence of VH CDR1 the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 80 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 81 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 84 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 85 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 86 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0119] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 80, or the amino acid sequence set forth in SEQ ID NO: 80 comprising 1, 2, or 3 amino acid variations(e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 81, or the amino acid sequence set forth in SEQ ID NO: 81 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 84, or the amino acid sequence set forth in SEQ ID NO: 84 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 85; or the amino acid sequence set forth in SEQ ID NO: 85 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 86, or the amino acid sequence set forth in SEQ ID NO: 86 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0120] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 80, or the amino acid sequence set forth in SEQ ID NO: 80 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 81, or the amino acid sequence set forth in SEQ ID NO: 81 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 84, or the amino acid sequence set forth in SEQ ID NO: 84 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 85; or the amino acid sequence set forth in SEQ ID NO: 85 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 86, or the amino acid sequence set forth in SEQ ID NO: 86 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0121] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3; the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 80; the amino acid sequence of VH CDR3 consistsIllof the amino acid sequence set forth in SEQ ID NO: 81 ; the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 84; the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 85; and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 86.

[0122] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 80 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 81 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 84 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 85 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 86 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0123] In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 87; and the amino acid sequence of the VL comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 88. In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 87; and the amino acid sequence of the VL comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 88. In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 87 ; and the amino acid sequence of the VL comprises an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQID NO: 88. Tn some embodiments, the amino acid sequence of the VH comprises the amino acid sequence set forth in SEQ ID NO: 87; and the amino acid sequence of the VL comprises the amino acid sequence set forth in SEQ ID NO: 88.

[0124] In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 87; and the amino acid sequence of the VL consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 88. In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 87; and the amino acid sequence of the VL consists of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 88. In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 87; and the amino acid sequence of the VL consists of an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 88. In some embodiments, the amino acid sequence of the VH consists of the amino acid sequence set forth in SEQ ID NO: 87; and the amino acid sequence of the VL consists of the amino acid sequence set forth in SEQ ID NO: 88.

[0125] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 80, or the amino acid sequence set forth in SEQ ID NO: 80 comprising I, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 81, or the amino acid sequence set forth in SEQ ID NO: 81 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 89, or the amino acid sequence set forth in SEQ ID NO: 89 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2comprises the amino acid sequence set forth in SEQ TD NO: 74, or the amino acid sequence set forth in SEQ ID NO: 74 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 68, or the amino acid sequence set forth in SEQ ID NO: 68 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0126] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 80, or the amino acid sequence set forth in SEQ ID NO: 80 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 81, or the amino acid sequence set forth in SEQ ID NO: 81 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 89, or the amino acid sequence set forth in SEQ ID NO: 89 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 74, or the amino acid sequence set forth in SEQ ID NO: 74 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 68, or the amino acid sequence set forth in SEQ ID NO: 68 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0127] In some embodiments, the amino acid sequence of VH CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3; the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 80; the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 81; the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 89; the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 74; and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 68.

[0128] In some embodiments, the amino acid sequence of VH CDR1 the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g.,substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 80 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 81 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 89 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 74 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 68 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0129] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 80, or the amino acid sequence set forth in SEQ ID NO: 80 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 81, or the amino acid sequence set forth in SEQ ID NO: 81 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 89, or the amino acid sequence set forth in SEQ ID NO: 89 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 74, or the amino acid sequence set forth in SEQ ID NO: 74 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 68, or the amino acid sequence set forth in SEQ ID NO: 68 comprising 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0130] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3, or the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQID NO: 80, or the amino acid sequence set forth in SEQ ID NO: 80 comprising no more than 1 , 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 81, or the amino acid sequence set forth in SEQ ID NO: 81 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 89, or the amino acid sequence set forth in SEQ ID NO: 89 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 74, or the amino acid sequence set forth in SEQ ID NO: 74 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 68, or the amino acid sequence set forth in SEQ ID NO: 68 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0131] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3; the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 80; the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 81; the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 89; the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 74; and the amino acid sequence of VL CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 68.

[0132] In some embodiments, the amino acid sequence of VH CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 3 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 80 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 81 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR1 consists of the amino acid sequence set forth in SEQ ID NO: 89 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of VL CDR2 consists of the amino acid sequence set forth in SEQ ID NO: 74 comprising no more than 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, e...

Claims

CLAIMSWhat Is Claimed Is:

1. A CLEC2D binding protein comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises:(a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 3; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 4; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 5; and(b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 6; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 8.

2. The CLEC2D binding protein of claim 1, wherein(a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 9; and(b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 10.

3. A CLEC2D binding protein comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises:(a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 3; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 4; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 5; and(b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 66; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 67; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 68.

4. The CLEC2D binding protein of claim 3, wherein(a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 9; and(b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 69.

5. A CLEC2D binding protein comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises:(a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 3; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 4; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 5; and(b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 70; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 71; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 68.

6. The CLEC2D binding protein of claim 5, wherein(a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 9; and(b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 72.

7. A CLEC2D binding protein comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises:(a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 3; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 4; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 5; and(b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 73; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 74; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 75.

8. The CLEC2D binding protein of claim 7, wherein(a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 9; and(b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 76.

9. A CLEC2D binding protein comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises:(a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 3; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 77; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 78; and(b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 6; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 8.

10. The CLEC2D binding protein of claim 5, wherein(a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 79; and(b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 10.

11. A CLEC2D binding protein comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises:(a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 3; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 80; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 81; and(b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 6; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 8.

12. The CLEC2D binding protein of claim 11, wherein(a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 82; and(b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 10.

13. A CLEC2D binding protein comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises:(a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 3; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 77; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 78; and(b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 6; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 8.

14. The CLEC2D binding protein of claim 13, wherein(a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 83; and(b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 10.

15. A CLEC2D binding protein comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises:(a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 3; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 77; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 78; and(b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 70; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 71; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 68.

16. The CLEC2D binding protein of claim 15, wherein(a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 83; and(b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 72.

17. A CLEC2D binding protein comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises:(a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 3; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 80; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 81; and(b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 73; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 74; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 75.

18. The CLEC2D binding protein of claim 17, wherein(a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 82; and(b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 76.

19. A CLEC2D binding protein comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises:(a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 3; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 80; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 81; and(b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 84; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 85; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 86.

20. The CLEC2D binding protein of claim 19, wherein(a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 87; and(b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 88.

21. A CLEC2D binding protein comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises:(a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 3; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 80; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 81; and(b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 89; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 74; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 68.

22. The CLEC2D binding protein of claim 21, wherein(a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 87; and(b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 90.

23. A CLEC2D binding protein comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises:(a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 91; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 92; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 93; and(b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 6; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 152.

24. The CLEC2D binding protein of claim 23, wherein(a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 4; and(b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 95.

25. A CLEC2D binding protein comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises:(a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 91; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 92; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 96; and(b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 97; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 98.

26. The CLEC2D binding protein of claim 25, wherein(a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 99; and(b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 100.

27. A CLEC2D binding protein comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises:(a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 91; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 92; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 101; and(b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 97; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 102.

28. The CLEC2D binding protein of claim 27, wherein(a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 103; and(b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 104.

29. A CLEC2D binding protein comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises:(a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 105; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 106; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 107; and(b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 6; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 108.

30. The CLEC2D binding protein of claim 30, wherein(a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 109; and(b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 110.

31. A CLEC2D binding protein comprising a binding domain that specifically binds CLEC2D e.g., hCLEC2D), wherein the binding domain comprises:(a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 91; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 92; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 111; and(b) a VL region comprising (i) a CDR-LI comprising the amino acid sequence set forth in SEQ ID NO: 97; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 112.

32. The CLEC2D binding protein of claim 31 , wherein(a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 113; and(b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 114.

33. A CLEC2D binding protein comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises:(a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 3; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 4; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 115; and(b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 97; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 116.

34. The CLEC2D binding protein of claim 33, wherein(a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 117; and(b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 118.

35. A CLEC2D binding protein comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises:(a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 119; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 120; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 121; and(b) a VL region comprising (i) a CDR-LI comprising the amino acid sequence set forth in SEQ ID NO: 6; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 122.

36. The CLEC2D binding protein of claim 35, wherein(a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 123; and(b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 124.

37. A CLEC2D binding protein comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises:(a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 91; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 92; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 153; and(b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 97; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 125.

38. The CLEC2D binding protein of claim 37, wherein(a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 126; and(b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 127.

39. A CLEC2D binding protein comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises:(a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 119; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 120; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 128; and(b) a VL region comprising (i) a CDR-LI comprising the amino acid sequence set forth in SEQ ID NO: 6; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 129.

40. The CLEC2D binding protein of claim 39, wherein(a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 130; and(b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 131.

41. A CLEC2D binding protein comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises:(a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 91; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 92; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 132; and(b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 97; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 133.

42. The CLEC2D binding protein of claim 41, wherein(a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 134; and(b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 135.

43. A CLEC2D binding protein comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises:(a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 136; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 137; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 138; and(b) a VL region comprising (i) a CDR-LI comprising the amino acid sequence set forth in SEQ ID NO: 97; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 139.

44. The CLEC2D binding protein of claim 43, wherein(a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 140; and(b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 141.

45. A CLEC2D binding protein comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises:(a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 136; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 137; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 142; and(b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 6; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 7; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 143.

46. The CLEC2D binding protein of claim 45, wherein(a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 144; and(b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 145.

47. A CLEC2D binding protein comprising a binding domain that specifically binds CLEC2D e.g., hCLEC2D), wherein the binding domain comprises:(a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 146; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 77; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 78; and(b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 147; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 74; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 75.

48. The CLEC2D binding protein of claim 47, wherein(a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 148; and(b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 148.

49. A CLEC2D binding protein comprising a binding domain that specifically binds CLEC2D (e.g., hCLEC2D), wherein the binding domain comprises:(a) a VH region comprising (i) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 146; (ii) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 77; and (iii) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 78; and(b) a VL region comprising (i) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 66; (ii) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 71; and (iii) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 150.

50. The CLEC2D binding protein of claim 49, wherein(a) the amino acid sequence of the VH region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 148; and(b) the amino acid sequence of the VL region is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NO: 151.

51. The CLEC2D binding protein of any one of the preceding claims, comprising a heavy chain (HC).

52. The CLEC2D binding protein of any one of the preceding claims, comprising a light chain (LC).

53. The CLEC2D binding protein of any one of the preceding claims, wherein the CLEC2D binding protein (or the binding domain) comprises an antibody.

54. The CLEC2D binding protein of any one of the preceding claims, wherein the CLEC2D binding protein (or the binding domain) comprises an IgG (e.g., IgGi, IgGi (e.g., IgG2a or IgG2b), IgGv IgG4), IgE, IgM, IgD, or IgA (e.g., IgAi or IgAa) antibody.

55. The CEEC2D binding protein of any one of the preceding claims, wherein the CLEC2D binding protein (or the binding domain) comprises one or more of a monoclonal antibody, monospecific antibody, multispecific antibody, human antibody, humanized antibody, chimeric antibody, and / or murine antibody, or a functional fragment or functional variant of any of the foregoing.

56. The CLEC2D binding protein of any one of the preceding claims, wherein the CLEC2D binding protein (or the binding domain) comprises one or more of a full-length antibody, scFv, Fab, F(ab')2, Fab', Fv, single domain antibody (e.g., a VHH), scFv-Fc, Fab-Fc, and / or single domain antibody-Fc (e.g., VHH-Fc).

57. The CEEC2D binding protein of any one of the preceding claims, wherein the CEEC2D binding protein comprises an Ig Fc (e.g., a hlg Fc) region.

58. The CEEC2D binding protein of any one of the preceding claims, wherein the Ig Fc (e.g., a hlg Fc) region comprises at least a portion of a hinge region, a CH2 region, and a CH3 region.

59. The CEEC2D binding protein of any one of the preceding claims, wherein the Ig Fc (e.g., a hlg Fc) region comprises a hinge region, a CH2 region, and a CH3 region.

60. The CEEC2D binding protein of any one of the preceding claims, wherein the Ig Fc (e.g., a hlg Fc) region is a hlgG (e.g., hlgGl, hIgG2, hIgG3, hIgG4).

61. The CEEC2D binding protein of any one of the preceding claims, wherein the Ig Fc (e.g., a hlg Fc) region is part of a full-length antibody.

62. The CEEC2D binding protein of any one of the preceding claims, wherein the CEEC2D binding protein comprises a first Ig Fc (e.g., a first hlg Fc) region and a second Ig Fc (e.g., a first hlg Fc) region.

63. The CEEC2D binding protein of any one of the preceding claims, wherein the first Ig Fc (e.g., the first hlg Fc) region and the second Ig Fc (e.g., the second hlg Fc) each comprises at least a portion of a hinge region, a CH2 region, and a CH3 region.

64. The CEEC2D binding protein of any one of the preceding claims, wherein the first Ig Fc (e.g., the first hlg Fc) region and the second Ig Fc (e.g., the second hlg Fc) each comprises a hinge region, a CH2 region, and a CH3 region.

65. The CEEC2D binding protein of any one of the preceding claims, wherein the first Ig Fc (e.g., the first hlg Fc) region and the second Ig Fc (e.g., the second hlg Fc) each is a hlgG (e.g., hlgGl, hIgG2, hIgG3, h!gG4).

66. The CLEC2D binding protein of any one of the preceding claims, wherein the first Ig Fc (e.g., the first hlg Fc) and the second Ig Fc (e.g., the second hlg Fc) regions arc part of a full- length antibody.

67. The CLEC2D binding protein of any one of the preceding claims, wherein the Ig Fc e.g., the hlg Fc), the first Ig Fc (e.g., the first hlg Fc), and / or the second Ig Fc (e.g., the second hlg Fc) comprises one or more amino acid variation and / or varied glycosylation relative to a reference Ig Fc region (e.g., a reference hlg Fc).

68. The CLEC2D binding protein of any one of the preceding claims, wherein the Ig Fc (e.g., the hlg Fc), the first Ig Fc (e.g., the first hlg Fc), and / or the second Ig Fc (e.g., the second hlg Fc) exhibits an alteration in one or more effector function relative to a reference Ig Fc region (e.g., a reference hlg Fc).

69. The CLEC2D binding protein of any one of the preceding claims, wherein the Ig Fc (e.g., the hlg Fc), the first Ig Fc (e.g., the first hlg Fc), and / or the second Ig Fc (e.g., the second hlg Fc) exhibits enhanced effector function relative to a reference Ig Fc region.

70. The CLEC2D binding protein of any one of the preceding claims, wherein the Ig Fc (e.g., the hlg Fc), the first Ig Fc (e.g., the first hlg Fc), and / or the second Ig Fc (e.g., the second hlg Fc) exhibits reduced effector function relative to a reference Ig Fc region (e.g., a reference hlg Fc).

71. The CLEC2D binding protein of any one of the preceding claims, wherein the Ig Fc (e.g., the hlg Fc), the first Ig Fc (e.g., the first hlg Fc), and / or the second Ig Fc (e.g., the second hlg Fc) comprises one or more amino acid variation and / or varied glycosylation relative to a reference Ig Fc region (e.g., a reference hlg Fc), wherein the one or more amino acid variations and / or varied glycosylation alter one or more effector function.

72. The CLEC2D binding protein of any one of the preceding claims, wherein the Ig Fc (e.g., the hlg Fc), the first Ig Fc (e.g., the first hlg Fc), and / or the second Ig Fc (e.g., the second hlg Fc) comprises one or more amino acid variation and / or varied glycosylation relative to a reference Ig Fc region (e.g., a reference hlg Fc), wherein the one or more amino acid variations and / or varied glycosylation enhance one or more effector function.

73. The CLEC2D binding protein of any one of the preceding claims, wherein the Ig Fc (e.g., the hlg Fc), the first Ig Fc (e.g., the first hlg Fc), and / or the second Ig Fc (e.g., the second hlg Fc) comprises one or more amino acid variation and / or varied glycosylation relative to a reference IgFc region (e.g., a reference hlg Fc), wherein the one or more amino acid variations and / or varied glycosylation reduce one or more effector function.

74. The CLEC2D binding protein of any one of the preceding claims, wherein the effector comprises ADCC, CDC, and / or binding affinity to one or more Fc receptor (e.g., an Fey receptor (e.g., FcyRI, Fey R Ila, FcyRIIc, FcyRIIIa, and / or FcyRIIIb (e.g., FcyRI, Fcylla, and / or Fcyllla))).

75. The CLEC2D binding protein of any one of the preceding claims, wherein the antigen binding domain specifically binds CLEC2D (e.g., hCLEC2D) expressed on the surface of a cell (e.g., a target cell).

76. The CLEC2D binding protein of any one the preceding claims, wherein binding of the CLEC2D binding protein to CLEC2D inhibits (e.g., partially, substantially, fully) binding of CLEC2D to CD 161.

77. The CLEC2D binding protein of any one of the preceding claims, further comprising a heterologous moiety (e.g., a heterologous protein).

78. The CLEC2D binding protein of any one of the preceding claims, further comprising 2, 3, 4, or 5 or more heterologous moieties.

79. The CLEC2D binding protein of any one of claims 77-78, wherein the heterologous moiety is attached to the N-terminus, C-terminus, and / or internally between the N- and C- terminus of the CLEC2D binding protein.

80. The CLEC2D binding protein of any one of claims 77-79, wherein the heterologous moiety (e.g., heterologous polypeptide) is directly attached to the CLEC2D binding protein.

81. The CLEC2D binding protein of any one of claims 77-80, wherein the heterologous moiety (e.g., heterologous polypeptide) is indirectly attached to the CLEC2D binding protein.

82. The CLEC2D binding protein of any one of claims 77-81, wherein the heterologous moiety (e.g., heterologous polypeptide) is indirectly attached to the CLEC2D binding protein via a linker.

83. The CLEC2D binding protein of any one of claims 77-82, wherein the heterologous moiety is a peptide, polypeptide, protein, nucleic acid molecule (e.g., DNA, RNA), carbohydrate, lipid, polymer, or small molecule.

84. The CLEC2D binding protein of any one of claims 77-83, wherein the heterologous moiety is a detectable tag and / or a reporter gene.

85. The CLEC2D binding protein of any one of claim 77-84, wherein the heterologous moiety is a therapeutic agent.

86. The CLEC2D binding protein of any one of the preceding claims, wherein the CLEC2D binding protein is isolated.

87. The CLEC2D binding protein of any one of the preceding claims, wherein the CLEC2D binding protein is recombinant.

88. A conjugate comprising the CLEC2D binding protein of any one of claims 1-87 and a heterologous moiety.

89. The conjugate of any one of claims 88, further comprising 2, 3, 4, or 5 or more heterologous moieties.

90. The conjugate of any one of claims 88-89, wherein the heterologous moiety is attached to the N-terminus, C-terminus, and / or internally between the N- and C-terminus of the CLEC2D binding protein.

91. The conjugate of any one of claims 88-90, wherein the heterologous moiety (e.g., heterologous polypeptide) is directly attached to the CLEC2D binding protein.

92. The conjugate of any one of claims 88-91, wherein the heterologous moiety (e.g., heterologous polypeptide) is indirectly attached to the CLEC2D binding protein.

93. The conjugate of any one of claims 88-92, wherein the heterologous moiety (e.g., heterologous polypeptide) is indirectly attached to the CLEC2D binding protein via a linker.

94. The conjugate of any one of claims 88-93, wherein the heterologous moiety is a peptide, polypeptide, carbohydrate, lipid, polymer, or small molecule.

95. The conjugate of any one of claims 88-94, wherein the heterologous moiety is a therapeutic agent.

96. The conjugate of any one of claims 88-95, wherein the therapeutic agent is a small molecule.

97. A fusion protein comprising the CLEC2D binding protein of any one of claims 1-87 and a heterologous protein.

98. The fusion protein of claim 97, wherein the heterologous protein comprises a cytokine (or functional fragment or functional valiant thereof), a chemokine (or a functional fragment or functional variant thereof), or an antibody (or a functional fragment or functional variant thereof).

99. The fusion protein of claim 97-98, wherein the heterologous protein is fused to the N- tcrminus, C-tcrminus, and / or internally between the N- and C-tcrminus of the endonuclease.

100. The fusion protein of claim 97-99, wherein the heterologous protein is fused directly to the endonuclease.

101. The fusion protein of claim 97-100, wherein the heterologous protein is fused indirectly to the endonuclease.

102. The fusion protein of claim 97-101, wherein the heterologous protein is fused indirectly to the endonuclease via a peptide linker.

103. A nucleic acid molecule encoding the CLEC2D binding protein of any one of claims 1-87 or the fusion protein of any one of claims 97-102.

104. The nucleic acid molecule of claim 103, wherein the nucleic acid molecule is a DNA or RNA (e.g., mRNA) molecule.

105. The nucleic acid molecule of any one of claims 103-104, wherein the nucleic acid molecule is codon optimized.

106. The nucleic acid molecule of any one of claims 103-105, further comprising one or more transcription or translation regulatory elements (e.g., promoter, enhancer (e.g., cell or tissue specific transcription regulatory elements).

107. A vector comprising the nucleic acid molecule of any one of claims 103-106.

108. The vector of claim 107, wherein the vector is a viral vector or a non-viral vector (e.g., plasmid, minicircle).

109. The vector of any one of claims 107-108, wherein the carrier is a viral vector (e.g., an adeno associated viral (AAV) vector, a lentiviral vector, an adenoviral vector).

110. A carrier comprising the CLEC2D binding protein of any one of claims 1-87, the fusion protein of any one of claims 97-102, the conjugate of any one of claims 88-96, the nucleic acid molecule of any one of claims 103-106, the vector of any one of claims 107-109, the cell of claim 112, or the pharmaceutical composition of claim 113.

111. The carrier of claim 110, wherein the carrier is a nanoparticle, polymer, virus (e.g., a recombinant virus), virus like particle, virosome, fusosome, vesicle, or lipid-based carrier (e.g., a lipid nanoparticle (LNP), liposome, lipoplex, nanoliposome, an exosome, or a micelle).

112. A cell comprising the CLEC2D binding protein of any one of claims 1-87, the fusion protein of any one of claims 97-102, the conjugate of any one of claims 88-96, the nucleic acidmolecule of any one of claims 103-106, the vector of any one of claims 107-109, the carrier of any one of claims 110-111, or the pharmaceutical composition of claim 113.

113. A pharmaceutical composition comprising the CLEC2D binding protein of any one of claims 1-87, the fusion protein of any one of claims 97-102, the conjugate of any one of claims 88-96, the nucleic acid molecule of any one of claims 103-106, the vector of any one of claims 107-109, the cell of claim 112, or the carrier of any one of claims 110-111, and a pharmaceutically acceptable excipient.

114. A kit comprising the CLEC2D binding protein of any one of claims 1-87, the fusion protein of any one of claims 97-102, the conjugate of any one of claims 88-96, the nucleic acid molecule of any one of claims 103-106, the vector of any one of claims 107-109, the cell of claim 112, the carrier of any one of claims 110-111, or the pharmaceutical composition of claim 113; and optionally instructions for using any one or more of the foregoing.

115. A kit comprising the CLEC2D binding protein of any one of claims 1-87, the fusion protein of any one of claims 97-102, the conjugate of any one of claims 88-96, the nucleic acid molecule of any one of claims 103-106, the vector of any one of claims 107-109, the cell of claim 112, the carrier of any one of claims 110-111, or the pharmaceutical composition of claim 113; and optionally a labeled secondary antibody that specifically binds the CLEC2D binding protein of any one of claims 1-87, the fusion protein of any one of claims 97-102, or the conjugate of any one of claims 88-96.

116. A method of manufacturing the CLEC2D binding protein of any one of claims 1-87, the fusion protein of any one of claims 97-102, the conjugate of any one of claims 88-96, the method comprising: introducing into a cell the nucleic acid molecule of any one of claim 103-106, the vector of any one of claims 107-109, or the carrier of any one of claims 110-111; culturing the cell under conditions that allow for expression of the CLEC2D binding protein, the conjugate, or the fusion protein; and optionally recovering the expressed the CLEC2D binding protein, the conjugate, or the fusion protein from the culture; and optionally purifying the expressed the CLEC2D binding protein, the conjugate, or the fusion protein from the culture.

117. A method of delivering a CLEC2D binding protein, fusion protein, a conjugate, nucleic acid molecule, vector, carrier, cell, or pharmaceutical composition to a cell, the method comprising, delivering to the cell the CLEC2D binding protein of any one of claims 1-87, the fusion protein of any one of claims 97-102, the conjugate of any one of claims 88-96, the nucleic acid molecule of any one of claims 103-106, the vector of any one of claims 107-109, the cell of claim 112, the carrier of any one of claims 110-111, or the pharmaceutical composition of claim 113, to thereby deliver the CLEC2D binding protein, the fusion protein, the conjugate protein, the nucleic acid molecule, the vector, the carrier, the cell, or the pharmaceutical composition to the cell.

118. A method of delivering a CLEC2D binding protein, fusion protein, a conjugate, nucleic acid molecule, vector, carrier, cell, or pharmaceutical composition, to a subject, the method comprising, administering to the subject the CLEC2D binding protein of any one of claims 1-87, the fusion protein of any one of claims 97-102, the conjugate of any one of claims 88-96, the nucleic acid molecule of any one of claims 103-106, the vector of any one of claims 107-109, the cell of claim 112, the carrier of any one of claims 110-111, or the pharmaceutical composition of claim 113, to thereby deliver the CLEC2D binding protein, the fusion protein, the conjugate protein, the nucleic acid molecule, the vector, the carrier, the cell, or the pharmaceutical composition to the subject.

119. A method of delivering a CLEC2D binding protein, fusion protein, a conjugate, nucleic acid molecule, vector, carrier, cell, or pharmaceutical composition, to a cell in a subject, the method comprising, administering to the subject the CLEC2D binding protein of any one of claims 1-87, the fusion protein of any one of claims 97-102, the conjugate of any one of claims 88-96, the nucleic acid molecule of any one of claims 103-106, the vector of any one of claims 107-109, the cell of claim 112, the carrier of any one of claims 110-111, or the pharmaceutical composition of claim 113, to thereby deliver the CLEC2D binding protein, the fusion protein, the conjugate protein, the nucleic acid molecule, the vector, the carrier, the cell, or the pharmaceutical composition to the cell in the subject.

120. A method of inhibiting binding of CLEC2D to CD161 in a subject, the method comprising administering to the subject the CLEC2D binding protein of any one of claims 1-87, the fusion protein of any one of claims 97-102, the conjugate of any one of claims 88-96, the nucleic acid molecule of any one of claims 103-106, the vector of any one of claims 107-109, thecell of claim 112, the carrier of any one of claims 1 10-111 , or the pharmaceutical composition of claim 113, to thereby inhibit binding of CLEC2D to CD161.

121. A method of treating, ameliorating, or preventing a disease in a subject in need thereof, the method comprising administering to the subject the CLEC2D binding protein of any one of claims 1-87, the fusion protein of any one of claims 97-102, the conjugate of any one of claims 88-96, the nucleic acid molecule of any one of claims 103-106, the vector of any one of claims 107-109, the cell of claim 112, the carrier of any one of claims 110-111, or the pharmaceutical composition of claim 113, to thereby treat, ameliorate, or prevent a disease in the subject.

122. A method of treating, ameliorating, or preventing cancer in a subject in need thereof, the method comprising administering to the subject the CLEC2D binding protein of any one of claims 1-87, the fusion protein of any one of claims 97-102, the conjugate of any one of claims 88-96, the nucleic acid molecule of any one of claims 103-106, the vector of any one of claims 107-109, the cell of claim 112, the carrier of any one of claims 110-111, or the pharmaceutical composition of claim 113, to thereby treat, ameliorate, or prevent the cancer in the subject.

123. An in vitro method for detecting a population of CLEC2D-expressing cells (e.g., a population of cells expressing CLEC2D on the cell surface) in a subject, the method comprising(a) contacting a sample comprising a population of cells from the subject with theCLEC2D binding protein of any one of claims 1-87, or the conjugate of any one of claims 88-96, or the fusion protein of any one of claims 97-102; and(b) detecting the binding of the CLEC2D binding protein, the conjugate, or the fusion protein to a population of cells in the sample; wherein the binding of the CLEC2D binding protein, the conjugate, or the fusion protein to a population of cells within the sample indicates the presence of a population of CLEC2D- expressing cells (e.g., a population of cells expressing CLEC2D on the cell surface).

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