ANTI-Dectin-1 ANTIBODIES AND METHODS OF USE THEREOF

Abstract

The present disclosure relates to antibodies that bind to human Dectin-1, multispecific (e.g., bispecific) binding molecules, and methods of use and production related thereto.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to U.S. Provisional Application Serial No. 63 / 327,288, filed April 4, 2022, the disclosure of each of which is incorporated herein by reference in its entirety.

[0003] Reference to an electronic sequence listing

[0004] The contents of the electronic sequence listing (186542000640seqlist.xml; size: 306,885 bytes; and creation date: March 31, 2023) are incorporated herein by reference in their entirety. Technical Field

[0005] The present disclosure relates to antibodies, multispecific (eg, bispecific) binding molecules that bind to human Dectin-1, and methods of use and production thereof. Background Art

[0006] Phagocytosis is the primary mechanism used to remove pathogens and cellular debris. Professional phagocytes, such as monocytes, macrophages, dendritic cells, and granulocytes, specifically recognize and engulf abnormal or disease-causing host or foreign agents. Engulfed material is destroyed via the endolysosomal pathway within phagocytes. Furthermore, dendritic cells and macrophages can present antigens to cells of the adaptive immune system to further promote pathogen elimination.

[0007] Dectin-1 is a C-type lectin receptor that recognizes β-glucan and promotes antifungal phagocytic activity. It is expressed on phagocytes and has been clearly shown to be sufficient for phagocytosis. Dectin-1 can be used to target phagocytosis and eliminate pathogens with antibodies.

[0008] Targeted removal and degradation of accumulated pathogens without increasing overall phagocytosis would be beneficial. The present disclosure provides solutions to these problems and describes other advantages.

[0009] All references cited herein, including patent applications, patent publications, and scientific literature, are hereby incorporated by reference in their entirety to the same extent as if each reference were specifically and individually indicated to be incorporated by reference. Summary of the Invention

[0010] The present disclosure relates to antibodies, multispecific (e.g., bispecific) binding molecules that bind to human Dectin-1, and methods of use and production thereof. Described herein are methods for targeted phagocytosis to remove pathogens (including host cells / host cell products, microorganisms or their products, etc.) after administration of a multispecific (e.g., bispecific) binding molecule comprising a Dectin-1 binding arm and a second arm that specifically binds to pathogens (including host cells / host cell products, microorganisms or their products, etc.). The multispecific (e.g., bispecific) binding molecule allows phagocytes to engage with the target pathogen and form synapses therebetween and promotes the aggregation of Dectin-1 on the phagocytes. This stimulates phagocytosis of the target pathogen and simultaneously stimulates phagocytes to secrete cytokines via the Dectin-1 / Syk / NfkB pathway. In addition, antigens from the engulfed material are presented on the surface of dendritic cells / macrophages to enhance the adaptive immune response against the pathogen. Overall, it is believed that Dectin-1 agonistic, multispecific (eg, bispecific) binding molecules can promote immune stimulation, targeted phagocytosis, and neoantigen presentation / activation of the adaptive immune system to eliminate pathogens.

[0011] Thus, the present disclosure describes, among other things, the generation and functional characterization of: an agonistic anti-human Dectin-1 antibody that exhibits high-affinity binding to Dectin-1 and can promote immune stimulation; and antibody variants that are believed to modulate their binding affinity or reduce their immunogenic potential (i.e., by restoring some residues to human germline residues and / or removing potential human T-cell epitopes). Further described is the generation of a bispecific antibody format comprising an anti-human Dectin-1 antibody and an antibody targeting an antigen on a pathogen, with data supporting target engagement, immune stimulation, phagocytosis, and antigen presentation.

[0012] In some embodiments, provided herein is an antibody or antigen-binding fragment thereof that binds to human Dectin-1, wherein the antibody or fragment comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; wherein the VH domain comprises the amino acid sequence QVQLVQSG AEVKKPGASVKVSCKSSGYTFTX1YYIHWVRQAPGQGLEWMGWINPNSGX2TNYAQKFQGRITMTRDTSISTAYLELSRLRSDDTAVFYCAX3X4X5X6X7X8X9X 10 X 11 X 12 WGQGTLVTVSS, wherein X1 is D, A or G; wherein X2 is D, A or G; wherein X3 is R, A or G; wherein X4 is N, A or G; wherein X5 is S, A or G; wherein X6 is A or G; wherein X7 is S, A or G; wherein X8 is Y, A or G; wherein X9 is S, A or G; wherein X10 is F, A or G; where X 11 is A or G; and where X 12 is Y, A or G (SEQ ID NO:63); wherein the VL domain comprises the amino acid sequence DIQMTQSPSSVSASVGDRVTI TCRASQGISSWLAWYQQKPGKAPKLLIFGASSLQSGVPSRFSGSGSGTDFTLTVSSLQPEDFATYYCX1X2AX3X4X5X6X7X8FGPGTKVDIE, wherein X1 is Q, A or G; X2 is Q, A or G; X3 is F, Y, A or G; wherein X4 is S, A or G; wherein X5 is F, A or G; wherein X6 is P, A or G; wherein X7 is F, A or G; and wherein X8 is T, A or G (SEQ ID NO:65). In some embodiments, the antibody does not include a CDR-H1 comprising the amino acid sequence of DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence of WINPNSGDTNYAQKFQG (SEQ ID NO: 2), a CDR-H3 comprising the amino acid sequence of NSGSYSFGY (SEQ ID NO: 3), a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFT (SEQ ID NO: 6). In some embodiments, the VH domain comprises 1, 2 or fewer, 3 or fewer, 4 or fewer, or 5 or fewer substitutions compared to the amino acid sequence of SEQ ID NO: 62; and / or wherein the VL domain comprises 1, 2 or fewer, 3 or fewer, 4 or fewer, or 5 or fewer substitutions compared to the amino acid sequence of SEQ ID NO: 64. In some embodiments, the antibody or fragment binds to human Dectin-1 expressed on the surface of a cell with an EC50 of less than 2 nM; is capable of binding to human or cynomolgus monkey Dectin-1; and / or does not compete with the natural ligand of human Dectin-1.

[0013] In some embodiments, provided herein is an antibody or antigen-binding fragment thereof that binds to human Dectin-1, wherein the antibody or fragment comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; wherein the VH domain comprises: a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1) or AYYI (SEQ ID NO: 16); a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2) or WINPNSGATNYAQKFQG (SEQ ID NO: 19); and a CDR-H3 comprising an amino acid sequence selected from the group consisting of NSGSYSFGY (SEQ ID NO: 3), ASGSYSFGY (SEQ ID NO: 22), NSGSASFGY (SEQ ID NO: 24), NAGSYSFGY (SEQ ID NO: 27), NSASYSFGY (SEQ ID NO: 29), NSGAYSFGY (SEQ ID NO: 31), NSGSYAFGY (SEQ ID NO: 32). NO:33), NSGSYSAGY (SEQ ID NO:35), NSGSYSFAY (SEQ ID NO:37) and NSGSYSFGA (SEQ ID NO:39); and wherein the VL domain comprises: a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO:4); a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising an amino acid sequence selected from the group consisting of QQAYSFPFT (SEQ ID NO:6), QQAASFPFT (SEQ ID NO:41), QQAFSFPFT (SEQ ID NO:42), AQAYSFPFT (SEQ ID NO:43), QAAYSFPFT (SEQ ID NO:44), QQAYAFPFT (SEQ ID NO:45), QQAYSAPFT (SEQ ID NO:46), QQAYSFAFT (SEQ ID NO:47), QQAYSFPAT (SEQ ID NO:48), and QQAYSFPFA (SEQ ID NO:49).In some embodiments, the antibody does not include a CDR-H1 comprising the amino acid sequence of DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence of WINPNSGDTNYAQKFQG (SEQ ID NO: 2), a CDR-H3 comprising the amino acid sequence of NSGSYSFGY (SEQ ID NO: 3), a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAY SFPFT (SEQ ID NO: 6). In some embodiments, the VH domain includes a CDR-H1 comprising the amino acid sequence of DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence of WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence of NSGSYSFGY (SEQ ID NO: 3). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence AYYI (SEQ ID NO: 16), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGATNY AQKFQG (SEQ ID NO: 19), and a CDR-H3 comprising the amino acid sequence NSGSYS FGY (SEQ ID NO: 3). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence ASGSYSFGY (SEQ ID NO: 22). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence of DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence of WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence of NSGSASFGY (SEQ ID NO: 24).In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NAGSYSFGY (SEQ ID NO: 27). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSASYSFGY (SEQ ID NO: 29). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGAYSFGY (SEQ ID NO: 31). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGS YAFGY (SEQ ID NO: 33). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGSYSAGY (SEQ ID NO: 35). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGSYSFAY (SEQ ID NO: 37). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGS YSFGA (SEQ ID NO: 39).In some embodiments, the VH domain further comprises: FR1, comprising an amino acid sequence selected from the group consisting of QVQLVQSGAEVKKPGASV KVSCKSSGYTFT (SEQ ID NO:50) and QVQLVQSGAEVKKPGASVK VSCKASGYTFT (SEQ ID NO:51); FR2, comprising the amino acid sequence of HWVRQAPGQGLEWMG (SEQ ID NO:52); FR3, comprising an amino acid sequence selected from the group consisting of RITMTRDTSISTAYLELSRLRSDDTAVF YCAR (SEQ ID NO:53) and RVTMTRDTSISTAYMELSRLRSDDTAVYYCAR (SEQ ID NO:54); and FR4, comprising the amino acid sequence of WGQGTLVTVSS (SEQ ID NO:55). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFT (SEQ ID NO: 6). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAASFPFT (SEQ ID NO: 41). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASS LQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAFSFPFT (SEQ ID NO: 42). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of AQAYSFPFT (SEQ ID NO: 43). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QAAYSFPFT (SEQ ID NO: 44).In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYAFPFT (SEQ ID NO: 45). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGI SSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSAPFT (SEQ ID NO: 46). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSFAFT (SEQ ID NO: 47). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSFPAT (SEQ ID NO: 48). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFA (SEQ ID NO: 49). In some embodiments, the VL domain further comprises: FR1 comprising the amino acid sequence of DIQMTQSPSSVSASVGDRVTITC (SEQ ID NO:56); FR2 comprising an amino acid sequence selected from the group consisting of WYQQKPGKAPKLLIF (SEQ ID NO:57) and W YQQKPGKAPKLLIY (SEQ ID NO:58); FR3 comprising an amino acid sequence selected from the group consisting of GVPSRFSGSGSGTDFTLTVSSLQPEDFATYYC (SEQ ID NO:59) and GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC (SEQ ID NO:60); and FR4 comprising the amino acid sequence of FGPGTKVDIE (SEQ ID NO:61).

[0014] In some embodiments, provided herein is an antibody or antigen-binding fragment thereof that binds to human Dectin-1, wherein the antibody or fragment comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; wherein the VH domain comprises: a CDR-H1 comprising the amino acid sequence GYTF TDYY (SEQ ID NO: 7) or GYTFTAYY (SEQ ID NO: 17); a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8) or INPNSGAT (SEQ ID NO: 20); and a CDR-H3 comprising an amino acid sequence selected from the group consisting of ARNSGSYSFGY (SEQ ID NO: 9), ARASGSYSFGY (SEQ ID NO: 23), ARNSGSASFGY (SEQ ID NO: 25), AANSGSYS FGY (SEQ ID NO: 26), ARNAGSYSFGY (SEQ ID NO: 28), ARNSASYSFGY (SEQ ID NO: 30), ARNSGAYSFGY (SEQ ID NO: 31). NO:32), ARNSGSYAFGY (SEQ ID NO:34), ARNSGSYSAGY (SEQ ID NO:36), ARNSGSYSFAY (SEQ ID NO:38), and ARNSGSYSFGA (SEQ ID NO:40); and wherein the VL domain comprises: a CDR-L1 comprising the amino acid sequence of QGI SSW (SEQ ID NO: 10); a CDR-L2 comprising the amino acid sequence of GAS (SEQ ID NO: 11), and a CDR-L3 comprising an amino acid sequence selected from the group consisting of QQAYSFPFT (SEQ ID NO: 12), QQAASFPFT (SEQ ID NO: 41), QQAFSFPFT (SEQ ID NO: 42), AQAYSFPFT (SEQ ID NO: 43), QAAYSFPFT (SEQ ID NO: 44), QQAYAFPFT (SEQ ID NO: 45), QQAYSAPFT (SEQ ID NO: 46), QQAYSFAFT (SEQ ID NO: 47), QQAYSFPAT (SEQ ID NO: 48). NO:48) and QQAYSFPFA (SEQ ID NO:49).In some embodiments, the antibody does not include a CDR-H1 comprising the amino acid sequence GYTFTD YY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8), a CDR-H3 comprising the amino acid sequence ARNSGSYSFGY (SEQ ID NO: 9), a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO: 12). In some embodiments, the VH domain includes a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence ARNSGSYSFGY (SEQ ID NO: 9). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTAYY (SEQ ID NO: 17), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence ARNSGSYSFGY (SEQ ID NO: 9). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGA T (SEQ ID NO: 20), and a CDR-H3 comprising the amino acid sequence ARNSGSYSFGY (SEQ ID NO: 9). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence AR ASGSYSFGY (SEQ ID NO: 23). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence ARNSGSASFGY (SEQ ID NO: 25). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence AANSGSYSFGY (SEQ ID NO: 26).In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence G YTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence ARNAGSYSFGY (SEQ ID NO: 28). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence AR NSASYSFGY (SEQ ID NO: 30). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence ARNSGAYSFGY (SEQ ID NO: 32). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence ARNSGSYAFGY (SEQ ID NO: 34). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence ARNSGSYSAGY (SEQ ID NO: 36). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence ARNSGSYSFAY (SEQ ID NO: 38). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence of GYTFTDYY (SEQ ID NO:7), a CDR-H2 comprising the amino acid sequence of INPNSGDT (SEQ ID NO:8), and a CDR-H3 comprising the amino acid sequence of ARNSGSYSFGA (SEQ ID NO:40).In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO: 12). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QQAASFPFT (SEQ ID NO: 41). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QQAFSFPFT (SEQ ID NO: 42). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence AQAYSFPFT (SEQ ID NO: 43). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence QG ISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QAAYSFPFT (SEQ ID NO: 44). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QQAYAFPFT (SEQ ID NO: 45). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QQAYSAPFT (SEQ ID NO: 46). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QQAYSFAFT (SEQ ID NO: 47).In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QQAYSFPA T (SEQ ID NO: 48). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QQAY SFPFA (SEQ ID NO: 49).

[0015] In some embodiments, provided herein is an antibody or antigen-binding fragment thereof that binds to human Dectin-1, wherein the antibody or fragment comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; wherein the VH domain comprises: a CDR-H1 comprising the amino acid sequence GYTF TDY (SEQ ID NO: 13) or GYTFTAY (SEQ ID NO: 18); a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14) or NPNSGA (SEQ ID NO: 21); and a CDR-H3 comprising an amino acid sequence selected from the group consisting of NSGSYSFGY (SEQ ID NO: 15), ASGSYSFGY (SEQ ID NO: 22), NSGSASFGY (SEQ ID NO: 24), NAGSYSFGY (SEQ ID NO: 27), NSASYSFGY (SEQ ID NO: 29), NSGAYSFGY (SEQ ID NO: 31), NSGSYAFGY (SEQ ID NO: 33), NSGSYSAGY (SEQ ID NO: 34). NO:35), NSGSYSFAY (SEQ ID NO:37) and NSGSYSFGA (SEQ ID NO:39); and wherein the VL domain comprises: a CDR-L1 comprising the amino acid sequence of RASQG ISSWLA (SEQ ID NO:4); a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising an amino acid sequence selected from the group consisting of QQAYSFPFT (SEQ ID NO:6), QQAASFPFT (SEQ ID NO:41), QQAFSFPFT (SEQ ID NO:42), AQAYSFPFT (SEQ ID NO:43), QAAYSFPFT (SEQ ID NO:44), QQAYAFPFT (SEQ ID NO:45), QQAYSAPFT (SEQ ID NO:46), QQAYSFAFT (SEQ ID NO:47), QQAYSFPAT (SEQ ID NO:48), and QQAYSFPFA (SEQ ID NO:49).In some embodiments, the antibody does not include a CDR-H1 comprising the amino acid sequence of GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence of NPNSGD (SEQ ID NO: 14), a CDR-H3 comprising the amino acid sequence of NSGSYSFGY (SEQ ID NO: 15), a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFT (SEQ ID NO: 6). In some embodiments, the VH domain includes a CDR-H1 comprising the amino acid sequence of GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence of NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence of NSGSYSFGY (SEQ ID NO: 15). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYT FTAY (SEQ ID NO: 18), a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 15). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNSGA (SEQ ID NO: 21), and a CDR-H3 comprising the amino acid sequence NSGSYSF GY (SEQ ID NO: 15). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence ASGSYSFGY (SEQ ID NO: 22). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence NAGSYSFGY (SEQ ID NO: 27). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence NSASYSFGY (SEQ ID NO: 29).In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence NSGAYSFGY (SEQ ID NO: 31). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence NSGSYAFGY (SEQ ID NO: 33). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence NSGSYSAGY (SEQ ID NO: 35). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence NSGSYSFAY (SEQ ID NO: 37). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence NSGSYSFGA (SEQ ID NO: 39). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO: 6). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence of QQAASFPFT (SEQ ID NO:41).In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAF SFPFT (SEQ ID NO: 42). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of AQAYSFPFT (SEQ ID NO: 43). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QAAYSFPFT (SEQ ID NO: 44). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYAFPFT (SEQ ID NO: 45). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSA PFT (SEQ ID NO: 46). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSFAFT (SEQ ID NO: 47). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence of QQAYSFPAT (SEQ ID NO:48).In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFA (SEQ ID NO:49).

[0016] In some embodiments, the VH domain comprises an amino acid sequence selected from the group consisting of SEQ ID Nos: 62 and 82-93. In some embodiments, in some embodiments according to any of the embodiments described herein, the VL domain comprises an amino acid sequence selected from the group consisting of SEQ ID Nos: 64 and 94-102. In some embodiments, the VH domain comprises an amino acid sequence selected from the group consisting of SEQ ID Nos: 62 and 82-93 and / or the VL domain comprises an amino acid sequence selected from the group consisting of SEQ ID Nos: 64 and 94-102. In some embodiments, the antibody does not include a VH domain comprising the amino acid sequence of SEQ ID NO: 62 and a VL domain comprising the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 62 and the VL domain comprises the amino acid sequence of SEQ ID NO: 94. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 62 and the VL domain comprises the amino acid sequence of SEQ ID NO: 95. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94.In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99.In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94.In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99.In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94.In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99.In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94.In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99.In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:93, and the VL domain comprises the amino acid sequence of SEQ ID NO:102.

[0017] In some embodiments, provided herein is an antibody or antigen-binding fragment thereof that binds to human Dectin-1, wherein the antibody or fragment comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; wherein the VH domain comprises the amino acid sequence QVQLVQSG AEVKKPGASVKVSCKX1SGYTFTX2YYX3HWVRQAPGQGLEWMG WINPNSGX4TNYAQKFQGRX5TMTRDTSISTAYX6ELSRLRSDDTAV X7YCARNSGSYSFGYWGQGTLVTVSS; wherein X1 is S or A; wherein X2 is D or G; wherein X3 is I or M; wherein X4 is D or G; wherein X5 is I or V; wherein X6 is L or M; and wherein X7 is F or Y (SEQ ID NO:80); and wherein the VL domain comprises the amino acid sequence DIQMTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKAPKLLIX1X2ASSLQSGVPSRFSGSGSGTDFTLTX3SSLQPEDFATYYCQQAYSFPFTFGPGTKVDIE; wherein X1 is F or Y; wherein X2 is G or A; and wherein X3 is V or I (SEQ ID NO:81). In some embodiments, the antibody does not include a CDR-H1 comprising the amino acid sequence of DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence of WINPNSGDTNYAQKFQG (SEQ ID NO: 2), a CDR-H3 comprising the amino acid sequence of NSGSYSFGY (SEQ ID NO: 3), a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFT (SEQ ID NO: 6).

[0018] In some embodiments, provided herein is an antibody or antigen-binding fragment thereof that binds to human Dectin-1, wherein the antibody or fragment comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; wherein the VH domain comprises: a CDR-H1 comprising an amino acid sequence selected from the group consisting of DYYI (SEQ ID NO: 1), DYYM (SEQ ID NO: 66), and GYYM (SEQ ID NO: 67); a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2) or WINPNSGGTNYAQKFQG (SEQ ID NO: 70); and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3); and wherein the VL domain comprises: a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO: 4); a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO: 5) or AASSLQS (SEQ ID NO: 61). In some embodiments, the antibody does not include a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3), a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO: 6). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence D YYM (SEQ ID NO: 66), a CDR-H2 comprising the amino acid sequence WINPNSGDT NYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGS YSFGY (SEQ ID NO: 3).In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence of GYYM (SEQ ID NO: 67), a CDR-H2 comprising the amino acid sequence of WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence of NSGSYSFGY (SEQ ID NO: 3). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence of DYYM (SEQ ID NO: 66), a CDR-H2 comprising the amino acid sequence of WINPNSGGTNYAQKFQG (SEQ ID NO: 70), and a CDR-H3 comprising the amino acid sequence of NSGSYSFGY (SEQ ID NO: 3). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence of GYYM (SEQ ID NO:67), a CDR-H2 comprising the amino acid sequence of WINPNSGGTNYAQKFQG (SEQ ID NO:70), and a CDR-H3 comprising the amino acid sequence of NSGSYSFGY (SEQ ID NO:3). In some embodiments, the VH domain further comprises: FR1 comprising an amino acid sequence selected from the group consisting of QVQLVQSGAEVKKPGASVKVSCKSSGYTFT (SEQ ID NO:50) and QVQLVQSGAEVKKP GASVKVSCKASGYTFT (SEQ ID NO:76); FR2 comprising the amino acid sequence of HWVRQAPGQGLEWMG (SEQ ID NO:52); FR3 comprising an amino acid sequence selected from the group consisting of RITMTRDTSISTAYLELSRLRS DDTAVFYCAR (SEQ ID NO:53) and RVTMTRDTSISTAYMELSRLRS DDTAVYYCAR (SEQ ID NO:77); and FR4 comprising the amino acid sequence of WGQGTLVTVSS (SEQ ID NO:55). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFT (SEQ ID NO: 6). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of AASSLQS (SEQ ID NO: 73), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFT (SEQ ID NO: 6).In some embodiments, the VL domain further comprises: FR1 comprising the amino acid sequence of DIQMTQSPSSVSASVGDRVTITC (SEQ ID NO:56); FR2 comprising an amino acid sequence selected from the group consisting of WYQQKPGKAPKLLIF (SEQ ID NO:57) and WYQQKPGKAPKLLIY (SEQ ID NO:78); FR3 comprising an amino acid sequence selected from the group consisting of GVPSRFSGSGSGTDFTLTVSSLQPEDFATYYC (SEQ ID NO:59) and GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC (SEQ ID NO:79); and FR4 comprising the amino acid sequence of FGPGTKVDIE (SEQ ID NO:61). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence of DYYM (SEQ ID NO: 199), a CDR-H2 comprising the amino acid sequence of WINPNEGDTNYAQKFEG (SEQ ID NO: 200), and a CDR-H3 comprising the amino acid sequence of NTGAYSFGY (SEQ ID NO: 204); and wherein the VL domain comprises: a CDR-L1 comprising the amino acid sequence of R ASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASDLQS (SEQ ID NO: 206), and a CDR-L3 comprising the amino acid sequence of QQAYG FPFT (SEQ ID NO: 207). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence of DYYM (SEQ ID NO: 199), a CDR-H2 comprising the amino acid sequence of WINPNEGDTNYAQKFQE (SEQ ID NO: 201), and a CDR-H3 comprising the amino acid sequence of NTGAYSFGY (SEQ ID NO: 204); and wherein the VL domain comprises: a CDR-L1 comprising the amino acid sequence of RASQGISSWL A (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASDLQS (SEQ ID NO: 206), and a CDR-L3 comprising the amino acid sequence of HQAYSFPFT (SEQ ID NO: 208).

[0019] In some embodiments, provided herein is an antibody or antigen-binding fragment thereof that binds to human Dectin-1, wherein the antibody or fragment comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; wherein the VH domain comprises: a CDR-H1 comprising an amino acid sequence selected from the group consisting of GYTFTDY Y (SEQ ID NO: 7) and GYTFTGYY (SEQ ID NO: 68); a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8) or INPNSGGT (SEQ ID NO: 71); and a CDR-H3 comprising the amino acid sequence A RNSGSYSFGY (SEQ ID NO: 9); and wherein the VL domain comprises: a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10); a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11) or AAS (SEQ ID NO: 74), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO: 12). In some embodiments, the antibody does not include a CDR-H1 comprising the amino acid sequence of GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence of INPNSGDT (SEQ ID NO: 8), a CDR-H3 comprising the amino acid sequence of ARNSGSYSFGY (SEQ ID NO: 9), a CDR-L1 comprising the amino acid sequence of QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence of GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFT (SEQ ID NO: 12). In some embodiments, the VH domain includes a CDR-H1 comprising the amino acid sequence of GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence of INPNSGDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence of ARNSGSYSFGY (SEQ ID NO: 9). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence of GYTFTGYY (SEQ ID NO:68), a CDR-H2 comprising the amino acid sequence of INPNSGDT (SEQ ID NO:8), and a CDR-H3 comprising the amino acid sequence of ARNSGSYSFGY (SEQ ID NO:9).In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYT FTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGGT (SEQ ID NO: 71), and a CDR-H3 comprising the amino acid sequence ARNSGSYSFGY (SEQ ID NO: 9). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTGYY (SEQ ID NO: 68), a CDR-H2 comprising the amino acid sequence INPNSGGT (SEQ ID NO: 71), and a CDR-H3 comprising the amino acid sequence ARNS GSYSFGY (SEQ ID NO: 9). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO: 12). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence of AAS (SEQ ID NO: 74), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFT (SEQ ID NO: 12). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence of GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence of INPNEGDT (SEQ ID NO: 202), and a CDR-H3 comprising the amino acid sequence of ARNTGAYSFGY (SEQ ID NO: 205); and wherein the VL domain comprises a CDR-L1 comprising the amino acid sequence of QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence of GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence of QQAYGFPFT (SEQ ID NO: 207).In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence of GYTFTDYY (SEQ ID NO:7), a CDR-H2 comprising the amino acid sequence of INPNEGDT (SEQ ID NO:202), and a CDR-H3 comprising the amino acid sequence of ARNTGAYSFGY (SEQ ID NO:205); and wherein the VL domain comprises a CDR-L1 comprising the amino acid sequence of Q GISSW (SEQ ID NO:10), a CDR-L2 comprising the amino acid sequence of GAS (SEQ ID NO:11), and a CDR-L3 comprising the amino acid sequence of HQAYSFPFT (SEQ ID NO:208).

[0020] In some embodiments, provided herein is an antibody or antigen-binding fragment thereof that binds to human Dectin-1, wherein the antibody or fragment comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; wherein the VH domain comprises: a CDR-H1 comprising an amino acid sequence selected from the group consisting of GYTFTDY (SEQ ID NO: 13) and GYTFTGY (SEQ ID NO: 69); a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14) or NP NSGG (SEQ ID NO: 72); and a CDR-H3 comprising the amino acid sequence NSGSYS FGY (SEQ ID NO: 15); and wherein the VL domain comprises: a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO: 4); a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO: 5) or AASSLQS (SEQ ID NO: 75), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO: 6). In some embodiments, the antibody does not include a CDR-H1 comprising the amino acid sequence of GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence of NPNSGD (SEQ ID NO: 14), a CDR-H3 comprising the amino acid sequence of NSGSYSFGY (SEQ ID NO: 15), a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFT (SEQ ID NO: 6). In some embodiments, the VH domain includes a CDR-H1 comprising the amino acid sequence of GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence of NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence of NSGSYSFGY (SEQ ID NO: 15). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence of GYTFTGY (SEQ ID NO:69), a CDR-H2 comprising the amino acid sequence of NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence of NSGSYSFGY (SEQ ID NO: 15).In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNSGG (SEQ ID NO: 72), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 15). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTGY (SEQ ID NO: 69), a CDR-H2 comprising the amino acid sequence NPNSGG (SEQ ID NO: 72), and a CDR-H3 comprising the amino acid sequence NSGSYS FGY (SEQ ID NO: 15). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO: 6). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of AASSLQS (SEQ ID NO: 75), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFT (SEQ ID NO: 6). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence of GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence of NPNEGD (SEQ ID NO: 203), and a CDR-H3 comprising the amino acid sequence of NTGAYSFGY (SEQ ID NO: 204); and wherein the VL domain comprises: a CDR-L1 comprising the amino acid sequence of RASQGISSWL A (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASDLQS (SEQ ID NO: 206), and a CDR-L3 comprising the amino acid sequence of QQAYGFPFT (SEQ ID NO: 207).In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence of GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence of NPNEGD (SEQ ID NO: 203), and a CDR-H3 comprising the amino acid sequence of NTGAYSFGY (SEQ ID NO: 204); and wherein the VL domain comprises: a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASDLQS (SEQ ID NO: 206), and a CDR-L3 comprising the amino acid sequence of HQAYSFPFT (SEQ ID NO: 208).

[0021] In some embodiments, the VH domain comprises an amino acid sequence selected from the group consisting of SEQ ID Nos: 62 and 103-109. In some embodiments, the VL domain comprises an amino acid sequence selected from the group consisting of SEQ ID Nos: 64 and 110-113. In some embodiments, the VH domain comprises an amino acid sequence selected from the group consisting of SEQ ID Nos: 62 and 103-109 and / or the VL domain comprises an amino acid sequence selected from the group consisting of SEQ ID Nos: 64 and 110-113. In some embodiments, the antibody does not include a VH domain comprising the amino acid sequence of SEQ ID NO: 62 and a VL domain comprising the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 62 and the VL domain comprises the amino acid sequence of SEQ ID NO: 110. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 62 and the VL domain comprises the amino acid sequence of SEQ ID NO: 111. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 112. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 113. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 103, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 103, and the VL domain comprises the amino acid sequence of SEQ ID NO: 110. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 103, and the VL domain comprises the amino acid sequence of SEQ ID NO: 111. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 103, and the VL domain comprises the amino acid sequence of SEQ ID NO: 112. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 103, and the VL domain comprises the amino acid sequence of SEQ ID NO: 113. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 104, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 104, and the VL domain comprises the amino acid sequence of SEQ ID NO: 110.In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 104, and the VL domain comprises the amino acid sequence of SEQ ID NO: 111. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 104, and the VL domain comprises the amino acid sequence of SEQ ID NO: 112. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 104, and the VL domain comprises the amino acid sequence of SEQ ID NO: 113. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 105, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 105, and the VL domain comprises the amino acid sequence of SEQ ID NO: 110. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 105, and the VL domain comprises the amino acid sequence of SEQ ID NO: 111. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 105, and the VL domain comprises the amino acid sequence of SEQ ID NO: 112. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 105, and the VL domain comprises the amino acid sequence of SEQ ID NO: 113. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 106, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 106, and the VL domain comprises the amino acid sequence of SEQ ID NO: 110. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 106, and the VL domain comprises the amino acid sequence of SEQ ID NO: 111. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 106, and the VL domain comprises the amino acid sequence of SEQ ID NO: 112. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 106, and the VL domain comprises the amino acid sequence of SEQ ID NO: 113. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 107, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 107, and the VL domain comprises the amino acid sequence of SEQ ID NO: 110.In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 107, and the VL domain comprises the amino acid sequence of SEQ ID NO: 111. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 107, and the VL domain comprises the amino acid sequence of SEQ ID NO: 112. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 107, and the VL domain comprises the amino acid sequence of SEQ ID NO: 113. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 108, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 108, and the VL domain comprises the amino acid sequence of SEQ ID NO: 110. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 108, and the VL domain comprises the amino acid sequence of SEQ ID NO: 111. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 108, and the VL domain comprises the amino acid sequence of SEQ ID NO: 112. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 108, and the VL domain comprises the amino acid sequence of SEQ ID NO: 113. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 109, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 109, and the VL domain comprises the amino acid sequence of SEQ ID NO: 110. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 109, and the VL domain comprises the amino acid sequence of SEQ ID NO: 111. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 109, and the VL domain comprises the amino acid sequence of SEQ ID NO: 112. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 109, and the VL domain comprises the amino acid sequence of SEQ ID NO: 11.

[0022] In some embodiments, the VH domain comprises an amino acid sequence selected from the group consisting of SEQ ID Nos: 62, 103-109, 194-196, 209, 211, 213, 215, and 220. In some embodiments, the VL domain comprises an amino acid sequence selected from the group consisting of SEQ ID Nos: 64, 110-113, 197, 198, 210, 212, 214, 216, and 221. In some embodiments, the VH domain comprises an amino acid sequence selected from the group consisting of SEQ ID Nos: 62, 103-109, 194-196, 209, 211, 213, 215, and 220, and the VL domain comprises an amino acid sequence selected from the group consisting of SEQ ID Nos: 64, 110-113, 197, 198, 210, 212, 214, 216, and 221. In some embodiments, the VH domain comprises an amino acid sequence selected from the group consisting of SEQ ID Nos: 62, 194-196, 209, 211, 213, 215, and 220. In some embodiments, the VL domain comprises an amino acid sequence selected from the group consisting of SEQ ID Nos: 64, 197, 198, 210, 212, 214, 216, and 221. In some embodiments, the VH domain comprises an amino acid sequence selected from the group consisting of SEQ ID Nos: 62, 194-196, 209, 211, 213, 215, and 220, and the VL domain comprises an amino acid sequence selected from the group consisting of SEQ ID Nos: 64, 197, 198, 210, 212, 214, 216, and 221. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 209, and the VL domain comprises the amino acid sequence of SEQ ID NO: 210. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 211, and the VL domain comprises the amino acid sequence of SEQ ID NO: 212. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 213, and the VL domain comprises the amino acid sequence of SEQ ID NO: 214. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 220, and the VL domain comprises the amino acid sequence of SEQ ID NO: 221. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 195, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64.

[0023] In some embodiments, provided herein is an antibody or antigen-binding fragment thereof that binds to human Dectin-1, wherein the antibody or fragment comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; wherein the VH domain comprises: a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1) or DYYM (SEQ ID NO: 199); a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), WINPNEGDTNYAQKFEG (SEQ ID NO: 200), or WINPNEGDTNYAQKFQE (SEQ ID NO: 201); and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3), NSGSASFGY (SEQ ID NO: 187), NSGSYSAGY (SEQ ID NO: 190), or NTGAYSFGY (SEQ ID NO: 201). and wherein the VL domain comprises: a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO:4); a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO:5) or GASDLQS (SEQ ID NO:206), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFT (SEQ ID NO:6), QAAYSFPFT (SEQ ID NO:192), QQAYSAPFT (SEQ ID NO:193), QQAYGFPFT (SEQ ID NO:207), or HQAYSFPFT (SEQ ID NO:208); wherein the antibody does not include a CDR-H1 comprising the amino acid sequence of DYYI (SEQ ID NO:1), a CDR-H2 comprising the amino acid sequence of WINPNSGDTNYAQKFQG (SEQ ID NO:2), a CDR-H3 comprising the amino acid sequence of NSGSYSFGY (SEQ ID NO:3). NO:3), CDR-H3 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO:4), CDR-L1 comprising the amino acid sequence GASSLQS (SEQ ID NO:5), and CDR-L3 comprising the amino acid sequence QQAYSF PFT (SEQ ID NO:6).In some embodiments, the VH domain includes a CDR-H1 comprising the amino acid sequence of DYYM (SEQ ID NO: 199), a CDR-H2 comprising the amino acid sequence of WINPNEGDTNYAQKFEG (SEQ ID NO: 200), and a CDR-H3 comprising the amino acid sequence of NTGAYSFGY (SEQ ID NO: 204), and the VL domain includes a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASDLQS (SEQ ID NO: 206), and a CDR-L3 comprising the amino acid sequence of QQAYGFPFT (SEQ ID NO: 207). In some embodiments, the VH domain includes a CDR-H1 comprising the amino acid sequence of DYYM (SEQ ID NO: 199), a CDR-H2 comprising the amino acid sequence of WINPNEGDTNYAQ KFQE (SEQ ID NO: 201), and a CDR-H3 comprising the amino acid sequence of NTGAYS FGY (SEQ ID NO: 204), and the VL domain includes a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASDLQS (SEQ ID NO: 206), and a CDR-L3 comprising the amino acid sequence of HQAYSFPFT (SEQ ID NO: 208). In some embodiments, the VH domain includes a CDR-H1 comprising the amino acid sequence of DYYI (SEQ ID NO:1), a CDR-H2 comprising the amino acid sequence of WINPNSGDTNYAQKFQG (SEQ ID NO:2), and a CDR-H3 comprising the amino acid sequence of NSGSASFGY (SEQ ID NO:187), and the VL domain includes a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFT (SEQ ID NO:6).In some embodiments, the VH domain includes a CDR-H1 comprising the amino acid sequence of DYYI (SEQ ID NO:1), a CDR-H2 comprising the amino acid sequence of WI NPNSGDTNYAQKFQG (SEQ ID NO:2), and a CDR-H3 comprising the amino acid sequence of NSGSYSAGY (SEQ ID NO:190), and the VL domain includes a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFT (SEQ ID NO:6). In some embodiments, the VH domain includes a CDR-H1 comprising the amino acid sequence of DYYI (SEQ ID NO:1), a CDR-H2 comprising the amino acid sequence of WINPNSGDTNYAQKFQG (SEQ ID NO:2), and a CDR-H3 comprising the amino acid sequence of NSGSYSFGY (SEQ ID NO:3), and the VL domain includes a CDR-L1 comprising the amino acid sequence of RASQGIS SWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence of QAAYSFPFT (SEQ ID NO:192). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence of DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence of WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence of NSGSYSFGY (SEQ ID NO: 3), and the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSAPFT (SEQ ID NO: 193). In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 209, and the VL domain comprises the amino acid sequence of SEQ ID NO: 210. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 211, and the VL domain comprises the amino acid sequence of SEQ ID NO: 212. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 220, and the VL domain comprises the amino acid sequence of SEQ ID NO: 221.In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 194, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 196, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 197. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 198.

[0024] In some embodiments, the antibody or fragment is a human, humanized, or chimeric antibody or fragment. In some embodiments, the antibody or fragment binds to human Dectin-1 expressed on the surface of macrophages, monocytes, dendritic cells, and / or granulocytes. In some embodiments, the antigen-binding antibody fragment is a Fab, Fab', F(ab')2, Fv, Fab'-SH, F(ab')2, single-chain antibody, nanobody, or scFv fragment. In some embodiments, the antibody further comprises an Fc region. In some embodiments, the Fc region is a human IgG Fc region. In some embodiments, the Fc region is a human IgG1 or human IgG4 Fc region. In some embodiments, the Fc region is a human IgG1 Fc region comprising S239D and I332E substitutions according to EU numbering. In some embodiments, the Fc region is a human IgG1 Fc region comprising S239D, A330L, and I332E substitutions according to EU numbering. In some embodiments, the Fc region is a human IgG1 Fc region comprising G236A, S239D, A330L, and I332E substitutions according to EU numbering. In some embodiments, the Fc region is a human IgG4 Fc region comprising S228P substitutions according to EU numbering. In some embodiments, the antibody or fragment is a multispecific antibody or fragment. In some embodiments, the antibody or fragment is a bispecific antibody, fragment, or diabody comprising a first antigen-binding domain comprising a VH domain and a VL domain that bind to human Dectin-1 and a second antigen-binding domain that binds to a target of interest, or comprising a first antigen-binding domain that binds to a target of interest and a second antigen-binding domain comprising a VH domain and a VL domain that bind to human Dectin-1. In some embodiments, the bispecific antibody comprises: a first antibody arm comprising a single-chain variable fragment (scFv) comprising a VH domain and a VL domain that bind to human Dectin-1 and a first Fc region; and a second antibody arm comprising an antibody heavy chain comprising a VH domain of a second antigen-binding domain and a second Fc region of the VH domain connected to the second antigen-binding domain, the antibody heavy chain being associated with an antibody light chain comprising a VL domain of the second antigen-binding domain. In some embodiments, the VH domain that binds to human Dectin-1 comprises the amino acid sequence of SEQ ID NO: 220, and wherein the VL domain that binds to human Dectin-1 comprises the amino acid sequence of SEQ ID NO: 221. In some embodiments, the scFv comprises the amino acid sequence of SEQ ID NO: 222. In some embodiments, the first antibody arm comprises the amino acid sequence of SEQ ID NO: 224 or 225.In some embodiments, the second antigen binding domain binds CD20 and comprises a VH domain comprising the sequence of SEQ ID NO: 129 and a VL domain comprising the sequence of SEQ ID NO: 130. In some embodiments, the second antigen binding domain binds Trop-2 and comprises a VH domain comprising the sequence of SEQ ID NO: 139 and a VL domain comprising the sequence of SEQ ID NO: 140. In some embodiments, the second antigen binding domain binds light chain amyloid and comprises a VH domain comprising the sequence of SEQ ID NO: 143 and a VL domain comprising the sequence of SEQ ID NO: 144. In some embodiments, the first Fc region comprises one or more knob-forming mutations and the second Fc region comprises one or more cognate hole-forming mutations, or wherein the second Fc region comprises one or more knob-forming mutations and the first Fc region comprises one or more cognate hole-forming mutations. In some embodiments, according to EU numbering, the first Fc region comprises a T366W substitution, and the second Fc region comprises a T366S, L368A, and Y407V substitution. In some embodiments, the first antibody arm comprises a first joint between the VH domain and the VL domain and a second joint between the VL domain and the first Fc region. In some embodiments, the first joint comprises one or more repeats of the sequence GGG GS (SEQ ID NO: 115). In some embodiments, the first joint comprises the sequence GGGGSGGGGSGGGGS (SEQ ID NO: 116) or GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 117). In some embodiments, the second joint comprises the sequence EPKRSDKTHTCPPC (SEQ ID NO: 118) or SATHT CPPC (SEQ ID NO: 119). In some embodiments, the bispecific antibody comprises a first IgG antibody comprising a first antigen-binding domain covalently attached to a second IgG antibody comprising a second antigen-binding domain. In some embodiments, the bispecific antibody comprises: a first antibody arm comprising a first antibody heavy chain comprising a VH domain comprising a first antigen-binding domain and a first Fc region; and a second antibody arm comprising a second antibody heavy chain comprising a VH domain comprising a second antigen-binding domain and a second Fc region, wherein the first Fc region comprises one or more knob-forming mutations and the second Fc region comprises one or more homologous hole-forming mutations. In some embodiments, according to EU numbering, the first Fc region comprises a T366W substitution and the second Fc region comprises T366S, L368A, and Y407V substitutions.In some embodiments, the bispecific antibody comprises: a first antibody arm comprising a first antibody heavy chain comprising a VH domain comprising a first antigen-binding domain and a first Fc region; and a second antibody arm comprising a second antibody heavy chain comprising a VH domain comprising a second antigen-binding domain and a second Fc region, wherein the first Fc region comprises one or more hole-forming mutations and the second Fc region comprises one or more cognate knob-forming mutations. In some embodiments, according to EU numbering, the first Fc region comprises T366S, L368A, and Y407V substitutions, and the second Fc region comprises a T366W substitution. In some embodiments, the bispecific antibody comprises two antibody heavy chains and two antibody light chains, wherein the VH domain of the first antibody heavy chain and the VL domain of the first antibody light chain form an antigen binding domain that binds to human Dectin-1, and wherein the VH domain of the second antibody heavy chain and the VL domain of the second antibody light chain form an antigen binding domain that binds to a target of interest; wherein the VH domain of the first antibody heavy chain comprises the amino acid sequence of SEQ ID NO: 209, and wherein the VL domain of the first antibody light chain comprises the amino acid sequence of SEQ ID NO: 210. In some embodiments, the bispecific antibody comprises two antibody heavy chains and two antibody light chains, wherein the VH domain of the first antibody heavy chain forms an antigen-binding domain that binds to human Dectin-1 with the VL domain of the first antibody light chain, and wherein the VH domain of the second antibody heavy chain forms an antigen-binding domain that binds to a target of interest with the VL domain of the second antibody light chain; wherein the VH domain of the first antibody heavy chain comprises the amino acid sequence of SEQ ID NO: 220, and wherein the VL domain of the first antibody light chain comprises the amino acid sequence of SEQ ID NO: 221. In some embodiments, the first antibody heavy chain comprises a C→S substitution at position 5 according to IMGT hinge numbering, and wherein the first antibody light chain comprises a C→S substitution at the terminal residue of the light chain constant domain. In some embodiments, the first antibody heavy chain comprises the amino acid sequence of SEQ ID NO: 219, and wherein the first antibody light chain comprises the amino acid sequence of SEQ ID NO: 223. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 213, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 214. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 195, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64.In some embodiments, the bispecific antibody comprises: a first IgG antibody comprising a first antigen-binding domain conjugated to biotin or a derivative thereof that binds avidin; and a second IgG antibody comprising a second antigen-binding domain conjugated to avidin, streptavidin, neutravidin, or a derivative thereof that binds biotin, wherein biotin or a derivative thereof that binds avidin binds to avidin, streptavidin, neutravidin, or a derivative thereof that binds biotin. In some embodiments, the bispecific antibody comprises: a first IgG antibody comprising a first antigen-binding domain conjugated to avidin, streptavidin, neutravidin, or a derivative thereof that binds biotin; and a second IgG antibody comprising a second antigen-binding domain conjugated to biotin or a derivative thereof that binds avidin, wherein biotin or a derivative thereof that binds avidin binds to avidin, streptavidin, neutravidin, or a derivative thereof that binds biotin.

[0025] In some embodiments, provided herein is a multispecific (e.g., bispecific) binding molecule comprising: a first antibody or antigen-binding fragment thereof comprising a first antigen-binding domain, wherein the first antigen-binding domain binds to human Dectin-1; and a second antibody or antigen-binding fragment thereof comprising a second antigen-binding domain, wherein the second antigen-binding domain binds to a target of interest; wherein the first antigen-binding domain comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; wherein the VH domain of the first antigen-binding domain comprises: a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1) or DYYM (SEQ ID NO: 199); a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), WINPNEGDTNYAQKFEG (SEQ ID NO: 200), or WINPNEGDTNYAQKFQE (SEQ ID NO: 201); and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3), NSGSASFGY (SEQ ID NO: 4). ID NO: 187), NSGSYSAGY (SEQ ID NO: 190), or NTGAYSFG Y (SEQ ID NO: 204); and wherein the VL domain of the first antigen binding domain comprises: a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4); a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5) or GASDL QS (SEQ ID NO: 206), and a CDR-L3 comprising the amino acid sequence of QQAYSFP FT (SEQ ID NO: 6), QAAYSFPFT (SEQ ID NO: 192), QQAYSA PFT (SEQ ID NO: 193), QQAYGFPFT (SEQ ID NO: 207), or HQA YSFPFT (SEQ ID NO: 208); wherein the multispecific binding molecule does not include a CDR-H1 comprising the amino acid sequence of DYYI (SEQ ID NO: 1), a CDR-L2 comprising the amino acid sequence of WINPNSGDTNYAQKFQG (SEQ ID NO: 2 NO:2), CDR-H2 comprising the amino acid sequence of NSGSYSFGY (SEQ ID NO:3), CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO:4), CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO:5) and CDR-L3 comprising the amino acid sequence of QQA YSFPFT (SEQ ID NO:6).In some embodiments, the VH domain of the first antigen binding domain comprises: a CDR-H1 comprising the amino acid sequence of DYYM (SEQ ID NO: 199), a CDR-H2 comprising the amino acid sequence of WINPNEGDTNYAQKFEG (SEQ ID NO: 200), and a CDR-H3 comprising the amino acid sequence of NTGAYSFGY (SEQ ID NO: 204), and the VL domain of the first antigen binding domain comprises: a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASDLQS (SEQ ID NO: 206), and a CDR-L3 comprising the amino acid sequence of QQAYGFPFT (SEQ ID NO: 207). In some embodiments, the VH domain of the first antigen binding domain comprises: a CDR-H1 comprising the amino acid sequence of D YYM (SEQ ID NO: 199), a CDR-H2 comprising the amino acid sequence of WINPNEG DTNYAQKFQE (SEQ ID NO: 201), and a CDR-H3 comprising the amino acid sequence of NTGAYSFGY (SEQ ID NO: 204), and the VL domain of the first antigen binding domain comprises: a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASDLQS (SEQ ID NO: 206), and a CDR-L3 comprising the amino acid sequence of HQAYSFPFT (SEQ ID NO: 208). In some embodiments, the VH domain of the first antigen binding domain comprises: a CDR-H1 comprising the amino acid sequence of DYYI (SEQ ID NO:1), a CDR-H2 comprising the amino acid sequence of WINPNSGDTNYAQKFQG (SEQ ID NO:2), and a CDR-H3 comprising the amino acid sequence of NSGSASFGY (SEQ ID NO:187), and the VL domain of the first antigen binding domain comprises: a CDR-L1 comprising the amino acid sequence of R ASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence of GA SSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence of QQAYSFP FT (SEQ ID NO:6).In some embodiments, the VH domain of the first antigen binding domain comprises: a CDR-H1 comprising the amino acid sequence of DYYI (SEQ ID NO:1), a CDR-H2 comprising the amino acid sequence of WINPNSGDTNYAQKFQG (SEQ ID NO:2), and a CDR-H3 comprising the amino acid sequence of NSGSYSAGY (SEQ ID NO:190), and the VL domain of the first antigen binding domain comprises: a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFT (SEQ ID NO:6). In some embodiments, the VH domain of the first antigen binding domain comprises: a CDR-H1 comprising the amino acid sequence of DY YI (SEQ ID NO:1), a CDR-H2 comprising the amino acid sequence of WINPNSGDTN YAQKFQG (SEQ ID NO:2), and a CDR-H3 comprising the amino acid sequence of NSGSYSFGY (SEQ ID NO:3), and the VL domain of the first antigen binding domain comprises: a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence of QAAYSFPFT (SEQ ID NO:192). In some embodiments, the VH domain of the first antigen binding domain comprises: a CDR-H1 comprising the amino acid sequence of DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence of WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence of NSGSYSFGY (SEQ ID NO: 3), and the VL domain of the first antigen binding domain comprises: a CDR-L1 comprising the amino acid sequence of RASQGISWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSAPFT (SEQ ID NO: 193). In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 209, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 210.In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 211, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 212. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 220, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 221. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 194, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 196, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 197. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 198. In some embodiments, the VH domain of the first antibody arm comprises the amino acid sequence of SEQ ID NO: 220, and wherein the VL domain of the second antibody arm comprises the amino acid sequence of SEQ ID NO: 221.

[0026] In some embodiments, a multispecific (e.g., bispecific) binding molecule is provided herein, comprising: a first antibody arm comprising a single-chain variable fragment (scFv) and a first Fc region comprising a VH domain and a VL domain of the present disclosure that binds to human Dectin-1; and a second antibody arm comprising an antibody heavy chain comprising a VH domain associated with an antibody light chain comprising a VL domain and a second Fc region connected to the VH domain, wherein the VH domain and the VL domain of the second antibody arm form an antigen binding domain that binds to a target of interest (e.g., in addition to human Dectin-1). In some embodiments, the scFv of the first antibody arm comprises a VH domain comprising the amino acid sequence of SEQ ID NO: 209 and a VL domain comprising the amino acid sequence of SEQ ID NO: 210. In some embodiments, the scFv of the first antibody arm comprises a VH domain comprising the amino acid sequence of SEQ ID NO: 213 and a VL domain comprising the amino acid sequence of SEQ ID NO: 214. In some embodiments, the scFv of the first antibody arm comprises a VH domain comprising the amino acid sequence of SEQ ID NO: 220 and a VL domain comprising the amino acid sequence of SEQ ID NO: 221. In some embodiments, the scFv of the first antibody arm comprises the amino acid sequence QVQLVQSGAEVKKPGASVKVSCKASGYTFTDY YMHWVRQAPGQGLEWMGWINPNEGDTNYAQKFEGRITMTRDTSISTAYMELSRLRSDDTAVYYCARNTGAYSFGYWGCGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKCPKLLIYGASDLQSGVPSRFSGSGSGTDFTL TISSLQPEDFATYYCQQAYGFPFTFGPGTKVDIKEPK (SEQ ID NO: 222). In some embodiments,The first antibody arm comprises the amino acid sequence QVQLVQSG AEVKKPGASVKVSCKASGYTFTDYYMHWVRQAPGQGLEWMGWINPNEGDTNYAQKFEGRITMTRDTSISTAYMELSRLRSDDTAVYYCARNTGAYSFGYWGCGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKCPKLLIYGASDLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAYGFPFTFGPGTKVDIKEPKRSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:224) or QVQLVQSGAEV KKPGASVKVSCKASGYTFTDYYMHWVRQAPGQGLEWMGWINPNEGDTNYAQKFEGRITMTRDTSISTAYMELSRLRSDDTAVYYCARNTGAYSFGYWGCGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKCPKLLIYGASDLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAYGFPFTFGPGTKVDIKEPKRSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:225).

[0027] In some embodiments, the first VH domain comprises the amino acid sequence of SEQ ID NO: 213, and the first VL domain comprises the amino acid sequence of SEQ ID NO: 214. In some embodiments, the first VH domain comprises the amino acid sequence of SEQ ID NO: 220, and the first VL domain comprises the amino acid sequence of SEQ ID NO: 221. In some embodiments, the antibody heavy chain of the first antibody arm has a C→S amino acid substitution at position 5 according to IMGT hinge numbering, position 220 according to the EU index, or position 233 according to Kabat numbering. In some embodiments, the antibody heavy chain of the first antibody arm comprises the sequence

[0028] ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 219). In some embodiments, the antibody light chain of the first antibody arm has a C→S at the terminal residue of the light chain constant domain (e.g., CK domain). In some embodiments, the antibody light chain of the first antibody arm comprises the sequence RADAAPTVSIFPPSSEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSKDSTYSMSSTLTLTKDEYERHNSYTCEATHKTSTSPIVKSFNRNES (SEQ ID NO: 223). In some embodiments, the first VH domain comprises the amino acid sequence of SEQ ID NO: 213; the first VL domain comprises the amino acid sequence of SEQ ID NO: 214; the antibody heavy chain of the first antibody arm has a C→S amino acid substitution at position 5 according to IMGT hinge numbering, position 220 according to the EU index, or position 233 according to Kabat numbering; and the antibody light chain of the first antibody arm has a C→S at the terminal residue of the light chain constant domain (e.g., CK domain). In some embodiments, the first VH domain comprises the amino acid sequence of SEQ ID NO: 220; the first VL domain comprises the amino acid sequence of SEQ ID NO: 221; the antibody heavy chain of the first antibody arm has a C→S amino acid substitution at position 5 according to IMGT hinge numbering, position 220 according to the EU index, or position 233 according to Kabat numbering; and the antibody light chain of the first antibody arm has a C→S at the terminal residue of the light chain constant domain (e.g., CK domain).In some embodiments, the first VH domain comprises the amino acid sequence of SEQ ID NO: 213; the first VL domain comprises the amino acid sequence of SEQ ID NO: 214; the antibody heavy chain of the first antibody arm comprises the sequence of SEQ ID NO: 219; and the antibody light chain of the first antibody arm comprises the sequence of SEQ ID NO: 223. In some embodiments, the first VH domain comprises the amino acid sequence of SEQ ID NO: 220; the first VL domain comprises the amino acid sequence of SEQ ID NO: 221; the antibody heavy chain of the first antibody arm comprises the sequence of SEQ ID NO: 219; and the antibody light chain of the first antibody arm comprises the sequence of SEQ ID NO: 223.

[0029] In some embodiments, the target of interest is a pathogen. In some embodiments, the pathogen is a bacterial cell, a fungal cell, a virus, a senescent cell, a tumor cell, a protein aggregate (e.g., beta amyloid, or lambda or kappa light chain amyloid), an LDL particle, a mast cell, an eosinophil, an ILC2 cell, or an inflammatory immune cell. In some embodiments, the target of interest is an antigen expressed on the surface of a bacterial cell, a fungal cell, a senescent cell, a tumor cell, a mast cell, an eosinophil, an ILC2 cell, or an inflammatory immune cell. In some embodiments, the target of interest is a surface antigen of a virus. In some embodiments, the target of interest is an antigen expressed on the surface of a cancer cell. In some embodiments, the target of interest is CD70, HER2, DLL3, adhesion protein -4, TROP-2, mesothelin, LIV-1, C-MET, FOLR1, CD20, CCR8, CD33, or EG FR. In some embodiments, the target of interest is CD20; the second antigen binding domain comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; and the VH domain of the second antigen binding domain comprises the sequence QVQLQQPGAELVKPGASVKMSCKA SGYTFTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSLTSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSA (SEQ ID NO: 129) and / or the VL domain of the second antigen binding domain comprises the sequence QIVLSQSPAILSASPGEKVTMTCRASSSVSYIHWFQQ KPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWTSNPPTFGGGTKLEIK (SEQ ID NO: 130). In some embodiments, the antibody comprises two antibody heavy chains, and wherein each of the antibody heavy chains comprises an amino acid substitution at one or more of positions 234, 235, and 237 according to EU numbering. In some embodiments, each of the antibody heavy chains comprises L234A, L235E, and G237A substitutions according to EU numbering. In some embodiments, the antibody comprises two antibody heavy chains, and wherein only one of the antibody heavy chains comprises H435R and Y436F substitutions according to EU numbering. In some embodiments, the antibody comprises two arms, and only one of the antibody arms comprises a heavy chain comprising F126C and C220V substitutions and a light chain comprising S121C and C214V substitutions according to EU numbering.In some embodiments, the bispecific antibody comprises a first antibody heavy chain and a second antibody heavy chain, wherein the VH domain of the first antibody heavy chain forms an antigen-binding domain with the VL domain of the first antibody light chain, wherein the VH domain of the second antibody heavy chain forms an antigen-binding domain with the VL domain of the second antibody light chain, wherein according to EU numbering, the first antibody heavy chain comprises F126C, C220V and T366W substitutions, wherein the first antibody light chain comprises S121C and C214V substitutions, and wherein the second antibody heavy chain comprises T366S, L368A, Y407V, H435R and Y436F substitutions. In some embodiments, the first antibody heavy chain and the second antibody heavy chain further comprise L234A, L235E and G237A substitutions according to EU numbering.

[0030] In some embodiments, the first antibody heavy chain and the second antibody heavy chain comprise a human IgG1 Fc domain. In some embodiments, the antibody comprises a first antibody heavy chain and a second antibody heavy chain, wherein at least one or both of the first antibody heavy chain and the second antibody heavy chain are non-fucosylated or comprise reduced fucosylation. In some embodiments, the antibody can be produced in a cell line that knocks out α1,6-fucosyltransferase (Fut8) or α-1,3-mannosyl-glycoprotein 2-β-N-acetylglucosaminyltransferase (MGAT1). In some embodiments, the antibody can be produced in a cell line that overexpresses β1,4-N-acetylglucosaminyltransferase III (GnT-III). In other embodiments, the cell line additionally overexpresses Golgi μ-mannosidase II (ManII). In some embodiments, the antibody can be produced in a cell line treated with a mannosidase I inhibitor, such as kifunine.

[0031] In some embodiments, provided herein is a multispecific binding molecule comprising: (a) a first antibody or antigen-binding fragment thereof comprising a first antigen-binding domain, wherein the first antigen-binding domain binds to human Dectin-1; and (b) a second antibody or antigen-binding fragment thereof comprising a second antigen-binding domain, wherein the second antigen-binding domain binds to a target of interest; wherein the first antigen-binding domain comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; wherein the VH domain of the first antigen-binding domain comprises the amino acid sequence QVQLVQSGAEVKKPGASVKVSCKSS GYTFTX1YYIHWVRQAPGQGLEWMGWINPNSGX2TNYAQKFQGR ITMTRDTSISTAYLELSRLRSDDTAVFYCAX3X4X5X6X7X8X9X 10 X 11 X 12WGQGTLVTVSS, wherein X1 is D, A or G; wherein X2 is D, A or G; wherein X3 is R, A or G; wherein X4 is N, A or G; wherein X5 is S, A or G; wherein X6 is A or G; wherein X7 is S, A or G; wherein X8 is Y, A or G; wherein X9 is S, A or G; wherein X 10 is F, A or G; where X 11 is A or G; and where X 12 is Y, A or G (SEQ ID NO: 63); and wherein the VL domain of the first antigen binding domain comprises the amino acid sequence DIQMTQSPSSVSASVGDRVT ITCRASQGISSWLAWYQQKPGKAPKLLIFGASSLQSGVPSRFSGSGSGTDFTLTVSSLQPEDFATYYCX1X2AX3X4X5X6X7X8FGPGTKVDIE, wherein X1 is Q, A or G; X2 is Q, A or G; X3 is F, Y, A or G; wherein X4 is S, A or G; wherein X5 is F, A or G; wherein X6 is P, A or G; wherein X7 is F, A or G; and wherein X8 is T, A or G (SEQ ID NO: 65). In some embodiments, the first antigen binding domain does not include a CDR-H1 comprising the amino acid sequence of DY YI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence of WINPNSGDTNYA QKFQG (SEQ ID NO: 2), a CDR-H3 comprising the amino acid sequence of NSGSYSFG Y (SEQ ID NO: 3), a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFT (SEQ ID NO: 6). In some embodiments, the VH domain of the first antigen binding domain comprises 1, 2 or fewer, 3 or fewer, 4 or fewer, or 5 or fewer substitutions compared to the amino acid sequence of SEQ ID NO: 62; and / or wherein the VL domain of the first antigen binding domain comprises 1, 2 or fewer, 3 or fewer, 4 or fewer, or 5 or fewer substitutions compared to the amino acid sequence of SEQ ID NO: 64. In some embodiments, the first antigen binding domain binds to human Dectin-1 expressed on the surface of a cell with an EC50 of less than 2 nM; is capable of binding to human or cynomolgus monkey Dectin-1; and / or does not compete with the natural ligand of human Dectin-1.

[0032] In some embodiments, provided herein is a multispecific binding molecule comprising: (a) a first antibody or antigen-binding fragment thereof comprising a first antigen-binding domain, wherein the first antigen-binding domain binds to human Dectin-1; and (b) a second antibody or antigen-binding fragment thereof comprising a second antigen-binding domain, wherein the second antigen-binding domain binds to a target of interest; wherein the first antigen-binding domain comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; wherein the VH domain of the first antigen-binding domain comprises: a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1) or AYY I (SEQ ID NO: 16); a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2) or WINPNSGATNYAQKFQG (SEQ ID NO: 19); and a CDR-H3 comprising an amino acid sequence selected from the group consisting of: NSGSYSFGY (SEQ ID NO: 3), ASGSYSFGY (SEQ ID NO: 4), or SNAP-Y ... NO:22), NSGSASFGY (SEQ ID NO:24), NAGSYSFGY (SEQ ID NO:27), NSASYSFGY (SEQ ID NO:29), NSGAYSFGY (SEQ ID NO:31), NSGSYAFGY (SEQ ID NO:33), NSGSYSAGY (SEQ ID NO:35), NSGSYSFAY (SEQ ID NO:37), and NSGSYSFGA (SEQ ID NO:39); and wherein the VL domain of the first antigen binding domain comprises: a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO:4); a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising an amino acid sequence selected from the group consisting of QQAYSFPFT (SEQ ID NO:6), QQAASFPFT (SEQ ID NO:41), QQAFSFPFT (SEQ ID NO:42), AQAYSFPFT (SEQ ID NO:43), NO:43), QAAYSFPFT (SEQ ID NO:44), QQAYAFPFT (SEQ ID NO:45), QQAYSAPFT (SEQ ID NO:46), QQAYSFAFT (SEQ ID NO:47), QQAYSFPAT (SEQ ID NO:48) and QQAYSFPFA (SEQ ID NO:49).In some embodiments, the first antigen binding domain does not include a CDR-H1 comprising the amino acid sequence of DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence of WINPNSGDTNYAQKFQG (SEQ ID NO: 2), a CDR-H3 comprising the amino acid sequence of NSGSYSFGY (SEQ ID NO: 3), a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFT (SEQ ID NO: 6).

[0033] In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WI NPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence AYYI (SEQ ID NO: 16), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGATNYAQKFQG (SEQ ID NO: 19), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence ASGSYSFGY (SEQ ID NO: 22). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGSASFGY (SEQ ID NO: 24). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NAGSYSFGY (SEQ ID NO: 27). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSASYSFGY (SEQ ID NO: 29).In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGAYSFGY (SEQ ID NO: 31). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGSYAFGY (SEQ ID NO: 33). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGSYSAGY (SEQ ID NO: 35). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGSYSAGY (SEQ ID NO: 37). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINP NSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGSYSFGA (SEQ ID NO: 39).In some embodiments, the VH domain of the first antigen binding domain further comprises: FR1, comprising an amino acid sequence selected from the group consisting of QVQLVQSGAEVKKPGASVKVSCKSSGYTFT (SEQ ID NO: 50) and Q VQLVQSGAEVKKPGASVKVSCKASGYTFT (SEQ ID NO: 51); FR2, comprising the amino acid sequence of HWVRQAPGQ GLEWMG (SEQ ID NO: 52); FR3, comprising an amino acid sequence selected from the group consisting of RITMTR DTSISTAYLELSRLRSDDTAVFYCAR (SEQ ID NO: 53) and RVTMTR DTSISTAYMELSRLRSDDTAVYYCAR (SEQ ID NO: 54); and FR4 comprising the amino acid sequence of WGQGTLVTVSS (SEQ ID NO: 55). In some embodiments, the VL domain of the first antigen binding domain comprises a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO: 6). In some embodiments, the VL domain of the first antigen binding domain comprises a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence GASS LQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence QQAASFPFT (SEQ ID NO: 41). In some embodiments, the VL domain of the first antigen binding domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAFSFPFT (SEQ ID NO: 42). In some embodiments, the VL domain of the first antigen binding domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of A QAYSFPFT (SEQ ID NO: 43).In some embodiments, the VL domain of the first antigen binding domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QAAYSFPFT (SEQ ID NO: 44). In some embodiments, the VL domain of the first antigen binding domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYAFPFT (SEQ ID NO: 45). In some embodiments, the VL domain of the first antigen binding domain comprises a CDR-L1 comprising the amino acid sequence of RASQGI SSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSAPFT (SEQ ID NO: 46). In some embodiments, the VL domain of the first antigen binding domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSFAFT (SEQ ID NO: 47). In some embodiments, the VL domain of the first antigen binding domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GAS SLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSFPAT (SEQ ID NO: 48). In some embodiments, the VL domain of the first antigen binding domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFA (SEQ ID NO: 49).In some embodiments, the VL domain of the first antigen binding domain further comprises: FR1, comprising the amino acid sequence DIQMTQSPSSVSASVGDRVTITC (SEQ ID NO:56); FR2, comprising an amino acid sequence selected from the group consisting of WYQQKPGKAPKLLIF (SEQ ID NO:57) and WYQQKPGKAPKLLIY (SEQ ID NO:58); FR3, comprising an amino acid sequence selected from the group consisting of GVPSRFSGSGSGTDF TLTVSSLQPEDFATYYC (SEQ ID NO:59) and GVPSRFSGSGSGTDFT LTISSLQPEDFATYYC (SEQ ID NO:60); and FR4 comprising the amino acid sequence FGPGTKVDIE (SEQ ID NO:61).

[0034] In some embodiments, provided herein is a multispecific binding molecule comprising: (a) a first antibody or antigen-binding fragment thereof comprising a first antigen-binding domain, wherein the first antigen-binding domain binds to human Dectin-1; and (b) a second antibody or antigen-binding fragment thereof comprising a second antigen-binding domain, wherein the second antigen-binding domain binds to a target of interest; wherein the first antigen-binding domain comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; wherein the VH domain of the first antigen-binding domain comprises: a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7) or GYTFTAYY (SEQ ID NO: 17); a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8) or INPNSGAT (SEQ ID NO: 20); and a CDR-H3 comprising an amino acid sequence selected from the group consisting of ARNSGSYSFGY (SEQ ID NO: 9), ARASGSYSFGY (SEQ ID NO: 23), ARNSGSASFGY (SEQ ID NO: 14), or ARNSGSYSFGY (SEQ ID NO: 15). NO: 25), AANSGSYSFGY (SEQ ID NO: 26), ARNAGSYSFGY (SEQ ID NO: 28), ARNSASYSFGY (SEQ ID NO: 30), ARNSGAYSFGY (SEQ ID NO: 32), ARNSGSYAFGY (SEQ ID NO: 34), ARNSGSYSAGY (SEQ ID NO: 36), ARNSGS YSFAY (SEQ ID NO: 38), and ARNSGSYSFGA (SEQ ID NO: 40); and wherein the VL domain of the first antigen binding domain comprises: a CDR-L1 comprising the amino acid sequence Q GISSW (SEQ ID NO: 10); a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising an amino acid sequence selected from the group consisting of QQAYSFPFT (SEQ ID NO: 12), QQAASFPFT (SEQ ID NO: 41), QQAFSFPFT (SEQ ID NO: 42), AQAYSFPFT (SEQ ID NO: 43); NO:43), QAAYSFPFT (SEQ ID NO:44), QQAYAFPFT (SEQ ID NO:45), QQAYSAPFT (SEQ ID NO:46), QQAYSFAFT (SEQ ID NO:47), QQAYSFPAT (SEQ ID NO:48) and QQAYSFPFA (SEQ ID NO:49).In some embodiments, the first antigen binding domain does not include a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8), a CDR-H3 comprising the amino acid sequence ARNSGS YSFGY (SEQ ID NO: 9), a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO: 12). In some embodiments, the VH domain of the first antigen binding domain includes a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence ARNSGS YSFGY (SEQ ID NO: 9). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence GYTFTAYY (SEQ ID NO: 17), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence ARNSGSYSFGY (SEQ ID NO: 9). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGAT (SEQ ID NO: 20), and a CDR-H3 comprising the amino acid sequence ARNSGSYSFGY (SEQ ID NO: 9). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence ARASGSYSFGY (SEQ ID NO: 23). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence ARNSGSASFGY (SEQ ID NO: 25).In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence AANSGS YSFGY (SEQ ID NO: 26). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence ARNAGSYSFGY (SEQ ID NO: 28). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence ARNSASYSFGY (SEQ ID NO: 30). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence GYTF TDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence ARNSGAYSFGY (SEQ ID NO: 32). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence ARNSGSYAFGY (SEQ ID NO: 34). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence ARNSGS YSAGY (SEQ ID NO: 36). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO:7), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO:8), and a CDR-H3 comprising the amino acid sequence ARNSGSYSFAY (SEQ ID NO:38).In some embodiments, the VH domain of the first antigen-binding domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence ARNSGSYSFGA (SEQ ID NO: 40). In some embodiments, the VL domain of the first antigen-binding domain comprises a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO: 12). In some embodiments, the VL domain of the first antigen-binding domain comprises a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QQA ASFPFT (SEQ ID NO: 41). In some embodiments, the VL domain of the first antigen binding domain comprises a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QQAFSFPFT (SEQ ID NO: 42). In some embodiments, the VL domain of the first antigen binding domain comprises a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence AQAYSFPFT (SEQ ID NO: 43). In some embodiments, the VL domain of the first antigen binding domain comprises a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QAAYSFPFT (SEQ ID NO: 44). In some embodiments, the VL domain of the first antigen binding domain comprises a CDR-L1 comprising the amino acid sequence QGIS SW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QQAYAFPFT (SEQ ID NO: 45).In some embodiments, the VL domain of the first antigen binding domain comprises a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence Q QAYSAPFT (SEQ ID NO: 46). In some embodiments, the VL domain of the first antigen binding domain comprises a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QQAYSFAFT (SEQ ID NO: 47). In some embodiments, the VL domain of the first antigen binding domain comprises a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QQAYSFPAT (SEQ ID NO: 48). In some embodiments, the VL domain of the first antigen binding domain comprises a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QQAYSFPFA (SEQ ID NO: 49). In some embodiments, the VH domain of the first antigen binding domain comprises: a CDR-H1 comprising the amino acid sequence of GYTFT DYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence of INPNEGDT (SEQ ID NO: 202), and a CDR-H3 comprising the amino acid sequence of ARNTGAYSFGY (SEQ ID NO: 205); and wherein the VL domain of the first antigen binding domain comprises: a CDR-L1 comprising the amino acid sequence of QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence of GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence of QQAYGFPFT (SEQ ID NO: 207).In some embodiments, the VH domain of the first antigen binding domain comprises: a CDR-H1 comprising the amino acid sequence of GYTFTDYY (SEQ ID NO:7), a CDR-H2 comprising the amino acid sequence of I NPNEGDT (SEQ ID NO:202), and a CDR-H3 comprising the amino acid sequence of ARN TGAYSFGY (SEQ ID NO:205); and wherein the VL domain of the first antigen binding domain comprises: a CDR-L1 comprising the amino acid sequence of QGISSW (SEQ ID NO:10), a CDR-L2 comprising the amino acid sequence of GAS (SEQ ID NO:11), and a CDR-L3 comprising the amino acid sequence of HQAYSFPFT (SEQ ID NO:208).

[0035] In some embodiments, provided herein is a multispecific binding molecule comprising: (a) a first antibody or antigen-binding fragment thereof comprising a first antigen-binding domain, wherein the first antigen-binding domain binds to human Dectin-1; and (b) a second antibody or antigen-binding fragment thereof comprising a second antigen-binding domain, wherein the second antigen-binding domain binds to a target of interest; wherein the first antigen-binding domain comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; wherein the VH domain of the first antigen-binding domain comprises: a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13) or GYTFTAY (SEQ ID NO: 18); a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14) or NPNSGA (SEQ ID NO: 21); and a CDR-H3 comprising an amino acid sequence selected from the group consisting of: NSGSYSFGY (SEQ ID NO: 15), ASGSYSFGY (SEQ ID NO: 22), NSGSASFGY (SEQ ID NO: 23), or NSGSYSFGY (SEQ ID NO: 24). NO:24), NAGSYSFGY (SEQ ID NO:27), NSASYSFGY (SEQ ID NO:29), NSGAYSFGY (SEQ ID NO:31), NSGSYAFGY (SEQ ID NO:33), NSGSYSAGY (SEQ ID NO:35), NSGSYSFAY (SEQ ID NO:37), and NSGSYSFGA (SEQ ID NO:39); and wherein the VL domain of the first antigen binding domain comprises: a CDR-L1 comprising the amino acid sequence of RASQGISSWL A (SEQ ID NO:4); a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising an amino acid sequence selected from the group consisting of QQAYSFPFT (SEQ ID NO:6), QQAASFPFT (SEQ ID NO:41), QQAFSFPFT (SEQ ID NO:42), AQAYSFPFT (SEQ ID NO:43), QAAYSFPFT (SEQ ID NO:44). NO:44), QQAYAFPFT (SEQ ID NO:45), QQAYSAPFT (SEQ ID NO:46), QQAYSFAFT (SEQ ID NO:47), QQAYSFPAT (SEQ ID NO:48) and QQAYSFPFA (SEQ ID NO:49).In some embodiments, the first antigen binding domain does not include a CDR-H1 comprising the amino acid sequence of GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence of PNSGD (SEQ ID NO: 14), a CDR-H3 comprising the amino acid sequence of NSGSYSFG Y (SEQ ID NO: 15), a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFT (SEQ ID NO: 6). In some embodiments, the VH domain of the first antigen binding domain comprises: a CDR-H1 comprising the amino acid sequence of DYYM (SEQ ID NO: 199), a CDR-H2 comprising the amino acid sequence of WINPNEGDTNYAQKFEG (SEQ ID NO: 200), and a CDR-H3 comprising the amino acid sequence of NTGAYSFGY (SEQ ID NO: 204); and wherein the VL domain of the first antigen binding domain comprises: a CDR-L1 comprising the amino acid sequence of RAS QGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASD LQS (SEQ ID NO: 206), and a CDR-L3 comprising the amino acid sequence of QQAYGFP FT (SEQ ID NO: 207). In some embodiments, the VH domain of the first antigen binding domain comprises: a CDR-H1 comprising the amino acid sequence of DYYM (SEQ ID NO: 199), a CDR-H2 comprising the amino acid sequence of WINPNEGDTNYAQKFQE (SEQ ID NO: 201), and a CDR-H3 comprising the amino acid sequence of NTGAYSFGY (SEQ ID NO: 204); and wherein the VL domain of the first antigen binding domain comprises: a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASDLQS (SEQ ID NO: 206), and a CDR-L3 comprising the amino acid sequence of HQAYSFPFT (SEQ ID NO: 208).

[0036] In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence NSGS YSFGY (SEQ ID NO: 15). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence GYTFTAY (SEQ ID NO: 18), a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 15). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNSGA (SEQ ID NO: 21), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 15). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence ASGSYSFGY (SEQ ID NO: 22). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence NAGSYSFGY (SEQ ID NO: 27). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence NSASYSFGY (SEQ ID NO: 29). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence NSGAYSFGY (SEQ ID NO: 31).In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence NSGSYAFGY (SEQ ID NO: 33). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence NSGSYSAGY (SEQ ID NO: 35). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence NSGSYSFAY (SEQ ID NO: 37). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence NSGSYSFGA (SEQ ID NO: 39). In some embodiments, the VL domain of the first antigen binding domain comprises a CDR-L1 comprising the amino acid sequence of RASQGI SSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFT (SEQ ID NO: 6). In some embodiments, the VL domain of the first antigen binding domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAASFPFT (SEQ ID NO: 41). In some embodiments, the VL domain of the first antigen binding domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence of QQAFSFPFT (SEQ ID NO:42).In some embodiments, the VL domain of the first antigen binding domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of AQAYSFPFT (SEQ ID NO: 43). In some embodiments, the VL domain of the first antigen binding domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QAAY SFPFT (SEQ ID NO: 44). In some embodiments, the VL domain of the first antigen binding domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYAFPFT (SEQ ID NO: 45). In some embodiments, the VL domain of the first antigen binding domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYAFPFT (SEQ ID NO: 46). In some embodiments, the VL domain of the first antigen binding domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSW LA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSFAFT (SEQ ID NO: 47). In some embodiments, the VL domain of the first antigen binding domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSFPAT (SEQ ID NO: 48). In some embodiments, the VL domain of the first antigen binding domain comprises a CDR-L1 comprising the amino acid sequence of RAS QGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence of GASSLQ S (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFA (SEQ ID NO:49).In some embodiments, the VH domain of the first antigen binding domain comprises: a CDR-H1 comprising the amino acid sequence of GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence of NPNEGD (SEQ ID NO: 203), and a CDR-H3 comprising the amino acid sequence of NTGAYSFGY (SEQ ID NO: 204); and wherein the VL domain of the first antigen binding domain comprises: a CDR-L1 comprising the amino acid sequence of RASQG ISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASDLQ S (SEQ ID NO: 206), and a CDR-L3 comprising the amino acid sequence of QQAYGFPFT (SEQ ID NO: 207).

[0037] In some embodiments, the VH domain of the first antigen binding domain comprises an amino acid sequence selected from the group consisting of SEQ ID No: 62 and 82-93. In some embodiments, in some embodiments according to any of the embodiments described herein, the VL domain of the first antigen binding domain comprises an amino acid sequence selected from the group consisting of SEQ ID No: 64 and 94-102. In some embodiments, the VH domain of the first antigen binding domain comprises an amino acid sequence selected from the group consisting of SEQ ID No: 62 and 82-93 and / or the VL domain of the first antigen binding domain comprises an amino acid sequence selected from the group consisting of SEQ ID No: 64 and 94-102. In some embodiments, the first antigen binding domain does not include a VH domain comprising the amino acid sequence of SEQ ID NO: 62 and a VL domain comprising the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 94. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 95. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 96. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 97. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 98. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 99. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 101.In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 102. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 94. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 95. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 96. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 97. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 98. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 99. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 102. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 64.In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 94. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 95. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 96. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 97. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 98. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 99. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 102. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 94. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 95.In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 96. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 97. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 98. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 99. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 102. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 94. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 95. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 96. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 97.In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 98. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 99. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 102. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 94. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 95. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 96. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 97. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 98. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 99.In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 102. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 94. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 95. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 96. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 97. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 98. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 99. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 101.In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 102. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 94. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 95. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 96. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 97. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 98. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 99. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 102. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 64.In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 94. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 95. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 96. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 97. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 98. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 99. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 102. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 94. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 95.In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 96. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 97. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 98. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 99. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 102. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 94. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 95. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 96. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 97.In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 98. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 99. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 102. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 94. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 95. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 96. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 97. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 98. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 99.In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 102. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 94. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 95. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 96. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 97. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 98. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 99. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 101.In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 102. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 209, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 210. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 211, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 212. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 213, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 214. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 220, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 221. In some embodiments, the first antibody heavy chain comprises a C→S substitution at position 5 according to IMGT hinge numbering, and wherein the first antibody light chain comprises a C→S substitution at the terminal residue of the light chain constant domain. In some embodiments, the first antibody heavy chain comprises the amino acid sequence of SEQ ID NO: 219, and wherein the first antibody light chain comprises the amino acid sequence of SEQ ID NO: 223.

[0038] In some embodiments, provided herein is a multispecific binding molecule comprising: (a) a first antibody or antigen-binding fragment thereof comprising a first antigen-binding domain, wherein the first antigen-binding domain binds to human Dectin-1; and (b) a second antibody or antigen-binding fragment thereof comprising a second antigen-binding domain, wherein the second antigen-binding domain binds to a target of interest; wherein the first antigen-binding domain comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; wherein the VH domain of the first antigen-binding domain comprises the amino acid sequence QVQLVQSGAEVKKPGASVKVSCKX1SGYTFTX2YYX3HWVRQAPGQGLEWMGWINPNSGX4TNYAQKFQ GRX5TMTRDTSISTAYX6ELSRLRSDDTAVX7YCARNSGSYSFGYW GQGTLVTVSS; wherein X1 is S or A; wherein X2 is D or G; wherein X3 is I or M; wherein X4 is D or G; wherein X5 is I or V; wherein X6 is L or M; and wherein X7 is F or Y (SEQ ID NO: 80); and wherein the VL domain of the first antigen binding domain comprises the amino acid sequence DIQMTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKAPKLLIX1X2ASSLQSGVPSRFSGSGSGTDFTLTX3SSLQPEDFATYYCQQAYSFPFTFGPGTKVDIE; wherein X1 is F or Y; wherein X2 is G or A; and wherein X3 is V or I (SEQ ID NO: 81). In some embodiments, the first antigen binding domain does not include a CDR-H1 comprising the amino acid sequence of DY YI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence of WINPNSGDTNYA QKFQG (SEQ ID NO: 2), a CDR-H3 comprising the amino acid sequence of NSGSYSFG Y (SEQ ID NO: 3), a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFT (SEQ ID NO: 6).

[0039] In some embodiments, provided herein is a multispecific binding molecule comprising: (a) a first antibody or antigen-binding fragment thereof comprising a first antigen-binding domain, wherein the first antigen-binding domain binds to human Dectin-1; and (b) a second antibody or antigen-binding fragment thereof comprising a second antigen-binding domain, wherein the second antigen-binding domain binds to a target of interest; wherein the first antigen-binding domain comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; wherein the VH domain of the first antigen-binding domain comprises: a CDR-H1 comprising an amino acid sequence selected from the group consisting of DYYI (SEQ ID NO: 1), DYYM (SEQ ID NO: 66), and GYYM (SEQ ID NO: 67); a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2) or WINPNSGGTNYAQKFQG (SEQ ID NO: 70); and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 81). NO:3); and wherein the VL domain of the first antigen binding domain comprises: a CDR-L1 comprising the amino acid sequence RAS QGISSWLA (SEQ ID NO:4); a CDR-L2 comprising the amino acid sequence GASSLQ S (SEQ ID NO:5) or AASSLQS (SEQ ID NO:73), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO:6). In some embodiments, the first antigen binding domain does not include a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQ G (SEQ ID NO: 2), a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3), a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO: 6). In some embodiments, the VH domain of the first antigen binding domain includes a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3).In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence DYYM (SEQ ID NO: 66), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence GYYM (SEQ ID NO: 67), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence DYYM (SEQ ID NO: 66), a CDR-H2 comprising the amino acid sequence WINPNSGGTNYAQKFQG (SEQ ID NO: 70), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence GYYM (SEQ ID NO: 67), a CDR-H2 comprising the amino acid sequence WINPNSGGTNYAQKFQG (SEQ ID NO: 70), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3). In some embodiments, the VH domain of the first antigen binding domain further comprises: FR1, comprising an amino acid sequence selected from the group consisting of QV QLVQSGAEVKKPGASVKVSCKSSGYTFT (SEQ ID NO: 50) and QVQ LVQSGAEVKKPGASVKVSCKASGYTFT (SEQ ID NO: 76); FR2, comprising the amino acid sequence HWVRQAPGQGL EWMG (SEQ ID NO: 52); FR3, comprising an amino acid sequence selected from the group consisting of RITMTRDTSISTAYLELSRLRSDDTAVFYCAR (SEQ ID NO: 53) and RVTMTRDTSI STAYMELSRLRSDDTAVYYCAR (SEQ ID NO: 77); and FR4 comprising the amino acid sequence WGQGTLVTVSS (SEQ ID NO: 55).In some embodiments, the VL domain of the first antigen binding domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFT (SEQ ID NO: 6). In some embodiments, the VL domain of the first antigen binding domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of AASSLQS (SEQ ID NO: 73), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFT (SEQ ID NO: 6). In some embodiments, the VL domain of the first antigen binding domain further comprises: FR1 comprising the amino acid sequence DIQMTQSPSSV SASVGDRVTITC (SEQ ID NO: 56); FR2 comprising an amino acid sequence selected from the group consisting of WYQQKPGKAPKLLIF (SEQ ID NO: 57) and WYQQKPGKAPKLLIY (SEQ ID NO: 78); FR3 comprising an amino acid sequence selected from the group consisting of GVPSRFSGSGSGTDFTLTVSSLQPEDFATYYC (SEQ ID NO: 59) and GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC (SEQ ID NO: 79); and FR4 comprising the amino acid sequence FGPGTK VDIE (SEQ ID NO: 61).

[0040] In some embodiments, provided herein is a multispecific binding molecule comprising: (a) a first antibody or antigen-binding fragment thereof comprising a first antigen-binding domain, wherein the first antigen-binding domain binds to human Dectin-1; and (b) a second antibody or antigen-binding fragment thereof comprising a second antigen-binding domain, wherein the second antigen-binding domain binds to a target of interest; wherein the first antigen-binding domain comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; wherein the VH domain of the first antigen-binding domain comprises: a CDR-H1 comprising an amino acid sequence selected from the group consisting of GYTFTDYY (SEQ ID NO: 7) and GYTFTGYY (SEQ ID NO: 68); a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8) or INPNSGGT (SEQ ID NO: 71); and a CDR-H3 comprising the amino acid sequence ARNSGSYSFGY (SEQ ID NO: 9); and wherein the VL domain of the first antigen-binding domain comprises: a CDR-H2 comprising the amino acid sequence QGISSW (SEQ ID NO: 103); NO: 10), a CDR-L1 comprising the amino acid sequence of GAS (SEQ ID NO: 11) or AAS (SEQ ID NO: 74), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFT (SEQ ID NO: 12). In some embodiments, the first antigen-binding domain does not include a CDR-H1 comprising the amino acid sequence of GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence of INPNSGDT (SEQ ID NO: 8), a CDR-H3 comprising the amino acid sequence of ARNSGSYSFGY (SEQ ID NO: 9), a CDR-L1 comprising the amino acid sequence of QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence of GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFT (SEQ ID NO: 12). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO:7), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO:8), and a CDR-H3 comprising the amino acid sequence ARNSGSYSFGY (SEQ ID NO:9).In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence GYTFTGYY (SEQ ID NO: 68), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence ARNSGSYSFGY (SEQ ID NO: 9). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGGT (SEQ ID NO: 71), and a CDR-H3 comprising the amino acid sequence ARNSGSYSFGY (SEQ ID NO: 9). In some embodiments, the VH domain of the first antigen-binding domain comprises a CDR-H1 comprising the amino acid sequence GYTFTGYY (SEQ ID NO: 68), a CDR-H2 comprising the amino acid sequence INPNSGGT (SEQ ID NO: 71), and a CDR-H3 comprising the amino acid sequence ARNSGSYSFGY (SEQ ID NO: 9). In some embodiments, the VL domain of the first antigen-binding domain comprises a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO: 12). In some embodiments, the VL domain of the first antigen-binding domain comprises a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence AAS (SEQ ID NO: 74), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO: 12).

[0041] In some embodiments, provided herein is a multispecific binding molecule comprising: (a) a first antibody or antigen-binding fragment thereof comprising a first antigen-binding domain, wherein the first antigen-binding domain binds to human Dectin-1; and (b) a second antibody or antigen-binding fragment thereof comprising a second antigen-binding domain, wherein the second antigen-binding domain binds to a target of interest; wherein the first antigen-binding domain comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; wherein the VH domain of the first antigen-binding domain comprises: a CDR-H1 comprising an amino acid sequence selected from the group consisting of GYTFTDY (SEQ ID NO: 13) and GYTFTGY (SEQ ID NO: 69); a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14) or NPNSGG (SEQ ID NO: 72); and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 15); and wherein the VL domain of the first antigen-binding domain comprises: a CDR-H2 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO: 16). NO: 4); a CDR-L1 comprising the amino acid sequence GASSLQS (SEQ ID NO: 5) or AASSLQS (SEQ ID NO: 75); and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO: 6). In some embodiments, the first antigen-binding domain does not include a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14), a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 15), a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO: 6). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 15).In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence GYTFTGY (SEQ ID NO: 69), a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 15). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNSGG (SEQ ID NO: 72), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 15). In some embodiments, the VH domain of the first antigen binding domain comprises a CDR-H1 comprising the amino acid sequence GYTFTGY (SEQ ID NO: 69), a CDR-H2 comprising the amino acid sequence NPNSGG (SEQ ID NO: 72), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 15). In some embodiments, the VL domain of the first antigen binding domain comprises a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO: 6). In some embodiments, the VL domain of the first antigen binding domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence of AASSLQS (SEQ ID NO:75), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFT (SEQ ID NO:6).

[0042] In some embodiments, the VH domain of the first antigen-binding domain comprises an amino acid sequence selected from the group consisting of SEQ ID No: 62 and 103-109. In some embodiments, the VL domain of the first antigen-binding domain comprises an amino acid sequence selected from the group consisting of SEQ ID No: 64 and 110-113. In some embodiments, the VH domain of the first antigen-binding domain comprises an amino acid sequence selected from the group consisting of SEQ ID No: 62 and 103-109 and / or the VL domain of the first antigen-binding domain comprises an amino acid sequence selected from the group consisting of SEQ ID No: 64 and 110-113. In some embodiments, the first antigen-binding domain does not include a VH domain comprising the amino acid sequence of SEQ ID NO: 62 and a VL domain comprising the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain of the first antigen-binding domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain of the first antigen-binding domain comprises the amino acid sequence of SEQ ID NO: 110. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 111. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 112. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 113. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 103, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 103, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 110. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 103, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 111. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 103, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 112.In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 103, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 113. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 104, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 104, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 110. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 104, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 111. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 104, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 112. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 104, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 113. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 105, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 105, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 110. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 105, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 111. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 105, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 112. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO:105, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO:113.In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 106, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 106, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 110. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 106, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 111. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 106, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 112. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 106, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 113. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 107, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 107, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 110. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 107, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 111. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 107, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 112. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 107, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 113. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 108, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 64.In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 108, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 110. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 108, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 111. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 108, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 112. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 108, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 113. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 109, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 109, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 110. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 109, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 111. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 109, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 112. In some embodiments, the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 109, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 113.

[0043] In some embodiments, provided herein is a multispecific binding molecule comprising: a first arm comprising a single-chain variable fragment (scFv) that binds to human Dectin-1 and a first Fc region, wherein the scFv comprises a first VH domain and a first VL domain; and a second arm comprising a second antibody comprising a second antigen-binding domain and a second Fc region, wherein the second antigen-binding domain binds to a target of interest; wherein the VH domain of the first antibody arm comprises the amino acid sequence of SEQ ID NO: 220, and wherein the VL domain of the second antibody arm comprises the amino acid sequence of SEQ ID NO: 221. In some embodiments, the scFv comprises the amino acid sequence of SEQ ID NO: 222. In some embodiments, the first arm comprises the amino acid sequence of SEQ ID NO: 224 or 225.

[0044] In some embodiments, provided herein is a multispecific binding molecule comprising: a first arm comprising a first antibody heavy chain and a first antibody light chain, wherein the first antibody heavy chain comprises a first VH domain and a first Fc region, wherein the first antibody light chain comprises a first VL domain, and wherein the first VH domain and the VL domain form a first antigen-binding domain that binds to human Dectin-1; and a second arm comprising a second antibody heavy chain and a second antibody light chain, wherein the second antibody heavy chain comprises a second VH domain and a second Fc region, wherein the second antibody light chain comprises a second VL domain, and wherein the second VH domain and the second VL domain form a second antigen-binding domain that binds to a target of interest; wherein the first VH domain comprises the amino acid sequence of SEQ ID NO: 209 and the first VL domain comprises the amino acid sequence of SEQ ID NO: 210. In some embodiments, provided herein is a multispecific binding molecule comprising: a first arm comprising a first antibody heavy chain and a first antibody light chain, wherein the first antibody heavy chain comprises a first VH domain and a first Fc region, wherein the first antibody light chain comprises a first VL domain, and wherein the first VH domain and the VL domain form a first antigen-binding domain that binds to human Dectin-1; and a second arm comprising a second antibody heavy chain and a second antibody light chain, wherein the second antibody heavy chain comprises a second VH domain and a second Fc region, wherein the second antibody light chain comprises a second VL domain, and wherein the second VH domain and the second VL domain form a second antigen-binding domain that binds to a target of interest; wherein the first VH domain comprises the amino acid sequence of SEQ ID NO: 220 and the first VL domain comprises the amino acid sequence of SEQ ID NO: 221. In some embodiments, the first antibody heavy chain comprises a C→S substitution at position 5 according to IMGT hinge numbering, and wherein the first antibody light chain comprises a C→S substitution at the terminal residue of the light chain constant domain. In some embodiments, the first antibody heavy chain comprises the amino acid sequence of SEQ ID NO: 219, and wherein the first antibody light chain comprises the amino acid sequence of SEQ ID NO: 223.

[0045] In some embodiments, the target of interest is a pathogen. In some embodiments, the pathogen is a bacterial cell, a fungal cell, a virus, a senescent cell, a tumor cell, a protein aggregate (e.g., beta amyloid, or lambda or kappa light chain amyloid), an LDL particle, a mast cell, an eosinophil, an ILC2 cell, or an inflammatory immune cell. In some embodiments, the target of interest is an antigen expressed on the surface of a bacterial cell, a fungal cell, a senescent cell, a tumor cell, a mast cell, an eosinophil, an ILC2 cell, or an inflammatory immune cell. In some embodiments, the target of interest is a surface antigen of a virus. In some embodiments, the target of interest is CD70, HER2, DLL3, adhesion protein -4, TR OP-2, mesothelin, LIV-1, C-MET, FOLR1, CD20, CCR8, CD33, or E GFR. In some embodiments, the first antigen binding domain: binds to human Dectin-1 expressed on the surface of macrophages, monocytes, dendritic cells, or granulocytes; binds to human Dectin-1 expressed on the surface of cells with an EC50 of less than 2 nM; is capable of binding to human or cynomolgus monkey Dectin-1; and / or does not compete with the natural ligand of human Dectin-1. In some embodiments, the second antigen binding domain binds to CD20 and comprises a VH domain comprising the sequence of SEQ ID NO: 129 and a VL domain comprising the sequence of SEQ ID NO: 130. In some embodiments, the second antigen binding domain binds to Trop-2 and comprises a VH domain comprising the sequence of SEQ ID NO: 139 and a VL domain comprising the sequence of SEQ ID NO: 140. In some embodiments, the second antigen binding domain binds to light chain amyloid and comprises a VH domain comprising the sequence of SEQ ID NO: 143 and a VL domain comprising the sequence of SEQ ID NO: 144. In some embodiments, one or both of the first antibody or fragment and the second antibody or fragment are human or humanized antibodies or fragments. In some embodiments, one or both of the first antibody or fragment and the second antibody or fragment are Fab, Fab', F(ab')2, Fv, Fab'-SH, F(ab')2, single-chain antibodies, nano antibodies or scFv fragments. In some embodiments, one or both of the first antibody or fragment and the second antibody or fragment also include an Fc domain. In some embodiments, the first antibody or fragment is a Fab fragment, and wherein the second antibody or fragment is, for example, a full-length antibody comprising an antibody heavy chain and an antibody light chain. In some embodiments, the first antibody or fragment and the second antibody or fragment are both full-length antibodies, for example, each comprising an antibody heavy chain and an antibody light chain.In some embodiments, the multispecific binding molecule comprises: a first antibody arm comprising a single-chain variable fragment (scFv) comprising a VH domain and a VL domain that binds to human Dectin-1 and a first Fc region; and a second antibody arm comprising an antibody heavy chain comprising the VH domain of the second antigen-binding domain and a second Fc region connected to the VH domain of the second antigen-binding domain, the antibody heavy chain associated with an antibody light chain comprising the VL domain of the second antigen-binding domain. In some embodiments, the first Fc region comprises one or more knob-forming mutations and the second Fc region comprises one or more homologous hole-forming mutations, or wherein the second Fc region comprises one or more knob-forming mutations and the first Fc region comprises one or more homologous hole-forming mutations. In some embodiments, according to EU numbering, the first Fc region comprises a T366W substitution and the second Fc region comprises T366S, L368A, and Y407V substitutions. In some embodiments, the first antibody arm comprises a first joint between the VH domain and the VL domain and a second joint between the VL domain and the first Fc region. In some embodiments, the first joint comprises one or more repeats of the sequence GGGGS (SEQ ID NO: 115). In some embodiments, the first joint comprises the sequence GGGGSGGGGSGGGGS (SEQ ID NO: 116) or GGG GSGGGGSGGGGSGGGGS (SEQ ID NO: 117). In some embodiments, the second joint comprises the sequence EPKRSDKTHTCPPC (SEQ ID NO: 118) or SATHT CPPC (SEQ ID NO: 119). In some embodiments, the first antibody or fragment is coupled to avidin, streptavidin, neutralizing avidin or its derivative binding to biotin, and the second antibody or fragment is coupled to biotin or its derivative binding to avidin; or wherein the second antibody or fragment is coupled to avidin, streptavidin, neutralizing avidin or its derivative binding to biotin, and the first antibody or fragment is coupled to biotin or its derivative binding to avidin; and wherein the first antibody or fragment is bound to the second antibody or fragment via an interaction between avidin, streptavidin, neutralizing avidin or its derivative binding to biotin and biotin or its derivative binding to avidin. In some embodiments, the first antibody or fragment is a Fab fragment coupled to monomeric streptavidin (mSA), and wherein the second antibody or fragment is a biotinylated antibody comprising an antibody heavy chain and an antibody light chain. In some embodiments, the first antibody or fragment is a full-length antibody coupled to monomeric streptavidin (mSA), and wherein the second antibody or fragment is a biotinylated full-length antibody.In some embodiments, the multispecific binding molecule comprises a first IgG antibody comprising a first antigen-binding domain covalently linked to a second IgG antibody comprising a second antigen-binding domain. In some embodiments, the multispecific binding molecule comprises: a first antibody arm comprising a VH domain and a first Fc region comprising the first antigen-binding domain, and a first antibody light chain comprising a VL domain of the first antigen-binding domain; and a second antibody arm comprising a second antibody heavy chain comprising a VH domain and a second Fc region comprising the second antigen-binding domain, and a second antibody light chain comprising a VL domain of the second antigen-binding domain, wherein the first Fc region comprises one or more knob-forming mutations, and the second Fc region comprises one or more homologous hole-forming mutations. In some embodiments, according to EU numbering, the first Fc region comprises a T366W substitution, and wherein the second Fc region comprises T366S, L368A, and Y407V substitutions. In some embodiments, the multispecific binding molecule comprises: a first antibody arm comprising a VH domain comprising a first antigen-binding domain and a first Fc region; and a second antibody arm comprising a VH domain comprising a second antigen-binding domain and a second Fc region, wherein the first Fc region comprises one or more hole-forming mutations and the second Fc region comprises one or more homologous knob-forming mutations. In some embodiments, the first Fc region comprises T366S, L368A, and Y407V substitutions according to EU numbering, and wherein the second Fc region comprises a T366W substitution. In some embodiments, the multispecific binding molecule comprises two antibody Fc regions, and wherein each of the antibody heavy chains comprises an amino acid substitution at one or more of positions 234, 235, and 237 according to EU numbering. In some embodiments, each of the antibody Fc regions comprises L234A, L235E, and G237A substitutions according to EU numbering. In some embodiments, the Fc region is a human IgG Fc region. In some embodiments, the Fc region is a human IgG1 or human IgG4 Fc region. In some embodiments, the Fc region is a human IgG1 Fc region comprising S239D and I332E substitutions according to EU numbering. In some embodiments, the Fc region is a human IgG1 Fc region comprising S239D, A330L, and I332E substitutions according to EU numbering. In some embodiments, the Fc region is a human IgG1 Fc region comprising G236A, S239D, A330L, and I332E substitutions according to EU numbering. In some embodiments, the Fc region is a human IgG4 Fc region comprising S228P substitution according to EU numbering. In some embodiments, the multispecific binding molecule comprises two antibody heavy chains, and wherein only one of the antibody heavy chains comprises H435R and Y436F substitutions according to EU numbering.In some embodiments, only one of the antibody arms comprises a heavy chain comprising F126C and C220V substitutions and a light chain comprising S121C and C214V substitutions, according to EU numbering. In some embodiments, the multispecific binding molecule comprises a first antibody heavy chain and a first antibody light chain and a second antibody heavy chain and a second antibody light chain, wherein the VH domain of the first antibody heavy chain forms a first antigen-binding domain with the VL domain of the first antibody light chain, wherein the VH domain of the second antibody heavy chain forms a second antigen-binding domain with the VL domain of the second antibody light chain, wherein, according to EU numbering, the first antibody heavy chain comprises F126C, C220V, and T366W substitutions, wherein the first antibody light chain comprises S121C and C214V substitutions, and wherein the second antibody heavy chain comprises T366S, L368A, Y407V, H435R, and Y436F substitutions. In some embodiments, the first antibody heavy chain and the second antibody heavy chain further comprise L234A, L235E, and G237A substitutions according to EU numbering. In some embodiments, the first antibody heavy chain and the second antibody heavy chain comprise human IgG1 Fc domains. In some embodiments, at least one or both of the antibody heavy chains are non-fucosylated or comprise reduced fucosylation. In some embodiments, the antibody can be produced in a cell line in which α1,6-fucosyltransferase (Fut8) or α-1,3-mannosyl-glycoprotein 2-β-N-acetylglucosaminyltransferase (MGAT1) is knocked out. In some embodiments, the antibody can be produced in a cell line that overexpresses β1,4-N-acetylglucosaminyltransferase III (GnT-III). In other embodiments, the cell line additionally overexpresses Golgi μ-mannosidase II (ManII). In some embodiments, the antibody can be produced in a cell line treated with a mannosidase I inhibitor, such as kifunine.

[0046] In some embodiments, a polynucleotide is provided herein, and the polynucleotide encodes an antibody or multispecific binding molecule of any one of the above-mentioned embodiments. In some embodiments, a vector (e.g., an expression vector) is provided herein, and the vector comprises the polynucleotide of any one of the above-mentioned embodiments. In some embodiments, a host cell (e.g., an isolated host cell or cell line) is provided herein, and the host cell comprises the polynucleotide or vector of any one of the above-mentioned embodiments. In some embodiments, a method for producing an antibody or multispecific binding molecule is provided herein, and the method is included in culturing the host cell of any one of the above-mentioned embodiments under conditions suitable for producing the antibody or multispecific binding molecule. In some embodiments, the method further includes recovering the antibody or multispecific binding molecule. In some embodiments, a pharmaceutical composition is provided herein, and the pharmaceutical composition comprises the antibody or multispecific binding molecule and a pharmaceutically acceptable carrier of any one of the above-mentioned embodiments.

[0047] In some embodiments, there is provided herein a method for treating a disease or illness, the method comprising administering an effective amount of an antibody, a multispecific binding molecule or a composition of any one of the above-mentioned embodiments to an individual in need thereof. In some embodiments, the first target of interest is human Dectin-1, and wherein the second target of interest is a pathogen. In some embodiments, the pathogen is a bacterial cell, a fungal cell, a virus, a senescent cell, a tumor cell, a protein aggregate (e.g., beta amyloid, or lambda or kappa light chain amyloid), an LDL particle, a mast cell, an eosinophil, an ILC2 cell or an inflammatory immune cell. In some embodiments, the target of interest is an antigen expressed on the surface of a bacterial cell, a fungal cell, a senescent cell, a tumor cell, a mast cell, an eosinophil, an ILC2 cell or an inflammatory immune cell. In some embodiments, the target of interest is a surface antigen of a virus. In some embodiments, the disease or condition is cancer, bacterial infection, fungal infection, viral infection, mast cell disease or condition, systemic mastocytosis, amyloidosis (e.g., light chain amyloidosis or Alzheimer's disease), or a disease or condition associated with aging. In some embodiments, the target of interest is CD70, HER2, DLL3, fibronectin-4, TROP-2, mesothelin, LIV-1, C-MET, FOLR1, CD20, CCR8, CD33, or EGFR. In some embodiments, the individual is a human.

[0048] In some embodiments, provided herein is a method of treating cancer, comprising administering to a subject in need thereof an effective amount of a composition comprising a multispecific binding molecule according to any one of the above embodiments, wherein the multispecific binding molecule comprises: (a) a first antibody or antigen-binding fragment thereof comprising a first antigen-binding domain according to any one of the above embodiments, wherein the first antigen-binding domain binds to human Dectin-1; and (b) a second antibody or antigen-binding fragment thereof comprising a second antigen-binding domain, wherein the second antigen-binding domain binds to CD70, HER2, DLL3, nectin-4, TROP-2, mesothelin, LIV-1, C-MET, FOLR1, CD20, CCR8, CD33, or EGFR. In some embodiments, the second antigen-binding domain binds to, for example, human CD70, human HER2, human DLL3, human nectin-4, human TROP-2, human mesothelin, human LIV-1, human C-MET, human FOLR1, human CD20, human CCR8, human CD33, or human EGFR expressed on the surface of a cancer cell.

[0049] In some embodiments, the second antigen binding domain binds CD20; wherein the second antigen binding domain comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; and wherein the VH domain of the second antigen binding domain comprises the sequence QVQLQQPGAEL VKPGASVKMSCKASGYTFTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSLTSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSA (SEQ ID NO: 129) and / or wherein the VL domain of the second antigen binding domain comprises the sequence QIVLSQSPAILSASPGEKV TMTCRASSSVSYIHWFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWTSNPPTFGGGTKLEIK (SEQ ID NO: 130). In some embodiments, a multispecific binding molecule comprises: a first antibody arm comprising a first antigen-binding domain and a first Fc region; and a second antibody arm comprising a second antigen-binding domain and a second Fc region, wherein the first Fc region comprises one or more knob-forming mutations and the second Fc region comprises one or more homologous hole-forming mutations. In some embodiments, according to EU numbering, the first Fc region comprises a T366W substitution and the second Fc region comprises T366S, L368A, and Y407V substitutions. In some embodiments, a multispecific binding molecule comprises: a first antibody arm comprising a first antigen-binding domain and a first Fc region; and a second antibody arm comprising a second antigen-binding domain and a second Fc region, wherein the first Fc region comprises one or more hole-forming mutations and the second Fc region comprises one or more homologous knob-forming mutations. In some embodiments, according to EU numbering, the first Fc region comprises T366S, L368A, and Y407V substitutions and the second Fc region comprises a T366W substitution. In some embodiments, the antibody comprises two antibody Fc regions, and wherein each of the antibody Fc regions comprises an amino acid substitution at one or more of positions 234, 235, and 237 according to EU numbering. In some embodiments, each of the antibody heavy chains comprises L234A, L235E, and G237A substitutions according to EU numbering. In some embodiments, the antibody comprises two antibody heavy chains, and wherein only one of the antibody heavy chains comprises H435R and Y436F substitutions according to EU numbering. In some embodiments, only one of the antibody arms comprises a heavy chain comprising F126C and C220V substitutions and a light chain comprising S121C and C214V substitutions according to EU numbering.In some embodiments, the bispecific antibody comprises two antibody heavy chains and two antibody light chains, wherein the VH domain of the first antibody heavy chain forms an antigen-binding domain with the VL domain of the first antibody light chain, wherein the VH domain of the second antibody heavy chain forms an antigen-binding domain with the VL domain of the second antibody light chain, wherein according to EU numbering, the first antibody heavy chain comprises F126C, C220V and T366W substitutions, wherein the first antibody light chain comprises S121C and C214V substitutions, and wherein the second antibody heavy chain comprises T366S, L368A, Y407V, H435R and Y436F substitutions. In some embodiments, the first antibody heavy chain and the second antibody heavy chain further comprise L234A, L235E and G237A substitutions according to EU numbering. In some embodiments, the first antibody heavy chain and the second antibody heavy chain comprise a human IgG1 Fc domain. In some embodiments, the Fc region is a human IgG1 or human IgG4 Fc region. In some embodiments, the Fc region is a human IgG1 Fc region comprising S239D and I332E substitutions according to EU numbering. In some embodiments, the Fc region is a human IgG1 Fc region comprising S239D, A330L, and I332E substitutions according to EU numbering. In some embodiments, the Fc region is a human IgG1 Fc region comprising G236A, S239D, A330L, and I332E substitutions according to EU numbering. In some embodiments, the Fc region is a human IgG4 Fc region comprising S228P substitutions according to EU numbering. In some embodiments, at least one or both of the antibody heavy chains are non-fucosylated or comprise reduced fucosylation. In some embodiments, the antibodies can be produced in a cell line in which α1,6-fucosyltransferase (Fu t8) or α-1,3-mannosyl-glycoprotein 2-β-N-acetylglucosaminyltransferase (MGAT1) is knocked out. In some embodiments, the antibodies can be produced in a cell line that overexpresses β1,4-N-acetylglucosamine transferase III (GnT-III). In other embodiments, the cell line also overexpresses Golgi μ-mannosidase II (ManII). In some embodiments, the antibodies can be produced in a cell line treated with a mannosidase I inhibitor, such as kifunine. In some embodiments, the individual is human.

[0050] In some embodiments, provided herein is a kit or article of manufacture comprising the antibody, multispecific binding molecule, or composition of any of the above embodiments and instructions for using the antibody, multispecific binding molecule, or composition according to the methods of any of the above embodiments.

[0051] It should be understood that one, some or all of the properties of the various embodiments described herein may be combined to form other embodiments of the present disclosure. These and other aspects of the present disclosure will become apparent to those skilled in the art. These and other embodiments of the present disclosure are further described by the following detailed description. BRIEF DESCRIPTION OF THE DRAWINGS

[0052] Figures 1A-1C Figure 2 shows the binding analysis of anti-human Dectin-1 antibody (clone 2M24) in human and monkey monocytes derived from peripheral blood mononuclear cells (PBMC) by flow cytometry. Single cells, live cells and CD14+ cells were gated to identify monocytes. Cells were incubated with 2M24 anti-Dectin-1 primary antibody or mIgG1 isotype control antibody, and then incubated with fluorescent anti-mouse secondary antibody. Primary antibody was used for serial dose titration. Figure 1A Shown is the binding analysis of anti-human Dectin-1 clone 2M24 in human monocytes. Figure 1B Shown is the binding analysis of anti-human Dectin-1 clone 2M24 antibody in cynomolgus monkey monocytes. Figure 1C Comparison of binding between the 2M24 clone and other Dectin-1 antibodies identified from immunization of ATX-Gx Alloy transgenic mice, as well as commercial anti-Dectin-1 antibodies, to human monocytes, HEK cells overexpressing human Dectin-1, and cynomolgus monkey monocytes is depicted. The anti-human Dectin-1 clone 2M24 antibody exhibits high affinity for human and cynomolgus monkey Dectin-1 expressed in monocytes and exhibits higher affinity than other anti-Dectin-1 antibodies, including commercial antibodies.

[0053] Figures 2A-2B Figure 3 shows phagocytosis of pHrodo-labeled polystyrene anti-mouse Fc IgG beads conjugated with anti-Dectin-1 antibody 2M24 or isotype control antibody by HEK-Blue hDectin-1a cells and human monocytes. Polystyrene anti-mouse Fc IgG beads (approximately 3.4 μm) were labeled with a pH-sensitive fluorescent dye (pHrodo red) and conjugated with Dectin-1 antibody 2M24 or isotype control. The beads were then incubated with cultured HEK-Blue hDectin-1a cells or human monocytes at a ratio of 1:2 (cell:bead). HEK-Blue hDectin-1a cells were labeled with the cell-permeable dye Calcein AM. Phagocytosis of the beads was monitored by IncuCyte live cell imaging. Phagocytosis was quantified using IncuCyte analysis software and expressed as the overlap of red object counts (pHrodo) and calcein-positive cells. Figure 2AShown are phagocytosis of beads in HEK-Blue hDectin-1a cells over 2.5 hours (top) and representative images of pHrodo-positive cells at 2.5 hours of phagocytosis (bottom). Figure 2B Shown are phagocytosis of beads in human monocytes over a 4-hour period (top) and representative images of pHrodo-positive cells at 2.5 hours of phagocytosis (bottom). In the representative images, engulfed beads fluoresce brightly within the phagosome.

[0054] Figures 3A-3B Binding of fully human 2M24 anti-Dectin-1 antibody (hIgG4) or isotype control antibody in HEK-BluehDectin-1a cells and primary human monocytes is shown. Figure 3A Binding analysis of the fully human 2M24 anti-Dectin-1 antibody to HEK cells is shown. Figure 3B Binding to primary human monocytes is shown. The primary antibody was used for serial dose titration, followed by a fluorescent secondary antibody raised against the primary antibody. The fully human 2M24 anti-Dectin-1 hIgG4 antibody binds to cells expressing Dectin-1 with high affinity.

[0055] Figure 4 Targeted phagocytosis of Dectin-1-expressing cells on pHrodo-labeled polystyrene biotin beads conjugated with fully human 2M24 anti-Dectin-1 antibody (hIgG4) or isotype control antibody is shown. Polystyrene biotin beads were labeled with pHrodo red and conjugated with anti-Dectin-1 antibody 2M24 or isotype control via streptavidin. The conjugated beads were mixed with cells at a ratio of 1:3 and phagocytosis of the beads was monitored by IncuCyte live cell imaging. PHrodo-biotin beads conjugated with streptavidin 2M24 anti-Dectin-1 hIgG4 antibody are shown for HEK-Blue hDectin-1a cells (top left), human monocytes (top right), and human macrophages (bottom). Fully human 2M24 anti-Dectin-1 antibody (hIgG4) promotes phagocytosis of cells expressing Dectin-1.

[0056] Figures 5A-5B Shown are the results of a secreted alkaline phosphatase reporter gene assay for Dectin-1 in HEK-Blue hDectin-1a cells. Figure 5AResults of a secretory alkaline phosphatase assay using immobilized fully human 2M24 anti-Dectin-1 antibody are shown. Fully human 2M24 (hIgG4) anti-Dectin-1 antibody or isotype control antibody was immobilized overnight in U-bottom polypropylene microtiter plates at a range of 0.1-10 μg per well. HEK-Blue hDectin-1a cells were then cultured for 22 hours, and alkaline phosphatase secretion in the supernatant was assessed at OD 630 nm. Figure 5B Shown are the results of a secretory alkaline phosphatase assay using bead-conjugated fully human 2M24 anti-Dectin-1 antibody. Biotin beads of 3 μm, 10 μm, and 16.5 μm sizes were conjugated to streptavidin 2M24 (hIgG4) anti-Dectin-1 antibody. The antibody-conjugated beads were mixed with HEK-Blue hDectin-1a cells for 22 hours, and the supernatant was assessed for alkaline phosphatase secretion at OD 630nm. Bars represent mean ± sd; n = 2 replicates. 2M24 (hIgG4) anti-Dectin-1 antibody, both immobilized and bead-conjugated, induced alkaline phosphatase secretion in HEK-Blue hDectin-1a cells.

[0057] Figures 6A-6B Shown are cytokine secretion from primary human macrophages stimulated with anti-Dectin-1 (15E2) antibody in solution. Primary human macrophages and primary monocytes were stimulated with 10 μg / ml 15E2 anti-Dectin-1 antibody or isotype antibody in solution for 24 hours, and TNFα and IL-6 secretion were assessed by ELISA analysis of the supernatants. Zymosan was used as a positive control for cytokine secretion. Bars represent mean ± SD; n = 2 replicates. Figure 6A Results are shown for primary human monocytes stimulated with soluble 15E2 anti-Dectin-1 antibody, whereas Figure 6B Results are shown for stimulated primary human macrophages.Soluble 15E2 anti-Dectin-1 antibody did not induce cytokine secretion in primary human monocytes and macrophages.

[0058] Figures 7A-7B Shown are cytokine secretion from human primary monocytes and PBMCs stimulated with immobilized 2M24 or 15E2 anti-Dectin-1 antibodies. Anti-Dectin-1 antibodies or isotype control antibodies were immobilized at 10 μg per well in U-bottom polypropylene microtiter plates overnight, followed by incubation of human monocytes or human PBMCs for 24 hours. TNFα, IL6, and IFNg secretion were assessed by ELISA analysis of the supernatants. Figure 7A shows cytokine secretion by human monocytes after stimulation with immobilized anti-Dectin-1 antibody. Figure 7BShown are cytokine secretion by cultured human PBMCs after stimulation. Bars represent mean ± SD; n = 2 replicates. The 2M24 anti-Dectin-1 antibody induced cytokine secretion in primary human monocytes and PBMCs and exhibited superior immunostimulation compared to the 15E2 Dectin-1 agonist antibody.

[0059] Figure 8 Shown are the results of a competition assay using the 12M4 anti-Dectin-1 antibody clone and the natural ligand for Dectin-1. HEK-Blue hDectin-1a cells were incubated on ice for 30 minutes with a 1 / 3 titration of the 2M24 (hIgG4) anti-Dectin-1 antibody or the commercial 15E2, 259931, and GE2 anti-Dectin-1 antibodies starting at 300 nM in the presence of 8 μg / ml biotin-laminarin. Binding of laminarin to Dectin-1 was assessed by flow cytometry using streptavidin-Alexa fluor 647. The 2M24 (hIgG4) anti-Dectin-1 antibody did not compete with the natural ligand for binding to Dectin-1.

[0060] Figure 9 A summary of the functional characterization of the 2M24 and 15E2 anti-Dectin-1 antibodies is depicted.

[0061] Figures 10A-10B A schematic diagram of the generation of bispecific antibodies by click chemistry is shown. Figure 10A Differential labeling of antibodies with MTA or FOL reagent is depicted. Figure 10B Covalent cross-linking of antibodies via specific MTA-FOL interactions is depicted.

[0062] Figure 11A Potential modes of activity employed by anti-Dectin-1 agonistic bispecific antibodies to eliminate target cancer cells are shown. These include immune stimulation, phagocytosis, neoantigen presentation, and activation of T and B lymphocytes of the adaptive immune system.

[0063] Figure 11B A list of potential targets for cancer cell depletion is shown.

[0064] Figures 12A-12B Shown are the characterization of a click-chemistry conjugated bispecific antibody comprising anti-Dectin-1 (clone 2M24) and anti-hCD70 arms. Figure 12A Shown are SDS-PAGE analyses of covalently conjugated antibody pairs (2M24 / anti-hCD20, 2M24 / anti-hCD70, and isotype control) under non-reducing and reducing conditions. Figure 12BShown are flow cytometry-based characterization of the binding of bispecific antibodies (2M24 / anti-hCD70 or isotype control) to Dectin-1-expressing HEK293 cells (upper left) and two renal cancer cell lines—A498 (upper right) and 786-0 (lower left). Figure 12B EC50 concentrations (nM) based on nonlinear regression fitting are also depicted (bottom right).The anti-Dectin-1 / anti-hCD70 bispecific antibody bound to cells expressing Dectin-1 or CD70 with an affinity of 1.8 nM or 12.34 nM, respectively.

[0065] Figure 13 The coupling of HEK293 cell lines expressing Dectin-1 and A498 renal cancer cell lines induced by 2M24 / anti-hCD70 bispecific antibodies is shown. Flow cytometric analysis of co-cultures of HEK293 cells (labeled with calcein green) and A498 cells (labeled with calcein red) in the presence of 2M24 / anti-hCD70 bispecific antibodies or isotype controls (left) is shown. Double positive signals (green + red +, squares) indicate the coupling of HEK293 and A498 cells. Coupling efficiency is also shown, which is quantified as the percentage of cells forming doublets with HEK293 cells relative to total target cells (A498) (right). Bars represent mean ± sd; n = 3 replicates. 2M24 / anti-hCD70 bispecific antibodies induce the coupling of HEK293 cell lines expressing Dectin-1 and A498 renal cancer cell lines.

[0066] Figures 14A-14B The coupling of Dectin-1-expressing cells and B cells induced by the anti-Dectin-1 / anti-hCD20 bispecific antibody is shown. Figure 14A The coupling of HEK293 cells expressing Dectin-1 and B cells induced by anti-Dectin-1 / anti-hCD20 bispecific antibodies is shown. Flow cytometric analysis of co-cultures of HEK293 cells (labeled with calcein green) and Raji cells (labeled with calcein red) in the presence of 2M24 / anti-hCD70 bispecific antibodies or isotype controls (left) is shown. Double positive signals (green + red +; box) indicate the coupling of HEK293 and Raji cells. Also shown is the coupling efficiency, which is quantified as the percentage of cells forming doublets with HEK293 cells relative to total target cells (Raji) (right). Bars represent mean ± sd; n = 2 replicates. Figure 14BShown are the results of a similar experiment conducted to evaluate the coupling of human M0 macrophages and Raji cells induced by the anti-Dectin-1 / anti-hCD20 bispecific antibody. Bars represent mean ± SD; n = 2 replicates. The 2M24 / anti-hCD20 bispecific induced the coupling of Dectin-1-expressing cells and CDC20-positive B cells (Raji cells).

[0067] Figure 15 Results of a secretory alkaline phosphatase reporter gene assay for Dectin-1 performed in HEK-Blue hDectin-1a cells using an anti-Dectin-1 / anti-CD20 bispecific antibody in the presence of Raji cells are shown. 2M24 (hIgG4) / anti-CD20 bispecific antibody was incubated with Raji cells and then washed twice to remove unbound bispecific antibody. Raji cells were then mixed with HEK-Blue hDectin-1a cells at a ratio of 200,000 Raji cells to 100,000 HEK cells for 22 hours. Secreted alkaline phosphatase in the supernatant was assessed at OD 630nm. Bars represent mean ± sd; n = 2 replicates. Raji cells coated with anti-Dectin-1 / anti-CD20 bispecific antibody induced alkaline phosphatase secretion in HEK-Blue hDectin-1a cells.

[0068] Figure 16 Induction of phagocytosis of Raji cells by HEK 293 cells expressing Dectin-1 by an anti-Dectin-1 / anti-hCD20 bispecific antibody is shown. Representative incucyte images (left) illustrating phagocytosis of Raji cells by HEK cells (arrows) at 16 hours versus 0 hours are shown. Yellow fluorescence indicates colocalization. The reduction of the calcein red signal in Raji cells at 16 hours indicates phagocytosis-mediated cell death. Quantification of the overlap or colocalization of HEK (calcein green) and Raji (calcein red) in the different treatment groups is shown (right). Pre-incubation of HEK cells with the ADCP inhibitor Latrunculin A blocked phagocytosis mediated by the 15E2 / anti-hCD20 bispecific antibody. (n=2 replicates).

[0069] Figure 17Shown is the coupling of Dectin-1-expressing cells and HER2-expressing cells induced by anti-Dectin-1 / anti-hHER2 bispecific antibodies. Flow cytometric analysis of co-cultures of HEK 293 cells expressing Dectin-1 (labeled with calcein green) and SKBR3 cells expressing HER2 (labeled with pHrodo red) in the presence of 15E2 / anti-hHER2 bispecific antibodies or isotype controls is shown (left). Double-positive signals (green + red +, boxes) indicate coupling of HEK293 and SKBR3 cells. Also shown is the coupling efficiency, which is quantified as the percentage of cells that form doublets with Dectin-1-expressing cells relative to total target cells (SKBR3) (right). Bars represent mean ± sd; n = 2 replicates. Anti-Dectin-1 / anti-hHER2 bispecific antibodies induce coupling of Dectin-1 and HER2-positive cancer cells.

[0070] Figure 18 Shown is the coupling of HEK293 cells expressing Dectin-1 and BaF3 cells expressing CD94 induced by anti-Dectin-1 / anti-hCD94 bispecific antibodies. Flow cytometric analysis of co-cultures of HEK293 cells (labeled with calcein green) and BaF3 cells (labeled with pHrodo red) in the presence of 2M24 / anti-hCD94 bispecific antibodies or isotype control is shown (left). Double-positive signals (green + red +; boxes) indicate coupling of HEK293 and BaF3 cells. Also shown is the coupling efficiency, which is quantified as the percentage of cells that form doublets with HEK293 cells relative to total target cells (BaF3) (right). Bars represent mean ± sd; n = 2 replicates. Anti-Dectin-1 / anti-hCD94 bispecific antibodies induce coupling of cells expressing Dectin-1 and CD94.

[0071] Figures 19A-19B Schematic representation of Fab 2M24-mSA or full-length 2M24-mSA bound to a biotinylated target antibody is shown. Figure 19A Chimeric fusions of monomeric streptavidin (mSA) and Fab 2M24 or full-length 2M24 are shown. mSA is genetically fused to Fab 2M24 or full-length 2M24. Figure 19B Conjugation of Fab 2M24-mSA or 2M24-mSA to a biotinylated target antibody is shown. The chimeric fusion was incubated with the biotinylated target antibody to generate a bispecific antibody comprising a Dectin-1 binding arm and a second arm that binds to a target receptor or protein of interest.

[0072] Figures 20A-20CBiochemical and functional characterization of the Fab 2M24-mSA fusion protein is shown. Figure 20A HPLC characterization of the recombinant Fab 2M24-mSA is shown. Figure 20B Shown is SDS-PAGE analysis of Fab 2M24-mSA purified under reducing conditions. Figure 20C The results show that Fab 2M24-mSA is stable and overexpresses human Dectin-1 (EC 50 Flow cytometric characterization of binding to HEK 293 cells expressing Dectin-1 with an affinity of 1.45 nM. Fab 2M24, fused to monomeric streptavidin, binds to cells expressing Dectin-1 with an affinity of 1.45 nM.

[0073] Figures 21A-21B Shown is the phagocytosis of pHrodo-labeled polystyrene biotin beads conjugated to Fab-2M24 anti-Dectin-1 antibody labeled with monomeric streptavidin (Fab-2M24-mSA). Figure 21A Shown are duplex formation with Fab-2M24-mSA conjugated to biotin beads and phagocytosis of beads by HEK-Blue hDectin-1a cells, assessed by flow cytometry. Figure 21B Phagocytosis of pHrodo-biotin beads (approximately 3 μm) conjugated to Fab-2M24-mSA assessed by IncuCyte real-time imaging (top), and representative images of pHrodo-positive cells (engulfed beads fluoresce bright red in phagosomes) versus no-bead controls at 3 hours of phagocytosis (bottom). Fab2M24-mSA fusion induces bead binding and phagocytosis by HEK 293 cells expressing Dectin-1.

[0074] Figures 22A-22D Shown are bispecific complexes containing Fab 2M24-mSA and target biotinylated antibody. Figure 22A ), biotinylated anti-hCD19 ( Figure 22B ), biotinylated anti-hCD70 ( Figure 22C ) or biotinylated anti-β-amyloid 1-42 ( Figure 22D ) HPLC analysis of Fab 2M24-mSA in complex. Each graph contains an overlay of the A280 traces for Fab 2M24-mSA alone, the target biotinylated antibody alone, and Fab 2M24-mSA in complex with the biotinylated target antibody.

[0075] Figure 23Shown is the coupling of HEK293 cells expressing Dectin-1 and Raji cells expressing CD20 induced by Fab 2M24-mSA / biotin anti-hCD20 bispecific antibody. Flow cytometric analysis of co-cultures of HEK293 (labeled with calcein green) and Raji (labeled with calcein red) in the presence of Fab 2M24-mSA / biotin anti-hCD20 bispecific antibody or isotype bispecific control is shown (left). Co-cultures were incubated at 4°C or 37°C. Double positive signals (green + red +; dotted squares) indicate coupling of HEK293 and Raji cells. Coupling efficiency is also shown, which is quantified as the percentage of cells forming doublets relative to total target cells (Raji) (right). Bars represent mean ± sd; n = 4 replicates. Fab 2M24-mSA / biotin anti-hCD20 bispecific antibody induced the coupling of HEK293 cells expressing Dectin-1 and Raji cells.

[0076] Figure 24 Schematic diagram of targeted phagocytosis of amyloid deposits in amyloidosis using a Dectin-1 agonistic bispecific antibody.

[0077] Figures 25A-25B A strategy for targeted depletion of mast cells using a Dectin-1 agonistic bispecific antibody is shown. Figure 25A Schematic diagram of mast cell depletion by Dectin-1 agonistic bispecific antibody. Figure 25B A list of potential targets for mast cell depletion is shown.

[0078] Figure 26 Phagocytosis of large (approximately 16.2 μm) pHrodo-labeled beads by human dendritic cells is shown. Figure 26 Shown are quantification of bead phagocytosis over 12 hours (left) and representative images of pHrodo-positive cells at 3 hours of phagocytosis (engulfed beads fluoresce bright red in phagosomes; right). Dectin-1 antibody promotes directed phagocytosis of beads in cultured monocyte-derived dendritic cells.

[0079] Figure 27 Schematic diagram of Dectin-1 agonistic bispecific antibodies targeting microbial depletion. Bispecific antibodies with Dectin-1-binding arms and microbial agent-binding arms are generated to target bacteria, viruses, or fungi (top). Dectin-1 bispecific antibodies utilize Dectin-1-expressing phagocytes to eliminate bacterial, viral, or fungal pathogens (bottom).

[0080] Figures 28A-28BBinding of a bispecific antibody composed of a Dectin-1 antibody (clone 15E2) conjugated to an anti-H3N2 hemagglutinin antibody (clone 12CA5) to H3N2 influenza virus and cells expressing Dectin-1 is shown. Figure 28A Figure 2 shows an ELISA-based binding analysis of an anti-Dectin-1 / anti-hemagglutinin bispecific antibody to H3N2 influenza virus. A 96-well microtiter plate was coated with H3N2 influenza virus particles and then incubated with monoclonal antibodies, bispecific antibodies, and isotype controls. After extensive washing, the primary antibody was detected with a secondary anti-mouse FcgR HRP antibody. Figure 28B Figure 2 shows flow cytometry analysis of binding of an anti-Dectin-1 / anti-hemagglutinin bispecific antibody to Dectin-1-expressing HEK cells. HEK cells were incubated with primary antibodies and then probed with secondary fluorescent antibodies raised against either anti-Dectin-1 (anti-mIgG2a APC) or hemagglutinin (anti-mIgG2b PB). The anti-Dectin-1 / anti-hemagglutinin bispecific antibody efficiently bound to H3N2 influenza virus and Dectin-1-expressing HEK cells.

[0081] Figures 29A-29B The use of anti-Dectin-1 antibodies to deliver antigens for vaccine development and the use of anti-Dectin-1 antibodies fused to target antigens for delivery to APCs ( Figure 29A ) or anti-Dectin-1 bispecific antibodies for targeted delivery of pathogens (e.g., cells, microorganisms, proteins, etc.) to APCs ( Figure 29B ) schematic diagram.

[0082] Figure 30 Figure 3 shows the phagocytosis of human dendritic cells on pHrodo-labeled polystyrene anti-mouse Fc IgG beads (approximately 3.4 μm) conjugated to Dectin-1 antibody (15E2) or isotype control antibody. Polystyrene anti-mouse Fc IgG beads were labeled with a pH-sensitive fluorescent dye (pHrodo red) and conjugated to Dectin-1 antibody or isotype control. The beads were then incubated with cultured monocyte-derived dendritic cells at a ratio of 1:3 (cell:bead). Phagocytosis of the beads was monitored by IncuCyte live cell imaging. Phagocytosis was quantified using IncuCyte analysis software and expressed as the total integrated intensity (sum of fluorescence intensity) of the red object (pHrodo) in the image. Figure 30 Shown are quantification of bead phagocytosis over 9 hours (top) and representative images of pHrodo-positive cells at 3 hours of phagocytosis (engulfed beads fluoresce brightly red in phagosomes; bottom).

[0083] Figures 31A-31CShown is the phagocytosis of SARS-CoV-2 spike protein-coated beads by HEK 293 cells expressing Dectin-1. Figure 31A Schematic diagram of the experiment. Beads coated with the spike protein from SARS-CoV-2 were coupled to HEK293 cells expressing Dectin-1 via an anti-Dectin-1 bispecific antibody containing a Dectin-1 protein-binding arm and a spike protein-binding arm. Figure 31B Shown are flow cytometric characterization of engagement of effectors (HEK 293 cells) and targets (spike-coated beads) by bispecific antibodies and isotype controls (Panel A), and quantification of coupling efficiency based on the doublet population (Panel B). Figure 31C Shown is the phagocytosis of SARS-CoV-2 spike protein-coated beads by HEK 293 cells in a co-culture experiment. Phagocytosis of pHrodo-labeled beads was monitored by changes in pHrodo fluorescence induced by acidic pH in the phagosome. Figure 31C Shown are quantification of phagocytosis (left), quantified by Incucyte analysis software and expressed as the overlap of red object counts (pHrodo) and calcein-positive cells, and representative images of pHrodo-positive cells at 2 hours of phagocytosis (engulfed beads fluoresce bright red in phagosomes; right).

[0084] Figure 32A and 32B Bispecific antibody designs are shown for human bispecific antibodies (eg, human IgG1 bispecific antibodies) targeting Dectin-1 and a disease target or antigen. Figure 32A One arm (2M24A.X) with VH domain A and VL domain B targets human Dectin-1, while the other arm (2M24B.X) with VH domain C and VL domain D targets a disease target or antigen. Figure 32B Provided is an exemplary mechanism of action diagram of an anti-Dectin-1 bispecific antibody with an active Fc domain, which targets hDectin-1 on myeloid cells (via the first arm), antigens on target cells / pathogens (via the second arm), and Fc receptors on myeloid and NK cells, triggering strong immune stimulation and phagocytosis.

[0085] Figure 33A and 33B Bispecific antibodies with one arm targeting hDectin-1 and the other targeting hCD20 (using the variable domain of rituximab) are shown to bind to cells expressing either human Dectin-1 or human CD20. Figure 33A(Upper panel) shows the binding of a bispecific antibody targeting hDectin-1 and hCD20 (2M24 / CD20) or a bispecific antibody targeting hDectin-1 and RSV (2M24 / RSV) to HEK293 cells stably expressing human Dectin-1 assessed by flow cytometry. Figure 33A (Lower panel) shows the binding of bispecific antibody 2M24 / RSV hIgG1-FITC conjugate and 2M24 bivalent hIgG1-FITC conjugate to PBMCs assessed by flow cytometry. Figure 33B Binding of rituximab (human IgG1), 2M24 / CD20 with active human IgG1 Fc, 2M24 / CD20 with inert human IgG1 Fc, 2M24 / RSV with active human IgG1 Fc, or 2M24 / RSV with inert human IgG1 Fc to the CD20-expressing B-cell lymphoma Raji cell line is shown.

[0086] Figure 34A and 34B It was shown that a bispecific antibody targeting hDectin-1 and hCD20 (2M24 / CD20) induces the association of cells expressing Dectin-1 and CD20. Figure 34A To assess the coupling of HEK293 cells expressing Dectin-1 (effector cells) and Raji cells expressing CD20 (target cells), cells were differentially labeled with either calcein green (effector cells) or calcein red (target cells) dyes. Labeled cells were co-cultured and treated with hIgG1 inert 2M24 / CD20 or 2M24 / RSV (control) bispecific antibodies to induce effector cell: target cell coupling. Double positive staining (calcein green +, calcein red +, squares) indicates successful coupling of effector cell: target cells. Figure 34B : Dose titration of bispecific antibodies in effector cell:target cell co-cultures. Coupling efficiency was quantified as the percentage of cells bound or coupled to effector cells relative to total target cells.

[0087] Figure 35A and 35B We show that a bispecific antibody targeting hDectin-1 and hCD20 (2M24 / CD20) with active hIgG1 Fc does not induce monocyte depletion through antibody-dependent cellular cytotoxicity (ADCC) or antibody-dependent cellular phagocytosis (ADCP). Figure 35A ) and donor 77( Figure 35B) were treated with increasing concentrations of 2M24 / CD20 bispecific antibody (hIgG1 active or inert isotype) and rituximab for 24 hours and subsequently analyzed by flow cytometry to quantify the levels of remaining viable CD14+ monocytes (as a percentage of isotype control).

[0088] Figure 36A and 36B It was shown that a bispecific antibody targeting hDectin-1 and hCD20 (2M24 / CD20) with active hIgG1 Fc caused better B cell depletion than rituximab. Figure 36A ) and 84( Figure 36B ) PBMCs were treated with increasing concentrations of the indicated antibodies for 24 h and subsequently analyzed by flow cytometry to quantify the levels of remaining viable CD19+ B cells (reported as the percentage of B cells in isotype control-treated PBMCs).

[0089] Figure 37A and 37B Rituximab induced higher B cell tailoring (CD19 downregulation) compared to the 2M24 / CD20 active IgG1 bispecific antibody. B cell numbers from two healthy donors, donor 83 ( Figure 37A ) and donor 84( Figure 37B The effects of the 2M24 / CD20 bispecific antibody and rituximab on CD19 expression on B cells were assessed using the mean fluorescence intensity (MFI) of CD19 staining using anti-CD19 (BV605 conjugated). EC50 values ​​were calculated based on nonlinear regression analysis.

[0090] Figure 38Figure 24 shows the difference cytokine release induced by 2M24 / CD20 active IgG1 bispecific antibody compared with rituximab. In the supernatant separated from the healthy donor PBMC treated with 2M24 / CD20 active hIgG1 bispecific antibody, rituximab or isotype control, cytokine quantification based on ELISA (mesoscale discovery) is carried out. PBMC is stimulated overnight with antibody, and then supernatant is analyzed with MSD. The cytokine tested is IFNγ, IL-12p70, IL-6, TNFα, IL-1β, IL-4, IL-13, IL-10 and IL-8. Each figure shows that cytokine secretion (in pg / mL) changes with the antibody for treatment (from left to right: 2M24 / CD20 hIgG1 bispecific antibody, 2M24 / RSV hIgG1 bispecific antibody, rituximab hIgG1 and isotype control hIgG1).

[0091] Figure 39A and 39B It was shown that in co-cultures of human macrophages and GFP-expressing Raji B cells, the 2M24 / CD20 hIgG1 (active isotype) bispecific antibody induced better B cell depletion and lower CD19 trimming compared to rituximab. Figure 39A : Flow cytometric analysis of co-cultures of human macrophages and Raji-GFP cells (3:1 ratio) in the presence of 2M24 / CD20 hIgG1 (active isotype) bispecific antibody, 2M24 / RSV control, fucosylated rituximab, or isotype hIgG1 control. Co-cultures were incubated at 37°C for 24 hours and then stained with PE a-CD206 Ab to mark macrophages and BV-605a-CD19 antibody to mark Raji cells. The number of remaining live / Raji-GFP+ cells was assessed at the end of the experiment. Primary antibodies were used for serial dose titration. Figure 39B : Assessment of CD19 on Raji-GFP cells after 24 hours. B cell receptor manipulation is shown as a decrease in CD19 MFI in the presence of anti-Dectin-1 / anti-hCD20 bispecific antibody or rituximab.

[0092] Figures 40A-40CIt was shown that the 2M24 / CD20 active IgG1 bispecific antibody induced better tissue B cell depletion in single cell suspensions of renal cancer biopsies than rituximab. Single cell suspensions from two renal cancer tissue biopsies were analyzed by flow cytometry in the presence of 2M24 / CD20 hIgG1 (active or inert) bispecific antibody, 2M24 / RSV hIgG1 control, fucosylated rituximab and corresponding isotype controls. Renal cancer tissue biopsies were dissociated into single cell suspensions and treated with primary antibodies (2 μg / ml) for 24 hours at 37°C. Immune cell populations were analyzed by flow cytometry. Cells were initially gated for live cells and further divided into CD45+ cells (immune cells) and CD45- cells (non-immune cells), and then CD19+ (B cells) and CD3+ (T cells) cells were identified within the CD45+ cell population ( Figure 40A and 40B The number of remaining B cells was assessed using anti-CD19 antibody and expressed as a percentage relative to the CD45+ immune cell population ( Figure 40C ).

[0093] Figures 41A-41C Anti-Dectin 1 antibody (clone 2M24) was shown to induce Dectin 1 aggregation and TNFα secretion by human macrophages. Cytokine secretion was tested by cultured macrophages and single cell suspensions of renal cancer biopsies stimulated with immobilized anti-Dectin-1 antibody (clone 2M24) or 2M24 / CD20 bispecific antibody. Anti-Dectin-1 antibody (clone 2M24), isotype control, or 2M24 / CD20 bispecific antibody were immobilized at 10 μg per well in U-bottom polypropylene microtiter plates overnight, and then human monocyte-derived macrophages ( Figure 41A and 41B ) or single cell suspensions from renal cancer biopsies ( Figure 41C The cells were cultured for 24 hours and the supernatant was evaluated for TNFα secretion by ELISA. As a positive control, the cells were stimulated with zymosan.

[0094] Figure 42Figure 20 shows that immobilized anti-Dectin 1 antibody (clone 2M24) promotes immune stimulation in single cell suspensions of renal cancer biopsies. Single cell suspensions from renal cancer biopsies were treated with immobilized anti-Dectin-1 antibody (clone 2M24) or isotype control hIgG4 antibody for 24 hours. The release of various cytokines in the supernatant was analyzed by ELISA, including IFNγ, IL-6, TNFα, IL-23, IL-12p70, IL-10 and IL-13. Each figure shows that the amount (pg / mL) of cytokines changes with antibody treatment. The results of using renal cancer donor 3 (left) or donor 4 (right) to treat with anti-Dectin-1 antibody (clone 2M24) or isotype control hIgG4 antibody are shown.

[0095] Figure 43 The effect of the 2M24 / CD20 bispecific antibody on CD16 expression in human NK cells is shown compared to rituximab or an isotype control (RSV). The results show that CD16 antigen levels on NK cells are better maintained in PBMCs treated with the 2M24 / CD20 bispecific antibody compared to rituximab.

[0096] Figure 44 The effect of the 2M24 / CD20 bispecific antibody on CD19 expression in human B cells is shown compared to rituximab or an isotype control (2M24 / RSV bispecific antibody). The results show that CD19 antigen levels are better maintained on B cells treated with the 2M24 / CD20 bispecific antibody than with rituximab.

[0097] Figure 45 Depletion of human B cells by a 2M24 / CD20 bispecific antibody derived from rituximab or a 2M24 / CD20 bispecific antibody derived from obinutuzumab was shown. The results showed that the 2M24 / CD20 bispecific antibody derived from the rituximab arm depleted B cells better than the bispecific antibody derived from obinutuzumab.

[0098] Figure 46 Shown is the design of an exploratory study of the safety and efficacy of the 2M24 / CD20 bispecific antibody in non-human primates.

[0099] Figure 47 and 48 Depletion of circulating B cells in cynomolgus monkeys by the 2M24 / CD20 hIgG1 bispecific antibody produced in cells treated with kifunine (KIF) is shown. Figure 47: B cell depletion in monkeys treated with 5 mg / kg 2M24 / CD20 hIgG1 KIF (top) or 2M24 / CD20 hIgG1 inert (bottom). Figure 48 : B cell depletion in monkeys treated with 5 mg / kg rituximab hIgG1 KIF.

[0100] Figure 49A and 49B Depletion of tissue-resident B cells in cynomolgus monkeys by the 2M24 / CD20 hIgG1 bispecific antibody produced in cells treated with kifunine (KIF) is shown. Figure 49A : B cell depletion in the bone marrow of monkeys treated with 5 mg / kg 2M24 / CD20 hIgG1 KIF or rituximab hIgG1 KIF. Figure 49B : B cell depletion in lymph nodes of monkeys treated with 5 mg / kg 2M24 / CD20hIgG1KIF or rituximab hIgG1KIF.

[0101] Figure 50 Ex vivo depletion of B cells from cynomolgus monkey PBMCs is shown.

[0102] Figure 51 The format of a bispecific molecule is shown, which uses knobs-in-hole technology to pair an anti-CD20 conventional half antibody with an anti-Dectin-1 single-chain variable fragment (scFv) Fc fusion arm (2M24 scFv / CD20). H: 2M24 VH domain; L: 2M24 VL domain.

[0103] Figures 52A-52C Shown are the purification and functional characterization of the 2M24 / CD20 bispecific antibody. Figure 52A Purification of the molecules by size exclusion chromatography (SEC) is shown. Figure 52B It was shown that the purified bispecific antibodies promoted targeted immune stimulation as assessed in an NFκB reporter assay. Figure 52C Depletion of human B cells by the 2M24 scFv / CD20 bispecific antibody is shown.

[0104] Figures 53A-53C Shown is the development and characterization of an anti-Dectin-1 (2M24) / anti-Trop-2 bispecific antibody. Figure 53A Purification of the 2M24 / Trop-2 bispecific antibody by SEC is shown (left). The purified antibody was analyzed by SDS-PAGE under non-reducing (NR) or reducing (R) conditions (right). Figure 53B and 53C The molecule was shown to bind with high affinity to HEK cells expressing Dectin-1 ( Figure 53B) and moderate affinity binding to the Trop-2 expressing A431 cancer cell line ( Figure 53C ).

[0105] Figure 54 Trop-2 expression levels on cancer cells are shown.

[0106] Figures 55A-55D The 2M24 / Trop-2 bispecific antibody showed the interaction with the Trop-2 expressing cell line HeLa ( Figure 55A )、BxPC-3( Figure 55B )、SiHa( Figure 55C ) and Capan-2( Figure 55D The EC50 for binding to each cell line is shown, as determined using four-parameter logistic (4PL) nonlinear regression.

[0107] Figure 56A and 56B Depletion of Trop-2 expressing cell lines using the 2M24 / Trop-2 bispecific antibody is shown ( Figure 56A Middle are SKBR3 cells; Figure 56B A431 cells in the middle).

[0108] Figure 57A and 57B Trop-2 and Dectin-1 expression in lung cancer biopsies is shown.

[0109] Figure 58 Depletion of Trop-2-positive cancer cells in lung cancer biopsies is shown.

[0110] Figure 59A Activity of the 2M24 / Trop-2 bispecific antibody in an NFκB reporter gene assay is shown.

[0111] Figures 59B-59E The 2M24 / Trop-2 bispecific antibody was shown to promote antigen presentation and T cell activation. Figure 59B A schematic diagram of the analysis setup is provided. Figure 59C In this study, macrophages and SKBR3 breast cancer cells were co-incubated in the presence of 2M24 / Trop-2hIgG1 or the control 2M24 / RSV hIgG1 bispecific antibody. Phagocytosis or depletion of SKBR3 cells was assessed by flow cytometry by staining for EPCAM expression on SKBR3 cells. Data are reported relative to the control bispecific 2M24 / RSV. Figure 59D IFNγ levels in the supernatant were quantified using the BD OptiEIA kit. Figure 59EThe expression of CD69 (an early activation marker) on T cells was assessed by flow cytometry. Data are reported relative to total CD3+ T cells.

[0112] Figure 60A and 60B Shown is the design and production of the 2M24 / fibronectin-4 bispecific antibody. Figure 60A A schematic of the bispecific molecule is shown. Figure 60B Purification of the bispecific antibody using Protein A chromatography is shown.

[0113] Figure 61A and 61B Cancer cell lines ( Figure 61A ) and cancer cells from primary tumor biopsies ( Figure 61B ) on adhesion protein-4 expression.

[0114] Figure 62 Binding of the 2M24 / fibronectin-4 bispecific antibody to HEK cells expressing Dectin-1 (top) or A431 cells expressing fibronectin-4 (bottom) is shown.

[0115] Figure 63 Figure 2 shows stimulation of Dectin-1 by the 2M24 / nectin-4 bispecific antibody in an NFκB reporter gene assay. The top panel shows a schematic diagram of the assay. The bottom panel shows the results quantified based on SEAP levels in the culture medium.

[0116] Figure 64A and 64B Depletion of cancer cells expressing fibronectin-4 by the 2M24 / fibronectin-4 bispecific antibody is shown. Figure 64A Phagocytosis / depletion detected by flow cytometry is shown. Figure 64B Depletion relative to RSV control is shown.

[0117] Figures 65A-65C The 2M24 / 11-1F4 bispecific antibody was shown to bind to light chain amyloid. Figure 65A Purification of the parent anti-amyloid antibody 11-1F4 (top) and the 2M24 / 11-1F4 bispecific antibody (bottom) by SEC is shown. Figure 65B and 65C Shown by Octet, 11-1F4 parent antibody ( Figure 65B ) or 2M24 / 11-1F4 bispecific antibody ( Figure 65C ) to recombinant light chain amyloid proteins from different patients (AL30, AL47, AL48, and AL55).

[0118] Figure 66Phagocytosis of light chain amyloid fibrils by monocytes is shown.

[0119] Figure 67 The ability to modulate the functional activity of a bone marrow cell engager of the present disclosure having an arm that binds Dectin-1 and an arm that binds a target of interest and an Fc region is demonstrated.

[0120] Figure 68A and 68B Characterization of 2M24 variant binding to Dectin-1 is shown. Figure 68A A schematic diagram of the assay used to measure binding via a biosensor (Octet) is provided. Figure 68B Variant off-rates fitted to the biosensor data are shown.

[0121] Figure 69A and 69B Shown are the effects of modulating the Fc region (in this example, KIF-treated hIgG1 and hIgG4) on B cell depletion using PBMCs obtained from two donors using bone marrow cell engagers targeting hDectin-1 (via 2M24) and hCD20. The hIgG4 Fc includes the S228P mutation (numbering according to the EU index).

[0122] Figures 70A-70D The effect of modulating the Fc region (in this case, mutations that enhance Fcγ receptor binding) by a bone marrow cell engager targeting hDectin-1 (via 2M24) on binding to the Fcγ receptor CD16a F variant using ELISA is shown. The Fc mutations used are as follows. SDIE: hIgG1 Fc with S239D and I332E mutations. SDALIE: hIgG1 Fc with S239D, A330L, and I332E mutations. GAALIE: hIgG1 Fc with G236A, S239D, A330L, and I332E mutations. NF: non-fucosylated. All numbering is according to the EU index. The Fc region also includes knob / hole and RF mutations on one Fc chain to facilitate purification (H435R and Y436F in the CH3 domain as described by Jendeberg, L. et al. (1997, J. Immunological Meth., 201: 25-34)).

[0123] Figure 71 Shown is how the binding affinity of 2M24 variants with alanine substitutions was compared to the parent antibody using a biosensor assay.

[0124] Figures 72A-72C Characterization of 2M24 variants 2M24.116 and 2M24.119 is shown. Figure 72AIt was shown that the 2M24 variant in the bispecific antibody with an anti-Trop2 binding arm displayed similar potency to the parental 2M24 / Trop2 bispecific antibody in a SEAP reporter gene assay. Figure 72B It is shown that the 2M24 / Trop2, 2M24.116 / Trop2 and 2M24.119 / Trop2 bispecific antibodies exhibited similar binding to Trop2-expressing A431 cells. The EC50 value for each tested antibody is shown. Figure 72C It is shown that 2M24.116 and 2M24.119 show approximately equivalent binding to HEK cells expressing Dectin-1, and the 2M24 / Trop2, 2M24.116 / Trop2, and 2M24.119 / Trop2 bispecific antibodies show similar binding to HEK cells expressing Dectin-1. The EC50 value for each antibody tested is shown.

[0125] Figure 73 Figure 2 shows a diagram of a bispecific binding protein targeting Dectin-1 (e.g., using 2M24 variable domains) and a target of interest, comprising disulfide engineering to drive the correct pairing of the heavy and light chain variable domains. A traditional bispecific antibody format (left) and a format in which one arm (i.e., the arm that binds Dectin-1) is an scFv format (right) are shown. The heavy chain is paired with a knob-in-hole mutation. In the Dectin-1 binding arm, the cysteine ​​that forms the natural disulfide bond between the heavy chain and the light chain has been removed, and cysteine ​​substitutions have been introduced to produce non-natural disulfide bonds. The arm that binds the target of interest has a natural disulfide bond, so the variable domains of each arm can be distinguished by the disulfide bond positions.

[0126] Figure 74A and 74B Alignments between the 2M24 VH domain and the CTX-2026 VH domain, and between the 2M24 VL domain and the CTX-2026 VL domain are shown. Intrachain disulfide bonds are shown in solid lines; interchain disulfide bonds introduced by cysteine ​​substitutions in the 2M24 VH and VL domains are shown in dashed lines. Figure 74A P1 substitution is shown; Figure 74B P2 substitutions are shown. The depicted sequence corresponds to 2M24 P1 VH ( Figure 74A SEQ ID NO: 213, 2M24 P1 VL ( Figure 74A SEQ ID NO: 214, 2M24 P2 VH ( Figure 74B SEQ ID NO: 215, 2M24P2 VL ( Figure 74BSEQ ID NO: 216, CTX-2026VH ( Figure 74A and 74B SEQ ID NO: 217 and CTX-2026VL ( Figure 74A and 74B SEQ ID NO: 218 of 6XLQ_C).

[0127] Figure 75A Results from a SEAP secretion assay using hDectin-1 expressing HEK cells with a SEAP Dectin-1 reporter gene and Raji cells (expressing CD20) are shown. Bispecific antibodies targeting Dectin-1 and CD20 were assayed using DuetMab substitution to drive the heavy / light chain pairing (Duet), 2M24P1 VH and VL domains (hG1 SS P1), 2M24 P2 VH and VL domains (hG1 SSP2), a control 2M24 / RSV bispecific antibody, and a control 2M24 antibody. OD values ​​based on the SEAP reporter gene in hDectin-1 expressing HEK cells. 630 Tracking was performed as a function of antibody concentration.

[0128] Figure 75B Shown are the results of a B cell depletion assay using healthy donor PBMCs from two donors (left and right). The ability of a bispecific antibody (one arm of which has the 2M24 P1 VH and VL domains and the other arm has an anti-CD20 binding domain (active hIgG1 Fc)) to deplete B cells was compared to an isotype control RSV antibody. The graph shows the level of remaining live CD19+ B cells (reported as % B cells in isotype control-treated PBMCs) after 24 hours of incubation as a function of antibody concentration.

[0129] Figure 76A Protein A purification of 2M24 / CD20 bispecific binding proteins is shown, wherein the 2M24 arms are in scFv format (format as shown on the right). Bispecific binding proteins with the parental 2M24 scFv are compared to bispecific binding proteins with the 2M24 P1 variant scFv. The percentage of each species purified as oligomers versus monomers is depicted for each binding protein. 60-70% of the parental 2M24 scFv / CD20 bispecific antibody was in monomeric form, compared to over 96% of the 2M24 P1 variant scFv / CD20 bispecific antibody in monomeric form, indicating that the disulfide variant is more stable / less prone to oligomerization during Protein A affinity purification.

[0130] Figure 76BBinding of the 2M24 / CD20 bispecific binding protein to hDectin-1 expressing HEK cells (top) or CD20 expressing Raji cells (bottom) is shown compared to the secondary antibody alone. A4: 2M24 parental VH and VL domains. A37: 2M24P1 variant VH and VL domains.

[0131] Figure 76C Activity of the 2M24 / CD20 bispecific binding protein in a SEAP reporter gene assay is shown using a 1:1 ratio of hDectin-1-expressing HEK cells (carrying the SEAP Dectin-1 reporter gene) to Raji cells (expressing CD20). A4: 2M24 parental VH and VL domains. A37: 2M24 P1 variant VH and VL domains. B01: mIgG2a negative control.

[0132] Figure 76D The ability of 2M24 / CD20 bispecific binding proteins with 2M24 arms in scFv format (parental 2M24 or P1 variant 2M24 variable domain) to deplete B cells in human PBMCs from two healthy donors (left and right) was compared to isotype controls.

[0133] Figure 76E Shown is the abundance of oligomers versus monomers in Protein A purifications of 2M24 / CD20 bispecific binding proteins with the 2M24 arms in scFv format (parental 2M24) (top left) or 2M24 / CD20 bispecific binding proteins with the 2M24 arms in scFv format (P1 variant 2M24) (top right) after 1 week at 5° C. or 25° C. The stability (depicted as % monomeric species) of parental 2M24 and P1 variant 2M24 at 5° C. and 25° C. (bottom) is shown.

[0134] Figure 77 Shown is the relationship between B cell depletion (CD19+% of CD45+ cells) and antibody concentration in human PBMCs from two healthy donors (left and right) after 24 h incubation with 2M24 / CD20 bispecific binding protein having human IgG4, human IgG1 or afucosylated human IgG1 Fc region compared to isotype control. DETAILED DESCRIPTION

[0135] Several aspects are described below in conjunction with example applications for illustration. It should be understood that many specific details, relationships, and methods have been described to provide a comprehensive understanding of the features described herein. However, those skilled in the relevant art will readily recognize that the features described herein can be practiced without one or more specific details or using other methods. The features described herein are not limited by the actions or event sequences shown, as some actions can occur in different orders and / or simultaneously with other actions or events. In addition, not all actions or events shown need to be implemented according to the methods of the features described herein.

[0136] Unless the context clearly indicates otherwise, as used herein, the singular forms "a," "an," and "the" are intended to include the plural forms as well. Furthermore, if the terms "including," "includes," "having," "has," "with," or variations thereof are used in the detailed description and / or claims, such terms are intended to be inclusive in a manner similar to the term "comprising." As used herein, the term "comprising" is synonymous with "including" or "containing" and is inclusive or open-ended.

[0137] Unless otherwise indicated, any reference to "or" herein is intended to encompass "and / or." As used herein, the term "about" with respect to a number means plus or minus 10% of that number. The term "about" with respect to a range means the range with 10% less than the lower value and 10% plus the upper value.

[0138] I. Antibodies and Multispecific Binding Proteins

[0139] In certain aspects, the present disclosure provides antigen binding domains, antibodies and antibody fragments that bind to human Dectin-1, and multispecific (e.g., bispecific) binding molecules comprising them. In some embodiments, provided herein are anti-Dectin-1 antigen binding domains 2M24 and variants thereof, which are described in International Application No. PCT / US2021 / 071752, filed October 6, 2021.

[0140] In some embodiments, antibody and immunoglobulin are used interchangeably and are used herein in the broadest sense and encompass a variety of antibody structures, including but not limited to monoclonal antibodies (e.g., full-length or intact monoclonal antibodies), polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), antibody fragments, and single domain antibodies (as described in more detail herein), so long as they exhibit the desired antigen-binding activity.

[0141] In some embodiments, an antibody (immunoglobulin) refers to a protein having a structure substantially similar to that of a natural antibody, or a protein having a heavy chain and a light chain variable region having a structure substantially similar to that of a natural heavy chain and light chain variable region. Natural antibodies refer to naturally occurring immunoglobulin molecules with different structures. For example, the IgG class natural immunoglobulin is a heterotetrameric glycoprotein of about 150,000 daltons consisting of two light chains and two heavy chains connected by disulfide bonds. From N-terminus to C-terminus, each heavy chain has a variable region (VH), also referred to as a variable heavy chain domain or a heavy chain variable domain, followed by three constant domains (CH1, CH2, and CH3), also referred to as a heavy chain constant region. Similarly, from N-terminus to C-terminus, each light chain has a variable region (VL), also referred to as a variable light chain domain or a light chain variable domain, followed by a constant light chain (CL) domain, also referred to as a light chain constant region. The subunit structure and three-dimensional configuration of different classes of immunoglobulins are well known, and are generally described in, for example, Abbas et al., 2000, Cellular and Mol and Kindt et al., Kuby Immunology, 6th edition, WH Freeman and Co., page 91 (2007). Depending on the amino acid sequence of the heavy chain constant domain, antibodies (immunoglobulins) can be designated as different classes. Antibodies are mainly divided into five classes: α (IgA), δ (IgD), ε (IgE), γ (IgG) or μ (IgM), some of which can be further divided into subtypes, such as γ1 (IgG1), γ2 (IgG2), γ3 (IgG3), γ4 (IgG4), α1 (IgA1) and α2 (IgA2). Based on the amino acid sequence of its constant domain, the light chain of antibody can be designated as one of two types (called κ and λ). Immunoglobulin is essentially composed of two Fab molecules and an Fc domain, connected via immunoglobulin hinge region.

[0142] In some embodiments, Fc, Fc region or Fc domain refers to the C-terminal region of the antibody heavy chain containing at least a portion of the constant region. The term includes native Fc region and variant Fc region. Fc can refer to the last two constant region immunoglobulin domains (e.g., CH2 and CH3) of IgA, IgD and IgG, the last three constant region immunoglobulin domains of IgE and IgM, and optionally, all or part of the flexible hinge at the N-terminus of these domains. For IgA and IgM, Fc may include a J chain. The IgG Fc region includes IgG CH2 and IgG CH3 domains, and in some cases, includes a hinge. Unless otherwise indicated herein, the numbering of the amino acid residues in the Fc region or constant region is according to the EU numbering system, also referred to as the EU index, as in Kabat et al., Sequences of Proteins of Immunological Interest, 5th edition Public Health Service, National Institutes of Health, Bethesda, Md., 1991. Human IgG Fc domains are particularly useful in the present disclosure, and may be Fc domains from human IgG1, IgG2, or IgG4.

[0143] As is known in the art, the variable domains of the heavy and light chains of antibodies (VH and VL, respectively) generally have a similar structure, wherein each domain comprises four conserved framework regions (FRs) and three hypervariable regions (HVRs). (See, e.g., Kindt et al., Kuby Immunology, 6th edition, WH Freeman and Co., page 91 (2007)). Framework (or "FR" as used herein) may refer to variable domain residues other than CDR residues. The FR of a variable domain is generally composed of four FR domains: FR1, FR2, FR3, and FR4. Thus, HVR and FR sequences generally appear in the following sequence in VH (or VL): FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4. In some embodiments, FR1, FR2, FR3, and / or FR4 of the present disclosure refer to human framework regions, i.e., human framework regions of a VH domain or a VL domain.

[0144] In some embodiments, the antigen binding domain, antibody or fragment comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; wherein the VH domain comprises the amino acid sequence QVQLVQSGAEVKKPGASVKVSCKSSGYTFTX1YYIHWVRQAPGQGLEWMGWINPNSGX2TNYAQKFQGRITMTRDTSISTAYLELSRLRSDDTAVFYCAX3X4X5X6X7X8X9X10 X 11 X 12 WGQGTLVTVSS, wherein X1 is D, A or G; wherein X2 is D, A or G; wherein X3 is R, A or G; wherein X4 is N, A or G; wherein X5 is S, A or G; wherein X6 is A or G; wherein X7 is S, A or G; wherein X8 is Y, A or G; wherein X9 is S, A or G; wherein X 10 is F, A or G; where X 11 is A or G; and where X 12 is Y, A or G (SEQ ID NO:63); and wherein the VL domain comprises the amino acid sequence DIQMTQSPSS VSASVGDRVTITCRASQGISSWLAWYQQKPGKAPKLLIFGASSLQSGVPSRFSGSGSGTDFTLTVSSLQPEDFATYYCX1X2AX3X4X5X6X7X8FGPGTKVDIE, wherein X1 is Q, A or G; X2 is Q, A or G; X3 is F, Y, A or G; wherein X4 is S, A or G; wherein X5 is F, A or G; wherein X6 is P, A or G; wherein X7 is F, A or G; and wherein X8 is T, A or G (SEQ ID NO:65). In some embodiments, the antigen binding domain, antibody, or fragment does not include a CDR-H1 comprising the amino acid sequence of DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence of WINPNSGDTNYAQKFQG (SEQ ID NO: 2), a CDR-H3 comprising the amino acid sequence of NSGSYSFGY (SEQ ID NO: 3), a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQA YSFPFT (SEQ ID NO: 6). In some embodiments, the VH domain comprises 1, 2 or fewer, 3 or fewer, 4 or fewer, or 5 or fewer substitutions compared to the amino acid sequence of SEQ ID NO: 62; and / or wherein the VL domain comprises 1, 2 or fewer, 3 or fewer, 4 or fewer, or 5 or fewer substitutions compared to the amino acid sequence of SEQ ID NO: 64. In some embodiments, the antigen binding domain, antibody, or fragment binds to human Dectin-1 expressed on the surface of a cell with an EC50 of less than 2 nM; is capable of binding to human or cynomolgus monkey Dectin-1; and / or does not compete with the natural ligand of human Dectin-1.

[0145] In some embodiments, the antigen binding domain, antibody or fragment comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; wherein the VH domain comprises: a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1) or AYYI (SEQ ID NO: 16); a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2) or WINPNSGATNYAQKFQG (SEQ ID NO: 19); and a CDR-H3 comprising an amino acid sequence selected from the group consisting of NSGSYSFGY (SEQ ID NO: 3), ASGSYSFGY (SEQ ID NO: 22), NSGSASFGY (SEQ ID NO: 24), NAGSYSFGY (SEQ ID NO: 27), NSASYSFGY (SEQ ID NO: 29), NSGAYSFGY (SEQ ID NO: 31), NSGSYAFGY (SEQ ID NO: 33), NSGSYSAGY (SEQ ID NO: 34). NO:35), NSGSYSFAY (SEQ ID NO:37) and NSGSYSFGA (SEQ ID NO:39); and wherein the VL domain comprises: a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO:4); a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising an amino acid sequence selected from the group consisting of QQAYSFPFT (SEQ ID NO:6), QQAASFPFT (SEQ ID NO:41), QQAFSFPFT (SEQ ID NO:42), AQAYSFPFT (SEQ ID NO:43), QAAYSFPFT (SEQ ID NO:44), QQAYAFPFT (SEQ ID NO:45), QQAYSAPFT (SEQ ID NO:46), QQAYSFAFT (SEQ ID NO:47), QQAYSFPAT (SEQ ID NO:48) and QQAYSFPFA (SEQ ID NO:49).In some embodiments, the antigen binding domain, antibody, or fragment does not include a CDR-H1 comprising the amino acid sequence of DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence of WINPNSGDTNYAQKFQ G (SEQ ID NO: 2), a CDR-H3 comprising the amino acid sequence of NSGSYSFGY (SEQ ID NO: 3), a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFT (SEQ ID NO: 6). In some embodiments, the VH domain includes a CDR-H1 comprising the amino acid sequence of DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence of WINPNSGDTNYAQKFQ G (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence of NSGSYSFGY (SEQ ID NO: 3). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence AYYI (SEQ ID NO: 16), a CDR-H2 comprising the amino acid sequence W INPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGATNYAQKFQG (SEQ ID NO: 19), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence ASGSYSFGY (SEQ ID NO: 22). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence of DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence of WIN PNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence of NSGSASFGY (SEQ ID NO: 24).In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NAGSYSFGY (SEQ ID NO: 27). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSASYSFGY (SEQ ID NO: 29). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WIN PNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGAYSFGY (SEQ ID NO: 31). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGSYAFGY (SEQ ID NO: 33). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGSYSAGY (SEQ ID NO: 35). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGSYSFAY (SEQ ID NO: 37). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence of DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence of WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence of NSGSYSFGA (SEQ ID NO: 39).In some embodiments, the VH domain further comprises: FR1 comprising an amino acid sequence selected from the group consisting of QVQLVQSGAEVKKPGASVKVSCKSSGYTFT (SEQ ID NO:50) and Q VQLVQSGAEVKKPGASVKVSCKASGYTFT (SEQ ID NO:51); FR2 comprising the amino acid sequence of HWVRQAPGQ GLEWMG (SEQ ID NO:52); FR3 comprising an amino acid sequence selected from the group consisting of RITMTR DTSISTAYLELSRLRSDDTAVFYCAR (SEQ ID NO:53) and RVTMTRDTSISTAYMELSRLRSDDTAVYYCAR (SEQ ID NO:54); and FR4 comprising the amino acid sequence of WGQGTLVTVSS (SEQ ID NO:55). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSF PFT (SEQ ID NO: 6). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAASFPFT (SEQ ID NO: 41). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAFSFPFT (SEQ ID NO: 42). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of AQAYSFPFT (SEQ ID NO: 43). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QAAYSFPFT (SEQ ID NO: 44).In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYAFPFT (SEQ ID NO: 45). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSAPFT (SEQ ID NO: 46). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSFAFT (SEQ ID NO: 47). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGI SSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSFPAT (SEQ ID NO: 48). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFA (SEQ ID NO: 49). In some embodiments, the VL domain further comprises: FR1 comprising the amino acid sequence of DIQMTQSPSSVSASVGDR VTITC (SEQ ID NO:56); FR2 comprising an amino acid sequence selected from the group consisting of WYQQKPGK APKLLIF (SEQ ID NO:57) and WYQQKPGKAPKLLIY (SEQ ID NO:58); FR3 comprising an amino acid sequence selected from the group consisting of GVPSRFSG SGSGTDFTLTVSSLQPEDFATYYC (SEQ ID NO:59) and GVPSRFSGS GSGTDFTLTISSLQPEDFATYYC (SEQ ID NO:60); and FR4 comprising the amino acid sequence of FGPGTKVDIE (SEQ ID NO:61).

[0146] Various definitions of CDR sequences for antibody variable domains are known in the art; see, for example, Kabat (Sequences of Proteins of Immunological Interest, Fifth Edition, NIH Publication 91-3242, Bethesda MD (1991), Vols. 1-3) and Chothia. Unless otherwise indicated, CDR sequences are described herein according to the IMGT definition. See, for example, www.imgt.org / IMGTScientificChart / Nomenclature / IMGT-FRCDRdefinit ion.html.

[0147] In some embodiments, the antigen binding domain, antibody or fragment comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; wherein the VH domain comprises: a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO:7) or GYTFTAYY (SEQ ID NO:17); a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO:8) or INPNS GAT (SEQ ID NO:20); and a CDR-H3 comprising an amino acid sequence selected from the group consisting of ARNSGSYSFGY (SEQ ID NO:9), ARAS GSYSFGY (SEQ ID NO:23), ARNSGSASFGY (SEQ ID NO:25), AANSGSYSFGY (SEQ ID NO:26), ARNAGSYSFGY (SEQ ID NO:28), ARNSASYSFGY (SEQ ID NO:30), ARNSGAYSFGY (SEQ ID NO:32), ARNSGSYAFGY (SEQ ID NO:33). NO:34), ARNSGSYSAGY (SEQ ID NO:36), ARNSGSYSFAY (SEQ ID NO:38), and ARNSGSYSFGA (SEQ ID NO:40); and wherein the VL domain comprises: a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO:10); a CDR-L2 comprising the amino acid sequence GA S (SEQ ID NO:11), and a CDR-L3 comprising an amino acid sequence selected from the group consisting of QQAYSFPFT (SEQ ID NO:12), QQAASFPF T (SEQ ID NO:41), QQAFSFPFT (SEQ ID NO:42), AQAYSFPF T (SEQ ID NO:43), QAAYSFPFT (SEQ ID NO:44), QQAYAFPF T (SEQ ID NO:45), QQAYSAPFT (SEQ ID NO:46), QQAYSFA FT (SEQ ID NO:47), QQAYSFPAT (SEQ ID NO:48), and QQAYSF PFA (SEQ ID NO:49). NO:49).In some embodiments, the antigen binding domain, antibody or fragment does not include a CDR-H1 comprising the amino acid sequence of GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence of INPNSGDT (SEQ ID NO: 8), a CDR-H3 comprising the amino acid sequence of ARNSGSYSFGY (SEQ ID NO: 9), a CDR-L1 comprising the amino acid sequence of QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence of GA S (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFT (SEQ ID NO: 12). In some embodiments, the VH domain includes a CDR-H1 comprising the amino acid sequence of GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence of INPNSGDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence of ARNSGSYSFGY (SEQ ID NO: 9). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTAYY (SEQ ID NO: 17), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence ARNSGSYSFGY (SEQ ID NO: 9). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGAT (SEQ ID NO: 20), and a CDR-H3 comprising the amino acid sequence ARNSGSYSFGY (SEQ ID NO: 9). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDY Y (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence ARASGSYSFGY (SEQ ID NO: 23). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO:7), a CDR-H2 comprising the amino acid sequence INP NSGDT (SEQ ID NO:8), and a CDR-H3 comprising the amino acid sequence ARNSGSAS FGY (SEQ ID NO:25).In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence AANSGSYSFGY (SEQ ID NO: 26). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence ARNAGSYSFGY (SEQ ID NO: 28). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence ARNSASYSFGY (SEQ ID NO: 30). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNS GDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence ARNSGAYSFG Y (SEQ ID NO: 32). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence ARNSGSYAFGY (SEQ ID NO: 34). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence ARNSGSYSAGY (SEQ ID NO: 36). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence of GYTFTDYY (SEQ ID NO:7), a CDR-H2 comprising the amino acid sequence of INPNSGDT (SEQ ID NO:8), and a CDR-H3 comprising the amino acid sequence of ARNSGSYSFAY (SEQ ID NO:38).In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence INPNSG DT (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence ARNSGSYSFGA (SEQ ID NO: 40). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QQAYSF PFT (SEQ ID NO: 12). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QQA ASFPFT (SEQ ID NO: 41). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QQAFSFPFT (SEQ ID NO: 42). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence AQAYSFPFT (SEQ ID NO: 43). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QAAYSFPFT (SEQ ID NO: 44). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QQAYAFPFT (SEQ ID NO: 45). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QQAYSAPFT (SEQ ID NO: 46).In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QQAYSFAFT (SEQ ID NO: 47). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QQAYSFPAT (SEQ ID NO: 48). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QQAYSFPFA (SEQ ID NO: 49).

[0148] In some embodiments, the antigen binding domain, antibody or fragment comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; wherein the VH domain comprises: a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13) or GYTFTAY (SEQ ID NO: 18); a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14) or NPNS GA (SEQ ID NO: 21); and a CDR-H3 comprising an amino acid sequence selected from the group consisting of NSGSYSFGY (SEQ ID NO: 15), ASGSYS FGY (SEQ ID NO: 22), NSGSASFGY (SEQ ID NO: 24), NAGSY SFGY (SEQ ID NO: 27), NSASYSFGY (SEQ ID NO: 29), NSGA YSFGY (SEQ ID NO: 31), NSGSYAFGY (SEQ ID NO: 33), NSG SYSAGY (SEQ ID NO: 34). NO:35), NSGSYSFAY (SEQ ID NO:37), and NS GSYSFGA (SEQ ID NO:39); and wherein the VL domain comprises: a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO:4); a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising an amino acid sequence selected from the group consisting of QQAYSFPFT (SEQ ID NO:6), Q QAASFPFT (SEQ ID NO:41), QQAFSFPFT (SEQ ID NO:42), A QAYSFPFT (SEQ ID NO:43), QAAYSFPFT (SEQ ID NO:44), Q QAYAFPFT (SEQ ID NO:45), QQAYSAPFT (SEQ ID NO:46), Q QAYSFAFT (SEQ ID NO:47), QQAYSFPAT (SEQ ID NO:48), and Q QAYSFPFA (SEQ ID NO:49).In some embodiments, the antibody does not include a CDR-H1 comprising the amino acid sequence of GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence of NPNSGD (SEQ ID NO: 14), a CDR-H3 comprising the amino acid sequence of NSGSYSFGY (SEQ ID NO: 15), a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFT (SEQ ID NO: 6). In some embodiments, the VH domain includes a CDR-H1 comprising the amino acid sequence of GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence of NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence of NSGSYSFGY (SEQ ID NO: 15). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTAY (SEQ ID NO: 18), a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 15). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNSGA (SEQ ID NO: 21), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 15). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence ASGSYSFGY (SEQ ID NO: 22). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence NAGSYSFGY (SEQ ID NO: 27). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence NSASYSFGY (SEQ ID NO: 29).In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence NSGAYSFGY (SEQ ID NO: 31). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence NSGSYAFGY (SEQ ID NO: 33). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence NSGSYSAGY (SEQ ID NO: 35). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence NSGSYSFAY (SEQ ID NO: 37). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence NSGSYSFGA (SEQ ID NO: 39). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence GAS SLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO: 6). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence of QQAASFPFT (SEQ ID NO:41).In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence QQAFSFPFT (SEQ ID NO: 42). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence AQAYSFPFT (SEQ ID NO: 43). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence RASQGI SSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence QAAYSFPFT (SEQ ID NO: 44). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAY AFPFT (SEQ ID NO: 45). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSAPFT (SEQ ID NO: 46). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSFAFT (SEQ ID NO: 47). In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence of QQAYSFPAT (SEQ ID NO:48).In some embodiments, the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence of QQAYSF PFA (SEQ ID NO:49).

[0149] In some embodiments, the VH domain comprises an amino acid sequence selected from the group consisting of SEQ ID Nos: 62 and 82-93. In some embodiments, in some embodiments according to any of the embodiments described herein, the VL domain comprises an amino acid sequence selected from the group consisting of SEQ ID Nos: 64 and 94-102. In some embodiments, the VH domain comprises an amino acid sequence selected from the group consisting of SEQ ID Nos: 62 and 82-93 and / or the VL domain comprises an amino acid sequence selected from the group consisting of SEQ ID Nos: 64 and 94-102. In some embodiments, the antibody does not include a VH domain comprising the amino acid sequence of SEQ ID NO: 62 and a VL domain comprising the amino acid sequence of SEQ ID NO: 64. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 62 and the VL domain comprises the amino acid sequence of SEQ ID NO: 94. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 62 and the VL domain comprises the amino acid sequence of SEQ ID NO: 95. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain compr...

Claims

1. An antibody or antigen-binding fragment thereof that binds to human Dectin-1, wherein the antibody or fragment comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; The VH domain comprises the amino acid sequence QVQLVQSGAEVKKPGASVKVSCKSSGYTFTX1YYIHWVRQAPGQGLEWMGWINPNSGX2TNYAQKFQGRITMTRDTSISTAYLELSRLRSDDTAVFYCAX3X4X5X6X7X8X9X 10 X 11 X 12 WGQGTLVTVSS, wherein X1 is D, A or G; wherein X2 is D, A or G; wherein X3 is R, A or G; wherein X4 is N, A or G; wherein X5 is S, A or G; wherein X6 is A or G; wherein X7 is S, A or G; wherein X8 is Y, A or G; wherein X9 is S, A or G; wherein X 10 is F, A or G; where X 11 is A or G; and where X 12 is Y, A or G (SEQ ID NO:63); and wherein the VL domain comprises the amino acid sequence DIQMTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKAPKLLIFGASSLQSGVPSRFSGSGSGTDFTLTVSSLQPEDFATYYCX1X2AX3X4X5X6X7X8FGPGTKVDIE, wherein X1 is Q, A or G; X2 is Q, A or G; X3 is F, Y, A or G; wherein X4 is S, A or G; wherein X5 is F, A or G; wherein X6 is P, A or G; wherein X7 is F, A or G; and wherein X8 is T, A or G (SEQ ID NO:65).

2. The antibody of claim 1, wherein the antibody does not include a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3), a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO: 6).

3. The antibody of claim 1 or claim 2, wherein the VH domain comprises 1, 2 or fewer, 3 or fewer, 4 or fewer, or 5 or fewer substitutions compared to the amino acid sequence of SEQ ID NO: 62; and / or wherein the VL domain comprises 1, 2 or fewer, 3 or fewer, 4 or fewer, or 5 or fewer substitutions compared to the amino acid sequence of SEQ ID NO:

64.

4. The antibody of any one of claims 1 to 3, wherein the antibody or fragment: (a) binds to human Dectin-1 expressed on the cell surface with an EC50 of less than 2 nM; (b) capable of binding to human or cynomolgus monkey Dectin-1; and / or (c) Does not compete with the natural ligand of human Dectin-1.

5. An antibody or antigen-binding fragment thereof that binds to human Dectin-1, wherein the antibody or fragment comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; wherein the VH domain comprises: a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1) or AYYI (SEQ ID NO: 16); a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2) or WINPNSGATNYAQKFQG (SEQ ID NO: 19); and a CDR-H3 comprising an amino acid sequence selected from the group consisting of NSGSYSFGY (SEQ ID NO: 3), ASGSYSFGY (SEQ ID NO: 22), NSGSASFGY (SEQ ID NO: 24), NAGSYSFGY (SEQ ID NO: 27), NSASYSFGY (SEQ ID NO: 29), NSGAYSFGY (SEQ ID NO: 31), NSGSYAFGY (SEQ ID NO: 33), NSGSYSAGY (SEQ ID NO: 35), NSGSYSFAY (SEQ ID NO: 37), and NSGSYSFGA (SEQ ID NO: 39); and wherein the VL domain comprises: a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO:4); a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising an amino acid sequence selected from the group consisting of QQAYSFPFT (SEQ ID NO:6), QQAASFPFT (SEQ ID NO:41), QQAFSFPFT (SEQ ID NO:42), AQAYSFPFT (SEQ ID NO:43), QAAYSFPFT (SEQ ID NO:44), QQAYAFPFT (SEQ ID NO:45), QQAYSAPFT (SEQ ID NO:46), QQAYSFAFT (SEQ ID NO:47), QQAYSFPAT (SEQ ID NO:48) and QQAYSFPFA (SEQ ID NO:49).

6. The antibody of claim 5, wherein the antibody does not include a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3), a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO: 6).

7. The antibody of any one of claims 1-6, wherein the VH domain comprises: (a) a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3); (b) CDR-H1 comprising the amino acid sequence AYYI (SEQ ID NO: 16), CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3); (c) a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGATNYAQKFQG (SEQ ID NO: 19), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3); (d) CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and CDR-H3 comprising the amino acid sequence ASGSYSFGY (SEQ ID NO: 22); (e) CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and CDR-H3 comprising the amino acid sequence NSGSASFGY (SEQ ID NO: 24); (f) CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and CDR-H3 comprising the amino acid sequence NAGSYSFGY (SEQ ID NO: 27); (g) a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSASYSFGY (SEQ ID NO: 29); (h) CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and CDR-H3 comprising the amino acid sequence NSGAYSFGY (SEQ ID NO: 31); (i) a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGSYAFGY (SEQ ID NO: 33); (j) a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGSYSAGY (SEQ ID NO: 35); (k) a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGSYSFAY (SEQ ID NO: 37); or (1) CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and CDR-H3 comprising the amino acid sequence NSGSYSFGA (SEQ ID NO: 39).

8. The antibody of any one of claims 1-7, wherein the VH domain further comprises: (a) FR1 comprising an amino acid sequence selected from the group consisting of QVQLVQSGAEVKKPGASVKVSCKSSGYTFT (SEQ ID NO: 50) and QVQLVQSGAEVKKPGASVKVSCKASGYTFT (SEQ ID NO: 51); (b) FR2 comprising the amino acid sequence HWVRQAPGQGLEWMG (SEQ ID NO: 52); (c) FR3 comprising an amino acid sequence selected from the group consisting of RITMTRDTSISTAYLELSRLRSDDTAVFYCAR (SEQ ID NO: 53) and RVTMTRDTSISTAYMELSRLRSDDTAVYYCAR (SEQ ID NO: 54); and (d) FR4 comprising the amino acid sequence WGQGTLVTVSS (SEQ ID NO: 55).

9. The antibody of any one of claims 1-8, wherein the VH domain comprises an amino acid sequence selected from the group consisting of SEQ ID Nos: 62 and 82-93.

10. The antibody of any one of claims 1-9, wherein the VL domain comprises: (a) a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO:6); (b) a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence QQAASFPFT (SEQ ID NO:41); (c) a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence QQAFSFPFT (SEQ ID NO:42); (d) a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence AQAYSFPFT (SEQ ID NO:43); (e) a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence QAAYSFPFT (SEQ ID NO:44); (f) a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence QQAYAFPFT (SEQ ID NO:45); (g) a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence QQAYSAPFT (SEQ ID NO:46); (h) a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence QQAYSFAFT (SEQ ID NO:47); (i) a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence QQAYSFPAT (SEQ ID NO:48); or (j) CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO:4), CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO:5), and CDR-L3 comprising the amino acid sequence QQAYSFPFA (SEQ ID NO:49).

11. The antibody of any one of claims 1-10, wherein the VL domain further comprises: (a) FR1 comprising the amino acid sequence DIQMTQSPSSVSASVGDRVTITC (SEQ ID NO: 56); (b) FR2 comprising an amino acid sequence selected from the group consisting of WYQQKPGKAPKLLIF (SEQ ID NO: 57) and WYQQKPGKAPKLLIY (SEQ ID NO: 58); (c) FR3 comprising an amino acid sequence selected from the group consisting of GVPSRFSGSGSGTDFTLTVSSLQPEDFATYYC (SEQ ID NO: 59) and GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC (SEQ ID NO: 60); and (d) FR4 comprising the amino acid sequence FGPGTKVDIE (SEQ ID NO: 61).

12. The antibody of any one of claims 1-11, wherein the VL domain comprises an amino acid sequence selected from the group consisting of SEQ ID Nos: 64 and 94-102.

13. The antibody of any one of claims 1 to 6, wherein: (1) the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94; (2) the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95; (3) the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96; (4) the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97; (5) the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98; (6) the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99; (7) the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100; (8) the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101; (9) the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102; (10) the VH domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (11) the VH domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94; (12) the VH domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95; (13) the VH domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96; (14) the VH domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97; (15) the VH domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98; (16) the VH domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99; (17) the VH domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100; (18) the VH domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101; (19) the VH domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102; (20) the VH domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (21) the VH domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94; (22) the VH domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95; (23) the VH domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96; (24) the VH domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97; (25) the VH domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98; (26) the VH domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99; (27) the VH domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100; (28) the VH domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101; (29) the VH domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102; (30) the VH domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (31) the VH domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94; (32) the VH domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95; (33) the VH domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96; (34) the VH domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97; (35) the VH domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98; (36) the VH domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99; (37) the VH domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100; (38) the VH domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101; (39) the VH domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102; (40) the VH domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (41) the VH domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94; (42) the VH domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95; (43) the VH domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96; (44) the VH domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97; (45) the VH domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98; (46) the VH domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99; (47) the VH domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100; (48) the VH domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101; (49) the VH domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102; (50) the VH domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (51) the VH domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94; (52) the VH domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95; (53) the VH domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96; (54) the VH domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97; (55) the VH domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98; (56) the VH domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99; (57) the VH domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100; (58) the VH domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101; (59) the VH domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102; (60) the VH domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (61) the VH domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94; (62) the VH domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95; (63) the VH domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96; (64) the VH domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97; (65) the VH domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98; (66) the VH domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99; (67) the VH domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100; (68) the VH domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101; (69) the VH domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102; (70) the VH domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (71) the VH domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94; (72) the VH domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95; (73) the VH domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96; (74) the VH domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97; (75) the VH domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98; (76) the VH domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99; (77) the VH domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100; (78) the VH domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101; (79) the VH domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102; (80) the VH domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (81) the VH domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94; (82) the VH domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95; (83) the VH domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96; (84) the VH domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97; (85) the VH domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98; (86) the VH domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99; (87) the VH domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100; (88) the VH domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101; (89) the VH domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102; (90) the VH domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (91) the VH domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94; (92) the VH domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95; (93) the VH domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96; (94) the VH domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97; (95) the VH domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98; (96) the VH domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99; (97) the VH domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100; (98) the VH domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101; (99) the VH domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102; (100) the VH domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (101) the VH domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94; (102) the VH domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95; (103) the VH domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96; (104) the VH domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97; (105) the VH domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98; (106) the VH domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99; (107) the VH domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100; (108) the VH domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101; (109) the VH domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102; (110) the VH domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (111) the VH domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94; (112) the VH domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95; (113) the VH domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96; (114) the VH domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97; (115) the VH domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98; (116) the VH domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99; (117) the VH domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100; (118) the VH domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101; (119) the VH domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102; (120) the VH domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (121) the VH domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94; (122) the VH domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95; (123) the VH domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96; (124) the VH domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97; (125) the VH domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98; (126) the VH domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99; (127) the VH domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100; (128) the VH domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101; or (129) The VH domain comprises the amino acid sequence of SEQ ID NO:93, and the VL domain comprises the amino acid sequence of SEQ ID NO:

102.

14. An antibody or antigen-binding fragment thereof that binds to human Dectin-1, wherein the antibody or fragment comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; wherein the VH domain comprises the amino acid sequence QVQLVQSGAEVKKPGASVKVSCKX1SGYTFTX2YYX3HWVRQAPGQGLEWMGWINPNSGX4TNYAQKFQGRX5TMTRDTSISTAYX6ELSRLRSDDTAVX7YCARNSGSYSFGYWGQGTLVTVSS; wherein X1 is S or A; wherein X2 is D or G; wherein X3 is I or M; wherein X4 is D or G; wherein X5 is I or V; wherein X6 is L or M; and wherein X7 is F or Y (SEQ ID NO:80); and wherein the VL domain comprises the amino acid sequence DIQMTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKAPKLLIX1X2ASSLQSGVPSRFSGSGSGTDFTLTX3SSLQPEDFATYYCQQAYSFPFTFGPGTKVDIE; wherein X1 is F or Y; wherein X2 is G or A; and wherein X3 is V or I (SEQ ID NO: 81).

15. An antibody or antigen-binding fragment thereof that binds to human Dectin-1, wherein the antibody or fragment comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; wherein the VH domain comprises: a CDR-H1 comprising an amino acid sequence selected from the group consisting of DYYI (SEQ ID NO: 1), DYYM (SEQ ID NO: 66), and GYYM (SEQ ID NO: 67); a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2) or WINPNSGGTNYAQKFQG (SEQ ID NO: 70); and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3); and wherein the VL domain comprises: a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO:4); a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO:5) or AASSLQS (SEQ ID NO:73), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO:6).

16. The antibody of claim 14 or claim 15, wherein the antibody does not include a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3), a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO: 6).

17. The antibody of any one of claims 14-16, wherein the VH domain comprises: (a) a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3); (b) CDR-H1 comprising the amino acid sequence DYYM (SEQ ID NO:66), CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO:2), and CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO:3); (c) a CDR-H1 comprising the amino acid sequence GYYM (SEQ ID NO: 67), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3); (d) a CDR-H1 comprising the amino acid sequence DYYM (SEQ ID NO:66), a CDR-H2 comprising the amino acid sequence WINPNSGGTNYAQKFQG (SEQ ID NO:70), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO:3); or (e) CDR-H1 comprising the amino acid sequence GYYM (SEQ ID NO: 67), CDR-H2 comprising the amino acid sequence WINPNSGGTNYAQKFQG (SEQ ID NO: 70), and CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3).

18. The antibody of any one of claims 14-17, wherein the VH domain further comprises: (a) FR1 comprising an amino acid sequence selected from the group consisting of QVQLVQSGAEVKKPGASVKVSCKSSGYTFT (SEQ ID NO: 50) and QVQLVQSGAEVKKPGASVKVSCKASGYTFT (SEQ ID NO: 76); (b) FR2 comprising the amino acid sequence HWVRQAPGQGLEWMG (SEQ ID NO: 52); (c) FR3 comprising an amino acid sequence selected from the group consisting of RITMTRDTSISTAYLELSRLRSDDTAVFYCAR (SEQ ID NO: 53) and RVTMTRDTSISTAYMELSRLRSDDTAVYYCAR (SEQ ID NO: 77); and (d) FR4 comprising the amino acid sequence WGQGTLVTVSS (SEQ ID NO: 55).

19. The antibody of any one of claims 14-18, wherein the VH domain comprises an amino acid sequence selected from the group consisting of SEQ ID Nos: 62 and 103-109.

20. The antibody of any one of claims 14-19, wherein the VL domain comprises: (a) a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO:6); or (b) CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO:4), CDR-L2 comprising the amino acid sequence AASSLQS (SEQ ID NO:73), and CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO:6).

21. The antibody of any one of claims 14-20, wherein the VL domain further comprises: (a) FR1 comprising the amino acid sequence DIQMTQSPSSVSASVGDRVTITC (SEQ ID NO: 56); (b) FR2 comprising an amino acid sequence selected from the group consisting of WYQQKPGKAPKLLIF (SEQ ID NO: 57) and WYQQKPGKAPKLLIY (SEQ ID NO: 78); (c) FR3 comprising an amino acid sequence selected from the group consisting of GVPSRFSGSGSGTDFTLTVSSLQPEDFATYYC (SEQ ID NO: 59) and GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC (SEQ ID NO: 79); and (d) FR4 comprising the amino acid sequence FGPGTKVDIE (SEQ ID NO: 61).

22. The antibody of any one of claims 14-21, wherein the VL domain comprises an amino acid sequence selected from the group consisting of SEQ ID Nos: 64 and 110-113.

23. The antibody of any one of claims 14-16, wherein: (1) the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 110; (2) the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 111; (3) the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 112; (4) the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 113; (5) the VH domain comprises the amino acid sequence of SEQ ID NO: 103, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (6) the VH domain comprises the amino acid sequence of SEQ ID NO: 103, and the VL domain comprises the amino acid sequence of SEQ ID NO: 110; (7) the VH domain comprises the amino acid sequence of SEQ ID NO: 103, and the VL domain comprises the amino acid sequence of SEQ ID NO: 111; (8) the VH domain comprises the amino acid sequence of SEQ ID NO: 103, and the VL domain comprises the amino acid sequence of SEQ ID NO: 112; (9) the VH domain comprises the amino acid sequence of SEQ ID NO: 103, and the VL domain comprises the amino acid sequence of SEQ ID NO: 113; (10) the VH domain comprises the amino acid sequence of SEQ ID NO: 104, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (11) the VH domain comprises the amino acid sequence of SEQ ID NO: 104, and the VL domain comprises the amino acid sequence of SEQ ID NO: 110; (12) the VH domain comprises the amino acid sequence of SEQ ID NO: 104, and the VL domain comprises the amino acid sequence of SEQ ID NO: 111; (13) the VH domain comprises the amino acid sequence of SEQ ID NO: 104, and the VL domain comprises the amino acid sequence of SEQ ID NO: 112; (14) the VH domain comprises the amino acid sequence of SEQ ID NO: 104, and the VL domain comprises the amino acid sequence of SEQ ID NO: 113; (15) the VH domain comprises the amino acid sequence of SEQ ID NO: 105, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (16) the VH domain comprises the amino acid sequence of SEQ ID NO: 105, and the VL domain comprises the amino acid sequence of SEQ ID NO: 110; (17) the VH domain comprises the amino acid sequence of SEQ ID NO: 105, and the VL domain comprises the amino acid sequence of SEQ ID NO: 111; (18) the VH domain comprises the amino acid sequence of SEQ ID NO: 105, and the VL domain comprises the amino acid sequence of SEQ ID NO: 112; (19) the VH domain comprises the amino acid sequence of SEQ ID NO: 105, and the VL domain comprises the amino acid sequence of SEQ ID NO: 113; (20) the VH domain comprises the amino acid sequence of SEQ ID NO: 106, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (21) the VH domain comprises the amino acid sequence of SEQ ID NO: 106, and the VL domain comprises the amino acid sequence of SEQ ID NO: 110; (22) the VH domain comprises the amino acid sequence of SEQ ID NO: 106, and the VL domain comprises the amino acid sequence of SEQ ID NO: 111; (23) the VH domain comprises the amino acid sequence of SEQ ID NO: 106, and the VL domain comprises the amino acid sequence of SEQ ID NO: 112; (24) the VH domain comprises the amino acid sequence of SEQ ID NO: 106, and the VL domain comprises the amino acid sequence of SEQ ID NO: 113; (25) the VH domain comprises the amino acid sequence of SEQ ID NO: 107, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (26) the VH domain comprises the amino acid sequence of SEQ ID NO: 107, and the VL domain comprises the amino acid sequence of SEQ ID NO: 110; (27) the VH domain comprises the amino acid sequence of SEQ ID NO: 107, and the VL domain comprises the amino acid sequence of SEQ ID NO: 111; (28) the VH domain comprises the amino acid sequence of SEQ ID NO: 107, and the VL domain comprises the amino acid sequence of SEQ ID NO: 112; (29) the VH domain comprises the amino acid sequence of SEQ ID NO: 107, and the VL domain comprises the amino acid sequence of SEQ ID NO: 113; (30) the VH domain comprises the amino acid sequence of SEQ ID NO: 108, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (31) the VH domain comprises the amino acid sequence of SEQ ID NO: 108, and the VL domain comprises the amino acid sequence of SEQ ID NO: 110; (32) the VH domain comprises the amino acid sequence of SEQ ID NO: 108, and the VL domain comprises the amino acid sequence of SEQ ID NO: 111; (33) the VH domain comprises the amino acid sequence of SEQ ID NO: 108, and the VL domain comprises the amino acid sequence of SEQ ID NO: 112; (34) the VH domain comprises the amino acid sequence of SEQ ID NO: 108, and the VL domain comprises the amino acid sequence of SEQ ID NO: 113; (35) the VH domain comprises the amino acid sequence of SEQ ID NO: 109, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (36) the VH domain comprises the amino acid sequence of SEQ ID NO: 109, and the VL domain comprises the amino acid sequence of SEQ ID NO: 110; (37) the VH domain comprises the amino acid sequence of SEQ ID NO: 109, and the VL domain comprises the amino acid sequence of SEQ ID NO: 111; (38) the VH domain comprises the amino acid sequence of SEQ ID NO: 109, and the VL domain comprises the amino acid sequence of SEQ ID NO: 112; or (39) The VH domain comprises the amino acid sequence of SEQ ID NO:109, and the VL domain comprises the amino acid sequence of SEQ ID NO:

113.

24. The antibody of claim 15, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 213, and the VL domain comprises the amino acid sequence of SEQ ID NO:

214.

25. The antibody of claim 15, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 195, and the VL domain comprises the amino acid sequence of SEQ ID NO:

64.

26. An antibody or antigen-binding fragment thereof that binds to human Dectin-1, wherein the antibody or fragment comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; wherein the VH domain comprises: a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1) or DYYM (SEQ ID NO: 199); a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), WINPNEGDTNYAQKFEG (SEQ ID NO: 200), or WINPNEGDTNYAQKFQE (SEQ ID NO: 201); and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3), NSGSASFGY (SEQ ID NO: 187), NSGSYSAGY (SEQ ID NO: 190), or NTGAYSFGY (SEQ ID NO: 204); and wherein the VL domain comprises: a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO:4); a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO:5) or GASDLQS (SEQ ID NO:206), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO:6), QAAYSFPFT (SEQ ID NO:192), QQAYSAPFT (SEQ ID NO:193), QQAYGFPFT (SEQ ID NO:207) or HQAYSFPFT (SEQ ID NO:208); wherein the antibody does not include a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3), a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO: 5) and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO: 6).

27. The antibody of claim 26, wherein: (a) the VH domain comprises: a CDR-H1 comprising the amino acid sequence of DYYM (SEQ ID NO: 199), a CDR-H2 comprising the amino acid sequence of WINPNEGDTNYAQKFEG (SEQ ID NO: 200), and a CDR-H3 comprising the amino acid sequence of NTGAYSFGY (SEQ ID NO: 204), and the VL domain comprises: a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASDLQS (SEQ ID NO: 206), and a CDR-L3 comprising the amino acid sequence of QQAYGFPFT (SEQ ID NO: 207); (b) the VH domain comprises: a CDR-H1 comprising the amino acid sequence of DYYM (SEQ ID NO: 199), a CDR-H2 comprising the amino acid sequence of WINPNEGDTNYAQKFQE (SEQ ID NO: 201), and a CDR-H3 comprising the amino acid sequence of NTGAYSFGY (SEQ ID NO: 204), and the VL domain comprises: a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASDLQS (SEQ ID NO: 206), and a CDR-L3 comprising the amino acid sequence of HQAYSFPFT (SEQ ID NO: 208); (c) the VH domain comprises: a CDR-H1 comprising the amino acid sequence of DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence of WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence of NSGSASFGY (SEQ ID NO: 187), and the VL domain comprises: a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFT (SEQ ID NO: 6); (d) the VH domain comprises: a CDR-H1 comprising the amino acid sequence of DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence of WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence of NSGSYSAGY (SEQ ID NO: 190), and the VL domain comprises: a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFT (SEQ ID NO: 6); (e) the VH domain comprises: a CDR-H1 comprising the amino acid sequence of DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence of WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence of NSGSYSFGY (SEQ ID NO: 3), and the VL domain comprises: a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QAAYSFPFT (SEQ ID NO: 192); or (f) the VH domain comprises: CDR-H1 comprising the amino acid sequence of DYYI (SEQ ID NO:1), CDR-H2 comprising the amino acid sequence of WINPNSGDTNYAQKFQG (SEQ ID NO:2), and CDR-H3 comprising the amino acid sequence of NSGSYSFGY (SEQ ID NO:3), and the VL domain comprises: CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO:4), CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO:5), and CDR-L3 comprising the amino acid sequence of QQAYSAPFT (SEQ ID NO:193).

28. The antibody of claim 26 or claim 27, wherein: (a) the VH domain comprises the amino acid sequence of SEQ ID NO: 209, and the VL domain comprises the amino acid sequence of SEQ ID NO: 210; (b) the VH domain comprises the amino acid sequence of SEQ ID NO: 211, and the VL domain comprises the amino acid sequence of SEQ ID NO: 212; (c) the VH domain comprises the amino acid sequence of SEQ ID NO: 220, and the VL domain comprises the amino acid sequence of SEQ ID NO: 221; (d) the VH domain comprises the amino acid sequence of SEQ ID NO: 194, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (e) the VH domain comprises the amino acid sequence of SEQ ID NO: 196, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (f) the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 197; or (g) the VH domain comprises the amino acid sequence of SEQ ID NO:62, and the VL domain comprises the amino acid sequence of SEQ ID NO:

198.

29. The antibody of any one of claims 1-28, wherein the antibody or fragment binds to human Dectin-1 expressed on the surface of macrophages, monocytes, dendritic cells and / or granulocytes.

30. The antibody of any one of claims 1-29, wherein the antigen-binding antibody fragment is a Fab, Fab', F(ab')2, Fv, Fab'-SH, F(ab')2, single-chain antibody, nanobody or scFv fragment.

31. The antibody of any one of claims 1-29, wherein the antibody further comprises an Fc region.

32. The antibody of claim 31, wherein the Fc region is a human IgG Fc region.

33. The antibody of claim 32, wherein the Fc region is a human IgG1 or human IgG4 Fc region.

34. The antibody of claim 33, wherein the Fc region is: (a) a human IgG1 Fc region comprising S239D and I332E substitutions according to EU numbering; (b) a human IgG1 Fc region comprising, according to EU numbering, S239D, A330L and I332E substitutions; (c) a human IgG1 Fc region comprising, according to EU numbering, substitutions G236A, S239D, A330L, and I332E; or (d) Human IgG4 Fc region comprising the S228P substitution according to EU numbering.

35. The antibody of claim 33, wherein the antibody comprises two antibody heavy chains, and wherein each of the antibody heavy chains comprises an amino acid substitution at one or more of positions 234, 235, and 237 according to EU numbering.

36. The antibody of claim 35, wherein each of the antibody heavy chains comprises L234A, L235E and G237A substitutions according to EU numbering.

37. The antibody of any one of claims 33-36, wherein the antibody comprises two antibody heavy chains, and wherein only one of the antibody heavy chains comprises H435R and Y436F substitutions according to EU numbering.

38. The antibody of any one of claims 31-37, wherein the Fc region is non-fucosylated or comprises reduced fucosylation.

39. The antibody of any one of claims 1-38, wherein the antibody or fragment is a multispecific antibody or fragment.

40. The antibody of claim 39, wherein the antibody or fragment is a bispecific antibody, fragment or diabody comprising a first antigen binding domain comprising the VH domain and VL domain that bind to human Dectin-1 and a second antigen binding domain comprising a second VH domain and a second VL domain that bind to a target of interest.

41. The antibody of claim 40, wherein the bispecific antibody comprises a first IgG antibody comprising the first antigen binding domain covalently linked to a second IgG antibody comprising the second antigen binding domain.

42. The antibody of claim 40, wherein the bispecific antibody comprises: a first antibody arm comprising a first antibody heavy chain comprising the VH domain of the first antigen binding domain and a first Fc region; and a second antibody arm comprising a second antibody heavy chain comprising the VH domain of the second antigen binding domain and a second Fc region, wherein the first Fc region comprises one or more knob-forming mutations and the second Fc region comprises one or more homologous hole-forming mutations.

43. The antibody of claim 42, wherein the first Fc region comprises a T366W substitution according to EU numbering, and wherein the second Fc region comprises T366S, L368A, and Y407V substitutions.

44. The antibody of claim 40, wherein the bispecific antibody comprises: a first antibody arm comprising a first antibody heavy chain comprising the VH domain of the first antigen binding domain and a first Fc region; and a second antibody arm comprising a second antibody heavy chain comprising the VH domain of the second antigen binding domain and a second Fc region, wherein the first Fc region comprises one or more hole-forming mutations and the second Fc region comprises one or more homologous knob-forming mutations.

45. The antibody of claim 44, wherein the first Fc region comprises T366S, L368A, and Y407V substitutions according to EU numbering, and wherein the second Fc region comprises a T366W substitution.

46. ​​An antibody as described in claim 40, wherein the bispecific antibody comprises: a first antibody arm, which comprises a single-chain variable fragment (scFv) comprising the VH domain and VL domain that bind to human Dectin-1 and a first Fc region; and a second antibody arm, which comprises an antibody heavy chain comprising the VH domain of the second antigen-binding domain and a second Fc region of the VH domain connected to the second antigen-binding domain, and the antibody heavy chain is associated with an antibody light chain comprising the VL domain of the second antigen-binding domain.

47. The antibody of claim 46, wherein the first Fc region comprises one or more knob-forming mutations and the second Fc region comprises one or more homologous hole-forming mutations, or wherein the second Fc region comprises one or more knob-forming mutations and the first Fc region comprises one or more homologous hole-forming mutations.

48. The antibody of claim 46 or claim 47, wherein the first antibody arm comprises a first linker between the VH domain and the VL domain and a second linker between the VL domain and the first Fc region.

49. The antibody of claim 48, wherein the first linker comprises one or more repeats of the sequence GGGGS (SEQ ID NO: 115).

50. The antibody of claim 49, wherein the first linker comprises the sequence GGGGSGGGGSGGGGS (SEQ ID NO: 116) or GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 117).

51. The antibody of any one of claims 48-50, wherein the second linker comprises the sequence EPKRSDKTHTCPPC (SEQ ID NO: 118) or SATHTCPPC (SEQ ID NO: 119).

52. The antibody of any one of claims 46-51, wherein the VH domain that binds to human Dectin-1 comprises the amino acid sequence of SEQ ID NO: 220, and wherein the VL domain that binds to human Dectin-1 comprises the amino acid sequence of SEQ ID NO:

221.

53. The antibody of claim 46, wherein the scFv comprises the amino acid sequence of SEQ ID NO:

222.

54. The antibody of claim 46, wherein the first antibody arm comprises the amino acid sequence of SEQ ID NO: 224 or 225.

55. The antibody of claim 40, wherein the bispecific antibody comprises a first IgG antibody comprising the first antigen binding domain coupled to biotin or a derivative thereof that binds avidin, and a second IgG antibody comprising the second antigen binding domain coupled to avidin, streptavidin, neutravidin, or a derivative thereof that binds biotin, wherein the biotin or a derivative thereof that binds avidin binds the avidin, streptavidin, neutravidin, or a derivative thereof that binds biotin.

56. An antibody as described in claim 40, wherein the bispecific antibody comprises a first IgG antibody comprising the first antigen binding domain coupled to avidin, streptavidin, neutravidin or a derivative thereof that binds biotin, and a second IgG antibody comprising the second antigen binding domain coupled to biotin or a derivative thereof that binds avidin, wherein the biotin or a derivative thereof that binds avidin binds the avidin, streptavidin, neutravidin or a derivative thereof that binds biotin.

57. The antibody of claim 31, wherein the bispecific antibody comprises two antibody heavy chains and two antibody light chains, wherein the VH domain of the first antibody heavy chain forms an antigen binding domain that binds to human Dectin-1 with the VL domain of the first antibody light chain, wherein the VH domain of the second antibody heavy chain forms an antigen binding domain that binds to a target of interest with the VL domain of the second antibody light chain; wherein the VH domain of the first antibody heavy chain comprises the amino acid sequence of SEQ ID NO: 209, and wherein the VL domain of the first antibody light chain comprises the amino acid sequence of SEQ ID NO:

210.

58. The antibody of claim 31, wherein the bispecific antibody comprises two antibody heavy chains and two antibody light chains, wherein the VH domain of the first antibody heavy chain forms an antigen binding domain that binds to human Dectin-1 with the VL domain of the first antibody light chain, wherein the VH domain of the second antibody heavy chain forms an antigen binding domain that binds to a target of interest with the VL domain of the second antibody light chain; wherein the VH domain of the first antibody heavy chain comprises the amino acid sequence of SEQ ID NO: 220, and wherein the VL domain of the first antibody light chain comprises the amino acid sequence of SEQ ID NO:

221.

59. The antibody of claim 58, wherein the first antibody heavy chain comprises a C→S substitution at position 5 according to IMGT hinge numbering, and wherein the first antibody light chain comprises a C→S substitution at the terminal residue of the light chain constant domain.

60. The antibody of claim 58, wherein the first antibody heavy chain comprises the amino acid sequence of SEQ ID NO:219, and wherein the first antibody light chain comprises the amino acid sequence of SEQ ID NO:

223.

61. The antibody of any one of claims 40-60, wherein the target of interest is a pathogen.

62. The antibody of claim 61, wherein the pathogen is a bacterial cell, a fungal cell, a virus, a senescent cell, a tumor cell, a protein aggregate, an LDL particle, a mast cell, an eosinophil, an ILC2 cell, or an inflammatory immune cell.

63. The antibody of claim 62, wherein the target of interest is an antigen expressed on the surface of a bacterial cell, a fungal cell, a senescent cell, a tumor cell, a mast cell, an eosinophil, an ILC2 cell, or an inflammatory immune cell.

64. The antibody of claim 62, wherein the target of interest is a surface antigen of a virus.

65. The antibody of claim 61 or claim 62, wherein the target of interest is an antigen expressed on the surface of a cancer cell.

66. The antibody of claim 65, wherein the target of interest is CD70, HER2, DLL3, adhesion protein-4, TROP-2, mesothelin, LIV-1, C-MET, FOLR1, CD20, CCR8, CD33 or EGFR.

67. The antibody of claim 62, wherein the target of interest is beta amyloid, lambda light chain amyloid, or kappa light chain amyloid.

68. The antibody of any one of claims 31-67, wherein the antibody comprises two arms, wherein only one of the two antibody arms comprises a heavy chain comprising F126C and C220V substitutions and a light chain comprising S121C and C214V substitutions according to EU numbering.

69. The antibody of claim 31, wherein the bispecific antibody comprises two antibody heavy chains and two antibody light chains, wherein the VH domain of the first antibody heavy chain forms an antigen binding domain with the VL domain of the first antibody light chain, wherein the VH domain of the second antibody heavy chain forms an antigen binding domain with the VL domain of the second antibody light chain, wherein according to EU numbering, the first antibody heavy chain comprises F126C, C220V, and T366W substitutions, wherein the first antibody light chain comprises S121C and C214V substitutions, and wherein the second antibody heavy chain comprises T366S, L368A, Y407V, H435R, and Y436F substitutions.

70. The antibody of claim 69, wherein the first antibody heavy chain and the second antibody heavy chain further comprise L234A, L235E and G237A substitutions according to EU numbering.

71. A multispecific binding molecule comprising: (a) a first antibody or antigen-binding fragment thereof comprising a first antigen-binding domain, wherein the first antigen-binding domain binds to human Dectin-1; and (b) a second antibody or antigen-binding fragment thereof comprising a second antigen-binding domain, wherein the second antigen-binding domain binds to the target of interest; wherein the first antigen binding domain comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; The VH domain of the first antigen binding domain comprises the amino acid sequence QVQLVQSGAEVKKPGASVKVSCKSSGYTFTX1YYIHWVRQAPGQGLEWMGWINPNSGX2TNYAQKFQGRITMTRDTSISTAYLELSRLRSDDTAVFYCAX3X4X5X6X7X8X9X 10 X 11 X 12 WGQGTLVTVSS, wherein X1 is D, A or G; wherein X2 is D, A or G; wherein X3 is R, A or G; wherein X4 is N, A or G; wherein X5 is S, A or G; wherein X6 is A or G; wherein X7 is S, A or G; wherein X8 is Y, A or G; wherein X9 is S, A or G; wherein X 10 is F, A or G; where X 11 is A or G; and where X 12 is Y, A or G (SEQ ID NO:63); and wherein the VL domain of the first antigen binding domain comprises the amino acid sequence DIQMTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKAPKLLIFGASSLQSGVPSRFSGSGSGTDFTLTVSSLQPEDFATYYCX1X2AX3X4X5X6X7X8FGPGTKVDIE, wherein X1 is Q, A or G; X2 is Q, A or G; X3 is F, Y, A or G; wherein X4 is S, A or G; wherein X5 is F, A or G; wherein X6 is P, A or G; wherein X7 is F, A or G; and wherein X8 is T, A or G (SEQ ID NO:65).

72. The multispecific binding molecule of claim 71, wherein the antibody does not comprise a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3), a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO: 6).

73. The multispecific binding molecule of claim 71 or claim 72, wherein the VH domain of the first antigen binding domain comprises 1, 2 or fewer, 3 or fewer, 4 or fewer, or 5 or fewer substitutions compared to the amino acid sequence of SEQ ID NO:62; and / or wherein the VL domain of the first antigen binding domain comprises 1, 2 or fewer, 3 or fewer, 4 or fewer, or 5 or fewer substitutions compared to the amino acid sequence of SEQ ID NO:

64.

74. The multispecific binding molecule of any one of claims 71-73, wherein the first antigen binding domain: (a) binds to human Dectin-1 expressed on the cell surface with an EC50 of less than 2 nM; (b) capable of binding to human or cynomolgus monkey Dectin-1; and / or (c) Does not compete with the natural ligand of human Dectin-1.

75. A multispecific binding molecule comprising: (a) a first antibody or antigen-binding fragment thereof comprising a first antigen-binding domain, wherein the first antigen-binding domain binds to human Dectin-1; and (b) a second antibody or antigen-binding fragment thereof comprising a second antigen-binding domain, wherein the second antigen-binding domain binds to the target of interest; wherein the first antigen binding domain comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; wherein the VH domain of the first antigen binding domain comprises: a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1) or AYYI (SEQ ID NO: 16); a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2) or WINPNSGATNYAQKFQG (SEQ ID NO: 19); and a CDR-H3 comprising an amino acid sequence selected from the group consisting of NSGSYSFGY (SEQ ID NO: 3), ASGSYSFGY (SEQ ID NO: 22), NSGSASFGY (SEQ ID NO: 24), NAGSYSFGY (SEQ ID NO: 27), NSASYSFGY (SEQ ID NO: 29), NSGAYSFGY (SEQ ID NO: 31), NSGSYAFGY (SEQ ID NO: 33), NSGSYSAGY (SEQ ID NO: 35), NSGSYSFAY (SEQ ID NO: 37), and NSGSYSFGA (SEQ ID NO: 38). NO:39); and wherein the VL domain of the first antigen binding domain comprises: a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO:4); a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising an amino acid sequence selected from the group consisting of QQAYSFPFT (SEQ ID NO:6), QQAASFPFT (SEQ ID NO:41), QQAFSFPFT (SEQ ID NO:42), AQAYSFPFT (SEQ ID NO:43), QAAYSFPFT (SEQ ID NO:44), QQAYAFPFT (SEQ ID NO:45), QQAYSAPFT (SEQ ID NO:46), QQAYSFAFT (SEQ ID NO:47), QQAYSFPAT (SEQ ID NO:48) and QQAYSFPFA (SEQ ID NO:49).

76. The multispecific binding molecule of claim 75, wherein the antibody does not comprise a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3), a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO: 6).

77. The multispecific binding molecule of any one of claims 71-76, wherein the VH domain of the first antigen binding domain comprises: (a) a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3); (b) CDR-H1 comprising the amino acid sequence AYYI (SEQ ID NO: 16), CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3); (c) a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGATNYAQKFQG (SEQ ID NO: 19), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3); (d) CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and CDR-H3 comprising the amino acid sequence ASGSYSFGY (SEQ ID NO: 22); (e) CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and CDR-H3 comprising the amino acid sequence NSGSASFGY (SEQ ID NO: 24); (f) CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and CDR-H3 comprising the amino acid sequence NAGSYSFGY (SEQ ID NO: 27); (g) a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSASYSFGY (SEQ ID NO: 29); (h) CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and CDR-H3 comprising the amino acid sequence NSGAYSFGY (SEQ ID NO: 31); (i) a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGSYAFGY (SEQ ID NO: 33); (j) a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGSYSAGY (SEQ ID NO: 35); (k) a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGSYSFAY (SEQ ID NO: 37); or (1) CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and CDR-H3 comprising the amino acid sequence NSGSYSFGA (SEQ ID NO: 39).

78. The multispecific binding molecule of any one of claims 71-77, wherein the VH domain of the first antigen binding domain further comprises: (a) FR1 comprising an amino acid sequence selected from the group consisting of QVQLVQSGAEVKKPGASVKVSCKSSGYTFT (SEQ ID NO: 50) and QVQLVQSGAEVKKPGASVKVSCKASGYTFT (SEQ ID NO: 51); (b) FR2 comprising the amino acid sequence HWVRQAPGQGLEWMG (SEQ ID NO: 52); (c) FR3 comprising an amino acid sequence selected from the group consisting of RITMTRDTSISTAYLELSRLRSDDTAVFYCAR (SEQ ID NO: 53) and RVTMTRDTSISTAYMELSRLRSDDTAVYYCAR (SEQ ID NO: 54); and (d) FR4 comprising the amino acid sequence WGQGTLVTVSS (SEQ ID NO: 55).

79. The multispecific binding molecule of any one of claims 71-78, wherein the VH domain of the first antigen binding domain comprises an amino acid sequence selected from the group consisting of SEQ ID Nos: 62 and 82-93.

80. The multispecific binding molecule of any one of claims 71-79, wherein the VL domain of the first antigen binding domain comprises: (a) a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO:6); (b) a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence QQAASFPFT (SEQ ID NO:41); (c) a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence QQAFSFPFT (SEQ ID NO:42); (d) a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence AQAYSFPFT (SEQ ID NO:43); (e) a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence QAAYSFPFT (SEQ ID NO:44); (f) a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence QQAYAFPFT (SEQ ID NO:45); (g) a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence QQAYSAPFT (SEQ ID NO:46); (h) a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence QQAYSFAFT (SEQ ID NO:47); (i) a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence QQAYSFPAT (SEQ ID NO:48); or (j) CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO:4), CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO:5), and CDR-L3 comprising the amino acid sequence QQAYSFPFA (SEQ ID NO:49).

81. The multispecific binding molecule of any one of claims 71-80, wherein the VL domain of the first antigen binding domain further comprises: (a) FR1 comprising the amino acid sequence DIQMTQSPSSVSASVGDRVTITC (SEQ ID NO: 56); (b) FR2 comprising an amino acid sequence selected from the group consisting of WYQQKPGKAPKLLIF (SEQ ID NO: 57) and WYQQKPGKAPKLLIY (SEQ ID NO: 58); (c) FR3 comprising an amino acid sequence selected from the group consisting of GVPSRFSGSGSGTDFTLTVSSLQPEDFATYYC (SEQ ID NO: 59) and GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC (SEQ ID NO: 60); and (d) FR4 comprising the amino acid sequence FGPGTKVDIE (SEQ ID NO: 61).

82. The multispecific binding molecule of any one of claims 71-81, wherein the VL domain of the first antigen binding domain comprises an amino acid sequence selected from the group consisting of SEQ ID Nos: 64 and 94-102.

83. The multispecific binding molecule of any one of claims 71-76, wherein in the first antigen binding domain: (1) the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94; (2) the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95; (3) the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96; (4) the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97; (5) the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98; (6) the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99; (7) the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100; (8) the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101; (9) the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102; (10) the VH domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (11) the VH domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94; (12) the VH domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95; (13) the VH domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96; (14) the VH domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97; (15) the VH domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98; (16) the VH domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99; (17) the VH domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100; (18) the VH domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101; (19) the VH domain comprises the amino acid sequence of SEQ ID NO: 82, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102; (20) the VH domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (21) the VH domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94; (22) the VH domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95; (23) the VH domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96; (24) the VH domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97; (25) the VH domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98; (26) the VH domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99; (27) the VH domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100; (28) the VH domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101; (29) the VH domain comprises the amino acid sequence of SEQ ID NO: 83, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102; (30) the VH domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (31) the VH domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94; (32) the VH domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95; (33) the VH domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96; (34) the VH domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97; (35) the VH domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98; (36) the VH domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99; (37) the VH domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100; (38) the VH domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101; (39) the VH domain comprises the amino acid sequence of SEQ ID NO: 84, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102; (40) the VH domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (41) the VH domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94; (42) the VH domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95; (43) the VH domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96; (44) the VH domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97; (45) the VH domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98; (46) the VH domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99; (47) the VH domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100; (48) the VH domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101; (49) the VH domain comprises the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102; (50) the VH domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (51) the VH domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94; (52) the VH domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95; (53) the VH domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96; (54) the VH domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97; (55) the VH domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98; (56) the VH domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99; (57) the VH domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100; (58) the VH domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101; (59) the VH domain comprises the amino acid sequence of SEQ ID NO: 86, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102; (60) the VH domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (61) the VH domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94; (62) the VH domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95; (63) the VH domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96; (64) the VH domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97; (65) the VH domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98; (66) the VH domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99; (67) the VH domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100; (68) the VH domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101; (69) the VH domain comprises the amino acid sequence of SEQ ID NO: 87, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102; (70) the VH domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (71) the VH domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94; (72) the VH domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95; (73) the VH domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96; (74) the VH domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97; (75) the VH domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98; (76) the VH domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99; (77) the VH domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100; (78) the VH domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101; (79) the VH domain comprises the amino acid sequence of SEQ ID NO: 88, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102; (80) the VH domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (81) the VH domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94; (82) the VH domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95; (83) the VH domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96; (84) the VH domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97; (85) the VH domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98; (86) the VH domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99; (87) the VH domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100; (88) the VH domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101; (89) the VH domain comprises the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102; (90) the VH domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (91) the VH domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94; (92) the VH domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95; (93) the VH domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96; (94) the VH domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97; (95) the VH domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98; (96) the VH domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99; (97) the VH domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100; (98) the VH domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101; (99) the VH domain comprises the amino acid sequence of SEQ ID NO: 90, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102; (100) the VH domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (101) the VH domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94; (102) the VH domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95; (103) the VH domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96; (104) the VH domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97; (105) the VH domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98; (106) the VH domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99; (107) the VH domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100; (108) the VH domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101; (109) the VH domain comprises the amino acid sequence of SEQ ID NO: 91, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102; (110) the VH domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (111) the VH domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94; (112) the VH domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95; (113) the VH domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96; (114) the VH domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97; (115) the VH domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98; (116) the VH domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99; (117) the VH domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100; (118) the VH domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101; (119) the VH domain comprises the amino acid sequence of SEQ ID NO: 92, and the VL domain comprises the amino acid sequence of SEQ ID NO: 102; (120) the VH domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (121) the VH domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises the amino acid sequence of SEQ ID NO: 94; (122) the VH domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises the amino acid sequence of SEQ ID NO: 95; (123) the VH domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises the amino acid sequence of SEQ ID NO: 96; (124) the VH domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises the amino acid sequence of SEQ ID NO: 97; (125) the VH domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises the amino acid sequence of SEQ ID NO: 98; (126) the VH domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises the amino acid sequence of SEQ ID NO: 99; (127) the VH domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises the amino acid sequence of SEQ ID NO: 100; (128) the VH domain comprises the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises the amino acid sequence of SEQ ID NO: 101; or (129) The VH domain comprises the amino acid sequence of SEQ ID NO:93, and the VL domain comprises the amino acid sequence of SEQ ID NO:

102.

84. A multispecific binding molecule comprising: (a) a first antibody or antigen-binding fragment thereof comprising a first antigen-binding domain, wherein the first antigen-binding domain binds to human Dectin-1; and (b) a second antibody or antigen-binding fragment thereof comprising a second antigen-binding domain, wherein the second antigen-binding domain binds to the target of interest; wherein the first antigen binding domain comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; wherein the VH domain of the first antigen binding domain comprises the amino acid sequence QVQLVQSGAEVKKPGASVKVSCKX1SGYTFTX2YYX3HWVRQAPGQGLEWMGWINPNSGX4TNYAQKFQGRX5TMTRDTSISTAYX6ELSRLRSDDTAVX7YCARNSGSYSFGYWGQGTLVTVSS; wherein X1 is S or A; wherein X2 is D or G; wherein X3 is I or M; wherein X4 is D or G; wherein X5 is I or V; wherein X6 is L or M; and wherein X7 is F or Y (SEQ ID NO:80); and wherein the VL domain of the first antigen binding domain comprises the amino acid sequence DIQMTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKAPKLLIX1X2ASSLQSGVPSRFSGSGSGTDFTLTX3SSLQPEDFATYYCQQAYSFPFTFGPGTKVDIE; wherein X1 is F or Y; wherein X2 is G or A; and wherein X3 is V or I (SEQ ID NO: 81).

85. A multispecific binding molecule comprising: (a) a first antibody or antigen-binding fragment thereof comprising a first antigen-binding domain, wherein the first antigen-binding domain binds to human Dectin-1; and (b) a second antibody or antigen-binding fragment thereof comprising a second antigen-binding domain, wherein the second antigen-binding domain binds to the target of interest; wherein the first antigen binding domain comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; wherein the VH domain of the first antigen binding domain comprises: a CDR-H1 comprising an amino acid sequence selected from the group consisting of DYYI (SEQ ID NO: 1), DYYM (SEQ ID NO: 66) and GYYM (SEQ ID NO: 67); a CDR-H2 comprising an amino acid sequence of WINPNSGDTNYAQKFQG (SEQ ID NO: 2) or WINPNSGGTNYAQKFQG (SEQ ID NO: 70); and a CDR-H3 comprising an amino acid sequence of NSGSYSFGY (SEQ ID NO: 3); and The VL domain of the first antigen binding domain comprises: a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO:4); a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO:5) or AASSLQS (SEQ ID NO:73); and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO:6).

86. The multispecific binding molecule of claim 84 or claim 85, wherein the antibody does not comprise a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3), a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO: 6).

87. The multispecific binding molecule of any one of claims 84-86, wherein the VH domain of the first antigen binding domain comprises: (a) a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3); (b) CDR-H1 comprising the amino acid sequence DYYM (SEQ ID NO:66), CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO:2), and CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO:3); (c) a CDR-H1 comprising the amino acid sequence GYYM (SEQ ID NO: 67), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3); (d) a CDR-H1 comprising the amino acid sequence DYYM (SEQ ID NO:66), a CDR-H2 comprising the amino acid sequence WINPNSGGTNYAQKFQG (SEQ ID NO:70), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO:3); or (e) CDR-H1 comprising the amino acid sequence GYYM (SEQ ID NO: 67), CDR-H2 comprising the amino acid sequence WINPNSGGTNYAQKFQG (SEQ ID NO: 70), and CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3).

88. The multispecific binding molecule of any one of claims 84-87, wherein the VH domain of the first antigen binding domain further comprises: (a) FR1 comprising an amino acid sequence selected from the group consisting of QVQLVQSGAEVKKPGASVKVSCKSSGYTFT (SEQ ID NO: 50) and QVQLVQSGAEVKKPGASVKVSCKASGYTFT (SEQ ID NO: 76); (b) FR2 comprising the amino acid sequence HWVRQAPGQGLEWMG (SEQ ID NO: 52); (c) FR3 comprising an amino acid sequence selected from the group consisting of RITMTRDTSISTAYLELSRLRSDDTAVFYCAR (SEQ ID NO: 53) and RVTMTRDTSISTAYMELSRLRSDDTAVYYCAR (SEQ ID NO: 77); and (d) FR4 comprising the amino acid sequence WGQGTLVTVSS (SEQ ID NO: 55).

89. The multispecific binding molecule of any one of claims 84-88, wherein the VH domain of the first antigen binding domain comprises an amino acid sequence selected from the group consisting of SEQ ID Nos: 62 and 103-109.

90. The multispecific binding molecule of any one of claims 84-89, wherein the VL domain of the first antigen binding domain comprises: (a) a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO:6); or (b) CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO:4), CDR-L2 comprising the amino acid sequence AASSLQS (SEQ ID NO:73), and CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO:6).

91. The multispecific binding molecule of any one of claims 84-90, wherein the VL domain of the first antigen binding domain further comprises: (a) FR1 comprising the amino acid sequence DIQMTQSPSSVSASVGDRVTITC (SEQ ID NO: 56); (b) FR2 comprising an amino acid sequence selected from the group consisting of WYQQKPGKAPKLLIF (SEQ ID NO: 57) and WYQQKPGKAPKLLIY (SEQ ID NO: 78); (c) FR3 comprising an amino acid sequence selected from the group consisting of GVPSRFSGSGSGTDFTLTVSSLQPEDFATYYC (SEQ ID NO: 59) and GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC (SEQ ID NO: 79); and (d) FR4 comprising the amino acid sequence FGPGTKVDIE (SEQ ID NO: 61).

92. The multispecific binding molecule of any one of claims 84-91, wherein the VL domain of the first antigen binding domain comprises an amino acid sequence selected from the group consisting of SEQ ID Nos: 64 and 110-113.

93. The multispecific binding molecule of any one of claims 84-86, wherein in the first antigen binding domain: (1) the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 110; (2) the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 111; (3) the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 112; (4) the VH domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises the amino acid sequence of SEQ ID NO: 113; (5) the VH domain comprises the amino acid sequence of SEQ ID NO: 103, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (6) the VH domain comprises the amino acid sequence of SEQ ID NO: 103, and the VL domain comprises the amino acid sequence of SEQ ID NO: 110; (7) the VH domain comprises the amino acid sequence of SEQ ID NO: 103, and the VL domain comprises the amino acid sequence of SEQ ID NO: 111; (8) the VH domain comprises the amino acid sequence of SEQ ID NO: 103, and the VL domain comprises the amino acid sequence of SEQ ID NO: 112; (9) the VH domain comprises the amino acid sequence of SEQ ID NO: 103, and the VL domain comprises the amino acid sequence of SEQ ID NO: 113; (10) the VH domain comprises the amino acid sequence of SEQ ID NO: 104, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (11) the VH domain comprises the amino acid sequence of SEQ ID NO: 104, and the VL domain comprises the amino acid sequence of SEQ ID NO: 110; (12) the VH domain comprises the amino acid sequence of SEQ ID NO: 104, and the VL domain comprises the amino acid sequence of SEQ ID NO: 111; (13) the VH domain comprises the amino acid sequence of SEQ ID NO: 104, and the VL domain comprises the amino acid sequence of SEQ ID NO: 112; (14) the VH domain comprises the amino acid sequence of SEQ ID NO: 104, and the VL domain comprises the amino acid sequence of SEQ ID NO: 113; (15) the VH domain comprises the amino acid sequence of SEQ ID NO: 105, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (16) the VH domain comprises the amino acid sequence of SEQ ID NO: 105, and the VL domain comprises the amino acid sequence of SEQ ID NO: 110; (17) the VH domain comprises the amino acid sequence of SEQ ID NO: 105, and the VL domain comprises the amino acid sequence of SEQ ID NO: 111; (18) the VH domain comprises the amino acid sequence of SEQ ID NO: 105, and the VL domain comprises the amino acid sequence of SEQ ID NO: 112; (19) the VH domain comprises the amino acid sequence of SEQ ID NO: 105, and the VL domain comprises the amino acid sequence of SEQ ID NO: 113; (20) the VH domain comprises the amino acid sequence of SEQ ID NO: 106, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (21) the VH domain comprises the amino acid sequence of SEQ ID NO: 106, and the VL domain comprises the amino acid sequence of SEQ ID NO: 110; (22) the VH domain comprises the amino acid sequence of SEQ ID NO: 106, and the VL domain comprises the amino acid sequence of SEQ ID NO: 111; (23) the VH domain comprises the amino acid sequence of SEQ ID NO: 106, and the VL domain comprises the amino acid sequence of SEQ ID NO: 112; (24) the VH domain comprises the amino acid sequence of SEQ ID NO: 106, and the VL domain comprises the amino acid sequence of SEQ ID NO: 113; (25) the VH domain comprises the amino acid sequence of SEQ ID NO: 107, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (26) the VH domain comprises the amino acid sequence of SEQ ID NO: 107, and the VL domain comprises the amino acid sequence of SEQ ID NO: 110; (27) the VH domain comprises the amino acid sequence of SEQ ID NO: 107, and the VL domain comprises the amino acid sequence of SEQ ID NO: 111; (28) the VH domain comprises the amino acid sequence of SEQ ID NO: 107, and the VL domain comprises the amino acid sequence of SEQ ID NO: 112; (29) the VH domain comprises the amino acid sequence of SEQ ID NO: 107, and the VL domain comprises the amino acid sequence of SEQ ID NO: 113; (30) the VH domain comprises the amino acid sequence of SEQ ID NO: 108, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (31) the VH domain comprises the amino acid sequence of SEQ ID NO: 108, and the VL domain comprises the amino acid sequence of SEQ ID NO: 110; (32) the VH domain comprises the amino acid sequence of SEQ ID NO: 108, and the VL domain comprises the amino acid sequence of SEQ ID NO: 111; (33) the VH domain comprises the amino acid sequence of SEQ ID NO: 108, and the VL domain comprises the amino acid sequence of SEQ ID NO: 112; (34) the VH domain comprises the amino acid sequence of SEQ ID NO: 108, and the VL domain comprises the amino acid sequence of SEQ ID NO: 113; (35) the VH domain comprises the amino acid sequence of SEQ ID NO: 109, and the VL domain comprises the amino acid sequence of SEQ ID NO: 64; (36) the VH domain comprises the amino acid sequence of SEQ ID NO: 109, and the VL domain comprises the amino acid sequence of SEQ ID NO: 110; (37) the VH domain comprises the amino acid sequence of SEQ ID NO: 109, and the VL domain comprises the amino acid sequence of SEQ ID NO: 111; (38) the VH domain comprises the amino acid sequence of SEQ ID NO: 109, and the VL domain comprises the amino acid sequence of SEQ ID NO: 112; or (39) The VH domain comprises the amino acid sequence of SEQ ID NO:109, and the VL domain comprises the amino acid sequence of SEQ ID NO:

113.

94. The multispecific binding molecule of claim 85, wherein the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO:213, and the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO:

214.

95. The multispecific binding molecule of claim 85, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 195, and the VL domain comprises the amino acid sequence of SEQ ID NO:

64.

96. A multispecific binding molecule comprising: (a) a first antibody or antigen-binding fragment thereof comprising a first antigen-binding domain, wherein the first antigen-binding domain binds to human Dectin-1; and (b) a second antibody or antigen-binding fragment thereof comprising a second antigen-binding domain, wherein the second antigen-binding domain binds to the target of interest; wherein the first antigen binding domain comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; wherein the VH domain of the first antigen binding domain comprises: a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1) or DYYM (SEQ ID NO: 199); a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), WINPNEGDTNYAQKFEG (SEQ ID NO: 200), or WINPNEGDTNYAQKFQE (SEQ ID NO: 201); and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3), NSGSASFGY (SEQ ID NO: 187), NSGSYSAGY (SEQ ID NO: 190), or NTGAYSFGY (SEQ ID NO: 204); and wherein the VL domain of the first antigen binding domain comprises: a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO:4); a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO:5) or GASDLQS (SEQ ID NO:206); and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO:6), QAAYSFPFT (SEQ ID NO:192), QQAYSAPFT (SEQ ID NO:193), QQAYGFPFT (SEQ ID NO:207) or HQAYSFPFT (SEQ ID NO:208); wherein the multispecific binding molecule does not include a CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3), a CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO: 6).

97. The multispecific binding molecule of claim 96, wherein: (a) the VH domain of the first antigen-binding domain comprises: a CDR-H1 comprising the amino acid sequence of DYYM (SEQ ID NO: 199), a CDR-H2 comprising the amino acid sequence of WINPNEGDTNYAQKFEG (SEQ ID NO: 200), and a CDR-H3 comprising the amino acid sequence of NTGAYSFGY (SEQ ID NO: 204), and the VL domain of the first antigen-binding domain comprises: a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASDLQS (SEQ ID NO: 206), and a CDR-L3 comprising the amino acid sequence of QQAYGFPFT (SEQ ID NO: 207); (b) the VH domain of the first antigen-binding domain comprises: a CDR-H1 comprising the amino acid sequence of DYYM (SEQ ID NO: 199), a CDR-H2 comprising the amino acid sequence of WINPNEGDTNYAQKFQE (SEQ ID NO: 201), and a CDR-H3 comprising the amino acid sequence of NTGAYSFGY (SEQ ID NO: 204), and the VL domain of the first antigen-binding domain comprises: a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASDLQS (SEQ ID NO: 206), and a CDR-L3 comprising the amino acid sequence of HQAYSFPFT (SEQ ID NO: 208); (c) the VH domain of the first antigen-binding domain comprises: a CDR-H1 comprising the amino acid sequence of DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence of WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence of NSGSASFGY (SEQ ID NO: 187), and the VL domain of the first antigen-binding domain comprises: a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFT (SEQ ID NO: 6); (d) the VH domain of the first antigen-binding domain comprises: a CDR-H1 comprising the amino acid sequence of DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence of WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence of NSGSYSAGY (SEQ ID NO: 190), and the VL domain of the first antigen-binding domain comprises: a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QQAYSFPFT (SEQ ID NO: 6); (e) the VH domain of the first antigen-binding domain comprises: a CDR-H1 comprising the amino acid sequence of DYYI (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence of WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence of NSGSYSFGY (SEQ ID NO: 3), and the VL domain of the first antigen-binding domain comprises: a CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence of GASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence of QAAYSFPFT (SEQ ID NO: 192); or (f) the VH domain of the first antigen-binding domain comprises: CDR-H1 comprising the amino acid sequence of DYYI (SEQ ID NO:1), CDR-H2 comprising the amino acid sequence of WINPNSGDTNYAQKFQG (SEQ ID NO:2), and CDR-H3 comprising the amino acid sequence of NSGSYSFGY (SEQ ID NO:3), and the VL domain of the first antigen-binding domain comprises: CDR-L1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO:4), CDR-L2 comprising the amino acid sequence of GASSLQS (SEQID NO:5), and CDR-L3 comprising the amino acid sequence of QQAYSAPFT (SEQ ID NO:193).

98. The multispecific binding molecule of claim 96 or claim 97, wherein: (a) the VH domain of the first antigen-binding domain comprises the amino acid sequence of SEQ ID NO: 209, and the VL domain of the first antigen-binding domain comprises the amino acid sequence of SEQ ID NO: 210; (b) the VH domain of the first antigen-binding domain comprises the amino acid sequence of SEQ ID NO: 211, and the VL domain of the first antigen-binding domain comprises the amino acid sequence of SEQ ID NO: 212; (c) the VH domain of the first antigen-binding domain comprises the amino acid sequence of SEQ ID NO: 220, and the VL domain of the first antigen-binding domain comprises the amino acid sequence of SEQ ID NO: 221; (d) the VH domain of the first antigen-binding domain comprises the amino acid sequence of SEQ ID NO: 194, and the VL domain of the first antigen-binding domain comprises the amino acid sequence of SEQ ID NO: 64; (e) the VH domain of the first antigen-binding domain comprises the amino acid sequence of SEQ ID NO: 196, and the VL domain of the first antigen-binding domain comprises the amino acid sequence of SEQ ID NO: 64; (f) the VH domain of the first antigen-binding domain comprises the amino acid sequence of SEQ ID NO: 62, and the VL domain of the first antigen-binding domain comprises the amino acid sequence of SEQ ID NO: 197; or (g) the VH domain of the first antigen-binding domain comprises the amino acid sequence of SEQ ID NO:62, and the VL domain of the first antigen-binding domain comprises the amino acid sequence of SEQ ID NO:

198.

99. The multispecific binding molecule of any one of claims 71-98, wherein the target of interest is a pathogen.

100. The multispecific binding molecule of claim 99, wherein the pathogen is a bacterial cell, a fungal cell, a virus, a senescent cell, a tumor cell, a protein aggregate, an LDL particle, a mast cell, an eosinophil, an ILC2 cell, or an inflammatory immune cell.

101. The multispecific binding molecule of claim 100, wherein the target of interest is an antigen expressed on the surface of a bacterial cell, a fungal cell, a senescent cell, a tumor cell, a mast cell, an eosinophil, an ILC2 cell, or an inflammatory immune cell.

102. The multispecific binding molecule of claim 100, wherein the target of interest is a surface antigen of the virus.

103. The multispecific binding molecule of claim 99 or claim 100, wherein the target of interest is an antigen expressed on the surface of a cancer cell.

104. The multispecific binding molecule of claim 103, wherein the target of interest is CD70, HER2, DLL3, adhesion protein-4, TROP-2, mesothelin, LIV-1, C-MET, FOLR1, CD20, CCR8, CD33 or EGFR.

105. The multispecific binding molecule of claim 100, wherein the target of interest is amyloid beta, amyloid lambda light chain, or amyloid kappa light chain.

106. The multispecific binding molecule of any one of claims 71-98, wherein the second antigen binding domain binds CD20 and comprises a VH domain comprising the sequence of SEQ ID NO: 129 and a VL domain comprising the sequence of SEQ ID NO:

130.

107. The multispecific binding molecule of any one of claims 71-98, wherein the second antigen binding domain binds Trop-2 and comprises a VH domain comprising the sequence of SEQ ID NO: 139 and a VL domain comprising the sequence of SEQ ID NO:

140.

108. The multispecific binding molecule of any one of claims 71-98, wherein the second antigen binding domain binds to light chain amyloid and comprises a VH domain comprising the sequence of SEQ ID NO: 143 and a VL domain comprising the sequence of SEQ ID NO:

144.

109. The multispecific binding molecule of any one of claims 71-98, wherein one or both of the first antibody or fragment and the second antibody or fragment are human or humanized antibodies or fragments.

110. The multispecific binding molecule of any one of claims 71-109, wherein one or both of the first antibody or fragment and the second antibody or fragment are Fab, Fab', F(ab')2, Fv, Fab'-SH, F(ab')2, single-chain antibodies, nanobodies, or scFv fragments.

111. The multispecific binding molecule of any one of claims 71-109, wherein one or both of the first antibody or fragment and the second antibody or fragment further comprises an Fc domain.

112. The multispecific binding molecule of any one of claims 71-109, wherein the first antibody or fragment is a Fab fragment, and wherein the second antibody comprises an antibody heavy chain and an antibody light chain.

113. The multispecific binding molecule of any one of claims 71-109, wherein the first antibody and the second antibody each comprise an antibody heavy chain and an antibody light chain.

114. A multispecific binding molecule as described in any one of claims 71-113, wherein the first antibody or fragment is coupled to avidin, streptavidin, neutravidin or a derivative thereof that binds biotin, and the second antibody or fragment is coupled to biotin or a derivative thereof that binds avidin; or wherein the second antibody or fragment is coupled to avidin, streptavidin, neutravidin or a derivative thereof that binds biotin, and the first antibody or fragment is coupled to biotin or a derivative thereof that binds avidin; and wherein the first antibody or fragment binds to the second antibody or fragment via an interaction between the avidin, streptavidin, neutravidin or a derivative thereof that binds biotin and the biotin or a derivative thereof that binds avidin.

115. A multispecific binding molecule as described in claim 114, wherein the first antibody or fragment is a Fab fragment coupled to monomeric streptavidin (mSA), and wherein the second antibody is a biotinylated antibody comprising an antibody heavy chain and an antibody light chain.

116. A multispecific binding molecule as described in claim 114, wherein the first antibody or fragment is a full-length antibody coupled to monomeric streptavidin (mSA), and wherein the second antibody is a biotinylated antibody comprising an antibody heavy chain and an antibody light chain.

117. The multispecific binding molecule of any one of claims 71-109, wherein the multispecific binding molecule comprises a first IgG antibody comprising the first antigen binding domain covalently linked to a second IgG antibody comprising the second antigen binding domain.

118. A multispecific binding molecule as described in any one of claims 71-109, wherein the multispecific binding molecule comprises: a first antibody arm, the first antibody arm comprising a single-chain variable fragment (scFv) comprising a VH domain and a VL domain that bind to human Dectin-1 and a first Fc region; and a second antibody arm, the second antibody arm comprising an antibody heavy chain comprising the VH domain of the second antigen-binding domain and a second Fc region of the VH domain connected to the second antigen-binding domain, the antibody heavy chain being associated with an antibody light chain comprising the VL domain of the second antigen-binding domain.

119. The multispecific binding molecule of claim 118, wherein the first Fc region comprises one or more knob-forming mutations and the second Fc region comprises one or more homologous hole-forming mutations, or wherein the second Fc region comprises one or more knob-forming mutations and the first Fc region comprises one or more homologous hole-forming mutations.

120. The multispecific binding molecule of claim 118 or claim 119, wherein the first antibody arm comprises a first linker between the VH domain and the VL domain and a second linker between the VL domain and the first Fc region.

121. The multispecific binding molecule of claim 120, wherein the first linker comprises one or more repeats of the sequence GGGGS (SEQ ID NO: 115).

122. The multispecific binding molecule of claim 121, wherein the first linker comprises the sequence GGGGSGGGGSGGGGS (SEQ ID NO: 116) or GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 117).

123. The multispecific binding molecule of any one of claims 120-122, wherein the second linker comprises the sequence EPKRSDKTHTCPPC (SEQ ID NO: 118) or SATHTCPPC (SEQ ID NO: 119).

124. A multispecific binding molecule as described in any one of claims 120-123, wherein the VH domain of the first antibody arm comprises the amino acid sequence of SEQ ID NO:220, and wherein the VL domain of the second antibody arm comprises the amino acid sequence of SEQ ID NO:

221.

125. The multispecific binding molecule of claim 124, wherein the scFv comprises the amino acid sequence of SEQ ID NO:

222.

126. The multispecific binding molecule of claim 124, wherein the first antibody arm comprises the amino acid sequence of SEQ ID NO: 224 or 225.

127. A multispecific binding molecule as described in any one of claims 71-109, wherein the multispecific binding molecule comprises: a first antibody arm, the first antibody arm comprising a first antibody heavy chain comprising the VH domain and a first Fc region of the first antigen binding domain, and a first antibody light chain comprising the VL domain of the first antigen binding domain; and a second antibody arm, the second antibody arm comprising a second antibody heavy chain comprising the VH domain and a second Fc region of the second antigen binding domain, and a second antibody light chain comprising the VL domain of the second antigen binding domain, wherein the first Fc region comprises one or more knob-forming mutations, and the second Fc region comprises one or more homologous hole-forming mutations.

128. The multispecific binding molecule of claim 119 or claim 127, wherein the first Fc region comprises a T366W substitution according to EU numbering, and wherein the second Fc region comprises T366S, L368A, and Y407V substitutions.

129. A multispecific binding molecule as described in any one of claims 71-109, wherein the multispecific binding molecule comprises: a first antibody arm, which comprises a first antibody heavy chain comprising the VH domain of the first antigen binding domain and a first Fc region; and a second antibody arm, which comprises a second antibody heavy chain comprising the VH domain of the second antigen binding domain and a second Fc region, wherein the first Fc region comprises one or more hole-forming mutations and the second Fc region comprises one or more homologous knob-forming mutations.

130. The multispecific binding molecule of claim 119 or claim 129, wherein the first Fc region comprises T366S, L368A, and Y407V substitutions according to EU numbering, and wherein the second Fc region comprises a T366W substitution.

131. The multispecific binding molecule of any one of claims 127-130, wherein the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO:209, and wherein the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO:

210.

132. The multispecific binding molecule of any one of claims 127-130, wherein the VH domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO: 220, and wherein the VL domain of the first antigen binding domain comprises the amino acid sequence of SEQ ID NO:

221.

133. The multispecific binding molecule of claim 132, wherein the first antibody heavy chain comprises a C→S substitution at position 5 according to IMGT hinge numbering, and wherein the first antibody light chain comprises a C→S substitution at the terminal residue of the light chain constant domain.

134. The multispecific binding molecule of claim 132, wherein the first antibody heavy chain comprises the amino acid sequence of SEQ ID NO:219, and wherein the first antibody light chain comprises the amino acid sequence of SEQ ID NO:

223.

135. The multispecific binding molecule of any one of claims 111-134, wherein one or both of the first antibody or fragment and the second antibody or fragment comprise a human IgG Fc region.

136. The multispecific binding molecule of claim 135, wherein the Fc region is a human IgGl or human IgG4 Fc region.

137. The multispecific binding molecule of claim 136, wherein the Fc region is: (a) a human IgG1 Fc region comprising S239D and I332E substitutions according to EU numbering; (b) a human IgG1 Fc region comprising, according to EU numbering, S239D, A330L and I332E substitutions; (c) a human IgG1 Fc region comprising, according to EU numbering, substitutions G236A, S239D, A330L, and I332E; or (d) Human IgG4 Fc region comprising the S228P substitution according to EU numbering.

138. The multispecific binding molecule of claim 136, wherein the multispecific binding molecule comprises two antibody heavy chains, and wherein each of the antibody heavy chains comprises an amino acid substitution at one or more of positions 234, 235, and 237 according to EU numbering.

139. The multispecific binding molecule of claim 138, wherein each of the antibody heavy chains comprises L234A, L235E, and G237A substitutions according to EU numbering.

140. The multispecific binding molecule of any one of claims 136-139, wherein the multispecific binding molecule comprises two antibody heavy chains, and wherein only one of the antibody heavy chains comprises H435R and Y436F substitutions according to EU numbering.

141. The multispecific binding molecule of any one of claims 111-140, wherein only one of the antibody arms comprises a heavy chain comprising F126C and C220V substitutions and a light chain comprising S121C and C214V substitutions according to EU numbering.

142. A multispecific binding molecule as described in any of claims 71-109, wherein the multispecific binding molecule comprises a first antibody heavy chain and a first antibody light chain and a second antibody heavy chain and a second antibody light chain, wherein the VH domain of the first antibody heavy chain forms a first antigen binding domain with the VL domain of the first antibody light chain, wherein the VH domain of the second antibody heavy chain forms a second antigen binding domain with the VL domain of the second antibody light chain, wherein according to EU numbering, the first antibody heavy chain comprises F126C, C220V and T366W substitutions, wherein the first antibody light chain comprises S121C and C214V substitutions, and wherein the second antibody heavy chain comprises T366S, L368A, Y407V, H435R and Y436F substitutions.

143. The multispecific binding molecule of claim 142, wherein the first antibody heavy chain and the second antibody heavy chain further comprise L234A, L235E and G237A substitutions according to EU numbering.

144. The multispecific binding molecule of any one of claims 111-143, wherein at least one or both of the first antibody heavy chain and the second antibody heavy chain are non-fucosylated or comprise reduced fucosylation.

145. A multispecific binding molecule comprising: (a) a first arm, comprising a single-chain variable fragment (scFv) that binds to human Dectin-1 and a first Fc region, wherein the scFv comprises a first VH domain and a first VL domain, and (b) a second arm comprising a second antibody comprising a second antigen binding domain and a second Fc region, wherein the second antigen binding domain binds a target of interest; wherein the VH domain of the first antibody arm comprises the amino acid sequence of SEQ ID NO:220, and wherein the VL domain of the second antibody arm comprises the amino acid sequence of SEQ ID NO:

221.

146. The multispecific binding molecule of claim 145, wherein the scFv comprises the amino acid sequence of SEQ ID NO:

222.

147. The multispecific binding molecule of claim 145, wherein the first arm comprises the amino acid sequence of SEQ ID NO: 224 or 225.

148. A multispecific binding molecule comprising: (a) a first arm, comprising a first antibody heavy chain and a first antibody light chain, wherein the first antibody heavy chain comprises a first VH domain and a first Fc region, wherein the first antibody light chain comprises a first VL domain, and wherein the first VH domain and the VL domain form a first antigen binding domain that binds to human Dectin-1; and (b) a second arm, comprising a second antibody heavy chain and a second antibody light chain, wherein the second antibody heavy chain comprises a second VH domain and a second Fc region, wherein the second antibody light chain comprises a second VL domain, and wherein the second VH domain and the second VL domain form a second antigen binding domain that binds a target of interest; in: The first VH domain comprises the amino acid sequence of SEQ ID NO: 209 and the first VL domain comprises the amino acid sequence of SEQ ID NO: 210, or The first VH domain comprises the amino acid sequence of SEQ ID NO:220 and the first VL domain comprises the amino acid sequence of SEQ ID NO:

221.

149. The multispecific binding molecule of claim 148, wherein the first antibody heavy chain comprises a C→S substitution at position 5 according to IMGT hinge numbering, and wherein the first antibody light chain comprises a C→S substitution at the terminal residue of the light chain constant domain.

150. The multispecific binding molecule of claim 148, wherein the first antibody heavy chain comprises the amino acid sequence of SEQ ID NO:219, and wherein the first antibody light chain comprises the amino acid sequence of SEQ ID NO:

223.

151. A polynucleotide encoding the antibody or multispecific binding molecule of any one of claims 1-150.

152. A vector comprising the polynucleotide of claim 151.

153. An isolated host cell comprising the polynucleotide of claim 151 or the vector of claim 152.

154. The isolated host cell of claim 153, wherein the host cell is a yeast, insect, plant or prokaryotic cell.

155. The isolated host cell of claim 153, wherein the host cell is a mammalian cell.

156. The isolated host cell of claim 155, wherein the mammalian cell is a Chinese Hamster Ovary (CHO) cell.

157. The isolated host cell of claim 155 or claim 156, wherein the host cell comprises an alpha 1,6-fucosyltransferase (Fut8) or alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosamine transferase (MGAT1) knockout.

158. The isolated host cell of claim 155 or claim 156, wherein the host cell overexpresses β1,4-N-acetylglucosamine transferase III (GnT-III).

159. The isolated host cell of claim 158, wherein the host cell further overexpresses Golgi μ-mannosidase II (ManII).

160. A method of producing an antibody or a multispecific binding molecule, the method comprising culturing the host cell of any one of claims 153-159 under conditions suitable for production of the antibody or multispecific binding molecule.

161. The method of claim 160, further comprising recovering the antibody or multispecific binding molecule.

162. The method of claim 160 or claim 161, wherein the host cell is treated with kifunine prior to producing the antibody or multispecific binding molecule.

163. An antibody or antigen-binding fragment thereof that binds to human Dectin-1, wherein the antibody or antigen-binding fragment thereof is produced by the method of any one of claims 160-162.

164. A pharmaceutical composition comprising the antibody or multispecific binding molecule of any one of claims 1-150 and 163 and a pharmaceutically acceptable carrier.

165. A method of treating a disease or disorder, the method comprising administering to an individual in need thereof an effective amount of the antibody of any one of claims 1-70, the multispecific binding molecule of any one of claims 71-150, or the composition of claim 164.

166. The method of claim 165, wherein the first target of interest is human Dectin-1, and wherein the second target of interest is a pathogen.

167. The method of claim 166, wherein the pathogen is a bacterial cell, a fungal cell, a virus, a senescent cell, a tumor cell, a protein aggregate, an LDL particle, a mast cell, an eosinophil, an ILC2 cell, or an inflammatory immune cell.

168. The method of claim 167, wherein the target of interest is an antigen expressed on the surface of a bacterial cell, a fungal cell, a senescent cell, a tumor cell, a mast cell, an eosinophil, an ILC2 cell, or an inflammatory immune cell.

169. The method of claim 167, wherein the target of interest is a surface antigen of the virus.

170. The method of any one of claims 165-169, wherein the disease or condition is cancer, a bacterial infection, a fungal infection, a viral infection, a mast cell disease or condition, systemic mastocytosis, amyloidosis, or an aging-related disease or condition.

171. The method of any one of claims 165-170, wherein the target of interest is an antigen expressed on the surface of a cancer cell.

172. The method of claim 171, wherein the second target of interest is CD70, HER2, DLL3, adhesion protein-4, TROP-2, mesothelin, LIV-1, C-MET, FOLR1, CD20, CCR8, CD33 or EGFR.

173. A method of treating cancer, the method comprising administering an effective amount of a composition comprising a multispecific binding molecule according to any one of claims 71-150, wherein the multispecific binding molecule comprises: (a) a first antibody or an antigen-binding fragment thereof, wherein the first antibody or the antigen-binding fragment thereof comprises a first antigen-binding domain that binds to human Dectin-1; and (b) a second antibody or antigen-binding fragment thereof, comprising a second antigen-binding domain, wherein the second antigen-binding domain binds to CD70, HER2, DLL3, adhesion protein-4, TROP-2, mesothelin, LIV-1, C-MET, FOLR1, CD20, CCR8, CD33 or EGFR.

174. The method of claim 173, wherein the second antigen binding domain binds CD20; wherein the second antigen binding domain comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; and wherein the VH domain of the second antigen binding domain comprises the sequence of SEQ ID NO: 129 and / or wherein the VL domain of the second antigen binding domain comprises the sequence of SEQ ID NO:

130.

175. The method of claim 173, wherein the second antigen binding domain binds Trop-2; wherein the second antigen binding domain comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; and wherein the VH domain of the second antigen binding domain comprises the sequence of SEQ ID NO: 139 and / or wherein the VL domain of the second antigen binding domain comprises the sequence of SEQ ID NO:

140.

176. The method of claim 173, wherein the second antigen binding domain binds to light chain amyloid; wherein the second antigen binding domain comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; and wherein the VH domain of the second antigen binding domain comprises the sequence of SEQ ID NO: 143 and / or wherein the VL domain of the second antigen binding domain comprises the sequence of (SEQ ID NO:

144.

177. The method of any one of claims 173 to 176, (a) the multispecific antibody comprises a first antibody arm comprising the first antigen-binding domain and a first Fc region and a second antibody arm comprising the second antigen-binding domain and a second Fc region, wherein the first Fc region comprises one or more knob-forming mutations, and the second Fc region comprises one or more homologous hole-forming mutations; or (b) The multispecific antibody comprises a first antibody arm comprising the first antigen-binding domain and a first Fc region and a second antibody arm comprising the second antigen-binding domain and a second Fc region, wherein the first Fc region comprises one or more hole-forming mutations and the second Fc region comprises one or more cognate knob-forming mutations.

178. The method of claim 177, wherein: (a) wherein the first Fc region comprises a T366W substitution, and wherein the second Fc region comprises T366S, L368A, and Y407V substitutions according to EU numbering; or (b) according to EU numbering, said first Fc region comprises T366S, L368A and Y407V substitutions, and wherein said second Fc region comprises a T366W substitution.

179. The method of any one of claims 173-178, wherein the antibody comprises two antibody heavy chains, and wherein only one of the antibody heavy chains comprises H435R and Y436F substitutions according to EU numbering.

180. The method of any one of claims 173-179, wherein only one of the antibody arms comprises a heavy chain comprising F126C and C220V substitutions and a light chain comprising S121C and C214V substitutions according to EU numbering.

181. The method of any one of claims 173-180, wherein the first antibody heavy chain and the second antibody heavy chain comprise a human IgGl Fc domain.

182. The method of any one of claims 173-181, wherein at least one or both of the first antibody heavy chain and the second antibody heavy chain are non-fucosylated or comprise reduced fucosylation.

183. The method of any one of claims 173-182, wherein the individual is a human.

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