Anti-lilrb1 and / or Anti-lilrb2 antibodies and uses thereof

Abstract

In certain aspects, provided herein are antibodies that bind to LILRB1 and uses thereof. In certain aspects, also provided herein are antibodies that bind to LILRB2 and uses thereof. In certain aspects, also provided herein are multispecific antibodies that bind to LILRB1 and LILRB2 and uses thereof.

Description

[0001] Cross-reference to related applications

[0002] This application claims priority to International Patent Application No. PCT / CN2023 / 074276, filed on February 2, 2023, the disclosure of which is incorporated herein by reference in its entirety.

[0003] sequence list

[0004] This application includes a computer-readable sequence list submitted together with this application in XML file format, the entire contents of which are incorporated herein by reference. The sequence list XML file submitted together with this application is named "14668-026-228_SEQ_LISTING.xml", was created on January 31, 2024, and has a size of 1,480,704 bytes. Technical Field

[0005] This disclosure relates in its entirety to binding agents, such as antibodies (including fragments thereof) that bind to LILRB1 and / or LILRB2, including anti-LILRB1 antibodies (including humanized anti-LILRB1 antibodies), anti-LILRB2 antibodies (including humanized anti-LILRB2 antibodies), and multispecific antibodies (including humanized multispecific antibodies) that bind to both LILRB1 and LILRB2, and methods of using thereof. Background Technology

[0006] Leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1), also known as Ig-like transcript 2 (ILT2), is a receptor for class I major histocompatibility complex (MHC) antigens containing an immunoreceptor tyrosine-based inhibitory motif and recognizes a broad spectrum of human leukocyte antigens (HLA)-A, HLA-B, HLA-C, and HLA-G alleles. LILRB1 uses its two distal membrane domains (D1 and D2) to recognize the a3 domain and b2m subunit of MHC molecules. LILRB1 is also the receptor for H301 / UL18 (a class I MHC homolog of human cytomegalovirus) (Yu et al. (2018) J Clin Invest 1523-1537). LILRB1 is expressed on all B cells, monocytes, macrophages, dendritic cells, myeloid-derived suppressor cells (MDSCs), as well as NK cells and T cell subsets, and transduces negative signals that downregulate the immune response (Chen et al. (2020) J Immunother Cancere000515).

[0007] Leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2), also known as Ig-like transcript 4 (ILT4), is an immunoreceptor tyrosine-based inhibitory motif-containing receptor for class I MHC antigens and recognizes a broad spectrum of HLA-A, HLA-B, HLA-C, and HLA-G alleles. LILRB2 uses its two membrane distal domains (D1 and D2) to recognize the a3 domain of MHC molecules. Angiopoietin-like proteins (ANGPTL), CD Id, Ab oligomers, and myelin inhibitors are also ligands for LILRB2 (Zhang et al. (2017) J Leukoc Biol 351-360). Ligand binding results in inhibitory signals and downregulation of the immune response. LILRB2 is expressed on monocytes, macrophages, dendritic cells, granulocytes, and myeloid-derived suppressor cells (MDSCs) (Siu et al. (2021) Clin Cancer Res 57-60).

[0008] LILRB1 and LILRB2 inhibit immune activation by binding MHC-I in cis and trans. They recruit SHP-1 and SHP-2 phosphatases that mediate various intracellular signaling pathways for inhibition (Chen et al. (2018) J Clin Invest 5647-5662). Both LILRB1 and LILRB2 are associated with advanced disease stage and poor prognosis in multiple tumor types (Chen et al. (2022) Int Immunopharmacol 108798 and Zhang et al. (2021) Front Oncol 668707). HLA plays a crucial role in cancer immunology. The strategy used by tumor cells to evade innate and adaptive immune responses is associated with aberrant expression of human leukocyte antigen (HLA)-G (Carosella et al. (2015) Adv Immunol 33-144). HLA-A, HLA-B, HLA-C, and HLA-G binding to LILRB1 and LILRB2 can directly inhibit immune cell function through receptor binding and / or through impairment of chemotaxis and phagocytosis (Morandi et al. (2014) Cytokine Growth Factor Rev 327-335). HLA-G is highly expressed in multiple tumor types and is associated with poor prognosis (Carosella et al. (2015) Adv Immunol 33-144). The interaction between HLA and macrophages due to LILRB1 inhibits phagocytic function (Barkal et al. (2018) Nat Immunol 76-84). HLA binding to LILRB1 can inhibit cytotoxic activity of NK and T cells (Dumont et al. (2019) Cancer Immunol Res 1619-1632 and Chen et al. (2020) J Immunother Cancer e000515). The interaction between HLA and monocytes due to LILRB2 inhibits maturation of human monocyte-derived antigen-presenting cells (APCs) (Liang et al. (2008) Proc Natl Acad Sci USA 8357-8362). HLA binding to LILRB1 and LILRB2 can inhibit the immune system by inducing dendritic cells and MDSCs (Zhang et al. (2017) J Leukoc Biol 351-360).

[0009] Many patients do not respond to T cell therapy due to tumor immune escape or tumor microenvironment. Some of these can be relieved from NK and myeloid cell therapy. Antibody-mediated blockade of LILRB1 and LILRB2 function will fill this unmet medical need by reversing the immunosuppressive tumor microenvironment. SUMMARY

[0010] The present disclosure provides an antibody or antigen-binding fragment thereof that binds LILRB1, for example, an antibody or antigen-binding fragment provided in Tables 4-6 and 13-15.

[0011] The present disclosure provides an antibody or antigen-binding fragment thereof that binds LILRB2, for example, an antibody or antigen-binding fragment provided in Tables 4-6 and 13-15.

[0012] The present disclosure also provides a multispecific antibody or antigen-binding fragment thereof comprising a first binding arm that binds to LILRB1 and a second binding arm that binds to LILRB2. The first binding domain contains a VH and VL comprising the same CDRs as any of the antibodies or fragments thereof provided herein, for example, in Tables 5-6 and 14-15. The second binding domain contains a VH and VL comprising the same CDRs as any of the antibodies or fragments thereof provided herein, for example, in Tables 5-6 and 14-15.

[0013] In some embodiments, the multispecific antibody or fragment thereof provided herein has the antibody format of an immunoglobulin-single-chain antibody fragment (IgG-ScFv). In some embodiments, the multispecific antibody or fragment thereof provided herein has the antibody format of a dual variable domain-immunoglobulin (DVD-Ig).

[0014] In some embodiments, the antibody provided herein is an IgG. In some embodiments, the antibody is a humanized antibody.

[0015] In another aspect, provided herein is a nucleic acid molecule encoding an antibody or antigen-binding fragment provided herein.

[0016] In another aspect, provided herein is a vector comprising a nucleic acid molecule encoding an antibody or antigen-binding fragment provided herein.

[0017] In yet another aspect, provided herein is a host cell transformed with a vector encoding an antibody or antigen-binding fragment provided herein.

[0018] In yet another aspect, provided herein is a composition comprising a therapeutically effective amount of an antibody or antigen-binding fragment, a nucleic acid molecule or vector encoding an antibody or antigen-binding fragment provided herein, and a pharmaceutically acceptable excipient.

[0019] In yet another aspect, provided herein is a method of preventing suppression of an immune cell or activation of a response mediated by an immune cell, the method comprising contacting the immune cell with an antibody or fragment thereof provided herein or a pharmaceutical composition provided herein. In some embodiments, the immune cell is an NK cell, a monocyte, a macrophage, a T cell, or a dendritic cell. In some embodiments, the T cell is a CD8 + T cell. In some embodiments, the immune cell expresses LILRB1 and / or LILRB2. In some embodiments, the response mediated by the immune cell is an anti-tumor response. In some embodiments, the tumor cell expresses HLA-A2, ANGPTL, and / or HLA-G.

[0020] In yet another aspect, provided herein is a method for treating a disease or disorder in a subject, the method comprising administering to the subject an antibody or antigen binding fragment provided herein or a pharmaceutical composition provided herein. In some embodiments, the disease or disorder is a cancer. In some embodiments, the cancer expresses HLA-A2, ANGPTL, and / or HLA-G. In some embodiments, the disease or disorder is a solid tumor or a hematological tumor. In some embodiments, the subject is a human subject.

[0021] In some embodiments, the antibody or antigen binding fragment is used as part of a combination therapy. In some embodiments, the antibody or antigen binding fragment is used in combination with a PD-1 inhibitor. In some embodiments, the PD-1 inhibitor is an anti-PD-1 antibody. In some embodiments, the anti-PD-1 antibody is Nivolumab. In some embodiments, the antibody or antigen binding fragment is used in combination with a PD-L1 inhibitor. In some embodiments, the PD-L1 inhibitor is an anti-PD-L1 antibody. In some embodiments, the anti-PD-L1 antibody is LAE005. In some embodiments, the antibody or antigen binding fragment is used in combination with an anti-CD47 antibody. In some embodiments, the anti-CD47 antibody is Hu5F9-G4. In some embodiments, the antibody or antigen binding fragment is used in combination with an anti-CD3 antibody. In some embodiments, the anti-CD3 antibody is OKT3. BRIEF DESCRIPTION OF DRAWINGS

[0022] Figure 1A and Figure 1BExemplary anti-LILRB1 and anti-LILRB2 antibodies were shown to block the interaction between LILRB1 or LILRB2 expressed at the surface of a cell line and APC-HLA-A2 / human MLANA (AAGIGILTV (SEQ ID NO: 1285)) MHC tetramer as assessed by flow cytometry. Anti-LILRB1 antibodies LK-RB1-3, LK-RB1-9, LK-RB1-12, LK-RB1-16, and LK-RB1-39 all blocked the interaction of LILRB1 with HLA-A2 Figure 1A ). Anti-LILRB2 antibodies LK-RB2-24, LK-RB2-1, LK-RB2-2, LK-RB2-3, LK-RB2-14, and LK-RB2-15 all blocked the interaction of LILRB2 with HLA-A2 Figure 1B .

[0023] Figure 2A and Figure 2B LK-RB1-9 was shown to bind to human LILRA1 with low affinity. Figure 2A The ability of hz73D1.vl, LK-RB1-9, and 15G8 to bind to CHOK1 -human LILRA2 cell line was shown by flow cytometry analysis. Figure 2B The ability of hz73D1.vl, LK-RB1-9, and 15G8 to bind to human LILRA1 protein was shown by ELISA analysis.

[0024] Figures 3A-3E Exemplary anti-LILRB1 and anti-LILRB2 antibodies were shown to dose-dependently bind to cynomolgus LILRB1 and cynomolgus LILRB2. Figure 3A Anti-LILRB1 antibodies LK-RB1-43, LK-RB1-11, LK-RB1-50, LK-RB1-58, and hz73D1.vl were shown to dose-dependently bind to cynomolgus LILRB1 protein by ELISA analysis. Figure 3B Anti-LILRB2 antibodies LK-RB2-30, LK-RB2-31, and hz73D1.vl were shown to dose-dependently bind to cynomolgus LILRB1 protein by ELISA analysis. Figures 3C-3E Exemplary anti-LILRB2 antibodies were shown to dose-dependently bind to a CHOK1 cell line overexpressing cynomolgus LILRB2 / cynomolgus LILRB2-Flag by flow cytometry analysis.

[0025] Figures 4A-4KHumanized anti-LILRB1 and anti-LILRB2 antibodies were shown to bind to human LILRB1 and / or LILRB2 with high affinity and block the interaction between human LILRB1 / 2 and HLA-G. Figure 4A and Figure 4B LK-RB1-9, LK-RB1-9.h1, LK-RB1-9.h2, LK-RB1-9.h3, LK-RB1-16, LK-RB1-16.h1, LK-RB1-16.h2, and LK-RB1-16.h3 were shown to bind to CHOK1 -human LILRB1 cell line by flow cytometry analysis. Figure 4C and Figure 4D LK-RB1-9, LK-RB1-9.h1, LK-RB1-9.h2, LK-RB1-9.h3, LK-RB1-16, LK-RB1-16.h1, LK-RB1-16.h2, and LK-RB1-16.h3 were shown to block the interaction between human LILRB1 and PE-HLA-G / human H2AFX (RIIPRHLQL (SEQ ID NO: 1284)) MHC tetramer as assessed by flow cytometry. Figure 4E LK-RB1-9, LK-RB1-9.h1, LK-RB1-9.h2, and LK-RB1-9.h3 were shown to bind to CHOK1 -human LILRA2 cell line in a dose-dependent manner by flow cytometry analysis. Figure 4F and Figure 4G LK-RB2-2, LK-RB2-2.h1, LK-RB2-2.h2, LK-RB2-2.h3, LK-RB2-24, LK-RB2-24.h1, LK-RB2-24.h2, and LK-RB2-24.h3 were shown to bind to CHOK1 -human LILRB2 cell line by flow cytometry analysis. Figures 4H-4I LK-RB2-2, LK-RB2-2.h1, LK-RB2-2.h2, LK-RB2-2.h3, LK-RB2-24, LK-RB2-24.h1, LK-RB2-24.h2, and LK-RB2-24.h3 were shown to block the interaction between human LILRB2 and PE-HLA-G / human H2AFX (RIIPRHLQL (SEQ ID NO: 1284)) MHC tetramer as assessed by flow cytometry. Figure 4J LK-RB2-24, LK-RB2-24.h1, LK-RB2-24.h2, and LK-RB2-24.h3 were shown to bind to CHOK1 -human LILRB1 cell line in a dose-dependent manner by flow cytometry analysis. Figure 4KLK-RB2-24, LK-RB2-24.h1, LK-RB2-24.h2, and LK-RB2-24.h3 dose-dependent ability to block the interaction between human LILRB1 and PE-HLA-G / human H2AFX (RIIPRHLQL (SEQ ID NO: 1284)) MHC tetramer as assessed by flow cytometry.

[0026] Figures 5A-5D Bispecific antibodies LK-RBi-05 and LK-RBi-08 bind to human LILRB1 / 2 with high affinity and block the interaction between human LILRB1 / 2 and HLA-G. Figure 5A LK-RBi-05, LK-RBi-08, LK-RB1-9.h1, LK-RB1-16.h3, 15G8, and hz73D1.v1 dose-dependent binding to human LILRB1 by flow cytometry analysis. Figure 5B LK-RBi-05, LK-RBi-08, LK-RB1-9.h1, LK-RB1-16.h3, 15G8, and hz73D1.v1 ability to block the interaction between human LILRB1 and PE-HLA-G / human H2AFX (RIIPRHLQL (SEQ ID NO: 1284)) MHC tetramer as assessed by flow cytometry. Figure 5C LK-RBi-05, LK-RBi-08, LK-RB2-2.h1, J19.h1, and hz73D1.v1 dose-dependent binding to human LILRB2 by flow cytometry analysis. Figure 5D LK-RBi-05, LK-RBi-08, LK-RB2-2.h1, J19.h1, and hz73D1.v1 ability to block the interaction between human LILRB2 and PE-HLA-G / human H2AFX (RIIPRHLQL (SEQ ID NO: 1284)) MHC tetramer as assessed by flow cytometry.

[0027] Figures 6A-6R Exemplary anti-LILRB1 antibodies activate LILRB1 -positive NK cells with high potency in co-cultures of primary human NK cells and K562 tumor cells expressing HLA-G. Figures 6A-6D % CD107a positive cells in LILRB1 -negative NK cells were not increased after treatment with 0.5 ug / ml and 0.05 ug / ml anti-LILRB1 antibodies. Figures 6E-6H % CD107a positive cells in LILRB1 -positive NK cells were significantly increased after treatment with 0.5 ug / ml and 0.05 ug / ml anti-LILRB1 antibodies.Figures 6I-6K A lack of dose-dependent increase in % CD 107a positive cells in LILRB1 negative NK cells after anti-LILRB1 antibody treatment is shown. Figures 6L-6N A dose-dependent increase in % CD 107a positive cells in LILRB1 positive NK cells after anti-LILRB1 antibody treatment is shown. Figure 6O and Figure 6P A dose-dependent effect on % CD 107a positive cells in LILRB1 negative NK cells after LK-RB1-9, LK-RB1-9.h1, LK-RB1-9.h2, LK-RB1-9.h3, LK-RB1-16, LK-RB1-16.h1, LK-RB1-16.h2, and LK-RB1-16.h3 treatment is shown. Figure 6Q and Figure 6R A dose-dependent increase in % CD 107a positive cells in LILRB1 positive NK cells after LK-RB1-9, LK-RB1-9.h1, LK-RB1-9.h2, LK-RB1-9.h3, LK-RB1-16, LK-RB1-16.h1, LK-RB1-16.h2, and LK-RB1-16.h3 treatment is shown.

[0028] Figures 7A-7I Exemplary anti-LILRB1 antibodies are shown to dose-dependently increase Hu5F9-G4 (anti-CD47) induced macrophage phagocytosis in co-cultures of human monocyte-derived macrophages and Raji (HLA-A2 positive) tumor cells. Figures 7A-7C Hu5F9-G4 induced macrophage phagocytosis of Raji cells is shown to be further increased by 2.5 ug / ml anti-LILRB1 antibody treatment. Figures 7D-7G A dose-dependent increase in Hu5F9-G4 induced macrophage phagocytosis of Raji cells by anti-LILRB1 antibody treatment is shown. Figure 7H and Figure 7I A dose-dependent increase in Hu5F9-G4 induced macrophage phagocytosis by LK-RB1-9, LK-RB1-9.h1, LK-RB1-16, LK-RB1-16.h3, and LK-RB1-55 treatment is shown.

[0029] Figure 8A and Figure 8B LK-RB1-9 and LK-RB1-9.h1 are shown to further increase nivolumab induced IFNy release from human primary CD8+ T cells in co-cultures of primary CD8+ T cells with CHOK1-HLA-G and PDL-1 and OKT3 cells.

[0030] Figures 9A-9H Exemplary anti-LILRB2 antibodies enhance LPS-induced TNFa release in human primary macrophages. Figure 9A LK-RB1-9 increases LPS-induced TNFa release in human primary macrophages. Figure 9B LK-RB1-9 does not change IL-10 release in LPS-stimulated human primary macrophages. Figure 9C LK-RB1-9.h1 and LK-RB1-16.h3 increase LPS-induced TNFa release in human primary macrophages. Figures 9D-9F LPS-induced TNFa release is significantly increased after 6 ug / ml anti-LILRB2 antibody treatment. Figure 9G LK-RB2-2.h1 increases LPS-induced TNFa release in human primary macrophages. Figure 9H LK-RB2-2.h1 decreases LPS-induced IL-10 release in human primary macrophages.

[0031] Figures 10A-10I Exemplary anti-LILRB2 antibodies enhance LPS-induced TNFa release in human PBMCs. Figure 10A and Figure 10B LPS-induced TNFa release is significantly increased after 60 ug / ml anti-LILRB2 antibody treatment. Figures 10C-10H Dose-dependent increase in LPS-induced TNFa release in human PBMCs after anti-LILRB2 antibody treatment is shown. Figure 10I Dose-dependent increase in LPS-induced TNFa release in human PBMCs after LK-RB2-2.h1 and LK-RB2-24.h3 treatment is shown.

[0032] Figures 11A-11F Exemplary anti-LILRB2 antibodies enhance anti-CD3 antibody-induced TNFa and IFN-g release in human primary PBMCs. Figure 11A and Figure 11B Dose-dependent increase in anti-CD3 antibody-induced TNFa release in human PBMCs after LK-RB2-2, LK-RB2-24, and LK-RB2-15 treatment is shown. Figure 11C and Figure 11D Dose-dependent increase in anti-CD3 antibody-induced IFN-g release in human PBMCs after LK-RB2-2, LK-RB2-24, and LK-RB2-15 treatment is shown. Figure 11E Dose-dependent increase in anti-CD3 antibody-induced TNFa release in human PBMCs after LK-RB2-2.h1 and LK-RB2-24.h3 treatment is shown. Figure 11FDose-dependent increase in anti-CD3 antibody-induced IFN-γ release in human PBMCs after LK-RB2-2.h1 and LK-RB2-24.h3 treatment is shown.

[0033] Figures 12A-12C LK-RB1-9.h1 and LK-RB1-16.h3 are shown to bind to human LILRB1 wild type, variant 2, and variant 3 with similar affinities. Figure 12A LK-RB1-9.h1 and LK-RB1-16.h3 are shown to bind to human LILRB1 wild type with the ability analyzed by ELISA. Figure 12B LK-RB1-9.h1 and LK-RB1-16.h3 are shown to bind to human LILRB1 variant 2 with the ability analyzed by ELISA. Figure 12C LK-RB1-9.h1 and LK-RB1-16.h3 are shown to bind to human LILRB1 variant 3 with the ability analyzed by ELISA.

[0034] Figures 13A-13H Dose-dependent increase in % CD107a positive cells in NK cells after anti-LILRB1 antibody and anti-LILRB1 / LILRB2 bispecific antibody treatment is shown. Figures 13A-13D Effect of LK-RBi-01, LK-RBi-02, LK-RBi-05, LK-RBi-06, LK-RBi-07, LK-RBi-08, LK-RBi-09, LK-RBi-10, LK-RBi-11, LK-RB1-9.h1, LK-RB1-16.h3, 15G8, and hz73D1.v1 on % CD107a positive cells in LILRB1 negative NK cells is shown. Figures 13E-13H Effect of LK-RBi-01, LK-RBi-02, LK-RBi-05, LK-RBi-06, LK-RBi-07, LK-RBi-08, LK-RBi-09, LK-RBi-10, LK-RBi-11, LK-RB1-9.h1, LK-RB1-16.h3, 15G8, and hz73D1.v1 on % CD107a positive cells in LILRB1 positive NK cells is shown.

[0035] Figures 14A-14FDose-dependent increase in phagocytosis in the presence of Hu5F9-G4 after treatment with bispecific antibodies LK-RBi-01, LK-RBi-02, LK-RBi-05, LK-RBi-06, LK-RBi-07, LK-RBi-08, LK-RBi-09, LK-RBi-10, LK-RBi-11, LK-RB1-9.h1, LK-RB1-16.h3, 15G8 and hz73D1.v1 is shown.

[0036] Figure 15 LK-RBi-05, LK-RBi-08, LK-RB1-9.h1 and LK-RB1-16.h3 are shown to increase LAE005-induced IFNy release by human primary CD8+ T cells in co-cultures of primary CD8+ T cells and CHOK1-HLA-G and PDL-1 and OKT3 cells.

[0037] Figure 16A and Figure 16B Anti-LILRB1 antibodies, anti-LILRB2 antibodies and bispecific anti-LILRB1 / LILRB2 antibodies are shown to activate LPS-induced human primary monocyte differentiated macrophages. Figure 16A LK-RB1-9.h1, LK-RB1-16.h3, LK-RB2-2.h1, LK-RBi-05, LK-RBi-08, LK-RB1-9.h1 / LK-RB2-2.h1 combination and LK-RB1-16.h3 / LK-RB2-2.h1 combination are shown to increase LPS-induced TNFa release in human primary macrophages. Figure 16B LK-RB2-2.h1, LK-RBi-05, LK-RBi-08, LK-RB1-9.h1 / LK-RB2-2.h1 combination and LK-RB1-16.h3 / LK-RB2-2.h1 combination are shown to reduce IL-10 release in LPS-stimulated human primary macrophages.

[0038] Figures 17A-17C Dose-dependent increase in LPS-induced TNFa release in human PBMCs after treatment with bispecific anti-LILRB1 / LILRB2 antibodies LK-RBi-01, LK-RBi-02, LK-RBi-05, LK-RBi-06, LK-RBi-07, LK-RBi-08 and LK-RBi-10 is shown.

[0039] Figure 18A and Figure 18BDose-dependent increase of TNFa release and IFN-g release induced by anti-CD3 antibody in human PBMCs after treatment with bispecific anti-LILRB1 / LILRB2 antibodies LK-RBi-05 and LK-RBi-08 is shown. Figure 18A LK-RBi-05, LK-RBi-08 and hz73D1.vl dose-dependently increase OKT3-induced TNFa release in human PBMCs is shown. Figure 18B LK-RBi-05, LK-RBi-08 and hz73D1.vl dose-dependently increase OKT3-induced IFN-g release in human PBMCs is shown.

[0040] Figure 19 Exemplary anti-LILRB1 antibodies, anti-LILRB2 antibodies, anti-LILRB1 / LILRB2 bispecific antibodies and antibody combinations increase TNFa release induced by Fc receptor cross-linking in human primary dendritic cells is shown. Bispecific anti-LILIRB1 / LILRB2 antibodies LK-RBi-05 and LK-RBi-08 have a stronger effect on increasing cytokine production compared to anti-LILRB1 antibodies LK-RB1-9.h1, LK-RB1-16.h3 and anti-LILRB2 antibody LK-RB2-2.h1. DETAILED DESCRIPTION

[0041] The present disclosure is based, in part, on novel antibodies that bind to LILRB1 and / or LILRB2 and their superior properties.

[0042] 5.1. Definitions

[0043] The techniques and procedures described or referenced herein include those commonly employed by those skilled in the art, well understood and / or conventionally employed, such as, for example, the techniques described in Sambrook et al., Molecular Cloning: A Laboratory Manual (3rd ed., 2001); Current Protocols in Molecular Biology (Ausubel et al. eds., 2003); Therapeutic Monoclonal Antibodies: From Bench to Clinic (An ed. 2009); Monoclonal Antibodies :Methods and Protocols (Albitar ed., 2010); and Antibody EngineeringVolumes 1 and 2 (Kontermann and Dubel, eds., 2ndEdition, 2010). Unless otherwise defined herein, scientific and technical terms used in this specification have the meanings that are commonly understood by one of ordinary skill in the art. For the purposes of interpreting this specification, the following descriptions of the terms apply and, unless otherwise indicated, the use of any singular’s term will also include the plural, and vice versa, where appropriate. In the event of any conflict between the description of the terms set forth herein and any document incorporated by reference herein, the description of the terms set forth herein shall control.

[0044] The term“LILRB1,” also known as CD85J, LIR1, ILT2, is a single-pass type I transmembrane protein with a predicted molecular weight of about 71 kDa. LILRB1 (human, rhesus, and cynomolgus) is characterized by an extracellular domain comprising four Ig-like C2-type domains, a transmembrane domain, and a long cytoplasmic domain containing 4 ITIM domains (see, e.g., Borges et al., 1997, J. Immunol., 159:5192-5196). These four Ig-like C2-type domains can be referred to herein as domain 1 (D1), domain 2 (D2), domain 3 (D3), and domain 4 (D4). D1 is located at the N-terminal portion of the protein, followed by D2, D3, and D4 in positions closest to the transmembrane region. As characterized in UniProtKB, human LILRB1 is a 650 amino acid (aa) protein - the signal sequence is aa 1-23, the extracellular domain is aa 24-461, the transmembrane region is aa 462-482, and the cytoplasmic domain is aa 483-650. Within the extracellular domain, D1 is aa 27-115, D2 is aa 116-221, D3 is aa 222-312, D4 is aa 313-409, and the“stalk region” is aa 410-461. Within the cytoplasmic domain, the ITIMs are aa 531-536, 560-565, 612-617, and 642-647. LILRB1 is expressed (to varying degrees) on natural killer (NK) cells, monocytes, macrophages, eosinophils, basophils, dendritic cells (DCs), T cell subsets, and B cells. Various ligands are known to interact with LILRB1, including HLA class I molecules (e.g., HLA-A, HLA-B, HLA-C, HLA-E, HLA-F, and HLA-G).

[0045] The term "LILRB2," also known as CD85D, LIR2, ILT4, is a single-pass type I transmembrane protein with a predicted molecular weight of about 65 kDa. ILT4 is characterized by an extracellular domain comprising four Ig-like C2-type domains, a transmembrane domain, and a long cytoplasmic domain containing 3 ITIM domains (see, e.g., Borges et al., 1997, J. Immunol., 159:5192-5196). As described for ILT2, these four Ig-like C2-type domains can be referred to herein as D1, D2, D3, and D4. D1 is located at the N-terminal portion of the protein, followed by D2, D3, and D4 in positions closest to the transmembrane region. As characterized in UniProtKB, human ILT4 is a 598 amino acid (aa) protein - the signal sequence is aa 1-21, the extracellular domain is aa 22-461, the transmembrane region is aa 462-482, and the cytoplasmic domain is aa 483-598. Within the extracellular domain, D1 is aa 27-110, D2 is aa 111-229, D3 is aa 230-318, D4 is aa 330-419, and the "stalk region" is aa 420-461. Within the cytoplasmic domain, the ITIMs are aa 531-536, 560-565, and 590-595. ILT4 is expressed on myeloid cells such as monocytes, macrophages, dendritic cells, but not on lymphocytes. ILT4 has been observed to bind to multiple ligands, in particular HLA class I molecules, ANGPTL proteins, myelin inhibitors, and beta-amyloid.

[0046] As used herein, the term "binding agent" or grammatical equivalents thereof refers to a molecule (e.g., an antibody) having one or more antigen binding sites that bind to an antigen. In some embodiments, a binding agent as described herein is an antibody (including multispecific antibodies and antibody fragments such as antigen-binding fragments or epitope-binding fragments) or other peptide-based molecule and conjugates of antibodies, antibody fragments, or peptide-based molecules (e.g., antibody-drug conjugates) that bind to LILRB1 (such as human LILRB1) and / or LILRB2 (such as human LILRB2).

[0047] The terms“antibody,”“immunoglobulin,” and“Ig” are used interchangeably herein and are used in the broadest sense and specifically encompass, for example, polyclonal antibodies, monoclonal antibodies (including agonist, antagonist, neutralizing antibodies, full-length monoclonal antibodies), antibody compositions with polyepitopic or monoeptiopic specificity, recombinantly produced antibodies, single domain (e.g., VHH) antibodies, monospecific antibodies, multispecific antibodies (including bispecific antibodies), synthetic antibodies, chimeric antibodies, humanized antibodies, or human antibody formats with full-length heavy and / or light chains. VHH as used herein refers to a domain antibody derived from the variable region of a heavy chain only antibody. Exemplary single domain antibodies include, but are not limited to, antibodies naturally lacking light chains such as those from camelid species (e.g., llama), single domain antibodies derived from conventional 4-chain antibodies, engineered antibodies, and single domain scaffolds other than those derived from antibodies. Single domain antibodies can be derived from any species, including but not limited to mouse, human, camel, llama, goat, rabbit, and bovine. VHH can also be derived from species other than camelids that can produce heavy chain antibodies naturally lacking light chains. Antibodies also include antibody fragments (and / or polypeptides comprising antibody fragments) that retain LILRB1 and / or LILRB2 binding characteristics. Non-limiting examples of antibody fragments include antigen binding and / or effector regions of antibodies, e.g., Fab, Fab', F(ab')2, Fv, scFv, (scFv)2, single chain antibody molecules, dual variable domain IgG (DVD-Ig), single variable domains, linear antibodies, V regions, multispecific antibodies formed from antibody fragments, F(ab)2, Fd, Fc, diabodies, dibody, disulfide linked Fv (dsFv), single domain antibodies (e.g., nanobodies), or other fragments (e.g., fragments composed of variable regions of the heavy and light chains that are not coupled covalently). In general, the variable (V) region domain can be any suitable arrangement of immunoglobulin heavy (VH) and / or light (VL) variable domains. For example, antibodies also include tetrameric antibodies comprising two heavy chains and two light chain molecules, antibody light chain monomers, and antibody heavy chain monomers. Thus, for example, the V region domain can be dimeric and contain a VHH-VHH, VH-VH, VH-VL, or VL-VL dimer that binds LILRB1 and / or LILRB2. If desired, the VH and VL can be covalently coupled, directly or through a linker, to form a single chain Fv (scFv). For ease of reference, scFv proteins are referred to herein as included in the category“antibody fragments.” Another form of an antibody fragment is a peptide comprising one or more complementarity determining regions (CDRs) of an antibody. CDRs (also known as“minimal recognition units” or“hypervariable regions”) can be obtained by constructing a polynucleotide that encodes one or more CDRs of interest.Such polynucleotides are prepared, for example, by using the polymerase chain reaction to synthesize the variable region using mRNA from antibody-producing cells as a template (see, e.g., Larrick et al., Methods: A Companion to Methods in Enzymology, 2: 106 (1991); Courtenay-Luck, “Genetic Manipulation of Monoclonal Antibodies,” in Monoclonal Antibodies Production, Engineering and Clinical Application, Ritter et al. (eds.), p. 166, Cambridge University Press (1995); and Ward et al., “Genetic Manipulation and Expression of Antibodies,” in Monoclonal Antibodies: Principles and Applications, Birch et al. (eds.), p. 137, Wiley-Liss, Inc. (1995)). Antibody fragments can be incorporated into, e.g., single domain antibodies, maxibodies, minibodies, intrabodies, diabodies, triabodies, tetrabodies, variable domains of new antigen receptors (v-NARs), and dual single-chain Fv regions (see, e.g., Hollinger and Hudson, Nature Biotechnology, 23(9): 1126-1136, 2005). In some embodiments, antibodies comprising VH and / or VL contain light and / or heavy chain constant regions, such as one or more constant regions, including one or more IgGl, IgG2, IgG3, and / or IgG4 constant regions. In some embodiments, antibodies can include epitope-binding fragments of any of the above. The antibodies described herein can be of any class (e.g., IgG, IgE, IgM, IgD, and IgA) or any subclass (e.g., IgGl, IgG2, IgG3, IgG4, IgAl, and IgA2) of immunoglobulin molecule.

[0048] The term “monospecific,” when used in reference to a binding agent (e.g., an antibody) as used herein, indicates a binding agent having one or more binding sites that each bind to the same epitope of the same antigen.

[0049] The term "multispecific" when used in reference to a binding agent (e.g., an antibody) means that the binding agent is capable of specifically binding to at least two different epitopes, e.g., two binding sites, each formed by a pair of antibody heavy chain variable domains (VH) and antibody light chain variable domains (VL) or each formed by a pair of VHH domains that bind to different antigens or to different epitopes on the same antigen. Such bispecific binding agents (e.g., antibodies) can have a 1+1 format (comprising one binding site for a first antigen or epitope and one binding site for a second antigen or epitope). Other bispecific binding agent (e.g., antibody) formats can be 2+1 or 1+2 format (comprising two binding sites for a first antigen or epitope and one binding site for a second antigen or epitope) or 2+2 format (comprising two binding sites for a first antigen or epitope and two binding sites for a second antigen or epitope). When a bispecific binding agent (e.g., an antibody) comprises two antigen binding sites, each antigen binding site can bind to a different epitope. Such bispecific binding agents (e.g., antibodies) can bind to two different epitopes on the same antigen (e.g., epitopes on LILRB1 or LILRB2).

[0050] The terms "identical" or percent "identity," in the context of two or more nucleic acids or polypeptides, refer to two or more sequences or subsequences that are the same or have a specified percentage of nucleotides or amino acid residues that are the same, when compared and aligned for maximum correspondence, not considering any conservative amino acid substitutions as part of the sequence identity. Percent identity can be measured using sequence comparison software or algorithms or by visual inspection. Various algorithms and software are well known in the art for obtaining sequence alignments of amino acid or nucleotide sequences. These include, but are not limited to, BLAST, ALIGN, Megalign, BestFit, the GCG Wisconsin Package, and variants thereof. In some embodiments, two nucleic acids or polypeptides are substantially identical, meaning that when compared and aligned for maximum correspondence, they have at least 70%, at least 75%, at least 80%, at least 85%, or at least 90% and in some embodiments at least 95%, 96%, 97%, 98%, or 99% nucleotide or amino acid residue identity, as measured using a sequence comparison algorithm or by visual inspection. In some embodiments, the identity exists over a region that is at least about 10 residues, at least about 20 residues, at least about 40-60 residues, at least about 60-80 residues, or any integer value therebetween, in length of the amino acid sequence. In some embodiments, the identity exists over a region that is longer than 60-80 residues, such as at least about 80-100 residues, and in some embodiments, the sequences are substantially identical over the entire length of the sequences being compared, such as the coding region of a target protein or antibody. In some embodiments, the identity exists over a region that is at least about 10 bases, at least about 20 bases, at least about 40-60 bases, at least about 60-80 bases, or any integer value therebetween, in length of the nucleotide sequence. In some embodiments, the identity exists over a region that is longer than 60-80 bases, such as at least about 80-1000 bases or more, and in some embodiments, the sequences are substantially identical over the entire length of the sequences being compared, such as a nucleotide sequence encoding a protein of interest.

[0051] A "conservative amino acid substitution" is one in which one amino acid residue is replaced with another amino acid residue having a side chain with a similar chemical properties. Families of amino acid residues having similar side chains are commonly defined in the art, including basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine), and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). For example, substitution of a phenylalanine for a tyrosine is a conservative substitution. Generally, a conservative substitution in a sequence of a polypeptide, soluble protein, and / or antibody of the present disclosure does not eliminate binding of the polypeptide, soluble protein, or antibody containing the amino acid sequence to a target binding site. Methods of identifying amino acid conservative substitutions that do not eliminate binding are well known in the art.

[0052] As used herein, an "antigen" is a moiety or molecule that contains an epitope to which a binding agent (e.g., an antibody) can bind. Thus, an antigen can be bound by an antibody. In some embodiments, an antigen bound by a binding agent (e.g., an antibody) described herein is LILRB1 (e.g., human LILRB1) or a fragment thereof, including a fragment comprising one or more domains of LILRB1. In some embodiments, an antigen bound by a binding agent (e.g., an antibody) described herein is LILRB2 (e.g., human LILRB2) or a fragment thereof, including a fragment comprising one or more domains of LILRB2. A target antigen can be a polypeptide, a carbohydrate, a nucleic acid, a lipid, a hapten, or other naturally occurring or synthetic compound. In some embodiments, a target antigen is a polypeptide. In certain embodiments, an antigen is associated with a cell, e.g., is present on or in a cell.

[0053] As used herein, an "epitope" is a term in the art and refers to a localized region of an antigen to which a binding molecule (e.g., an antibody) can bind specifically. An epitope can be a linear epitope or a conformational, non-linear, or discontinuous epitope. In the case of a polypeptide antigen, for example, an epitope can be a contiguous amino acid of a polypeptide ("linear" epitope), or an epitope can comprise amino acids from two or more non-contiguous regions of a polypeptide ("conformational," "non-linear," or "discontinuous" epitope). It will be appreciated by those skilled in the art that, generally, a linear epitope can or can not depend on secondary, tertiary, or quaternary structure. For example, in some embodiments, a binding molecule binds a set of amino acids regardless of whether they are folded in a native three-dimensional protein structure. In other embodiments, a binding molecule requires that the amino acid residues making up an epitope exhibit a particular conformation (e.g., bend, twist, flip, or fold) in order to recognize and bind that epitope.

[0054] When two antibodies recognize the same, overlapping, or adjacent epitopes in three-dimensional space, the antibody binds to a reference antibody at the “epitope”, “substantially identical epitope”, or “identical epitope.” The most widely used and rapid method for determining whether two antibodies bind to the same, overlapping, or adjacent epitopes in three-dimensional space is a competition assay, which can be configured in many different ways, for example, using labeled antigens or labeled antibodies. In some assays, the antigen is immobilized on a 96-well plate or expressed on a cell surface, and radioactive, fluorescent, or enzyme labeling is used to measure the ability of the unlabeled antibody to block the binding of the labeled antibody.

[0055] Epitope binning is the process of grouping antibodies based on the epitopes they recognize. More specifically, epitope binning includes methods and systems for distinguishing the epitope recognition characteristics of different antibodies. It uses competitive assays combined with computational processes to cluster antibodies based on their epitope recognition characteristics and identify antibodies with different binding specificities.

[0056] A "complete" antibody is an antibody that contains an antigen-binding site, as well as a CL and at least heavy chain constant regions CH1, CH2, and CH3. The constant regions may include human constant regions or amino acid sequence variants thereof. In some embodiments, a complete antibody has one or more effector functions.

[0057] The term "binds" or "binding" refers to interactions between molecules, including, for example, the formation of a complex. Interactions can be, for example, non-covalent interactions, including hydrogen bonds, ionic bonds, hydrophobic interactions, and / or van der Waals interactions. Complexes can also comprise the binding of two or more molecules held together by covalent or non-covalent bonds, interactions, or forces. The strength of the total non-covalent interaction between a single antigen-binding site on an antibody and a single epitope of a target molecule (such as an antigen) is the affinity of the antibody or functional fragment for that epitope. The dissociation rate (k0) of a binding molecule (e.g., an antibody) to a monovalent antigen is also considered. off ) and association rate (k on The ratio (k) off / k on ) is the dissociation constant K D It is negatively correlated with affinity. K D The lower the value, the higher the antibody affinity. K D The value varies for different antibody and antigen complexes and depends on k. on and k off Both. The dissociation constant K of the antibody presented in this article. DDetermination can be made using any of the methods provided herein or any other method well known to one of skill in the art. Affinity at one binding site does not always reflect the true strength of the interaction between an antibody and an antigen. When a complex antigen containing multiple repeating antigenic determinants, such as a multivalent antigen, is contacted with an antibody containing multiple binding sites, the interaction of the antibody with the antigen at one site will increase the likelihood of a reaction at a second site. The strength of such multiple interactions between a multivalent antibody and an antigen is referred to as avidity.

[0058] With respect to the binding molecules described herein, the terms such as "binds to," "binds specifically to," and like terms are also used interchangeably herein and refer to a binding molecule or antigen binding domain that specifically binds to an antigen, such as a polypeptide. Binding molecules or antigen binding domains that bind or specifically bind to an antigen can be identified, for example, by immunoassays, or other techniques known to those of skill in the art. In some embodiments, a binding molecule or antigen binding domain binds or specifically binds to an antigen when it binds to the antigen with greater affinity than to binding to any cross-reactive antigens, as determined using experimental techniques such as enzyme-linked immunosorbent assay (ELISA). Typically, the specific or selective reaction will be at least twice the background signal or noise and can be more than 10 times background. See, e.g., Paul, ed., Fundamental Immunology (2nded. 1989), Ch. 1, for a discussion of binding specificities. Fundamental Immunology 332-36 (Paul, ed., 2nd ed., 1989). In certain embodiments, the extent of binding of a binding molecule or antigen binding domain to a "non-target" protein is less than about 10% of the binding of the binding molecule or antigen binding domain to its particular target antigen, e.g., as determined by fluorescence activated cell sorting (FACS) analysis. Binding molecules or antigen binding domains that bind to an antigen include those that are capable of binding the antigen with sufficient affinity such that the binding molecule is useful as a therapeutic and / or diagnostic agent, e.g., in targeting the antigen. In certain embodiments, a binding molecule or antigen binding domain that binds to an antigen has a dissociation constant (Kd) of less than or equal to 1 µM, 800 nM, 600 nM, 550 nM, 500 nM, 300 nM, 250 nM, 100 nM, 50 nM, 10 nM, 5 nM, 4 nM, 3 nM, 2 nM, 1 nM, 0.9 nM, 0.8 nM, 0.7 nM, 0.6 nM, 0.5 nM, 0.4 nM, 0.3 nM, 0.2 nM, or 0.1 nM. In certain embodiments, a binding molecule or antigen binding domain binds to an epitope of an antigen that is conserved among antigens from different species. d ) In certain embodiments, a binding molecule or antigen binding domain binds to an epitope of an antigen that is conserved among antigens from different species.

[0059] “Binding affinity” generally refers to the strength of the sum total of noncovalent interactions between a single binding site of a molecule (e.g., a binding agent, such as an antibody) and its binding partner (e.g., an antigen, such as LILRB1 and / or LILRB2). Unless otherwise indicated, as used herein, “binding affinity” refers to the intrinsic binding affinity that reflects a 1 : 1 interaction between members of a binding pair (e.g., an antibody and an antigen). The affinity of a binding molecule X for its binding partner Y can generally be represented by the dissociation constant (K D ). Affinity can be measured by routine methods known in the art, including those described herein. Low affinity antibodies generally bind antigen slowly and tend to dissociate readily, whereas high affinity antibodies generally bind antigen more quickly and tend to remain bound for longer periods of time. Various methods of measuring binding affinity are known in the art, any of which can be used for the purposes of the present disclosure. In one embodiment, “K D ” or “K D values” can be measured by biolayer interferometry (BLI) using, for example, an Octet QK384 system (ForteBio, Menlo Park, CA). Alternatively, K D can also be measured in a radiolabeled antigen binding assay (RIA), e.g., with a Fab form of the antibody of interest and its antigen (Chen et al. (1999) J. Mol Biol 293:865-881) or using surface plasmon resonance (SPR) assays by BIACORE TM using, for example, a BIACORE TM -2000 or BIACORE TM -3000 (BIACORE TM , Inc., Piscataway, NJ). “On-rate” or “rate of association” or “association rate” or “k on ” and “off-rate” or “rate of dissociation” or “dissociation rate” or “k off ” can also be determined using the same SPR or BLI techniques described above, respectively, using, for example, an Octet QK384 system (ForteBio, Menlo Park, CA) or BIACORE TM -2000 or BIACORE TM -3000 (BIACORE TM , Inc., Piscataway, NJ).

[0060] The term "compete," when used in the context of a binding agent (e.g., an antibody), means a binding agent that competes for binding to the same epitope or binding site on a target, which includes competition between such binding agents as determined by an assay in which the binding agent under study prevents or inhibits specific binding of a reference molecule (e.g., a reference ligand or a reference antigen-binding protein, such as a reference antibody) to a common antigen (e.g., LILRB1 and / or LILRB2). Numerous types of competitive binding assays can be used to determine whether a test binding agent competes with a reference molecule for binding to LILRB1 (e.g., human LILRB1) or LILRB2 (e.g., human LILRB2). Examples of assays that can be employed include solid phase direct or indirect radioimmunoassay (RIA); solid phase direct or indirect enzyme immunoassay (EIA), sandwich competition assays (see, e.g., Stahli et al., (1983) Methods in Enzymology 9:242-253); solid phase direct biotin-avidin EIA (see, e.g., Kirkland et al., (1986) J. Immunol. 137:3614-3619 or Cheung et al., (1990) Virology 176:546-552); solid phase direct labeled assays; solid phase direct labeled sandwich assays (see, e.g., Harlow and Lane, (1988) Antibodies, A Laboratory Manual, Cold Spring Harbor Pres); solid phase direct label RIA using 1-125 labeling (see, e.g., Morel et al., (1988) Molec. Immunol. 25:7-15); and direct labeled RIA (Moldenhauer et al., (1990) Scand. J. Immunol. 32:77-82). Typically, such assays involve the use of purified antigen (e.g., LILRB1, such as human LILRB1, or LILRB2, such as human LILRB2) bound to a solid surface or cell, which carries either an unlabelled test antigen-binding protein (e.g., a test LILRB1 antibody or a test LILRB2 antibody) or a labeled reference antigen-binding protein (e.g., a reference LILRB1 antibody or a reference LILRB2 antibody). Competitive inhibition can be measured by determining the amount of label bound to the solid surface or cell in the presence of the test antigen-binding protein. Typically, the test antigen-binding protein is present in excess. Antibodies identified by competition assays (competing antibodies) include antibodies that bind to the same epitope as the reference antibody and / or antibodies that bind to an adjacent epitope sufficiently close to the epitope bound by the reference antibody so as to cause steric hindrance of the antibodies (e.g., analogous epitopes or overlapping epitopes).Typically, the competing antibody will inhibit the specific binding of the reference antibody to the common antigen by at least 20%, e.g., at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, or 75% when present in excess. In some cases, the binding is inhibited by at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more.

[0061] Antibody "effector functions" refer to those biological activities attributable to the Fc region (e.g., native sequence Fc region or amino acid sequence variant Fc region) of an antibody, and vary with the antibody isotype. Examples of antibody effector functions include: Clq binding and complement dependent cytotoxicity; Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; down regulation of B cell receptor (BCR) surface expression; and B cell activation.

[0062] The term "Fc region" is used herein to define a C-terminal region of an immunoglobulin heavy chain, including, for example, native-sequence Fc regions, recombinant Fc regions, and variant Fc regions. While the boundaries of the Fc region of an immunoglobulin heavy chain might vary, the human IgG heavy chain Fc region is usually defined to stretch from an amino acid residue Cys226, or from Pro230, to the carboxy-terminus. The C-terminal lysine (residue 447 according to EU numbering system) of the Fc region can be removed, e.g., during production or purification of the antibody or by recombinantly engineering the nucleic acid encoding the antibody heavy chain. Accordingly, a composition of intact antibodies can contain a population of antibodies with all K447 residues removed, a population of antibodies with no K447 residues removed, and a population of antibodies with a mixture of antibodies with and without K447 residues. A "functional Fc region" has an "effector function" of a native sequence Fc region. Exemplary "effector functions" include Clq binding; CDC; Fc receptor binding; ADCC; phagocytosis; down regulation of cell surface receptors (e.g., B cell receptor), etc. Such effector functions typically require the Fc region to be combined with a binding site or binding domain (e.g., an antibody variable region or domain) and can be assessed using various assays known to the skilled artisan. A "native sequence Fc region" comprises an amino acid sequence that is identical to the amino acid sequence of a naturally occurring Fc region, and is not manipulated, modified and / or altered by the hand of man (e.g., isolated, purified, selected, including or combined with other sequences such as variable region sequences). Native sequence human Fc regions include a native sequence human IgGl Fc region (non-A and A allotypes); native sequence human IgG2 Fc region; native sequence human IgG3 Fc region; and native sequence human IgG4 Fc region, and naturally occurring variants thereof. A "variant Fc region" comprises an amino acid sequence that differs from that of a native sequence Fc region by virtue of at least one amino acid modification (e.g., substitution, addition, or deletion). In certain embodiments, a variant Fc region has at least one amino acid substitution compared to a native sequence Fc region or to the Fc region of a parent polypeptide, e.g., from about one to about ten amino acid substitutions, or from about one to about five amino acid substitutions, in the native sequence Fc region or in the Fc region of the parent polypeptide. A variant Fc region herein can have at least about 80% homology to a native sequence Fc region and / or to the Fc region of a parent polypeptide, or at least about 90% homology thereto, e.g., at least about 95% homology thereto.

[0063] In certain embodiments, a binding molecule or antigen binding domain can comprise a "chimeric" sequence in which a portion of the heavy and / or light chain is identical with, or homologous to, a corresponding sequence in an antibody derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical with, or homologous to, a corresponding sequence in an antibody derived from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies, so long as they exhibit the desired biological activity (see U.S. Patent No. 4,816,567; and Morrison et al., 1984, Proc. Natl. Acad. Sci. USA 81 :6851-55). Chimeric sequences can include humanized sequences.

[0064] In certain embodiments, a binding molecule or antigen binding domain can comprise portions of "humanized" forms of non-human (e.g., camelid, murine, non-human primate) antibodies, which include sequences from human immunoglobulin (e.g., acceptor antibody) in which native CDR residues are replaced by residues from corresponding CDR of a non-human species (e.g., donor antibody), such as camelid, mouse, rat, rabbit, or non-human primate, that have the desired specificity, affinity, and capability. In some cases, one or more FR region residues of the human immunoglobulin sequence are replaced by corresponding non-human residues. Moreover, humanized antibodies can comprise residues that are not found in the recipient antibody or in the donor antibody. These modifications are made to further optimize antibody performance. A humanized antibody heavy or light chain can comprise substantially all of at least one or more variable regions, in which all or substantially all of the CDRs correspond to those of a non-human immunoglobulin and all or substantially all of the FRs are those of a human immunoglobulin sequence. In certain embodiments, a humanized antibody will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin. For further details, see Jones et al., Nature 321 :522-25 (1986); Riechmann et al., Nature 332:323-29 (1988); Presta, Curr. Op. Struct. Biol. 2:593-96 (1992); Carter et al., Proc. Natl. Acad. Sci. USA 89:4285-89 (1992); U.S. Patents: 6,800,738; 6,719,971; 6,639,055; 6,407,213; and 6,054,297.

[0065] In certain embodiments, the binding molecule or antigen binding domain can comprise portions of "fully human antibodies" or "human antibodies," where the terms are used interchangeably herein and refer to antibodies comprising human variable regions and, e.g., human constant regions. The binding molecule can comprise antibody sequences. In particular embodiments, the terms refer to antibodies comprising variable and constant regions of human origin. In certain embodiments, "fully human" antibodies can also encompass antibodies that bind polypeptides and are encoded by nucleic acid sequences that are naturally occurring somatic variants of human germline immunoglobulin nucleic acid sequences. The term "fully human antibody" includes antibodies having variable and constant regions corresponding to those of human germline immunoglobulin sequences as described by Kabat et al. (see Kabat et al. (1991) Sequences of Proteins of Immunological Interest , 5th Ed., U.S. Department of Health and Human Services, NIH Publication No. 91-3242). A "human antibody" is one having an amino acid sequence corresponding to that of an antibody produced by a human and / or has been made using any of the techniques for producing human antibodies. This definition of a human antibody specifically excludes a humanized antibody comprising non-human antigen binding residues. Human antibodies can be produced using various techniques known in the art, including phage-display libraries (Hoogenboom and Winter, J. Mol. Biol. 227:381 (1991); Marks et al., J. Mol. Biol. 222:581 (1991)) and yeast display libraries (Chao et al., Nature Protocols 1 :755-68 (2006)). Methods for making human monoclonal antibodies are also described in Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, Inc., pp. 77-96 (1985); Boerner et al., J. Immunol. 147(l):86-95 (1991); and van Dijk and van de Winkel, Curr. Opin. Pharmacol. 5:368-74 (2001). Human antibodies can be prepared by administering the antigen to a transgenic animal that has been modified to produce such antibodies in response to challenge by the antigen, but whose endogenous loci have been disabled so that the animal produces no endogenous antibodies, e.g., a mouse (for XENOMOUSE® technology see, e.g., U.S. Pat. Nos. 6,075,181 and 6,150,582; and PCT applications WO 1998 / 00079 and WO 1998 / 24893; and Mendez et al., Nature Genetics 15: 146-156 (1997)). Monoclonal Antibodies and Cancer Therapy 77(1985); Boerner et al., J. Immunol. 147(l):86-95 (1991); and van Dijk and van de Winkel, Curr. Opin. Pharmacol. 5:368-74 (2001). Human antibodies can be prepared by administering the antigen to a transgenic animal that has been modified to produce such antibodies in response to challenge by the antigen, but whose endogenous loci have been disabled so that the animal produces no endogenous antibodies, e.g., a mouse (for XENOMOUSE TMTechniques, see, e.g., Jakobovits, Curr. Opin. Biotechnol. 6(5):561-66 (1995); Bruggemann and Taussing, Curr. Opin. Biotechnol. 8(4):455-58 (1997); and U.S. Pat. Nos. 6,075,181 and 6,150,584). See also, e.g., Li et al., Proc. Natl. Acad. Sci. USA 103:3557-62 (2006) for human antibodies generated via human B-cell hybridoma technology.

[0066] In certain embodiments, a binding molecule or antigen binding domain can comprise portions of a "recombinant human antibody," where the phrase includes human antibodies that are prepared, expressed, created or isolated by recombinant means, such as antibodies expressed using a recombinant expression vector transfected into a host cell, antibodies isolated from a recombinant, combinatorial human antibody library, antibodies isolated from an animal (e.g., a mouse or a cow) that is transgenic for human immunoglobulin genes (see e.g., Taylor, L. D. et al., Nucl. Acids Res. 20:6287-6295 (1992)) or antibodies prepared, expressed, created or isolated by any other means involving splicing of human immunoglobulin gene sequences to other DNA sequences. Such recombinant human antibodies can have variable and constant regions derived from human germline immunoglobulin sequences (see Kabat, E. A. et al. (1991) Sequences of Proteins of Immunological Interest, Fifth Edition, U.S. Department of Health and Human Services, NIH Publication No. 91-3242). However, in certain embodiments, such recombinant human antibodies are subjected to in vitro mutagenesis (or, when an animal transgenic for human Ig sequences is used, in vivo somatic mutagenesis), and thus the amino acid sequences of the VH and VL regions of the recombinant antibodies are sequences that, while derived from and related to human germline VH and VL sequences, can not naturally exist within the human antibody germline repertoire in vivo. Sequences of Proteins of Immunological Interest In certain embodiments, a binding molecule or antigen binding domain can comprise portions of a "recombinant human antibody," where the phrase includes human antibodies that are prepared, expressed, created or isolated by recombinant means, such as antibodies expressed using a recombinant expression vector transfected into a host cell, antibodies isolated from a recombinant, combinatorial human antibody library, antibodies isolated from an animal (e.g., a mouse or a cow) that is transgenic for human immunoglobulin genes (see e.g., Taylor, L. D. et al., Nucl. Acids Res. 20:6287-6295 (1992)) or antibodies prepared, expressed, created or isolated by any other means involving splicing of human immunoglobulin gene sequences to other DNA sequences. Such recombinant human antibodies can have variable and constant regions derived from human germline immunoglobulin sequences (see Kabat, E. A. et al. (1991) Sequences of Proteins of Immunological Interest, Fifth Edition, U.S. Department of Health and Human Services, NIH Publication No. 91-3242). However, in certain embodiments, such recombinant human antibodies are subjected to in vitro mutagenesis (or, when an animal transgenic for human Ig sequences is used, in vivo somatic mutagenesis), and thus the amino acid sequences of the VH and VL regions of the recombinant antibodies are sequences that, while derived from and related to human germline VH and VL sequences, can not naturally exist within the human antibody germline repertoire in vivo.

[0067] In certain embodiments, the binding molecule or antigen binding domain can comprise a portion of a "monoclonal antibody," where the term as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, e.g., the individual antibodies comprising the population are identical except for possible naturally occurring mutations that can be present in minor amounts or known post- translational modifications, such as isomerization of amino acids or deamidation, methionine oxidation or asparagine or glutamine deamidation, each monoclonal antibody typically will recognize a single epitope on an antigen. In particular embodiments, a "monoclonal antibody" as used herein is an antibody produced by a single hybridoma or other cell. The term "monoclonal" does not refer to a particular method of making the antibody. For example, the monoclonal antibodies useful in the present disclosure can be made by the hybridoma method first described by Kohler et al., Nature 256:495 (1975), or can be made using recombinant DNA methods in bacterial cells or eukaryotic animal or eukaryotic plant cells (see, e.g., U.S. Patent No. 4,816,567). For example, "monoclonal antibodies" can also be isolated from a phage antibody library using the techniques described in Clackson et al., Nature 352:624-28 (1991) and Marks et al., J. Mol. Biol. 222:581-97 (1991). Other methods used to prepare clonal cell lines and monoclonal antibodies expressed therefrom are also well known in the art. See, e.g., Short Protocols in Molecular Biology (Ausubel et al. eds., 5th ed., 2002).

[0068] The terms "antigen binding fragment," "antigen binding domain," "antigen binding region," and like terms refer to a portion of an antibody that comprises amino acid residues (e.g., CDRs) that interact with an antigen and confer specificity and affinity for the antigen to the binding fragment, domain, or region. As used herein, "antigen binding fragment" includes "antibody fragments" that comprise a portion of an antibody, including one or more CDRs, such as an antigen binding region or variable region of an antibody.

[0069] Antibodies described herein include, but are not limited to, synthetic antibodies, monoclonal antibodies, recombinantly produced antibodies, multispecific antibodies (e.g., bispecific antibodies), human antibodies, humanized antibodies, chimeric antibodies, intrabodies, single-chain Fvs (scFv) (e.g., including monospecific, bispecific, etc.), camelized antibodies, Fab fragments, F(ab') fragments, disulfide-linked Fvs (sdFv), anti-idiotypic (anti-Id) antibodies, and epitope binding fragments of any of the above.

[0070] In some embodiments, the antibodies described herein include immunoglobulin molecules and immunologically active portions of immunoglobulin molecules, including molecules comprising one or more antigen binding sites that bind to a LILRB1 antigen and / or a LILRB2 antigen.

[0071] An antibody can be of any type (e.g., IgG, IgE, IgM, IgD, IgA, or IgY), any class (e.g., IgGl, IgG2, IgG3, IgG4, IgAl, or IgA2), or any subclass (e.g., IgG2a or IgG2b) of immunoglobulin molecule. In some embodiments, the antibodies described herein are IgG antibodies (e.g., human IgG) or a class (e.g., human IgGl, IgG2, IgG3, or IgG4) or subclass thereof.

[0072] A typical 4-chain antibody unit is a heterotetrameric glycoprotein composed of two identical light (L) chains and two identical heavy (H) chains. In the case of IgG, this 4-chain unit typically is about 150,000 Daltons. Each L chain is linked to a H chain by one covalent disulfide bond, while the two H chains are linked to each other by one or more disulfide bonds depending on the H chain isotype. Each H chain and L chain also has regularly spaced intrachain disulfide bridges. Each H chain has at the N-terminus a variable domain (VH) followed by three constant domains (CH) for each a and y chain and four CH domains for p and e isotypes. Each L chain has at the N-terminus a variable domain (VL) followed by a constant domain (CL) at its other end. The VL is aligned with the VHand the CL is aligned with the first constant domain of the heavy chain (CH1). Particular amino acid residues are believed to form an interface between the light chain variable domain and the heavy chain variable domain. The pairing between a VHand a VLtogether forms a single antigen binding site. For the structure and properties of the different classes of antibodies, see, e.g., Basic and Clinical Immunology (Stites et al. eds., 8th ed. 1994); and Basic and Clinical Immunology 71 (Stites et al. eds., 8th ed., 1994); and Immunobiology (Janeway et al. eds., 5th ed., 2001).

[0073] In some embodiments, the antibody is a 4-chain antibody unit comprising two heavy (H) chain / light (L) chain pairs. In another embodiment, the amino acid sequences of the H chains are identical and the amino acid sequences of the L chains are identical. In other embodiments, the amino acid sequences of the H chains are different from one another. Additionally or alternatively, the amino acid sequences of the L chains are different from one another. In some embodiments, the antibody comprises a first H / L chain pair and a second H / L chain pair, wherein the first H / L chain pair binds to a LILRB1 antigen and the second H / L chain pair binds to a non-LILRB1 (such as LILRB2) antigen. In some embodiments, the antibody is a 2-chain antibody unit comprising a VHH-VHH pair. In further embodiments, the amino acid sequences of the VHHs are identical. In other embodiments, the amino acid sequences of the VHHs are different from one another. For example, the antibody comprises a first VHH and a second VHH, wherein the first VHH binds to a LILRB1 antigen and the second VHH binds to a non-LILRB1 (such as LILRB2) antigen. In some embodiments, the H and / or L chains comprise a constant region, e.g., a human constant region. In some embodiments, the L chain constant region of such antibodies is a kappa or lambda light chain constant region, e.g., a human kappa or lambda light chain constant region. In some embodiments, the H chain constant region of such antibodies comprises a gamma heavy chain constant region, e.g., a human gamma heavy chain constant region. In some embodiments, such antibodies comprise an IgG constant region, e.g., a human IgG constant region (e.g., an IgGl, IgG2, IgG3, and / or IgG4 constant region).

[0074] An antibody or fragment thereof can preferentially bind to LILRB1 (such as human LILRB1) and / or LILRB2 (such as human LILRB2), meaning that the antibody or fragment thereof binds to LILRB1 and / or LILRB2 with greater affinity than it binds to a control protein (e.g., an unrelated control protein, such as chicken egg protein lysozyme), and / or binds to human LILRB1 and / or LILRB2 with greater affinity than it binds to an unrelated control protein. For example, an antibody or fragment thereof can specifically recognize and bind to LILRB1 and / or LILRB2 or a portion of each. By "specifically binds" is meant that the antibody or fragment thereof binds to LILRB1 and / or LILRB2 with at least 5, 10, 15, 20, 25, 50, 100, 250, 500, 1000, or 10,000 times the affinity of its binding to an unrelated control protein (e.g., chicken egg protein lysozyme). In some embodiments, an antibody or fragment thereof can bind LILRB1 and / or LILRB2 substantially exclusively (e.g., is capable of distinguishing LILRB1 and / or LILRB2 from other known polypeptides, e.g., by virtue of a measurable difference in binding affinity). In some embodiments, a LILRB1 binding agent (e.g., an antibody) can react with LILRB1 sequences other than the human LILRB1 sequence (e.g., a cynomolgus monkey LILRB1 sequence). In other embodiments, a LILRB1 binding agent (e.g., an antibody) does not react with non-human (such as a cynomolgus monkey LILRB1 sequence). In some embodiments, a LILRB2 binding agent (e.g., an antibody) can react with LILRB2 sequences other than the human LILRB2 sequence (e.g., a cynomolgus monkey LILRB2 sequence). In other embodiments, a LILRB2 binding agent (e.g., an antibody) does not react with non-human (such as a cynomolgus monkey LILRB2 sequence).

[0075] The term "Fab" or "Fab region" refers to the region of an antibody that binds to an antigen. A conventional IgG typically comprises two Fab regions, each on one of the two arms of the Y-shaped IgG structure. Each Fab region is typically composed of one variable and one constant region of each of the heavy and light chains. More specifically, the variable and constant regions of the heavy chain in a Fab region are the VH and CH1 regions, and the variable and constant regions of the light chain in a Fab region are the VL and CL regions. The VH, CH1, VL, and CL in a Fab region can be arranged in various ways to confer antigen binding ability according to the present disclosure. For example, the VH and CH1 regions can be on one polypeptide, and the VL and CL regions can be on a separate polypeptide, similar to the Fab regions of a conventional IgG. Alternatively, the VH, CH1, VL, and CL regions can all be on the same polypeptide and oriented in different orders, as described in more detail in the subsections below.

[0076] The terms "variable region," "variable domain," "V region," or "V domain" refer to a portion of the light or heavy chain of an antibody, typically located at the amino terminus of the light or heavy chain and having a length of approximately 120 to 130 amino acids in the heavy chain and approximately 100 to 110 amino acids in the light chain, and are used for the binding and specificity of each specific antibody to its specific antigen. The variable region of the heavy chain may be referred to as "VH." The variable region of the light chain may be referred to as "VL." The term "variable" refers to the fact that certain segments of the variable region differ widely in sequence between antibodies. The V region mediates antigen binding and defines the specificity of a particular antibody to its specific antigen. However, variability is not uniformly distributed across the 110-amino acid span of the variable region. Instead, the V region consists of less variable (e.g., relatively invariant) extensions of approximately 15 to 30 amino acids called frame regions (FRs), which are separated by shorter regions of approximately 9 to 12 amino acids each called "hypervariates," which have greater variability (e.g., extreme variability). The variable regions of both the heavy and light chains each contain four free-floating regions (FRs), predominantly employing a β-sheet configuration, connected by three hypervariable regions that form loops connecting the β-sheet structure and, in some cases, form part of the β-sheet structure. The hypervariable regions in each chain are held together closely by the FRs and, together with hypervariable regions from the other chain, contribute to the formation of the antibody's antigen-binding site (see, for example, Rabat et al.). Sequences of Proteins of Immunological Interest (5th edition, 1991). Constant regions do not directly participate in antibody-antigen binding but exhibit various effector functions, such as antibody involvement in antibody-dependent cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Variable regions vary widely in sequence among different antibodies. In a specific implementation, the variable region is the human variable region.

[0077] The terms “variable region residue numbering according to Kabat” or “amino acid position numbering as in Rabat” and variations thereof refer to the numbering system for the heavy chain variable region or light chain variable region used in Rabat et al., supra, for antibody compilation. Using this numbering system, the actual linear amino acid sequence can contain fewer or additional amino acids associated with the shortening of, or insertions into, the variable domain FRs or CDRs of the variable domain. For example, a heavy chain variable domain can include a single amino acid insertion of residue 52 (residue 52a according to Kabat) after residue 52 and three inserted residues (e.g., residues 82a, 82b, and 82c according to Kabat, etc.) after residue 82. For a given antibody, the Kabat numbering of residues can be determined by alignment of the sequence of the antibody with the sequence of the “standard” Rabat numbering in regions of homology. The Rabat numbering system is typically used when referring to residues in the variable domain (approximately residues 1-107 of the light chain and residues 1-113 of the heavy chain) (e.g., Rabat et al., supra). The “EU numbering system” or “EU index” is typically used when referring to residues in an immunoglobulin heavy chain constant region (e.g., the EU index reported in Rabat et al., supra). The “EU index as in Rabat” refers to the residue numbering of the human IgG 1 EU antibody. Other numbering systems have been described, e.g., AbM, Chothia, Contact, IMGT, and AHon.

[0078] As used herein, when referring to antibodies, the term “heavy chain” refers to a polypeptide chain of about 50 kDa-70 kDa, where the amino-terminal portion includes a variable region of about 120 to 130 or more amino acids, and the carboxy-terminal portion includes a constant region. Based on the amino acid sequence of the heavy chain constant region, the constant region can be one of five different types, referred to as alpha (a), delta (d), epsilon (e), gamma (g), and mu (m). The different types of heavy chains vary in size: a, d, and g contain approximately 450 amino acids, while m and e contain approximately 550 amino acids. When combined with a light chain, these different types of heavy chains give rise to five well-known classes (e.g., isotypes) of antibodies: IgA, IgD, IgE, IgG, and IgM, including four IgG subclasses, IgG1, IgG2, IgG3, and IgG4.

[0079] As used herein, when referring to antibodies, the term “light chain” refers to a polypeptide chain of about 25 kDa, where the amino-terminal portion includes a variable region of about 100 to about 110 or more amino acids, and the carboxy-terminal portion includes a constant region. The approximate length of a light chain is 211 to 217 amino acids. There are two different types, designated kappa (K) or lambda (l), based on the amino acid sequence of the constant domain.

[0080] As used herein, the terms "hypervariable region," "HVR," "complementarity determining region," and "CDR" are used interchangeably. "CDR" refers to one of three hypervariable regions (H1, H2, or H3) within the non -framework region of an immunoglobulin (Ig or antibody) VH beta-sheet framework, or one of three hypervariable regions (L1, L2, or L3) within the non -framework region of an antibody VL P-sheet framework. CDR1, CDR2, and CDR3 in a VH domain are also referred to as HCDR1, HCDR2, and HCDR3, respectively. CDR1, CDR2, and CDR3 in a VL domain are also referred to as LCDR1, LCDR2, and LCDR3, respectively. Thus, CDRs are sequences of variability interspersed within the framework sequences.

[0081] CDR regions are well known to those skilled in the art and have been defined by well-known numbering systems. For example, Rabat Complementarity Determining Regions (CDRs) are based on sequence variability and are the most commonly used (see, e.g., Kabat et al., supra; Nick Deschacht et al., J Immunol 2010; 184:5696-5704). Chothia, on the other hand, refers to the location of structural loops (see, e.g., Chothia and Lesk, J. Mol. Biol. 196:901-17 (1987)). When numbered using the Rabat numbering convention, the end of the Chothia CDR-H1 loop varies between H32 and H34, depending on the length of the loop (this is because the Rabat numbering scheme places insertions at H35A and H35B; if neither 35A nor 35B is present, the loop ends at 32; if only 35A is present, the loop ends at 33; if both 35A and 35B are present, the loop ends at 34). AbM hypervariable regions represent a compromise between Rabat CDRs and Chothia structural loops, and are used by Oxford Molecular's AbM antibody modeling software (see, e.g., Martin et al., Proc. Natl. Acad. Sci. USA 86: 9263-9267 (1989)). "Contact" hypervariable regions are based on an analysis of available complex crystal structures. Another universal numbering system that has been developed and is widely adopted is ImMunoGeneTics (IMGT®) Antibody Engineering Vol. 2 (Kontermann and Du¨bel, eds., 2nded. 2010). "contact" hypervariable regions are based on an analysis of available complex crystal structures. Another universal numbering system that has been developed and is widely adopted is ImMunoGeneTics (IMGT®) (Lafranc et al., Dev. Comp. Immunol. 27(1):55-77 (2003)). IMGT is an integrated information system for the immunoglobulins (IG), T cell receptors (TCR), and major histocompatibility complex (MHC) in humans and other vertebrates. In this context, CDR refers to both by amino acid sequence and position within a light or heavy chain. Since the "positions" of CDRs within the structure of immunoglobulin variable domains are conserved between species and occur in structures called loops, CDR and framework residues are readily identified by using a numbering system that aligns variable domain sequences according to structural features. This information can be used to graft and substitute CDR residues from an immunoglobulin of one species into an acceptor framework typically from a human antibody. An additional numbering system (AHon) has been developed by Honegger and Pluckthun, J. Mol. Biol. 309:657-70 (2001). The correspondence between numbering systems, including for example, the Kabat numbering and the IMGT unique numbering system, is well known to those skilled in the art (see, e.g., Kabat, supra; Chothia and Lesk, supra; Martin, supra; Lefranc et al., supra). The residues from each of these hypervariable regions or CDRs are illustrated in the following tables.

[0082] Exemplary CDRs according to various numbering systems

[0083]

[0084] The boundaries of a given CDR can vary depending on the scheme used to identify. Thus, unless otherwise specified, the terms "CDR" and "complementarity determining region" of a given antibody or region thereof, such as a variable region, and individual CDRs of an antibody or region thereof (e.g., CDR-H1, CDR-H2) are understood to encompass complementarity determining regions as defined by any of the known schemes described herein above. In some cases, the scheme used to identify a particular CDR or CDRs, such as the CDRs defined by IMGT, Kabat, Chothia, or Contact methods, is specified. In other cases, the particular amino acid sequence of a CDR is given. It should be noted that CDR regions can also be defined by a combination of various numbering systems (e.g., a combination of Kabat and Chothia numbering systems or a combination of Kabat and IMGT numbering systems. Thus, the term such as "CDR1 as shown in a particular VH" includes any CDR1 as defined by the exemplary CDR numbering systems described above, but is not limited thereto. Once a variable region (e.g., VH or VL) is given, one of skill in the art will understand that the CDRs within that region can be defined by different numbering systems or combinations thereof.

[0085] Hypervariable regions can include the "extended hypervariable regions" of 24-36 or 24-34 (LI), 46-56 or 50-56 (L2), and 89-97 or 89-96 (L3) in the VL, and 26-35 or 26-35A (HI), 50-65 or 49-65 (H2), and 93-102, 94-102 or 95-102 (H3) in the VH.

[0086] The term "constant region" or "constant domain" refers to the carboxy-terminal portion of the light and heavy chains that is not directly involved in binding of an antibody to an antigen but exhibits various effector functions such as interaction with the Fc receptor. The term refers to the portion of an immunoglobulin molecule that has a more conserved amino acid sequence in comparison to other portions of the immunoglobulin that contain the antigen binding sites (i.e., the variable regions). The constant region can contain the CHI, CH2 and CH3 regions of the heavy chain and the CL region of the light chain.

[0087] The term "framework" or "FR" refers to those variable region residues that are flanking the CDRs. FR residues are found, for example, in chimeric antibodies, humanized antibodies, human antibodies, domain antibodies, diabodies, linear antibodies and bispecific antibodies. FR residues are those variable domain residues other than hypervariable region residues or CDR residues.

[0088] "Percent (%) amino acid sequence identity" and "homology" with respect to a peptide, polypeptide, or antibody sequence is defined as the percentage of amino acid residues in a candidate sequence that are identical with the amino acid residues in the specific peptide or polypeptide sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as BLAST, BLAST-2, ALIGN or MEGALIGN TM (DNASTAR) software. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms needed to achieve the maximum alignment over the full length of the sequences being compared.

[0089] The term "specificity" refers to the selective recognition of a particular epitope of an antigen by an antigen binding protein. For example, a native antibody is monospecific. The term "multispecific" as used herein means that the antigen binding protein has two or more antigen binding sites, where at least two of the antigen binding sites bind to different antigens. "Bispecific" as used herein means that the antigen binding protein has two different antigen binding specificities. The term "monospecific" antibody as used herein means an antigen binding protein having one or more binding sites that bind to the same antigen.

[0090] The term "valency" as used herein denotes the presence of a particular number of binding sites in an antigen binding protein. For example, a natural antibody or full-length antibody has two binding sites and is bivalent. Thus, the terms "trivalent," "tetravalent," "pentavalent," and "hexavalent" denote the presence of two binding sites, three binding sites, four binding sites, five binding sites, and six binding sites, respectively, in an antigen binding protein.

[0091] The terms "polypeptide" and "peptide" and "protein" are used interchangeably herein and refer to polymers of amino acids of any length. The polymer can be linear or branched, it can comprise modified amino acids, and it can be interrupted by non-amino acids. The term also encompasses an amino acid polymer that has been modified by the addition of a non-amino acid moiety. For example, a glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation or modification. The definition also includes polypeptides containing one or more analogs of an amino acid (including, but not limited to, unnatural amino acids) and other modifications known in the art. It is understood that, because the polypeptides of the disclosure can be based on antibodies or other members of the immunoglobulin superfamily, in certain embodiments, "polypeptide" can exist as a single chain or as two or more associated chains.

[0092] "Polynucleotide" or "nucleic acid" are used interchangeably herein to refer to polymers of nucleotides of any length and include DNA and RNA. The nucleotides can be deoxyribonucleotides, ribonucleotides, modified nucleotides or bases, and / or their analogs, or any substrate that can be incorporated into a polymer by DNA or RNA polymerase or by a synthetic reaction. A polynucleotide can comprise modified nucleotides, such as methylated nucleotides and their analogs. "Oligonucleotide" as used herein refers to a short, usually single-stranded, synthetic polynucleotide, which is usually, but not necessarily, less than about 200 nucleotides in length. The terms "oligonucleotide" and "polynucleotide" are not mutually exclusive. The above description for polynucleotide applies equally and fully to oligonucleotide. Cells that produce the binding molecules of the disclosure can include parental hybridoma cells, as well as bacterial and eukaryotic host cells into which nucleic acids encoding the antibodies have been introduced. Unless otherwise indicated, the left-hand end of any single-stranded polynucleotide sequence as disclosed herein is the 5' terminus; the left-hand direction of a double-stranded polynucleotide sequence is referred to as the 5' direction. The direction of 5' to 3' addition of nascent RNA transcripts is referred to as the transcriptional direction; sequence regions on the DNA strand having the same sequence as the RNA transcript are referred to as "upstream sequences" to the 5' end of the RNA transcript; sequence regions on the DNA strand having the same sequence as the RNA transcript are referred to as "downstream sequences" to the 3' end of the RNA transcript.

[0093] An "isolated nucleic acid" is a nucleic acid (e.g., RNA, DNA, or mixed nucleic acid) that is substantially separated from other genomic DNA sequences and proteins or complexes (such as ribosomes and polymerases) that naturally accompany the native sequence. An "isolated" nucleic acid molecule is one that is separated from other nucleic acid molecules present in the natural source of the nucleic acid molecule. In addition, an "isolated" nucleic acid molecule, such as a cDNA molecule, can be substantially free of other cellular material, or culture medium when produced by recombinant techniques, or substantially free of chemical precursors or other chemicals when chemically synthesized. In particular embodiments, one or more nucleic acid molecules encoding an antibody as described herein are isolated or purified. The term includes nucleic acid sequences that have been removed from their naturally occurring environment and includes recombinant or cloned DNA molecules and chemical syntheses or biologically synthesized analogs. A substantially pure molecule can include an isolated form of the molecule. In particular, an "isolated" nucleic acid molecule encoding an antibody described herein is a nucleic acid molecule that is identified and separated from at least one contaminant nucleic acid molecule with which it is ordinarily associated in the

[0094] Unless otherwise specified, a "nucleotide sequence encoding an amino acid sequence" includes all nucleotide sequences, which result in the encoding of the amino acid sequence, due to the genetic code. The phrase nucleotide sequence encoding a protein or an RNA can also include introns to the extent that the coding nucleotide sequence for the protein can contain introns in certain forms.

[0095] The term "control sequences" refers to DNA sequences necessary for the expression of an operably linked coding sequence in a particular host organism. The control sequences that are appropriate for a given host organism are readily identifiable and are well known in the art. For example, suitable control sequences for use in prokaryotic microorganisms include promoter, optionally an operator sequence, and a ribosome binding site. Eukaryotic cells are known to utilize promoters, polyadenylation signals, and enhancers.

[0096] As used herein, the term "operably linked" and similar phrases (e.g., in a gene fusion) when used in reference to nucleic acids or amino acids, refers to the operable linkage of nucleic acid sequences or amino acid sequences in a functional relationship to one another. For example, operably linked promoter, enhancer elements, open reading frames, 5' and 3' UTRs, and terminator sequences result in the accurate production of a nucleic acid molecule (e.g., RNA). In some embodiments, operably linked nucleic acid elements result in the transcription of an open reading frame and ultimately the production of a polypeptide (i.e., expression of the open reading frame). As another example, operably linked peptides are peptides in which functional domains are placed at appropriate distances from one another to impart the intended function of each domain.

[0097] The term "vector" refers to an agent that is used to carry or comprise a nucleic acid sequence, including, for example, a nucleic acid sequence encoding a binding molecule (e.g., an antibody) as described herein, in order to introduce the nucleic acid sequence into a host cell. Vectors suitable for use include, for example, expression vectors, plasmids, phage vectors, viral vectors, episomes, and artificial chromosomes, which can include a selection sequence or marker that is operable for stable integration into the host cell chromosome. Additionally, the vector can include one or more selection marker genes and appropriate expression control sequences. Selection marker genes that can be included, for example, provide resistance to antibiotics or toxins, complement auxotrophic deficiencies, or supply critical nutrients not in the culture media. Expression control sequences can include constitutive and inducible promoters, transcription enhancers, transcription terminators, and the like, which are well known in the art. When two or more nucleic acid molecules are to be co-expressed (e.g., both an antibody heavy and light chain or both an antibody VH and VL), the two nucleic acid molecules can be inserted, for example, into a single expression vector or into separate expression vectors. For single vector expression, the encoding nucleic acids can be operably linked to one common expression control sequence or to different expression control sequences, such as one inducible promoter and one constitutive promoter. Confirmation that a nucleic acid molecule has been introduced into a host cell can be made using methods well known in the art. Such methods include, for example, nucleic acid analysis (such as Northern blotting of mRNA or polymerase chain reaction (PCR) amplification), immunoblotting of gene product expression, or other suitable analytical methods that test for expression of the introduced nucleic acid sequence or its corresponding gene product. It will be understood by one of ordinary skill in the art that the nucleic acid molecule is expressed in an amount sufficient to produce the desired product, and it will further be understood that expression levels can be optimized using methods well known in the art to obtain sufficient expression.

[0098] The term "host" as used herein refers to an animal, such as a mammal (e.g., a human).

[0099] The term "host cell" as used herein refers to a particular subject cell that can be transfected with a nucleic acid molecule, as well as the progeny or potential progeny of such a cell. Progeny of a cell may

[0100] The term "transfected" or "transformed" or "transduced" as used herein refers to the process of transferring or introducing an exogenous nucleic acid into a host cell. A "transfected" or "transformed" or "transduced" cell is a cell that has been transfected, transformed, or transduced with an exogenous nucleic acid. The cell includes the original subject cell, as well as its progeny.

[0101] The term "pharmaceutically acceptable" means approved by a regulatory agency of the Federal or a state government or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia for use in humans or animals. United States Pharmacopeia 、 European PharmacopeiaRemington’s Pharmaceutical Sciences or other generally recognized pharmacopeia for use in animals and more particularly in humans.

[0102] “Excipient” means a pharmaceutically acceptable material, composition or vehicle, such as a liquid or solid filler, diluent, solvent or encapsulating material. Excipients include, for example, encapsulating materials or additives, such as absorption accelerators, antioxidants, binders, buffering agents, carriers, coatings, colorants, diluents, disintegrants, emulsifiers, effervescent agents, fillers, flavorants, humectants, lubricants, perfumes, preservatives, propellants, release agents, sterilants, sweeteners, solubilizers, wetting agents, and mixtures thereof. The term “excipient” can also refer to a diluent, adjuvant (e.g., Freund’s adjuvant (complete or incomplete)) or vehicle.

[0103] In some embodiments, the excipient is a pharmaceutically acceptable excipient. Examples of pharmaceutically acceptable excipients include buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid; low molecular weight (e.g., fewer than about 10 amino acid residues) polypeptides; proteins such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, arginine, or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugar alcohols such as mannitol or sorbitol; salt-forming counterions such as sodium; and / or nonionic surfactants such as TWEEN TM , polyethylene glycol (PEG), and PLURONICS TM . Other examples of pharmaceutically acceptable excipients are described in Remington and Gennaro, 5.2. Binding Molecules (18th Ed., 1990).

[0104] In one embodiment, each component is "pharmaceutically acceptable" in the sense of being compatible with the other ingredients of a pharmaceutical formulation and suitable for use in contact with the tissue or organ of humans and animals without excessive toxicity, irritation, allergic response, immunogenecity, or other problems or complications commensurate with a reasonable benefit / risk ratio. See, e.g., Lippincott Williams & Wilkins: Philadelphia, PA, 2005; Handbook of Pharmaceutical Excipients, 6thEdition; Rowe et al., Eds.; the Pharmaceutical Press and the American Pharmaceutical Association: 2009; Handbook of Pharmaceutical Additives, 3rdEdition; Ash and Ash, Eds.; Gower Publishing Company: 2007; Pharmaceutical Preformulation and Formulation, 2ndEdition; Gibson, Ed.; CRC Press LLC: Boca Raton, FL, 2009. In some embodiments, a pharmaceutically acceptable excipient is non-toxic to the cells or mammals exposed to it at the doses and concentrations employed. In some embodiments, a pharmaceutically acceptable excipient is an aqueous pH buffered solution.

[0105] In some embodiments, the excipient is a sterile liquid such as water and oils, including those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil and the like. Water is an exemplary excipient when the composition (e.g., pharmaceutical composition) is administered intravenously. Saline solutions and aqueous dextrose and glycerol solutions can also be employed as liquid excipients, particularly for injectable solutions. The excipient can further include starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, ethanol and the like. The composition, if desired, can also contain minor amounts of wetting or emulsifying agents, or pH buffering agents. The composition can take the form of solutions, suspensions, emulsion, tablets, pills, capsules, powders, sustained release formulations and the like. Oral composition (including formulation) can include standard excipients such as, for example, pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharin, cellulose, magnesium carbonate, etc.

[0106] Compositions, including pharmaceutical compounds, can contain a prophylactically or therapeutically effective amount of, for example, a LILRB1 and / or LILRB2 binding agent (e.g., an antibody) in isolated or purified form, and a suitable amount of excipient(s) so as to provide the form for proper administration to a subject, e.g., a patient. The formulation should suit the mode of administration.

[0107] An “effective amount” is generally an amount that is sufficient to reduce the severity and / or frequency of symptoms, eliminate symptoms and / or their underlying cause, prevent or delay occurrence of symptoms and / or their underlying cause, and / or ameliorate or remedy damage caused or related to a disease, disorder, or condition. In some embodiments, an effective amount is a therapeutically effective amount or a prophylactically effective amount.

[0108] As used herein, the term “therapeutically effective amount” refers to the amount of an agent (e.g., an antibody described herein or any other agent described herein) that is sufficient to reduce and / or ameliorate the severity and / or duration of a given disease, disorder, or condition and / or symptoms associated therewith. A therapeutically effective amount of an agent, including a therapeutic agent, can be an amount required to: (i) reduce, delay or ameliorate progression or course of a given disease, disorder, or condition, (ii) reduce, delay or ameliorate recurrence, development or onset of a given disease, disorder, or condition, and / or (iii) improve or enhance the prophylactic or therapeutic effect(s) of another therapy (e.g., a therapy other than administration of an antibody described herein). A “therapeutically effective amount” of a substance / molecule / agent (e.g., an anti-LILRB1 antibody, an anti-LILRB2 antibody, or a multi-specific antibody that binds to both LILRB1 and LILRB2) of the present disclosure can vary depending on such factors as the disease state, age, sex, and weight of the individual, and the ability of the substance / molecule / agent to elicit a desired response in the individual. A therapeutically effective amount encompasses an amount in which the therapeutic benefits exceed any toxic or deleterious effects of the substance / molecule / agent. In certain embodiments, the term “therapeutically effective amount” refers to the amount of a binding agent effective to “treat” a disease, disorder, or condition in a subject or mammal.

[0109] The terms “subject” and “patient” are used interchangeably. As used herein, in certain embodiments, a subject is a mammal, such as a non-primate mammal or a primate (e.g., a human). In specific embodiments, a subject is a human. In one embodiment, a subject is a mammal (e.g., a human) diagnosed with a disease or disorder. In another embodiment, a subject is a mammal (e.g., a human) at risk of developing a disease or disorder.

[0110] “Administer” or “administration” refers to the act of injecting or otherwise physically delivering a substance that is present outside of the body into the body of a patient, such as by mucosal, intradermal, intravenous, intramuscular delivery, and / or any other physical delivery method described herein or known in the art.

[0111] As used herein, the term “treatment” refers to reducing or ameliorating the progression, severity, and / or duration of a given disease, disorder, or condition and / or symptoms associated therewith, such as (i) reducing, delaying or ameliorating the progression or course of a given disease, disorder, or condition, (ii) reducing, delaying or ameliorating the recurrence, development or onset of a given disease, disorder, or condition, and / or (iii) improving or enhancing the prophylactic or therapeutic effect of another therapy (e.g., a therapy other than administration of a binding agent described herein). The term “treatment” includes management and amelioration of a disease. The terms “manage,” “managing,” and “management” refer to the beneficial effects a subject experiences from a therapy that does not necessarily result in a cure of the disease.

[0112] A “prophylactically effective amount” is the amount of a pharmaceutical composition that, when administered to a subject, will have the intended prophylactic effect (e.g., preventing or delaying the onset (or recurrence) of a disease, disorder, or condition, or reducing the likelihood of the onset (or recurrence) of a disease, disorder, or condition or associated symptoms).

[0113] A complete therapeutic or prophylactic effect does not necessarily occur by administration of one dose and can only occur after administration of a series of doses. Thus, a therapeutically or prophylactically effective amount can be administered in one or more administrations.

[0114] The terms “prevent,” “preventing,” and “prevention” refer to reducing the likelihood of the onset (or recurrence) of a disease, disorder, condition, or associated symptoms (e.g., diabetes or cancer).

[0115] As used herein, the term “immune response” includes responses from both the innate immune system and the adaptive immune system. It includes cell-mediated responses and / or humoral immune responses. It includes both T cell and B cell responses, as well as responses from other cells of the immune system, such as natural killer (NK) cells, monocytes, macrophages, dendritic cells, etc.

[0116] As used herein, to "delay" the development of a cancer means to postpone, hinder, slow, retard, stabilize, and / or defer the development of the disease. This delay can be of varying lengths of time, depending on the history of the disease and / or the individual being treated. As will be apparent to those of ordinary skill in the art, a sufficient or significant delay can in effect encompass prevention, in that the individual does not develop the disease. A method that "delays" the development of a cancer is a method that, when compared to not using the method, decreases the likelihood of the disease developing in a given timeframe and / or decreases the extent of the disease in a given timeframe. Such comparisons are typically based on clinical studies, using statistically significant numbers of individuals. Development of a cancer can be detected using standard methods, including but not limited to computed axial tomography (CAT scan), magnetic resonance imaging (MRI), abdominal ultrasound, coagulation testing, arteriography, or biopsy. Development can also refer to progression of a cancer that can not initially be detectable, and includes occurrence, recurrence, and onset.

[0117] The terms "about" and "approximately" mean within 20%, within 15%, within 10%, within 9%, within 8%, within 7%, within 6%, within 5%, within 4%, within 3%, within 2%, within 1%, or less of a given value or range.

[0118] As used herein, comparative terms such as reduce, decrease, increase, or any grammatical variation thereof, as used herein, can refer to some change from a reference. In some embodiments, such change can refer to about 10%, or about 20%, or about 30%, or about 40%, or about 50%, or about 60%, or about 70%, or about 80%, or about 90% higher than the reference, or about 1-fold, or about 2-fold, or about 3-fold, or about 4-fold, or about 5-fold, or about 10-fold, or about 20-fold, or about 30-fold, or about 40-fold, or about 100-fold or more. In some embodiments, such change can refer to about 1%, or about 2%, or about 3%, or about 4%, or about 5%, or about 6%, or about 7%, or about 8%, or about 9%, or about 10%, or about 20%, or about 30%, or about 40%, or about 50%, or about 60%, or about 70%, or about 80%, or about 90%, or about 95%, or about 96%, or about 97%, or about 98%, or about 99% of the reference.

[0119] As used in this disclosure and claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0120] In some embodiments, the terms "first," "second," "third," "fourth," and like terms in component names are used to distinguish and identify more than one component sharing a particular identity in their names. For example, "first antibody" and "second antibody" are used to distinguish two antibodies.

[0121] It should be understood that wherever embodiments are described herein using the term "comprising" or "containing", other similar embodiments described using the terms "consisting of and / or "consisting essentially of are also provided. It should also be understood that wherever embodiments are described herein using the phrase "consisting essentially of, other similar embodiments described using the phrase "consisting of are also provided.

[0122] The term "between" as used in a phrase such as "between A and B" or "between A and B" means a range that includes both A and B.

[0123] The term "and / or" as used herein in a phrase such as "A and / or B" is intended to encompass both A and B. A or B; A (alone); and B (alone). Likewise, the term "and / or" as used in a phrase such as "A, B, and / or C" is intended to encompass each of the following embodiments: A, B, and C; A, B, or C; A or C; A or B; B or C; A and C; A and B; B and C; A (alone); B (alone); and C (alone).

[0124] The term "optional" or "optionally" means that the subsequent description can or can not occur, so that the description includes instances where the situation occurs and instances where it does not.

[0125] 5.2.1. Antibodies that bind to LILRB1

[0126] 5.2.2. Antibodies that bind to LILRB2

[0127] In one aspect, provided herein are binding agents (e.g., antibodies, including fragments thereof) that are capable of binding to LILRB1. In some embodiments, the antibodies provided herein bind to human LILRB1. In some embodiments, the antibodies provided herein bind to Rhesus LILRB1. In some embodiments, the antibodies provided herein bind to cynomolgus LILRB1.

[0128] As used herein, LILRB1 refers to a LILRB1 polypeptide, a LILRB1 polypeptide fragment, a LILRB1 peptide, or a LILRB1 epitope. In some embodiments, a LILRB1 binding agent is derived from a human or humanized antibody (e.g., comprising a human framework region) that binds LILRB1 (including a LILRB1 polypeptide, a LILRB1 polypeptide fragment, a LILRB1 peptide, or a LILRB1 epitope). In some embodiments, a binding agent (e.g., an antibody, including fragments thereof) can bind to LILRB1 expressed on the surface of a mammalian (e.g., human) cell, including an immune cell (e.g., an NK cell or a T cell) that expresses LILRB1. In some embodiments, a binding agent (e.g., an antibody, including fragments thereof) provided herein binds to a LILRB1 extracellular epitope exposed on a cell, such as an immune cell. In some embodiments, a binding agent (e.g., an antibody, including fragments thereof) that binds to LILRB1 (such as human LILRB1 or a portion thereof) is described herein. In some embodiments, LILRB1 is human LILRB1. In some embodiments, a binding agent provided herein is a human LILRB1 binding agent (e.g., an antibody that binds to human LILRB1).

[0129] In some embodiments, the anti-LILRB1 antibody provided herein is an antagonist antibody. In one embodiment, the antibody according to this disclosure is a LILRB1 antagonist that has no agonistic activity or low agonistic activity. In another embodiment, an antibody or functional fragment comprising an antigen-binding moiety binds to the target protein LILRB1 and reduces the binding of a LILRB1 ligand to LILRB1 to a basal level. In one aspect of this embodiment, the antibody or functional fragment reduces the amount of ligand bound to LILRB1. In another aspect of this embodiment, the antibody or functional fragment completely prevents the binding of a LILRB1 ligand to LILRB1. In some embodiments, the ligand is an MHC I molecule. In some embodiments, the ligand is HLA-A2. In some embodiments, the ligand is HLA-G. In some embodiments, the anti-LILRB1 antibody or functional fragment provided herein inhibits one or more of these LILRB1 functional properties. As determined according to the methods known in the art and described herein, antibodies that inhibit one or more of these LILRB1 functional properties (e.g., biochemical, immunochemical, cellular, physiological, or other biological activities) will be understood to be associated with a statistically significant reduction in a specific activity observed in the absence of an antibody (e.g., or when a control antibody of unrelated specificity is present). In some embodiments, antibodies inhibiting LILRB1 activity achieve at least 10%, at least 50%, 80%, or 90% of such a statistically significant reduction in the measured parameter, and in some embodiments, the antibodies of this disclosure inhibit greater than 95%, 98%, or 99% of LILRB1 functional activity.

[0130] In some embodiments, the anti-LILRB1 antibody provided herein is available in quantities of ≤1 μM, ≤100 nM, ≤10 nM, ≤1 nM, ≤0.1 nM, ≤0.01 nM, or ≤0.001 nM (e.g., 10 μM). -8 M or smaller, such as 10 -8 M to 10 -13 M, for example, 10 -9 M to 10 -13 The dissociation constant (K) of M) D The antibody binds to LILRB1 (e.g., human LILRB1). Various methods for measuring binding affinity are known in the art, any of which can be used for the purposes of this disclosure, including by RIA, for example with the Fab form of the antibody of interest and its antigen (Chen et al., 1999, J. Mol Biol 293:865-81); by biolayer interferometry (BLI) or surface plasmon resonance (SPR) assays, and by... (using examples) Red96 system) or via (using, e.g., TM-2000, or TM-3000). The "on-rate" or "rate of association" or "association rate" or "kon" can also be determined using the same Biolayer Interferometry (BLI) or Surface Plasmon Resonance (SPR) techniques described above using, e.g., Red96, TM-2000, TM-3000 system, TM-8K, or TM-8K+ system.

[0131] In one embodiment, the anti-LILRB1 antibodies of the present disclosure do not cross-react with one or more LILRB or LILRA family members (e.g., LILRB2, LILRA1, LILRA2, etc.). In one embodiment, the anti-LILRB1 antibodies of the present disclosure cross-react with one or more LILRB and LILRA family members (e.g., LILRB2, LILRA1, LILRA2, etc.).

[0132] In some embodiments, the anti-LILRB1 antibodies provided herein are those described in Section 7, below. Accordingly, in some embodiments, the antibodies provided herein comprise one or more CDR sequences of any of SEQ ID NOs: 283-400 and 1155-1166. The CDR sequences can be determined according to well-known numbering systems. In some embodiments, the CDRs are numbered according to IMGT. In some embodiments, the CDRs are numbered according to Kabat. In some embodiments, the CDRs are numbered according to AbM. In other embodiments, the CDRs are numbered according to Chothia. In other embodiments, the CDRs are numbered according to Contact. In some embodiments, the anti-LILRB1 antibodies are humanized. In some embodiments, the anti-LILRB1 antibodies comprise an acceptor human framework, e.g., a human immunoglobulin framework or a human consensus framework.

[0133] In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 283. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 285. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 287. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 289. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 291. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 293. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 295. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 297. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 299. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 301. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 303. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 305. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 307.In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 309. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 311. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 313. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 315. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 317. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 319. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 321. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 323. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 325. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 327. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 329. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 331. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 333.In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 335. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 337. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 339. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 341. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 343. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 345. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 347. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 349. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 351. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 353. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 355. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 357. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 359.In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 361. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 363. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 365. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 367. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 369. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 371. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 373. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 375. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 377. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 379. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 381. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 383. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 385.In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 387. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 389. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 391. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 393. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 395. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 397. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 399. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 1155. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 1157. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 1159. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 1161. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 1163. In some embodiments, an anti-LILRB1 antibody provided herein comprises an HCDR1, an HCDR2, and an HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 1165. The CDR sequences can be determined according to well-known numbering systems or combinations thereof. In some embodiments, the CDRs are numbered according to IMGT numbering.In some embodiments, the CDRs are numbered according to Kabat. In some embodiments, the CDRs are numbered according to AbM. In other embodiments, the CDRs are numbered according to Chothia. In other embodiments, the CDRs are numbered according to Contact.

[0134] In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 284. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 286. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 288. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 290. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 292. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 294. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 296. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 298. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 300. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 302. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 304. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 306. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 308.In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 310. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 312. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 314. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 316. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 318. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 320. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 322. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 324. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 326. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 328. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 330. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 332. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 334.In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 336. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 338. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 340. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 342. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 344. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 346. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 348. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 350. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 352. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 354. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 356. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 358. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 360.In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 362. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 364. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 366. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 368. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 370. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 372. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 374. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 376. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 378. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 380. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 382. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 384. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 386.In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 388. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 390. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 392. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 394. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 396. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 398. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 400. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 1156. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 1158. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 1160. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 1162. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 1164. In some embodiments, an anti-LILRB1 antibody provided herein comprises a LCDR1, a LCDR2, and a LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 1166. The CDR sequences can be determined according to well-known numbering systems or combinations thereof. In some embodiments, the CDRs are numbered according to IMGT numbering.In some embodiments, the CDRs are numbered according to Kabat. In some embodiments, the CDRs are numbered according to AbM. In other embodiments, the CDRs are numbered according to Chothia. In other embodiments, the CDRs are numbered according to Contact.

[0135] In some embodiments, the antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 283, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 284. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 283, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 284.

[0136] In some embodiments, the antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 285, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 286. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 285, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 286.

[0137] In some embodiments, the antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 287, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 288. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 287, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 288.

[0138] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 289, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 290. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 289, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 290.

[0139] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 291, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 292. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 291, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 292.

[0140] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 293, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 294. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 293, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 294.

[0141] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 295, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 296. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 295, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 296.

[0142] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 297, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 298. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 297, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 298.

[0143] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 299, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 300. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 299, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 300.

[0144] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 301, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 302. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 301, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 302.

[0145] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 303, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 304. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 303, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 304.

[0146] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 305, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 306. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 305, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 306.

[0147] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 307, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 308. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 307, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 308.

[0148] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 309, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 310. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 309, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 310.

[0149] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 311, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 312. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 311, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 312.

[0150] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 313, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 314. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 313, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 314.

[0151] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 315, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 316. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 315, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 316.

[0152] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 317, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 318. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 317, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 318.

[0153] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 319, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 320. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 319, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 320.

[0154] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 321, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 322. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 321, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 322.

[0155] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 323, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 324. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 323, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 324.

[0156] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 325, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 326. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 325, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 326.

[0157] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 327, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 328. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 327, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 328.

[0158] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 329, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 330. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 329, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 330.

[0159] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 331, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 332. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 331, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 332.

[0160] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 333, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 334. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 333, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 334.

[0161] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 335, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 336. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 335, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 336.

[0162] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 337, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 338. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 337, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 338.

[0163] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 339, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 340. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 339, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 340.

[0164] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 341, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 342. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 341, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 342.

[0165] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 343, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 344. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 343, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 344.

[0166] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 345, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 346. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 345, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 346.

[0167] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 347, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 348. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 347, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 348.

[0168] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 349, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 350. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 349, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 350.

[0169] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 351, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 352. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 351, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 352.

[0170] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 353, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 354. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 353, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 354.

[0171] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 355, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 356. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 355, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 356.

[0172] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 357, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 358. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 357, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 358.

[0173] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 359, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 360. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 359, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 360.

[0174] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 361, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 362. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 361, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 362.

[0175] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 363, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 364. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 363, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 364.

[0176] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 365, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 366. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 365, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 366.

[0177] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 367, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 368. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 367, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 368.

[0178] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 369, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 370. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 369, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 370.

[0179] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 371, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 372. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 371, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 372.

[0180] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 373, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 374. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 373, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 374.

[0181] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 375, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 376. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 375, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 376.

[0182] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 377, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 378. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 377, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 378.

[0183] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 379, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 380. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 379, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 380.

[0184] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 381, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 382. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 381, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 382.

[0185] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 383, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 384. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 383, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 384.

[0186] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 385, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 386. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 385, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 386.

[0187] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 387, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 388. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 387, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 388.

[0188] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 389, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 390. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 389, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 390.

[0189] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 391, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 392. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 391, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 392.

[0190] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 393, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 394. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 393, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 394.

[0191] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 395, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 396. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 395, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 396.

[0192] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 397, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 398. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 397, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 398.

[0193] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 399, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 400. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 399, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 400.

[0194] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 1155, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 1156. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 1155, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 1156.

[0195] In some embodiments, an antibody or antigen-binding fragment provided herein comprises an HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 1157, and / or an LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 1158. In some embodiments, an antibody or antigen-binding fragment provided herein comprises an HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 1157, and an LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 1158.

[0196] In some embodiments, an antibody or antigen-binding fragment provided herein comprises an HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 1159, and / or an LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 1160. In some embodiments, an antibody or antigen-binding fragment provided herein comprises an HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 1159, and an LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 1160.

[0197] In some embodiments, an antibody or antigen-binding fragment provided herein comprises an HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 1161, and / or an LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 1162. In some embodiments, an antibody or antigen-binding fragment provided herein comprises an HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 1161, and an LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 1162.

[0198] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 1163, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 1164. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 1163, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 1164.

[0199] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and / or HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 1165, and / or a LCDR1, LCDR2, and / or LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 1166. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a HCDR1, HCDR2, and HCDR3 as shown in a VH comprising the amino acid sequence of SEQ ID NO: 1165, and a LCDR1, LCDR2, and LCDR3 as shown in a VL comprising the amino acid sequence of SEQ ID NO: 1166.

[0200] CDR sequences can be determined according to well-known numbering systems, or combinations thereof. In some embodiments, the CDRs are numbered according to IMGT. In some embodiments, the CDRs are numbered according to Rabat. In some embodiments, the CDRs are numbered according to AbM. In other embodiments, the CDRs are numbered according to Chothia. In other embodiments, the CDRs are numbered according to Contact.

[0201] In other embodiments, provided herein is an antibody that binds to LILRB1, the antibody comprising (a) a VH region, the VH region comprising (i) a HCDR1 comprising an amino acid sequence that has at least 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with any one of SEQ ID NOs: 495, 501, 507, 513, 519, 525, 531, 537, 543, 549, 555, 561, 567, 573, 579, 585, 591, 597, 603, 609, 615, 621, 627, 633, 639, 645, 651, 657, 663, 669, 675, 681, 687, 693, 699, 705, 711, 717, 723, 729, 735, 741, 747, 753, 759, 765, 771, 777, 783, 789, 795, 801, 807, 813, 819, 825, 831, 837, and 843; (ii) a HCDR2 comprising an amino acid sequence that has at least 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with any one of SEQ ID NOs: 496, 502, 508, 514, 520, 526, 532, 538, 544, 550, 556, 562, 568, 574, 580, 586, 592, 598, 604, 610, 616, 622, 628, 634, 640, 646, 652, 658, 664, 670, 676, 682, 688, 694, 700, 706, 712, 718, 724, 730, 736, 742, 748, 754, 760, 766, 772, 778, 784, 790, 796, 802, 808, 814, 820, 826, 832, 838, and 844;(iii) a HCDR3 comprising an amino acid sequence that has at least 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with any one of SEQ ID NOs: 497, 503, 509, 515, 521, 527, 533, 539, 545, 551, 557, 563, 569, 575, 581, 587, 593, 599, 605, 611, 617, 623, 629, 635, 641, 647, 653, 659, 665, 671, 677, 683, 689, 695, 701, 707, 713, 719, 725, 731, 737, 743, 749, 755, 761, 767, 773, 779, 785, 791, 797, 803, 809, 815, 821, 827, 833, 839, 845, and 1179; and / or (b) a VL region comprising (i) an LCDR1 comprising an amino acid sequence that has at least 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with any one of SEQ ID NOs: 498, 504, 510, 516, 522, 528, 534, 540, 546, 552, 558, 564, 570, 576, 582, 588, 594, 600, 606, 612, 618, 624, 630, 636, 642, 648, 654, 660, 666, 672, 678, 684, 690, 696, 702, 708, 714, 720, 726, 732, 738, 744, 750, 756, 762, 768, 774, 780, 786, 792, 798, 804, 810, 816, 822, 828, 834, 840, and 846;(ii) a LCDR2 comprising an amino acid sequence having at least 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to any one of SEQ ID NOs: 499, 505, 511, 517, 523, 529, 535, 541, 547, 553, 559, 565, 571, 577, 583, 589, 595, 601, 607, 613, 619, 625, 631, 637, 643, 649, 655, 661, 667, 673, 679, 685, 691, 697, 703, 709, 715, 721, 727, 733, 739, 745, 751, 757, 763, 769, 775, 781, 787, 793, 799, 805, 811, 817, 823, 829, 835, 841, 847, and 1281; and (iii) a LCDR3 comprising an amino acid sequence having at least 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100% sequence identity to any one of SEQ ID NOs: 500, 506, 512, 518, 524, 530, 536, 542, 548, 554, 560, 566, 572, 578, 584, 590, 596, 602, 608, 614, 620, 626, 632, 638, 644, 650, 656, 662, 668, 674, 680, 686, 692, 698, 704, 710, 716, 722, 728, 734, 740, 746, 752, 758, 764, 770, 776, 782, 788, 794, 800, 806, 812, 818, 824, 830, 836, 842, and 848. In some embodiments, the anti-LILRB1 antibody is humanized. In some embodiments, the anti-LILRB1 antibody comprises an acceptor human framework, e.g., a human immunoglobulin framework or a human consensus framework.

[0202] In some specific embodiments, in the antibody or antigen binding fragment provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 495, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 496, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 497, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 498, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 499, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 500.

[0203] In some embodiments, in the antibodies or antigen binding fragments provided herein, HCDR1 comprises the amino acid sequence of SEQ ID NO: 501, HCDR2 comprises the amino acid sequence of SEQ ID NO: 502, HCDR3 comprises the amino acid sequence of SEQ ID NO: 503, LCDR1 comprises the amino acid sequence of SEQ ID NO: 504, LCDR2 comprises the amino acid sequence of SEQ ID NO: 505, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 506.

[0204] In some embodiments, in the antibodies or antigen binding fragments provided herein, HCDR1 comprises the amino acid sequence of SEQ ID NO: 507, HCDR2 comprises the amino acid sequence of SEQ ID NO: 508, HCDR3 comprises the amino acid sequence of SEQ ID NO: 509, LCDR1 comprises the amino acid sequence of SEQ ID NO: 510, LCDR2 comprises the amino acid sequence of SEQ ID NO: 511, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 512.

[0205] In some embodiments, in the antibodies or antigen binding fragments provided herein, HCDR1 comprises the amino acid sequence of SEQ ID NO: 513, HCDR2 comprises the amino acid sequence of SEQ ID NO: 514, HCDR3 comprises the amino acid sequence of SEQ ID NO: 515, LCDR1 comprises the amino acid sequence of SEQ ID NO: 516, LCDR2 comprises the amino acid sequence of SEQ ID NO: 517, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 518.

[0206] In some embodiments, in the antibodies or antigen binding fragments provided herein, HCDR1 comprises the amino acid sequence of SEQ ID NO: 519, HCDR2 comprises the amino acid sequence of SEQ ID NO: 520, HCDR3 comprises the amino acid sequence of SEQ ID NO: 521, LCDR1 comprises the amino acid sequence of SEQ ID NO: 522, LCDR2 comprises the amino acid sequence of SEQ ID NO: 523, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 524.

[0207] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 525, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 526, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 527, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 528, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 529, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 530.

[0208] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 531, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 532, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 533, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 534, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 535, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 536.

[0209] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 537, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 538, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 539, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 540, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 541, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 542.

[0210] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 543, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 544, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 545, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 546, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 547, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 548.

[0211] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 549, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 550, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 551, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 552, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 553, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 554.

[0212] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 555, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 556, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 557, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 558, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 559, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 560.

[0213] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 561, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 562, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 563, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 564, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 565, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 566.

[0214] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 567, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 568, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 569, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 570, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 571, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 572.

[0215] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 573, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 574, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 575, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 576, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 577, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 578.

[0216] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 579, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 580, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 581, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 582, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 583, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 584.

[0217] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 585, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 586, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 587, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 588, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 589, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 590.

[0218] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 591, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 592, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 593, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 594, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 595, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 596.

[0219] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 597, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 598, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 599, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 600, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 601, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 602.

[0220] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 603, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 604, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 605, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 606, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 607, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 608.

[0221] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 609, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 610, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 611, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 612, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 613, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 614.

[0222] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 615, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 616, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 617, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 618, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 619, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 620.

[0223] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 621, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 622, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 623, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 624, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 625, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 626.

[0224] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 627, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 628, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 629, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 630, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 631, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 632.

[0225] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 633, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 634, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 635, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 636, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 637, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 638.

[0226] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 639, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 640, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 641, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 642, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 643, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 644.

[0227] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 645, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 646, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 647, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 648, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 649, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 650.

[0228] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 651, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 652, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 653, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 654, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 655, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 656.

[0229] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 657, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 658, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 659, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 660, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 661, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 662.

[0230] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 663, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 664, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 665, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 666, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 667, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 668.

[0231] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 669, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 670, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 671, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 672, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 673, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 674.

[0232] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 675, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 676, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 677, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 678, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 679, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 680.

[0233] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 681, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 682, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 683, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 684, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 685, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 686.

[0234] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 687, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 688, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 689, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 690, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 691, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 692.

[0235] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 693, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 694, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 695, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 696, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 697, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 698.

[0236] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 699, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 700, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 701, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 702, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 703, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 704.

[0237] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 705, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 706, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 707, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 708, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 709, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 710.

[0238] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 711, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 712, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 713, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 714, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 715, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 716.

[0239] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 717, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 718, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 719, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 720, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 721, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 722.

[0240] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 723, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 724, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 725, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 726, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 727, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 728.

[0241] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 729, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 730, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 731, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 732, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 733, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 734.

[0242] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 735, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 736, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 737, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 738, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 739, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 740.

[0243] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 741, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 742, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 743, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 744, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 745, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 746.

[0244] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 747, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 748, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 749, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 750, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 751, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 752.

[0245] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 753, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 754, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 755, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 756, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 757, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 758.

[0246] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 759, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 760, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 761, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 762, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 763, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 764.

[0247] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 765, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 766, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 767, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 768, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 769, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 770.

[0248] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 771, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 772, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 773, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 774, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 775, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 776.

[0249] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 777, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 778, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 779, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 780, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 781, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 782.

[0250] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 783, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 784, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 785, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 786, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 787, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 788.

[0251] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 789, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 790, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 791, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 792, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 793, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 794.

[0252] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 795, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 796, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 797, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 798, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 799, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 800.

[0253] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 801, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 802, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 803, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 804, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 805, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 806.

[0254] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 807, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 808, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 809, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 810, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 811, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 812.

[0255] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 813, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 814, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 815, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 816, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 817, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 818.

[0256] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 819, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 820, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 821, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 822, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 823, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 824.

[0257] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 825, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 826, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 827, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 828, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 829, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 830.

[0258] In some embodiments, in the antibodies or antigen binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 831, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 832, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 833, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 834, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 835, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 836.

[0259] In some embodiments, in the antibodies or antigen-binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 837, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 838, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 839, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 840, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 841, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 842.

[0260] In some embodiments, in the antibodies or antigen-binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 843, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 844, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 845, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 846, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 847, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 848.

[0261] In some embodiments, in the antibodies or antigen-binding fragments provided herein, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 543, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 544, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 1179, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 546, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 1281, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 548.

[0262] In some embodiments, the antibody further comprises one or more framework regions of SEQ ID NOs: 283-400 and 1155-1166.

[0263] In some embodiments, an antibody provided herein is a humanized antibody. The framework regions described herein are determined based on the boundaries of the CDR numbering system. In other words, if the CDRs are determined by, e.g., Kabat, IMGT, or Chothia, the framework regions are the amino acid residues in the variable region in the order of FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4 that surround the CDRs from N-terminus to C-terminus. For example, FR1 is defined as the amino acid residues N-terminal to the CDR1 amino acid residues as defined by, e.g., the Kabat numbering system, the IMGT numbering system, or the Chothia numbering system, FR2 is defined as the amino acid residues between the CDR1 amino acid residues and the CDR2 amino acid residues as defined by, e.g., the Kabat numbering system, the IMGT numbering system, or the Chothia numbering system, FR3 is defined as the amino acid residues between the CDR2 amino acid residues and the CDR3 amino acid residues as defined by, e.g., the Kabat numbering system, the IMGT numbering system, or the Chothia numbering system, and FR4 is defined as the amino acid residues C-terminal to the CDR3 amino acid residues as defined by, e.g., the Kabat numbering system, the IMGT numbering system, or the Chothia numbering system.

[0264] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 283. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 284. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 283 and a VL comprising the amino acid sequence of SEQ ID NO: 284.

[0265] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 285. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 286. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 285 and a VL comprising the amino acid sequence of SEQ ID NO: 286.

[0266] In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 287. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 288. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 287 and a VL comprising the amino acid sequence of SEQ ID NO: 288.

[0267] In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 289. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 290. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 289 and a VL comprising the amino acid sequence of SEQ ID NO: 290.

[0268] In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 291. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 292. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 291 and a VL comprising the amino acid sequence of SEQ ID NO: 292.

[0269] In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 293. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 294. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 293 and a VL comprising the amino acid sequence of SEQ ID NO: 294.

[0270] In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 295. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 296. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 295 and a VL comprising the amino acid sequence of SEQ ID NO: 296.

[0271] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 297. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 298. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 297 and a VL comprising the amino acid sequence of SEQ ID NO: 298.

[0272] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 299. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 300. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 299 and a VL comprising the amino acid sequence of SEQ ID NO: 300.

[0273] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 301. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 302. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 301 and a VL comprising the amino acid sequence of SEQ ID NO: 302.

[0274] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 303. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 304. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 303 and a VL comprising the amino acid sequence of SEQ ID NO: 304.

[0275] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 305. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 306. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 305 and a VL comprising the amino acid sequence of SEQ ID NO: 306.

[0276] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 307. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 308. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 307 and a VL comprising the amino acid sequence of SEQ ID NO: 308.

[0277] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 309. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 310. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 309 and a VL comprising the amino acid sequence of SEQ ID NO: 310.

[0278] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 311. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 312. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 311 and a VL comprising the amino acid sequence of SEQ ID NO: 312.

[0279] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 313. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 314. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 313 and a VL comprising the amino acid sequence of SEQ ID NO: 314.

[0280] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 315. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 316. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 315 and a VL comprising the amino acid sequence of SEQ ID NO: 316.

[0281] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 317. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 318. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 317 and a VL comprising the amino acid sequence of SEQ ID NO: 318.

[0282] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 319. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 320. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 319 and a VL comprising the amino acid sequence of SEQ ID NO: 320.

[0283] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 321. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 322. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 321 and a VL comprising the amino acid sequence of SEQ ID NO: 322.

[0284] In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 323. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 324. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 323 and a VL comprising the amino acid sequence of SEQ ID NO: 324.

[0285] In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 325. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 326. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 325 and a VL comprising the amino acid sequence of SEQ ID NO: 326.

[0286] In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 327. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 328. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 327 and a VL comprising the amino acid sequence of SEQ ID NO: 328.

[0287] In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 329. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 330. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 329 and a VL comprising the amino acid sequence of SEQ ID NO: 330.

[0288] In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 331. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 332. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 331 and a VL comprising the amino acid sequence of SEQ ID NO: 332.

[0289] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 333. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 334. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 333 and a VL comprising the amino acid sequence of SEQ ID NO: 334.

[0290] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 335. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 336. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 335 and a VL comprising the amino acid sequence of SEQ ID NO: 336.

[0291] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 337. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 338. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 337 and a VL comprising the amino acid sequence of SEQ ID NO: 338.

[0292] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 339. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 340. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 339 and a VL comprising the amino acid sequence of SEQ ID NO: 340.

[0293] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 341. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 342. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 341 and a VL comprising the amino acid sequence of SEQ ID NO: 342.

[0294] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 343. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 344. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 343 and a VL comprising the amino acid sequence of SEQ ID NO: 344.

[0295] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 345. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 346. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 345 and a VL comprising the amino acid sequence of SEQ ID NO: 346.

[0296] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 347. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 348. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 347 and a VL comprising the amino acid sequence of SEQ ID NO: 348.

[0297] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 349. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 350. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 349 and a VL comprising the amino acid sequence of SEQ ID NO: 350.

[0298] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 351. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 352. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 351 and a VL comprising the amino acid sequence of SEQ ID NO: 352.

[0299] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 353. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 354. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 353 and a VL comprising the amino acid sequence of SEQ ID NO: 354.

[0300] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 355. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 356. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 355 and a VL comprising the amino acid sequence of SEQ ID NO: 356.

[0301] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 357. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 358. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 357 and a VL comprising the amino acid sequence of SEQ ID NO: 358.

[0302] In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 359. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 360. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 359 and a VL comprising the amino acid sequence of SEQ ID NO: 360.

[0303] In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 361. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 362. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 361 and a VL comprising the amino acid sequence of SEQ ID NO: 362.

[0304] In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 363. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 364. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 363 and a VL comprising the amino acid sequence of SEQ ID NO: 364.

[0305] In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 365. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 366. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 365 and a VL comprising the amino acid sequence of SEQ ID NO: 366.

[0306] In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 367. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 368. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 367 and a VL comprising the amino acid sequence of SEQ ID NO: 368.

[0307] In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 369. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 370. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 369 and a VL comprising the amino acid sequence of SEQ ID NO: 370.

[0308] In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 371. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 372. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 371 and a VL comprising the amino acid sequence of SEQ ID NO: 372.

[0309] In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 373. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 374. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 373 and a VL comprising the amino acid sequence of SEQ ID NO: 374.

[0310] In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 375. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 376. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 375 and a VL comprising the amino acid sequence of SEQ ID NO: 376.

[0311] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 377. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 378. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 377 and a VL comprising the amino acid sequence of SEQ ID NO: 378.

[0312] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 379. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 380. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 379 and a VL comprising the amino acid sequence of SEQ ID NO: 380.

[0313] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 381. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 382. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 381 and a VL comprising the amino acid sequence of SEQ ID NO: 382.

[0314] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 383. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 384. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 383 and a VL comprising the amino acid sequence of SEQ ID NO: 384.

[0315] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 385. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 386. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 385 and a VL comprising the amino acid sequence of SEQ ID NO: 386.

[0316] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 387. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 388. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 387 and a VL comprising the amino acid sequence of SEQ ID NO: 388.

[0317] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 389. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 390. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 389 and a VL comprising the amino acid sequence of SEQ ID NO: 390.

[0318] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 391. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 392. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 391 and a VL comprising the amino acid sequence of SEQ ID NO: 392.

[0319] In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 393. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 394. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 393 and a VL comprising the amino acid sequence of SEQ ID NO: 394.

[0320] In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 395. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 396. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 395 and a VL comprising the amino acid sequence of SEQ ID NO: 396.

[0321] In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 397. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 398. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 397 and a VL comprising the amino acid sequence of SEQ ID NO: 398.

[0322] In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 399. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 400. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 399 and a VL comprising the amino acid sequence of SEQ ID NO: 400.

[0323] In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 1155. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 1156. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 1155 and a VL comprising the amino acid sequence of SEQ ID NO: 1156.

[0324] In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 1157. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 1158. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 1157 and a VL comprising the amino acid sequence of SEQ ID NO: 1158.

[0325] In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 1159. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 1160. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 1159 and a VL comprising the amino acid sequence of SEQ ID NO: 1160.

[0326] In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 1161. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 1162. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 1161 and a VL comprising the amino acid sequence of SEQ ID NO: 1162.

[0327] In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 1163. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 1164. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 1163 and a VL comprising the amino acid sequence of SEQ ID NO: 1164.

[0328] In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 1165. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VL comprising the amino acid sequence of SEQ ID NO: 1166. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 1165 and a VL comprising the amino acid sequence of SEQ ID NO: 1166.

[0329] In certain embodiments, the antibody or antigen-binding fragment thereof described herein comprises an amino acid sequence having a certain percent identity relative to any of the antibodies provided herein (e.g., those described in Section 7, infra).

[0330] In certain embodiments, an antibody or antigen-binding fragment thereof described herein comprises an amino acid sequence having a certain percentage of identity (such as at least about 80%, or at least about 81%, or at least about 82%, or at least about 83%, or at least about 84%, or at least about 85%, or at least about 86%, or at least about 87%, or at least about 88%, or at least about 89%, or at least about 90%, or at least about 91%, or at least about 92%, or at least about 93%, or at least about 94%, or at least about 95%, or at least about 96%, or at least about 97%, or at least about 98%, or at least about 99% or more) relative to any antibody or fragment thereof provided herein (e.g., CDRs, VH, or VL in Tables 5-6 and 14-15). In some embodiments, an antibody or antigen-binding fragment thereof described herein comprises the CDRs of any antibody or fragment thereof provided herein (e.g., as described in Tables 5-6 and 14-15).

[0331] Determination of the percent identity between two sequences (e.g., amino acid sequences or nucleic acid sequences) can be accomplished using a mathematical algorithm. A non-limiting example of a mathematical algorithm that is suitable for comparing two sequences is the algorithm of Karlin and Altschul, Proc. Natl. Acad. Sci. U.S.A. 87:2264 2268 (1990), modified as in Karlin and Altschul, Proc. Natl. Acad. Sci. U.S.A. 90:5873 5877 (1993). Such an algorithm is incorporated in the NBLAST and XBLAST programs of Altschul et al., J. Mol. Biol. 215:403 (1990). BLAST nucleotide searches can be performed with the NBLAST nucleotide program parameters set to, e.g., score = 100, wordlength = 12 to obtain nucleotide sequences homologous to nucleic acid molecules described herein. BLAST protein searches can be performed with the XBLAST program parameters set to, e.g., score = 50, wordlength = 3 to obtain amino acid sequences homologous to protein molecules described herein. To obtain gapped alignments for comparison purposes, Gapped BLAST can be utilized as described in Altschul et al., Nucleic Acids Res. 25:3389 3402 (1997). In some embodiments, the percent identity between two sequences is determined by the number of residues, excluding or including conservative amino acid substitutions or degenerate nucleotide substitutions, that are different between the two sequences in an alignment of the two sequences over either (i) the full length of the shorter sequence, (ii) the full length of the longer sequence, (iii) the average length of the two sequences, (iv) the total length of the non-gapped portions of the alignment, (v) the length of the alignment not including overhangs, or (vi) the length of the alignment including overhangs. As used herein, overhangs with respect to a sequence alignment refer to either or both ends of the alignment in which residues of one sequence are considered to be aligned with no residues (i.e., a gap) in the other sequence. Alternatively, PSIBLAST can be used to perform an iterative search that detects distant relationships between molecules (Id.). When utilizing BLAST, gapped BLAST and PSI Blast programs, the default parameters of the respective programs can be used (e.g., the default parameters of XBLAST and NBLAST) (see, e.g., National Center for Biotechnology Information (NCBI), World Wide Web: ncbi.nlm.nih.gov). Another non-limiting example of a mathematical algorithm that is suitable for sequence comparison is the algorithm of Myers and Miller, CABIOS 4: 11-17 (1998). Such an algorithm is incorporated in the ALIGN program (version 2.0), which is part of the GCG sequence alignment software package. When utilizing the ALIGN program for comparing amino acid sequences, a PAM120 weight residue table, a gap length penalty of 12, and a gap penalty of 4 can be used.Similar techniques can be used to determine percent identity between two sequences using, for example, those techniques described supra where gaps are or are not permitted. In calculating percent identity, typically only exact matches are counted.

[0332] In some embodiments, an antibody described herein, or antigen binding fragment thereof provided herein, contains substitutions (e.g., conservative substitutions), insertions or deletions relative to a reference sequence, but the antibody comprising that sequence retains the ability to bind to LILRB1. In some embodiments, a total of from 1 to 10 amino acids have been substituted, inserted and / or deleted in the reference amino acid sequence. In some embodiments, substitutions, insertions, or deletions occur in regions outside the CDRs (i.e., in the FRs and / or constant regions).

[0333] In some embodiments, one or more CDRs along the VH (e.g., CDR1, CDR2, or CDR3) and / or VL (e.g., CDR1, CDR2, or CDR3) regions of the LILRB1 binding domains described herein can vary by one, two, three, four, five, or six amino acid positions, so long as binding to LILRB1 (e.g., human LILRB1) is maintained (e.g., substantially maintained, e.g., at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95%). For example, in some embodiments, the positions defining the CDRs of any of Tables 5-6 and 14-15 can be varied by shifting the N-terminal and / or C-terminal boundaries of the CDRs by one, two, three, four, five, or six amino acids, so long as binding to LILRB1 (e.g., human LILRB1) is maintained (e.g., substantially maintained, e.g., at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95%). Additionally or alternatively, in some embodiments, the length of one or more CDRs along the VH (e.g., CDR1, CDR2, or CDR3) and / or VL (e.g., CDR1, CDR2, or CDR3) regions of the LILRB1 binding domains described herein can vary (e.g., be shorter or longer) by one, two, three, four, five, or more amino acids, so long as binding to LILRB1 (e.g., human LILRB1) is maintained (e.g., substantially maintained, e.g., at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95%). For example, in some embodiments, the VH and / or VL CDR1, CDR2, and / or CDR3 described herein can be one, two, three, four, five, or more amino acids shorter than one or more of the CDRs described by SEQ ID NOS: 495-848, 1179, and 1281, so long as binding to LILRB1 (e.g., human LILRB1) is maintained (e.g., substantially maintained, e.g., at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95%). In other embodiments, the VH and / or VL CDR1, CDR2, and / or CDR3 described herein can be one, two, three, four, five, or more amino acids longer than one or more of the CDRs described by SEQ ID NOS: 495-848, 1179, and 1281, so long as binding to LILRB1 (e.g., human LILRB1) is maintained (e.g., substantially maintained, e.g., at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95%).In some embodiments, the amino-terminal end of a VH and / or VL CDR1, CDR2, and / or CDR3 described herein can be extended or shortened by one, two, three, four, five or more amino acids compared to one or more of the CDRs described by SEQ ID NOs: 495-848, 1179, and 1281, so long as binding to LILRB1 (e.g., human LILRB1) is maintained (e.g., substantially maintained, e.g., at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95%). Additionally or alternatively, in some embodiments, the carboxy-terminal end of a VH and / or VL CDR1, CDR2, and / or CDR3 described herein can be extended or shortened by one, two, three, four, five or more amino acids compared to one or more of the CDRs described by SEQ ID NOs: 495-848, 1179, and 1281, so long as binding to LILRB1 (e.g., human LILRB1) is maintained (e.g., substantially maintained, e.g., at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95%). Any method known in the art can be used to determine whether binding to LILRB1 (e.g., human LILRB1) is maintained, such as the binding assays and conditions described in the “Examples” section described herein.

[0334] In other embodiments, the antibodies or antigen-binding fragments thereof described herein further comprise conservative sequence modifications (e.g., in the LILRB1 binding domain). Conservative sequence modifications include conservative amino acid substitutions, which include substitutions where an amino acid residue is replaced with a residue having a similar side chain. Families of amino acid residues having similar side chains have been defined in the art. Thus, in some embodiments, a predicted non-essential amino acid residue in LILRB1 is replaced with another amino acid residue from the same side chain family. Methods of identifying amino acid conservative substitutions that do not abrogate antigen binding, and nucleotides that encode them, are well known in the art (see, e.g., Brummell et al., Biochem. 32:1180-1187 (1993); Kobayashi et al. Protein Eng. 12(10):879-884 (1999); and Burks et al. Proc. Natl. Acad. Sci. USA 94:412-417 (1997)). In some embodiments, the conservative sequence modifications described herein modify 50%, or 55%, or 60%, or 65%, or 70%, or 75%, or 80%, or 85%, or 90%, or 95%, or 98%, or 99% of the amino acid sequence of a binding agent (e.g., an antibody), including a human LILRB1 binding agent. In some embodiments, the amino acid sequence modifications refer to up to 1, 2, 3, 4, 5, or 6 amino acid substitutions to a CDR, such as those described in any of Tables 5-6 and 14-15. Thus, for example, each such CDR can contain up to 5 conservative amino acid substitutions, e.g., up to (no more than) 4 conservative amino acid substitutions, e.g., up to (no more than) 3 conservative amino acid substitutions, e.g., up to (no more than) 2 conservative amino acid substitutions, or no more than 1 conservative amino acid substitution. In some embodiments, the LILRB1 binding domain contains one or more (including six) CDRs that are at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a CDR of any of the antibodies or fragments thereof provided herein (e.g., in Tables 5-6 and 14-15).

[0335] In some embodiments, the LILRB1 binding domain contains a VH and VL that contain CDRs identical to a CDR of any of the antibodies or fragments thereof provided herein (e.g., in Tables 5-6 and 14-15). In some embodiments, the amino acid sequence modifications do not include any modifications within an SDR. In some embodiments, the amino acid sequence modifications do not include any modifications within a CDR (such as CDR1, CDR2, CDR3, or any combination thereof). In another embodiment, the amino acid sequence modifications are in the framework or constant region.

[0336] In some embodiments, an antibody provided herein contains a substitution (e.g., a conservative substitution), an insertion, or a deletion relative to a reference sequence, but the anti-LILRB1 antibody comprising the sequence retains the ability to bind to LILRB1. In some embodiments, a total of from 1 to 10 amino acids have been substituted, inserted and / or deleted in the reference amino acid sequence. In some embodiments, the substitution, insertion, or deletion occurs in a region outside the CDRs (i.e., in the FRs). Optionally, an anti-LILRB1 antibody provided herein includes a post-translational modification of a reference sequence.

[0337] In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 283, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 284. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 285, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 286. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 287, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 288. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 289, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 290.In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 291, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 292. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 293, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 294. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 295, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 296. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 297, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 298.In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 299, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 300. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 301, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 302. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 303, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 304. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 305, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 306.In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 307, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 308. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 309, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 310. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 311, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 312. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 313, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 314.In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 315, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 316. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 317, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 318. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 319, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 320. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 321, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 322.In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 323, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 324. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 325, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 326. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 327, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 328. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 329, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 330.In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 331, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 332. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 333, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 334. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 335, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 336. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 337, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 338.In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 339, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 340. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 341, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 342. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 343, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 344. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 345, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 346.In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 347, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 348. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 349, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 350. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 351, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 352. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 353, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 354.In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 355, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 356. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 357, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 358. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 359, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 360. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 361, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 362.In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 363, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 364. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 365, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 366. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 367, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 368. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 369, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 370.In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 371, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 372. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 373, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 374. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 375, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 376. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 377, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 378.In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 379, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 380. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 381, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 382. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 383, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 384. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 385, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 386.In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 387, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 388. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 389, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 390. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 391, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 392. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 393, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 394.In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 395, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 396. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 397, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 398. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 399, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 400. In some embodiments, the antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 1155, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 1156.In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 1157, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 1158. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 1159, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 1160. In some embodiments, an antibody or antigen-binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 1161, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 1162.In some embodiments, the antibody or antigen binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 1163, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 1164. In some embodiments, the antibody or antigen binding fragment provided herein comprises a VH domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 1165, and a VL domain having at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 1166. In all of the above embodiments, the antibody binds to LILRB1.

[0338] In some embodiments, functional epitopes can be mapped, e.g., by combinatorial alanine scanning, to identify amino acids in the LILRB1 protein that are necessary for interaction with the anti-LILRB1 antibodies provided herein. In some embodiments, the conformation and crystal structure of an anti-LILRB1 antibody that binds to LILRB1 can be used to identify epitopes. In some embodiments, the present disclosure provides antibodies that specifically bind to the same epitope as any of the anti-LILRB1 antibodies provided herein. For example, in some embodiments, an antibody or antigen-binding fragment provided herein binds to the same epitope as an anti-LILRB1 antibody comprising a VH comprising the amino acid sequence of SEQ ID NO: 283 and a VL comprising the amino acid sequence of SEQ ID NO: 284. In some embodiments, an antibody or antigen-binding fragment provided herein binds to the same epitope as an anti-LILRB1 antibody comprising a VH comprising the amino acid sequence of SEQ ID NO: 285 and a VL comprising the amino acid sequence of SEQ ID NO: 286. In some embodiments, an antibody or antigen-binding fragment provided herein binds to the same epitope as an anti-LILRB1 antibody comprising a VH comprising the amino acid sequence of SEQ ID NO: 287 and a VL comprising the amino acid sequence of SEQ ID NO: 288. In some embodiments, an antibody or antigen-binding fragment provided herein binds to the same epitope as an anti-LILRB1 antibody comprising a VH comprising the amino acid sequence of SEQ ID NO: 289 and a VL comprising the amino acid sequence of SEQ ID NO: 290. In some embodiments, an antibody or antigen-binding fragment provided herein binds to the same epitope as an anti-LILRB1 antibody comprising a VH comprising the amino acid sequence of SEQ ID NO: 291 and a VL comprising the amino acid sequence of SEQ ID NO: 292. In some embodiments, an antibody or antigen-binding fragment provided herein binds to the same epitope as an anti-LILRB1 antibody comprising a VH comprising the amino acid sequence of SEQ ID NO: 293 and a VL comprising the amino acid sequence of SEQ ID NO: 294. In some embodiments, an antibody or antigen-binding fragment provided herein binds to the same epitope as an anti-LILRB1 antibody comprising a VH comprising the amino acid sequence of SEQ ID NO: 295 and a VL comprising the amino acid sequence of SEQ ID NO: 296. In some embodiments, an antibody or antigen-binding fragment provided herein binds to the same epitope as an anti-LILRB1 antibody comprising a VH comprising the amino acid sequence of SEQ ID NO: 297 and a VL comprising the amino acid sequence of SEQ ID NO: 298.In some embodiments, an antibody or antigen-binding fragment provided herein binds to the same epitope as an anti-LILRB1 antibody comprising a VH comprising the amino acid sequence of SEQ ID NO: 299 and a VL comprising the amino acid sequence of SEQ ID NO: 300. In some embodiments, an antibody or antigen-binding fragment provided herein binds to the same epitope as an anti-LILRB1 antibody comprising a VH comprising the amino acid sequence of SEQ ID NO: 301 and a VL comprising the amino acid sequence of SEQ ID NO: 302. In some embodiments, an antibody or antigen-binding fragment provided herein binds to the same epitope as an anti-LILRB1 antibody comprising a VH comprising the amino acid sequence of SEQ ID NO: 303 and a VL comprising the amino acid sequence of SEQ ID NO: 304. In some embodiments, an antibody or antigen-binding fragment provided herein binds to the same epitope as an anti-LILRB1 antibody comprising a VH comprising the amino acid sequence of SEQ ID NO: 305 and a VL comprising the amino acid sequence of SEQ ID NO: 306. In some embodiments, an antibody or antigen-binding fragment provided herein binds to the same epitope as an anti-LILRB1 antibody comprising a VH comprising the amino acid sequence of SEQ ID NO: 307 and a VL comprising the amino acid sequence of SEQ ID NO: 308. In some embodiments, an antibody or antigen-binding fragment provided herein binds to the same epitope as an anti-LILRB1 antibody comprising a VH comprising the amino acid sequence of SEQ ID NO: 309 and a VL comprising the amino acid sequence of SEQ ID NO: 310. In some embodiments, an antibody or antigen-binding fragment provided herein binds to the same epitope as an anti-LILRB1 antibody comprising a VH comprising the amino acid sequence of SEQ ID NO: 311 and a VL comprising the amino acid sequence of SEQ ID NO: 312. In some embodiments, an antibody or antigen-binding fragment provided herein binds to the same epitope as an anti-LILRB1 antibody comprising a VH comprising the amino acid sequence of SEQ ID NO: 313 and a VL comprising the amino acid sequence of SEQ ID NO: 314. In some embodiments, an antibody or antigen-binding fragment provided herein binds to the same epitope as an anti-LILRB1 antibody comprising a VH comprising the amino acid sequence of SEQ ID NO: 315 and a VL comprising the amino acid sequence of SEQ ID NO: 316.In some embodiments, an antibody or antigen-binding fragment provided herein binds to the same epitope as an anti-LILRB1 antibody comprising a VH comprising the amino acid sequence of SEQ ID NO: 317 and a VL comprising the amino acid sequence of SEQ ID NO: 318. In some embodiments, an antibody or antigen-binding fragment provided herein binds to the same epitope as an anti-LILRB1 antibody comprising a VH comprising the amino acid sequence of SEQ ID NO: 319 and a VL comprising the amino acid sequence of SEQ ID NO: 320. In some embodiments, an antibody or antigen-binding fragment provided herein binds to the same epitope as an anti-LILRB1 antibody comprising a VH comprising the amino acid sequence of SEQ ID NO: 321 and a VL comprising the amino acid sequence of SEQ ID NO: 322. In some embodiments, an antibody or antigen-binding fragment provided herein binds to the same epitope as an anti-LILRB1 antibody comprising a VH comprising the amino acid sequence of SEQ ID NO: 323 and a VL comprising the amino acid sequence of SEQ ID NO: 324. In some embodiments, an antibody or antigen-binding fragment provided herein binds to the same epitope as an anti-LILRB1 antibody comprising a VH comprising the amino acid sequence of SEQ ID NO: 325 and a VL comprising the amino acid sequence of SEQ ID NO: 326. In some embodiments, an antibody or antigen-binding fragment provided herein binds to the same epitope as an anti-LILRB1 antibody comprising a VH comprising the amino acid sequence of SEQ ID NO: 327 and a VL comprising the amino acid sequence of SEQ ID NO: 328. In some embodiments, an antibody or antigen-binding fragment provided herein binds to the same epitope as an anti-LILRB1 antibody comprising a VH comprising the amino acid sequence of SEQ ID NO: 329 and a VL comprising the amino acid sequence of SEQ ID NO: 330. In some embodiments, an antibody or antigen-binding fragment provided herein binds to the same epitope as an anti-LILRB1 antibody comprising a VH comprising the amino acid sequence of SEQ ID NO: 331 and a VL comprising the amino acid sequence of SEQ ID NO: 332. In some embodiments, an antibody or antigen-binding fragment provided herein binds to the same epitope as an anti-LILRB1 antibody comprising a VH comprising the amino acid sequence of SEQ ID NO: 333 and a VL comprising the amino acid sequence of SEQ ID NO: 334.In some embodiments, an antibody or antigen-binding fragment provided herein binds to the same epitope as an anti-LILRB1 antibody comprising a VH comprising the amino acid sequence of SEQ ID NO: 335 and a VL comprising the amino acid sequence of SEQ ID NO: 336. In some embodiments, an antibody or antigen-binding fragment provided herein binds to the same epitope as an anti-LILRB1 antibody comprising a VH comprising the amino acid sequence of SEQ ID NO: 337 and a VL comprising the amino acid sequence of SEQ ID NO: 338. In some embodiments, an antibody or antigen-binding fragment provided herein binds to the same epitope as an anti-LILRB1 antibody comprising a VH comprising the amino acid sequence of SEQ ID NO: 339 and a VL comprising the amino acid sequence of SEQ ID NO: 340. In some embodiments, an antibody or antigen-binding fragment provided herein binds to the same epitope as an anti-LILRB1 antibody comprising a VH comprising the...

Claims

1. An antibody or antigen-binding fragment thereof that binds to LILRB1, wherein the antibody or antigen-binding fragment comprises: (1). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:1155 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:1156. (2). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:1157 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:1158. (3). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:1159 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:1160. (4). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:1161 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:1162. (5) HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:1163 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:1164. (6) HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:1165 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:1166. (7). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:283 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

284. (8). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:285 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

286. (9) HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:287 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

288. (10). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:289 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

290. (11). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:291 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

292. (12). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:293 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

294. (13). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:295 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

296. (14). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:297 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

298. (15). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:299 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

300. (16). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:301 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

302. (17). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:303 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

304. (18). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:305 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

306. (19). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:307 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

308. (20). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:309 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

310. (21). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:311 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

312. (22). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:313 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

314. (23). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:315 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

316. (24). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:317 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

318. (25). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:319 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

320. (26). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:321 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

322. (27). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:323 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

324. (28). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:325 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

326. (29). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:327 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

328. (30). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:329 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

330. (31). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:331 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

332. (32). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:333 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

334. (33). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:335 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

336. (34). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:337 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

338. (35). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:339 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

340. (36). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:341 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

342. (37). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:343 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

344. (38). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:345 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

346. (39). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:347 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

348. (40) HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:349 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

350. (41). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:351 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

352. (42). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:353 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

354. (43). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:355 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

356. (44). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:357 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

358. (45) HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:359 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

360. (46). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:361 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

362. (47). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:363 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

364. (48). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:365 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

366. (49) HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:367 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

368. (50) HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:369 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

370. (51). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:371 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

372. (52). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:373 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

374. (53). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:375 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

376. (54). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:377 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

378. (55). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:379 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

380. (56). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:381 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

382. (57). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:383 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

384. (58). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:385 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

386. (59). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:387 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

388. (60) HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:389 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

390. (61). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:391 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

392. (62). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:393 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

394. (63). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:395 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

396. (64). HCDR1, HCDR2, and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:397, and LCDR1, LCDR2, and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:398; or (65) HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:399 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

400.

2. The antibody or antigen-binding fragment according to claim 1, wherein: (1). The HCDR1 contains the amino acid sequence of SEQ ID NO:543, the HCDR2 contains the amino acid sequence of SEQ ID NO:544, the HCDR3 contains the amino acid sequence of SEQ ID NO:1179, the LCDR1 contains the amino acid sequence of SEQ ID NO:546, the LCDR2 contains the amino acid sequence of SEQ ID NO:1281, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

548. (2). The HCDR1 contains the amino acid sequence of SEQ ID NO:585, the HCDR2 contains the amino acid sequence of SEQ ID NO:586, the HCDR3 contains the amino acid sequence of SEQ ID NO:587, the LCDR1 contains the amino acid sequence of SEQ ID NO:588, the LCDR2 contains the amino acid sequence of SEQ ID NO:589, and the LCDR3 contains the amino acid sequence of SEQ ID NO:590; (3). The HCDR1 contains the amino acid sequence of SEQ ID NO:495, the HCDR2 contains the amino acid sequence of SEQ ID NO:496, the HCDR3 contains the amino acid sequence of SEQ ID NO:497, the LCDR1 contains the amino acid sequence of SEQ ID NO:498, the LCDR2 contains the amino acid sequence of SEQ ID NO:499, and the LCDR3 contains the amino acid sequence of SEQ ID NO:500; (4). The HCDR1 contains the amino acid sequence of SEQ ID NO:501, the HCDR2 contains the amino acid sequence of SEQ ID NO:502, the HCDR3 contains the amino acid sequence of SEQ ID NO:503, the LCDR1 contains the amino acid sequence of SEQ ID NO:504, the LCDR2 contains the amino acid sequence of SEQ ID NO:505, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

506. (5). The HCDR1 contains the amino acid sequence of SEQ ID NO:507, the HCDR2 contains the amino acid sequence of SEQ ID NO:508, the HCDR3 contains the amino acid sequence of SEQ ID NO:509, the LCDR1 contains the amino acid sequence of SEQ ID NO:510, the LCDR2 contains the amino acid sequence of SEQ ID NO:511, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

512. (6). The HCDR1 contains the amino acid sequence of SEQ ID NO:513, the HCDR2 contains the amino acid sequence of SEQ ID NO:514, the HCDR3 contains the amino acid sequence of SEQ ID NO:515, the LCDR1 contains the amino acid sequence of SEQ ID NO:516, the LCDR2 contains the amino acid sequence of SEQ ID NO:517, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

518. (7). The HCDR1 contains the amino acid sequence of SEQ ID NO:519, the HCDR2 contains the amino acid sequence of SEQ ID NO:520, the HCDR3 contains the amino acid sequence of SEQ ID NO:521, the LCDR1 contains the amino acid sequence of SEQ ID NO:522, the LCDR2 contains the amino acid sequence of SEQ ID NO:523, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

524. (8). The HCDR1 contains the amino acid sequence of SEQ ID NO:525, the HCDR2 contains the amino acid sequence of SEQ ID NO:526, the HCDR3 contains the amino acid sequence of SEQ ID NO:527, the LCDR1 contains the amino acid sequence of SEQ ID NO:528, the LCDR2 contains the amino acid sequence of SEQ ID NO:529, and the LCDR3 contains the amino acid sequence of SEQ ID NO:530; (9). The HCDR1 contains the amino acid sequence of SEQ ID NO:531, the HCDR2 contains the amino acid sequence of SEQ ID NO:532, the HCDR3 contains the amino acid sequence of SEQ ID NO:533, the LCDR1 contains the amino acid sequence of SEQ ID NO:534, the LCDR2 contains the amino acid sequence of SEQ ID NO:535, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

536. (10). The HCDR1 contains the amino acid sequence of SEQ ID NO:537, the HCDR2 contains the amino acid sequence of SEQ ID NO:538, the HCDR3 contains the amino acid sequence of SEQ ID NO:539, the LCDR1 contains the amino acid sequence of SEQ ID NO:540, the LCDR2 contains the amino acid sequence of SEQ ID NO:541, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

542. (11). The HCDR1 contains the amino acid sequence of SEQ ID NO:543, the HCDR2 contains the amino acid sequence of SEQ ID NO:544, the HCDR3 contains the amino acid sequence of SEQ ID NO:545, the LCDR1 contains the amino acid sequence of SEQ ID NO:546, the LCDR2 contains the amino acid sequence of SEQ ID NO:547, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

548. (12). The HCDR1 contains the amino acid sequence of SEQ ID NO:549, the HCDR2 contains the amino acid sequence of SEQ ID NO:550, the HCDR3 contains the amino acid sequence of SEQ ID NO:551, the LCDR1 contains the amino acid sequence of SEQ ID NO:552, the LCDR2 contains the amino acid sequence of SEQ ID NO:553, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

554. (13). The HCDR1 contains the amino acid sequence of SEQ ID NO:555, the HCDR2 contains the amino acid sequence of SEQ ID NO:556, the HCDR3 contains the amino acid sequence of SEQ ID NO:557, the LCDR1 contains the amino acid sequence of SEQ ID NO:558, the LCDR2 contains the amino acid sequence of SEQ ID NO:559, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

560. (14). The HCDR1 contains the amino acid sequence of SEQ ID NO:561, the HCDR2 contains the amino acid sequence of SEQ ID NO:562, the HCDR3 contains the amino acid sequence of SEQ ID NO:563, the LCDR1 contains the amino acid sequence of SEQ ID NO:564, the LCDR2 contains the amino acid sequence of SEQ ID NO:565, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

566. (15). The HCDR1 contains the amino acid sequence of SEQ ID NO:567, the HCDR2 contains the amino acid sequence of SEQ ID NO:568, the HCDR3 contains the amino acid sequence of SEQ ID NO:569, the LCDR1 contains the amino acid sequence of SEQ ID NO:570, the LCDR2 contains the amino acid sequence of SEQ ID NO:571, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

572. (16). The HCDR1 contains the amino acid sequence of SEQ ID NO:573, the HCDR2 contains the amino acid sequence of SEQ ID NO:574, the HCDR3 contains the amino acid sequence of SEQ ID NO:575, the LCDR1 contains the amino acid sequence of SEQ ID NO:576, the LCDR2 contains the amino acid sequence of SEQ ID NO:577, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

578. (17). The HCDR1 contains the amino acid sequence of SEQ ID NO:579, the HCDR2 contains the amino acid sequence of SEQ ID NO:580, the HCDR3 contains the amino acid sequence of SEQ ID NO:581, the LCDR1 contains the amino acid sequence of SEQ ID NO:582, the LCDR2 contains the amino acid sequence of SEQ ID NO:583, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

584. (18). The HCDR1 contains the amino acid sequence of SEQ ID NO:591, the HCDR2 contains the amino acid sequence of SEQ ID NO:592, the HCDR3 contains the amino acid sequence of SEQ ID NO:593, the LCDR1 contains the amino acid sequence of SEQ ID NO:594, the LCDR2 contains the amino acid sequence of SEQ ID NO:595, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

596. (19). The HCDR1 contains the amino acid sequence of SEQ ID NO:597, the HCDR2 contains the amino acid sequence of SEQ ID NO:598, the HCDR3 contains the amino acid sequence of SEQ ID NO:599, the LCDR1 contains the amino acid sequence of SEQ ID NO:600, the LCDR2 contains the amino acid sequence of SEQ ID NO:601, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

602. (20). The HCDR1 contains the amino acid sequence of SEQ ID NO:603, the HCDR2 contains the amino acid sequence of SEQ ID NO:604, the HCDR3 contains the amino acid sequence of SEQ ID NO:605, the LCDR1 contains the amino acid sequence of SEQ ID NO:606, the LCDR2 contains the amino acid sequence of SEQ ID NO:607, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

608. (21). The HCDR1 contains the amino acid sequence of SEQ ID NO:609, the HCDR2 contains the amino acid sequence of SEQ ID NO:610, the HCDR3 contains the amino acid sequence of SEQ ID NO:611, the LCDR1 contains the amino acid sequence of SEQ ID NO:612, the LCDR2 contains the amino acid sequence of SEQ ID NO:613, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

614. (22). The HCDR1 contains the amino acid sequence of SEQ ID NO:615, the HCDR2 contains the amino acid sequence of SEQ ID NO:616, the HCDR3 contains the amino acid sequence of SEQ ID NO:617, the LCDR1 contains the amino acid sequence of SEQ ID NO:618, the LCDR2 contains the amino acid sequence of SEQ ID NO:619, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

620. (23). The HCDR1 contains the amino acid sequence of SEQ ID NO:621, the HCDR2 contains the amino acid sequence of SEQ ID NO:622, the HCDR3 contains the amino acid sequence of SEQ ID NO:623, the LCDR1 contains the amino acid sequence of SEQ ID NO:624, the LCDR2 contains the amino acid sequence of SEQ ID NO:625, and the LCDR3 contains the amino acid sequence of SEQ ID NO:626; (24). The HCDR1 contains the amino acid sequence of SEQ ID NO:627, the HCDR2 contains the amino acid sequence of SEQ ID NO:628, the HCDR3 contains the amino acid sequence of SEQ ID NO:629, the LCDR1 contains the amino acid sequence of SEQ ID NO:630, the LCDR2 contains the amino acid sequence of SEQ ID NO:631, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

632. (25). The HCDR1 contains the amino acid sequence of SEQ ID NO:633, the HCDR2 contains the amino acid sequence of SEQ ID NO:634, the HCDR3 contains the amino acid sequence of SEQ ID NO:635, the LCDR1 contains the amino acid sequence of SEQ ID NO:636, the LCDR2 contains the amino acid sequence of SEQ ID NO:637, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

638. (26). The HCDR1 contains the amino acid sequence of SEQ ID NO:639, the HCDR2 contains the amino acid sequence of SEQ ID NO:640, the HCDR3 contains the amino acid sequence of SEQ ID NO:641, the LCDR1 contains the amino acid sequence of SEQ ID NO:642, the LCDR2 contains the amino acid sequence of SEQ ID NO:643, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

644. (27). The HCDR1 contains the amino acid sequence of SEQ ID NO:645, the HCDR2 contains the amino acid sequence of SEQ ID NO:646, the HCDR3 contains the amino acid sequence of SEQ ID NO:647, the LCDR1 contains the amino acid sequence of SEQ ID NO:648, the LCDR2 contains the amino acid sequence of SEQ ID NO:649, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

650. (28). The HCDR1 contains the amino acid sequence of SEQ ID NO:651, the HCDR2 contains the amino acid sequence of SEQ ID NO:652, the HCDR3 contains the amino acid sequence of SEQ ID NO:653, the LCDR1 contains the amino acid sequence of SEQ ID NO:654, the LCDR2 contains the amino acid sequence of SEQ ID NO:655, and the LCDR3 contains the amino acid sequence of SEQ ID NO:656; (29). The HCDR1 contains the amino acid sequence of SEQ ID NO:657, the HCDR2 contains the amino acid sequence of SEQ ID NO:658, the HCDR3 contains the amino acid sequence of SEQ ID NO:659, the LCDR1 contains the amino acid sequence of SEQ ID NO:660, the LCDR2 contains the amino acid sequence of SEQ ID NO:661, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

662. (30). The HCDR1 contains the amino acid sequence of SEQ ID NO:663, the HCDR2 contains the amino acid sequence of SEQ ID NO:664, the HCDR3 contains the amino acid sequence of SEQ ID NO:665, the LCDR1 contains the amino acid sequence of SEQ ID NO:666, the LCDR2 contains the amino acid sequence of SEQ ID NO:667, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

668. (31). The HCDR1 contains the amino acid sequence of SEQ ID NO:669, the HCDR2 contains the amino acid sequence of SEQ ID NO:670, the HCDR3 contains the amino acid sequence of SEQ ID NO:671, the LCDR1 contains the amino acid sequence of SEQ ID NO:672, the LCDR2 contains the amino acid sequence of SEQ ID NO:673, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

674. (32). The HCDR1 contains the amino acid sequence of SEQ ID NO:675, the HCDR2 contains the amino acid sequence of SEQ ID NO:676, the HCDR3 contains the amino acid sequence of SEQ ID NO:677, the LCDR1 contains the amino acid sequence of SEQ ID NO:678, the LCDR2 contains the amino acid sequence of SEQ ID NO:679, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

680. (33). The HCDR1 contains the amino acid sequence of SEQ ID NO:681, the HCDR2 contains the amino acid sequence of SEQ ID NO:682, the HCDR3 contains the amino acid sequence of SEQ ID NO:683, the LCDR1 contains the amino acid sequence of SEQ ID NO:684, the LCDR2 contains the amino acid sequence of SEQ ID NO:685, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

686. (34). The HCDR1 contains the amino acid sequence of SEQ ID NO:687, the HCDR2 contains the amino acid sequence of SEQ ID NO:688, the HCDR3 contains the amino acid sequence of SEQ ID NO:689, the LCDR1 contains the amino acid sequence of SEQ ID NO:690, the LCDR2 contains the amino acid sequence of SEQ ID NO:691, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

692. (35). The HCDR1 contains the amino acid sequence of SEQ ID NO:693, the HCDR2 contains the amino acid sequence of SEQ ID NO:694, the HCDR3 contains the amino acid sequence of SEQ ID NO:695, the LCDR1 contains the amino acid sequence of SEQ ID NO:696, the LCDR2 contains the amino acid sequence of SEQ ID NO:697, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

698. (36). The HCDR1 contains the amino acid sequence of SEQ ID NO:699, the HCDR2 contains the amino acid sequence of SEQ ID NO:700, the HCDR3 contains the amino acid sequence of SEQ ID NO:701, the LCDR1 contains the amino acid sequence of SEQ ID NO:702, the LCDR2 contains the amino acid sequence of SEQ ID NO:703, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

704. (37). The HCDR1 contains the amino acid sequence of SEQ ID NO:705, the HCDR2 contains the amino acid sequence of SEQ ID NO:706, the HCDR3 contains the amino acid sequence of SEQ ID NO:707, the LCDR1 contains the amino acid sequence of SEQ ID NO:708, the LCDR2 contains the amino acid sequence of SEQ ID NO:709, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

710. (38). The HCDR1 contains the amino acid sequence of SEQ ID NO:711, the HCDR2 contains the amino acid sequence of SEQ ID NO:712, the HCDR3 contains the amino acid sequence of SEQ ID NO:713, the LCDR1 contains the amino acid sequence of SEQ ID NO:714, the LCDR2 contains the amino acid sequence of SEQ ID NO:715, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

716. (39). The HCDR1 contains the amino acid sequence of SEQ ID NO:717, the HCDR2 contains the amino acid sequence of SEQ ID NO:718, the HCDR3 contains the amino acid sequence of SEQ ID NO:719, the LCDR1 contains the amino acid sequence of SEQ ID NO:720, the LCDR2 contains the amino acid sequence of SEQ ID NO:721, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

722. (40). The HCDR1 contains the amino acid sequence of SEQ ID NO:723, the HCDR2 contains the amino acid sequence of SEQ ID NO:724, the HCDR3 contains the amino acid sequence of SEQ ID NO:725, the LCDR1 contains the amino acid sequence of SEQ ID NO:726, the LCDR2 contains the amino acid sequence of SEQ ID NO:727, and the LCDR3 contains the amino acid sequence of SEQ ID NO:728; (41). The HCDR1 contains the amino acid sequence of SEQ ID NO:729, the HCDR2 contains the amino acid sequence of SEQ ID NO:730, the HCDR3 contains the amino acid sequence of SEQ ID NO:731, the LCDR1 contains the amino acid sequence of SEQ ID NO:732, the LCDR2 contains the amino acid sequence of SEQ ID NO:733, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

734. (42). The HCDR1 contains the amino acid sequence of SEQ ID NO:735, the HCDR2 contains the amino acid sequence of SEQ ID NO:736, the HCDR3 contains the amino acid sequence of SEQ ID NO:737, the LCDR1 contains the amino acid sequence of SEQ ID NO:738, the LCDR2 contains the amino acid sequence of SEQ ID NO:739, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

740. (43). The HCDR1 contains the amino acid sequence of SEQ ID NO:741, the HCDR2 contains the amino acid sequence of SEQ ID NO:742, the HCDR3 contains the amino acid sequence of SEQ ID NO:743, the LCDR1 contains the amino acid sequence of SEQ ID NO:744, the LCDR2 contains the amino acid sequence of SEQ ID NO:745, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

746. (44). The HCDR1 contains the amino acid sequence of SEQ ID NO:747, the HCDR2 contains the amino acid sequence of SEQ ID NO:748, the HCDR3 contains the amino acid sequence of SEQ ID NO:749, the LCDR1 contains the amino acid sequence of SEQ ID NO:750, the LCDR2 contains the amino acid sequence of SEQ ID NO:751, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

752. (45). The HCDR1 contains the amino acid sequence of SEQ ID NO:753, the HCDR2 contains the amino acid sequence of SEQ ID NO:754, the HCDR3 contains the amino acid sequence of SEQ ID NO:755, the LCDR1 contains the amino acid sequence of SEQ ID NO:756, the LCDR2 contains the amino acid sequence of SEQ ID NO:757, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

758. (46). The HCDR1 contains the amino acid sequence of SEQ ID NO:759, the HCDR2 contains the amino acid sequence of SEQ ID NO:760, the HCDR3 contains the amino acid sequence of SEQ ID NO:761, the LCDR1 contains the amino acid sequence of SEQ ID NO:762, the LCDR2 contains the amino acid sequence of SEQ ID NO:763, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

764. (47). The HCDR1 contains the amino acid sequence of SEQ ID NO:765, the HCDR2 contains the amino acid sequence of SEQ ID NO:766, the HCDR3 contains the amino acid sequence of SEQ ID NO:767, the LCDR1 contains the amino acid sequence of SEQ ID NO:768, the LCDR2 contains the amino acid sequence of SEQ ID NO:769, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

770. (48). The HCDR1 contains the amino acid sequence of SEQ ID NO:771, the HCDR2 contains the amino acid sequence of SEQ ID NO:772, the HCDR3 contains the amino acid sequence of SEQ ID NO:773, the LCDR1 contains the amino acid sequence of SEQ ID NO:774, the LCDR2 contains the amino acid sequence of SEQ ID NO:775, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

776. (49). The HCDR1 contains the amino acid sequence of SEQ ID NO:777, the HCDR2 contains the amino acid sequence of SEQ ID NO:778, the HCDR3 contains the amino acid sequence of SEQ ID NO:779, the LCDR1 contains the amino acid sequence of SEQ ID NO:780, the LCDR2 contains the amino acid sequence of SEQ ID NO:781, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

782. (50). The HCDR1 contains the amino acid sequence of SEQ ID NO:783, the HCDR2 contains the amino acid sequence of SEQ ID NO:784, the HCDR3 contains the amino acid sequence of SEQ ID NO:785, the LCDR1 contains the amino acid sequence of SEQ ID NO:786, the LCDR2 contains the amino acid sequence of SEQ ID NO:787, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

788. (51). The HCDR1 contains the amino acid sequence of SEQ ID NO:789, the HCDR2 contains the amino acid sequence of SEQ ID NO:790, the HCDR3 contains the amino acid sequence of SEQ ID NO:791, the LCDR1 contains the amino acid sequence of SEQ ID NO:792, the LCDR2 contains the amino acid sequence of SEQ ID NO:793, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

794. (52). The HCDR1 contains the amino acid sequence of SEQ ID NO:795, the HCDR2 contains the amino acid sequence of SEQ ID NO:796, the HCDR3 contains the amino acid sequence of SEQ ID NO:797, the LCDR1 contains the amino acid sequence of SEQ ID NO:798, the LCDR2 contains the amino acid sequence of SEQ ID NO:799, and the LCDR3 contains the amino acid sequence of SEQ ID NO:800; (53). The HCDR1 contains the amino acid sequence of SEQ ID NO:801, the HCDR2 contains the amino acid sequence of SEQ ID NO:802, the HCDR3 contains the amino acid sequence of SEQ ID NO:803, the LCDR1 contains the amino acid sequence of SEQ ID NO:804, the LCDR2 contains the amino acid sequence of SEQ ID NO:805, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

806. (54). The HCDR1 contains the amino acid sequence of SEQ ID NO:807, the HCDR2 contains the amino acid sequence of SEQ ID NO:808, the HCDR3 contains the amino acid sequence of SEQ ID NO:809, the LCDR1 contains the amino acid sequence of SEQ ID NO:810, the LCDR2 contains the amino acid sequence of SEQ ID NO:811, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

812. (55). The HCDR1 contains the amino acid sequence of SEQ ID NO:813, the HCDR2 contains the amino acid sequence of SEQ ID NO:814, the HCDR3 contains the amino acid sequence of SEQ ID NO:815, the LCDR1 contains the amino acid sequence of SEQ ID NO:816, the LCDR2 contains the amino acid sequence of SEQ ID NO:817, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

818. (56). The HCDR1 contains the amino acid sequence of SEQ ID NO:819, the HCDR2 contains the amino acid sequence of SEQ ID NO:820, the HCDR3 contains the amino acid sequence of SEQ ID NO:821, the LCDR1 contains the amino acid sequence of SEQ ID NO:822, the LCDR2 contains the amino acid sequence of SEQ ID NO:823, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

824. (57). The HCDR1 contains the amino acid sequence of SEQ ID NO:825, the HCDR2 contains the amino acid sequence of SEQ ID NO:826, the HCDR3 contains the amino acid sequence of SEQ ID NO:827, the LCDR1 contains the amino acid sequence of SEQ ID NO:828, the LCDR2 contains the amino acid sequence of SEQ ID NO:829, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

830. (58). The HCDR1 contains the amino acid sequence of SEQ ID NO:831, the HCDR2 contains the amino acid sequence of SEQ ID NO:832, the HCDR3 contains the amino acid sequence of SEQ ID NO:833, the LCDR1 contains the amino acid sequence of SEQ ID NO:834, the LCDR2 contains the amino acid sequence of SEQ ID NO:835, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

836. (59). The HCDR1 contains the amino acid sequence of SEQ ID NO:837, the HCDR2 contains the amino acid sequence of SEQ ID NO:838, the HCDR3 contains the amino acid sequence of SEQ ID NO:839, the LCDR1 contains the amino acid sequence of SEQ ID NO:840, the LCDR2 contains the amino acid sequence of SEQ ID NO:841, and the LCDR3 contains the amino acid sequence of SEQ ID NO:842; or (60). The HCDR1 contains the amino acid sequence of SEQ ID NO:843, the HCDR2 contains the amino acid sequence of SEQ ID NO:844, the HCDR3 contains the amino acid sequence of SEQ ID NO:845, the LCDR1 contains the amino acid sequence of SEQ ID NO:846, the LCDR2 contains the amino acid sequence of SEQ ID NO:847, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

848.

3. The antibody or antigen-binding fragment according to claim 1 or 2, comprising: (1). VH containing the amino acid sequence of SEQ ID NO:1155 and VL containing the amino acid sequence of SEQ ID NO:1156; (2). VH containing the amino acid sequence of SEQ ID NO:1157 and VL containing the amino acid sequence of SEQ ID NO:1158; (3). VH containing the amino acid sequence of SEQ ID NO:1159 and VL containing the amino acid sequence of SEQ ID NO:1160; (4). VH containing the amino acid sequence of SEQ ID NO:1161 and VL containing the amino acid sequence of SEQ ID NO:1162; (5). VH containing the amino acid sequence of SEQ ID NO:1163 and VL containing the amino acid sequence of SEQ ID NO:1164; (6). VH containing the amino acid sequence of SEQ ID NO:1165 and VL containing the amino acid sequence of SEQ ID NO:1166; (7). VH containing the amino acid sequence of SEQ ID NO:283 and VL containing the amino acid sequence of SEQ ID NO:284; (8). VH containing the amino acid sequence of SEQ ID NO:285 and VL containing the amino acid sequence of SEQ ID NO:286; (9). VH containing the amino acid sequence of SEQ ID NO:287 and VL containing the amino acid sequence of SEQ ID NO:288; (10). VH containing the amino acid sequence of SEQ ID NO:289 and VL containing the amino acid sequence of SEQ ID NO:290; (11). VH containing the amino acid sequence of SEQ ID NO:291 and VL containing the amino acid sequence of SEQ ID NO:292; (12). VH containing the amino acid sequence of SEQ ID NO:293 and VL containing the amino acid sequence of SEQ ID NO:294; (13). VH containing the amino acid sequence of SEQ ID NO:295 and VL containing the amino acid sequence of SEQ ID NO:296; (14). VH containing the amino acid sequence of SEQ ID NO:297 and VL containing the amino acid sequence of SEQ ID NO:298; (15). VH containing the amino acid sequence of SEQ ID NO:299 and VL containing the amino acid sequence of SEQ ID NO:300; (16). VH containing the amino acid sequence of SEQ ID NO:301 and VL containing the amino acid sequence of SEQ ID NO:302; (17). VH containing the amino acid sequence of SEQ ID NO:303 and VL containing the amino acid sequence of SEQ ID NO:304; (18). VH containing the amino acid sequence of SEQ ID NO:305 and VL containing the amino acid sequence of SEQ ID NO:306; (19). VH containing the amino acid sequence of SEQ ID NO:307 and VL containing the amino acid sequence of SEQ ID NO:308; (20). VH containing the amino acid sequence of SEQ ID NO:309 and VL containing the amino acid sequence of SEQ ID NO:310; (21). VH containing the amino acid sequence of SEQ ID NO:311 and VL containing the amino acid sequence of SEQ ID NO:312; (22). VH containing the amino acid sequence of SEQ ID NO:313 and VL containing the amino acid sequence of SEQ ID NO:314; (23). VH containing the amino acid sequence of SEQ ID NO:315 and VL containing the amino acid sequence of SEQ ID NO:316; (24). VH containing the amino acid sequence of SEQ ID NO:317 and VL containing the amino acid sequence of SEQ ID NO:318; (25). VH containing the amino acid sequence of SEQ ID NO:319 and VL containing the amino acid sequence of SEQ ID NO:320; (26). VH containing the amino acid sequence of SEQ ID NO:321 and VL containing the amino acid sequence of SEQ ID NO:322; (27). VH containing the amino acid sequence of SEQ ID NO:323 and VL containing the amino acid sequence of SEQ ID NO:324; (28). VH containing the amino acid sequence of SEQ ID NO:325 and VL containing the amino acid sequence of SEQ ID NO:326; (29). VH containing the amino acid sequence of SEQ ID NO:327 and VL containing the amino acid sequence of SEQ ID NO:328; (30). VH containing the amino acid sequence of SEQ ID NO:329 and VL containing the amino acid sequence of SEQ ID NO:330; (31). VH containing the amino acid sequence of SEQ ID NO:331 and VL containing the amino acid sequence of SEQ ID NO:332; (32). VH containing the amino acid sequence of SEQ ID NO:333 and VL containing the amino acid sequence of SEQ ID NO:334; (33). VH containing the amino acid sequence of SEQ ID NO:335 and VL containing the amino acid sequence of SEQ ID NO:336; (34). VH containing the amino acid sequence of SEQ ID NO:337 and VL containing the amino acid sequence of SEQ ID NO:338; (35). VH containing the amino acid sequence of SEQ ID NO:339 and VL containing the amino acid sequence of SEQ ID NO:340; (36). VH containing the amino acid sequence of SEQ ID NO:341 and VL containing the amino acid sequence of SEQ ID NO:342; (37). VH containing the amino acid sequence of SEQ ID NO:343 and VL containing the amino acid sequence of SEQ ID NO:344; (38). VH containing the amino acid sequence of SEQ ID NO:345 and VL containing the amino acid sequence of SEQ ID NO:346; (39). VH containing the amino acid sequence of SEQ ID NO:347 and VL containing the amino acid sequence of SEQ ID NO:348; (40). VH containing the amino acid sequence of SEQ ID NO:349 and VL containing the amino acid sequence of SEQ ID NO:350; (41). VH containing the amino acid sequence of SEQ ID NO:351 and VL containing the amino acid sequence of SEQ ID NO:352; (42). VH containing the amino acid sequence of SEQ ID NO:353 and VL containing the amino acid sequence of SEQ ID NO:354; (43). VH containing the amino acid sequence of SEQ ID NO:355 and VL containing the amino acid sequence of SEQ ID NO:356; (44). VH containing the amino acid sequence of SEQ ID NO:357 and VL containing the amino acid sequence of SEQ ID NO:358; (45). VH containing the amino acid sequence of SEQ ID NO:359 and VL containing the amino acid sequence of SEQ ID NO:360; (46). VH containing the amino acid sequence of SEQ ID NO:361 and VL containing the amino acid sequence of SEQ ID NO:362; (47). VH containing the amino acid sequence of SEQ ID NO:363 and VL containing the amino acid sequence of SEQ ID NO:364; (48). VH containing the amino acid sequence of SEQ ID NO:365 and VL containing the amino acid sequence of SEQ ID NO:366; (49). VH containing the amino acid sequence of SEQ ID NO:367 and VL containing the amino acid sequence of SEQ ID NO:368; (50). VH containing the amino acid sequence of SEQ ID NO:369 and VL containing the amino acid sequence of SEQ ID NO:370; (51). VH containing the amino acid sequence of SEQ ID NO:371 and VL containing the amino acid sequence of SEQ ID NO:372; (52). VH containing the amino acid sequence of SEQ ID NO:373 and VL containing the amino acid sequence of SEQ ID NO:374; (53). VH containing the amino acid sequence of SEQ ID NO:375 and VL containing the amino acid sequence of SEQ ID NO:376; (54). VH containing the amino acid sequence of SEQ ID NO:377 and VL containing the amino acid sequence of SEQ ID NO:378; (55). VH containing the amino acid sequence of SEQ ID NO:379 and VL containing the amino acid sequence of SEQ ID NO:380; (56). VH containing the amino acid sequence of SEQ ID NO:381 and VL containing the amino acid sequence of SEQ ID NO:382; (57). VH containing the amino acid sequence of SEQ ID NO:383 and VL containing the amino acid sequence of SEQ ID NO:384; (58). VH containing the amino acid sequence of SEQ ID NO:385 and VL containing the amino acid sequence of SEQ ID NO:386; (59). VH containing the amino acid sequence of SEQ ID NO:387 and VL containing the amino acid sequence of SEQ ID NO:388; (60). VH containing the amino acid sequence of SEQ ID NO:389 and VL containing the amino acid sequence of SEQ ID NO:390; (61). VH containing the amino acid sequence of SEQ ID NO:391 and VL containing the amino acid sequence of SEQ ID NO:392; (62). VH containing the amino acid sequence of SEQ ID NO:393 and VL containing the amino acid sequence of SEQ ID NO:394; (63). VH containing the amino acid sequence of SEQ ID NO:395 and VL containing the amino acid sequence of SEQ ID NO:396; (64). VH containing the amino acid sequence of SEQ ID NO:397 and VL containing the amino acid sequence of SEQ ID NO:398; or (65). VH containing the amino acid sequence of SEQ ID NO:399 and VL containing the amino acid sequence of SEQ ID NO:

400.

4. An antibody or antigen-binding fragment thereof that binds to LILRB2, wherein the antibody or antigen-binding fragment comprises: (1). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:1167 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:1168. (2). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:1169 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:1170. (3). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:1171 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:1172. (4). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:1173 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:1174. (5) HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:1175 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:1176. (6). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:1177 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:1178. (7). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:401 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

402. (8). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:403 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:404; (9) HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:405 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

406. (10). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:407 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

408. (11). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:409 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

410. (12). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:411 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

412. (13). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:413 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

414. (14). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:415 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

416. (15). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:417 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

418. (16). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:419 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

420. (17). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:421 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

422. (18). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:423 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

424. (19). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:425 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

426. (20). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:427 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

428. (21). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:429 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

430. (22). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:431 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

432. (23). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:433 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

434. (24). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:435 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

436. (25). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:437 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

438. (26). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:439 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

440. (27). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:441 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

442. (28). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:443 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

444. (29). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:445 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

446. (30). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:447 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

448. (31). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:449 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

450. (32). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:451 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

452. (33). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:453 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

454. (34). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:455 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

456. (35). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:457 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

458. (36). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:459 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

460. (37). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:461 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

462. (38). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:463 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

464. (39). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:465 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

466. (40) HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:467 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

468. (41). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:469 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

470. (42). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:471 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

472. (43). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:473 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

474. (44). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:475 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

476. (45) HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:477 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

478. (46). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:479 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

480. (47). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:481 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

482. (48). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:483 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:484; (49). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:485 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

486. (50) HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:487 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

488. (51). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:489 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

490. (52). HCDR1, HCDR2, and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:491, and LCDR1, LCDR2, and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:492; or (53). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:493 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:

494.

5. The antibody or antigen-binding fragment according to claim 4, wherein: (1). The HCDR1 contains the amino acid sequence of SEQ ID NO:855, the HCDR2 contains the amino acid sequence of SEQ ID NO:856, the HCDR3 contains the amino acid sequence of SEQ ID NO:857, the LCDR1 contains the amino acid sequence of SEQ ID NO:858, the LCDR2 contains the amino acid sequence of SEQ ID NO:1282, and the LCDR3 contains the amino acid sequence of SEQ ID NO:860; (2). The HCDR1 contains the amino acid sequence of SEQ ID NO:987, the HCDR2 contains the amino acid sequence of SEQ ID NO:988, the HCDR3 contains the amino acid sequence of SEQ ID NO:989, the LCDR1 contains the amino acid sequence of SEQ ID NO:990, the LCDR2 contains the amino acid sequence of SEQ ID NO:991, and the LCDR3 contains the amino acid sequence of SEQ ID NO:992; (3). The HCDR1 contains the amino acid sequence of SEQ ID NO:849, the HCDR2 contains the amino acid sequence of SEQ ID NO:850, the HCDR3 contains the amino acid sequence of SEQ ID NO:851, the LCDR1 contains the amino acid sequence of SEQ ID NO:852, the LCDR2 contains the amino acid sequence of SEQ ID NO:853, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

854. (4). The HCDR1 contains the amino acid sequence of SEQ ID NO:855, the HCDR2 contains the amino acid sequence of SEQ ID NO:856, the HCDR3 contains the amino acid sequence of SEQ ID NO:857, the LCDR1 contains the amino acid sequence of SEQ ID NO:858, the LCDR2 contains the amino acid sequence of SEQ ID NO:859, and the LCDR3 contains the amino acid sequence of SEQ ID NO:860; (5). The HCDR1 contains the amino acid sequence of SEQ ID NO:861, the HCDR2 contains the amino acid sequence of SEQ ID NO:862, the HCDR3 contains the amino acid sequence of SEQ ID NO:863, the LCDR1 contains the amino acid sequence of SEQ ID NO:864, the LCDR2 contains the amino acid sequence of SEQ ID NO:865, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

866. (6). The HCDR1 contains the amino acid sequence of SEQ ID NO:867, the HCDR2 contains the amino acid sequence of SEQ ID NO:868, the HCDR3 contains the amino acid sequence of SEQ ID NO:869, the LCDR1 contains the amino acid sequence of SEQ ID NO:870, the LCDR2 contains the amino acid sequence of SEQ ID NO:871, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

872. (7). The HCDR1 contains the amino acid sequence of SEQ ID NO:873, the HCDR2 contains the amino acid sequence of SEQ ID NO:874, the HCDR3 contains the amino acid sequence of SEQ ID NO:875, the LCDR1 contains the amino acid sequence of SEQ ID NO:876, the LCDR2 contains the amino acid sequence of SEQ ID NO:877, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

878. (8). The HCDR1 contains the amino acid sequence of SEQ ID NO:879, the HCDR2 contains the amino acid sequence of SEQ ID NO:880, the HCDR3 contains the amino acid sequence of SEQ ID NO:881, the LCDR1 contains the amino acid sequence of SEQ ID NO:882, the LCDR2 contains the amino acid sequence of SEQ ID NO:883, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

884. (9). The HCDR1 contains the amino acid sequence of SEQ ID NO:885, the HCDR2 contains the amino acid sequence of SEQ ID NO:886, the HCDR3 contains the amino acid sequence of SEQ ID NO:887, the LCDR1 contains the amino acid sequence of SEQ ID NO:888, the LCDR2 contains the amino acid sequence of SEQ ID NO:889, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

890. (10). The HCDR1 contains the amino acid sequence of SEQ ID NO:891, the HCDR2 contains the amino acid sequence of SEQ ID NO:892, the HCDR3 contains the amino acid sequence of SEQ ID NO:893, the LCDR1 contains the amino acid sequence of SEQ ID NO:894, the LCDR2 contains the amino acid sequence of SEQ ID NO:895, and the LCDR3 contains the amino acid sequence of SEQ ID NO:896; (11). The HCDR1 contains the amino acid sequence of SEQ ID NO:897, the HCDR2 contains the amino acid sequence of SEQ ID NO:898, the HCDR3 contains the amino acid sequence of SEQ ID NO:899, the LCDR1 contains the amino acid sequence of SEQ ID NO:900, the LCDR2 contains the amino acid sequence of SEQ ID NO:901, and the LCDR3 contains the amino acid sequence of SEQ ID NO:902; (12). The HCDR1 contains the amino acid sequence of SEQ ID NO:903, the HCDR2 contains the amino acid sequence of SEQ ID NO:904, the HCDR3 contains the amino acid sequence of SEQ ID NO:905, the LCDR1 contains the amino acid sequence of SEQ ID NO:906, the LCDR2 contains the amino acid sequence of SEQ ID NO:907, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

908. (13). The HCDR1 contains the amino acid sequence of SEQ ID NO:909, the HCDR2 contains the amino acid sequence of SEQ ID NO:910, the HCDR3 contains the amino acid sequence of SEQ ID NO:911, the LCDR1 contains the amino acid sequence of SEQ ID NO:912, the LCDR2 contains the amino acid sequence of SEQ ID NO:913, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

914. (14). The HCDR1 contains the amino acid sequence of SEQ ID NO:915, the HCDR2 contains the amino acid sequence of SEQ ID NO:916, the HCDR3 contains the amino acid sequence of SEQ ID NO:917, the LCDR1 contains the amino acid sequence of SEQ ID NO:918, the LCDR2 contains the amino acid sequence of SEQ ID NO:919, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

920. (15). The HCDR1 contains the amino acid sequence of SEQ ID NO:921, the HCDR2 contains the amino acid sequence of SEQ ID NO:922, the HCDR3 contains the amino acid sequence of SEQ ID NO:923, the LCDR1 contains the amino acid sequence of SEQ ID NO:924, the LCDR2 contains the amino acid sequence of SEQ ID NO:925, and the LCDR3 contains the amino acid sequence of SEQ ID NO:926; (16). The HCDR1 contains the amino acid sequence of SEQ ID NO:927, the HCDR2 contains the amino acid sequence of SEQ ID NO:928, the HCDR3 contains the amino acid sequence of SEQ ID NO:929, the LCDR1 contains the amino acid sequence of SEQ ID NO:930, the LCDR2 contains the amino acid sequence of SEQ ID NO:931, and the LCDR3 contains the amino acid sequence of SEQ ID NO:932; (17). The HCDR1 contains the amino acid sequence of SEQ ID NO:933, the HCDR2 contains the amino acid sequence of SEQ ID NO:934, the HCDR3 contains the amino acid sequence of SEQ ID NO:935, the LCDR1 contains the amino acid sequence of SEQ ID NO:936, the LCDR2 contains the amino acid sequence of SEQ ID NO:937, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

938. (18). The HCDR1 contains the amino acid sequence of SEQ ID NO:939, the HCDR2 contains the amino acid sequence of SEQ ID NO:940, the HCDR3 contains the amino acid sequence of SEQ ID NO:941, the LCDR1 contains the amino acid sequence of SEQ ID NO:942, the LCDR2 contains the amino acid sequence of SEQ ID NO:943, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

944. (19). The HCDR1 contains the amino acid sequence of SEQ ID NO:945, the HCDR2 contains the amino acid sequence of SEQ ID NO:946, the HCDR3 contains the amino acid sequence of SEQ ID NO:947, the LCDR1 contains the amino acid sequence of SEQ ID NO:948, the LCDR2 contains the amino acid sequence of SEQ ID NO:949, and the LCDR3 contains the amino acid sequence of SEQ ID NO:950; (20). The HCDR1 contains the amino acid sequence of SEQ ID NO:951, the HCDR2 contains the amino acid sequence of SEQ ID NO:952, the HCDR3 contains the amino acid sequence of SEQ ID NO:953, the LCDR1 contains the amino acid sequence of SEQ ID NO:954, the LCDR2 contains the amino acid sequence of SEQ ID NO:955, and the LCDR3 contains the amino acid sequence of SEQ ID NO:956; (21). The HCDR1 contains the amino acid sequence of SEQ ID NO:957, the HCDR2 contains the amino acid sequence of SEQ ID NO:958, the HCDR3 contains the amino acid sequence of SEQ ID NO:959, the LCDR1 contains the amino acid sequence of SEQ ID NO:960, the LCDR2 contains the amino acid sequence of SEQ ID NO:961, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

962. (22). The HCDR1 contains the amino acid sequence of SEQ ID NO:963, the HCDR2 contains the amino acid sequence of SEQ ID NO:964, the HCDR3 contains the amino acid sequence of SEQ ID NO:965, the LCDR1 contains the amino acid sequence of SEQ ID NO:966, the LCDR2 contains the amino acid sequence of SEQ ID NO:967, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

968. (23). The HCDR1 contains the amino acid sequence of SEQ ID NO:969, the HCDR2 contains the amino acid sequence of SEQ ID NO:970, the HCDR3 contains the amino acid sequence of SEQ ID NO:971, the LCDR1 contains the amino acid sequence of SEQ ID NO:972, the LCDR2 contains the amino acid sequence of SEQ ID NO:973, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

974. (24). The HCDR1 contains the amino acid sequence of SEQ ID NO:975, the HCDR2 contains the amino acid sequence of SEQ ID NO:976, the HCDR3 contains the amino acid sequence of SEQ ID NO:977, the LCDR1 contains the amino acid sequence of SEQ ID NO:978, the LCDR2 contains the amino acid sequence of SEQ ID NO:979, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

980. (25). The HCDR1 contains the amino acid sequence of SEQ ID NO:981, the HCDR2 contains the amino acid sequence of SEQ ID NO:982, the HCDR3 contains the amino acid sequence of SEQ ID NO:983, the LCDR1 contains the amino acid sequence of SEQ ID NO:984, the LCDR2 contains the amino acid sequence of SEQ ID NO:985, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

986. (26). The HCDR1 contains the amino acid sequence of SEQ ID NO:993, the HCDR2 contains the amino acid sequence of SEQ ID NO:994, the HCDR3 contains the amino acid sequence of SEQ ID NO:995, the LCDR1 contains the amino acid sequence of SEQ ID NO:996, the LCDR2 contains the amino acid sequence of SEQ ID NO:997, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

998. (27). The HCDR1 contains the amino acid sequence of SEQ ID NO:999, the HCDR2 contains the amino acid sequence of SEQ ID NO:1000, the HCDR3 contains the amino acid sequence of SEQ ID NO:1001, the LCDR1 contains the amino acid sequence of SEQ ID NO:1002, the LCDR2 contains the amino acid sequence of SEQ ID NO:1003, and the LCDR3 contains the amino acid sequence of SEQ ID NO:1004. (28). The HCDR1 contains the amino acid sequence of SEQ ID NO:1005, the HCDR2 contains the amino acid sequence of SEQ ID NO:1006, the HCDR3 contains the amino acid sequence of SEQ ID NO:1007, the LCDR1 contains the amino acid sequence of SEQ ID NO:1008, the LCDR2 contains the amino acid sequence of SEQ ID NO:1009, and the LCDR3 contains the amino acid sequence of SEQ ID NO:1010. (29). The HCDR1 contains the amino acid sequence of SEQ ID NO:1011, the HCDR2 contains the amino acid sequence of SEQ ID NO:1012, the HCDR3 contains the amino acid sequence of SEQ ID NO:1013, the LCDR1 contains the amino acid sequence of SEQ ID NO:1014, the LCDR2 contains the amino acid sequence of SEQ ID NO:1015, and the LCDR3 contains the amino acid sequence of SEQ ID NO:1016. (30). The HCDR1 contains the amino acid sequence of SEQ ID NO:1017, the HCDR2 contains the amino acid sequence of SEQ ID NO:1018, the HCDR3 contains the amino acid sequence of SEQ ID NO:1019, the LCDR1 contains the amino acid sequence of SEQ ID NO:1020, the LCDR2 contains the amino acid sequence of SEQ ID NO:1021, and the LCDR3 contains the amino acid sequence of SEQ ID NO:1022. (31). The HCDR1 contains the amino acid sequence of SEQ ID NO:1023, the HCDR2 contains the amino acid sequence of SEQ ID NO:1024, the HCDR3 contains the amino acid sequence of SEQ ID NO:1025, the LCDR1 contains the amino acid sequence of SEQ ID NO:1026, the LCDR2 contains the amino acid sequence of SEQ ID NO:1027, and the LCDR3 contains the amino acid sequence of SEQ ID NO:1028. (32). The HCDR1 contains the amino acid sequence of SEQ ID NO:1029, the HCDR2 contains the amino acid sequence of SEQ ID NO:1030, the HCDR3 contains the amino acid sequence of SEQ ID NO:1031, the LCDR1 contains the amino acid sequence of SEQ ID NO:1032, the LCDR2 contains the amino acid sequence of SEQ ID NO:1033, and the LCDR3 contains the amino acid sequence of SEQ ID NO:1034. (33). The HCDR1 contains the amino acid sequence of SEQ ID NO:1035, the HCDR2 contains the amino acid sequence of SEQ ID NO:1036, the HCDR3 contains the amino acid sequence of SEQ ID NO:1037, the LCDR1 contains the amino acid sequence of SEQ ID NO:1038, the LCDR2 contains the amino acid sequence of SEQ ID NO:1039, and the LCDR3 contains the amino acid sequence of SEQ ID NO:1040. (34). The HCDR1 contains the amino acid sequence of SEQ ID NO:1041, the HCDR2 contains the amino acid sequence of SEQ ID NO:1042, the HCDR3 contains the amino acid sequence of SEQ ID NO:1043, the LCDR1 contains the amino acid sequence of SEQ ID NO:1044, the LCDR2 contains the amino acid sequence of SEQ ID NO:1045, and the LCDR3 contains the amino acid sequence of SEQ ID NO:1046. (35). The HCDR1 contains the amino acid sequence of SEQ ID NO:1047, the HCDR2 contains the amino acid sequence of SEQ ID NO:1048, the HCDR3 contains the amino acid sequence of SEQ ID NO:1049, the LCDR1 contains the amino acid sequence of SEQ ID NO:1050, the LCDR2 contains the amino acid sequence of SEQ ID NO:1051, and the LCDR3 contains the amino acid sequence of SEQ ID NO:1052. (36). The HCDR1 contains the amino acid sequence of SEQ ID NO:1053, the HCDR2 contains the amino acid sequence of SEQ ID NO:1054, the HCDR3 contains the amino acid sequence of SEQ ID NO:1055, the LCDR1 contains the amino acid sequence of SEQ ID NO:1056, the LCDR2 contains the amino acid sequence of SEQ ID NO:1057, and the LCDR3 contains the amino acid sequence of SEQ ID NO:1058. (37). The HCDR1 contains the amino acid sequence of SEQ ID NO:1059, the HCDR2 contains the amino acid sequence of SEQ ID NO:1060, the HCDR3 contains the amino acid sequence of SEQ ID NO:1061, the LCDR1 contains the amino acid sequence of SEQ ID NO:1062, the LCDR2 contains the amino acid sequence of SEQ ID NO:1063, and the LCDR3 contains the amino acid sequence of SEQ ID NO:1064. (38). The HCDR1 contains the amino acid sequence of SEQ ID NO:1065, the HCDR2 contains the amino acid sequence of SEQ ID NO:1066, the HCDR3 contains the amino acid sequence of SEQ ID NO:1067, the LCDR1 contains the amino acid sequence of SEQ ID NO:1068, the LCDR2 contains the amino acid sequence of SEQ ID NO:1069, and the LCDR3 contains the amino acid sequence of SEQ ID NO:1070. (39). The HCDR1 contains the amino acid sequence of SEQ ID NO:1071, the HCDR2 contains the amino acid sequence of SEQ ID NO:1072, the HCDR3 contains the amino acid sequence of SEQ ID NO:1073, the LCDR1 contains the amino acid sequence of SEQ ID NO:1074, the LCDR2 contains the amino acid sequence of SEQ ID NO:1075, and the LCDR3 contains the amino acid sequence of SEQ ID NO:1076. (40). The HCDR1 contains the amino acid sequence of SEQ ID NO:1077, the HCDR2 contains the amino acid sequence of SEQ ID NO:1078, the HCDR3 contains the amino acid sequence of SEQ ID NO:1079, the LCDR1 contains the amino acid sequence of SEQ ID NO:1080, the LCDR2 contains the amino acid sequence of SEQ ID NO:1081, and the LCDR3 contains the amino acid sequence of SEQ ID NO:1082. (41). The HCDR1 contains the amino acid sequence of SEQ ID NO:1083, the HCDR2 contains the amino acid sequence of SEQ ID NO:1084, the HCDR3 contains the amino acid sequence of SEQ ID NO:1085, the LCDR1 contains the amino acid sequence of SEQ ID NO:1086, the LCDR2 contains the amino acid sequence of SEQ ID NO:1087, and the LCDR3 contains the amino acid sequence of SEQ ID NO:1088. (42). The HCDR1 contains the amino acid sequence of SEQ ID NO:1089, the HCDR2 contains the amino acid sequence of SEQ ID NO:1090, the HCDR3 contains the amino acid sequence of SEQ ID NO:1091, the LCDR1 contains the amino acid sequence of SEQ ID NO:1092, the LCDR2 contains the amino acid sequence of SEQ ID NO:1093, and the LCDR3 contains the amino acid sequence of SEQ ID NO:1094. (43). The HCDR1 contains the amino acid sequence of SEQ ID NO:1095, the HCDR2 contains the amino acid sequence of SEQ ID NO:1096, the HCDR3 contains the amino acid sequence of SEQ ID NO:1097, the LCDR1 contains the amino acid sequence of SEQ ID NO:1098, the LCDR2 contains the amino acid sequence of SEQ ID NO:1099, and the LCDR3 contains the amino acid sequence of SEQ ID NO:1100. (44). The HCDR1 contains the amino acid sequence of SEQ ID NO:1101, the HCDR2 contains the amino acid sequence of SEQ ID NO:1102, the HCDR3 contains the amino acid sequence of SEQ ID NO:1103, the LCDR1 contains the amino acid sequence of SEQ ID NO:1104, the LCDR2 contains the amino acid sequence of SEQ ID NO:1105, and the LCDR3 contains the amino acid sequence of SEQ ID NO:1106. (45). The HCDR1 contains the amino acid sequence of SEQ ID NO:1107, the HCDR2 contains the amino acid sequence of SEQ ID NO:1108, the HCDR3 contains the amino acid sequence of SEQ ID NO:1109, the LCDR1 contains the amino acid sequence of SEQ ID NO:1110, the LCDR2 contains the amino acid sequence of SEQ ID NO:1111, and the LCDR3 contains the amino acid sequence of SEQ ID NO:1112. (46). The HCDR1 contains the amino acid sequence of SEQ ID NO:1113, the HCDR2 contains the amino acid sequence of SEQ ID NO:1114, the HCDR3 contains the amino acid sequence of SEQ ID NO:1115, the LCDR1 contains the amino acid sequence of SEQ ID NO:1116, the LCDR2 contains the amino acid sequence of SEQ ID NO:1117, and the LCDR3 contains the amino acid sequence of SEQ ID NO:1118. (47). The HCDR1 contains the amino acid sequence of SEQ ID NO:1119, the HCDR2 contains the amino acid sequence of SEQ ID NO:1120, the HCDR3 contains the amino acid sequence of SEQ ID NO:1121, the LCDR1 contains the amino acid sequence of SEQ ID NO:1122, the LCDR2 contains the amino acid sequence of SEQ ID NO:1123, and the LCDR3 contains the amino acid sequence of SEQ ID NO:1124; or (48). The HCDR1 contains the amino acid sequence of SEQ ID NO:1125, the HCDR2 contains the amino acid sequence of SEQ ID NO:1126, the HCDR3 contains the amino acid sequence of SEQ ID NO:1127, the LCDR1 contains the amino acid sequence of SEQ ID NO:1128, the LCDR2 contains the amino acid sequence of SEQ ID NO:1129, and the LCDR3 contains the amino acid sequence of SEQ ID NO:1130.

6. The antibody or antigen-binding fragment according to claim 4 or 5, comprising: (1). VH containing the amino acid sequence of SEQ ID NO:1167 and VL containing the amino acid sequence of SEQ ID NO:1168; (2). VH containing the amino acid sequence of SEQ ID NO:1169 and VL containing the amino acid sequence of SEQ ID NO:1170; (3). VH containing the amino acid sequence of SEQ ID NO:1171 and VL containing the amino acid sequence of SEQ ID NO:1172; (4). VH containing the amino acid sequence of SEQ ID NO:1173 and VL containing the amino acid sequence of SEQ ID NO:1174; (5). VH containing the amino acid sequence of SEQ ID NO:1175 and VL containing the amino acid sequence of SEQ ID NO:1176; (6). VH containing the amino acid sequence of SEQ ID NO:1177 and VL containing the amino acid sequence of SEQ ID NO:1178; (7). VH containing the amino acid sequence of SEQ ID NO:401 and VL containing the amino acid sequence of SEQ ID NO:402; (8). VH containing the amino acid sequence of SEQ ID NO:403 and VL containing the amino acid sequence of SEQ ID NO:404; (9). VH containing the amino acid sequence of SEQ ID NO:405 and VL containing the amino acid sequence of SEQ ID NO:406; (10). VH containing the amino acid sequence of SEQ ID NO:407 and VL containing the amino acid sequence of SEQ ID NO:408; (11). VH containing the amino acid sequence of SEQ ID NO:409 and VL containing the amino acid sequence of SEQ ID NO:410; (12). VH containing the amino acid sequence of SEQ ID NO:411 and VL containing the amino acid sequence of SEQ ID NO:412; (13). VH containing the amino acid sequence of SEQ ID NO:413 and VL containing the amino acid sequence of SEQ ID NO:414; (14). VH containing the amino acid sequence of SEQ ID NO:415 and VL containing the amino acid sequence of SEQ ID NO:416; (15). VH containing the amino acid sequence of SEQ ID NO:417 and VL containing the amino acid sequence of SEQ ID NO:418; (16). VH containing the amino acid sequence of SEQ ID NO:419 and VL containing the amino acid sequence of SEQ ID NO:420; (17). VH containing the amino acid sequence of SEQ ID NO:421 and VL containing the amino acid sequence of SEQ ID NO:422; (18). VH containing the amino acid sequence of SEQ ID NO:423 and VL containing the amino acid sequence of SEQ ID NO:424; (19). VH containing the amino acid sequence of SEQ ID NO:425 and VL containing the amino acid sequence of SEQ ID NO:426; (20). VH containing the amino acid sequence of SEQ ID NO:427 and VL containing the amino acid sequence of SEQ ID NO:428; (21). VH containing the amino acid sequence of SEQ ID NO:429 and VL containing the amino acid sequence of SEQ ID NO:430; (22). VH containing the amino acid sequence of SEQ ID NO:431 and VL containing the amino acid sequence of SEQ ID NO:432; (23). VH containing the amino acid sequence of SEQ ID NO:433 and VL containing the amino acid sequence of SEQ ID NO:434; (24). VH containing the amino acid sequence of SEQ ID NO:435 and VL containing the amino acid sequence of SEQ ID NO:436; (25). VH containing the amino acid sequence of SEQ ID NO:437 and VL containing the amino acid sequence of SEQ ID NO:438; (26). VH containing the amino acid sequence of SEQ ID NO:439 and VL containing the amino acid sequence of SEQ ID NO:440; (27). VH containing the amino acid sequence of SEQ ID NO:441 and VL containing the amino acid sequence of SEQ ID NO:442; (28). VH containing the amino acid sequence of SEQ ID NO:443 and VL containing the amino acid sequence of SEQ ID NO:444; (29). VH containing the amino acid sequence of SEQ ID NO:445 and VL containing the amino acid sequence of SEQ ID NO:446; (30). VH containing the amino acid sequence of SEQ ID NO:447 and VL containing the amino acid sequence of SEQ ID NO:448; (31). VH containing the amino acid sequence of SEQ ID NO:449 and VL containing the amino acid sequence of SEQ ID NO:450; (32). VH containing the amino acid sequence of SEQ ID NO:451 and VL containing the amino acid sequence of SEQ ID NO:452; (33). VH containing the amino acid sequence of SEQ ID NO:453 and VL containing the amino acid sequence of SEQ ID NO:454; (34). VH containing the amino acid sequence of SEQ ID NO:455 and VL containing the amino acid sequence of SEQ ID NO:456; (35). VH containing the amino acid sequence of SEQ ID NO:457 and VL containing the amino acid sequence of SEQ ID NO:458; (36). VH containing the amino acid sequence of SEQ ID NO:459 and VL containing the amino acid sequence of SEQ ID NO:460; (37). VH containing the amino acid sequence of SEQ ID NO:461 and VL containing the amino acid sequence of SEQ ID NO:462; (38). VH containing the amino acid sequence of SEQ ID NO:463 and VL containing the amino acid sequence of SEQ ID NO:464; (39). VH containing the amino acid sequence of SEQ ID NO:465 and VL containing the amino acid sequence of SEQ ID NO:466; (40). VH containing the amino acid sequence of SEQ ID NO:467 and VL containing the amino acid sequence of SEQ ID NO:468; (41). VH containing the amino acid sequence of SEQ ID NO:469 and VL containing the amino acid sequence of SEQ ID NO:470; (42). VH containing the amino acid sequence of SEQ ID NO:471 and VL containing the amino acid sequence of SEQ ID NO:472; (43). VH containing the amino acid sequence of SEQ ID NO:473 and VL containing the amino acid sequence of SEQ ID NO:474; (44). VH containing the amino acid sequence of SEQ ID NO:475 and VL containing the amino acid sequence of SEQ ID NO:476; (45). VH containing the amino acid sequence of SEQ ID NO:477 and VL containing the amino acid sequence of SEQ ID NO:478; (46). VH containing the amino acid sequence of SEQ ID NO:479 and VL containing the amino acid sequence of SEQ ID NO:480; (47). VH containing the amino acid sequence of SEQ ID NO:481 and VL containing the amino acid sequence of SEQ ID NO:482; (48). VH containing the amino acid sequence of SEQ ID NO:483 and VL containing the amino acid sequence of SEQ ID NO:484; (49). VH containing the amino acid sequence of SEQ ID NO:485 and VL containing the amino acid sequence of SEQ ID NO:486; (50). VH containing the amino acid sequence of SEQ ID NO:487 and VL containing the amino acid sequence of SEQ ID NO:488; (51). VH containing the amino acid sequence of SEQ ID NO:489 and VL containing the amino acid sequence of SEQ ID NO:490; (52). VH containing the amino acid sequence of SEQ ID NO:491 and VL containing the amino acid sequence of SEQ ID NO:492; or (53). VH containing the amino acid sequence of SEQ ID NO:493 and VL containing the amino acid sequence of SEQ ID NO:

494.

7. A multispecific antibody or a fragment thereof, the multispecific antibody or fragment thereof comprising a first binding domain to LILRB1 and a second binding domain to LILRB2, wherein the first binding domain comprises the antibody or antigen-binding fragment thereof according to claims 1 to 3, and wherein optionally the second binding domain comprises the antibody or antigen-binding fragment thereof according to claims 4 to 6.

8. A multispecific antibody or a fragment thereof, the multispecific antibody or fragment thereof comprising a first binding domain to LILRB1 and a second binding domain to LILRB2, wherein the second binding domain comprises the antibody or antigen-binding fragment thereof according to claims 4 to 6, and wherein optionally the first binding domain comprises the antibody or antigen-binding fragment thereof according to claims 1 to 3.

9. The multispecific antibody or fragment thereof according to claim 7 or 8, wherein the multispecific antibody or fragment thereof is in the antibody form of an immunoglobulin-single-chain antibody fragment (IgG-ScFv).

10. The multispecific antibody or fragment thereof according to claim 7 or 8, wherein the multispecific antibody or fragment thereof has an antibody form with a dual variable domain-immunoglobulin (DVD-Ig).

11. The multispecific antibody or a fragment thereof according to claim 7 or 8, The first binding domain includes any one or more of (1) to (6): (1). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:1155 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:1156. (2). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:1157 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:1158. (3). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:1159 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:1160. (4). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:1161 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:1162. (5). HCDR1, HCDR2, and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO: 1163, and LCDR1, LCDR2, and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO: 1164; or (6). HCDR1, HCDR2, and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO: 1165, and LCDR1, LCDR2, and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO: 1166; and The second binding domain comprises one or more of (1) to (6): (1). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:1167 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:1168. (2). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:1169 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:1170. (3). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:1171 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:1172. (4). HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:1173 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:1174. (5). HCDR1, HCDR2, and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO: 1175, and LCDR1, LCDR2, and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO: 1176; or (6) HCDR1, HCDR2 and HCDR3 as shown in VH containing the amino acid sequence of SEQ ID NO:1177 and LCDR1, LCDR2 and LCDR3 as shown in VL containing the amino acid sequence of SEQ ID NO:1178.

12. The multispecific antibody or fragment thereof according to claim 11, The first binding domain includes any one or more of (1) to (6): (1). VH containing the amino acid sequence of SEQ ID NO:1155 and VL containing the amino acid sequence of SEQ ID NO:1156; (2). VH containing the amino acid sequence of SEQ ID NO:1157 and VL containing the amino acid sequence of SEQ ID NO:1158; (3). VH containing the amino acid sequence of SEQ ID NO:1159 and VL containing the amino acid sequence of SEQ ID NO:1160; (4). VH containing the amino acid sequence of SEQ ID NO:1161 and VL containing the amino acid sequence of SEQ ID NO:1162; (5) VH containing the amino acid sequence of SEQ ID NO:1163 and VL containing the amino acid sequence of SEQ ID NO:1164; or (6). VH containing the amino acid sequence of SEQ ID NO:1165 and VL containing the amino acid sequence of SEQ ID NO:1166; and The second binding domain comprises one or more of (1) to (6): (1). VH containing the amino acid sequence of SEQ ID NO:1167 and VL containing the amino acid sequence of SEQ ID NO:1168; (2). VH containing the amino acid sequence of SEQ ID NO:1169 and VL containing the amino acid sequence of SEQ ID NO:1170; (3). VH containing the amino acid sequence of SEQ ID NO:1171 and VL containing the amino acid sequence of SEQ ID NO:1172; (4). VH containing the amino acid sequence of SEQ ID NO:1173 and VL containing the amino acid sequence of SEQ ID NO:1174; (5). VH containing the amino acid sequence of SEQ ID NO:1175 and VL containing the amino acid sequence of SEQ ID NO:1176; or (6). VH containing the amino acid sequence of SEQ ID NO:1177 and VL containing the amino acid sequence of SEQ ID NO:1178.

13. The multispecific antibody or fragment thereof according to claim 11 or 12, wherein the multispecific antibody or fragment thereof comprises: (1). A first polypeptide containing the amino acid sequence of SEQ ID NO:1180 and a second polypeptide containing the amino acid sequence of SEQ ID NO:1181; (2). A first polypeptide containing the amino acid sequence of SEQ ID NO:1182 and a second polypeptide containing the amino acid sequence of SEQ ID NO:1183; (3). A first polypeptide containing the amino acid sequence of SEQ ID NO:1184 and a second polypeptide containing the amino acid sequence of SEQ ID NO:1185; (4). A first polypeptide containing the amino acid sequence of SEQ ID NO:1186 and a second polypeptide containing the amino acid sequence of SEQ ID NO:1187; (5). A first polypeptide containing the amino acid sequence of SEQ ID NO:1188 and a second polypeptide containing the amino acid sequence of SEQ ID NO:1189; (6). A first polypeptide containing the amino acid sequence of SEQ ID NO:1190 and a second polypeptide containing the amino acid sequence of SEQ ID NO:1191; (7). A first polypeptide containing the amino acid sequence of SEQ ID NO:1192 and a second polypeptide containing the amino acid sequence of SEQ ID NO:1193; (8). A first polypeptide containing the amino acid sequence of SEQ ID NO:1194 and a second polypeptide containing the amino acid sequence of SEQ ID NO:1195; (9) A first polypeptide containing the amino acid sequence of SEQ ID NO:1196 and a second polypeptide containing the amino acid sequence of SEQ ID NO:1197; (10). A first polypeptide containing the amino acid sequence of SEQ ID NO:1198 and a second polypeptide containing the amino acid sequence of SEQ ID NO:1199; (11) A first polypeptide containing the amino acid sequence of SEQ ID NO: 1200 and a second polypeptide containing the amino acid sequence of SEQ ID NO: 1201; or (12). A first polypeptide containing the amino acid sequence of SEQ ID NO:1202 and a second polypeptide containing the amino acid sequence of SEQ ID NO:1203.

14. The antibody or antigen-binding fragment according to any one of claims 1 to 13, wherein the antibody is IgG.

15. A nucleic acid molecule encoding an antibody or antigen-binding fragment according to any one of claims 1 to 14.

16. A vector comprising the nucleic acid molecule according to claim 15.

17. A host cell, said host cell being transformed with the vector according to claim 16.

18. A composition comprising a therapeutically effective amount of an antibody or antigen-binding fragment according to any one of claims 1 to 14, a nucleic acid molecule according to claim 15, or a carrier according to claim 16, and a pharmaceutically acceptable excipient.

19. A method for preventing the inhibition or activation of immune cell-mediated responses by immune cells, the method comprising contacting the immune cells with an antibody or fragment thereof according to any one of claims 1 to 14 or a pharmaceutical composition according to claim 18.

20. The method of claim 19, wherein the immune cell is an NK cell, macrophage, T cell, or dendritic cell.

21. The method of claim 20, wherein the T cell is CD8. + T cells.

22. The method according to any one of claims 19 to 21, wherein the immune cells express LILRB1 and / or LILRB2.

23. The method according to any one of claims 19 to 22, wherein the response mediated by the immune cells is an antitumor response, optionally wherein the tumor cells express HLA-A2, HLA-G and / or ANGPTL.

24. A method for treating a disease or disorder in a subject, the method comprising administering to the subject an antibody or antigen-binding fragment according to any one of claims 1 to 14 or a pharmaceutical composition according to claim 18.

25. The method of claim 24, wherein the disease or disorder is cancer, optionally the cancer expressing HLA-A2, HLA-G and / or ANGPTL.

26. The method of claim 24, wherein the disease or disorder is a solid tumor or a hematologic malignancy.

27. The method according to any one of claims 24 to 26, wherein the subject is a human subject.

28. The method of claim 24, wherein the antibody or antigen-binding fragment is used as part of a combination therapy.

29. The method of claim 28, wherein the antibody or antigen-binding fragment is used in combination with a PD-1 inhibitor, wherein optionally, the PD-1 inhibitor is an anti-PD-1 antibody, wherein optionally, the anti-PD-1 antibody is nivolumab.

30. The method of claim 28, wherein the antibody or antigen-binding fragment is used in combination with a PD-L1 inhibitor, wherein optionally, the PD-L1 inhibitor is an anti-PD-L1 antibody, wherein optionally, the anti-PD-L1 antibody is LAE005.

31. The method of claim 28, wherein the antibody or antigen-binding fragment is used in combination with an anti-CD47 antibody, wherein optionally the anti-CD47 antibody is Hu5F9-G4.

32. The method of claim 28, wherein the antibody or antigen-binding fragment is used in combination with an anti-CD3 antibody, wherein optionally the anti-CD3 antibody is OKT3.

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