Anti-Dectin-1 Antibody and Method of Use Thereof

Abstract

The present disclosure relates to antibodies, multispecific (e.g., bispecific) binding molecules that bind to human Dectin-1, and related methods of use and production. Disclosed herein is a method of targeted phagocytosis for removing disease-causing agents, including host cells / host cell products, microorganisms, or products thereof, by administering a multispecific (e.g., bispecific) binding molecule that comprises a Dectin-1 binding arm and a second arm that specifically binds to the agent. The multispecific (e.g., bispecific) binding molecule allows phagocytes to engage with the target agent and form a synapse between them, promoting the clustering of Dectin-1 on the phagocyte. This stimulates phagocytosis of the target agent and also stimulates cytokine secretion by the phagocyte via the Dectin-1 / Syk / NfkB pathway.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 63 / 327,288, filed April 4, 2022, the disclosure of which is incorporated herein by reference in its entirety.

[0002] Reference to the electronic sequence listing The contents of the electronic sequence listing (186542000640seqlist.xml, size: 306,885 bytes, created on March 31, 2023) are incorporated herein by reference in their entirety.

[0003] The present disclosure relates to antibodies, multispecific (eg, bispecific) binding molecules that bind to human Dectin-1, and related methods of use and production. [Background technology]

[0004] 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 ingest abnormal or disease-causing host or foreign material. The ingested material is destroyed through the phagocyte's endolysosomal pathway. Additionally, dendritic cells and macrophages can present antigens to cells of the adaptive immune system to further facilitate the elimination of disease-causing agents.

[0005] Dectin-1 is a C-type lectin receptor that recognizes β-glucans and promotes antifungal phagocytic activity. Dectin-1 is expressed on phagocytes and has been clearly shown to be sufficient for phagocytic activation. Dectin-1 can be used for antibody-targeted phagocytosis and elimination of disease-causing agents.

[0006] It would be beneficial to develop targeted removal and degradation of accumulated disease-causing agents without increasing overall phagocytosis. The present disclosure provides a solution to this problem and describes other advantages.

[0007] All references cited herein, including patent applications, patent publications, and scientific literature, are incorporated by reference in their entirety as if each individual reference was specifically and individually indicated to be incorporated by reference. Summary of the Invention [Means for solving the problem]

[0008] The present disclosure relates to antibodies, multispecific (e.g., bispecific) binding molecules that bind to human Dectin-1, and related methods of use and production. Disclosed herein are methods of targeted phagocytosis for the removal of disease-causing agents, including host cells / host cell products, microorganisms, or their products, by administering a multispecific (e.g., bispecific) binding molecule comprising a Dectin-1-binding arm and a second arm that specifically binds to the agent. The multispecific (e.g., bispecific) binding molecule enables phagocytes to engage with the target agent, form a synapse therebetween, and promote the clustering of Dectin-1 on the phagocyte. This stimulates phagocytosis of the target agent and simultaneously stimulates cytokine secretion by the phagocyte via the Dectin-1 / Syk / NfkB pathway. Furthermore, antigens from the endocytosed agent are presented on the surface of dendritic cells / macrophages, enhancing the adaptive immune response against the disease-causing agent. Overall, Dectin-1 agonist multispecific (e.g., bispecific) binding molecules are believed to promote immunostimulation, targeted phagocytosis, and neoantigen presentation / activation of the adaptive immune system to eliminate disease-causing agents.

[0009] Thus, the present disclosure describes, inter alia, the generation and functional characterization of agonistic anti-human Dectin-1 antibodies that exhibit high-affinity binding to Dectin-1 and can promote immune stimulation, as well as variants of the antibodies that may modulate their binding affinity or reduce their immunogenic potential (i.e., by reverting some residues to human germline residues and / or removing potential human T-cell epitopes). Additionally, the generation of bispecific antibody formats comprising an anti-human Dectin-1 antibody and an antibody targeting an antigen on a disease-causing agent is also described, with data supporting target engagement, immune stimulation, phagocytosis, and antigen presentation.

[0010] In some embodiments, there is provided 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; and the VH domain has the amino acid sequence QVQLVQSGAEVKKPGASVKVSCKSSGYTFTX1YYIHWVRQAPGQGLEWMGWINPNSGX2TNYAQKFQGRITMTRDTSISTAYLELSRLRSDDTAVFYCAX3X4X5X6X7X8X9X 10 X 11 X 12 WGQGTLVTVSS [where X1 is D, A, or G, X2 is D, A, or G, X3 is R, A, or G, X4 is N, A, or G, X5 is S, A, or G, X6 is A or G, X7 is S, A, or G, X8 is Y, A, or G, X9 is S, A, or G, and X 10 is F, A, or G, and X 11 is A or G and X 12X1 is Q, A, or G; X2 is Q, A, or G; X3 is F, Y, A, or G; X4 is S, A, or G; X5 is F, A, or G; X6 is P, A, or G; X7 is F, A, or G; and X8 is T, A, or G (SEQ ID NO: 65). In some embodiments, 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). In some embodiments, the VH domain comprises 1, no more than 2, no more than 3, no more than 4, or no more than 5 substitutions compared to the amino acid sequence of SEQ ID NO: 62, and / or the VL domain comprises 1, no more than 2, no more than 3, no more than 4, or no more than 5 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 Dectin-1; and / or does not compete with the natural ligand of human Dectin-1.

[0011] In some embodiments, there is provided 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 CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1) or AYYI (SEQ ID NO: 16), CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2) or WINPNSGATNYAQKFQG (SEQ ID NO: 19), and CDR-H3 comprising the amino acid sequence 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: 36), NSGSYSFY (SEQ ID NO: 37), NSGSYSFY (SEQ ID NO: 38), NSGSYSFY (SEQ ID NO: 39), NSGSYSFY (SEQ ID NO: 40), NSGSYSFY (SEQ ID NO: 41), NSGSYSFY (SEQ ID NO: 42), NSGSYSFY (SEQ ID NO: 43), NSGSYSFY (SEQ ID NO: 44), NSGSYSFY (SEQ ID NO: 45), NSGSYSFY (SEQ ID NO: 46), NSGSYSFY (SEQ ID NO: 47), NSGSYSFY (SEQ ID NO: 48), NSGSYSFY (SEQ ID NO: 49), NSGAYSFGY (SEQ ID NO: 50), and a CDR-H3 comprising an amino acid sequence selected from the group consisting of NSGSYSFGA (SEQ ID NO:37), and NSGSYSFGA (SEQ ID NO:39); and a CDR-L1 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). In some embodiments, 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).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 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 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 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 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 NSASYSFGY (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 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 NSGSYSFGA (SEQ ID NO: 39). In some embodiments, the VH domain further comprises an FR1 comprising an amino acid sequence selected from the group consisting of QVQLVQSGAEVKKPGASVKVSCKSSGYTFT (SEQ ID NO: 50) and QVQLVQSGAEVKKPGASVKVSCKASGYTFT (SEQ ID NO: 51), an FR2 comprising the amino acid sequence HWVRQAPGQGLEWMG (SEQ ID NO: 52), an FR3 comprising an amino acid sequence selected from the group consisting of RITMTRDTSISTAYLELSRLRSDDTAVFYCAR (SEQ ID NO: 53) and RVTMTRDTSISTAYMELSRLRSDDTAVYYCAR (SEQ ID NO: 54), and an FR4 comprising the amino acid sequence WGQGTLVTVSS (SEQ ID NO: 55). 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 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). 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 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). 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 QQAYAFPFT (SEQ ID NO:45). 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 QQAYSAPFT (SEQ ID NO:46). 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 QQAYSFAFT (SEQ ID NO:47). 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 QQAYSFPAT (SEQ ID NO:48).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 QQAYSFPFA (SEQ ID NO:49). In some embodiments, the VL domain further comprises an FR1 comprising the amino acid sequence DIQMTQSPSSVSASVGDRVTITC (SEQ ID NO:56), an FR2 comprising an amino acid sequence selected from the group consisting of WYQQKPGKAPKLLIF (SEQ ID NO:57) and WYQQKPGKAPKLLIY (SEQ ID NO:58), an FR3 comprising an amino acid sequence selected from the group consisting of GVPSRFSGSGSGTDFTLTVSSLQPEDFATYYC (SEQ ID NO:59) and GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC (SEQ ID NO:60), and an FR4 comprising the amino acid sequence FGPGTKVDIE (SEQ ID NO:61).

[0012] In some embodiments, there is provided 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 CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7) or GYTFTAYY (SEQ ID NO: 17), and CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8) or INPNSGAT (SEQ ID NO: 20), and a CDR-H3 comprising any one of ARNSGSYSFGY (SEQ ID NO: 9), ARASGSYSFGY (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: 34), ARNSGSYSAGY (SEQ ID NO: 36), and CDR-H3 comprising an amino acid sequence selected from the group consisting of ARNSGSYSFAY (SEQ ID NO: 38), and ARNSGSYSFGA (SEQ ID NO: 40); and CDR-L1, the VL domain of which comprises a CDR-L2 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 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), and QQAYSFPFA (SEQ ID NO: 49). In some embodiments, the antibody does not comprise 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 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, a 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 ARNSGSYSFGY (SEQ ID NO:9). In some embodiments, a 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, a 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, a 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 ARASGSYSFGY (SEQ ID NO:23). In some embodiments, a 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, a 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, a 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, a 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, a 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 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 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 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).

[0013] In some embodiments, there is provided 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 CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13) or GYTFTAY (SEQ ID NO: 18), and CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14) or NPNSGA (SEQ ID NO: 21), and 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: 35), NSGSYSFAY (SEQ ID NO: 37), and and CDR-H3 comprising an amino acid sequence selected from the group consisting of NSGSYSFGA (SEQ ID NO:39); and CDR-L1, the VL domain of which comprises a CDR-L2 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). In some embodiments, the antibody does not comprise 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 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 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, a 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, a 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, a 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 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). 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 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).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 QQAYAFPFT (SEQ ID NO:45). 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 QQAYSAPFT (SEQ ID NO:46). 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 QQAYSFAFT (SEQ ID NO:47). 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 QQAYSFPAT (SEQ ID NO:48). 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 QQAYSFPFA (SEQ ID NO:49).

[0014] 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 comprise 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: 9 ...5. 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: 104. In some embodiments, the VH 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.

[0015] In some embodiments, there is provided 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 has the amino acid sequence QVQLVQSGAEVKKPGASVKVSCKX1SGYTFTX2YYX3HWVRQAPGQGLEWMGWINPNSGX4TNYAQKFQGRX5TMTRDTSISTAYX6ELSRLRSDDTAVX7YCARNSGSYSFGYWGQGTLVTVSS, wherein X1 is S or A, X2 is D or G, and X3 is I or M; , X4 is D or G, X5 is I or V, X6 is L or M, and X7 is F or Y] (SEQ ID NO: 80); and the VL domain comprises the amino acid sequence DIQMTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKAPKLLIX1X2ASSLQSGVPSRFSGSGSGTDFTLTX3SSLQPEDFATYYCQQAYSFPFTFGPGTKVDIE [wherein X1 is F or Y, X2 is G or A, and X3 is V or I] (SEQ ID NO: 81). In some embodiments, 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).

[0016] 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; 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 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). In some embodiments, 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). 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 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 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 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 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 further comprises an FR1 comprising an amino acid sequence selected from the group consisting of QVQLVQSGAEVKKPGASVKVSCKSSGYTFT (SEQ ID NO:50) and QVQLVQSGAEVKKPGASVKVSCKASGYTFT (SEQ ID NO:76), an FR2 comprising the amino acid sequence HWVRQAPGQGLEWMG (SEQ ID NO:52), an FR3 comprising an amino acid sequence selected from the group consisting of RITMTRDTSISTAYLELSRLRSDDTAVFYCAR (SEQ ID NO:53) and RVTMTRDTSISTAYMELSRLRSDDTAVYYCAR (SEQ ID NO:77), and an FR4 comprising the amino acid sequence WGQGTLVTVSS (SEQ ID NO:55). 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 RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence AASSLQS (SEQ ID NO: 73), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO: 6).In some embodiments, the VL domain further comprises an FR1 comprising the amino acid sequence DIQMTQSPSSVSASVGDRVTITC (SEQ ID NO: 56), an FR2 comprising an amino acid sequence selected from the group consisting of WYQQKPGKAPKLLIF (SEQ ID NO: 57) and WYQQKPGKAPKLLIY (SEQ ID NO: 78), an FR3 comprising an amino acid sequence selected from the group consisting of GVPSRFSGSGSGTDFTLTVSSLQPEDFATYYC (SEQ ID NO: 59) and GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC (SEQ ID NO: 79), and an FR4 comprising the amino acid sequence FGPGTKVDIE (SEQ ID NO: 61). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence DYYM (SEQ ID NO: 199), a CDR-H2 comprising the amino acid sequence WINPNEGDTNYAQKFEG (SEQ ID NO: 200), and a CDR-H3 comprising the amino acid sequence NTGAYSFGY (SEQ ID NO: 204), and 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 GASDLQS (SEQ ID NO: 206), and a CDR-L3 comprising the amino acid sequence QQAYGFPFT (SEQ ID NO: 207). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence DYYM (SEQ ID NO: 199), a CDR-H2 comprising the amino acid sequence WINPNEGDTNYAQKFQE (SEQ ID NO: 201), and a CDR-H3 comprising the amino acid sequence NTGAYSFGY (SEQ ID NO: 204), and 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 GASDLQS (SEQ ID NO: 206), and a CDR-L3 comprising the amino acid sequence HQAYSFPFT (SEQ ID NO: 208).

[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; the VH domain comprises CDR-H1 comprising an amino acid sequence selected from the group consisting of GYTFTDYY (SEQ ID NO: 7) and GYTFTGYY (SEQ ID NO: 68), CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8) or INPNSGGT (SEQ ID NO: 71), and CDR-H3 comprising the amino acid sequence ARNSGSYSFGY (SEQ ID NO: 9); and the VL domain comprises CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11) or AAS (SEQ ID NO: 74), and CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO: 12). In some embodiments, the antibody does not comprise 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 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 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 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 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 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 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 AAS (SEQ ID NO:74), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO:12). 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 INPNEGDT (SEQ ID NO: 202), and a CDR-H3 comprising the amino acid sequence ARNTGAYSFGY (SEQ ID NO: 205), and 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 QQAYGFPFT (SEQ ID NO: 207). 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 INPNEGDT (SEQ ID NO: 202), and a CDR-H3 comprising the amino acid sequence ARNTGAYSFGY (SEQ ID NO: 205), and 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 HQAYSFPFT (SEQ ID NO: 208).

[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; 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 NPNSGG (SEQ ID NO: 72), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 15); and 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 comprise 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 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 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 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 NSGSYSFGY (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 RASQGISSWLA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence AASSLQS (SEQ ID NO:75), 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 GYTFTDY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence NPNEGD (SEQ ID NO: 203), and a CDR-H3 comprising the amino acid sequence NTGAYSFGY (SEQ ID NO: 204), and 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 GASDLQS (SEQ ID NO: 206), and a CDR-L3 comprising the amino acid sequence QQAYGFPFT (SEQ ID NO: 207). 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 NPNEGD (SEQ ID NO: 203), and a CDR-H3 comprising the amino acid sequence NTGAYSFGY (SEQ ID NO: 204), and 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 GASDLQS (SEQ ID NO: 206), and a CDR-L3 comprising the amino acid sequence HQAYSFPFT (SEQ ID NO: 208).

[0019] 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 comprise 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.

[0020] 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.

[0021] In some embodiments, there is provided 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 CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1) or DYYM (SEQ ID NO: 199), CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), WINPNEGDTNYAQKFEG (SEQ ID NO: 200), or WINPNEGDTNYAQKFQE (SEQ ID NO: 201), and 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 the VL domain comprises CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), and CDR-H3 comprising the amino acid sequence GA Provided herein is an antibody or fragment comprising a CDR-L2 comprising SSLQS (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 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).In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence DYYM (SEQ ID NO: 199), a CDR-H2 comprising the amino acid sequence WINPNEGDTNYAQKFEG (SEQ ID NO: 200), and a CDR-H3 comprising the amino acid sequence NTGAYSFGY (SEQ ID NO: 204), and 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 GASDLQS (SEQ ID NO: 206), and a CDR-L3 comprising the amino acid sequence QQAYGFPFT (SEQ ID NO: 207). In some embodiments, the VH domain comprises a CDR-H1 comprising the amino acid sequence DYYM (SEQ ID NO: 199), a CDR-H2 comprising the amino acid sequence WINPNEGDTNYAQKFQE (SEQ ID NO: 201), and a CDR-H3 comprising the amino acid sequence NTGAYSFGY (SEQ ID NO: 204), and 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 GASDLQS (SEQ ID NO: 206), and a CDR-L3 comprising the amino acid sequence HQAYSFPFT (SEQ ID NO: 208). 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 NSGSASFGY (SEQ ID NO: 187), and 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 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: 190), and 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 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), and 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 QAAYSFPFT (SEQ ID NO: 192). 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), and 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 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.

[0022] 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 a S228P substitution 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 binds to human Dectin-1 and a second antigen-binding domain that binds to a target of interest, or a bispecific antibody, fragment, or diabody 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 binds 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 binds 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 associated with an antibody light chain comprising a VL domain of a second antigen-binding domain, and a second Fc region connected to the VH 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 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 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, 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 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, the first Fc region comprises a T366W substitution according to EU numbering, and the second Fc region comprises T366S, L368A, and Y407V substitutions. In some embodiments, 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. In some embodiments, the first linker comprises one or more repeats of the sequence GGGGS (SEQ ID NO: 115). In some embodiments, the first linker comprises the sequence GGGGSGGGGSGGGGS (SEQ ID NO: 116) or GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 117). In some embodiments, the second linker comprises the sequence EPKRSDKTHTCPPC (SEQ ID NO: 118) or SATHTCPPC (SEQ ID NO: 119). In some embodiments, the bispecific antibody 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 bispecific antibody comprises a first antibody arm comprising a first antibody heavy chain comprising a VH domain of 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 of 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 cognate hole-forming mutations. In some embodiments, the first Fc region comprises a T366W substitution according to EU numbering 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 of 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 of 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, the first Fc region comprises T366S, L368A, and Y407V substitutions according to EU numbering, 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 a first antibody heavy chain, together with the VL domain of the first antibody light chain, forms an antigen-binding domain that binds to human Dectin-1, and the VH domain of a second antibody heavy chain, together with the VL domain of the second antibody light chain, forms an antigen-binding domain that binds to a target of interest, and wherein the VH domain of the first antibody heavy chain comprises the amino acid sequence of SEQ ID NO: 209 and 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 a first antibody heavy chain, together with the VL domain of the first antibody light chain, forms an antigen-binding domain that binds to human Dectin-1, and the VH domain of a second antibody heavy chain, together with the VL domain of the second antibody light chain, forms an antigen-binding domain that binds to a target of interest, and wherein the VH domain of the first antibody heavy chain comprises the amino acid sequence of SEQ ID NO: 220 and 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 the IMGT hinge numbering, and 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 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, a bispecific antibody comprises a first IgG antibody comprising a first antigen-binding domain linked to biotin or an avidin-binding derivative thereof, and a second IgG antibody comprising a second antigen-binding domain linked to avidin, streptavidin, neutravidin, or a biotin-binding derivative thereof, wherein the biotin or an avidin-binding derivative thereof is bound to the avidin, streptavidin, neutravidin, or biotin-binding derivative thereof. In some embodiments, a bispecific antibody comprises a first IgG antibody comprising a first antigen-binding domain linked to avidin, streptavidin, neutravidin, or a biotin-binding derivative thereof, and a second IgG antibody comprising a second antigen-binding domain linked to biotin or an avidin-binding derivative thereof, wherein the biotin or an avidin-binding derivative thereof is bound to the avidin, streptavidin, neutravidin, or biotin-binding derivative thereof.

[0023] In some embodiments, a multispecific (e.g., bispecific) binding molecule comprises a first antibody or antigen-binding fragment thereof comprising a first antigen-binding domain that binds to human Dectin-1, and a second antibody or antigen-binding fragment thereof comprising a second antigen-binding domain that 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; and the VH domain of the first antigen-binding domain comprises the amino acid sequence DYYI (SEQ ID NO: 1) or DYYM (SEQ ID NO: 19). 9), 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); the L 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); Provided herein is a multispecific binding molecule that 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).In some embodiments, the VH domain of the first antigen-binding domain comprises CDR-H1 comprising the amino acid sequence DYYM (SEQ ID NO: 199), CDR-H2 comprising the amino acid sequence WINPNEGDTNYAQKFEG (SEQ ID NO: 200), and CDR-H3 comprising the amino acid sequence NTGAYSFGY (SEQ ID NO: 204), and the VL domain of the first antigen-binding domain comprises CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), CDR-L2 comprising the amino acid sequence GASDLQS (SEQ ID NO: 206), and CDR-L3 comprising the amino acid sequence QQAYGFPFT (SEQ ID NO: 207). In some embodiments, the VH domain of the first antigen-binding domain comprises CDR-H1 comprising the amino acid sequence DYYM (SEQ ID NO: 199), CDR-H2 comprising the amino acid sequence WINPNEGDTNYAQKFQE (SEQ ID NO: 201), and CDR-H3 comprising the amino acid sequence NTGAYSFGY (SEQ ID NO: 204), and the VL domain of the first antigen-binding domain comprises CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), CDR-L2 comprising the amino acid sequence GASDLQS (SEQ ID NO: 206), and CDR-L3 comprising the amino acid sequence HQAYSFPFT (SEQ ID NO: 208). In some embodiments, the VH domain of the first antigen-binding domain comprises 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: 187), and the VL domain of the first antigen-binding domain comprises 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 QQAYSFPFT (SEQ ID NO: 6).In some embodiments, the VH domain of the first antigen-binding domain comprises 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 NSGSYSAGY (SEQ ID NO: 190), and the VL domain of the first antigen-binding domain comprises 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 QQAYSFPFT (SEQ ID NO: 6). In some embodiments, the VH domain of the first antigen-binding domain comprises 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 NSGSYSFGY (SEQ ID NO: 3), and the VL domain of the first antigen-binding domain comprises 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 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 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), 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), and a CDR-L3 comprising the amino acid sequence 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 the VL domain of the first antibody arm comprises the amino acid sequence of SEQ ID NO:221.

[0024] In some embodiments, provided herein are multispecific (e.g., bispecific) binding molecules comprising a single-chain variable fragment (scFv) comprising a VH domain and a VL domain of the present disclosure that binds to human Dectin-1 and a first antibody arm comprising a first Fc region, 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 VL domain of the second antibody arm form an antigen-binding domain that binds to a target of interest (e.g., other than 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 QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYMHWVRQAPGQGLEWMGWINPNEGDTNYAQKFEGRITMTRDTSISTAYMELSRLRSDDTAVYYCARNTGAYSFGYWGCGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKCPKLLIYGASDLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAYGFPFTFGPGTKVDIKEPK (SEQ ID NO: 222).Amino acid sequence: QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYMHWVRQAPGQGLEWMGWINPNEGDTNYAQKFEGRITMTRDTSISTAYMELSRLRSDDTAVYYCARNTGAYSFGYWGCGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKCPKLLIYGASDLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAYGFPFTFGPGT KVDIKEPKRSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 224) orQVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYMHWVRQAPGQGLEWMGWINPNEGDTNYAQKFEGRITMTRDTSISTAYMELSRLRSDDTAVYYCARNTGAYSFGYWGCGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKCPKLLIYGASDLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAYGFPFTFGPGTKVDI KEPKRSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 225).

[0025] 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 the IMGT hinge numbering, position 220 according to the EU index, or position 233 according to the Kabat numbering. In some embodiments, the antibody heavy chain of the first antibody arm comprises the sequence ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (sequence number 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 the IMGT hinge numbering, position 220 according to the EU index, or position 233 according to the 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., the 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 the IMGT hinge numbering, position 220 according to the EU index, or position 233 according to the 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., the 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.

[0026] In some embodiments, the target of interest is a disease-causing agent. In some embodiments, the disease-causing agent is a bacterial cell, a fungal cell, a virus, a senescent cell, a tumor cell, a protein aggregate (e.g., amyloid beta, 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, Nectin-4, TROP-2, mesothelin, LIV-1, C-MET, FOLR1, CD20, CCR8, CD33, or EGFR. 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; the VH domain of the second antigen-binding domain comprises the sequence QVQLQQPGAELVKPGASVKMSCKASGYTFTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSLTSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSA (SEQ ID NO: 129), and / or the VL domain of the second antigen-binding domain comprises the sequence QIVLSQSPAILSASPGEKVTMTCRASSSVSYIHWFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWTSNPPTFGGGTKLEIK (SEQ ID NO: 130). In some embodiments, the antibody comprises two antibody heavy chains, each of which 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 an L234A, an L235E, and a G237A substitution according to EU numbering. In some embodiments, the antibody comprises two antibody heavy chains, only one of which comprises an H435R and a Y436F substitution 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 according to EU numbering and a light chain comprising S121C and C214V substitutions. 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 and 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 the first antibody heavy chain comprises F126C, C220V, and T366W substitutions according to EU numbering, the first antibody light chain comprises S121C and C214V substitutions, and 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.

[0027] 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 two of the first antibody heavy chain and the second antibody heavy chain are non-fucosylated or have reduced fucosylation. In some embodiments, the antibody may be produced in a cell line with an α1,6-fucosyltransferase (Fut8) or α-1,3-mannosyl-glycoprotein 2-β-N-acetylglucosaminyltransferase (MGAT1) knockout. In some embodiments, the antibody may be produced in a cell line overexpressing β1,4-N-acetylglucosaminyltransferase III (GnT-III). In further embodiments, the cell line further overexpresses Golgi μ-mannosidase II (ManII). In some embodiments, the antibody may be produced in a cell line treated with an inhibitor of mannosidase I, such as kifunensine.

[0028] In some embodiments, a multispecific binding molecule comprises: (a) a first antibody, or antigen-binding fragment thereof, comprising 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 that 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; and the VH domain of the first antigen-binding domain has the amino acid sequence QVQLVQSGAEVKKPGASVKVSCKSSGYTFTX1YYIHWVRQAPGQGLEWMGWINPNSGX2TNYAQKFQGRITMTRDTSISTAYLELSRLRSDDTAVFYCAX3X4X5X6X7X8X9X 10 X 11 X 12 WGQGTLVTVSS [where X1 is D, A, or G, X2 is D, A, or G, X3 is R, A, or G, X4 is N, A, or G, X5 is S, A, or G, X6 is A or G, X7 is S, A, or G, X8 is Y, A, or G, X9 is S, A, or G, and X 10 is F, A, or G, and X 11 is A or G and X 12X1 is Q, A, or G; X2 is Q, A, or G; X3 is F, Y, A, or G; X4 is S, A, or G; X5 is F, A, or G; X6 is P, A, or G; X7 is F, A, or G; and X8 is T, A, or G (SEQ ID NO: 65). In some embodiments, the first antigen-binding domain 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). In some embodiments, the VH domain of the first antigen-binding domain comprises 1, no more than 2, no more than 3, no more than 4, or no more than 5 substitutions compared to the amino acid sequence of SEQ ID NO: 62, and / or the VL domain of the first antigen-binding domain comprises 1, no more than 2, no more than 3, no more than 4, or no more than 5 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 Dectin-1; and / or does not compete with the natural ligand of human Dectin-1.

[0029] In some embodiments, a multispecific binding molecule comprises: (a) a first antibody or antigen-binding fragment thereof comprising 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 that 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; and the VH domain of the first antigen-binding domain comprises CDR-H1 comprising the amino acid sequence DYYI (SEQ ID NO: 1) or AYYI (SEQ ID NO: 16), CDR-H2 comprising the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2) or WINPNSGATNYAQKFQG (SEQ ID NO: 19), and CDR-H3 comprising the amino acid sequence 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 ( and a CDR-H3 comprising an amino acid sequence selected from the group consisting of NSGSYSAGY (SEQ ID NO: 33), NSGSYSAGY (SEQ ID NO: 35), NSGSYSFAY (SEQ ID NO: 37), and NSGSYSFGA (SEQ ID NO: 39); and 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).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 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).

[0030] 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 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 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 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 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 QVQLVQSGAEVKKPGASVKVSCKASGYTFT (SEQ ID NO: 51); FR2 comprising the amino acid sequence HWVRQAPGQGLEWMG (SEQ ID NO: 52); FR3 comprising an amino acid sequence selected from the group consisting of RITMTRDTSISTAYLELSRLRSDDTAVFYCAR (SEQ ID NO: 53) and RVTMTRDTSISTAYMELSRLRSDDTAVYYCAR (SEQ ID NO: 54); 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 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 GASSLQS (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 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 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 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 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).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 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 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). 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 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 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). 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 QQAYSFPFA (SEQ ID NO:49). In some embodiments, the VL domain of the first antigen-binding domain further comprises an FR1 comprising the amino acid sequence DIQMTQSPSSVSASVGDRVTITC (SEQ ID NO: 56), an FR2 comprising an amino acid sequence selected from the group consisting of WYQQKPGKAPKLLIF (SEQ ID NO: 57) and WYQQKPGKAPKLLIY (SEQ ID NO: 58), an FR3 comprising an amino acid sequence selected from the group consisting of GVPSRFSGSGSGTDFTLTVSSLQPEDFATYYC (SEQ ID NO: 59) and GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC (SEQ ID NO: 60), and an FR4 comprising the amino acid sequence FGPGTKVDIE (SEQ ID NO: 61).

[0031] In some embodiments, a multispecific binding molecule comprises: (a) a first antibody or antigen-binding fragment thereof comprising a first antigen-binding domain that binds to human Dectin-1; and a second antibody or antigen-binding fragment thereof comprising a second antigen-binding domain that 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; and the VH domain of the first antigen-binding domain comprises CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7) or GYTFTAYY (SEQ ID NO: 17), CDR-H2 comprising the amino acid sequence INPNSGDT (SEQ ID NO: 8) or INPNSGAT (SEQ ID NO: 20), and CDR-H3 comprising the amino acid sequence ARNSGSYSFGY (SEQ ID NO: 9), ARASGSYSFGY (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), AR and CDR-H3 comprising an amino acid sequence selected from the group consisting of NSGSYAFGY (SEQ ID NO: 34), ARNSGSYSAGY (SEQ ID NO: 36), ARNSGSYSFAY (SEQ ID NO: 38), and ARNSGSYSFGA (SEQ ID NO: 40); and the VL domain of the first antigen-binding domain comprises CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO: 12), QQAA and a CDR-L3 comprising an amino acid sequence selected from the group consisting of QQAYSFPFT (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 first antigen-binding domain does not comprise 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 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 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 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 AANSGSYSFGY (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 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 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 ARNSGSYSAGY (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 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 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 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 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 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 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 CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and 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 CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7), CDR-H2 comprising the amino acid sequence INPNEGDT (SEQ ID NO: 202), and CDR-H3 comprising the amino acid sequence ARNTGAYSFGY (SEQ ID NO: 205), and the VL domain of the first antigen-binding domain comprises CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and CDR-L3 comprising the amino acid sequence QQAYGFPFT (SEQ ID NO: 207).In some embodiments, the VH domain of the first antigen-binding domain comprises CDR-H1 comprising the amino acid sequence GYTFTDYY (SEQ ID NO: 7), CDR-H2 comprising the amino acid sequence INPNEGDT (SEQ ID NO: 202), and CDR-H3 comprising the amino acid sequence ARNTGAYSFGY (SEQ ID NO: 205), and the VL domain of the first antigen-binding domain comprises CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and CDR-L3 comprising the amino acid sequence HQAYSFPFT (SEQ ID NO: 208).

[0032] In some embodiments, a multispecific binding molecule comprises: (a) a first antibody or antigen-binding fragment thereof comprising a first antigen-binding domain that binds to human Dectin-1; and a second antibody or antigen-binding fragment thereof comprising a second antigen-binding domain that 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; and the VH domain of the first antigen-binding domain comprises CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13) or GYTFTAY (SEQ ID NO: 18), and CDR-H2 comprising the amino acid sequence NPNSGD (SEQ ID NO: 14) or NPNSGA (SEQ ID NO: 21), and a CDR-H3 comprising the amino acid sequence 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), and a CDR-H3 comprising an amino acid sequence selected from the group consisting of NSGSYSAGY (SEQ ID NO: 35), NSGSYSFAY (SEQ ID NO: 37), and NSGSYSFGA (SEQ ID NO: 39); 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).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 CDR-H1 comprising the amino acid sequence DYYM (SEQ ID NO: 199), CDR-H2 comprising the amino acid sequence WINPNEGDTNYAQKFEG (SEQ ID NO: 200), and CDR-H3 comprising the amino acid sequence NTGAYSFGY (SEQ ID NO: 204), and the VL domain of the first antigen-binding domain comprises CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), CDR-L2 comprising the amino acid sequence GASDLQS (SEQ ID NO: 206), and CDR-L3 comprising the amino acid sequence QQAYGFPFT (SEQ ID NO: 207). In some embodiments, the VH domain of the first antigen-binding domain comprises CDR-H1 comprising the amino acid sequence DYYM (SEQ ID NO: 199), CDR-H2 comprising the amino acid sequence WINPNEGDTNYAQKFQE (SEQ ID NO: 201), and CDR-H3 comprising the amino acid sequence NTGAYSFGY (SEQ ID NO: 204), and the VL domain of the first antigen-binding domain comprises CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), CDR-L2 comprising the amino acid sequence GASDLQS (SEQ ID NO: 206), and CDR-L3 comprising the amino acid sequence HQAYSFPFT (SEQ ID NO: 208).

[0033] 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 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 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 GASSLQS (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 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 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 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 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). 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 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 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). 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 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 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). 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 QQAYSFPFA (SEQ ID NO: 49).In some embodiments, the VH domain of the first antigen-binding domain comprises CDR-H1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 13), CDR-H2 comprising the amino acid sequence NPNEGD (SEQ ID NO: 203), and CDR-H3 comprising the amino acid sequence NTGAYSFGY (SEQ ID NO: 204), and the VL domain of the first antigen-binding domain comprises CDR-L1 comprising the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), CDR-L2 comprising the amino acid sequence GASDLQS (SEQ ID NO: 206), and CDR-L3 comprising the amino acid sequence QQAYGFPFT (SEQ ID NO: 207).

[0034] 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 NOs: 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 NOs: 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 NOs: 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 NOs: 64, and 94-102. In some embodiments, the first antigen-binding domain does not comprise 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. 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 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 the IMGT hinge numbering, and 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 the first antibody light chain comprises the amino acid sequence of SEQ ID NO:223.

[0035] In some embodiments, a multispecific binding molecule comprises: (a) a first antibody, or antigen-binding fragment thereof, comprising a first antigen-binding domain that binds to human Dectin-1; and a second antibody, or antigen-binding fragment thereof, comprising a second antigen-binding domain that 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; and the VH domain of the first antigen-binding domain has the amino acid sequence QVQLVQSGAEVKKPGASVKVSCKX1SGYTFTX2YYX3HWVRQAPGQGLEWMGWINPNSGX4TNYAQKFQGRX5TMTRDTSISTAYX6ELSRLRSDDTAVX7YCARNSGSYSFGYWGQGTLVTVSS, , X1 is S or A, X2 is D or G, X3 is I or M, X4 is D or G, X5 is I or V, X6 is L or M, and X7 is F or Y (SEQ ID NO: 80); and the VL domain of the first antigen-binding domain comprises the amino acid sequence DIQMTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKAPKLLIX1X2ASSLQSGVPSRFSGSGSGTDFTLTX3SSLQPEDFATYYCQQAYSFPFTFGPGTKVDIE (wherein X1 is F or Y, X2 is G or A, and 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 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).

[0036] In some embodiments, a multispecific binding molecule comprises: (a) a first antibody or antigen-binding fragment thereof comprising a first antigen-binding domain that binds to human Dectin-1; and a second antibody or antigen-binding fragment thereof comprising a second antigen-binding domain that 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; and 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), and the amino acid sequence WI Provided herein is a multispecific binding molecule comprising a CDR-H2 comprising NPNSGDTNYAQKFQG (SEQ ID NO: 2) or WINPNSGGTNYAQKFQG (SEQ ID NO: 70), and a CDR-H3 comprising the amino acid sequence NSGSYSFGY (SEQ ID NO: 3); 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). In some embodiments, the first antigen-binding domain 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). 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 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 QVQLVQSGAEVKKPGASVKVSCKSSGYTFT (SEQ ID NO: 50) and QVQLVQSGAEVKKPGASVKVSCKASGYTFT (SEQ ID NO: 76); FR2 comprising the amino acid sequence HWVRQAPGQGLEWMG (SEQ ID NO: 52); FR3 comprising an amino acid sequence selected from the group consisting of RITMTRDTSISTAYLELSRLRSDDTAVFYCAR (SEQ ID NO: 53) and RVTMTRDTSISTAYMELSRLRSDDTAVYYCAR (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 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 AASSLQS (SEQ ID NO: 73), 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 further comprises an FR1 comprising the amino acid sequence DIQMTQSPSSVSASVGDRVTITC (SEQ ID NO: 56), an FR2 comprising an amino acid sequence selected from the group consisting of WYQQKPGKAPKLLIF (SEQ ID NO: 57) and WYQQKPGKAPKLLIY (SEQ ID NO: 78), an FR3 comprising an amino acid sequence selected from the group consisting of GVPSRFSGSGSGTDFTLTVSSLQPEDFATYYC (SEQ ID NO: 59) and GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC (SEQ ID NO: 79), and an FR4 comprising the amino acid sequence FGPGTKVDIE (SEQ ID NO: 61).

[0037] In some embodiments, a multispecific binding molecule comprising: (a) a first antibody or antigen-binding fragment thereof comprising a first antigen-binding domain that binds to human Dectin-1; and a second antibody or antigen-binding fragment thereof comprising a second antigen-binding domain that 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; and 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). and 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 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) or AAS (SEQ ID NO: 74), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO: 12). In some embodiments, the first antigen-binding domain does not comprise 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 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 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).

[0038] In some embodiments, a multispecific binding molecule comprises: (a) a first antibody or antigen-binding fragment thereof comprising a first antigen-binding domain that binds to human Dectin-1; and a second antibody or antigen-binding fragment thereof comprising a second antigen-binding domain that 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; 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); Provided herein is a multispecific binding molecule comprising 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); 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: 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 comprise 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 RASQGISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence AASSLQS (SEQ ID NO: 75), and a CDR-L3 comprising the amino acid sequence QQAYSFPFT (SEQ ID NO: 6).

[0039] 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 NOs: 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 NOs: 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 NOs: 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 NOs: 64, and 110-113. In some embodiments, the first antigen-binding domain does not comprise 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.

[0040] 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 the VL domain of the first 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.

[0041] 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, and the first antibody light chain comprises a first VL domain, wherein the first VH domain and 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, and the second antibody light chain comprises a second VL domain, wherein the second VH domain and 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, and the first antibody light chain comprises a first VL domain, wherein the first VH domain and 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, and the second antibody light chain comprises a second VL domain, wherein the second VH domain and 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 the IMGT hinge numbering, and 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 the first antibody light chain comprises the amino acid sequence of SEQ ID NO:223.

[0042] In some embodiments, the target of interest is a disease-causing agent. In some embodiments, the disease-causing agent is a bacterial cell, a fungal cell, a virus, a senescent cell, a tumor cell, a protein aggregate (e.g., amyloid beta, 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 viral surface antigen. In some embodiments, the target of interest is CD70, HER2, DLL3, nectin-4, TROP-2, mesothelin, LIV-1, C-MET, FOLR1, CD20, CCR8, CD33, or EGFR. 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 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 and second antibodies or fragments are human antibodies or fragments or humanized antibodies or fragments. In some embodiments, one or both of the first and second antibodies or fragments is a Fab, Fab', F(ab')2, Fv, Fab'-SH, F(ab')2, single chain antibody, nanobody, or scFv fragment. In some embodiments, one or both of the first and second antibodies or fragments further comprises an Fc domain.In some embodiments, the first antibody or fragment is a Fab fragment, and the second antibody or fragment is a full-length antibody, e.g., a full-length antibody comprising an antibody heavy chain and an antibody light chain. In some embodiments, both the first and second antibodies or fragments are full-length antibodies, e.g., 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 a VH domain of a second antigen-binding domain associated with an antibody light chain comprising a VL domain of the second antigen-binding domain, and a second Fc region connected to the VH 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 cognate hole-forming mutations, or 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, the first Fc region comprises a T366W substitution according to EU numbering, and the second Fc region comprises a T366S, L368A, and Y407V substitution according to EU numbering. In some embodiments, 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. In some embodiments, the first linker comprises one or more repeats of the sequence GGGGS (SEQ ID NO: 115). In some embodiments, the first linker comprises the sequence GGGGSGGGGSGGGGS (SEQ ID NO: 116) or GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 117). In some embodiments, the second linker comprises the sequence EPKRSDKTHTCPPC (SEQ ID NO: 118) or SATHTCPPC (SEQ ID NO: 119).In some embodiments, a first antibody or fragment is linked to avidin, streptavidin, neutravidin, or a biotin-linked derivative thereof, and a second antibody or fragment is linked to biotin or an avidin-linked derivative thereof; or a second antibody or fragment is linked to avidin, streptavidin, neutravidin, or a biotin-linked derivative thereof, and a first antibody or fragment is linked to biotin or an avidin-linked derivative thereof; the first antibody or fragment is linked to the second antibody or fragment via an interaction between avidin, streptavidin, neutravidin, or a biotin-linked derivative thereof and biotin or an avidin-linked derivative thereof. In some embodiments, the first antibody or fragment is a Fab fragment linked to monomeric streptavidin (mSA), and 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 linked to monomeric streptavidin (mSA), and 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 first antibody heavy chain comprising a VH domain of the first antigen-binding domain and a first Fc region, 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 of the second antigen-binding domain and a second Fc region, 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 cognate hole-forming mutations. In some embodiments, the first Fc region comprises a T366W substitution according to EU numbering, 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 VH domain of a first antigen-binding domain and a first Fc region, and a second antibody arm comprising a VH domain of 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, the first Fc region comprises T366S, L368A, and Y407V substitutions according to EU numbering, and the second Fc region comprises a T366W substitution. In some embodiments, a multispecific binding molecule comprises two antibody Fc regions, 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 a S228P substitution according to EU numbering. In some embodiments, the multispecific binding molecule comprises two antibody heavy chains, only one of which comprises H435R and Y436F substitutions according to EU numbering. In some embodiments, only one of the antibody arms comprises a heavy chain that includes F126C and C220V substitutions and a light chain that includes 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, and 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 the first antibody heavy chain comprises F126C, C220V, and T366W substitutions according to EU numbering, the first antibody light chain comprises S121C and C214V substitutions, and 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, at least one or two of the antibody heavy chains are non-fucosylated or comprise reduced fucosylation. In some embodiments, the antibody may be produced in a cell line with an α1,6-fucosyltransferase (Fut8) or α-1,3-mannosyl-glycoprotein 2-β-N-acetylglucosaminyltransferase (MGAT1) knockout. In some embodiments, the antibody may be produced in a cell line overexpressing β1,4-N-acetylglucosaminyltransferase III (GnT-III). In a further embodiment, the cell line further overexpresses Golgi μ-mannosidase II (ManII). In some embodiments, antibodies may be produced in cell lines treated with an inhibitor of mannosidase I, such as kifunensine.

[0043] In some embodiments, provided herein is a polynucleotide encoding the antibody or multispecific binding molecule of any one of the above embodiments. In some embodiments, provided herein is a vector (e.g., an expression vector) comprising the polynucleotide of any one of the above embodiments. In some embodiments, provided herein is a host cell (e.g., an isolated host cell or cell line) comprising the polynucleotide or vector of any one of the above embodiments. In some embodiments, provided herein is a method of producing an antibody or multispecific binding molecule, the method comprising culturing a host cell of any one of the above embodiments under conditions suitable for production of the antibody or multispecific binding molecule. In some embodiments, the method further comprises recovering the antibody or multispecific binding molecule. In some embodiments, provided herein is a pharmaceutical composition comprising the antibody or multispecific binding molecule of any one of the above embodiments and a pharmaceutically acceptable carrier.

[0044] In some embodiments, provided herein are methods for treating a disease or disorder, comprising administering to an individual in need thereof an effective amount of any one of the antibodies, multispecific binding molecules, or compositions described in the above embodiments. In some embodiments, the first target of interest is human Dectin-1, and the second target of interest is a disease-causing agent. In some embodiments, the disease-causing agent is a bacterial cell, a fungal cell, a virus, a senescent cell, a tumor cell, a protein aggregate (e.g., amyloid beta, 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 viral surface antigen. In some embodiments, the disease or disorder is cancer, a bacterial infection, a fungal infection, a viral infection, a mast cell disease or disorder, systemic mastocytosis, amyloidosis (e.g., light chain amyloidosis or Alzheimer's disease), or an age-related disease or disorder. In some embodiments, the target of interest is CD70, HER2, DLL3, Nectin-4, TROP-2, mesothelin, LIV-1, C-MET, FOLR1, CD20, CCR8, CD33, or EGFR. In some embodiments, the individual is a human.

[0045] In some embodiments, provided herein are methods of treating cancer, comprising administering to an individual in need thereof an effective amount of a composition comprising the multispecific binding molecule of any one of the preceding embodiments, wherein the multispecific binding molecule comprises: (a) a first antibody or antigen-binding fragment thereof comprising a first antigen-binding domain of any one of the preceding 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 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, e.g., expressed on the surface of a cancer cell.

[0046] In some embodiments, the second antigen-binding domain binds to CD20; the second antigen-binding domain comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; the VH domain of the second antigen-binding domain comprises the sequence QVQLQQPGAELVKPGASVKMSCKASGYTFTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSLTSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSA (SEQ ID NO: 129), and / or the VL domain of the second antigen-binding domain comprises the sequence QIVLSQSPAILSASPGEKVTMTCRASSSVSYIHWFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWTSNPPTFGGGTKLEIK (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 cognate hole-forming mutations. In some embodiments, the first Fc region comprises a T366W substitution according to EU numbering, 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 cognate knob-forming mutations. In some embodiments, the first Fc region comprises T366S, L368A, and Y407V substitutions according to EU numbering, and the second Fc region comprises a T366W substitution. In some embodiments, the antibody comprises two antibody Fc regions, each of which 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 only one of the antibody heavy chains comprises H435R and Y436F substitutions according to EU numbering, hi some embodiments, only one of the antibody arms comprises a heavy chain that comprises F126C and C220V substitutions according to EU numbering, and a light chain that comprises S121C and C214V substitutions according to EU numbering. In some embodiments, a bispecific antibody comprises two antibody heavy chains and two antibody light chains, wherein the VH domain of a first antibody heavy chain forms an antigen-binding domain with the VL domain of the first antibody light chain, and the VH domain of a second antibody heavy chain forms an antigen-binding domain with the VL domain of the second antibody light chain, wherein the first antibody heavy chain comprises F126C, C220V, and T366W substitutions according to EU numbering, the first antibody light chain comprises S121C and C214V substitutions, and the second antibody heavy chain comprises T366S, L368A, Y407V, H435R, and Y436F substitutions according to EU numbering. 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 a S228P substitution according to EU numbering. In some embodiments, at least one or two of the heavy chains of the antibody are nonfucosylated or comprise reduced fucosylation. In some embodiments, antibodies may be produced in cell lines with an α1,6-fucosyltransferase (Fut8) or α-1,3-mannosyl-glycoprotein 2-β-N-acetylglucosaminyltransferase (MGAT1) knockout.In some embodiments, the antibody may be produced in a cell line that overexpresses β1,4-N-acetylglucosaminyltransferase III (GnT-III). In further embodiments, the cell line further overexpresses Golgi μ-mannosidase II (ManII). In some embodiments, the antibody may be produced in a cell line treated with an inhibitor of mannosidase I, such as kifunensine. In some embodiments, the individual is human.

[0047] In some embodiments, provided herein is a kit or article of manufacture comprising the antibody, multispecific binding molecule, or composition of any one of the above embodiments and instructions for using the antibody, multispecific binding molecule, or composition according to the method of any one of the above embodiments.

[0048] It is to be understood that one, some, or all of the features 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 be apparent to those skilled in the art. These and other embodiments of the present disclosure are further described in the detailed description that follows. [Brief explanation of the drawings]

[0049] [Figure 1A] Figure 1 shows the binding analysis of anti-human Dectin-1 antibody (clone 2M24) on human monocytes and cynomolgus monkey monocytes derived from peripheral blood mononuclear cells (PBMCs) by flow cytometry. To identify monocytes, single viable CD14+ cells were gated. Cells were incubated with 2M24 anti-Dectin-1 primary antibody or mIgG1 isotype control antibody, followed by incubation with a fluorescent anti-mouse secondary antibody. Primary antibodies were used in serial dose titration. Figure 1 shows the binding analysis of anti-human Dectin-1 clone 2M24 on human monocytes. [Figure 1B]Figure 1 shows the binding analysis of anti-human Dectin-1 antibody (clone 2M24) on human monocytes and cynomolgus monkey monocytes derived from peripheral blood mononuclear cells (PBMCs) by flow cytometry. To identify monocytes, single viable CD14+ cells were gated. Cells were incubated with 2M24 anti-Dectin-1 primary antibody or mIgG1 isotype control antibody, followed by incubation with fluorescent anti-mouse secondary antibody. Primary antibodies were used in serial dose titration. Figure 1 shows the binding analysis of anti-human Dectin-1 clone 2M24 antibody on cynomolgus monkey monocytes. [Figure 1C] Flow cytometric binding analysis of anti-human dectin-1 antibody (clone 2M24) on human monocytes and cynomolgus monkey monocytes derived from peripheral blood mononuclear cells (PBMCs) is shown. To identify monocytes, single viable CD14+ cells were gated. Cells were incubated with the 2M24 anti-dectin-1 primary antibody or an mIgG1 isotype control antibody, followed by incubation with a fluorescent anti-mouse secondary antibody. The primary antibody was used in serial dose titration. Comparison of binding to human monocytes, human dectin-1-overexpressing HEK cells, and cynomolgus monkey monocytes is shown between the 2M24 clone and other dectin-1 antibodies identified from immunization of ATX-Gx Alloy transgenic mice and a commercially available anti-dectin-1 antibody. The anti-human dectin-1 clone 2M24 antibody exhibited high affinity for human dectin-1 and cynomolgus monkey dectin-1 expressed on monocytes, demonstrating superior affinity compared to other anti-dectin-1 antibodies, including commercially available antibodies.

[0050] [Figure 2A]This figure shows the phagocytosis of pHrodo-labeled polystyrene anti-mouse Fc IgG beads conjugated with the anti-Dectin-1 antibody 2M24 or an 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 the Dectin-1 antibody 2M24 or an isotype control. The beads were then incubated with cultured HEK-Blue hDectin-1a cells or human monocytes at a 1:2 (cell:bead) ratio. HEK-Blue hDectin-1a cells were labeled with the cell-permeable dye calcein AM. Bead engulfment was monitored by IncuCyte live-cell imaging. Phagocytosis was quantified using IncuCyte analysis software and expressed as the overlap of red object counts (pHrodo) relative to calcein-positive cells. Shown is the phagocytosis of beads by HEK-Blue hDectin-1a cells over a period of 2.5 hours (top) and a representative image of pHrodo-positive cells after 2.5 hours of phagocytosis (bottom). [Figure 2B]This figure shows the phagocytosis of pHrodo-labeled polystyrene anti-mouse Fc IgG beads conjugated with the anti-Dectin-1 antibody 2M24 or an 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 the Dectin-1 antibody 2M24 or an isotype control. The beads were then incubated with cultured HEK-Blue hDectin-1a cells or human monocytes at a 1:2 (cell:bead) ratio. HEK-Blue hDectin-1a cells were labeled with the cell-permeable dye calcein AM. Bead engulfment was monitored by IncuCyte live-cell imaging. Phagocytosis was quantified using IncuCyte analysis software and expressed as the overlap of red object counts (pHrodo) relative to calcein-positive cells. Shown are the phagocytosis of beads by human monocytes over a 4-hour period (top) and a representative image of a pHrodo-positive cell 2.5 hours after engulfment (bottom). In the representative image, the internalized beads are brightly fluorescent within the phagosome.

[0051] [Figure 3] Figure 1 shows the binding of the fully human 2M24 anti-Dectin-1 antibody (hIgG4) or an isotype control antibody to HEK-Blue hDectin-1a cells and primary human monocytes. (A) Binding analysis of the fully human 2M24 anti-Dectin-1 antibody to HEK cells. (B) Binding to primary human monocytes. Primary antibodies were used in serial dose titration, followed by a fluorescent secondary antibody against the primary antibody. The fully human 2M24 anti-Dectin-1 hIgG4 antibody bound with high affinity to Dectin-1-expressing cells.

[0052] [Figure 4]Figure 1 shows targeted phagocytosis of pHrodo-labeled polystyrene biotin beads conjugated to the fully human 2M24 anti-Dectin-1 antibody (hIgG4) or an isotype control antibody by Dectin-1-expressing cells. Polystyrene biotin beads were labeled with pHrodo Red and conjugated to the anti-Dectin-1 antibody 2M24 or an isotype control antibody via streptavidin. The conjugated beads were mixed with cells at a 1:3 ratio, and bead phagocytosis was monitored using IncuCyte live-cell imaging. Figure 2 shows phagocytosis of pHrodo-biotin beads conjugated to streptavidin 2M24 anti-Dectin-1 hIgG4 antibody for HEK-Blue hDectin-1a cells (top left), human monocytes (top right), and human macrophages (bottom). The fully human 2M24 anti-Dectin-1 antibody (hIgG4) promoted phagocytosis of Dectin-1-expressing cells.

[0053] [Figure 5A] This figure shows the results of a secreted alkaline phosphatase reporter assay of dectin-1 in HEK-Blue hDectin-1a cells. This figure shows the results of a secreted alkaline phosphatase assay performed using immobilized fully human 2M24 anti-Dectin-1 antibody. Fully human 2M24 (hIgG4) anti-Dectin-1 antibody or an isotype control antibody was immobilized overnight at 0.1–10 μg per well on a U-bottom polypropylene microtiter plate. HEK-Blue hDectin-1a cells were then cultured for 22 hours, and alkaline phosphatase secretion was assessed in the supernatant at OD 630 nm. [Figure 5B]Figure 1 shows the results of a secreted alkaline phosphatase reporter assay of dectin-1 in HEK-Blue hDectin-1a cells. This figure shows the results of a secreted alkaline phosphatase assay performed using bead-conjugated fully human 2M24 anti-Dectin-1 antibody. Biotin beads of 3, 10, and 16.5 μm in size 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 630 nm. Bars represent the mean ± standard deviation; n = 2 replicates. The 2M24 (hIgG4) anti-Dectin-1 antibody induced alkaline phosphatase secretion in HEK-Blue hDectin-1a cells in both immobilized and bead-conjugated forms.

[0054] [Figure 6A] Figure 1 shows the amount of cytokine secretion by human primary macrophages stimulated with anti-Dectin-1 (15E2) antibody in solution. Primary human macrophages and primary monocytes were stimulated with 15E2 anti-Dectin-1 antibody or isotype antibody at 10 μg / ml in solution for 24 hours, and the amounts of TNFα and IL-6 secreted were assessed by ELISA analysis of the supernatants. Zymosan was used as a positive control for cytokine secretion. Bars represent the mean ± standard deviation. n = 2 replicates. A shows the results for primary human monocytes stimulated with soluble 15E2 anti-Dectin-1 antibody, and B shows the results for stimulated primary human macrophages. Soluble 15E2 anti-Dectin-1 antibody did not induce cytokine secretion in primary human monocytes and macrophages. [Figure 6B]Figure 1 shows the amount of cytokine secretion by human primary macrophages stimulated with anti-Dectin-1 (15E2) antibody in solution. Primary human macrophages and primary monocytes were stimulated with 15E2 anti-Dectin-1 antibody or isotype antibody at 10 μg / ml in solution for 24 hours, and the amounts of TNFα and IL-6 secreted were assessed by ELISA analysis of the supernatants. Zymosan was used as a positive control for cytokine secretion. Bars represent the mean ± standard deviation. n = 2 replicates. A shows the results for primary human monocytes stimulated with soluble 15E2 anti-Dectin-1 antibody, and B shows the results for stimulated primary human macrophages. Soluble 15E2 anti-Dectin-1 antibody did not induce cytokine secretion in primary human monocytes and macrophages.

[0055] [Figure 7A] Figure 1 shows the amount of cytokine secretion by 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 overnight at 10 μg per well on U-bottom polypropylene microtiter plates, and human monocytes or human PBMCs were cultured for 24 hours. TNFα, IL6, and IFNg secretion were assessed by ELISA analysis of the supernatants. (A) Cytokine secretion by human monocytes after stimulation with immobilized anti-Dectin-1 antibodies. (B) Cytokine secretion by cultured human PBMCs after stimulation. Bars represent mean ± standard deviation; n = 2 replicates. 2M24 anti-Dectin-1 antibody induced cytokine secretion in both primary human monocytes and PBMCs, demonstrating superior immune stimulation compared with the 15E2 agonist Dectin-1 antibody. [Figure 7B]Figure 1 shows the amount of cytokine secretion by 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 overnight at 10 μg per well on U-bottom polypropylene microtiter plates, and human monocytes or human PBMCs were cultured for 24 hours. TNFα, IL6, and IFNg secretion were assessed by ELISA analysis of the supernatants. (A) Cytokine secretion by human monocytes after stimulation with immobilized anti-Dectin-1 antibodies. (B) Cytokine secretion by cultured human PBMCs after stimulation. Bars represent mean ± standard deviation; n = 2 replicates. 2M24 anti-Dectin-1 antibody induced cytokine secretion in both primary human monocytes and PBMCs, demonstrating superior immune stimulation compared with the 15E2 agonist Dectin-1 antibody.

[0056] [Figure 8] This figure shows the results of a competition assay performed using the 12M4 anti-Dectin-1 antibody clone and the natural ligand of Dectin-1. HEK-Blue hDectin-1a cells were incubated with 2M24 (hIgG4) anti-Dectin-1 antibody or 15E2, 259931, or GE2 anti-Dectin-1 commercial antibodies at a 1 / 3 dose titration starting at 300 nM in the presence of 8 μg / ml biotin-laminarin for 30 minutes on ice. Binding of laminarin to Dectin-1 was assessed by flow cytometry using Streptavidin-Alexa fluor 647. 2M24 (hIgG4) anti-Dectin-1 antibody did not compete with the natural ligand for binding to Dectin-1.

[0057] [Figure 9] 1 shows a summary of the functional characterization of the 2M24 and 15E2 anti-Dectin-1 antibodies.

[0058] [Figure 10] Figure 1 shows a schematic diagram of the generation of bispecific antibodies by click chemistry. (A) Differential labeling of antibodies with MTA or FOL reagents. (B) Covalent cross-linking of antibodies via specific MTA-FOL interactions.

[0059] [Figure 11A] We demonstrate the potential modes of action deployed by anti-Dectin-1 agonist bispecific antibodies to eliminate targeted cancer cells, including immunostimulation, phagocytosis, neoantigen presentation, and activation of T and B lymphocytes of the adaptive immune system.

[0060] [Figure 11B] A list of potential targets for cancer cell depletion is presented.

[0061] [Figure 12A] Figure 1 shows the characterization of a click chemistry-conjugated bispecific containing anti-Dectin-1 (clone 2M24) and anti-hCD70 arms. SDS-PAGE analysis of the covalently conjugated antibody pair (2M24 / anti-hCD20, 2M24 / anti-hCD70, and isotype control) under non-reducing and reducing conditions. [Figure 12B] Characterization of a click chemistry-conjugated bispecific containing anti-Dectin-1 (clone 2M24) and anti-hCD70 arms is shown. Flow cytometry-based characterization of bispecific (2M24 / anti-hCD70 or isotype control) binding to Dectin-1-expressing HEK293 cells (top left) and two renal cancer cell lines—A498 (top right) and 786-0 (bottom left)—is shown. EC50 concentrations (nM) based on nonlinear regression fitting are also shown (bottom right). The anti-Dectin-1 / anti-hCD70 bispecific binds to Dectin-1- or CD70-expressing cells with affinities of 1.8 nM or 12.34 nM, respectively.

[0062] [Figure 13]Figure 1 shows the ligation of dectin-1-expressing HEK293 and A498 renal carcinoma cells induced by the 2M24 / anti-hCD70 bispecific. Flow cytometry analysis of cocultures of HEK293 cells (labeled with calcein green) and A498 cells (labeled with calcein red) in the presence of the 2M24 / anti-hCD70 bispecific or isotype control is shown (left). Engagement between HEK293 and A498 cells is indicated by a double-positive signal (green + red + square box). Also shown is the ligation efficiency, quantified as the percentage of total target cells (A498) that formed doublets with HEK293 cells (right). Bars represent the mean ± standard deviation; n = 3 replicates. The 2M24 / anti-hCD70 bispecific antibody induced ligation between dectin-1-expressing HEK293 and A498 renal carcinoma cells.

[0063] [Figure 14A] Figure 1 shows the ligation of Dectin-1-expressing cells to B cells induced by anti-Dectin-1 / anti-hCD20 bispecific antibody. Figure 2 shows the ligation of Dectin-1-expressing HEK293 cells to B cells induced by anti-Dectin-1 / anti-hCD20 bispecific antibody. Flow cytometry analysis of cocultures of HEK293 cells (labeled with calcein green) and Raji cells (labeled with calcein red) in the presence of 2M24 / anti-hCD70 bispecific or isotype control (left). ligation of HEK293 to Raji cells is indicated by a double-positive signal (green + red +; square box). Ligation efficiency, quantified as the percentage of all target cells (Raji) that form doublets with HEK293 cells, is also shown (right). Bars represent the mean ± standard deviation; n = 2 replicates. [Figure 14B]Figure 1 shows the ligation of Dectin-1-expressing cells to B cells induced by an anti-Dectin-1 / anti-hCD20 bispecific antibody. Figure 2 shows the results of a similar experiment performed to evaluate the ligation of human M0 macrophages to Raji cells induced by an anti-Dectin-1 / anti-hCD20 bispecific. Bars represent the mean ± standard deviation; n = 2 replicates. 2M24 / anti-hCD20 bispecific induced the ligation of Dectin-1-expressing cells to CDC20-positive B cells (Raji cells).

[0064] [Figure 15] This figure shows the results of a Dectin-1-induced secreted alkaline phosphatase reporter assay in HEK-Blue hDectin-1a cells using an anti-Dectin-1 / anti-CD20 bispecific in the presence of Raji cells. The 2M24 (hIgG4) / anti-CD20 bispecific antibody was incubated with Raji cells, followed by two washes to remove unbound bispecific antibody. The 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 was assessed in the supernatant at OD 630 nm. Bars represent the mean ± standard deviation; n = 2 replicates. Raji cells coated with the anti-Dectin-1 / anti-CD20 bispecific induced alkaline phosphatase secretion in HEK-Blue hDectin-1a cells.

[0065] [Figure 16]Figure 1 shows the induction of Raji cell phagocytosis by Dectin-1-expressing HEK293 cells with anti-Dectin-1 / anti-hCD20 bispecific antibody. Representative Incucyte images showing phagocytosis of Raji cells (arrows) by HEK cells at 16 h and 0 h are shown (left). Colocalization is indicated by yellow fluorescence. The decrease in calcein red signal in Raji cells after 16 h indicates cell death due to phagocytosis. Quantification of overlap or colocalization of HEK (calcein green) and Raji (calcein red) in different treatment groups is shown (right). Preincubation of HEK cells with the ADCP inhibitor latrunculin A inhibits 15E2 / anti-hCD20 bispecific antibody-mediated phagocytosis (n = 2 replicates).

[0066] [Figure 17] Figure 1 shows the ligation of dectin-1-expressing cells to HER2-expressing cells induced by an anti-Dectin-1 / anti-hHER2 bispecific antibody. Flow cytometry analysis of cocultures of dectin-1-expressing HEK293 cells (labeled with calcein green) and HER2-expressing SKBR3 cells (labeled with pHrodo red) in the presence of 15E2 / anti-hHER2 bispecific or isotype control is shown (left). ligation between HEK293 and SKBR3 cells is indicated by a double-positive signal (green + red +; square box). Ligation efficiency, quantified as the percentage of total target cells (SKBR3) that form doublets with dectin-1-expressing cells, is also shown (right). Bars represent the mean ± standard deviation; n = 2 replicates. The anti-Dectin-1 / anti-hHER2 bispecific induces ligation of dectin-1 to HER2-positive cancer cells.

[0067] [Figure 18]Figure 1 shows the ligation of dectin-1-expressing HEK293 cells to CD94-expressing BaF3 cells induced by anti-Dectin-1 / anti-hCD94 bispecific. Flow cytometry analysis of cocultures of HEK293 cells (labeled with calcein green) and BaF3 cells (labeled with pHrodo red) in the presence of 2M24 / anti-hCD94 bispecific or isotype control is shown (left). Engagement of HEK293 cells to BaF3 cells is indicated by a double-positive signal (green + red +; square box). Also shown is the ligation efficiency, quantified as the percentage of total target cells (BaF3) that formed doublets with HEK293 cells (right). Bars represent the mean ± standard deviation; n = 2 replicates. The anti-Dectin-1 / anti-hCD94 bispecific induced ligation of dectin-1-expressing cells to CD94-expressing cells.

[0068] [Figure 19] Figure 1 shows a schematic diagram of Fab 2M24-mSA or full-length 2M24-mSA bound to a biotinylated target antibody. A shows a chimeric fusion of monomeric streptavidin (mSA) with Fab 2M24 or full-length 2M24. mSA is genetically fused to either Fab 2M24 or full-length 2M24. B shows the linkage of Fab 2M24-mSA or 2M24-mSA to a biotinylated target antibody. The chimeric fusion was incubated with a biotinylated target antibody to generate a bispecific comprising a Dectin-1-binding arm and a second arm that binds to a target receptor or protein of interest.

[0069] [Figure 20] Figure 1 shows biochemical and functional characterization of Fab 2M24-mSA fusion protein. A shows HPLC characterization of recombinant Fab 2M24-mSA. B shows SDS-PAGE analysis of purified Fab 2M24-mSA under reducing conditions. C shows flow cytometry characterization of Fab 2M24-mSA binding to HEK293 cells stably overexpressing human Dectin-1 (EC50 = 1.45 nM). Fab 2M24 fusion to monomeric streptavidin binds to Dectin-1-expressing cells with an affinity of 1.45 nM.

[0070] [Figure 21A] Figure 1 shows the phagocytosis of pHrodo-labeled polystyrene biotin beads conjugated with monomeric streptavidin-tagged Fab-2M24 anti-Dectin-1 antibody (Fab-2M24-mSA). Figure 2 shows the duplet formation of HEK-Blue hDectin-1a cells with Fab-2M24-mSA conjugated to biotin beads and the phagocytosis of the beads, as assessed by flow cytometry. [Figure 21B] Phagocytosis of pHrodo-labeled polystyrene biotin beads conjugated with Fab-2M24 anti-Dectin-1 antibody tagged with monomeric streptavidin (Fab-2M24-mSA) is shown. Phagocytosis of pHrodo biotin beads (approximately 3 μm) conjugated to Fab-2M24-mSA is assessed by IncuCyte live imaging (top). Representative images of pHrodo-positive cells (internalized beads emitting bright red fluorescence in phagosomes) versus no-bead controls after 3 hours of phagocytosis are shown (bottom). Fab 2M24-mSA fusions induced bead binding and phagocytosis by Dectin-1-expressing HEK293 cells.

[0071] [Figure 22] Panels A–D show bispecific complexes containing Fab 2M24-mSA and a target biotinylated antibody. HPLC analysis of Fab 2M24-mSA complexed with biotinylated anti-hCD20 (A), biotinylated anti-hCD19 (B), biotinylated anti-hCD70 (C), or biotinylated anti-Aβ 1-42 (D) is shown. The panels include overlaid A280 traces containing Fab 2M24-mSA alone, the target biotinylated antibody alone, and Fab 2M24-mSA complexed with a biotinylated target antibody.

[0072] [Figure 23]Figure 1 shows the ligation of Dectin-1-expressing HEK293 cells to CD20-expressing Raji cells induced by Fab 2M24-mSA / biotin anti-hCD20 bispecific antibody. Flow cytometry analysis of cocultures of HEK293 (labeled with calcein green) and Raji (labeled with calcein red) in the presence of Fab 2M24-mSA / biotin anti-hCD20 bispecific or an isotype bispecific control is shown (left). Cocultures were incubated at 4°C or 37°C. ligation of HEK293 and Raji cells is indicated by a double-positive signal (green + red +; dotted square). Ligation efficiency, quantified as the percentage of all target cells (Raji) that formed doublets, is also shown (right). Bars represent the mean ± standard deviation; n = 4 replicates. The Fab 2M24-mSA / biotin anti-hCD20 bispecific induced binding between Dectin-1-expressing HEK293 cells and Raji cells.

[0073] [Figure 24] FIG. 1 is a schematic diagram of targeted phagocytosis of amyloid deposits in amyloidosis using a Dectin-1 agonist bispecific antibody.

[0074] [Figure 25] Figure 1 shows a strategy for targeted depletion of mast cells using Dectin-1 agonist bispecific antibodies. (A) Schematic diagram of mast cell depletion with Dectin-1 agonist bispecific antibodies. (B) List of potential targets for mast cell depletion.

[0075] [Figure 26] Phagocytosis of large (approximately 16.2 μm) pHrodo-labeled beads by human dendritic cells is shown. Quantification of bead engulfment over 12 hours (left) and a representative image of pHrodo-positive cells after 3 hours of engulfment (engulfed beads fluoresce bright red in phagosomes; right). Dectin-1 antibody promoted directed engulfment of beads in cultured monocyte-derived dendritic cells.

[0076] [Figure 27] Schematic diagram of targeted depletion of microorganisms by Dectin-1 agonist bispecific antibodies. To target bacteria, viruses, or fungi, bispecific antibodies are engineered with a Dectin-1-binding arm and a microbial agent-binding arm (top). Dectin-1 bispecific antibodies deploy Dectin-1-expressing phagocytes to eliminate bacterial, viral, or fungal pathogens (bottom).

[0077] [Figure 28A] Figure 1 shows the binding of a bispecific antibody consisting of a Dectin-1 antibody (15E2 clone) conjugated to an anti-H3N2 hemagglutinin antibody (12CA5 clone) to H3N2 influenza virus and to Dectin-1-expressing cells. Figure 2 shows the binding analysis of an anti-Dectin-1 / anti-Hemagglutinin bispecific antibody to H3N2 influenza virus, assessed by ELISA. A 96-well microtiter plate was coated with H3N2 influenza virus particles, followed by incubation with single antibodies, bispecific antibodies, and an isotype control. After extensive washing, the primary antibody was detected with a secondary anti-mouse FcgR HRP antibody. [Figure 28B] Figure 1 shows the binding of a bispecific antibody consisting of a dectin-1 antibody (15E2 clone) conjugated to an anti-H3N2 hemagglutinin antibody (12CA5 clone) to H3N2 influenza virus and to dectin-1-expressing cells. Flow cytometric analysis of the binding of the anti-dectin-1 / anti-hemagglutinin bispecific antibody to HEK cells expressing dectin-1 was performed. HEK cells were incubated with the primary antibody, followed by secondary fluorescent antibody detection against anti-dectin-1 antibody (anti-mIgG2a APC) or hemagglutinin antibody (anti-mIgG2b PB). The anti-dectin-1 / anti-hemagglutinin bispecific antibody efficiently bound to both H3N2 influenza virus and HEK cells expressing dectin-1.

[0078] [Figure 29A]Schematic diagrams of antigen delivery using anti-Dectin-1 antibodies for vaccine generation are shown, showing the use of anti-Dectin-1 antibodies fused to target antigens for delivery to APCs (A), or the use of anti-Dectin-1 bispecific antibodies for targeted delivery of disease-causing agents (e.g., cells, microorganisms, proteins, etc.) to APCs (B). [Figure 29B] Schematic diagrams of antigen delivery using anti-Dectin-1 antibodies for vaccine generation are shown, showing the use of anti-Dectin-1 antibodies fused to target antigens for delivery to APCs (A), or the use of anti-Dectin-1 bispecific antibodies for targeted delivery of disease-causing agents (e.g., cells, microorganisms, proteins, etc.) to APCs (B).

[0079] [Figure 30] This figure shows the phagocytosis of pHrodo-labeled polystyrene anti-mouse Fc IgG beads (approximately 3.4 μm) conjugated with Dectin-1 antibody (15E2) or an isotype control antibody by human dendritic cells. Polystyrene anti-mouse Fc IgG beads were labeled with a pH-sensitive fluorescent dye (pHrodo Red) and conjugated with Dectin-1 antibody or an isotype control. The beads were then incubated with cultured monocyte-derived dendritic cells at a 1:3 (cell:bead) ratio. Bead engulfment was monitored by IncuCyte live-cell imaging. Phagocytosis was quantified using IncuCyte analysis software and expressed as the total integrated intensity (summed fluorescence intensity) of red objects (pHrodo) in the image. Quantification of bead engulfment over 9 hours (top) and a representative image of a pHrodo-positive cell 3 hours after engulfment (engulfed beads fluoresce bright red in the phagosome; bottom) are shown.

[0080] [Figure 31A]Phagocytosis of SARS-CoV-2 spike protein-coated beads by Dectin-1-expressing HEK293 cells. Schematic diagram of the experiment. Beads coated with spike protein from SARS-CoV-2 were linked to Dectin-1-expressing HEK293 cells by an anti-Dectin-1 bispecific antibody containing both a Dectin-1 protein-binding arm and a spike protein-binding arm. [Figure 31B] Phagocytosis of SARS-CoV-2 spike protein-coated beads by Dectin-1-expressing HEK293 cells. Flow cytometry characterization of effector (HEK293 cells) and target (spike-coated beads) engagement by bispecifics and isotype controls (Panel A) and quantification of ligation efficiency based on doublet population (Panel B). [Figure 31C] Phagocytosis of SARS-CoV-2 spike protein-coated beads by Dectin-1-expressing HEK 293 cells is shown. Phagocytosis of SARS-CoV-2 spike protein-coated beads by HEK 293 cells in a coculture experiment is shown. Phagocytosis of pHrodo-labeled beads was monitored by changes in pHrodo fluorescence as a result of the acidic pH within the phagosome. Quantification of phagocytosis, quantified by Incucyte analysis software and expressed as the overlap of red object counts (pHrodo) relative to calcein-positive cells (left), is shown, along with a representative image of pHrodo-positive cells 2 hours after phagocytosis (engulfed beads fluorescing bright red within the phagosome; right).

[0081] [Figure 32A]

[0023] Figure 1 shows a bispecific antibody design of a human bispecific antibody (e.g., a human IgG1 bispecific antibody) targeting Dectin-1 and a disease target or antigen. A schematic diagram of the design is provided. One arm (2M24A.X) with VH domain A and VL domain B targets human Dectin-1, and the other arm (2M24B.X) with VH domain C and VL domain D targets the disease target or antigen. [Figure 32B]

[0023] Figure 1 shows the bispecific antibody design of a human bispecific antibody (e.g., a human IgG1 bispecific antibody) targeting Dectin-1 and a disease target or antigen.

[0024] A schematic diagram of an exemplary mechanism of action of an anti-Dectin-1 bispecific antibody with an activating Fc domain targets hDectin-1 on myeloid cells (via the first arm), an antigen on the target cell / disease agent (via the second arm), and Fc receptors on myeloid cells and NK cells, inducing robust immune stimulation and phagocytosis.

[0082] [Figure 33A] Figure 1 shows that a bispecific antibody with one arm targeting hDectin-1 and the other targeting hCD20 (using the variable domain of rituximab) binds to cells expressing human Dectin-1 or human CD20. The top 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, as assessed by flow cytometry. The bottom panel shows the binding of the bispecific antibody 2M24 / RSV hIgG1-FITC conjugate and 2M24 bivalent hIgG1-FITC conjugate to PBMCs, as assessed by flow cytometry. [Figure 33B] Figure 1 shows that a bispecific antibody with one arm targeting hDectin-1 and the other arm targeting hCD20 (using the variable domain of rituximab) binds to cells expressing human Dectin-1 or human CD20. Figure 2 shows the binding of rituximab (human IgG1), 2M24 / CD20 with activating human IgG1 Fc, 2M24 / CD20 with inactivating human IgG1 Fc, 2M24 / RSV with activating human IgG1 Fc, or 2M24 / RSV with inactivating human IgG1 Fc to the CD20-expressing B cell lymphoma Raji cell line.

[0083] [Figure 34A]This shows that a bispecific antibody targeting hDectin-1 and hCD20 (2M24 / CD20) induces ligation between Dectin-1 and CD20-expressing cells. To assess ligation between Dectin-1-expressing HEK293 cells (effector) and CD20-expressing Raji cells (target), cells were differentially labeled with calcein green (effector) or calcein red (target) dye. Labeled cells were cocultured and treated with hIgG1-inactive 2M24 / CD20 or 2M24 / RSV (control) bispecific antibodies to induce effector:target ligation. Successful effector:target cell ligation was indicated by double positive staining (calcein green+, calcein red+, square box). [Figure 34B] Figure 1 shows that a bispecific antibody targeting hDectin-1 and hCD20 (2M24 / CD20) induces ligation of Dectin-1 to CD20-expressing cells. Figure 2 shows dose titration of the bispecific in effector:target cell co-cultures. Ligation efficiency was quantified as the percentage of total target cells that bound or ligated to effector cells.

[0084] [Figure 35A] This shows that a bispecific antibody targeting hDectin-1 and hCD20 (2M24 / CD20) with an activating hIgG1 Fc does not induce monocyte depletion by antibody-dependent cellular cytotoxicity (ADCC) or antibody-dependent cellular phagocytosis (ADCP). PBMCs from two healthy donors, donor 76 (A) and donor 77 (B), were treated with increasing concentrations of 2M24 / CD20 bispecific antibody (hIgG1 activating or inactive isotype) and rituximab for 24 hours and then analyzed by flow cytometry to quantify the levels of remaining viable CD14+ monocytes (as a percentage of isotype control). [Figure 35B]This shows that a bispecific antibody targeting hDectin-1 and hCD20 (2M24 / CD20) with an activating hIgG1 Fc does not induce monocyte depletion by antibody-dependent cellular cytotoxicity (ADCC) or antibody-dependent cellular phagocytosis (ADCP). PBMCs from two healthy donors, donor 76 (A) and donor 77 (B), were treated with increasing concentrations of 2M24 / CD20 bispecific antibody (hIgG1 activating or inactive isotype) and rituximab for 24 hours and then analyzed by flow cytometry to quantify the levels of remaining viable CD14+ monocytes (as a percentage of isotype control).

[0085] [Figure 36A] Figure 1 shows that a bispecific antibody targeting hDectin-1 and hCD20 (2M24 / CD20) with an activating hIgG1 Fc induces superior B cell depletion compared to rituximab. PBMCs from two healthy donors, donor 83 (A) and donor 84 (B), were treated with increasing concentrations of the indicated antibodies for 24 hours and then analyzed by flow cytometry to quantify the levels of remaining viable CD19+ B cells (reported as % of B cells in PBMCs treated with isotype control). [Figure 36B] Figure 1 shows that a bispecific antibody targeting hDectin-1 and hCD20 (2M24 / CD20) with an activating hIgG1 Fc induces superior B cell depletion compared to rituximab. PBMCs from two healthy donors, donor 83 (A) and donor 84 (B), were treated with increasing concentrations of the indicated antibodies for 24 hours and then analyzed by flow cytometry to quantify the levels of remaining viable CD19+ B cells (reported as % of B cells in PBMCs treated with isotype control).

[0086] [Figure 37A]This shows that rituximab induces greater B cell shaving (CD19 downregulation) than the 2M24 / CD20 activating IgG1 bispecific antibody. CD19 expression on B cells from two healthy donors, donor 83 (A) and donor 84 (B), was quantified by flow cytometry after 24 hours of incubation with increasing concentrations of the 2M24 / CD20 hIgG1 (activating isotype) bispecific antibody, rituximab, or an isotype control. The mean fluorescence intensity (MFI) of CD19 staining with anti-CD19 (BV605 conjugated) was used to assess the effect of the 2M24 / CD20 bispecific and rituximab on CD19 expression on B cells. EC50 values ​​were calculated based on nonlinear regression analysis. [Figure 37B] This shows that rituximab induces greater B cell shaving (CD19 downregulation) than the 2M24 / CD20 activating IgG1 bispecific antibody. CD19 expression on B cells from two healthy donors, donor 83 (A) and donor 84 (B), was quantified by flow cytometry after 24 hours of incubation with increasing concentrations of the 2M24 / CD20 hIgG1 (activating isotype) bispecific antibody, rituximab, or an isotype control. The mean fluorescence intensity (MFI) of CD19 staining with anti-CD19 (BV605 conjugated) was used to assess the effect of the 2M24 / CD20 bispecific and rituximab on CD19 expression on B cells. EC50 values ​​were calculated based on nonlinear regression analysis.

[0087] [Figure 38]Figure 1 shows the difference in cytokine release induced by the 2M24 / CD20 activating IgG1 bispecific antibody compared to rituximab. ELISA-based (mesoscale discovery) cytokine quantification was performed on supernatants isolated from healthy donor PBMCs treated with the 2M24 / CD20 activating hIgG1 bispecific, rituximab, or an isotype control. PBMCs were stimulated overnight with the antibodies, and the supernatants were subsequently analyzed by MSD. The cytokines tested were IFNγ, IL-12p70, IL-6, TNFα, IL-1β, IL-4, IL-13, IL-10, and IL-8. Each plot shows the amount of cytokine secretion (pg / mL) as a function of the antibody used for treatment (from left to right: 2M24 / CD20 hIgG1 bispecific, 2M24 / RSV hIgG1 bispecific, rituximab hIgG1, and isotype control hIgG1).

[0088] [Figure 39A] Figure 1 shows that the 2M24 / CD20 hIgG1 (activating isotype) bispecific antibody induces superior B cell depletion and less CD19 shaving compared to rituximab in cocultures of human macrophages and GFP-expressing Raji B cells. Flow cytometry analysis of cocultures of human macrophages and Raji-GFP cells (3:1 ratio) in the presence of the 2M24 / CD20 hIgG1 (activating isotype) bispecific, 2M24 / RSV control, fucosylated rituximab, or isotype hIgG1 control. Cocultures were incubated at 37°C for 24 hours and then stained with PE anti-CD206 antibody to label macrophages and BV-605 anti-CD19 antibody to label Raji cells. The number of remaining viable / Raji-GFP+ cells was assessed at the end of the experiment. Primary antibodies were used in serial dose titrations. [Figure 39B]Figure 1 shows that the 2M24 / CD20 hIgG1 (active isotype) bispecific antibody induces significant B cell depletion and lower CD19 shaving compared to rituximab in cocultures of human macrophages and GFP-expressing Raji B cells. CD19 assessment on Raji-GFP cells after 24 hours. B cell receptor shaving is shown as a decrease in CD19 MFI in the presence of anti-Dectin-1 / anti-hCD20 bispecific or rituximab.

[0089] [Figure 40A] This shows that the 2M24 / CD20 activating IgG1 bispecific antibody induces superior tissue B cell depletion compared to rituximab in single-cell suspensions of renal cancer specimens. Single-cell suspensions from two renal cancer tissue specimens were analyzed by flow cytometry in the presence of the 2M24 / CD20 hIgG1 (activating or inactivating) bispecific antibody, a 2M24 / RSV hIgG1 control, fucosylated rituximab, and their respective isotype controls. Renal cancer tissue specimens were dissociated into single-cell suspensions and treated with primary antibodies (2 μg / ml) at 37°C for 24 hours. Immune cell populations were analyzed by flow cytometry. Cells were first gated for live cells and further separated into CD45+ cells (immune cells) and CD45- cells (non-immune cells). Within the CD45+ population, CD19+ (B cells) and CD3+ (T cells) cells were identified (Figures A and B). The number of remaining B cells was assessed by anti-CD19 antibody and expressed as a percentage of the CD45+ immune cell population (C). [Figure 40B]This shows that the 2M24 / CD20 activating IgG1 bispecific antibody induces superior tissue B cell depletion compared to rituximab in single-cell suspensions of renal cancer specimens. Single-cell suspensions from two renal cancer tissue specimens were analyzed by flow cytometry in the presence of the 2M24 / CD20 hIgG1 (activating or inactivating) bispecific antibody, a 2M24 / RSV hIgG1 control, fucosylated rituximab, and their respective isotype controls. Renal cancer tissue specimens were dissociated into single-cell suspensions and treated with primary antibodies (2 μg / ml) at 37°C for 24 hours. Immune cell populations were analyzed by flow cytometry. Cells were first gated for live cells and further separated into CD45+ cells (immune cells) and CD45- cells (non-immune cells). Within the CD45+ population, CD19+ (B cells) and CD3+ (T cells) cells were identified (Figures A and B). The number of remaining B cells was assessed by anti-CD19 antibody and expressed as a percentage of the CD45+ immune cell population (C). [Figure 40C] This shows that the 2M24 / CD20 activating IgG1 bispecific antibody induces superior tissue B cell depletion compared to rituximab in single-cell suspensions of renal cancer specimens. Single-cell suspensions from two renal cancer tissue specimens were analyzed by flow cytometry in the presence of the 2M24 / CD20 hIgG1 (activating or inactivating) bispecific antibody, a 2M24 / RSV hIgG1 control, fucosylated rituximab, and their respective isotype controls. Renal cancer tissue specimens were dissociated into single-cell suspensions and treated with primary antibodies (2 μg / ml) at 37°C for 24 hours. Immune cell populations were analyzed by flow cytometry. Cells were first gated for live cells and further separated into CD45+ cells (immune cells) and CD45- cells (non-immune cells). Within the CD45+ population, CD19+ (B cells) and CD3+ (T cells) cells were identified (Figures A and B). The number of remaining B cells was assessed by anti-CD19 antibody and expressed as a percentage of the CD45+ immune cell population (C).

[0090] [Figure 41]Figures A–C show that anti-Dectin-1 antibody (clone 2M24) induces dectin-1 clustering and TNFα secretion from human macrophages. Cytokine secretion was examined by cultured macrophages and single-cell suspensions of renal cancer specimens stimulated with immobilized anti-Dectin-1 antibody (clone 2M24) or 2M24 / CD20 bispecific antibody. Anti-Dectin-1 antibody (clone 2M24), an isotype control, or 2M24 / CD20 bispecific antibody was immobilized overnight at 10 μg per well on a U-bottom polypropylene microtiter plate, followed by incubation with human monocyte-derived macrophages (A and B) or single-cell suspensions from renal cancer specimens (C). Cells were cultured for 24 hours, and the amount of TNFα secreted in the supernatant was assessed by ELISA. As a positive control, cells were stimulated with zymosan.

[0091] [Figure 42] This figure shows that immobilized anti-Dectin-1 antibody (clone 2M24) promotes immune stimulation in single-cell suspensions of kidney cancer specimens. Single-cell suspensions from kidney cancer specimens were treated with immobilized anti-Dectin-1 antibody (clone 2M24) or an isotype control hIgG4 antibody for 24 hours. Supernatants were analyzed by ELISA for the release of various cytokines, including IFNγ, IL-6, TNFα, IL-23, IL-12p70, IL-10, and IL-13. Each plot shows the amount of cytokine (pg / mL) as a function of antibody treatment. Results are shown for kidney cancer donor 3 (left) or donor 4 (right) treated with anti-Dectin-1 antibody (clone 2M24) or an isotype control hIgG4 antibody.

[0092] [Figure 43] Figure 1 shows the effect of the 2M24 / CD20 bispecific antibody on CD16 expression on human NK cells 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 compared to rituximab.

[0093] [Figure 44] Figure 1 shows the effect of the 2M24 / CD20 bispecific antibody on CD19 expression on human B cells compared to rituximab or an isotype control (2M24 / RSV bispecific). The results show that CD19 antigen levels are better maintained in B cells treated with the 2M24 / CD20 bispecific compared to rituximab.

[0094] [Figure 45] Figure 1 shows depletion of human B cells by the 2M24 / CD20 bispecific antibody derived from rituximab or the 2M24 / CD20 bispecific antibody derived from obinutuzumab. The results demonstrate that the 2M24 / CD20 bispecific derived from the rituximab arm is superior in depleting B cells compared to the bispecific derived from obinutuzumab.

[0095] [Figure 46] 1 shows the design of an exploratory study of the safety and efficacy of 2M24 / CD20 bispecific antibodies in non-human primates.

[0096] [Figure 47] Figure 1 shows depletion of circulating B cells in cynomolgus monkeys by the 2M24 / CD20 hIgG1 bispecific antibody generated in cells treated with kifunensine (KIF). Figure 1 shows depletion of B cells in monkeys treated with 5 mg / kg 2M24 / CD20 hIgG1 KIF (top) or inactive 2M24 / CD20 hIgG1 (bottom). [Figure 48] Figure 1 shows depletion of circulating B cells in cynomolgus monkeys by 2M24 / CD20 hIgG1 bispecific antibody generated on cells treated with kifunensine (KIF). Figure 2 shows depletion of B cells in monkeys treated with 5 mg / kg rituximab hIgG1 KIF.

[0097] [Figure 49A]Figure 1 shows depletion of tissue-resident B cells in cynomolgus monkeys by 2M24 / CD20 hIgG1 bispecific antibody generated from cells treated with kifunensine (KIF). Figure 2 shows depletion of B cells in bone marrow from monkeys treated with 5 mg / kg 2M24 / CD20 hIgG1 KIF or rituximab hIgG1 KIF. [Figure 49B] Figure 1 shows depletion of tissue-resident B cells in cynomolgus monkeys by 2M24 / CD20 hIgG1 bispecific antibody generated from cells treated with kifunensine (KIF). Figure 2 shows depletion of B cells in lymph nodes from monkeys treated with 5 mg / kg 2M24 / CD20 hIgG1 KIF or rituximab hIgG1 KIF.

[0098] [Figure 50] Figure 1 shows ex vivo depletion of B cells from cynomolgus monkey PBMCs.

[0099] [Figure 51] The format of a bispecific molecule (2M24 scFv / CD20) that pairs an anti-CD20 conventional half antibody with an anti-Dectin-1 single-chain variable fragment (scFv) Fc fusion arm using knob-into-hole technology is shown. H is the 2M24 VH domain, and L is the 2M24 VL domain.

[0100] [Figure 52A] Figure 1 shows the purification and functional characterization of the 2M24 / CD20 bispecific antibody. Figure 2 shows the purification of the molecule by size exclusion chromatography (SEC). [Figure 52B]

[0023] Figure 1 shows the purification and functional characterization of 2M24 / CD20 bispecific antibodies. The purified bispecific antibodies promoted targeted immune stimulation as assessed by an NFκB reporter assay. [Figure 52C] 1 shows purification and functional characterization of 2M24 / CD20 bispecific antibody. 2 shows depletion of human B cells by 2M24 scFv / CD20 bispecific antibody.

[0101] [Figure 53A]Figure 1 shows the generation and characterization of anti-Dectin-1 (2M24) / anti-Trop-2 bispecific antibodies. 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]

[0023] Figure 1 shows the generation and characterization of an anti-Dectin-1 (2M24) / anti-Trop-2 bispecific antibody, demonstrating high affinity binding of the molecule to Dectin-1-expressing HEK cells. [Figure 53C]

[0023] Figure 1 shows the generation and characterization of an anti-Dectin-1 (2M24) / anti-Trop-2 bispecific antibody, which exhibits moderate affinity binding to the Trop-2-expressing A431 cancer cell line.

[0102] [Figure 54] 1 shows the expression level of Trop-2 in cancer cells.

[0103] [Figure 55A] Figure 1 shows the binding of the 2M24 / Trop-2 bispecific antibody to the Trop-2-expressing cell line HeLa. The binding EC50 for the cell line was calculated using four-parameter logistic (4PL) nonlinear regression. [Figure 55B] Figure 1 shows the binding of 2M24 / Trop-2 bispecific antibodies to BxPC-3. Binding EC50s calculated using four-parameter logistic (4PL) nonlinear regression for the cell lines are shown. [Figure 55C] Figure 1 shows the binding of 2M24 / Trop-2 bispecific antibodies to SiHa. Binding EC50s calculated using four-parameter logistic (4PL) nonlinear regression for cell lines are shown. [Figure 55D] Figure 1 shows the binding of 2M24 / Trop-2 bispecific antibodies to Capan-2. Binding EC50s calculated using four-parameter logistic (4PL) nonlinear regression for cell lines are shown.

[0104] [Figure 56A] Figure 1 shows depletion of a Trop-2 expressing cell line (SKBR3 cells) using the 2M24 / Trop-2 bispecific antibody. [Figure 56B] Figure 1 shows depletion of a Trop-2 expressing cell line (A431 cells) using the 2M24 / Trop-2 bispecific antibody.

[0105] [Figure 57A] 1 shows Trop-2 and Dectin-1 expression in lung cancer specimens. [Figure 57B] 1 shows Trop-2 and Dectin-1 expression in lung cancer specimens.

[0106] [Figure 58] Depletion of Trop-2 positive cancer cells in lung cancer specimens.

[0107] [Figure 59A] Figure 1 shows the activity of the 2M24 / Trop-2 bispecific antibody in an NFκB reporter assay.

[0108] [Figure 59B] 1 shows that the 2M24 / Trop-2 bispecific antibody promotes antigen presentation and T cell activation. A schematic diagram of the assay setup is provided. [Figure 59C] These results demonstrate that the 2M24 / Trop-2 bispecific antibody promotes antigen presentation and T cell activation. Macrophages and SKBR3 breast cancer cells were co-incubated in the presence of 2M24 / Trop-2 hIgG1 or 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] Figure 1 shows that the 2M24 / Trop-2 bispecific antibody promotes antigen presentation and T cell activation. IFNγ levels in the supernatants were quantified using the BD OptiEIA kit. [Figure 59E]We demonstrate that the 2M24 / Trop-2 bispecific antibody enhances antigen presentation and T cell activation. Expression of CD69, an early activation marker, on T cells was assessed by flow cytometry. Data are reported relative to total CD3+ T cells.

[0109] [Figure 60A] 1 shows the design and production of 2M24 / Nectin-4 bispecific antibodies. A diagram of the bispecific molecule is shown. [Figure 60B] 1 shows the design and production of 2M24 / Nectin-4 bispecific antibodies. 2 shows the purification of the bispecific antibodies using Protein A chromatography.

[0110] [Figure 61A] 1 shows Nectin-4 expression in cancer cell lines. [Figure 61B] 1 shows Nectin-4 expression in cancer cells from primary tumor specimens.

[0111] [Figure 62] Binding of the 2M24 / Nectin-4 bispecific antibody to Dectin-1-expressing HEK cells (top) or Nectin-4-expressing A431 cells (bottom) is shown.

[0112] [Figure 63] Figure 1 shows stimulation of Dectin-1 in an NFκB reporter assay by the 2M24 / Nectin-4 bispecific antibody. The upper panel shows a diagram of the assay. The lower panel shows the quantification results based on SEAP levels in the medium.

[0113] [Figure 64A] Figure 1 shows depletion of Nectin-4-expressing cancer cells by 2M24 / Nectin-4 bispecific antibody. Detection of phagocytosis / depletion by flow cytometry. [Figure 64B] Figure 1 shows depletion of Nectin-4 expressing cancer cells by 2M24 / Nectin-4 bispecific antibody. Depletion is shown compared to RSV control.

[0114] [Figure 65A] 2 shows that the 2M24 / 11-1F4 bispecific antibody binds to light chain amyloid. Purification by SEC of the parent anti-amyloid antibody 11-1F4 (top) and the 2M24 / 11-1F4 bispecific antibody (bottom) is shown. [Figure 65B] Figure 1 shows that the 2M24 / 11-1F4 bispecific antibody binds to light chain amyloid. Octet shows binding of the 11-1F4 parent antibody (B) or the 2M24 / 11-1F4 bispecific antibody (C) to recombinant light chain amyloid from different patients (AL30, AL47, AL48, and AL55). [Figure 65C] Figure 1 shows that the 2M24 / 11-1F4 bispecific antibody binds to light chain amyloid. Octet shows binding of the 11-1F4 parent antibody (B) or the 2M24 / 11-1F4 bispecific antibody (C) to recombinant light chain amyloid from different patients (AL30, AL47, AL48, and AL55).

[0115] [Figure 66] This shows the phagocytosis of light chain amyloid fibrils by monocytes.

[0116] [Figure 67] 1 illustrates the ability to modulate the functional activity of myeloid engagers of the present disclosure using the arms that bind Dectin-1 and the arms that bind to a target of interest, as well as the Fc region.

[0117] [Figure 68A] Figure 1 shows the characterization of 2M24 variants binding to Dectin-1. A schematic diagram of the assay used to measure binding via a biosensor (Octet) is provided. [Figure 68B] Figure 1 shows the characterization of 2M24 variants binding to Dectin-1. The dissociation rates of the variants fitted from biosensor data are shown.

[0118] [Figure 69]Panels A and B show the effect of Fc region modulation (in this example, comparing KIF-treated hIgG1 and hIgG4) on B cell depletion by myeloid cell engagers targeting hDectin-1 (via 2M24) and hCD20 using PBMCs from two donors. The hIgG4 Fc contained the S228P mutation (numbering according to the EU index).

[0119] [Figure 70A] ELISA was used to demonstrate the effect of Fc region modulation (in this example, mutations that enhance Fc gamma receptor binding) on ​​binding to Fc gamma receptor CD16a F variants by myeloid cell engagers targeting hDectin-1 (via 2M24). The Fc mutations used were 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: nonfucosylated. All numbering is according to the EU index. The Fc region further contained knob / hole and RF mutations in one Fc chain for refinement (H435R and Y436F in the CH3 domain as described by Jendeberg, L. et al. (1997, J. Immunological Meth., 201:25-34)). [Figure 70B]ELISA was used to demonstrate the effect of Fc region modulation (in this example, mutations that enhance Fc gamma receptor binding) on ​​binding to Fc gamma receptor CD16a F variants by myeloid cell engagers targeting hDectin-1 (via 2M24). The Fc mutations used were 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: nonfucosylated. All numbering is according to the EU index. The Fc region further contained knob / hole and RF mutations in one Fc chain for refinement (H435R and Y436F in the CH3 domain as described by Jendeberg, L. et al. (1997, J. Immunological Meth., 201:25-34)). [Figure 70C] ELISA was used to demonstrate the effect of Fc region modulation (in this example, mutations that enhance Fc gamma receptor binding) on ​​binding to Fc gamma receptor CD16a F variants by myeloid cell engagers targeting hDectin-1 (via 2M24). The Fc mutations used were 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: nonfucosylated. All numbering is according to the EU index. The Fc region further contained knob / hole and RF mutations in one Fc chain for refinement (H435R and Y436F in the CH3 domain as described by Jendeberg, L. et al. (1997, J. Immunological Meth., 201:25-34)). [Figure 70D]ELISA was used to demonstrate the effect of Fc region modulation (in this example, mutations that enhance Fc gamma receptor binding) on ​​binding to Fc gamma receptor CD16a F variants by myeloid cell engagers targeting hDectin-1 (via 2M24). The Fc mutations used were 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: nonfucosylated. All numbering is according to the EU index. The Fc region further contained knob / hole and RF mutations in one Fc chain for refinement (H435R and Y436F in the CH3 domain as described by Jendeberg, L. et al. (1997, J. Immunological Meth., 201:25-34)).

[0120] [Figure 71] 1 shows the binding affinity of 2M24 variants with alanine substitutions compared to that of the parent antibody using a biosensor assay.

[0121] [Figure 72A] Figure 1 shows characterization of 2M24 variants 2M24.116 and 2M24.119, which show that 2M24 variants of bispecific antibodies with anti-Trop2 binding arms showed similar potency compared to the parent 2M24 / Trop2 bispecific in the SEAP reporter assay. [Figure 72B] Figure 1 shows characterization of 2M24 variants 2M24.116 and 2M24.119. The 2M24 / Trop2, 2M24.116 / Trop2, and 2M24.119 / Trop2 bispecific antibodies exhibited similar binding to A431 cells expressing Trop2. EC50 values ​​for each antibody tested are shown. [Figure 72C]Figure 1 shows characterization of 2M24 variants 2M24.116 and 2M24.119. 2M24.116 and 2M24.119 exhibited nearly identical binding to Dectin-1-expressing HEK cells, and the 2M24 / Trop2, 2M24.116 / Trop2, and 2M24.119 / Trop2 bispecific antibodies exhibited similar binding to Dectin-1-expressing HEK cells. EC50 values ​​for each antibody tested are shown.

[0122] [Figure 73] Figure 1 shows a schematic representation of a bispecific binding protein targeting Dectin-1 (e.g., using the variable domains of 2M24) and a target of interest, including 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 in an scFv format (right) are shown. The heavy chains are paired by knob-into-hole mutations. In the Dectin-1 binding arm, the cysteine ​​that forms the natural disulfide bond between the heavy and light chains has been removed, and a cysteine ​​substitution has been introduced that creates a non-native disulfide bond. The arm that binds the target of interest has a natural disulfide bond, allowing the variable domains of each arm to be differentiated by the disulfide bond position.

[0123] [Figure 74A]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 indicated by solid lines. Interchain disulfide bonds introduced by cysteine ​​substitutions in the 2M24 VH and VL domains are indicated by dotted lines. A indicates substitution of P1, and B indicates substitution of P2. The sequences shown correspond to sequence number 213 for 2M24 P1 VH (2M24_H in Figure 74A), sequence number 214 for 2M24 P1 VL (2M24_L in Figure 74A), sequence number 215 for 2M24 P2 VH (2M24_H in Figure 74B), sequence number 216 for 2M24 P2 VL (2M24_L in Figure 74B), sequence number 217 for CTX-2026 VH (6XLQ_B in Figures 74A and 74B), and sequence number 218 for CTX-2026 VL (6XLQ_C in Figures 74A and 74B). [Figure 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 indicated by solid lines. Interchain disulfide bonds introduced by cysteine ​​substitutions in the 2M24 VH and VL domains are indicated by dotted lines. A indicates substitution of P1, and B indicates substitution of P2. The sequences shown correspond to sequence number 213 for 2M24 P1 VH (2M24_H in Figure 74A), sequence number 214 for 2M24 P1 VL (2M24_L in Figure 74A), sequence number 215 for 2M24 P2 VH (2M24_H in Figure 74B), sequence number 216 for 2M24 P2 VL (2M24_L in Figure 74B), sequence number 217 for CTX-2026 VH (6XLQ_B in Figures 74A and 74B), and sequence number 218 for CTX-2026 VL (6XLQ_C in Figures 74A and 74B).

[0124] [Figure 75A]Figure 1 shows the results of a SEAP secretion assay using hDectin-1-expressing HEK cells with a SEAP Dectin-1 reporter and Raji cells (expressing CD20). Bispecific antibodies targeting Dectin-1 and CD20 were assayed using DuetMab substitution (Duet) to drive heavy chain / light chain pairing, 2M24 P1 VH and VL domains (hG1 SS P1), 2M24 P2 VH and VL domains (hG1 SS P2), a control 2M24 / RSV bispecific, and a control 2M24 antibody. OD630 based on the SEAP reporter of hDectin-1-expressing HEK cells was tracked as a function of antibody concentration.

[0125] [Figure 75B] This figure shows the results of a B cell depletion assay using healthy donor PBMCs from two donors (left and right). The ability of a bispecific antibody (active hIgG1 Fc) with the 2M24 P1 VH and VL domains in one arm and an anti-CD20 binding domain in the other arm to deplete B cells was compared to an isotype control RSV antibody. The plot shows the level of remaining viable CD19+ B cells (reported as a percentage of B cells in PBMCs treated with isotype control) versus antibody concentration after 24 hours of incubation.

[0126] [Figure 76A] Protein A purification of 2M24 / CD20 bispecific binding proteins in which the 2M24 arms are in scFv format (format indicated on the right) is shown. Bispecific binding proteins with the parental 2M24 scFv were compared to bispecific binding proteins with the 2M24 P1 variant scFv. For each binding protein, the percentage of each species purified as oligomers and monomers is shown. While 60-70% of the parental 2M24 scFv / CD20 bispecific was in monomeric form, >96% of the 2M24 P1 variant scFv / CD20 bispecific was monomeric, indicating that the disulfide variants were more stable and less prone to oligomerization during Protein A affinity purification.

[0127] [Figure 76B] Binding 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 parent VH and VL domains. A37: 2M24 P1 variant VH and VL domains.

[0128] [Figure 76C] Figure 1 shows the activity of the 2M24 / CD20 bispecific binding protein in a SEAP reporter assay using hDectin-1-expressing HEK cells with a SEAP Dectin-1 reporter and Raji cells (expressing CD20) in a 1:1 ratio. A4: 2M24 parent VH and VL domains. A37: 2M24 P1 variant VH and VL domains. B01: mIgG2a negative control.

[0129] [Figure 76D] The ability of 2M24 / CD20 bispecific binding proteins, in which the 2M24 arms are in scFv format (variable domains of either parental 2M24 or P1 variant 2M24), to deplete B cells from human PBMCs from two healthy donors (left and right) is compared to an isotype control.

[0130] [Figure 76E] A comparison of oligomer and monomer abundance after Protein A purification of 2M24 / CD20 bispecific binding proteins is shown for 2M24 / CD20 bispecific binding proteins in which the 2M24 arms are in scFv format (parental 2M24) after 1 week at 5° C. or 25° C. (top left) or for 2M24 / CD20 bispecific binding proteins in which the 2M24 arms are in scFv format (P1 variant 2M24) after 4 weeks at 5° C. or 25° C. (top right). The stability over time (expressed as % of monomer species) of parental 2M24 and P1 variant 2M24 at 5° C. and 25° C. is shown (bottom).

[0131] [Figure 77] B cell depletion (% CD19+ to CD45+ cells) from human PBMCs from two healthy donors versus antibody concentration after 24 hours of incubation for 2M24 / CD20 bispecific binding proteins with human IgG4, human IgG1, or nonfucosylated human IgG1 Fc regions (left and right) is shown compared to isotype control. DETAILED DESCRIPTION OF THE INVENTION

[0132] Some aspects are described below with reference to illustrative applications. It should be understood that numerous specific details, relationships, and methods are described to provide a thorough understanding of the features described herein. However, one skilled in the art will readily recognize that the features described herein can be implemented in other ways without one or more of the specific details. The features described herein are not limited to the illustrated order of acts or events, as some actions may occur in different orders and / or simultaneously with other actions or events. Furthermore, not all illustrated acts or events are required to implement a method in accordance with the features described herein.

[0133] As used herein, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. Furthermore, to the extent the terms "including," "includes," "having," "has," "with," or variations thereof are used in either the detailed description and / or the claims, such terms are intended to be inclusive in the same manner as the term "comprising." As used herein, the term "comprising" is synonymous with "including" or "containing" and is inclusive or open-ended.

[0134] References to "or" herein are intended to encompass "and / or" unless otherwise specified. As used herein, the term "about" with respect to a numerical value means a numerical value of +10% or -10% of that numerical value. The term "about" with respect to a range refers to the range minus 10% of its minimum value and plus 10% of its maximum value.

[0135] I. Antibodies and Multispecific Binding Proteins In certain aspects, the present disclosure provides antigen-binding domains, antibodies, and antibody fragments that bind to human Dectin-1, as well as multispecific (e.g., bispecific) binding molecules comprising the same. In some embodiments, provided herein is the anti-Dectin-1 antigen-binding domain 2M24, and variants thereof, described in International Application No. PCT / US2021 / 071752, filed October 6, 2021.

[0136] In some embodiments, antibody and immunoglobulin are used interchangeably and are used herein in the broadest sense to 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 (described in more detail herein), so long as they exhibit the desired antigen-binding activity.

[0137] In some embodiments, an antibody (immunoglobulin) refers to a protein having a structure substantially similar to that of a native antibody, or a protein having heavy and light chain variable regions having structures substantially similar to those of native heavy and light chain variable regions. A native antibody refers to naturally occurring immunoglobulin molecules with diverse structures. For example, the IgG class of native immunoglobulins is a heterotetrameric glycoprotein of approximately 150,000 daltons composed of two disulfide-bonded light chains and two heavy chains. From the N-terminus to the C-terminus, each heavy chain has a variable region (VH), also called a variable heavy domain or heavy chain variable domain, followed by three constant domains (CH1, CH2, and CH3), also called a heavy chain constant region. Similarly, from the N-terminus to the C-terminus, each light chain has a variable region (VL), also called a variable light domain or light chain variable domain, followed by a constant light (CL) domain, also called a light chain constant region. The subunit structures and three-dimensional configurations of different classes of immunoglobulins are well known and are generally described, for example, in Abbas et al., 2000, Cellular and Mol, and Kindt et al., Kuby Immunology, 6th ed., W.H. Freeman and Co., page 91 (2007). Depending on the amino acid sequence of the constant domain of their heavy chains, antibodies (immunoglobulins) are assigned to different classes. There are five major classes of antibodies: α (IgA), δ (IgD), ε (IgE), γ (IgG), or μ (IgM), some of which can be further divided into subtypes, e.g., γ1 (IgG1), γ2 (IgG2), γ3 (IgG3), γ4 (IgG4), α1 (IgA1), and α2 (IgA2). The light chain of an immunoglobulin can be assigned to one of two types, called kappa (κ) and lambda (λ), based on the amino acid sequence of its constant domain. An immunoglobulin basically consists of two Fab molecules and one Fc domain linked via the immunoglobulin hinge region.

[0138] In some embodiments, Fc, Fc region, or Fc domain refers to the C-terminal region of an antibody heavy chain containing at least a portion of the constant region. This term includes native-sequence Fc regions and variant Fc regions. 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 N-terminal to these domains. For IgA and IgM, Fc may also include the J chain. An IgG Fc region includes the IgG CH2 and IgG CH3 domains, and optionally includes the hinge. Unless otherwise specified herein, the numbering of amino acid residues in the Fc region or constant region follows the EU numbering system, also known as the EU index, as described in Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md., 1991. Human IgG Fc domains are particularly useful in the present disclosure and can be Fc domains derived from human IgG1, IgG2, or IgG4.

[0139] As is known in the art, antibody heavy and light chain variable domains (VH and VL, respectively) generally have similar structures, with each domain comprising four conserved framework regions (FR) and three complementarity-determining regions (CDR). (See, e.g., Kindt et al., Kuby Immunology, 6th ed., W.H. 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 generally consists of four FR domains: FR1, FR2, FR3, and FR4. Thus, the CDR and FR sequences generally appear in the order FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4 in VH (or VL). In some embodiments, FR1, FR2, FR3, and / or FR4 in the present disclosure refer to human framework regions, i.e., the framework regions of the VH or VL domain.

[0140] In some embodiments, the antigen-binding domain, antibody, or fragment comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; the VH domain has the amino acid sequence QVQLVQSGAEVKKPGASVKVSCKSSGYTFTX1YYIHWVRQAPGQGLEWMGWINPNSGX2TNYAQKFQGRITMTRDTSISTAYLELSRLRSDDTAVFYCAX3X4X5X6X7X8X9X 10 X 11 X 12 WGQGTLVTVSS [where X1 is D, A, or G, X2 is D, A, or G, X3 is R, A, or G, X4 is N, A, or G, X5 is S, A, or G, X6 is A or G, X7 is S, A, or G, X8 is Y, A, or G, X9 is S, A, or G, and X 10 is F, A, or G, and X 11 is A or G and X 12is Y, A, or G] (SEQ ID NO: 63); and the VL domain comprises the amino acid sequence DIQMTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKAPKLLIFGASSLQSGVPSRFSGSGSGTDFTLTVSSLQPEDFATYYCX1X2AX3X4X5X6X7X8FGPGTKVDIE [wherein Xi is Q, A, or G, X2 is Q, A, or G, X3 is F, Y, A, or G, X4 is S, A, or G, X5 is F, A, or G, X6 is P, A, or G, X7 is F, A, or G, and X8 is T, A, or G] (SEQ ID NO: 65). In some embodiments, the antigen-binding domain, antibody, or fragment 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). In some embodiments, the VH domain comprises 1, no more than 2, no more than 3, no more than 4, or no more than 5 substitutions compared to the amino acid sequence of SEQ ID NO: 62, and / or the VL domain comprises 1, no more than 2, no more than 3, no more than 4, or no more than 5 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 Dectin-1; and / or does not compete with the natural ligand of human Dectin-1.

[0141] In some embodiments, the antigen-binding domain, antibody, or fragment comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; 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 the amino acid sequence 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: 3 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). In some embodiments, the antigen-binding domain, antibody, or fragment 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).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 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 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 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 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 NSASYSFGY (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 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 NSGSYSFGA (SEQ ID NO: 39). In some embodiments, the VH domain further comprises an FR1 comprising an amino acid sequence selected from the group consisting of QVQLVQSGAEVKKPGASVKVSCKSSGYTFT (SEQ ID NO: 50) and QVQLVQSGAEVKKPGASVKVSCKASGYTFT (SEQ ID NO: 51), an FR2 comprising the amino acid sequence HWVRQAPGQGLEWMG (SEQ ID NO: 52), an FR3 comprising an amino acid sequence selected from the group consisting of RITMTRDTSISTAYLELSRLRSDDTAVFYCAR (SEQ ID NO: 53) and RVTMTRDTSISTAYMELSRLRSDDTAVYYCAR (SEQ ID NO: 54), and an FR4 comprising the amino acid sequence WGQGTLVTVSS (SEQ ID NO: 55). 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 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). 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 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). 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 QQAYAFPFT (SEQ ID NO:45). 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 QQAYSAPFT (SEQ ID NO:46). 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 QQAYSFAFT (SEQ ID NO:47). 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 QQAYSFPAT (SEQ ID NO:48).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 QQAYSFPFA (SEQ ID NO:49). In some embodiments, the VL domain further comprises an FR1 comprising the amino acid sequence DIQMTQSPSSVSASVGDRVTITC (SEQ ID NO:56), an FR2 comprising an amino acid sequence selected from the group consisting of WYQQKPGKAPKLLIF (SEQ ID NO:57) and WYQQKPGKAPKLLIY (SEQ ID NO:58), an FR3 comprising an amino acid sequence selected from the group consisting of GVPSRFSGSGSGTDFTLTVSSLQPEDFATYYC (SEQ ID NO:59) and GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC (SEQ ID NO:60), and an FR4 comprising the amino acid sequence FGPGTKVDIE (SEQ ID NO:61).

[0142] Multiple definitions of CDR sequences of 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 specified, CDR sequences are described herein according to the definitions of IMGT. See, for example, www.imgt.org / IMGTScientificChart / Nomenclature / IMGT-FRCDRdefinition.html.

[0143] In some embodiments, the antigen-binding domain, antibody, or fragment comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; 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 INPNSGAT (SEQ ID NO: 20), and a CDR-H3 comprising the amino acid sequence ARNSGSYSFGY (SEQ ID NO: 9), ARASGSYSFGY (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: 34), ARNSGSYSAGY (SEQ ID NO: 36), ARNSGSYSAGY (SEQ ID NO: 37), ARNSGSYSAGY (SEQ ID NO: 38), ARNSGSYSAGY (SEQ ID NO: 39), ARNSGSYSAGY (SEQ ID NO: 40), ARNSGSYSAGY (SEQ ID NO: 41), ARNSGSYSAGY (SEQ ID NO: 42), ARNSGSYSAGY (SEQ ID NO: 43), ARNSGSYSAGY (SEQ ID NO: 44), ARNSGSYSAGY (SEQ ID NO: 45), ARNSGSYSAGY (SEQ ID NO: 46), ARNSGSYSAGY (SEQ ID NO: 47), ARNSGSYSAGY (SEQ ID NO: 48), ARNSGSYSAGY (SEQ ID NO: 49), ARNSGSYSAGY (SEQ ID NO: 50), ARN and CDR-H3 comprising an amino acid sequence selected from the group consisting of RNSGSYSFAY (SEQ ID NO: 38), and ARNSGSYSFGA (SEQ ID NO: 40); the VL domain comprises CDR-L1 comprising the amino acid sequence QGISSW (SEQ ID NO: 10), CDR-L2 comprising the amino acid sequence GAS (SEQ ID NO: 11), and 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), and QQAYSFPFA (SEQ ID NO: 49). In some embodiments, the antigen-binding domain, antibody, or fragment does not comprise 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 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, a 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 ARNSGSYSFGY (SEQ ID NO:9). In some embodiments, a 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, a 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, a 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 ARASGSYSFGY (SEQ ID NO:23). In some embodiments, a 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, a 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, a 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, a 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, a 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 a...

Claims

1. (a) A first antibody or its antigen-binding fragment comprising a first antigen-binding domain that binds to human dectin-1, (b) A multispecific binding molecule comprising a second antibody or an antigen-binding fragment thereof, which includes a second antigen-binding domain that binds to a target, The first antigen-binding domain comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; (i) The VH domain of the first antigen-binding domain comprises: CDR-H1 containing the amino acid sequence DYYI (SEQ ID NO: 1) or DYYM (SEQ ID NO: 199); CDR-H2 containing the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), WINPNEGDTNYAQKFEG (SEQ ID NO: 200), or WINPNEGDTNYAQKFQE (SEQ ID NO: 201); and CDR-H3 containing 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); The VL domain of the first antigen-binding domain comprises CDR-L1 containing the amino acid sequence RASQGISSWLA (SEQ ID NO: 4); CDR-L2 containing the amino acid sequence GASSLQS (SEQ ID NO: 5) or GASDLQS (SEQ ID NO: 206); and CDR-L3 containing 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); or (ii) the VH domain of the first antigen-binding domain has the amino acid sequence QVQLVQSGAEVKKPGASVKVSCKSSGYTFTX ６ , ４ , ２ , １２ , １２ , １０ , １０ , ８ , ７ , ５ , ３ , １１ , １ , ９ , １１ YYIHWVQRQAPGQGLEWMGWINPNSGX ２ TNYAQKFQGRTMTRDTSISTAYLELSLRSDDTAVFYCAX ３ X ４ X ５ X ６ X ７ X ８ X ９ X １０ X １１ X １２ WGQGTVTVSS [where X １ is D, A, or G, and X ２ is D, A, or G, and X ３ is R, A, or G, and X ４ is N, A, or G, and X ５ is S, A, or G, and X ６ is A or G, and X ７ is S, A, or G, and X ８ is Y, A, or G, and X ９ is S, A, or G, and X １０ is F, A, or G, and X １１ is A or G, and X １２ is Y, A, or G] (SEQ ID NO: 63); The VL domain of the first antigen-binding domain is the amino acid sequence DIQMTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKAAPKLLIFGASSLQSGVPSRFSGSGSGTDFTLTVSSLQPEDFATYYCX １ X ２ AX ３ X ４ X ５ X ６ X ７ X ８ FGPGTKVDIE [Here, X １ However, it is Q, A, or G, and X ２ However, it is Q, A, or G, and X ３ However, it is F, Y, A, or G, and X ４ However, it is S, A, or G, and X ５ However, it is F, A, or G, and X ６ However, it is P, A, or G, and X ７ However, it is F, A, or G, and X ８ [but is T, A, or G] (Sequence ID 65); or (iii) The VH domain of the first antigen-binding domain comprises CDR-H1 containing the amino acid sequence DYYI (SEQ ID NO: 1) or AYYI (SEQ ID NO: 16); CDR-H2 containing the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2) or WINPNSGATNYAQKFQG (SEQ ID NO: 19); NSGSYSFGY (SEQ ID NO: 3), ASGSYSFGY (SEQ ID NO: 22), CDR-H3 comprises an amino acid sequence selected from the group consisting of 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); The VL domain of the first antigen-binding domain comprises CDR-L1 containing the amino acid sequence RASQGISSWLA (SEQ ID NO: 4); CDR-L2 containing the amino acid sequence GASSLQS (SEQ ID NO: 5); and CDR-L3 containing 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), QQAYAFFPFT (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); or (iv) The VH domain of the first antigen-binding domain comprises the amino acid sequence QVQLVQSGAEVKKPGASVKVSCKX 1 SGYTFTX 2 YYX 3 HWVRQAPGQGLEWMGWINPNSGX 4 TNYAQKFQGRX 5 TMTRDTSISTAYX 6 ELSRLRSDDTAVX 7 YCARNSGSYSFGYWGQGTLVTVSS [wherein X1 is S or A, X2 is D or G, X3 is I or M, X4 is D or G, X5 is I or V, X6 is L or M, and X7 is F or Y] (Sequence ID 80); The VL domain of the first antigen-binding domain contains the amino acid sequence DIQMTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKAAPKLLIX 1 X 2 ASSLQSGVPSRFSGSGSGTDFTLTX 3 SSLQPEDFATYYCQQAYSFPFTFGPGTKVDIE [where X 1 is F or Y, X 2 is G or A, and X 3 is V or I] (SEQ ID NO: 81); or (v) The VH domain of the first antigen-binding domain comprises: CDR-H1 containing 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); CDR-H2 containing the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2) or WINPNSGGTNYAQKFQG (SEQ ID NO: 70); and CDR-H3 containing the amino acid sequence NSGSYSFGY (SEQ ID NO: 3); The VL domain of the first antigen-binding domain comprises CDR-L1 containing the amino acid sequence RASQGISSWLA (SEQ ID NO: 4); CDR-L2 containing the amino acid sequence GASSLQS (SEQ ID NO: 5) or AASSLQS (SEQ ID NO: 73); and CDR-L3 containing the amino acid sequence QQAYSFPFT (SEQ ID NO: 6); The antibody does not contain CDR-H1 containing the amino acid sequence DYYI (SEQ ID NO: 1), CDR-H2 containing the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), CDR-H3 containing the amino acid sequence NSGSYSFGY (SEQ ID NO: 3), CDR-L1 containing the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), CDR-L2 containing the amino acid sequence GASSLQS (SEQ ID NO: 5), and CDR-L3 containing the amino acid sequence QQAYSFPFT (SEQ ID NO: 6). The aforementioned multispecific binding molecule.

2. (i) (a) The VH domain of the first antigen-binding domain comprises CDR-H1 containing the amino acid sequence of DYYM (SEQ ID NO: 199), CDR-H2 containing the amino acid sequence of WINPNEGDTNYAQKFEG (SEQ ID NO: 200), and CDR-H3 containing the amino acid sequence of NTGAYSFGY (SEQ ID NO: 204); and the VL domain of the first antigen-binding domain comprises CDR-L1 containing the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), CDR-L2 containing the amino acid sequence of GASDLQS (SEQ ID NO: 206), and CDR-L3 containing the amino acid sequence of QQAYGFPFT (SEQ ID NO: 207); (b) The VH domain of the first antigen-binding domain comprises CDR-H1 containing the amino acid sequence of DYYM (SEQ ID NO: 199), CDR-H2 containing the amino acid sequence of WINPNEGDTNYAQKFQE (SEQ ID NO: 201), and CDR-H3 containing the amino acid sequence of NTGAYSFGY (SEQ ID NO: 204); and the VL domain of the first antigen-binding domain comprises CDR-L1 containing the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), CDR-L2 containing the amino acid sequence of GASDLQS (SEQ ID NO: 206), and CDR-L3 containing the amino acid sequence of HQAYSFPFT (SEQ ID NO: 208); (c) The VH domain of the first antigen-binding domain comprises CDR-H1 containing the amino acid sequence of DYYI (SEQ ID NO: 1), CDR-H2 containing the amino acid sequence of WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and CDR-H3 containing the amino acid sequence of NSGSASFGY (SEQ ID NO: 187), and the VL domain of the first antigen-binding domain comprises CDR-L1 containing the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), CDR-L2 containing the amino acid sequence of GASSLQS (SEQ ID NO: 5), and CDR-L3 containing the amino acid sequence of QQAYSFPFT (SEQ ID NO: 6); (d) The VH domain of the first antigen-binding domain comprises CDR-H1 containing the amino acid sequence of DYYI (SEQ ID NO: 1), CDR-H2 containing the amino acid sequence of WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and CDR-H3 containing the amino acid sequence of NSGSYSAGY (SEQ ID NO: 190), and the VL domain of the first antigen-binding domain comprises CDR-L1 containing the amino acid sequence of RASQGISSWLA (SEQ ID NO: 4), CDR-L2 containing the amino acid sequence of GASSLQS (SEQ ID NO: 5), and CDR-L3 containing the amino acid sequence of QQAYSFPFT (SEQ ID NO: 6); (e) The VH domain of the first antigen-binding domain comprises CDR-H1 containing the amino acid sequence DYYI (SEQ ID NO: 1), CDR-H2 containing the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and CDR-H3 containing the amino acid sequence NSGSYSFGY (SEQ ID NO: 3), and the VL domain of the first antigen-binding domain comprises CDR-L1 containing the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), CDR-L2 containing the amino acid sequence GASSLQS (SEQ ID NO: 5), and CDR-L3 containing the amino acid sequence QAAYSFPFT (SEQ ID NO: 192); or (f) The VH domain of the first antigen-binding domain comprises CDR-H1 containing the amino acid sequence DYYI (SEQ ID NO: 1), CDR-H2 containing the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and CDR-H3 containing the amino acid sequence NSGSYSFGY (SEQ ID NO: 3), and the VL domain of the first antigen-binding domain comprises CDR-L1 containing the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), CDR-L2 containing the amino acid sequence GASSLQS (SEQ ID NO: 5), and CDR-L3 containing the amino acid sequence QQAYSAPFT (SEQ ID NO: 193); or (ii) The VH domain of the first antigen-binding domain, (g) CDR-H1 containing amino acid sequence DYYI (SEQ ID NO: 1), CDR-H2 containing amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and CDR-H3 containing amino acid sequence NSGSYSFGY (SEQ ID NO: 3); (h) CDR-H1 containing amino acid sequence AYYI (SEQ ID NO: 16), CDR-H2 containing amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and CDR-H3 containing amino acid sequence NSGSYSFGY (SEQ ID NO: 3); (i) CDR-H1 containing amino acid sequence DYYI (SEQ ID NO: 1), CDR-H2 containing amino acid sequence WINPNSGATNYAQKFQG (SEQ ID NO: 19), and CDR-H3 containing amino acid sequence NSGSYSFGY (SEQ ID NO: 3); (j) CDR-H1 containing amino acid sequence DYYI (SEQ ID NO: 1), CDR-H2 containing amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and CDR-H3 containing amino acid sequence ASGSYSFGY (SEQ ID NO: 22); (k) CDR-H1 containing amino acid sequence DYYI (SEQ ID NO: 1), CDR-H2 containing amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and CDR-H3 containing amino acid sequence NSGSASFGY (SEQ ID NO: 24); (l) CDR-H1 containing amino acid sequence DYYI (SEQ ID NO: 1), CDR-H2 containing amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and CDR-H3 containing amino acid sequence NAGSYSFGY (SEQ ID NO: 27); (m) CDR-H1 containing amino acid sequence DYYI (SEQ ID NO: 1), CDR-H2 containing amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and CDR-H3 containing amino acid sequence NSASYSFGY (SEQ ID NO: 29); (n) CDR-H1 containing amino acid sequence DYYI (SEQ ID NO: 1), CDR-H2 containing amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and CDR-H3 containing amino acid sequence NSGAYSFGY (SEQ ID NO: 31); (o) CDR-H1 containing amino acid sequence DYYI (SEQ ID NO: 1), CDR-H2 containing amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and CDR-H3 containing amino acid sequence NSGSYAFGY (SEQ ID NO: 33); (p) CDR-H1 containing amino acid sequence DYYI (SEQ ID NO: 1), CDR-H2 containing amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and CDR-H3 containing amino acid sequence NSGSYSAGY (SEQ ID NO: 35); (q) CDR-H1 containing amino acid sequence DYYI (SEQ ID NO: 1), CDR-H2 containing amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and CDR-H3 containing amino acid sequence NSGSYSFAY (SEQ ID NO: 37); or (r) CDR-H1 containing amino acid sequence DYYI (SEQ ID NO: 1), CDR-H2 containing amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and CDR-H3 containing amino acid sequence NSGSYSFGA (SEQ ID NO: 39) Including; The VL domain of the first antigen-binding domain is (s) CDR-L1 containing the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), CDR-L2 containing the amino acid sequence GASSLQS (SEQ ID NO: 5), and CDR-L3 containing the amino acid sequence QQAYSFPFT (SEQ ID NO: 6); (t) CDR-L1 containing the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), CDR-L2 containing the amino acid sequence GASSLQS (SEQ ID NO: 5), and CDR-L3 containing the amino acid sequence QQAASFPFT (SEQ ID NO: 41); (u) CDR-L1 containing the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), CDR-L2 containing the amino acid sequence GASSLQS (SEQ ID NO: 5), and CDR-L3 containing the amino acid sequence QQAFSFPFT (SEQ ID NO: 42); (v) CDR-L1 containing the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), CDR-L2 containing the amino acid sequence GASSLQS (SEQ ID NO: 5), and CDR-L3 containing the amino acid sequence AQAYSFPFT (SEQ ID NO: 43); (w) CDR-L1 containing the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), CDR-L2 containing the amino acid sequence GASSLQS (SEQ ID NO: 5), and CDR-L3 containing the amino acid sequence QAAYSFPFT (SEQ ID NO: 44); (x) CDR-L1 containing the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), CDR-L2 containing the amino acid sequence GASSLQS (SEQ ID NO: 5), and CDR-L3 containing the amino acid sequence QQAYAFPFT (SEQ ID NO: 45); (y) CDR-L1 containing the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), CDR-L2 containing the amino acid sequence GASSLQS (SEQ ID NO: 5), and CDR-L3 containing the amino acid sequence QQAYSAPFT (SEQ ID NO: 46); (z) CDR-L1 containing the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), CDR-L2 containing the amino acid sequence GASSLQS (SEQ ID NO: 5), and CDR-L3 containing the amino acid sequence QQAYSFAFT (SEQ ID NO: 47); (aa) CDR-L1 containing the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), CDR-L2 containing the amino acid sequence GASSLQS (SEQ ID NO: 5), and CDR-L3 containing the amino acid sequence QQAYSFPAT (SEQ ID NO: 48); or (bb) CDR-L1 containing the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), CDR-L2 containing the amino acid sequence GASSLQS (SEQ ID NO: 5), and CDR-L3 containing the amino acid sequence QQAYSFPFA (SEQ ID NO: 49). including; or (iii) The VH domain of the first antigen-binding domain, (cc) CDR-H1 containing amino acid sequence DYYI (SEQ ID NO: 1), CDR-H2 containing amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and CDR-H3 containing amino acid sequence NSGSYSFGY (SEQ ID NO: 3); (dd) CDR-H1 containing amino acid sequence DYYM (SEQ ID NO: 66), CDR-H2 containing amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and CDR-H3 containing amino acid sequence NSGSYSFGY (SEQ ID NO: 3); (ee) CDR-H1 containing amino acid sequence GYYM (SEQ ID NO: 67), CDR-H2 containing amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), and CDR-H3 containing amino acid sequence NSGSYSFGY (SEQ ID NO: 3); (ff) CDR-H1 containing the amino acid sequence DYYM (SEQ ID NO: 66), CDR-H2 containing the amino acid sequence WINPNSGGTNYAQKFQG (SEQ ID NO: 70), and CDR-H3 containing the amino acid sequence NSGSYSFGY (SEQ ID NO: 3); or CDR-H1 containing the amino acid sequence GYYM (SEQ ID NO: 67), CDR-H2 containing the amino acid sequence WINPNSGGTNYAQKFQG (SEQ ID NO: 70), and CDR-H3 containing the amino acid sequence NSGSYSFGY (SEQ ID NO: 3). Including; The VL domain of the first antigen-binding domain is (hh) CDR-L1 containing the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), CDR-L2 containing the amino acid sequence GASSLQS (SEQ ID NO: 5), and CDR-L3 containing the amino acid sequence QQAYSFPFT (SEQ ID NO: 6); or (ii) CDR-L1 containing the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), CDR-L2 containing the amino acid sequence AASSLQS (SEQ ID NO: 73), and CDR-L3 containing the amino acid sequence QQAYSFPFT (SEQ ID NO: 6) including, The multispecific binding molecule according to claim 1.

3. In the first antigen-binding domain, (1) The VH domain contains the amino acid sequence of SEQ ID NO: 220, and the VL domain contains the amino acid sequence of SEQ ID NO: 221; (2) The VH domain contains the amino acid sequence of SEQ ID NO: 62, and the VL domain contains the amino acid sequence of SEQ ID NO: 94; (3) The VH domain contains the amino acid sequence of SEQ ID NO: 62, and the VL domain contains the amino acid sequence of SEQ ID NO: 95; (4) The VH domain contains the amino acid sequence of SEQ ID NO: 62, and the VL domain contains the amino acid sequence of SEQ ID NO: 96; (5) The VH domain contains the amino acid sequence of SEQ ID NO: 62, and the VL domain contains the amino acid sequence of SEQ ID NO: 97; (6) The VH domain contains the amino acid sequence of SEQ ID NO: 62, and the VL domain contains the amino acid sequence of SEQ ID NO: 98; (7) The VH domain contains the amino acid sequence of SEQ ID NO: 62, and the VL domain contains the amino acid sequence of SEQ ID NO: 99; (8) The VH domain contains the amino acid sequence of SEQ ID NO: 62, and the VL domain contains the amino acid sequence of SEQ ID NO: 100; (9) The VH domain contains the amino acid sequence of SEQ ID NO: 62, and the VL domain contains the amino acid sequence of SEQ ID NO: 101; (10) The VH domain contains the amino acid sequence of SEQ ID NO: 62, and the VL domain contains the amino acid sequence of SEQ ID NO: 102; (11) The VH domain contains the amino acid sequence of SEQ ID NO: 82, and the VL domain contains the amino acid sequence of SEQ ID NO: 64; (12) The VH domain contains the amino acid sequence of SEQ ID NO: 82, and the VL domain contains the amino acid sequence of SEQ ID NO: 94; (13) The VH domain contains the amino acid sequence of SEQ ID NO: 82, and the VL domain contains the amino acid sequence of SEQ ID NO: 95; (14) The VH domain contains the amino acid sequence of SEQ ID NO: 82, and the VL domain contains the amino acid sequence of SEQ ID NO: 96; (15) The VH domain contains the amino acid sequence of SEQ ID NO: 82, and the VL domain contains the amino acid sequence of SEQ ID NO: 97; (16) The VH domain contains the amino acid sequence of SEQ ID NO: 82, and the VL domain contains the amino acid sequence of SEQ ID NO: 98; (17) The VH domain contains the amino acid sequence of SEQ ID NO: 82, and the VL domain contains the amino acid sequence of SEQ ID NO: 99; (18) The VH domain contains the amino acid sequence of SEQ ID NO: 82, and the VL domain contains the amino acid sequence of SEQ ID NO: 100; (19) The VH domain contains the amino acid sequence of SEQ ID NO: 82, and the VL domain contains the amino acid sequence of SEQ ID NO: 101; (20) The VH domain contains the amino acid sequence of SEQ ID NO: 82, and the VL domain contains the amino acid sequence of SEQ ID NO: 102; (21) The VH domain contains the amino acid sequence of SEQ ID NO: 83, and the VL domain contains the amino acid sequence of SEQ ID NO: 64; (22) The VH domain contains the amino acid sequence of SEQ ID NO: 83, and the VL domain contains the amino acid sequence of SEQ ID NO: 94; (23) The VH domain contains the amino acid sequence of SEQ ID NO: 83, and the VL domain contains the amino acid sequence of SEQ ID NO: 95; (24) The VH domain contains the amino acid sequence of SEQ ID NO: 83, and the VL domain contains the amino acid sequence of SEQ ID NO: 96; (25) The VH domain contains the amino acid sequence of SEQ ID NO: 83, and the VL domain contains the amino acid sequence of SEQ ID NO: 97; (26) The VH domain contains the amino acid sequence of SEQ ID NO: 83, and the VL domain contains the amino acid sequence of SEQ ID NO: 98; (27) The VH domain contains the amino acid sequence of SEQ ID NO: 83, and the VL domain contains the amino acid sequence of SEQ ID NO: 99; (28) The VH domain contains the amino acid sequence of SEQ ID NO: 83, and the VL domain contains the amino acid sequence of SEQ ID NO: 100; (29) The VH domain contains the amino acid sequence of SEQ ID NO: 83, and the VL domain contains the amino acid sequence of SEQ ID NO: 101; (30) The VH domain contains the amino acid sequence of SEQ ID NO: 83, and the VL domain contains the amino acid sequence of SEQ ID NO: 102; (31) The VH domain contains the amino acid sequence of SEQ ID NO: 84, and the VL domain contains the amino acid sequence of SEQ ID NO: 64; (32) The VH domain contains the amino acid sequence of SEQ ID NO: 84, and the VL domain contains the amino acid sequence of SEQ ID NO: 94; (33) The VH domain contains the amino acid sequence of SEQ ID NO: 84, and the VL domain contains the amino acid sequence of SEQ ID NO: 95; (34) The VH domain contains the amino acid sequence of SEQ ID NO: 84, and the VL domain contains the amino acid sequence of SEQ ID NO: 96; (35) The VH domain contains the amino acid sequence of SEQ ID NO: 84, and the VL domain contains the amino acid sequence of SEQ ID NO: 97; (36) The VH domain contains the amino acid sequence of SEQ ID NO: 84, and the VL domain contains the amino acid sequence of SEQ ID NO: 98; (37) The VH domain contains the amino acid sequence of SEQ ID NO: 84, and the VL domain contains the amino acid sequence of SEQ ID NO: 99; (38) The VH domain contains the amino acid sequence of SEQ ID NO: 84, and the VL domain contains the amino acid sequence of SEQ ID NO: 100; (39) The VH domain contains the amino acid sequence of SEQ ID NO: 84, and the VL domain contains the amino acid sequence of SEQ ID NO: 101; (40) 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; (41) The VH domain contains the amino acid sequence of SEQ ID NO: 85, and the VL domain contains the amino acid sequence of SEQ ID NO: 64; (42) The VH domain contains the amino acid sequence of SEQ ID NO: 85, and the VL domain contains the amino acid sequence of SEQ ID NO: 94; (43) The VH domain contains the amino acid sequence of SEQ ID NO: 85, and the VL domain contains the amino acid sequence of SEQ ID NO: 95; (44) The VH domain contains the amino acid sequence of SEQ ID NO: 85, and the VL domain contains the amino acid sequence of SEQ ID NO: 96; (45) The VH domain contains the amino acid sequence of SEQ ID NO: 85, and the VL domain contains the amino acid sequence of SEQ ID NO: 97; (46) The VH domain contains the amino acid sequence of SEQ ID NO: 85, and the VL domain contains the amino acid sequence of SEQ ID NO: 98; (47) The VH domain contains the amino acid sequence of SEQ ID NO: 85, and the VL domain contains the amino acid sequence of SEQ ID NO: 99; (48) The VH domain contains the amino acid sequence of SEQ ID NO: 85, and the VL domain contains the amino acid sequence of SEQ ID NO: 100; (49) The VH domain contains the amino acid sequence of SEQ ID NO: 85, and the VL domain contains the amino acid sequence of SEQ ID NO: 101; (50) 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; (51) The VH domain contains the amino acid sequence of SEQ ID NO: 86, and the VL domain contains the amino acid sequence of SEQ ID NO: 64; (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: 94; (53) The VH domain contains the amino acid sequence of SEQ ID NO: 86, and the VL domain contains the amino acid sequence of SEQ ID NO: 95; (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: 96; (55) The VH domain contains the amino acid sequence of SEQ ID NO: 86, and the VL domain contains the amino acid sequence of SEQ ID NO: 97; (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: 98; (57) The VH domain contains the amino acid sequence of SEQ ID NO: 86, and the VL domain contains the amino acid sequence of SEQ ID NO: 99; (58) The VH domain contains the amino acid sequence of SEQ ID NO: 86, and the VL domain contains the amino acid sequence of SEQ ID NO: 100; (59) The VH domain contains the amino acid sequence of SEQ ID NO: 86, and the VL domain contains the amino acid sequence of SEQ ID NO: 101; (60) 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; (61) The VH domain contains the amino acid sequence of SEQ ID NO: 87, and the VL domain contains the amino acid sequence of SEQ ID NO: 64; (62) The VH domain contains the amino acid sequence of SEQ ID NO: 87, and the VL domain contains the amino acid sequence of SEQ ID NO: 94; (63) The VH domain contains the amino acid sequence of SEQ ID NO: 87, and the VL domain contains the amino acid sequence of SEQ ID NO: 95; (64) The VH domain contains the amino acid sequence of SEQ ID NO: 87, and the VL domain contains the amino acid sequence of SEQ ID NO: 96; (65) The VH domain contains the amino acid sequence of SEQ ID NO: 87, and the VL domain contains the amino acid sequence of SEQ ID NO: 97; (66) The VH domain contains the amino acid sequence of SEQ ID NO: 87, and the VL domain contains the amino acid sequence of SEQ ID NO: 98; (67) The VH domain contains the amino acid sequence of SEQ ID NO: 87, and the VL domain contains the amino acid sequence of SEQ ID NO: 99; (68) The VH domain contains the amino acid sequence of SEQ ID NO: 87, and the VL domain contains the amino acid sequence of SEQ ID NO: 100; (69) The VH domain contains the amino acid sequence of SEQ ID NO: 87, and the VL domain contains the amino acid sequence of SEQ ID NO: 101; (70) 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; (71) The VH domain contains the amino acid sequence of SEQ ID NO: 88, and the VL domain contains the amino acid sequence of SEQ ID NO: 64; (72) The VH domain contains the amino acid sequence of SEQ ID NO: 88, and the VL domain contains the amino acid sequence of SEQ ID NO: 94; (73) The VH domain contains the amino acid sequence of SEQ ID NO: 88, and the VL domain contains the amino acid sequence of SEQ ID NO: 95; (74) The VH domain contains the amino acid sequence of SEQ ID NO: 88, and the VL domain contains the amino acid sequence of SEQ ID NO: 96; (75) The VH domain contains the amino acid sequence of SEQ ID NO: 88, and the VL domain contains the amino acid sequence of SEQ ID NO: 97; (76) The VH domain contains the amino acid sequence of SEQ ID NO: 88, and the VL domain contains the amino acid sequence of SEQ ID NO: 98; (77) The VH domain contains the amino acid sequence of SEQ ID NO: 88, and the VL domain contains the amino acid sequence of SEQ ID NO: 99; (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: 100; (79) The VH domain contains the amino acid sequence of SEQ ID NO: 88, and the VL domain contains the amino acid sequence of SEQ ID NO: 101; (80) 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; (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: 64; (82) The VH domain contains the amino acid sequence of SEQ ID NO: 89, and the VL domain contains the amino acid sequence of SEQ ID NO: 94; (83) The VH domain contains the amino acid sequence of SEQ ID NO: 89, and the VL domain contains the amino acid sequence of SEQ ID NO: 95; (84) The VH domain contains the amino acid sequence of SEQ ID NO: 89, and the VL domain contains the amino acid sequence of SEQ ID NO: 96; (85) The VH domain contains the amino acid sequence of SEQ ID NO: 89, and the VL domain contains the amino acid sequence of SEQ ID NO: 97; (86) The VH domain contains the amino acid sequence of SEQ ID NO: 89, and the VL domain contains the amino acid sequence of SEQ ID NO: 98; (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: 99; (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: 100; (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: 101; (90) 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; (91) The VH domain contains the amino acid sequence of SEQ ID NO: 90, and the VL domain contains the amino acid sequence of SEQ ID NO: 64; (92) The VH domain contains the amino acid sequence of SEQ ID NO: 90, and the VL domain contains the amino acid sequence of SEQ ID NO: 94; (93) The VH domain contains the amino acid sequence of SEQ ID NO: 90, and the VL domain contains the amino acid sequence of SEQ ID NO: 95; (94) The VH domain contains the amino acid sequence of SEQ ID NO: 90, and the VL domain contains the amino acid sequence of SEQ ID NO: 96; (95) The VH domain contains the amino acid sequence of SEQ ID NO: 90, and the VL domain contains the amino acid sequence of SEQ ID NO: 97; (96) The VH domain contains the amino acid sequence of SEQ ID NO: 90, and the VL domain contains the amino acid sequence of SEQ ID NO: 98; (97) The VH domain contains the amino acid sequence of SEQ ID NO: 90, and the VL domain contains the amino acid sequence of SEQ ID NO: 99; (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: 100; (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: 101; (100) 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; (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: 64; (102) The VH domain contains the amino acid sequence of SEQ ID NO: 91, and the VL domain contains the amino acid sequence of SEQ ID NO: 94; (103) The VH domain contains the amino acid sequence of SEQ ID NO: 91, and the VL domain contains the amino acid sequence of SEQ ID NO: 95; (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: 96; (105) The VH domain contains the amino acid sequence of SEQ ID NO: 91, and the VL domain contains the amino acid sequence of SEQ ID NO: 97; (106) The VH domain contains the amino acid sequence of SEQ ID NO: 91, and the VL domain contains the amino acid sequence of SEQ ID NO: 98; (107) The VH domain contains the amino acid sequence of SEQ ID NO: 91, and the VL domain contains the amino acid sequence of SEQ ID NO: 99; (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: 100; (109) The VH domain contains the amino acid sequence of SEQ ID NO: 91, and the VL domain contains the amino acid sequence of SEQ ID NO: 101; (110) The VH domain contains the amino acid sequence of SEQ ID NO: 91, and the VL domain contains the amino acid sequence of SEQ ID NO: 102; (111) The VH domain contains the amino acid sequence of SEQ ID NO: 92, and the VL domain contains the amino acid sequence of SEQ ID NO: 64; (112) The VH domain contains the amino acid sequence of SEQ ID NO: 92, and the VL domain contains the amino acid sequence of SEQ ID NO: 94; (113) The VH domain contains the amino acid sequence of SEQ ID NO: 92, and the VL domain contains the amino acid sequence of SEQ ID NO: 95; (114) The VH domain contains the amino acid sequence of SEQ ID NO: 92, and the VL domain contains the amino acid sequence of SEQ ID NO: 96; (115) The VH domain contains the amino acid sequence of SEQ ID NO: 92, and the VL domain contains the amino acid sequence of SEQ ID NO: 97; (116) The VH domain contains the amino acid sequence of SEQ ID NO: 92, and the VL domain contains the amino acid sequence of SEQ ID NO: 98; (117) The VH domain contains the amino acid sequence of SEQ ID NO: 92, and the VL domain contains the amino acid sequence of SEQ ID NO: 99; (118) The VH domain contains the amino acid sequence of SEQ ID NO: 92, and the VL domain contains the amino acid sequence of SEQ ID NO: 100; (119) The VH domain contains the amino acid sequence of SEQ ID NO: 92, and the VL domain contains the amino acid sequence of SEQ ID NO: 101; (120) 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; (121) The VH domain contains the amino acid sequence of SEQ ID NO: 93, and the VL domain contains the amino acid sequence of SEQ ID NO: 64; (122) The VH domain contains the amino acid sequence of SEQ ID NO: 93, and the VL domain contains the amino acid sequence of SEQ ID NO: 94; (123) The VH domain contains the amino acid sequence of SEQ ID NO: 93, and the VL domain contains the amino acid sequence of SEQ ID NO: 95; (124) The VH domain contains the amino acid sequence of SEQ ID NO: 93, and the VL domain contains the amino acid sequence of SEQ ID NO: 96; (125) The VH domain contains the amino acid sequence of SEQ ID NO: 93, and the VL domain contains the amino acid sequence of SEQ ID NO: 97; (126) The VH domain contains the amino acid sequence of SEQ ID NO: 93, and the VL domain contains the amino acid sequence of SEQ ID NO: 98; (127) The VH domain contains the amino acid sequence of SEQ ID NO: 93, and the VL domain contains the amino acid sequence of SEQ ID NO: 99; (128) The VH domain contains the amino acid sequence of SEQ ID NO: 93, and the VL domain contains the amino acid sequence of SEQ ID NO: 100; (129) The VH domain contains the amino acid sequence of SEQ ID NO: 93, and the VL domain contains the amino acid sequence of SEQ ID NO: 101; (130) The VH domain contains the amino acid sequence of SEQ ID NO: 93, and the VL domain contains the amino acid sequence of SEQ ID NO: 102; (131) The VH domain contains the amino acid sequence of SEQ ID NO: 62, and the VL domain contains the amino acid sequence of SEQ ID NO: 110; (132) The VH domain contains the amino acid sequence of SEQ ID NO: 62, and the VL domain contains the amino acid sequence of SEQ ID NO: 111; (133) The VH domain contains the amino acid sequence of SEQ ID NO: 62, and the VL domain contains the amino acid sequence of SEQ ID NO: 112; (134) The VH domain contains the amino acid sequence of SEQ ID NO: 62, and the VL domain contains the amino acid sequence of SEQ ID NO: 113; (135) 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; (136) 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; (137) 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; (138) 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; (139) 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; (140) 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; (141) 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; (142) 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; (143) 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; (144) 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; (145) 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; (146) 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; (147) 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; (148) 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; (149) 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; (150) 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; (151) 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; (152) 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; (153) 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; (154) 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; (155) 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; (156) 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; (157) 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; (158) 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; (159) The VH domain contains the amino acid sequence of SEQ ID NO: 107, and the VL domain contains the amino acid sequence of SEQ ID NO: 113; (160) 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; (161) 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; (162) 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; (163) 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; (164) 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; (165) 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; (166) 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; (167) 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; (168) 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; (169) The VH domain contains the amino acid sequence of SEQ ID NO: 109, and the VL domain contains the amino acid sequence of SEQ ID NO: 113; (170) 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; (171) The VH domain contains the amino acid sequence of SEQ ID NO: 195, and the VL domain contains the amino acid sequence of SEQ ID NO: 64; (172) 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; (173) 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; (174) 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; (175) The VH domain contains the amino acid sequence of SEQ ID NO: 196, and the VL domain contains the amino acid sequence of SEQ ID NO: 64; (176) The VH domain contains the amino acid sequence of SEQ ID NO: 62, and the VL domain contains the amino acid sequence of SEQ ID NO: 197; or (177) The VH domain contains the amino acid sequence of SEQ ID NO: 62, and the VL domain contains the amino acid sequence of SEQ ID NO: 198, The multispecific binding molecule according to claim 1.

4. The multispecific binding molecule according to any one of claims 1 to 3, wherein the target is a disease-causing substance.

5. (a) The disease-causing substance is a bacterial cell, a fungal cell, a virus, a senescent cell, a tumor cell, a protein aggregate, an LDL particle, a mast cell, a eosinophil, an ILC2 cell, or an inflammatory immune cell; (b) The target is an antigen expressed on the surface of the bacterial cell, fungal cell, senescent cell, tumor cell, mast cell, eosinophil, ILC2 cell, or inflammatory immune cell; (c) The target is a surface antigen of the virus; or (d) The target is an antigen expressed on the surface of cancer cells; The multispecific binding molecule according to claim 4.

6. The multispecific binding molecule according to any one of claims 1 to 3, wherein one or both of the first and second antibodies or antigen-binding fragments are a human antibody or antigen-binding fragment or a humanized antibody or antigen-binding fragment.

7. The multispecific binding molecule according to any one of claims 1 to 3, wherein one or both of the first and second antibody or antigen-binding fragments are Fab, Fab', F(ab')2, Fv, Fab'-SH, F(ab')2, single-chain antibody, nanobody, or scFv fragment.

8. (a) one or both of the first and second antibodies further comprises an Fc domain; (b) The first antibody or antigen-binding fragment is a Fab fragment, and the second antibody comprises an antibody heavy chain and an antibody light chain; (c) Both the first antibody and the second antibody include an antibody heavy chain and an antibody light chain; (d) The first antibody or antigen-binding fragment is linked to avidin, streptavidin, neutraavidin, or its biotin-binding derivative, and the second antibody or antigen-binding fragment is linked to biotin or its avidin-binding derivative; or the second antibody or antigen-binding fragment is linked to avidin, streptavidin, neutraavidin, or its biotin-binding derivative, and the first antibody or antigen-binding fragment is linked to biotin or its avidin-binding derivative; or the first antibody or antigen-binding fragment is linked to the second antibody or antigen-binding fragment via an interaction between the avidin, streptavidin, neutraavidin, or its biotin-binding derivative and the biotin or its avidin-binding derivative; or (e) The multispecific binding molecule comprises a first IgG antibody containing the first antigen-binding domain, which is covalently linked to a second IgG antibody containing the second antigen-binding domain, A multispecific binding molecule according to any one of claims 1 to 3.

9. The multispecificity binding molecule according to any one of claims 1 to 3, comprising: a first antibody arm comprising a single-stranded variable fragment (scFv) containing the VH domain and the VL domain that bind 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 associated with an antibody light chain containing the VL domain of the second antigen-binding domain, and a second Fc region connected to the VH domain of the second antigen-binding domain.

10. The multispecific binding molecule according to claim 9, wherein the first Fc region contains one or more knob-forming mutations and the second Fc region contains one or more congeneral hole-forming mutations, or the second Fc region contains one or more knob-forming mutations and the first Fc region contains one or more congeneral hole-forming mutations.

11. (a) the first Fc region includes T366W substitution by EU numbering, and the second Fc region includes T366S, L368A, and Y407V substitution; or (b) The first Fc region includes T366S, L368A, and Y407V substitutions according to EU numbering, and the second Fc region includes T366W substitution, The multispecific binding molecule according to claim 10.

12. The multispecific binding molecule according to claim 9, wherein the first antibody arm includes a first linker between the VH domain and the VL domain, and a second linker between the VL domain and the first Fc region.

13. (a) The VH domain of the first antibody arm comprises the amino acid sequence of SEQ ID NO: 220, and the VL domain of the first antibody arm comprises the amino acid sequence of SEQ ID NO: 221; (b) The scFv contains the amino acid sequence of SEQ ID NO: 222; and / or (c) The first antibody arm comprises the amino acid sequence of SEQ ID NO: 224 or 225, The multispecific binding molecule according to claim 12.

14. The multispecific binding molecule according to any one of claims 1 to 3, wherein the multispecific binding molecule comprises a first antibody arm comprising a first antibody heavy chain comprising the VH domain and the 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 comprising a second antibody heavy chain comprising the VH domain and the 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 congeneral hole-forming mutations.

15. The multispecific binding molecule according to claim 14, wherein the first Fc region includes a T366W substitution by EU numbering, and the second Fc region includes T366S, L368A, and Y407V substitutions.

16. The multispecificity binding molecule according to any one of claims 1 to 3, wherein the multispecificity binding molecule comprises a first antibody arm comprising a first antibody heavy chain comprising the VH domain and the first Fc region of the first antigen-binding domain, and a second antibody arm comprising a second antibody heavy chain comprising the VH domain and the second Fc region of the second antigen-binding domain, wherein the first Fc region comprises one or more hole-forming mutations, and the second Fc region comprises one or more congeneral knob-forming mutations.

17. The multispecific binding molecule according to claim 16, wherein the first Fc region includes T366S, L368A, and Y407V substitutions according to EU numbering, and the second Fc region includes a T366W substitution.

18. (a) 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; (b) 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; or (c) The first antibody heavy chain comprises the amino acid sequence of SEQ ID NO: 219, and the first antibody light chain comprises the amino acid sequence of SEQ ID NO:

223. The multispecific binding molecule according to claim 14.

19. One or both of the first and second antibody or antigen-binding fragments contain a human IgG Fc region, and / or At least one or two of the first antibody heavy chain and the second antibody heavy chain are non-fucosylated or have reduced fucosylation. The multispecific binding molecule according to claim 8.

20. The multispecific binding molecule according to claim 19, wherein the Fc region is a human IgG1 or human IgG4 Fc region.

21. (i) The Fc region is (a) Human IgG1 Fc region including S239D and I332E substitutions by EU numbering, (b) Human IgG1 Fc region including S239D, A330L, and I332E substitutions according to EU numbering, (c) Human IgG1 Fc region including EU numbering G236A, S239D, A330L, and I332E substitutions, or (d) A human IgG4 Fc region containing the S228P substitution according to EU numbering; (ii) The multispecificity binding molecule comprises two antibody heavy chains, each of which contains one or more amino acid substitutions at position 234, 235, and 237 according to EU numbering; If necessary, each of the antibody heavy chains may include L234A, L235E, and G237A substitutions according to EU numbering; (iii) The multispecific binding molecule comprises two antibody heavy chains, wherein only one of the antibody heavy chains contains the H435R and Y436F substitutions according to EU numbering; or (iv) One of the antibody arms comprises a heavy chain including F126C and C220V substitutions according to EU numbering and a light chain including S121C and C214V substitutions, The multispecific binding molecule according to claim 20.

22. The multispecificity 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, 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, the first antibody heavy chain includes F126C, C220V, and T366W substitutions according to EU numbering, the first antibody light chain includes S121C and C214V substitutions, and the second antibody heavy chain includes T366S, L368A, Y407V, H435R, and Y436F substitutions. If necessary, the first antibody heavy chain and the second antibody heavy chain further include EU numbering L234A, L235E, and G237A substitutions. A multispecific binding molecule according to any one of claims 1 to 3.

23. (a) A first arm comprising a single-stranded variable fragment (scFv) that binds to star dectin-1 and a first Fc region, wherein the scFv comprises a first VH domain and a first VL domain, (b) A multispecific binding molecule comprising: 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; (i) the VH domain of the first antibody arm comprises the amino acid sequence of SEQ ID NO: 220, and the VL domain of the first antibody arm comprises the amino acid sequence of SEQ ID NO: 221; (ii) the scFv comprises the amino acid sequence of SEQ ID NO: 222; and / or (iii) the first arm comprises the amino acid sequence of SEQ ID NO: 224 or 225, the multispecificity binding molecule.

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

221.

25. The multispecificity binding molecule according to claim 24, wherein the first antibody heavy chain comprises the amino acid sequence of SEQ ID NO: 219, and the first antibody light chain comprises the amino acid sequence of SEQ ID NO:

223.

26. An antibody or antigen-binding fragment thereof that binds to human dectin-1, wherein the antibody or antigen-binding fragment comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; (i) The VH domain comprises CDR-H1 containing the amino acid sequence DYYI (SEQ ID NO: 1) or DYYM (SEQ ID NO: 199); CDR-H2 containing the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), WINPNEGDTNYAQKFEG (SEQ ID NO: 200), or WINPNEGDTNYAQKFQE (SEQ ID NO: 201); and CDR-H3 containing 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); The VL domain comprises CDR-L1 containing the amino acid sequence RASQGISSWLA (SEQ ID NO: 4); CDR-L2 containing the amino acid sequence GASSLQS (SEQ ID NO: 5) or GASDLQS (SEQ ID NO: 206); and CDR-L3 containing 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); or (ii) The VH domain is an amino acid sequence QVQLVQSGAEVKKPGASVKVSCKSSGYTFTX 1 YYIHWVRQAPGQGLEWMGWINPNSGX 2 TNYAQKFQGRITMTRDTSISTAYLELSRRRSDDTAVFYCAX 3 X 4 X 5 X 6 X 7 X 8 X 9 X 10 X 11 X 12 WGQGTLVTVSS [where X 1 is D, A, or G, X 2 is D, A, or G, X 3 is R, A, or G, X 4 is N, A, or G, X 5 is S, A, or G, X 6 [X7 is A or G, X8 is S, A, or G, X9 is S, A, or G, X10 is F, A, or G, X11 is A or G, and X12 is Y, A, or G] (Sequence ID 63); The VL domain has the amino acid sequence DIQMTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKAAPKLLIFGASSLQSGVPSRFSGSGSGTTDFTLTVSSLQPEDFATYYCX X 1 X 2 X 3 X 4 X 5 X 6 X 7 X 8 FGPGTKVDIE [where X 1 is Q, A, or G, X 2 is Q, A, or G, X 3 is F, Y, A, or G, X 4 is S, A, or G, X 5 is F, A, or G, X 6 is P, A, or G, X 7 is F, A, or G, and X 8 [but is T, A, or G] (Sequence ID 65); or (iii) The VH domain comprises CDR-H1 containing the amino acid sequence DYYI (SEQ ID NO: 1) or AYYI (SEQ ID NO: 16); CDR-H2 containing the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2) or WINPNSGATNYAQKFQG (SEQ ID NO: 19); and CDR-H3 containing 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); The VL domain comprises CDR-L1 containing the amino acid sequence RASQGISSWLA (SEQ ID NO: 4); CDR-L2 containing the amino acid sequence GASSLQS (SEQ ID NO: 5); and CDR-L3 containing 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), QQAYAFFPFT (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); or (iv) The VH domain comprises the amino acid sequence QVQLVQSGAEVKKPGASVKVSCKX 1 SGYTFTX 2 YYX 3 HWVRQAPGQGLEWMGWINPNSGX 4 TNYAQKFQGRX 5 TMTRDTSISTAYX 6 ELSRLRSDDTAVX 7 YCARNSGSYSFGYWGQGTLVTVSS [where X1 is S or A, X2 is D or G, X3 is I or M, X4 is D or G, X5 is I or V, X6 is L or M, and X7 is F or Y] (Sequence ID 80); The VL domain contains the amino acid sequence DIQMTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKAAPKLLIX 1 X 2 ASSLQSGVPSRFSGSGSGTDFTTLTX 3 SSLQPEDFATYYCQQAYSFPFTFGPGTKVDIE [where X 1 is F or Y, X 2 is G or A, and X 3 is V or I] (SEQ ID NO: 81); or (v) The VH domain comprises CDR-H1 containing 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); CDR-H2 containing the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2) or WINPNSGGTNYAQKFQG (SEQ ID NO: 70); and CDR-H3 containing the amino acid sequence NSGSYSFGY (SEQ ID NO: 3); The VL domain comprises CDR-L1 containing the amino acid sequence RASQGISSWLA (SEQ ID NO: 4); CDR-L2 containing the amino acid sequence GASSLQS (SEQ ID NO: 5) or AASSLQS (SEQ ID NO: 73); and CDR-L3 containing the amino acid sequence QQAYSFPFT (SEQ ID NO: 6); The antibody does not contain CDR-H1 containing the amino acid sequence DYYI (SEQ ID NO: 1), CDR-H2 containing the amino acid sequence WINPNSGDTNYAQKFQG (SEQ ID NO: 2), CDR-H3 containing the amino acid sequence NSGSYSFGY (SEQ ID NO: 3), CDR-L1 containing the amino acid sequence RASQGISSWLA (SEQ ID NO: 4), CDR-L2 containing the amino acid sequence GASSLQS (SEQ ID NO: 5), and CDR-L3 containing the amino acid sequence QQAYSFPFT (SEQ ID NO: 6). An antibody or its antigen-binding fragment.

27. ​​(1) 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; (2) The VH domain contains the amino acid sequence of SEQ ID NO: 62, and the VL domain contains the amino acid sequence of SEQ ID NO: 94; (3) The VH domain contains the amino acid sequence of SEQ ID NO: 62, and the VL domain contains the amino acid sequence of SEQ ID NO: 95; (4) The VH domain contains the amino acid sequence of SEQ ID NO: 62, and the VL domain contains the amino acid sequence of SEQ ID NO: 96; (5) The VH domain contains the amino acid sequence of SEQ ID NO: 62, and the VL domain contains the amino acid sequence of SEQ ID NO: 97; (6) The VH domain contains the amino acid sequence of SEQ ID NO: 62, and the VL domain contains the amino acid sequence of SEQ ID NO: 98; (7) The VH domain contains the amino acid sequence of SEQ ID NO: 62, and the VL domain contains the amino acid sequence of SEQ ID NO: 99; (8) The VH domain contains the amino acid sequence of SEQ ID NO: 62, and the VL domain contains the amino acid sequence of SEQ ID NO: 100; (9) The VH domain contains the amino acid sequence of SEQ ID NO: 62, and the VL domain contains the amino acid sequence of SEQ ID NO: 101; (10) The VH domain contains the amino acid sequence of SEQ ID NO: 62, and the VL domain contains the amino acid sequence of SEQ ID NO: 102; (11) The VH domain contains the amino acid sequence of SEQ ID NO: 82, and the VL domain contains the amino acid sequence of SEQ ID NO: 64; (12) The VH domain contains the amino acid sequence of SEQ ID NO: 82, and the VL domain contains the amino acid sequence of SEQ ID NO: 94; (13) The VH domain contains the amino acid sequence of SEQ ID NO: 82, and the VL domain contains the amino acid sequence of SEQ ID NO: 95; (14) The VH domain contains the amino acid sequence of SEQ ID NO: 82, and the VL domain contains the amino acid sequence of SEQ ID NO: 96; (15) The VH domain contains the amino acid sequence of SEQ ID NO: 82, and the VL domain contains the amino acid sequence of SEQ ID NO: 97; (16) The VH domain contains the amino acid sequence of SEQ ID NO: 82, and the VL domain contains the amino acid sequence of SEQ ID NO: 98; (17) The VH domain contains the amino acid sequence of SEQ ID NO: 82, and the VL domain contains the amino acid sequence of SEQ ID NO: 99; (18) The VH domain contains the amino acid sequence of SEQ ID NO: 82, and the VL domain contains the amino acid sequence of SEQ ID NO: 100; (19) The VH domain contains the amino acid sequence of SEQ ID NO: 82, and the VL domain contains the amino acid sequence of SEQ ID NO: 101; (20) The VH domain contains the amino acid sequence of SEQ ID NO: 82, and the VL domain contains the amino acid sequence of SEQ ID NO: 102; (21) The VH domain contains the amino acid sequence of SEQ ID NO: 83, and the VL domain contains the amino acid sequence of SEQ ID NO: 64; (22) The VH domain contains the amino acid sequence of SEQ ID NO: 83, and the VL domain contains the amino acid sequence of SEQ ID NO: 94; (23) The VH domain contains the amino acid sequence of SEQ ID NO: 83, and the VL domain contains the amino acid sequence of SEQ ID NO: 95; (24) The VH domain contains the amino acid sequence of SEQ ID NO: 83, and the VL domain contains the amino acid sequence of SEQ ID NO: 96; (25) The VH domain contains the amino acid sequence of SEQ ID NO: 83, and the VL domain contains the amino acid sequence of SEQ ID NO: 97; (26) The VH domain contains the amino acid sequence of SEQ ID NO: 83, and the VL domain contains the amino acid sequence of SEQ ID NO: 98; (27) The VH domain contains the amino acid sequence of SEQ ID NO: 83, and the VL domain contains the amino acid sequence of SEQ ID NO: 99; (28) The VH domain contains the amino acid sequence of SEQ ID NO: 83, and the VL domain contains the amino acid sequence of SEQ ID NO: 100; (29) The VH domain contains the amino acid sequence of SEQ ID NO: 83, and the VL domain contains the amino acid sequence of SEQ ID NO: 101; (30) The VH domain contains the amino acid sequence of SEQ ID NO: 83, and the VL domain contains the amino acid sequence of SEQ ID NO: 102; (31) The VH domain contains the amino acid sequence of SEQ ID NO: 84, and the VL domain contains the amino acid sequence of SEQ ID NO: 64; (32) The VH domain contains the amino acid sequence of SEQ ID NO: 84, and the VL domain contains the amino acid sequence of SEQ ID NO: 94; (33) The VH domain contains the amino acid sequence of SEQ ID NO: 84, and the VL domain contains the amino acid sequence of SEQ ID NO: 95; (34) The VH domain contains the amino acid sequence of SEQ ID NO: 84, and the VL domain contains the amino acid sequence of SEQ ID NO: 96; (35) The VH domain contains the amino acid sequence of SEQ ID NO: 84, and the VL domain contains the amino acid sequence of SEQ ID NO: 97; (36) The VH domain contains the amino acid sequence of SEQ ID NO: 84, and the VL domain contains the amino acid sequence of SEQ ID NO: 98; (37) The VH domain contains the amino acid sequence of SEQ ID NO: 84, and the VL domain contains the amino acid sequence of SEQ ID NO: 99; (38) The VH domain contains the amino acid sequence of SEQ ID NO: 84, and the VL domain contains the amino acid sequence of SEQ ID NO: 100; (39) The VH domain contains the amino acid sequence of SEQ ID NO: 84, and the VL domain contains the amino acid sequence of SEQ ID NO: 101; (40) 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; (41) The VH domain contains the amino acid sequence of SEQ ID NO: 85, and the VL domain contains the amino acid sequence of SEQ ID NO: 64; (42) The VH domain contains the amino acid sequence of SEQ ID NO: 85, and the VL domain contains the amino acid sequence of SEQ ID NO: 94; (43) The VH domain contains the amino acid sequence of SEQ ID NO: 85, and the VL domain contains the amino acid sequence of SEQ ID NO: 95; (44) The VH domain contains the amino acid sequence of SEQ ID NO: 85, and the VL domain contains the amino acid sequence of SEQ ID NO: 96; (45) The VH domain contains the amino acid sequence of SEQ ID NO: 85, and the VL domain contains the amino acid sequence of SEQ ID NO: 97; (46) The VH domain contains the amino acid sequence of SEQ ID NO: 85, and the VL domain contains the amino acid sequence of SEQ ID NO: 98; (47) The VH domain contains the amino acid sequence of SEQ ID NO: 85, and the VL domain contains the amino acid sequence of SEQ ID NO: 99; (48) The VH domain contains the amino acid sequence of SEQ ID NO: 85, and the VL domain contains the amino acid sequence of SEQ ID NO: 100; (49) The VH domain contains the amino acid sequence of SEQ ID NO: 85, and the VL domain contains the amino acid sequence of SEQ ID NO: 101; (50) 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; (51) The VH domain contains the amino acid sequence of SEQ ID NO: 86, and the VL domain contains the amino acid sequence of SEQ ID NO: 64; (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: 94; (53) The VH domain contains the amino acid sequence of SEQ ID NO: 86, and the VL domain contains the amino acid sequence of SEQ ID NO: 95; (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: 96; (55) The VH domain contains the amino acid sequence of SEQ ID NO: 86, and the VL domain contains the amino acid sequence of SEQ ID NO: 97; (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: 98; (57) The VH domain contains the amino acid sequence of SEQ ID NO: 86, and the VL domain contains the amino acid sequence of SEQ ID NO: 99; (58) The VH domain contains the amino acid sequence of SEQ ID NO: 86, and the VL domain contains the amino acid sequence of SEQ ID NO: 100; (59) The VH domain contains the amino acid sequence of SEQ ID NO: 86, and the VL domain contains the amino acid sequence of SEQ ID NO: 101; (60) 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; (61) The VH domain contains the amino acid sequence of SEQ ID NO: 87, and the VL domain contains the amino acid sequence of SEQ ID NO: 64; (62) The VH domain contains the amino acid sequence of SEQ ID NO: 87, and the VL domain contains the amino acid sequence of SEQ ID NO: 94; (63) The VH domain contains the amino acid sequence of SEQ ID NO: 87, and the VL domain contains the amino acid sequence of SEQ ID NO: 95; (64) The VH domain contains the amino acid sequence of SEQ ID NO: 87, and the VL domain contains the amino acid sequence of SEQ ID NO: 96; (65) The VH domain contains the amino acid sequence of SEQ ID NO: 87, and the VL domain contains the amino acid sequence of SEQ ID NO: 97; (66) The VH domain contains the amino acid sequence of SEQ ID NO: 87, and the VL domain contains the amino acid sequence of SEQ ID NO: 98; (67) The VH domain contains the amino acid sequence of SEQ ID NO: 87, and the VL domain contains the amino acid sequence of SEQ ID NO: 99; (68) The VH domain contains the amino acid sequence of SEQ ID NO: 87, and the VL domain contains the amino acid sequence of SEQ ID NO: 100; (69) The VH domain contains the amino acid sequence of SEQ ID NO: 87, and the VL domain contains the amino acid sequence of SEQ ID NO: 101; (70) 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; (71) The VH domain contains the amino acid sequence of SEQ ID NO: 88, and the VL domain contains the amino acid sequence of SEQ ID NO: 64; (72) The VH domain contains the amino acid sequence of SEQ ID NO: 88, and the VL domain contains the amino acid sequence of SEQ ID NO: 94; (73) The VH domain contains the amino acid sequence of SEQ ID NO: 88, and the VL domain contains the amino acid sequence of SEQ ID NO: 95; (74) The VH domain contains the amino acid sequence of SEQ ID NO: 88, and the VL domain contains the amino acid sequence of SEQ ID NO: 96; (75) The VH domain contains the amino acid sequence of SEQ ID NO: 88, and the VL domain contains the amino acid sequence of SEQ ID NO: 97; (76) The VH domain contains the amino acid sequence of SEQ ID NO: 88, and the VL domain contains the amino acid sequence of SEQ ID NO: 98; (77) The VH domain contains the amino acid sequence of SEQ ID NO: 88, and the VL domain contains the amino acid sequence of SEQ ID NO: 99; (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: 100; (79) The VH domain contains the amino acid sequence of SEQ ID NO: 88, and the VL domain contains the amino acid sequence of SEQ ID NO: 101; (80) 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; (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: 64; (82) The VH domain contains the amino acid sequence of SEQ ID NO: 89, and the VL domain contains the amino acid sequence of SEQ ID NO: 94; (83) The VH domain contains the amino acid sequence of SEQ ID NO: 89, and the VL domain contains the amino acid sequence of SEQ ID NO: 95; (84) The VH domain contains the amino acid sequence of SEQ ID NO: 89, and the VL domain contains the amino acid sequence of SEQ ID NO: 96; (85) The VH domain contains the amino acid sequence of SEQ ID NO: 89, and the VL domain contains the amino acid sequence of SEQ ID NO: 97; (86) The VH domain contains the amino acid sequence of SEQ ID NO: 89, and the VL domain contains the amino acid sequence of SEQ ID NO: 98; (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: 99; (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: 100; (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: 101; (90) 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; (91) The VH domain contains the amino acid sequence of SEQ ID NO: 90, and the VL domain contains the amino acid sequence of SEQ ID NO: 64; (92) The VH domain contains the amino acid sequence of SEQ ID NO: 90, and the VL domain contains the amino acid sequence of SEQ ID NO: 94; (93) The VH domain contains the amino acid sequence of SEQ ID NO: 90, and the VL domain contains the amino acid sequence of SEQ ID NO: 95; (94) The VH domain contains the amino acid sequence of SEQ ID NO: 90, and the VL domain contains the amino acid sequence of SEQ ID NO: 96; (95) The VH domain contains the amino acid sequence of SEQ ID NO: 90, and the VL domain contains the amino acid sequence of SEQ ID NO: 97; (96) The VH domain contains the amino acid sequence of SEQ ID NO: 90, and the VL domain contains the amino acid sequence of SEQ ID NO: 98; (97) The VH domain contains the amino acid sequence of SEQ ID NO: 90, and the VL domain contains the amino acid sequence of SEQ ID NO: 99; (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: 100; (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: 101; (100) 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; (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: 64; (102) The VH domain contains the amino acid sequence of SEQ ID NO: 91, and the VL domain contains the amino acid sequence of SEQ ID NO: 94; (103) The VH domain contains the amino acid sequence of SEQ ID NO: 91, and the VL domain contains the amino acid sequence of SEQ ID NO: 95; (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: 96; (105) The VH domain contains the amino acid sequence of SEQ ID NO: 91, and the VL domain contains the amino acid sequence of SEQ ID NO: 97; (106) The VH domain contains the amino acid sequence of SEQ ID NO: 91, and the VL domain contains the amino acid sequence of SEQ ID NO: 98; (107) The VH domain contains the amino acid sequence of SEQ ID NO: 91, and the VL domain contains the amino acid sequence of SEQ ID NO: 99; (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: 100; (109) The VH domain contains the amino acid sequence of SEQ ID NO: 91, and the VL domain contains the amino acid sequence of SEQ ID NO: 101; (110) The VH domain contains the amino acid sequence of SEQ ID NO: 91, and the VL domain contains the amino acid sequence of SEQ ID NO: 102; (111) The VH domain contains the amino acid sequence of SEQ ID NO: 92, and the VL domain contains the amino acid sequence of SEQ ID NO: 64; (112) The VH domain contains the amino acid sequence of SEQ ID NO: 92, and the VL domain contains the amino acid sequence of SEQ ID NO: 94; (113) The VH domain contains the amino acid sequence of SEQ ID NO: 92, and the VL domain contains the amino acid sequence of SEQ ID NO: 95; (114) The VH domain contains the amino acid sequence of SEQ ID NO: 92, and the VL domain contains the amino acid sequence of SEQ ID NO: 96; (115) The VH domain contains the amino acid sequence of SEQ ID NO: 92, and the VL domain contains the amino acid sequence of SEQ ID NO: 97; (116) The VH domain contains the amino acid sequence of SEQ ID NO: 92, and the VL domain contains the amino acid sequence of SEQ ID NO: 98; (117) The VH domain contains the amino acid sequence of SEQ ID NO: 92, and the VL domain contains the amino acid sequence of SEQ ID NO: 99; (118) The VH domain contains the amino acid sequence of SEQ ID NO: 92, and the VL domain contains the amino acid sequence of SEQ ID NO: 100; (119) The VH domain contains the amino acid sequence of SEQ ID NO: 92, and the VL domain contains the amino acid sequence of SEQ ID NO: 101; (120) 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; (121) The VH domain contains the amino acid sequence of SEQ ID NO: 93, and the VL domain contains the amino acid sequence of SEQ ID NO: 64; (122) The VH domain contains the amino acid sequence of SEQ ID NO: 93, and the VL domain contains the amino acid sequence of SEQ ID NO: 94; (123) The VH domain contains the amino acid sequence of SEQ ID NO: 93, and the VL domain contains the amino acid sequence of SEQ ID NO: 95; (124) The VH domain contains the amino acid sequence of SEQ ID NO: 93, and the VL domain contains the amino acid sequence of SEQ ID NO: 96; (125) The VH domain contains the amino acid sequence of SEQ ID NO: 93, and the VL domain contains the amino acid sequence of SEQ ID NO: 97; (126) The VH domain contains the amino acid sequence of SEQ ID NO: 93, and the VL domain contains the amino acid sequence of SEQ ID NO: 98; (127) The VH domain contains the amino acid sequence of SEQ ID NO: 93, and the VL domain contains the amino acid sequence of SEQ ID NO: 99; (128) The VH domain contains the amino acid sequence of SEQ ID NO: 93, and the VL domain contains the amino acid sequence of SEQ ID NO: 100; (129) The VH domain contains the amino acid sequence of SEQ ID NO: 93, and the VL domain contains the amino acid sequence of SEQ ID NO: 101; (130) The VH domain contains the amino acid sequence of SEQ ID NO: 93, and the VL domain contains the amino acid sequence of SEQ ID NO: 102; (131) The VH domain contains the amino acid sequence of SEQ ID NO: 62, and the VL domain contains the amino acid sequence of SEQ ID NO: 110; (132) The VH domain contains the amino acid sequence of SEQ ID NO: 62, and the VL domain contains the amino acid sequence of SEQ ID NO: 111; (133) The VH domain contains the amino acid sequence of SEQ ID NO: 62, and the VL domain contains the amino acid sequence of SEQ ID NO: 112; (134) The VH domain contains the amino acid sequence of SEQ ID NO: 62, and the VL domain contains the amino acid sequence of SEQ ID NO: 113; (135) 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; (136) 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; (137) 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; (138) 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; (139) 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; (140) 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; (141) 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; (142) 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; (143) 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; (144) 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; (145) 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; (146) 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; (147) 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; (148) 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; (149) 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; (150) 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; (151) 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; (152) 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; (153) 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; (154) 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; (155) 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; (156) 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; (157) 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; (158) 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; (159) The VH domain contains the amino acid sequence of SEQ ID NO: 107, and the VL domain contains the amino acid sequence of SEQ ID NO: 113; (160) 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; (161) 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; (162) 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; (163) 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; (164) 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; (165) 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; (166) 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; (167) 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; (168) 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; (169) The VH domain contains the amino acid sequence of SEQ ID NO: 109, and the VL domain contains the amino acid sequence of SEQ ID NO: 113; (170) 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; (171) The VH domain contains the amino acid sequence of SEQ ID NO: 195, and the VL domain contains the amino acid sequence of SEQ ID NO: 64; (172) 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; (173) 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; (174) 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; (175) The VH domain contains the amino acid sequence of SEQ ID NO: 196, and the VL domain contains the amino acid sequence of SEQ ID NO: 64; (176) The VH domain contains the amino acid sequence of SEQ ID NO: 62, and the VL domain contains the amino acid sequence of SEQ ID NO: 197; or (177) The VH domain contains the amino acid sequence of SEQ ID NO: 62, and the VL domain contains the amino acid sequence of SEQ ID NO: 198, The antibody according to claim 26.

28. A polynucleotide encoding a multispecific binding molecule according to any one of claims 1 to 3, or an antibody or antigen-binding fragment thereof according to claim 26.

29. A vector comprising a polynucleotide as described in claim 28.

30. An isolated host cell containing the polynucleotide described in claim 28.

31. The isolated host cell according to claim 30, wherein the host cell is (a) a yeast, insect, plant, or prokaryotic cell; or (b) a mammalian cell; and optionally, the mammalian cell is a Chinese hamster ovary (CHO) cell.

32. A method for producing a multispecific binding molecule or an antibody or an antigen-binding fragment thereof, comprising culturing a host cell according to claim 30 under conditions suitable for the production of the multispecific binding molecule or the antibody or an antigen-binding fragment thereof, wherein the method optionally further comprises recovering the multispecific binding molecule or the antibody or an antigen-binding fragment thereof.

33. An antibody or antigen-binding fragment thereof that binds to human dectin-1, produced by the method described in claim 32.

34. A pharmaceutical composition comprising a multispecific binding molecule according to any one of claims 1 to 3 or an antibody or antigen-binding fragment according to claim 26, and a pharmaceutically acceptable carrier.

35. A composition for treating a disease or disorder in an individual requiring treatment of a disease or disorder, comprising a multispecific binding molecule according to any one of claims 1 to 3 or an antibody or antigen-binding fragment according to claim 26, and a pharmaceutically acceptable carrier.

36. The composition according to claim 35, wherein the first target is human dectin-1 and the second target is a disease-causing substance.

37. (a) The disease-causing substance is a bacterial cell, a fungal cell, a virus, a senescent cell, a tumor cell, a protein aggregate, an LDL particle, a mast cell, a eosinophil, an ILC2 cell, or an inflammatory immune cell; (b) The target is an antigen expressed on the surface of the bacterial cell, fungal cell, senescent cell, tumor cell, mast cell, eosinophil, ILC2 cell, or inflammatory immune cell; (c) The target is the surface antigen of the virus; (d) The disease or disorder is cancer, a bacterial infection, a fungal infection, a viral infection, a mast cell disease or disorder, systemic mastocytosis, amyloidosis, or an age-related disease or disorder; and / or (e) The target is an antigen expressed on the surface of cancer cells, The composition according to claim 36.

38. The composition according to claim 35, wherein the individual is a human.

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