Antibody capable of specifically recognizing NKG2A and application thereof

Abstract

Relates to an antibody or antigen binding fragment capable of specifically recognizing NKG2A, and a preparation method and application thereof.

Description

Antibodies specifically recognizing NKG2A and their applications

[0001] Cross-reference to related applications

[0002] This application claims priority to Chinese patent application No. 202211127889.0, application date September 16, 2022, and invention name “Antibodies specifically recognizing NKG2A and their applications”, and the entire contents of that application are incorporated herein by reference.

[0003] Submit sequence listing as XML file

[0004] The contents of the electronic sequence listing are incorporated herein by reference in their entirety: (NKG2A_WIPO_seq.xml; size: 108 KB; and creation date: 2022.09.06). Technical Field

[0005] The present invention relates to antibodies that specifically recognize NKG2A, as well as preparation methods and uses thereof, including methods for using the antibodies to treat cancer, viral diseases, autoimmune diseases and / or inflammatory diseases. Background Art

[0006] Natural killer (NK) cells are an important component of the innate immune system and are crucial immune regulatory cells for the body's resistance to infection and prevention of cell malignant transformation. Human NK cells account for approximately 10% to 15% of total blood lymphocytes. Current research suggests that NK cells specifically express CD56 and lack the T cell antigen CD3. NK cells have the following functions: (1) direct cytotoxic activity against virus-infected cells, leukemia cells, and other tumor cells; (2) secrete a variety of immunoregulatory cytokines (e.g., IFN-γ, TNF-α, GM-CSF); and (3) mediate antibody-dependent cellular cytotoxicity (ADCC) by binding to the Fc region of antibodies via the cell membrane FcγRIII (CD16).

[0007] NK cell inhibitory receptors, primarily composed of immunoglobulin-like receptors (KIRs) and C-type lectin-like receptors (such as NKG2A), bind to MHC class I molecules to exert an inhibitory effect. KIRs exert their inhibitory effects by binding to HLA-A, HLA-B, and HLA-C in MHC class I molecules, while NKG2A exerts its inhibitory effects by binding to HLA-E. NKG2A is more sensitive to MHC class I downregulation than KIRs, so NKG2A, as an inhibitory receptor on the surface of NK cells, plays a more important role in regulating NK cell function. Furthermore, NKG2A not only regulates the activation process of CD8+ T cells but also inhibits CD8+ T cell function during their interactions with target cells. Therefore, NKG2A is crucial in regulating the activities of NK and CD8+ T cells, playing a particularly central role in eliminating tumors and virus-infected cells.

[0008] NKG2A is a member of the natural killer cell receptor family 2 (NKG2), which also includes NKG2B / C / D / E / F. NKG2A is an inhibitory receptor member of the NKG2 receptor family, also known as natural killer cell lectin-like receptor C1 (KLRC1). It is a transmembrane protein preferentially expressed on the surface of NK cells. NKG2A is primarily expressed on NK cells and can also be expressed on some T cells. In human NK cells, this protein is co-expressed with the CD94 molecule on the surface of NK cells. After being linked by disulfide bonds to form a heterodimeric complex NKG2A-CD94, it is recognized by the non-classical major histocompatibility complex class I (MHC I) class molecule HLA-E on the target cells. The N-terminal NK cell cytoplasmic domain of the NKG2A protein contains two immunoreceptor tyrosine-based inhibitory motifs (ITIMs), which can transmit inhibitory signals to NK cells, inducing a cascade of inhibitory signals, thereby inhibiting the cytotoxic activity of NK and the secretion of cytokines.

[0009] Patent application WO2008009545A1 discloses anti-NKG2A antibodies, as well as related methods and materials for producing and using the antibodies. WO2020102501A1 discloses antibodies that specifically bind to NKG2A proteins with high affinity and exhibit functional properties required for treatment, such as for the treatment of cancer. WO2020094071A1 discloses antibodies targeting NKG2A, which have NKG2A binding affinity and anti-tumor activities. Currently, Monalizumab, as an antagonistic antibody drug for NKG2A receptors, has shown certain therapeutic effects in clinical trials for several tumor diseases, but there is still a need for therapeutic antibodies with stronger activity and higher affinity that can effectively inhibit or antagonize NKG2A in other ways, as well as related methods for treating diseases and / or conditions caused by NKG2A signaling pathway disorders, such as cancer, viral diseases, autoimmune diseases and / or inflammatory diseases.

[0010] The disclosures of all publications, patents, patent applications, and published patent applications mentioned herein are incorporated by reference in their entirety. Summary of the Invention

[0011] Application Overview

[0012] In some embodiments, an isolated anti-NKG2A antibody is provided, comprising a heavy chain variable domain (V H ), the V H The heavy chain complementarity determining region (HC-CDR) 1 comprises SNTMS (SEQ ID NO: 1); HC-CDR2 comprises NINTGGNTYYANWAKG (SEQ ID NO: 9); and HC-CDR3 comprises GSTIDSSGLSL (SEQ ID NO: 24); and a light chain variable domain (V L ), the V L It comprises: a light chain complementary determining region (LC-CDR) 1 comprising QASQNIGSDLA (SEQ ID NO: 33); a LC-CDR2 comprising LASTLAS (SEQ ID NO: 43); and a LC-CDR3 comprising QQX1WSSSNVDNV (SEQ ID NO: 66), wherein X1 is C, S or T.

[0013] In some embodiments, an isolated anti-NKG2A antibody is provided, comprising V H , the V Hcomprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1 or a variant thereof, wherein the variant comprises at most about 3 amino acid substitutions; an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9 or a variant thereof, wherein the variant comprises at most about 3 amino acid substitutions; and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24 or a variant thereof, wherein the variant comprises at most about 3 amino acid substitutions; and V L , the V L Comprising: LC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:33 or a variant thereof, wherein the variant comprises substitutions of up to about 3 amino acids; LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:43 or a variant thereof, wherein the variant comprises substitutions of up to about 3 amino acids; and LC-CDR3, which comprises the amino acid sequence shown in any one of SEQ ID NOs:51-53 or a variant thereof, wherein the variant comprises substitutions of up to about 3 amino acids.

[0014] In some embodiments, an isolated anti-NKG2A antibody is provided, comprising: V H , the V H Comprising V as shown in any one of the amino acid sequences of SEQ ID NOs: 68-71 H Contains HC-CDR1, HC-CDR2 and HC-CDR3, as well as V L , the V L Comprising V as shown in any one of the amino acid sequences of SEQ ID NOs: 92-95 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0015] In some embodiments, an isolated anti-NKG2A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 68 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:92 L Containing LC-CDR1, LC-CDR2 and LC-CDR3; (ii) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 69 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:93 LContaining LC-CDR1, LC-CDR2 and LC-CDR3; (iii) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 70 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:93 L Containing LC-CDR1, LC-CDR2 and LC-CDR3; (iv) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 69 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:94 L Containing LC-CDR1, LC-CDR2 and LC-CDR3; (v) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 70 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:94 L Containing LC-CDR1, LC-CDR2 and LC-CDR3; (vi) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 71 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:95 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0016] In some embodiments, an isolated anti-NKG2A antibody is provided, comprising: (i) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V Lcomprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 33, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 43, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 51, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs; (ii) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 33, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 43, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 52, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs; (iii) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 33, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 43, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 53, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0017] In some embodiments, any of the isolated anti-NKG2A antibodies described above comprises: V H , comprising an amino acid sequence as shown in any one of SEQ ID NOs: 68-71 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence as shown in any one of SEQ ID NOs: 68-71; and V L, which comprises the amino acid sequence shown in any one of SEQ ID NOs:92-95 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in any one of SEQ ID NOs:92-95.

[0018] In some embodiments, an isolated anti-NKG2A antibody is provided comprising: (i) V H , comprising the amino acid sequence of SEQ ID NO: 68 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 68; and V L , comprising the amino acid sequence of SEQ ID NO: 92 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 92; (ii) V H , comprising the amino acid sequence of SEQ ID NO: 69 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 69; and V L , comprising the amino acid sequence of SEQ ID NO: 93 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 93; (iii) V H , comprising the amino acid sequence of SEQ ID NO: 70 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 70; and V L , comprising the amino acid sequence of SEQ ID NO: 93 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 93; (iv) V H , comprising the amino acid sequence of SEQ ID NO: 69 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 69; and V L , comprising the amino acid sequence of SEQ ID NO: 94 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 94; (v) V H , comprising the amino acid sequence of SEQ ID NO: 70 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 70; and V L , comprising the amino acid sequence of SEQ ID NO: 94 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 94; (vi) V H, comprising the amino acid sequence of SEQ ID NO: 71 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 71; and V L , comprising the amino acid sequence of SEQ ID NO: 95 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 95.

[0019] In some embodiments, an isolated anti-NKG2A antibody is provided, comprising a heavy chain variable domain (V H ), the V H The invention comprises: a heavy chain complementary determining region (HC-CDR) 1 comprising NYHMS (SEQ ID NO: 2); HC-CDR2 comprising YIGAAX1X2X3YYASWAKG (SEQ ID NO: 65), wherein X1 is G, N or S, X2 is N or S, and X3 is A, I or T; and HC-CDR3 comprising GVIYNNL (SEQ ID NO: 25); and a light chain variable domain (V L ), the V L It comprises: a light chain complementary determining region (LC-CDR) 1 comprising QASESISNYLS (SEQ ID NO: 34); a LC-CDR2 comprising DASDLAS (SEQ ID NO: 44); and a LC-CDR3 comprising QX1TYGSINX2NYGVA (SEQ ID NO: 67), wherein X1 is A or C, and X2 is A, Q or S.

[0020] In some embodiments, an isolated anti-NKG2A antibody is provided, comprising V H , the V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2 or a variant thereof, wherein the variant comprises at most about 3 amino acid substitutions; an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 10-16 or a variant thereof, wherein the variant comprises at most about 3 amino acid substitutions; and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25 or a variant thereof, wherein the variant comprises at most about 3 amino acid substitutions; and V L , the V LComprising: LC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:34 or a variant thereof, wherein the variant comprises substitutions of up to about 3 amino acids; LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:44 or a variant thereof, wherein the variant comprises substitutions of up to about 3 amino acids; and LC-CDR3, which comprises the amino acid sequence shown in any one of SEQ ID NOs:54-57 or a variant thereof, wherein the variant comprises substitutions of up to about 3 amino acids.

[0021] In some embodiments, an isolated anti-NKG2A antibody is provided, comprising: V H , the V H Comprising V as shown in any one of the amino acid sequences of SEQ ID NOs: 72-84 H Contains HC-CDR1, HC-CDR2 and HC-CDR3, as well as V L , the V L Comprising V as shown in any one of the amino acid sequences of SEQ ID NOs: 96-101 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0022] In some embodiments, an isolated anti-NKG2A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 72 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:96 L Containing LC-CDR1, LC-CDR2 and LC-CDR3; (ii) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 73 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:97 L Containing LC-CDR1, LC-CDR2 and LC-CDR3; (iii) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 74 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:97 L Containing LC-CDR1, LC-CDR2 and LC-CDR3; (iv) VH , which comprises V as shown in the amino acid sequence SEQ ID NO: 75 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:97 L Containing LC-CDR1, LC-CDR2 and LC-CDR3; (v) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 76 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:97 L Containing LC-CDR1, LC-CDR2 and LC-CDR3; (vi) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 77 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:97 L Containing LC-CDR1, LC-CDR2 and LC-CDR3; (vii) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 78 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:97 L Containing LC-CDR1, LC-CDR2 and LC-CDR3; (viii) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 73 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:98 L Containing LC-CDR1, LC-CDR2 and LC-CDR3; (ix) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 74 H comprising HC-CDR1, HC-CDR2 and HC-CDR3; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:98 L Contains LC-CDR1, LC-CDR2 and LC-CDR3; (x) VH , which comprises V as shown in the amino acid sequence SEQ ID NO: 75 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:98 L Containing LC-CDR1, LC-CDR2 and LC-CDR3; (xi) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 76 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:98 L LC-CDR1, LC-CDR2 and LC-CDR3 included; (xii) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 77 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:98 L LC-CDR1, LC-CDR2 and LC-CDR3 included; (xiii) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 78 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:98 L Containing LC-CDR1, LC-CDR2 and LC-CDR3; (xiv) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 78 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:99 L Contains LC-CDR1, LC-CDR2 and LC-CDR3; (xv) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 78 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 100 L Containing LC-CDR1, LC-CDR2 and LC-CDR3; (xvi) VH , which comprises V as shown in the amino acid sequence SEQ ID NO: 79 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 100 L Containing LC-CDR1, LC-CDR2 and LC-CDR3; (xvii) V H , which comprises V as shown in the amino acid sequence SEQ ID NO:80 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 100 L LC-CDR1, LC-CDR2 and LC-CDR3 included; (xviii) V H , which comprises V as shown in the amino acid sequence SEQ ID NO:81 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:99 L Containing LC-CDR1, LC-CDR2 and LC-CDR3; (xix) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 82 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:99 L Contains LC-CDR1, LC-CDR2 and LC-CDR3; (xx) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 83 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:99 L Containing LC-CDR1, LC-CDR2 and LC-CDR3; (xxi) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 84 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:99 LContaining LC-CDR1, LC-CDR2 and LC-CDR3; (xxii) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 79 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:99 L Containing LC-CDR1, LC-CDR2 and LC-CDR3; (xxiii) V H , which comprises V as shown in the amino acid sequence SEQ ID NO:80 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:99 L LC-CDR1, LC-CDR2 and LC-CDR3 included; (xxiv) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 78 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 101 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0023] In some embodiments, an isolated anti-NKG2A antibody is provided, comprising: (i) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 54, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs; (ii) V H , the V Hcomprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 55, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs; (iii) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 56, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs; (iv) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 56, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs; (v) V H, the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 56, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs; (vi) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 55, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs; (vii) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 14, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 55, or the V LA variant comprising up to about 5 amino acid substitutions in its LC-CDRs; (viii) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 15, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 55, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs; (ix) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 55, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs; (x) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V Lcomprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 55, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs; (xi) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 55, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs; (xii) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 57, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0024] In some embodiments, any of the isolated anti-NKG2A antibodies described above comprises: V H , comprising an amino acid sequence as shown in any one of SEQ ID NOs: 72-84 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence as shown in any one of SEQ ID NOs: 72-84; and V L, which comprises the amino acid sequence shown in any one of SEQ ID NOs:96-101 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in any one of SEQ ID NOs:96-101.

[0025] In some embodiments, an isolated anti-NKG2A antibody is provided comprising: (i) V H , comprising the amino acid sequence of SEQ ID NO: 72 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 72; and V L , comprising the amino acid sequence of SEQ ID NO: 96 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 96; (ii) V H , comprising the amino acid sequence of SEQ ID NO: 73 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 73; and V L , comprising the amino acid sequence of SEQ ID NO: 97 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 97; (iii) V H , comprising the amino acid sequence of SEQ ID NO: 74 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 74; and V L , comprising the amino acid sequence of SEQ ID NO: 97 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 97; (iv) V H , comprising the amino acid sequence of SEQ ID NO: 75 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 75; and V L , comprising the amino acid sequence of SEQ ID NO: 97 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 97; (v) V H , comprising the amino acid sequence of SEQ ID NO: 76 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 76; and V L , comprising the amino acid sequence of SEQ ID NO: 97 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 97; (vi) V H, comprising the amino acid sequence of SEQ ID NO: 77 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 77; and V L , comprising the amino acid sequence of SEQ ID NO: 97 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 97; (vii) V H , comprising the amino acid sequence of SEQ ID NO: 78 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 78; and V L , comprising the amino acid sequence of SEQ ID NO: 97 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 97; (viii) V H , comprising the amino acid sequence of SEQ ID NO: 73 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 73; and V L , comprising the amino acid sequence of SEQ ID NO: 98 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 98; (ix) V H , comprising the amino acid sequence of SEQ ID NO: 74 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 74; and V L , comprising the amino acid sequence of SEQ ID NO: 98 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 98; (x) V H , comprising the amino acid sequence of SEQ ID NO: 75 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 75; and V L , comprising the amino acid sequence of SEQ ID NO: 98 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 98; (xi) V H , comprising the amino acid sequence of SEQ ID NO: 76 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 76; and V L , comprising the amino acid sequence of SEQ ID NO: 98 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 98; (xii) V H, comprising the amino acid sequence of SEQ ID NO: 77 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 77; and V L , comprising the amino acid sequence of SEQ ID NO: 98 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 98; (xiii) V H , comprising the amino acid sequence of SEQ ID NO: 78 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 78; and V L , comprising the amino acid sequence of SEQ ID NO: 98 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 98; (xiv) V H , comprising the amino acid sequence of SEQ ID NO: 78 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 78; and V L , comprising the amino acid sequence of SEQ ID NO: 99 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 99; (xv) V H , comprising the amino acid sequence of SEQ ID NO: 78 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 78; and V L , comprising the amino acid sequence of SEQ ID NO: 100 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 100; (xvi) V H , comprising the amino acid sequence of SEQ ID NO: 79 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 79; and V L , comprising the amino acid sequence of SEQ ID NO: 100 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 100; (xvii) V H , comprising the amino acid sequence of SEQ ID NO: 80 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 80; and V L , comprising the amino acid sequence of SEQ ID NO: 100 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 100; (xviii) V H, comprising the amino acid sequence of SEQ ID NO: 81 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 81; and V L , comprising the amino acid sequence of SEQ ID NO: 99 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 99; (xix) V H , comprising the amino acid sequence of SEQ ID NO: 82 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 82; and V L , comprising the amino acid sequence of SEQ ID NO: 99 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 99; (xx) V H , comprising the amino acid sequence of SEQ ID NO: 83 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 83; and V L , comprising the amino acid sequence of SEQ ID NO: 99 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 99; (xxi) V H , comprising the amino acid sequence of SEQ ID NO: 84 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 84; and V L , comprising the amino acid sequence of SEQ ID NO: 99 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 99; (xxii) V H , comprising the amino acid sequence of SEQ ID NO: 79 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 79; and V L , comprising the amino acid sequence of SEQ ID NO: 99 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 99; (xxiii) V H , comprising the amino acid sequence of SEQ ID NO: 80 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 80; and V L , comprising the amino acid sequence of SEQ ID NO: 99 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 99; (xxiv) V H, comprising the amino acid sequence of SEQ ID NO: 78 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 78; and V L , comprising the amino acid sequence of SEQ ID NO: 101 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 101.

[0026] In some embodiments, an isolated anti-NKG2A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 68 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 102 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0027] In some embodiments, an isolated anti-NKG2A antibody is provided, comprising: (i) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 35, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 45, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 51, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0028] In some embodiments, any of the isolated anti-NKG2A antibodies described above comprises: V H , comprising the amino acid sequence of SEQ ID NO: 68 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 68; and V L , which comprises the amino acid sequence shown in SEQ ID NO: 102 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 102.

[0029] In some embodiments, an isolated anti-NKG2A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 85 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 103 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0030] In some embodiments, an isolated anti-NKG2A antibody is provided, comprising: (i) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 17, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 26, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 36, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 46, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0031] In some embodiments, any of the isolated anti-NKG2A antibodies described above comprises: V H , comprising the amino acid sequence shown in SEQ ID NO: 85 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 85; and V L , which comprises the amino acid sequence shown in SEQ ID NO: 103 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 103.

[0032] In some embodiments, an isolated anti-NKG2A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 86 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L, which comprises V as shown in the amino acid sequence SEQ ID NO: 104 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0033] In some embodiments, an isolated anti-NKG2A antibody is provided, comprising: (i) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 18, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 27, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 37, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 47, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 59, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0034] In some embodiments, any of the isolated anti-NKG2A antibodies described above comprises: V H , comprising the amino acid sequence of SEQ ID NO: 86 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 86; and V L , which comprises the amino acid sequence shown in SEQ ID NO: 104 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 104.

[0035] In some embodiments, an isolated anti-NKG2A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 87 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 105 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0036] In some embodiments, an isolated anti-NKG2A antibody is provided, comprising: (i) V H , the V Hcomprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 4, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 19, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 28, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 38, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 48, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 60, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0037] In some embodiments, any of the isolated anti-NKG2A antibodies described above comprises: V H , comprising the amino acid sequence of SEQ ID NO: 87 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 87; and V L , which comprises the amino acid sequence shown in SEQ ID NO: 105 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 105.

[0038] In some embodiments, an isolated anti-NKG2A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 88 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 106 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0039] In some embodiments, an isolated anti-NKG2A antibody is provided, comprising: (i) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 5, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 20, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 29, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the VL comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 39, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 61, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0040] In some embodiments, any of the isolated anti-NKG2A antibodies described above comprises: V H , comprising the amino acid sequence set forth in SEQ ID NO: 88 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence set forth in SEQ ID NO: 88; and V L , which comprises the amino acid sequence shown in SEQ ID NO: 106 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 106.

[0041] In some embodiments, an isolated anti-NKG2A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 89 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 107 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0042] In some embodiments, an isolated anti-NKG2A antibody is provided, comprising: (i) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 6, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 30, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 49, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 62, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0043] In some embodiments, any of the isolated anti-NKG2A antibodies described above comprises: V H , comprising the amino acid sequence of SEQ ID NO: 89 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 89; and V L , which comprises the amino acid sequence shown in SEQ ID NO: 107 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 107.

[0044] In some embodiments, an isolated anti-NKG2A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO:90 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 108 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0045] In some embodiments, an isolated anti-NKG2A antibody is provided, comprising: (i) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 7, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 31, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 63, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0046] In some embodiments, any of the isolated anti-NKG2A antibodies described above comprises: V H , comprising the amino acid sequence shown in SEQ ID NO: 90 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 90; and V L, which comprises the amino acid sequence shown in SEQ ID NO: 108 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 108.

[0047] In some embodiments, an isolated anti-NKG2A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO:91 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 109 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0048] In some embodiments, an isolated anti-NKG2A antibody is provided, comprising: (i) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 8, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 23, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 32, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 42, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 50, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 64, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0049] In some embodiments, any of the isolated anti-NKG2A antibodies described above comprises: V H , comprising the amino acid sequence of SEQ ID NO: 91 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 91; and V L , which comprises the amino acid sequence shown in SEQ ID NO: 109 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 109.

[0050] In some embodiments, the isolated anti-NKG2A antibody binds to human NKG2A with a Kd value of 0.1 pM to about 10 nM.

[0051] In some embodiments, an isolated anti-NKG2A antibody is provided that competes with any of the above isolated anti-NKG2A antibodies for specific binding to NKG2A. In some embodiments, an isolated anti-NKG2A antibody is provided that specifically binds to the same epitope as any of the above isolated anti-NKG2A antibodies.

[0052] In some embodiments, any of the isolated anti-NKG2A antibodies described above comprises an Fc fragment. In some embodiments, the isolated anti-NKG2A antibody is a full-length IgG antibody. In some embodiments, the isolated anti-NKG2A antibody is a full-length IgG1, IgG2, IgG3, or IgG4 antibody. In some embodiments, the isolated anti-NKG2A antibody is a chimeric, fully human, or humanized antibody. In some embodiments, the isolated anti-NKG2A antibody is an antigen-binding fragment selected from the group consisting of Fab, Fab', F(ab)'2, Fab'-SH, single-chain Fv (scFv), Fv fragment, dAb, Fd, nanobody, diabody, and linear antibody.

[0053] In some embodiments, an isolated nucleic acid molecule is provided, encoding any of the anti-NKG2A antibodies described above. In some embodiments, a vector is provided, comprising any of the nucleic acid molecules described above. In some embodiments, a host cell is provided, comprising any of the anti-NKG2A antibodies described above, any of the nucleic acid molecules described above, or any of the vectors described above. In some embodiments, a method for producing an anti-NKG2A antibody is provided, comprising: a) culturing any of the host cells described above under conditions effective for expressing the anti-NKG2A antibody; and b) obtaining the expressed anti-NKG2A antibody from the host cell.

[0054] In some embodiments, a method of treating a disease or condition in a desired individual is provided, comprising administering to the individual an effective amount of any of the anti-NKG2A antibodies described above. In some embodiments, use of any of the anti-NKG2A antibodies described above in the preparation of a pharmaceutical composition for treating a disease or condition in a desired individual is provided. In some embodiments, use of any of the anti-NKG2A antibodies described above, or a pharmaceutical composition comprising an anti-NKG2A antibody, in the preparation of a medicament for treating a disease or condition is provided. In some embodiments, the disease or condition is related to the NKG2A signaling pathway, including cancer, viral diseases, autoimmune diseases, and / or inflammatory diseases or conditions. In some embodiments, the disease or condition is selected from, for example, cancer, such as renal cancer, bladder cancer, breast cancer, colon cancer, liver cancer, lung cancer, ovarian cancer, prostate cancer, pancreatic cancer, stomach cancer, uterine cancer, thyroid cancer, skin cancer, melanoma, xeroderma pigmentosum, keratoacanthoma, seminoma, follicular thyroid cancer, teratoma, squamous cell carcinoma, leukemia, acute lymphocytic leukemia, chronic lymphocytic leukemia, acute lymphoblastic leukemia, B cell lymphoma, T cell lymphoma, Hodgkin lymphoma , non-Hodgkin lymphoma, hairy cell lymphoma, Burketts lymphoma, multiple myeloma, acute and chronic myeloid leukemia, promyelocytic leukemia, myelodysplastic syndrome; viral diseases such as hepatitis A, hepatitis B, hepatitis C, influenza, chickenpox, adenovirus, herpes simplex type 1 (HSV-1), herpes simplex type 2 (HSV-2), rinderpest, rhinovirus, echovirus, rotavirus, respiratory syncytial virus, papillomavirus, cytomegalovirus, echinovirus s, arboviruses, hantaviruses, coxsackieviruses, mumps virus, measles virus, rubella virus, poliovirus, human immunodeficiency virus type 1 or type 2 (HIV-1, HIV-2); autoimmune diseases such as hemolytic anemia, pernicious anemia, polyarteritis nodosa, systemic lupus erythematosus, Wegener's granulomatosis, autoimmune hepatitis, Behçet's disease, Crohn's disease, primary biliary cirrhosis, scleroderma, ulcerative colitis, Sjogren's syndrome, type 1 diabetes mellitus, glucocorticoids, Uveitis, Graves' disease, Alzheimer's disease, thyroiditis; inflammatory diseases such as conjunctivitis, cystitis, dermatitis, diverticulitis, encephalitis, endocarditis, esophagitis, eustachian tube inflammation, fibrositis, folliculitis, gastritis, gastroenteritis, gingivitis, glossitis, hepatosplenomegaly, keratitis, otitis interna, laryngitis, lymphangitis, mastitis, otitis media, meningitis, metritis, mucositis, myocarditis, myositis, tympanitis, nephritis, neuritis, orchitis, osteochondritis, otitis, pericarditis, tenosynovitis, peritonitis, pharyngitis, phlebitis, etc.

[0055] Also provided are pharmaceutical compositions, kits, and manufactured products comprising any of the anti-NKG2A antibodies described above. BRIEF DESCRIPTION OF THE DRAWINGS

[0056] Figure 1 shows the binding affinities of rabbit whole or chimeric anti-NKG2A antibodies to human NKG2A as analyzed by ELISA. Figure 1A shows the binding affinities of exemplary rabbit anti-NKG2A antibodies ST14-R57, ST14-R58, ST14-R59, and ST14-R60 to human NKG2A. Figure 1B shows the binding affinities of exemplary rabbit anti-NKG2A antibodies ST14-R76, ST14-R77, and ST14-R78 to human NKG2A. Figure 1C shows the binding affinities of exemplary chimeric anti-NKG2A antibodies ST14-R79 and ST14-R90 to human NKG2A. Figure 1D shows the binding affinity of exemplary rabbit anti-NKG2A antibody ST14-R12 to human NKG2A. Figure 1E shows the binding affinity of exemplary chimeric anti-NKG2A antibody ST14-R358 to human NKG2A.

[0057] Figure 2 shows the binding affinities of rabbit whole or chimeric anti-NKG2A antibodies to human NKG2C as analyzed by ELISA. Figure 2A shows the binding affinities of exemplary rabbit anti-NKG2A antibodies ST14-R57, ST14-R58, ST14-R59, and ST14-R60 to human NKG2C. Figure 2B shows the binding affinities of exemplary rabbit anti-NKG2A antibodies ST14-R76, ST14-R77, and ST14-R78 to human NKG2C. Figure 2C shows the binding affinities of exemplary chimeric anti-NKG2A antibodies ST14-R79 and ST14-R90 to human NKG2C. Figure 2D shows the binding affinity of exemplary rabbit anti-NKG2A antibody ST14-R12 to human NKG2C. Figure 2E shows the binding affinity of exemplary chimeric anti-NKG2A antibody ST14-R358 to human NKG2C.

[0058] Figure 3 shows the activity of rabbit whole or chimeric anti-NKG2A antibodies in blocking NKL cell binding to HLA-E tetramers, as analyzed by FACS. Figure 3A shows the activity of exemplary rabbit anti-NKG2A antibodies ST14-R57, ST14-R58, ST14-R76, ST14-R77, and ST14-R78 in blocking NKL cell binding to HLA-E tetramers. Figure 3B shows the activity of exemplary chimeric anti-NKG2A antibodies ST14-R79 and ST14-R90 in blocking NKL cell binding to HLA-E tetramers. Figure 3C shows the activity of exemplary chimeric anti-NKG2A antibody ST14-R358 in blocking NKL cell binding to HLA-E tetramers.

[0059] Figure 4 shows the activity of rabbit anti-NKG2A antibodies in blocking the binding of NK92 cells to HLA-E tetramers as analyzed by FACS. Figure 4A shows the activity of exemplary rabbit anti-NKG2A antibodies ST14-R57, ST14-R58, ST14-R76, ST14-R77, and ST14-R78 in blocking the binding of NK92 cells to HLA-E tetramers. Figure 4B shows the activity of exemplary rabbit anti-NKG2A antibody ST14-R12 in blocking the binding of NK92 cells to HLA-E tetramers.

[0060] Figure 5 shows the cross-binding activity of rabbit whole or chimeric anti-NKG2A antibodies with rhesus monkey NKG2A as analyzed by ELISA. Figure 5A shows the cross-binding activity of exemplary rabbit anti-NKG2A antibodies ST14-R57 and ST14-R58 with rhesus monkey NKG2A. Figure 5B shows the cross-binding activity of exemplary rabbit anti-NKG2A antibodies ST14-R76, ST14-R77, and ST14-R78 with rhesus monkey NKG2A. Figure 5C shows the cross-binding activity of exemplary chimeric anti-NKG2A antibodies ST14-R79 and ST14-R90 with rhesus monkey NKG2A.

[0061] FIG6 shows the DELFIA EuTDA cytotoxicity assay showing that exemplary rabbit whole-antibody or chimeric anti-NKG2A antibodies ST14-R57, ST14-R76, ST14-R78, and ST14-R358 promote the killing activity of NKL cells against K562-E4 cells.

[0062] Figure 7 shows the activity of rabbit whole or chimeric anti-NKG2A antibodies in promoting NKL cytotoxicity based on CD107a labeling FACS analysis. Figure 7A shows that exemplary rabbit anti-NKG2A antibodies ST14-R57, ST14-R76, ST14-R77, and ST14-R78 enhance CD107a expression in NKL cells. Figure 7B shows that exemplary chimeric anti-NKG2A antibodies ST14-R79 and ST14-R90 enhance CD107a expression in NKL cells. Figure 7C shows that exemplary chimeric anti-NKG2A antibodies ST14-

[0063] R358 enhances CD107a expression in NKL cells.

[0064] FIG8 shows the binding affinity of humanized anti-NKG2A antibodies hum-ST14-R76-9, hum-ST14-R76-10, hum-ST14-R76-11, and hum-ST14-R76-12 to human NKG2A as analyzed by ELISA.

[0065] FIG9 shows the binding affinities of humanized anti-NKG2A antibodies hum-ST14-R76-9, hum-ST14-R76-10, hum-ST14-R76-11, and hum-ST14-R76-12 to CHO-huNKG2A cells analyzed by FACS.

[0066] FIG10 shows the activity of humanized anti-NKG2A antibodies hum-ST14-R76-9, hum-ST14-R76-10, hum-ST14-R76-11, and hum-ST14-R76-12 in blocking the binding of NKL cells to HLA-E tetramers as analyzed by FACS.

[0067] Figure 11A shows the cross-binding activity of humanized anti-NKG2A antibodies hum-ST14-R76-9, hum-ST14-R76-10, hum-ST14-R76-11, and hum-ST14-R76-12 with rhesus monkey NKG2A as analyzed by ELISA. Figure 11B shows the cross-binding activity of humanized anti-NKG2A antibodies hum-ST14-R76-9, hum-ST14-R76-10, hum-ST14-R76-11, and hum-ST14-R76-12 with CHO-rheNKG2A as analyzed by FACS.

[0068] FIG12 shows the DELFIA EuTDA cytotoxicity assay analysis of the cytotoxicity of humanized anti-NKG2A antibodies hum-ST14-R76-10, hum-ST14-R76-11, and hum-ST14-R76-12 in promoting NKL cells to kill K562-E4 cells.

[0069] FIG. 13 shows that humanized anti-NKG2A antibodies hum-ST14-R76-10 and hum-ST14-R76-12 enhance CD107a expression in NKL cells as analyzed by FACS.

[0070] FIG14 shows the cytotoxicity of humanized anti-NKG2A antibodies hum-ST14-R76-10, hum-ST14-R76-11, and hum-ST14-R76-12 against primary NK cells against K562-E4 cells as analyzed by DELFIA EuTDA cytotoxicity assay.

[0071] FIG15 shows the results of a pharmacokinetic study of exemplary anti-NKG2A antibodies in rats.

[0072] Detailed description of this application

[0073] On the one hand, the present application provides anti-NKG2A antibody molecules. Through a combination of 293T cell display library screening, antibody humanization, affinity maturation, and appropriately designed biochemical and biological experiments, a highly effective antibody molecule capable of binding to human NKG2A and inhibiting the interaction of human NKG2A with its receptor has been identified. The results presented herein show that compared with the known anti-NKG2A antibodies Monalizumab (NOVO NORDISK), NKG2A.9 (BRISTOL MYERS SQUIBB), and M15 (Shanghai Huaiyue), the antibodies in the present application bind to NKG2A, and surprisingly, in various biological experiments, the antibodies in the present application have been shown to be even more effective than Monalizumab (hereinafter referred to as Mon), NKG2A.9 (hereinafter referred to as A9), or M15.

[0074] The anti-NKG2A antibodies provided herein include, for example, full-length anti-NKG2A antibodies, anti-NKG2A single-chain antibodies (scFvs), anti-NKG2A Fc fusion proteins, multispecific (eg, bispecific) anti-NKG2A antibodies, anti-NKG2A immunoconjugates, and the like.

[0075] On the other hand, the present application provides an anti-NKG2A antibody, wherein the anti-NKG2A antibody comprises: a heavy chain variable domain (V H ), the V H The heavy chain complementarity determining region (HC-CDR) 1 comprises SNTMS (SEQ ID NO: 1); HC-CDR2 comprises NINTGGNTYYANWAKG (SEQ ID NO: 9); and HC-CDR3 comprises GSTIDSSGLSL (SEQ ID NO: 24); and a light chain variable domain (V L ), the V L It comprises: a light chain complementary determining region (LC-CDR) 1 comprising QASQNIGSDLA (SEQ ID NO: 33); a LC-CDR2 comprising LASTLAS (SEQ ID NO: 43); and a LC-CDR3 comprising QQX1WSSSNVDNV (SEQ ID NO: 66), wherein X1 is C, S or T.

[0076] On the other hand, the present application provides an anti-NKG2A antibody, wherein the anti-NKG2A antibody comprises: a heavy chain variable domain (V H ), the V HThe invention comprises: a heavy chain complementary determining region (HC-CDR) 1 comprising NYHMS (SEQ ID NO: 2); HC-CDR2 comprising YIGAAX1X2X3YYASWAKG (SEQ ID NO: 65), wherein X1 is G, N or S, X2 is N or S, and X3 is A, I or T; and HC-CDR3 comprising GVIYNNL (SEQ ID NO: 25); and a light chain variable domain (V L ), the V L It comprises: a light chain complementary determining region (LC-CDR) 1 comprising QASESISNYLS (SEQ ID NO: 34); a LC-CDR2 comprising DASDLAS (SEQ ID NO: 44); and a LC-CDR3 comprising QX1TYGSINX2NYGVA (SEQ ID NO: 67), wherein X1 is A or C, and X2 is A, Q or S.

[0077] On the other hand, the present application provides an anti-NKG2A antibody, wherein the anti-NKG2A antibody comprises: a heavy chain variable domain (V H ), the V H The heavy chain complementarity determining region (HC-CDR) 1 comprises SNTMS (SEQ ID NO: 1); HC-CDR2 comprises NINTGGNTYYANWAKG (SEQ ID NO: 9); and HC-CDR3 comprises GSTIDSSGLSL (SEQ ID NO: 24); and a light chain variable domain (V L ), the V L It comprises: a light chain complementarity determining region (LC-CDR) 1 comprising QASDSIGDWLA (SEQ ID NO: 35); a LC-CDR2 comprising KASILAS (SEQ ID NO: 45); and a LC-CDR3 comprising QQCWSSSNVDNV (SEQ ID NO: 51).

[0078] On the other hand, the present application provides an anti-NKG2A antibody, wherein the anti-NKG2A antibody comprises: a heavy chain variable domain (V H ), the V H The antibody comprises a heavy chain complementarity determining region (HC-CDR) 1 comprising GGYYMC (SEQ ID NO: 3); a HC-CDR2 comprising CIGTGSGSTYYASWAKG (SEQ ID NO: 17); and a HC-CDR3 comprising ESYAAYPDYGYGYNL (SEQ ID NO: 26); and a light chain variable domain (V L ), the V LIt comprises: a light chain complementarity determining region (LC-CDR) 1 comprising QASQSISSWLS (SEQ ID NO: 36); a LC-CDR2 comprising QASTLAS (SEQ ID NO: 46); and a LC-CDR3 comprising QANVGSDNAYVRA (SEQ ID NO: 58).

[0079] On the other hand, the present application provides an anti-NKG2A antibody, wherein the anti-NKG2A antibody comprises: a heavy chain variable domain (V H ), the V H The antibody comprises a heavy chain complementarity determining region (HC-CDR) 1 comprising GGYYMC (SEQ ID NO: 3); a HC-CDR2 comprising CIGTGSRSTYYASWAKG (SEQ ID NO: 18); and a HC-CDR3 comprising ESYAAYPDYGDGLDL (SEQ ID NO: 27); and a light chain variable domain (V L ), the V L It comprises: a light chain complementarity determining region (LC-CDR) 1 comprising QASQNINNWLS (SEQ ID NO: 37); a LC-CDR2 comprising QASKLAS (SEQ ID NO: 47); and a LC-CDR3 comprising QSNYGSTTTYVRA (SEQ ID NO: 59).

[0080] On the other hand, the present application provides an anti-NKG2A antibody, wherein the anti-NKG2A antibody comprises: a heavy chain variable domain (V H ), the V H The antibody comprises a heavy chain complementarity determining region (HC-CDR) 1 comprising SYHMI (SEQ ID NO: 4); a HC-CDR2 comprising GISSSGSTYYANWAKG (SEQ ID NO: 19); and a HC-CDR3 comprising GYGSTFTYYDPSRLDL (SEQ ID NO: 28); and a light chain variable domain (V L ), the V L It comprises: a light chain complementarity determining region (LC-CDR) 1 comprising QSSQSVYDNNLLS (SEQ ID NO: 38); a LC-CDR2 comprising GASKLAS (SEQ ID NO: 48); and a LC-CDR3 comprising LGAYNDDGDNA (SEQ ID NO: 60).

[0081] On the other hand, the present application provides an anti-NKG2A antibody, wherein the anti-NKG2A antibody comprises: a heavy chain variable domain (V H ), the V Hcomprising: a heavy chain complementarity determining region (HC-CDR) 1 comprising SVSVT (SEQ ID NO: 5); HC-CDR2 comprising YINTGGNTGYASWVKG (SEQ ID NO: 20); and HC-CDR3 comprising GAGFSTRLGL (SEQ ID NO: 29); and a light chain variable domain (V L ), the V L It comprises: a light chain complementarity determining region (LC-CDR) 1 comprising QASKSVAGNNELS (SEQ ID NO: 39); a LC-CDR2 comprising DASDLAS (SEQ ID NO: 44); and a LC-CDR3 comprising AGGYSDTSDNA (SEQ ID NO: 61).

[0082] On the other hand, the present application provides an anti-NKG2A antibody, wherein the anti-NKG2A antibody comprises: a heavy chain variable domain (V H ), the V H The antibody comprises a heavy chain complementarity determining region (HC-CDR) 1 comprising DYAIN (SEQ ID NO: 6); a HC-CDR2 comprising IIYDGSHNTWYASWVKG (SEQ ID NO: 21); and a HC-CDR3 comprising AYAIYDGYGYLIYGMDP (SEQ ID NO: 30); and a light chain variable domain (V L ), the V L It comprises: a light chain complementarity determining region (LC-CDR) 1 comprising QASQNIYSNLA (SEQ ID NO:40); a LC-CDR2 comprising LASTLAF (SEQ ID NO:49); and a LC-CDR3 comprising QSHDDTTAGPYGYA (SEQ ID NO:62).

[0083] On the other hand, the present application provides an anti-NKG2A antibody, wherein the anti-NKG2A antibody comprises: a heavy chain variable domain (V H ), the V H The heavy chain complementarity determining region (HC-CDR) 1 comprises TYTMG (SEQ ID NO: 7); HC-CDR2 comprises TINTGGTSVYASWAKG (SEQ ID NO: 22); and HC-CDR3 comprises GIYSGWNTPFKL (SEQ ID NO: 31); and a light chain variable domain (V L ), the V LIt comprises: a light chain complementarity determining region (LC-CDR) 1 comprising QASEDIENYLA (SEQ ID NO:41); a LC-CDR2 comprising DASDLAS (SEQ ID NO:44); and a LC-CDR3 comprising QSYYYTISSFG (SEQ ID NO:63).

[0084] On the other hand, the present application provides an anti-NKG2A antibody, wherein the anti-NKG2A antibody comprises: a heavy chain variable domain (V H ), the V H comprising: a heavy chain complementarity determining region (HC-CDR) 1 comprising SYDMN (SEQ ID NO: 8); HC-CDR2 comprising LMGIDGTTYYPNWAKG (SEQ ID NO: 23); and HC-CDR3 comprising NIYDDYYL (SEQ ID NO: 32); and a light chain variable domain (V L ), the V L It comprises: a light chain complementarity determining region (LC-CDR) 1 comprising QSSQSVYNNNALS (SEQ ID NO:42); a LC-CDR2 comprising GASTLAS (SEQ ID NO:50); and a LC-CDR3 comprising AGDYSSTSDDA (SEQ ID NO:64).

[0085] Also provided are nucleic acids encoding anti-NKG2A antibodies, compositions comprising anti-NKG2A antibodies, and methods of making and using anti-NKG2A antibodies.

[0086] definition

[0087] As used herein, "treatment" or "treating" is a method of obtaining beneficial or desired results, including clinical results. For the purposes of this application, the beneficial or desired clinical results include, but are not limited to, one or more of the following: alleviating one or more symptoms caused by the disease, reducing the extent of the disease, stabilizing the disease (e.g., preventing or delaying the worsening of the disease), preventing or delaying the spread of the disease (e.g., metastasis), preventing or delaying the recurrence of the disease, delaying or slowing the progression of the disease, improving the disease state, alleviating the disease (partially or completely), reducing the dose of one or more other drugs required to treat the disease, delaying the progression of the disease, improving or enhancing the quality of life, increasing body weight, and / or prolonging survival. At the same time, "treatment" also includes a reduction in the pathological consequences of the disease (e.g., tumor volume for cancer). The methods of the present application contemplate any one or more aspects of these treatments.

[0088] The term "antibody" includes full-length antibodies and antigen-binding fragments thereof. Full-length antibodies include two heavy chains and two light chains. The variable regions of the light and heavy chains are responsible for antigen binding. The variable regions in both chains typically include three hypervariable loops, known as complementarity determining regions (CDRs) (light chain (LC) CDRs include LC-CDR1, LC-CDR2, and LC-CDR3, and heavy chain (HC) CDRs include HC-CDR1, HC-CDR2, and HC-CDR3). The CDR boundaries of the antibodies or antigen-binding fragments disclosed herein can be defined or identified by the Kabat, Chothia, or Al-Lazikani conventions (Al-Lazikani 1997; Chothia 1985; Chothia 1987; Chothia 1989; Kabat 1987; Kabat 1991). The three CDR regions of the heavy or light chain are inserted between flanking segments called framework regions (FRs), which are more highly conserved than the CDR regions and form a scaffold that supports the hypervariable loops. The constant regions of the heavy and light chains are not involved in antigen binding but exhibit various effector functions. Antibodies are classified based on the amino acid sequence of their heavy chain constant regions. The five major classes or isotypes of antibodies are IgA, IgD, IgE, IgG, and IgM, which are characterized by having heavy chains of type α, δ, ε, γ, and μ, respectively. Several major antibody classes are divided into subclasses, such as IgG1 (γ1 heavy chain), IgG2 (γ2 heavy chain), IgG3 (γ3 heavy chain), IgG4 (γ4 heavy chain), IgA1 (α1 heavy chain), or IgA2 (α2 heavy chain).

[0089] As used herein, the term "antigen-binding fragment" includes antibody fragments, such as diabodies, Fab, Fab', F(ab')2, Fv fragments, disulfide-stabilized Fv fragments (dsFv), (dsFv)2, bispecific dsFv (dsFv-dsFv'), disulfide-stabilized diabodies (dsdiabodies), single-chain Fv (scFv), scFv dimers (divalent diabodies), multispecific antibodies composed of antibody fragments comprising one or more CDRs, single-domain antibodies, nanobodies, domain antibodies, bivalent domain antibodies, or any other antibody fragment that can bind to an antigen but does not contain a complete antibody structure. Antigen-binding fragments can bind to the same antigen as a parent antibody or parent antibody fragment (such as a parent scFv). Antigen-binding fragments also include fusion proteins comprising the above-mentioned antibody fragments. In some embodiments, an antigen-binding fragment may include one or more CDRs from a specific human antibody that are transplanted to a framework region from one or more different human antibodies.

[0090] As used herein, the term "epitope" refers to a specific group of atoms or amino acids on an antigen to which an antibody or antibody portion binds. If two antibodies or antibody portions exhibit competitive binding to an antigen, they likely bind to the same epitope on the antigen.

[0091] As used herein, a first antibody "competes" for binding to the NKG2A target with a second antibody when the first antibody, at equimolar concentrations, inhibits binding of the second antibody to the NKG2A target by at least 50% (e.g., at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99%), and vice versa. PCT Publication WO 03 / 48731 describes a high-throughput antibody "epitope binning" method based on cross-competition.

[0092] As used herein, the terms "specifically bind," "specifically recognize," or "specific for" refer to a measurable and reproducible interaction, e.g., binding of an antibody to a target that can confirm the presence of the target in a heterogeneous population of molecules, including biomolecules. For example, an antibody that specifically recognizes a target (which may be an epitope) means that the antibody binds to the target with greater affinity, avidity, more readily, and / or more persistently than it binds to other targets. In some embodiments, an antibody that specifically recognizes an antigen reacts with one or more antigenic determinants of the antigen with an affinity that is at least 10 times greater than its binding affinity to other targets.

[0093] As used herein, an "isolated" anti-NKG2A antibody is an anti-NKG2A antibody that (1) is not related to a naturally occurring protein, (2) does not contain other proteins from the same source, (3) is expressed by cells of a different species, or (4) does not occur in nature.

[0094] As used herein, the term "isolated nucleic acid" refers to a nucleic acid of genomic, cDNA, or synthetic origin, or a combination thereof. Depending on its origin, the "isolated nucleic acid" is (1) unrelated to all or part of the polynucleotide sequence found in nature, (2) operably linked to a polynucleotide sequence with which it is not naturally associated, or (3) not found in nature as part of a longer sequence.

[0095] As used herein, the term "CDR" or "complementarity determining region" refers to the non-contiguous antigen binding sites found within the variable domains of heavy and light chain polypeptides. In the literature Kabat et al., J. Biol. Chem. 252: 6609-6616 (1977); Kabat et al., USDept. of Health and Human Services, "Sequences of proteins of immunological interest" (1991); Chothia et al., J. Mol. Biol. 196: 901-917 (1987); Al-Lazikani B. et al. al., J. Mol. Biol., 273: 927-948 (1997); MacCallum et al., J. Mol. Biol. 262: 732-745 (1996); Abhinandan and Martin, Mol. Immunol., 45: 3832-3839 (2008); Lefranc MPet These specific regions are described in, for example, Desmond et al., Dev. Comp. Immunol., 27:55-77 (2003); and Honegger and Plückthun, J. Mol. Biol., 309:657-670 (2001), where these definitions include overlap or subsets of amino acid residues when compared to one another. However, any definition used to designate a CDR of an antibody, grafted antibody, or variant thereof is included within the scope of the term as defined and used herein. Table 1 lists the positions of the amino acid residues included in the CDRs defined by the various references cited above for comparison. Algorithms and binding interfaces for CDR prediction are known in the art, including, for example, Abhinandan and Martin, Mol. Immunol., 45: 3832-3839 (2008); Ehrenmann F. et al., Nucleic Acids Res., 38: D301-D307 (2010); and Adolf-Bryfogle J. et al., Nucleic Acids Res., 43: D432-D438 (2015). The contents of the references cited in this paragraph are incorporated herein by reference in their entirety for use in this application and in one or more claims that may be included in this article.

[0096] Table 1: CDR definitions 1The amino acid residue numbers refer to the nomenclature of Kabat et al. 2 The amino acid residue numbers refer to the nomenclature of Chothia et al. 3 The amino acid residue numbers refer to the nomenclature of MacCallum et al. 4 The amino acid residue numbers refer to the nomenclature of Lefranc et al. 5 The amino acid residue numbers refer to the nomenclature of Honegger and Plückthun.

[0097] The term "chimeric antibody" refers to an antibody in which a portion of the heavy chain and / or light chain is identical or homologous to the corresponding sequence in an antibody from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical or homologous to the corresponding sequence in an antibody from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies, as long as they have the biological activity described in the present application (see US Patent No. 4,816,567; and Morrison et al., Proc. Natl. Acad. Sci. USA, 81: 6851-6855 (1984)).

[0098] "Fv" is the smallest antibody fragment that contains a complete antigen recognition and binding site. This fragment is a dimer formed by a heavy chain variable domain and a light chain variable domain tightly non-covalently linked. Six hypervariable loops (3 loops each in the light chain and heavy chain) are derived from the folding of these two domains. The hypervariable loops provide the antibody with amino acid residues for binding to the antigen and confer specificity for binding to the antibody. However, even a single variable domain (or half of an Fv fragment, which only contains 3 CDRs specific for the antigen) has the ability to recognize and bind to the antigen, although its affinity is lower than that of the complete binding site.

[0099] "Single-chain Fv", also abbreviated as "sFv" or "scFv", is a Fv that contains V molecules linked into a single polypeptide chain. H and V L In some embodiments, the scFv polypeptide further comprises a V H and V LThe linker polypeptide between the domains allows the scFv to form an ideal structure for antigen binding. For an overview of scFv, see Pluckthun in The Pharmacology of Monoclonal Antibodies, vol. 113, Rosenburg and Moore eds., Springer-Verlag, New York, pp. 269-315 (1994).

[0100] The term "diabody" is used in V H and V L A small antibody fragment is prepared by constructing scFv fragments (see above) using short linkers (e.g., 5-10 residues) between the domains. This allows the variable domains to pair between chains rather than within the chain, resulting in a bivalent fragment, that is, a fragment with two antigen-binding sites. Bispecific diabodies are heterodimers of two "crossover" scFv fragments, in which the V domains of the two antibodies are H and V L The domains are located on different polypeptide chains. Diabodies are fully described in EP 404,097; WO 93 / 11161; Hollinger et al., Proc. Natl. Acad. Sci. USA, 90:6444-6448 (1993).

[0101] The "humanized" form of a non-human (such as a rodent) antibody is a chimeric antibody that includes minimal sequences from a non-human antibody. In most cases, a humanized antibody is a human immunoglobulin (recipient antibody) in which the hypervariable region (HVR) residues of the recipient antibody are replaced by hypervariable region residues from a non-human species such as a mouse, rat, rabbit or non-human mammal with ideal antibody specificity, affinity and performance (donor antibody). In some cases, residues in the human immunoglobulin framework region are replaced by corresponding non-human residues. In addition, a humanized antibody may include residues that are not present in either the recipient antibody or the donor antibody. These modifications can further improve the performance of the antibody. Typically, a humanized antibody will comprise substantially all, at least one, and usually two variable domains, wherein all or substantially all of the hypervariable loops correspond to the hypervariable loops of a non-human immunoglobulin, and all or substantially all of the framework regions are human immunoglobulin sequences. The human antibody optionally also comprises at least a portion of an immunoglobulin constant region (Fc), typically a constant region of a human immunoglobulin. For details, see Jones et al., Nature 321: 522-525 (1986); Riechmann et al., Nature 332: 323-329 (1988); and Presta, Curr. Op. Struct. Biol. 2: 593-596 (1992).

[0102] The "percent (%) amino acid sequence identity" or "homology" of the polypeptide and antibody sequences identified herein is defined as the percentage of identical amino acid residues in a candidate sequence and the polypeptide sequence being compared, when the sequences are aligned, considering conservative substitutions as part of the sequence identity. Percent amino acid sequence identity can be determined by various alignment methods within the skill in the art, for example, using publicly available computer software such as BLAST, BLAST-2, ALIGN, Megalign (DNASTAR), or MUSCLE software. One skilled in the art can determine appropriate parameters for measuring alignment, including any algorithm needed to maximize alignment over the full length of the sequences being compared. However, for the purposes of this article, percent amino acid sequence identity values ​​are generated using the sequence alignment computer program MUSCLE (Edgar, RC, Nucleic Acids Research 32(5):1792-1797, 2004; Edgar, RC, BMC Bioinformatics 5(1):113, 2004).

[0103] The term "Fc receptor" or "FcR" is used to describe a receptor that binds to the Fc region of an antibody. In some embodiments, the FcR described herein is an FcR that binds to an IgG antibody (a gamma receptor), including receptors of the FcγRI, FcγRII, and FcγRIII subclasses, including allelic variants and alternatively spliced ​​forms of these receptors. FcγRII receptors include FcγRIIA ("activating receptor") and FcγRIIB ("inhibiting receptor"), which have similar amino acid sequences and differ primarily in the cytoplasmic domain. The cytoplasmic domain of the activating receptor FcγRIIA contains an immunoreceptor tyrosine-based activation motif (ITAM). The cytoplasmic domain of the inhibitory receptor FcγRIIB contains an immunoreceptor tyrosine-based inhibition motif (ITIM) (see M.in Annu. Rev. Immunol. 15:203-234 (1997). The term also includes allotypes, such as the FcγRIIIA allotypes: FcγRIIIA-Phe158, FcγRIIIA-Val158, FcγRIIA-R131, and / or FcγRIIA-H131. FcRs are described in Ravetch and Kinet, Annu. Rev. Immunol 9:457-92 (1991) and Capel et al., Immunomethods 4:25-34 (1994); and de Haas et al., J. Lab. Clin. Med. 126:330-41 (1995). The term FcR in this application encompasses other types of FcRs, including those identified in the future. The term FcR also includes the neonatal receptor FcRn, which is responsible for the transfer of maternal IgGs to the newborn (Guyer et al., J. Immunol. 117:587 (1976) and Kim et al., J. Immunol. 24:249 (1994)).

[0104] The term "FcRn" refers to the neonatal Fc receptor (FcRn). FcRn is structurally similar to the major histocompatibility complex (MHC) and consists of an α chain non-covalently bound to β2 microglobulin. The various functions of the neonatal Fc receptor FcRn are reviewed in Ghetie and Ward (2000) Annu. Rev. Immunol. 18, 739-766. FcRn plays an important role in the passive transport of immunoglobulins (IgGs) from mother to newborn and in regulating serum IgG levels. As a salvage receptor, FcRn can bind and transport endocytosed IgGs in their intact form within and between cells, protecting them from the default degradation pathway.

[0105] The "CH1 domain" of a human IgG heavy chain constant region typically stretches from amino acid 118 to amino acid 215 (EU numbering system).

[0106] The "hinge region" is generally defined as stretching from Glu 216 to Pro 230 of human IgG1 (Burton, Molec. Immunol. 22: 161-206 (1985)). By placing the first and last cysteine ​​residues that form inter-heavy chain disulfide bonds in the same positions as in IgG1, the hinge regions of other IgG isotypes can be aligned with the IgG1 sequence.

[0107] The "CH2 domain" of the human IgG Fc region typically extends from amino acids 231 to 340. The CH2 domain is unique in that it does not closely pair with another domain. Instead, two N-terminally linked branched sugar chains are inserted between the two CH2 domains of the intact native IgG molecule. It is hypothesized that carbohydrates may serve as a substitute for domain-to-domain pairing, helping to maintain CH2 domain stability. Burton, Molec. Immunol. 22:161-206 (1985).

[0108] The "CH3" domain includes the CH2 domain extending from the C-terminal residue within the Fc region (from amino acid 341 to the C-terminus of the antibody sequence, usually amino acid residue 446 or 447 in IgG).

[0109] A "functional Fc fragment" possesses the "effector functions" of a native Fc region sequence. Exemplary "effector functions" include C1q binding; complement-dependent cytotoxicity (CDC); Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; and downregulation of cell surface receptors (e.g., B cell receptor; BCR). Such effector functions generally require the Fc region to be bound to a binding domain (e.g., an antibody variable region) and can be assessed using a variety of experimental methods known in the art.

[0110] IgG Fc variant antibodies with "altered" FcR binding affinity or ADCC activity have increased or decreased FcR binding activity and / or ADCC activity compared to the parent polypeptide or a polypeptide comprising a native Fc sequence. Fc variants that exhibit "enhanced binding" to FcRs have a higher binding affinity (e.g., lower apparent Kd or IC) to at least one FcR compared to the parent polypeptide or a polypeptide comprising a native IgG Fc sequence. 50In some embodiments, the binding capacity is enhanced by 3-fold, e.g., 5-, 10-, 25-, 50-, 60-, 100-, 150-, 200-, or even up to 500-fold, or the binding capacity is increased by 25% to 1000%, compared to the parent polypeptide. An Fc variant that exhibits "reduced binding" to an FcR has a lower affinity for at least one FcR (e.g., a higher apparent Kd or IC) than the parent polypeptide. 50 Compared with the parent polypeptide, its binding capacity is reduced by 40% or more.

[0111] "Antibody-dependent cell-mediated cytotoxicity" or "ADCC" is a form of cytotoxicity that refers to the binding of secreted Ig to Fc receptors (FcRs) present on certain cytotoxic cells (e.g., natural killer (NK) cells, neutrophils, and macrophages), enabling these cytotoxic effector cells to specifically bind to target cells bearing antigen and subsequently kill the target cells using cytotoxins. Antibodies "arm" the cytotoxic cells and are required for this killing. Of the major cell types that mediate ADCC, NK cells express only FcγRIII, while monocytes express FcγRI, FcγRII, and FcγRIII. The expression of FcRs on hematopoietic cells is summarized in Table 3 on page 464 of Ravetch and Kinet, Annu. Rev. Immunol 9:457-92 (1991). To assess the ADCC activity of a target molecule, an in vitro ADCC assay can be performed, as described in U.S. Patent Nos. 5,500,362 or 5,821,337. Effector cells suitable for such experiments include peripheral blood mononuclear cells (PBMC) and natural killer cells (NK). Alternatively, or in addition, the ADCC activity of the target molecule can also be assessed in vivo, for example, as described in the animal model disclosed in Clynes et al. PNAS (USA) 95: 652-656 (1998).

[0112] Polypeptides comprising Fc region variants exhibit "enhanced ADCC activity" or are capable of more effectively mediating ADCC in the presence of human effector cells, compared to polypeptides comprising wild-type IgG Fc polypeptides or parent polypeptides. When tested in substantially the same quantity as polypeptides comprising wild-type IgG Fc polypeptides (or parent polypeptides), such polypeptides comprising Fc region variants are capable of more effectively mediating ADCC, both in vitro and in vivo. Such variants are generally identified using any in vitro ADCC assay known in the art, such as assays or methods for identifying ADCC activity, such as in animal models. In some embodiments, such variants mediate ADCC 5- to 100-fold more efficiently, such as 25- to 50-fold more efficiently, than wild-type Fc (or parent polypeptide).

[0113] "Complement-dependent cytotoxicity" or "CDC" refers to the lysis of target cells in the presence of complement. Activation of the classical complement pathway is initiated by the binding of the first component of the complement system (Clq) to an antibody (of the appropriate structural subclass) that binds to the cognate antigen. To assess complement activation, a CDC assay, such as that described in Gazzano-Santoro et al., J. Immunol. Methods 202:163 (1996), can be performed. Polypeptide variants with altered Fc region amino acid sequences and increased or decreased Clq binding capacity are described in U.S. Patent No. 6,194,551 Bl and WO99 / 51642. The contents of these patent publications are expressly incorporated herein by reference. See also Idusogie et al. J. Immunol. 164:4178-4184 (2000).

[0114] Unless otherwise indicated, a "nucleotide sequence encoding an amino acid sequence" includes all nucleotide sequences that are degenerate versions of each other and encode the same amino acid sequence. A nucleotide sequence encoding a protein or RNA may also include introns, for example, a nucleotide sequence encoding a protein may contain introns in some forms.

[0115] The term "operably linked" refers to a functional connection between a regulatory sequence and a heterologous nucleotide sequence, thereby enabling expression of the latter. For example, a first nucleotide sequence is operably linked to a second nucleotide sequence when the first nucleotide sequence is in a functional relationship with the second nucleotide sequence. For example, a promoter is operably linked to a coding sequence if the promoter affects the transcription or expression of the coding sequence. Generally, operably linked DNA sequences are contiguous and, if necessary, can link two protein coding regions in the same reading frame.

[0116] "Homologous" refers to the sequence similarity or sequence identity between two polypeptides or between two nucleic acid molecules. If the same base or amino acid monomer subunit is present at the same position in two compared sequences, for example, adenine is present at the same position in two DNA molecules, then the two DNA molecules are homologous at that position. The percentage homology between two sequences refers to the ratio of the number of matching or homologous positions shared by the two sequences to the total number of positions multiplied by 100. For example, if 6 out of 10 positions in two sequences are matched or homologous, then the homology between the two sequences is 60%. For example, the DNA sequences ATTGCC and TATGGC have 50% homology. Generally speaking, when aligning two sequences, the comparison is performed with the goal of obtaining maximum homology.

[0117] An "effective amount" of an anti-NKG2A antibody or composition disclosed herein is an amount sufficient to achieve a specific purpose. An "effective amount" can be determined empirically and by known methods relevant to the stated purpose.

[0118] The term "therapeutically effective amount" refers to an amount of the anti-NKG2A antibody or composition thereof disclosed herein that is effective in treating an individual's disease or symptoms. For example, in the case of cancer, a therapeutically effective amount of an anti-NKG2A antibody or composition thereof refers to an amount that can reduce the number of cancer cells; reduce the size or weight of the tumor; inhibit (i.e., slow down or preferably stop to some extent) the infiltration of tumor cells into peripheral organs; inhibit (i.e., slow down or preferably stop to some extent) tumor metastasis; inhibit tumor growth to some extent, and / or alleviate one or more symptoms associated with cancer to some extent. The anti-NKG2A antibodies or compositions thereof disclosed herein are capable of preventing and / or killing existing tumor cells to some extent, and can be cytostatic or cytotoxic. In some embodiments, a therapeutically effective amount refers to an amount that can prolong the patient's survival. In some embodiments, a therapeutically effective amount refers to an amount that can improve the patient's progression-free survival.

[0119] As used herein, "pharmaceutically acceptable" or "pharmacologically compatible" refers to a material that is free of biological activity or other undesirable properties, e.g., a material that can be added to a pharmaceutical composition administered to a patient without causing a significant adverse biological reaction, or that does not interact in a deleterious manner with any other component contained in the composition. Pharmaceutically acceptable carriers or excipients preferably meet the required standards for toxicology or manufacturing testing and / or are included in the inactive ingredient guide compiled by the U.S. Food and Drug Administration.

[0120]

[0066] The embodiments of the present application described herein should be understood to include "consisting of" and / or "consisting essentially of" embodiments.

[0121] Reference herein to "about" for a value or parameter includes (and describes) variations of the value or parameter itself. For example, a description involving "about X" includes a description of "X".

[0122] As used herein, reference to "not" a value or parameter generally indicates and describes "other than" a value or parameter. For example, "the method cannot be used to treat type X cancer" means that the method is generally used to treat other types of cancer besides type X cancer.

[0123] As used herein and in the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0124] Anti-NKG2A antibody

[0125] On the one hand, the present application provides anti-human and / or rhesus monkey NKG2A antibodies that specifically bind to NKG2A. The anti-NKG2A antibodies include, but are not limited to, humanized antibodies, chimeric antibodies, mouse antibodies, human antibodies, and antibody molecules comprising heavy chain and / or light chain CDRs as described herein. On the one hand, the present application provides isolated antibodies that bind to NKG2A. Expected anti-NKG2A antibodies include, for example, full-length anti-NKG2A antibodies (such as full-length IgG1 or IgG4), anti-NKG2A single-chain antibodies, anti-NKG2A Fc fusion proteins, multispecific (such as bispecific) anti-NKG2A antibodies, anti-NKG2A immunoconjugates, and the like. In some embodiments, the anti-NKG2A antibody is a full-length antibody (such as full-length IgG1 or IgG4) or an antigen-binding fragment thereof that specifically binds to NKG2A. In some embodiments, the anti-NKG2A antibody is Fab, Fab', F(ab)'2, Fab'-SH, single-chain Fv (scFv), Fv fragment, dAb, Fd, nanobody, diabody or linear antibody. In some embodiments, the antibody that specifically binds to NKG2A means that the affinity of the antibody for binding to NKG2A is at least 10 times greater than the affinity for binding to a non-target (including 10, ... 2 , 10 3 , 10 4 , 10 5 , 10 6 , or 10 7 In some embodiments, a non-target antigen is an antigen that is not NKG2A. Binding affinity can be determined by methods known in the art, such as ELISA, fluorescence-activated cell sorting (FACS) analysis, or radioimmunoprecipitation assay (RIA). Kd values ​​can be determined by methods known in the art, such as surface plasmon resonance (SPR) or biolayer interferometry (BLI).

[0126] Although anti-NKG2A antibodies comprising human sequences (e.g., human heavy and light chain variable domains comprising human CDR sequences) are discussed extensively herein, non-human anti-NKG2A antibodies are also contemplated. In some embodiments, non-human anti-NKG2A antibodies comprise human CDR sequences of anti-NKG2A antibodies described herein and non-human framework sequences. In some embodiments, non-human framework sequences comprise any sequence used to generate heavy and / or light chain variable domains using one or more human CDR sequences as described herein, including, for example, mammals such as mice, rats, rabbits, pigs, cattle (e.g., cows, bulls, buffaloes), deer, sheep, goats, chickens, cats, dogs, ferrets, primates (e.g., small apes, macaques), etc. In some embodiments, non-human anti-NKG2A antibodies comprise anti-NKG2A antibodies generated by grafting one or more human CDR sequences described herein into non-human framework sequences (e.g., mouse or chicken framework sequences).

[0127] An exemplary extracellular region amino acid sequence of human NKG2A comprises or consists of the amino acid sequence set forth in SEQ ID NO: 114. An exemplary extracellular region amino acid sequence of rhesus monkey NKG2A comprises or consists of the amino acid sequence set forth in SEQ ID NO: 115.

[0128] In some embodiments, the anti-NKG2A antibodies described herein specifically recognize an epitope in human NKG2A. In some embodiments, the anti-NKG2A antibodies cross-react with NKG2A from species other than human. In some embodiments, the anti-NKG2A antibodies are completely specific for human NKG2A and do not cross-react with NKG2A from other non-human species.

[0129] In some embodiments, the anti-NKG2A antibody cross-reacts with at least one allelic variant of an NKG2A protein (or a fragment thereof). In some embodiments, the allelic variant has up to 30 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, or 30) amino acid substitutions (e.g., conservative substitutions) compared to a naturally occurring NKG2A protein (or a fragment thereof). In some embodiments, the anti-NKG2A antibody does not cross-react with any allelic variant of an NKG2A protein (or a fragment thereof).

[0130] In some embodiments, the anti-NKG2A antibody cross-reacts with at least one interspecies variant of the NKG2A protein. In some embodiments, for example, the NKG2A protein (or fragment thereof) is human NKG2A, and the interspecies variant of the NKG2A protein (or fragment thereof) is a variant in cynomolgus macaque. In some embodiments, the anti-NKG2A antibody does not cross-react with any interspecies variant of the NKG2A protein.

[0131] In some embodiments, as described herein, any anti-NKG2A antibody comprises an antibody heavy chain constant region and an antibody light chain constant region. In some embodiments, the anti-NKG2A antibody comprises an IgG1 heavy chain constant region. In some embodiments, the anti-NKG2A antibody comprises an IgG2 heavy chain constant region. In some embodiments, the anti-NKG2A antibody comprises an IgG3 heavy chain constant region. In some embodiments, the anti-NKG2A antibody comprises an IgG4 heavy chain constant region. In some embodiments, the heavy chain constant region comprises (consists of, or consists essentially of) the amino acid sequence of SEQ ID NO: 110. In some embodiments, the heavy chain constant region comprises (consists of, or consists essentially of) the amino acid sequence of SEQ ID NO: 111. In some embodiments, the anti-NKG2A antibody comprises a kappa light chain constant region. In some embodiments, the light chain constant region comprises (consists of, or consists essentially of) the amino acid sequence of SEQ ID NO: 112. In some embodiments, the anti-NKG2A antibody comprises a lambda light chain constant region. In some embodiments, the light chain constant region comprises (consists of, or consists essentially of) the amino acid sequence of SEQ ID NO: 113. In some embodiments, the anti-NKG2A antibody comprises an antibody heavy chain variable domain and an antibody light chain variable domain.

[0132] In some embodiments, the anti-NKG2A antibody comprises a heavy chain variable domain (V H ), the V H The heavy chain complementarity determining region (HC-CDR) 1 comprises SNTMS (SEQ ID NO: 1); HC-CDR2 comprises NINTGGNTYYANWAKG (SEQ ID NO: 9); and HC-CDR3 comprises GSTIDSSGLSL (SEQ ID NO: 24); and a light chain variable domain (V L ), the V LComprising: a light chain complementary determining region (LC-CDR) 1 comprising QASQNIGSDLA (SEQ ID NO: 33); a LC-CDR2 comprising LASTLAS (SEQ ID NO: 43); and a LC-CDR3 comprising QQX1WSSSNVDNV (SEQ ID NO: 66), wherein X1 is C, S, or T

[0133] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: an HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; an HC-CDR2 comprising the amino acid sequence shown in SEQ ID NO: 9 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and an HC-CDR3 comprising the amino acid sequence shown in SEQ ID NO: 24 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids.

[0134] In some embodiments, the anti-NKG2A antibody comprises V H , the V H It comprises: HC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO: 9, and HC-CDR3, which comprises the amino acid sequence shown in SEQ ID NO: 24.

[0135] In some embodiments, the anti-NKG2A antibody comprises V L , the V L Comprising: LC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:33 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:43 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; and LC-CDR3, which comprises the amino acid sequence shown in any one of SEQ ID NOs:51-53 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids.

[0136] In some embodiments, the anti-NKG2A antibody comprises V L , the V LIt comprises: LC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO: 33, LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO: 43, and LC-CDR3, which comprises the amino acid sequence shown in any one of SEQ ID NOs: 51-53.

[0137] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and V L , the V L Comprising: LC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:33 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:43 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; and LC-CDR3, which comprises the amino acid sequence shown in any one of SEQ ID NOs:51-53 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids.

[0138] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24; and V L , the V L It comprises: LC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO: 33, LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO: 43, and LC-CDR3, which comprises the amino acid sequence shown in any one of SEQ ID NOs: 51-53.

[0139] In some embodiments, the anti-NKG2A antibody comprises V H , the VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 33, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 43, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 51, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0140] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:33, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:43, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:51.

[0141] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 33, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 43, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 52, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0142] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:33, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:43, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:52.

[0143] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 33, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 43, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 53, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0144] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:33, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:43, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:53.

[0145] In some embodiments, the anti-NKG2A antibody comprises V H, the V H Comprising V as shown in any one of the amino acid sequences of SEQ ID NOs: 68-71 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , the V L Comprising V as shown in any one of the amino acid sequences of SEQ ID NOs: 92-95 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0146] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 68 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:92 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0147] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 69 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:93 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0148] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 70 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:93 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0149] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 69 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:94 LContains LC-CDR1, LC-CDR2 and LC-CDR3.

[0150] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 70 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:94 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0151] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 71 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:95 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0152] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 68-71 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence as set forth in any one of SEQ ID NOs: 68-71; and V L , the V L comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 92-95 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence as set forth in any one of SEQ ID NOs: 92-95. In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising the amino acid sequence shown in any one of SEQ ID NOs: 68-71, and V L , the V L Comprising the amino acid sequence shown in any one of SEQ ID NOs:92-95.

[0153] In some embodiments, the anti-NKG2A antibody comprises: V H , the VH comprising the amino acid sequence of SEQ ID NO: 68 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 68; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 92 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 92. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 68, and V L , the V L Comprising the amino acid sequence SEQ ID NO:92.

[0154] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 69 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 69; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 93 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 93. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 69, and V L , the V L Comprising the amino acid sequence SEQ ID NO:93.

[0155] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 70 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 70; and V L , the V Lcomprising the amino acid sequence of SEQ ID NO: 93 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 93. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 70, and V L , the V L Comprising the amino acid sequence SEQ ID NO:93.

[0156] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 69 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 69; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 94 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 94. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 69, and V L , the V L Comprising the amino acid sequence SEQ ID NO:94.

[0157] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 70 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 70; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 94 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 94. In some embodiments, the anti-NKG2A antibody comprises V H , the VH Comprising the amino acid sequence SEQ ID NO: 70, and V L , the V L Comprising the amino acid sequence SEQ ID NO:94.

[0158] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 71 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 71; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 95 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 95. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 71, and V L , the V L Comprising the amino acid sequence SEQ ID NO:95.

[0159] In some embodiments, the anti-NKG2A antibody comprises a heavy chain variable domain (V H ), the V H The invention comprises: a heavy chain complementary determining region (HC-CDR) 1 comprising NYHMS (SEQ ID NO: 2); HC-CDR2 comprising YIGAAX1X2X3YYASWAKG (SEQ ID NO: 65), wherein X1 is G, N or S, X2 is N or S, and X3 is A, I or T; and HC-CDR3 comprising GVIYNNL (SEQ ID NO: 25); and a light chain variable domain (V L ), the V L Comprising: a light chain complementary determining region (LC-CDR) 1 comprising QASESISNYLS (SEQ ID NO: 34); a LC-CDR2 comprising DASDLAS (SEQ ID NO: 44); and a LC-CDR3 comprising QX1TYGSINX2NYGVA (SEQ ID NO: 67), wherein X1 is A or C, and X2 is A, Q, or S

[0160] In some embodiments, the anti-NKG2A antibody comprises V H , the VH comprising: an HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO: 2 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; an HC-CDR2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10-16 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and an HC-CDR3 comprising the amino acid sequence shown in SEQ ID NO: 25 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids.

[0161] In some embodiments, the anti-NKG2A antibody comprises V H , the V H It comprises: HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10-16, and HC-CDR3 comprising the amino acid sequence shown in SEQ ID NO: 25.

[0162] In some embodiments, the anti-NKG2A antibody comprises V L , the V L Comprising: LC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:34 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:44 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; and LC-CDR3, which comprises the amino acid sequence shown in any one of SEQ ID NOs:54-57 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids.

[0163] In some embodiments, the anti-NKG2A antibody comprises V L , the V L It comprises: LC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO: 34, LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO: 44, and LC-CDR3, which comprises the amino acid sequence shown in any one of SEQ ID NOs: 54-57.

[0164] In some embodiments, the anti-NKG2A antibody comprises V H , the V Hcomprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 10-16 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and V L , the V L Comprising: LC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:34 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:44 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; and LC-CDR3, which comprises the amino acid sequence shown in any one of SEQ ID NOs:54-57 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids.

[0165] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 10-16, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and V L , the V L It comprises: LC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO: 34, LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO: 44, and LC-CDR3, which comprises the amino acid sequence shown in any one of SEQ ID NOs: 54-57.

[0166] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the VL comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 54, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0167] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:54.

[0168] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 55, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0169] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and V L, the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:55.

[0170] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 56, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0171] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:56.

[0172] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and VL , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 56, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0173] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:56.

[0174] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 56, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0175] In some embodiments, the anti-NKG2A antibody comprises V H , the V Hcomprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:56.

[0176] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 13, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 55, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0177] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:55.

[0178] In some embodiments, the anti-NKG2A antibody comprises V H , the V Hcomprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 14, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 55, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0179] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 14, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:55.

[0180] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 15, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 55, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0181] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 15, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:55.

[0182] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 55, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0183] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:55.

[0184] In some embodiments, the anti-NKG2A antibody comprises V H , the VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 55, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0185] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:55.

[0186] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 55, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0187] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:55.

[0188] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 57, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0189] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:57.

[0190] In some embodiments, the anti-NKG2A antibody comprises VH , the V H Comprising V as shown in any one of the amino acid sequences of SEQ ID NOs: 72-84 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , the V L Comprising V as shown in any one of the amino acid sequences of SEQ ID NOs: 96-101 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0191] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 72 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:96 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0192] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 73 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:97 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0193] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 74 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:97 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0194] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 75 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:97L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0195] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 76 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:97 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0196] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 77 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:97 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0197] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 78 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:97 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0198] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 73 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:98 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0199] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 74 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and VL , which comprises V as shown in the amino acid sequence SEQ ID NO:98 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0200] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 75 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:98 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0201] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 76 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:98 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0202] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 77 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:98 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0203] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 78 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:98 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0204] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 78H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:99 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0205] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 78 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 100 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0206] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 79 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 100 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0207] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO:80 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 100 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0208] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO:81 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:99 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0209] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 82 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:99 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0210] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 83 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:99 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0211] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 84 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:99 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0212] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 79 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:99 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0213] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO:80 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO:99 LContains LC-CDR1, LC-CDR2 and LC-CDR3.

[0214] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 78 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 101 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0215] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 72-84, or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence as set forth in any one of SEQ ID NOs: 72-84; and V L , the V L comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 96-101 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence as set forth in any one of SEQ ID NOs: 96-101. In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising the amino acid sequence shown in any one of SEQ ID NOs: 72-84, and V L , the V L Comprising the amino acid sequence shown in any one of SEQ ID NOs: 96-101.

[0216] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 72 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 72; and V L , the V Lcomprising the amino acid sequence of SEQ ID NO: 96 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 96. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 72, and V L , the V L Comprising the amino acid sequence SEQ ID NO:96.

[0217] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 73 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 73; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 97 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 97. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 73, and V L , the V L Comprising the amino acid sequence SEQ ID NO:97.

[0218] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 74 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 74; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 97 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 97. In some embodiments, the anti-NKG2A antibody comprises V H , the VH Comprising the amino acid sequence SEQ ID NO: 74, and V L , the V L Comprising the amino acid sequence SEQ ID NO:97.

[0219] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 75 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 75; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 97 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 97. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 75, and V L , the V L Comprising the amino acid sequence SEQ ID NO:97.

[0220] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 76 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 76; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 97 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 97. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 76, and V L , the V L Comprising the amino acid sequence SEQ ID NO:97.

[0221] In some embodiments, the anti-NKG2A antibody comprises: VH , the V H comprising the amino acid sequence of SEQ ID NO: 77 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 77; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 97 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 97. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 77, and V L , the V L Comprising the amino acid sequence SEQ ID NO:97.

[0222] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 78 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 78; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 97 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 97. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 78, and V L , the V L Comprising the amino acid sequence SEQ ID NO:97.

[0223] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 73 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 73; and V L, the V L comprising the amino acid sequence of SEQ ID NO: 98 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 98. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 73, and V L , the V L Comprising the amino acid sequence SEQ ID NO:98.

[0224] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 74 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 74; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 98 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 98. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 74, and V L , the V L Comprising the amino acid sequence SEQ ID NO:98.

[0225] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 75 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 75; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 98 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 98. In some embodiments, the anti-NKG2A antibody comprises VH , the V H Comprising the amino acid sequence SEQ ID NO: 75, and V L , the V L Comprising the amino acid sequence SEQ ID NO:98.

[0226] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 76 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 76; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 98 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 98. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 76, and V L , the V L Comprising the amino acid sequence SEQ ID NO:98.

[0227] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 77 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 77; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 98 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 98. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 77, and V L , the V L Comprising the amino acid sequence SEQ ID NO:98.

[0228] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 78 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 78; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 98 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 98. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 78, and V L , the V L Comprising the amino acid sequence SEQ ID NO:98.

[0229] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 78 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 78; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 99 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 99. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 78, and V L , the V L Comprising the amino acid sequence SEQ ID NO:99.

[0230] In some embodiments, the anti-NKG2A antibody comprises: V H , the V Hcomprising the amino acid sequence of SEQ ID NO: 78 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 78; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 100 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 100. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 78, and V L , the V L Comprising the amino acid sequence SEQ ID NO:100.

[0231] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 79 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 79; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 100 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 100. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 79, and V L , the V L Comprising the amino acid sequence SEQ ID NO:100.

[0232] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 80 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 80; and V L , the V Lcomprising the amino acid sequence of SEQ ID NO: 100 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 100. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 80, and V L , the V L Comprising the amino acid sequence SEQ ID NO:100.

[0233] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 81 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 81; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 99 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 99. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 81, and V L , the V L Comprising the amino acid sequence SEQ ID NO:99.

[0234] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 82 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 82; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 99 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 99. In some embodiments, the anti-NKG2A antibody comprises V H , the VH Comprising the amino acid sequence SEQ ID NO: 82, and V L , the V L Comprising the amino acid sequence SEQ ID NO:99.

[0235] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 83 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 83; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 99 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 99. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 83, and V L , the V L Comprising the amino acid sequence SEQ ID NO:99.

[0236] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 84 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 84; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 99 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 99. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 84, and V L , the V L Comprising the amino acid sequence SEQ ID NO:99.

[0237] In some embodiments, the anti-NKG2A antibody comprises: V H, the V H comprising the amino acid sequence of SEQ ID NO: 79 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 79; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 99 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 99. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 79, and V L , the V L Comprising the amino acid sequence SEQ ID NO:99.

[0238] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 80 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 80; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 99 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 99. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 80, and V L , the V L Comprising the amino acid sequence SEQ ID NO:99.

[0239] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 78 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 78; and V L , the VL comprising the amino acid sequence of SEQ ID NO: 101 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 78, and V L , the V L Comprising the amino acid sequence SEQ ID NO:101.

[0240] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 35, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 45, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 51, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0241] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:35, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:45, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:51.

[0242] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 68 HHC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 102 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0243] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 68 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 68; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 102 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 102. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 68, and V L , the V L Comprising the amino acid sequence SEQ ID NO:102.

[0244] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 17, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 26, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 36, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 46, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0245] In some embodiments, the anti-NKG2A antibody comprises V H , the V Hcomprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 17, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 26; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:36, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:46, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:58.

[0246] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 85 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 103 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0247] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 85 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 85; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 103 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 103. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 85, and V L , the V L Comprising the amino acid sequence SEQ ID NO:103.

[0248] In some embodiments, the anti-NKG2A antibody comprises V H , the V Hcomprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 18, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 27, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 37, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 47, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 59, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0249] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 18, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 27; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:37, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:47, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:59.

[0250] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 86 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 104 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0251] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 86 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 86; and V L , the VL comprising the amino acid sequence of SEQ ID NO: 104 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 104. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 86, and V L , the V L Comprising the amino acid sequence SEQ ID NO:104.

[0252] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 4, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 19, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 28, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 38, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 48, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 60, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0253] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 4, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 19, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 28; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:38, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:48, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:60.

[0254] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 87H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 105 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0255] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 87 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 87; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 105 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 105. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 87, and V L , the V L Comprising the amino acid sequence SEQ ID NO:105.

[0256] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 5, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 20, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 29, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 39, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 61, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0257] In some embodiments, the anti-NKG2A antibody comprises V H , the VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 5, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 20, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 29; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:39, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:61.

[0258] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 88 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 106 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0259] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 88 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 88; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 106 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 106. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 88, and V L , the V L Comprising the amino acid sequence SEQ ID NO:106.

[0260] In some embodiments, the anti-NKG2A antibody comprises V H , the V Hcomprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 6, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 21, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 30, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 49, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 62, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0261] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 6, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 30; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:40, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:49, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:62.

[0262] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 89 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 107 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0263] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 89 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 89; and V L , the VL comprising the amino acid sequence of SEQ ID NO: 107 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 107. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 89, and V L , the V L Comprising the amino acid sequence SEQ ID NO:107.

[0264] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 7, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 31, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 63, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0265] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 7, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 31; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:41, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:63.

[0266] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO:90H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 108 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0267] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 90 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 90; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 108 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 108. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 90, and V L , the V L Comprising the amino acid sequence SEQ ID NO:108.

[0268] In some embodiments, the anti-NKG2A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 8, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 23, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 32, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 42, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 50, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 64, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0269] In some embodiments, the anti-NKG2A antibody comprises V H , the VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 8, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 23, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 32; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:42, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:50, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:64.

[0270] In some embodiments, the anti-NKG2A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO:91 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 109 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0271] In some embodiments, the anti-NKG2A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 91 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 91; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 109 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 109. In some embodiments, the anti-NKG2A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 91, and V L , the V L Comprising the amino acid sequence SEQ ID NO:109.

[0272] In some embodiments, the above-mentioned amino acid substitutions are limited to the "exemplary substitutions" shown herein in Table 4. In some embodiments, the amino acid substitutions are limited to the "preferred substitutions" shown herein in Table 4.

[0273] In some embodiments, functional epitopes can be resolved using combinatorial alanine scanning. In this process, combinatorial alanine scanning can be used to identify amino acids in the NKG2A protein that are essential for interaction with the anti-NKG2A antibody. In some embodiments, the epitope is conformational and can be identified using a crystal structure of an anti-NKG2A antibody bound to the NKG2A protein.

[0274] In some embodiments, the present application provides antibodies that competitively bind to NKG2A with any of the anti-NKG2A antibodies described herein. In some embodiments, antibodies that can competitively bind to an epitope on NKG2A with any of the anti-NKG2A antibodies described herein are provided. In some embodiments, anti-NKG2A antibodies are provided that are combined with a V H and V L The anti-NKG2A antibody molecules bind to the same epitope, wherein the V H comprising the amino acid sequence shown in any one of SEQ ID NOs: 68-91, and said V L In some embodiments, an anti-NKG2A antibody is provided, which is combined with a V H and V L The anti-NKG2A antibody competitively binds to NKG2A, wherein the V H comprising the amino acid sequence shown in any one of SEQ ID NOs: 68-91, and said V L Comprising the amino acid sequence shown in any one of SEQ ID NOs: 92-109.

[0275] In some embodiments, competition assays can be used to identify monoclonal antibodies that compete with the anti-NKG2A antibodies described herein for binding to NKG2A. Competition assays can determine whether two antibodies bind to the same epitope by recognizing identical or spatially overlapping epitopes or by competitively inhibiting antigen binding of one antibody to the other. In certain embodiments, such competing antibodies bind to the same epitope as the antibodies described herein. Some exemplary competition assays include, but are not limited to, conventional assays described in Harlow and Lane (1988) Antibodies: A Laboratory Manual ch. 14 (Cold Spring Harbor Laboratory, Cold Spring Harbor, NY). Detailed exemplary methods for resolving epitopes bound by antibodies are described in Morris (1996) "Epitope Mapping Protocols," in Methods in Molecular Biology vol. 66 (Humana Press, Totowa, NJ). In some embodiments, each antibody is said to bind to the same epitope if it blocks 50% or more of the binding of the other antibody. In some embodiments, the antibody that competes with the anti-NKG2A antibodies described herein is a chimeric antibody, a humanized antibody, or a fully human antibody.

[0276] Exemplary anti-NKG2A antibody sequences are shown in Tables 2 and 3, where CDR numbering is performed according to the Kabat definition. Those skilled in the art will recognize that there are a variety of known algorithms for predicting the positions of CDRs and defining the variable regions of antibody light and heavy chains. H and / or V L Sequences, but based on prediction algorithms other than those exemplified in the table below, are also within the scope of this application.

[0277] Table 2 Exemplary anti-NKG2A antibody CDR sequences

[0278] Table 3 Exemplary sequences

[0279] NKG2A

[0280] NK cells are a type of innate lymphocyte that serve as immune sentinels, playing a crucial role in combating invading "non-self" target cells. Peripheral blood NK cells comprise approximately 10% to 15% of all circulating lymphocytes, but they can also be isolated from various tissues, including the spleen, liver, lung, and bone marrow. In adults, NK cells primarily develop from CD34 hematopoietic stem cells in the bone marrow. They interact with stromal cells within a microenvironment rich in cytokines and growth factors, supporting NK cell development and maturation. NK cells rapidly migrate from the blood to inflamed tissues or secondary lymphoid organs to perform immune surveillance against pathogens and tumors. Unlike T and B cells, NK cell activation does not require antigen sensitization, as NK cell effector functions are controlled by a limited set of NK cell-activating receptors (aNKRs) and NK cell-inhibitory receptors (iNKRs). Upon activation, NK cells also produce and secrete chemokines and cytokines, which play a key role in promoting inflammatory responses and priming other cells of the immune system such as dendritic cells or macrophages, thereby linking innate immunity with adaptive immunity (Elisa Zaghi et al., 2018, J Leukoc Biol.).

[0281] NK cell activation relies on the ability to discriminate between "self" and "non-self" through recognition of major histocompatibility complex (MHC) class I molecules by members of the iNKR family. Indeed, the interaction of these receptors with specific haplotypes of human leukocyte antigen (HLA) class I molecules on the surface of target cells is crucial for determining NK cell alloreactivity against "non-self." Currently, two major classes of receptors mediate "self" recognition: KIRs and C-type lectin receptors. The CD94 / NKG2 heterodimer is a representative example of a C-type lectin HLA-I-specific receptor: CD94 / NKG2A is an inhibitory receptor containing an ITIM in its cytoplasmic domain, while CD94 / NKG2C is an activating receptor lacking an ITIM in its cytoplasmic domain and binding to the DAP-12 ligand. These receptors interact with non-classical HLA-E molecules. Although NKG2A and NKG2C recognize overlapping HLA-E molecules, the inhibitory receptor displays a higher binding affinity for its ligand, overcoming the NK cell activation signal.

[0282] In humans, the NKG2A protein is encoded by the NKG2A gene. NKG2A is also known as CD159 antigen-like family member A, NK cell receptor A, NKG2A activating NK receptor, NKG2A / B activating NK receptor, killer cell lectin-like receptor C1 (CD159a), and NKG2A / NKG2B type II integral membrane protein. NKG2A belongs to the lectin receptor family, which also includes NKG2C, NKG2D, and NKG2E. NKG2A, NKG2C, and NKG2E share high homology in the amino acid sequences of their extracellular domains, but NKG2A is a functionally distinct receptor. NKG2A forms a heterodimer with CD94. In the NKG2 / CD94 heterodimer, NKG2A / CD94 is the only receptor with inhibitory function, while NKG2C / CD94 and NKG2E / CD94 are activating receptors. NKG2D is also an activating receptor, but does not form heterodimers with CD94, nor does NKG2D bind to HLA-E.

[0283] NKG2A is expressed on natural killer (NK) cells, effector / memory CD8 T cells, NKT cells, and γδ T cells. Approximately 50% of peripheral blood NK cells express NKG2A (Andre et al., 1999; Mahapatra et al., 2017; Manser and Uhrberg, 2016), and its expression on NK cells can be upregulated by stimulation with cytokines such as interleukin-15 (IL-15) (Brady et al., 2004; Mori et al., 1998). In healthy individuals, approximately 5% of human peripheral blood CD8+ T cells express cell surface NKG2A, but chronic antigenic stimulation can upregulate its expression (Bertone et al., 1999; McMahon et al., 2002; Mingari et al., 1998; Sheu et al., 2005).

[0284] The NKG2 / CD94 receptor recognizes non-classical major histocompatibility (MHC) class I molecules, human leukocyte antigen-E (HLA-E) in humans and Qa-1 in mice. NKG2A / CD94 binds to HLA-E with approximately six times greater affinity than NKG2C / CD94. Binding of HLA-E molecules expressed on target cells to NKG2A inhibits the cytotoxicity of NK cells. The N-terminal NK cell cytoplasmic domain of the NKG2A protein contains two immunoreceptor tyrosine-based inhibitory motifs (ITIMs), which transmit inhibitory signals to NK cells, inducing a cascade of inhibitory signals and thereby suppressing the effector functions of both T and NK cells.

[0285] Studies have reported that blocking the inhibitory NKG2A receptor can promote the effector functions of NK cells and CD8+ T cells, thereby enhancing tumor immunity in mice and humans. Monalizumab, a humanized anti-NKG2A antibody, has been shown to enhance NK cell activity against various tumor cells and rescue CD8+ T cell function in combination with PD-x blockade. Therefore, targeting NKG2A represents a novel checkpoint inhibitory mechanism that promotes anti-tumor immunity by enhancing the activity of both T and NK cells.

[0286] NKG2A ligand HLA-E

[0287] The ligands for the heterodimeric receptor NKG2A / CD94 are human HLA-E and its mouse homolog Qa-1b. These non-classical MHC class Ib molecules are conserved across populations and present signal peptides from classical MHC class I molecules (45). Polymorphic classical HLA class I molecules present antigenic peptide epitopes to the TCR on the surface of CD8 T cells. In contrast, HLA-E is a monomorphic non-classical HLA class I molecule that presents a limited set of conserved signal peptides. These signal peptides are derived from the leader sequence of classical HLA class I molecules. Both NKG2A and NKG2C form heterodimeric receptors with CD94 and target the same HLA-E tetramer complex, however, NKG2A / CD94 binding to HLA-E induces inhibitory signals for NKG2A, while NKG2C / CD94 binding to HLA-E induces activating signals for NKG2C. Importantly, the NKG2A / CD94 receptor has strong signal peptide specificity. Specifically, NKG2A / CD94 preferentially binds to HLA-E containing signal peptides, particularly those containing conserved leader peptides, but not to those lacking these peptides. Most HLA class I molecules share a common amino acid sequence, VMAPRTLLL, within their signal peptide region. Positions 7 and 8 can be altered between leucine and valine without affecting binding affinity.

[0288] Although most tissues express HLA-E at low basal cell surface levels, HLA-E is highly expressed in immune-privileged areas of the body, including trophoblasts of the placenta and ductal epithelial cells of the testis and epididymis, suggesting that HLA-E may play a role in counteracting potential attack by CD8 T cells and NK cells on partially HLA-mismatched fetal and haploid germ cells. Furthermore, expression of HLA-E or its mouse homolog, Qa-1b, protects tissue integrity during viral clearance and limits overactivation and apoptosis of CD8 T cells.

[0289] One strategy used by neoplastic cells to evade NK cell immune surveillance is downregulation of HLA, a mechanism also used by some viruses to evade lymphocyte cytotoxicity. However, certain cancer types, including renal cell carcinoma, acute myeloid leukemia (AML), and hepatocellular carcinoma, do not completely lack HLA-I and may even upregulate non-classical HLA-E and HLA-G. One possible explanation is that the expression of HLA-I self-molecules on tumor cells disrupts NK cell alloreactivity, rendering cancer cells resistant to NK cell lysis. Experimental evidence supporting this hypothesis demonstrates that renal cell carcinoma cells express HLA-E on their cell surface and are able to inhibit the effector function of tumor-infiltrating NK cells by upregulating CD94 / NKG2A heterodimers on NK cells. NK cells from AML patients have also been reported to exhibit decreased expression of the activating receptor NKp46, accompanied by increased NKG2A expression and impaired effector function. These phenotypic and functional abnormalities may be directly mediated by tumor cells, which not only express HLA-E on their surface but also release soluble molecules that can regulate NKRs (Elisa Zaghi et al., 2018, J Leukoc Biol.).

[0290] Full-length anti-NKG2A antibody

[0291] In some embodiments, the anti-NKG2A antibody is a full-length anti-NKG2A antibody. In some embodiments, the full-length anti-NKG2A antibody is IgA, IgD, IgE, IgG, or IgM. In some embodiments, the full-length anti-NKG2A antibody comprises an IgG constant region, such as a constant region of IgG1, IgG2, IgG3, IgG4, or a variant thereof. In some embodiments, the full-length anti-NKG2A antibody comprises a lambda light chain constant region. In some embodiments, the full-length anti-NKG2A antibody comprises a kappa light chain constant region. In some embodiments, the full-length anti-NKG2A antibody is a full-length human anti-NKG2A antibody. In some embodiments, the full-length anti-NKG2A antibody comprises a mouse immunoglobulin Fc sequence. In some embodiments, the full-length anti-NKG2A antibody comprises an altered or otherwise modified Fc sequence such that it has enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) effector functions.

[0292] Thus, for example, in some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody specifically binds to NKG2A. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0293] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG2 constant region is provided, wherein the anti-NKG2A antibody specifically binds to NKG2A. In some embodiments, the IgG2 is human IgG2. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0294] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG3 constant region is provided, wherein the anti-NKG2A antibody specifically binds to NKG2A. In some embodiments, the IgG3 is a human IgG3. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0295] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG4 constant region is provided, wherein the anti-NKG2A antibody specifically binds to NKG2A. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0296] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 1-8 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; an HC-CDR2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 9-23 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; and an HC-CDR3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 24-32 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; and b) a light chain variable domain comprising: an LC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: NOs:33-42 or a variant thereof, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids, LC-CDR2 comprising an amino acid sequence as shown in any one of SEQ ID NOs:43-50 or a variant thereof, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and LC-CDR3 comprising an amino acid sequence as shown in any one of SEQ ID NOs:51-64 or a variant thereof, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:113.

[0297] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG2 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 1-8 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; an HC-CDR2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 9-23 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; and an HC-CDR3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 24-32 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; and b) a light chain variable domain comprising: an LC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: NOs: 33-42 or a variant thereof, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; LC-CDR2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 43-50 or a variant thereof, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and LC-CDR3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 51-64 or a variant thereof, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids. In some embodiments, the IgG2 is a human IgG2. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0298] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG3 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 1-8 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions, an HC-CDR2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 9-23 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; and an HC-CDR3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 24-32 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; and b) a light chain variable domain comprising: an LC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 1-8 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions. NOs: 33-42 or a variant thereof, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; LC-CDR2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 43-50 or a variant thereof, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and LC-CDR3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 51-64 or a variant thereof, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids. In some embodiments, the IgG3 is a human IgG3. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0299] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG4 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 1-8 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; an HC-CDR2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 9-23 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; and an HC-CDR3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 24-32 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; and b) a light chain variable domain comprising: an LC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: NOs:33-42 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids, LC-CDR2, comprising an amino acid sequence as set forth in any one of SEQ ID NOs:43-50 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids, and LC-CDR3, comprising an amino acid sequence as set forth in any one of SEQ ID NOs:51-64 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:111. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:113.

[0300] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 1-8, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 9-23, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 24-32, or a variant of the heavy chain variable domain comprising up to about 5 (e.g., 1, 2, 3, 4, or 5) amino acid substitutions in the HC-CDR sequence; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 33-42, an LC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 43-50, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NOs: The amino acid sequence shown in any one of NOs:51-64, or a variant of the light chain variable domain, comprises a substitution of up to about 5 (e.g., 1, 2, 3, 4, or 5) amino acids in its LC-CDR sequence. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0301] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG4 constant region is provided, wherein the anti-NKG2A antibody comprises a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 1-8, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 9-23, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 24-32, or a variant of the heavy chain variable domain comprising up to about 5 (e.g., 1, 2, 3, 4, or 5) amino acid substitutions in the HC-CDR sequence; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 33-42, an LC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 43-50, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NOs: The amino acid sequence shown in any one of NOs:51-64, or a variant of the light chain variable domain, comprises a substitution of up to about 5 (e.g., 1, 2, 3, 4, or 5) amino acids in its LC-CDR sequence. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0302] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 1-8, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 9-23, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 24-32; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 33-42, an LC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 43-50, and an LC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 51-64. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0303] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG4 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 1-8, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 9-23, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 24-32; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 33-42, an LC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 43-50, and an LC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 51-64. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0304] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 33, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 43, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 51. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0305] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 33, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 43, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 52. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0306] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 33, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 43, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 53. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0307] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 54. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0308] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 55. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0309] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 56. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0310] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 56. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0311] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 56. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0312] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 55. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0313] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 55. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0314] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 15, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 55. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0315] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 55. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0316] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 55. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0317] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 55. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0318] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 57. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0319] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 35, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 45, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 51. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0320] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 3, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 17, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 26; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 36, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 46, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0321] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 3, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 18, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 27; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 37, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 47, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 59. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0322] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 4, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 19, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 28; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 38, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 48, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 60. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0323] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 5, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 20, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 29; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 39, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 61. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0324] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 6, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 30; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 49, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 62. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0325] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 7, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 31; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 63. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0326] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 8, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 23, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 32; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 42, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 50, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 64. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0327] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG4 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 33, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 43, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 51. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0328] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG4 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 33, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 43, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 52. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0329] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG4 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 33, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 43, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 53. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0330] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG4 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 54. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0331] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG4 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 55. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0332] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG4 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 56. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0333] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG4 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 56. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0334] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG4 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 56. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0335] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG4 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 55. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0336] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG4 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 55. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0337] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG4 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 15, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 55. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0338] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG4 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 55. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0339] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG4 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 55. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0340] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG4 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 55. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0341] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG4 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 57. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0342] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG4 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 35, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 45, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 51. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0343] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG4 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 3, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 17, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 26; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 36, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 46, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0344] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG4 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 3, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 18, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 27; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 37, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 47, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 59. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0345] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG4 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 4, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 19, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 28; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 38, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 48, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 60. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0346] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG4 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 5, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 20, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 29; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 39, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 61. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0347] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG4 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 6, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 30; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 49, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 62. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0348] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG4 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 7, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 31; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 63. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0349] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG4 constant region is provided, wherein the anti-NKG2A antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 8, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 23, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 32; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 42, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 50, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 64. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0350] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: a heavy chain variable domain (V H ), the V H comprising an amino acid sequence as shown in any one of SEQ ID NOs: 68-91 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence as shown in any one of SEQ ID NOs: 68-91; and a light chain variable domain (V L ), the V Lcomprising the amino acid sequence of any one of SEQ ID NOs: 92-109 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of any one of SEQ ID NOs: 92-109. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0351] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG2 constant region is provided, wherein the anti-NKG2A antibody comprises: a heavy chain variable domain (V H ), the V H comprising an amino acid sequence as shown in any one of SEQ ID NOs: 68-91 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence as shown in any one of SEQ ID NOs: 68-91; and a light chain variable domain (V L ), the V L The invention also provides an IgG2 antibody comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 92-109 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to any one of SEQ ID NOs: 92-109. In some embodiments, the IgG2 antibody is a human IgG2 antibody. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0352] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG3 constant region is provided, wherein the anti-NKG2A antibody comprises: a heavy chain variable domain (V H ), the V Hcomprising an amino acid sequence as shown in any one of SEQ ID NOs: 68-91 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence as shown in any one of SEQ ID NOs: 68-91; and a light chain variable domain (V L ), the V L The invention also provides an IgG3 antibody comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 92-109 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to any one of SEQ ID NOs: 92-109. In some embodiments, the IgG3 antibody is a human IgG3 antibody. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0353] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG4 constant region is provided, wherein the anti-NKG2A antibody comprises: a heavy chain variable domain (V H ), the V H comprising an amino acid sequence as shown in any one of SEQ ID NOs: 68-91 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence as shown in any one of SEQ ID NOs: 68-91; and a light chain variable domain (V L ), the V Lcomprising the amino acid sequence of any one of SEQ ID NOs: 92-109 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of any one of SEQ ID NOs: 92-109. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0354] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: a heavy chain variable domain (V H ), the V H comprising the amino acid sequence shown in any one of SEQ ID NOs: 68-91, and a light chain variable domain (V L ), the V L comprising the amino acid sequence of any one of SEQ ID NOs: 92-109. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0355] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG4 constant region is provided, wherein the anti-NKG2A antibody comprises: a heavy chain variable domain (V H ), the V Hcomprising the amino acid sequence shown in any one of SEQ ID NOs: 68-91, and a light chain variable domain (V L ), the V L comprising the amino acid sequence of any one of SEQ ID NOs: 92-109. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 111 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0356] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: V H , comprising the amino acid sequence of SEQ ID NO: 68 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 68; and V L , which comprises the amino acid sequence of SEQ ID NO: 92 or a variant thereof having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 92. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0357] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: V H, comprising the amino acid sequence of SEQ ID NO: 69 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 69; and V L , which comprises the amino acid sequence of SEQ ID NO: 93 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 93. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0358] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: V H , comprising the amino acid sequence of SEQ ID NO: 70 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 70; and V L , which comprises the amino acid sequence of SEQ ID NO: 93 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 93. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0359] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: V H, comprising the amino acid sequence of SEQ ID NO: 69 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 69; and V L , which comprises the amino acid sequence of SEQ ID NO: 94 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 94. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0360] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: V H , comprising the amino acid sequence of SEQ ID NO: 70 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 70; and V L , which comprises the amino acid sequence of SEQ ID NO: 94 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 94. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0361] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: V H, comprising the amino acid sequence of SEQ ID NO: 71 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 71; and V L , which comprises the amino acid sequence of SEQ ID NO: 95 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 95. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0362] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: V H , comprising the amino acid sequence of SEQ ID NO: 72 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 72; and V L , which comprises the amino acid sequence of SEQ ID NO: 96 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 96. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0363] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: V H, comprising the amino acid sequence of SEQ ID NO: 73 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 73; and V L , which comprises the amino acid sequence of SEQ ID NO: 97 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 97. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0364] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided, wherein the anti-NKG2A antibody comprises: V H , comprising the amino acid sequence of SEQ ID NO: 74 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 74; and V L , which comprises the amino acid sequence of SEQ ID NO: 97 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 97. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 110 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 113.

[0365] In some embodiments, a full-length anti-NKG2A antibody comprising an IgG1 constant region is provided...

Claims

An isolated anti-NKG2A antibody, wherein the anti-NKG2A antibody comprises: a heavy chain variable domain (V H ), the V H The invention comprises: a heavy chain complementary determining region (HC-CDR) 1 comprising SNTMS (SEQ ID NO: 1); HC-CDR2 comprising NINTGGNTYYANWAKG (SEQ ID NO: 9); and HC-CDR3 comprising GSTIDSSGLSL (SEQ ID NO: 24); and a light chain variable domain (V L ), the V L It comprises: a light chain complementary determining region (LC-CDR) 1 comprising QASQNIGSDLA (SEQ ID NO: 33); a LC-CDR2 comprising LASTLAS (SEQ ID NO: 43); and a LC-CDR3 comprising QQX1WSSSNVDNV (SEQ ID NO: 66), wherein X1 is C, S or T. The isolated anti-NKG2A antibody according to claim 1, comprising: (i) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 33, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 43, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 51; (ii) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:33, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:43, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:52; or (iii) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24; and V L , the V L It comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:33, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:43, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:

53. The isolated anti-NKG2A antibody according to any one of claims 1 to 2, comprising: (i) V H , comprising the amino acid sequence of SEQ ID NO: 68 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 68; and V L , comprising the amino acid sequence of SEQ ID NO: 92 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 92; (ii) V H , comprising the amino acid sequence of SEQ ID NO: 69 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 69; and V L , comprising the amino acid sequence of SEQ ID NO: 93 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 93; (iii) V H , comprising the amino acid sequence of SEQ ID NO: 70 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 70; and V L , which comprises the amino acid sequence of SEQ ID NO: 93 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 93; (iv) V H , comprising the amino acid sequence of SEQ ID NO: 69 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 69; and V L , comprising the amino acid sequence of SEQ ID NO: 94 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 94; (v) V H , comprising the amino acid sequence of SEQ ID NO: 70 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 70; and V L , which comprises the amino acid sequence of SEQ ID NO:94 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:94; or (vi) V H , comprising the amino acid sequence of SEQ ID NO: 71 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 71; and V L , which comprises the amino acid sequence of SEQ ID NO:95 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:

95. An isolated anti-NKG2A antibody, wherein the anti-NKG2A antibody comprises: a heavy chain variable domain (V H ), the V H The invention comprises: a heavy chain complementary determining region (HC-CDR) 1 comprising NYHMS (SEQ ID NO: 2); HC-CDR2 comprising YIGAAX1X2X3YYASWAKG (SEQ ID NO: 65), wherein X1 is G, N or S, X2 is N or S, and X3 is A, I or T; and HC-CDR3 comprising GVIYNNL (SEQ ID NO: 25); and a light chain variable domain (V L ), the V L It comprises: a light chain complementary determining region (LC-CDR) 1 comprising QASESISNYLS (SEQ ID NO: 34); a LC-CDR2 comprising DASDLAS (SEQ ID NO: 44); and a LC-CDR3 comprising QX1TYGSINX2NYGVA (SEQ ID NO: 67), wherein X1 is A or C, and X2 is A, Q or S. The isolated anti-NKG2A antibody according to claim 4, comprising: (i) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:54; (ii) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:55; (iii) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:56; (iv) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:56; (v) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:56; (vi) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:55; (vii) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 14, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:55; (viii) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 15, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:55; (ix) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:55; (x) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:34, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:55; (xi) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and V L , the V L comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO:34, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO:44, and a LC-CDR3 comprising the amino acid sequence of SEQ ID NO:55; or (xii) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and V L , the V L It comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:34, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:44, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:

57. The isolated anti-NKG2A antibody according to any one of claims 4-5, comprising: (i) V H , comprising the amino acid sequence of SEQ ID NO: 72 or a variant thereof, wherein the variant has at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 72; and V L , comprising the amino acid sequence of SEQ ID NO: 96 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 96; (ii) V H , comprising the amino acid sequence of SEQ ID NO: 73 or a variant thereof, wherein the variant has at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 73; and V L , comprising the amino acid sequence of SEQ ID NO: 97 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 97; (iii) V H , comprising the amino acid sequence of SEQ ID NO: 74 or a variant thereof, wherein the variant has at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 74; and V L , comprising the amino acid sequence of SEQ ID NO: 97 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 97; (iv) V H , comprising the amino acid sequence of SEQ ID NO: 75 or a variant thereof, wherein the variant has at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 75; and V L , comprising the amino acid sequence of SEQ ID NO: 97 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 97; (v) V H , comprising the amino acid sequence of SEQ ID NO: 76 or a variant thereof, wherein the variant has at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 76; and V L , comprising the amino acid sequence of SEQ ID NO: 97 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 97; (vi) V H , comprising the amino acid sequence of SEQ ID NO: 77 or a variant thereof, wherein the variant has at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 77; and V L , comprising the amino acid sequence of SEQ ID NO: 97 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 97; (vii) V H , comprising the amino acid sequence of SEQ ID NO: 78 or a variant thereof, wherein the variant has at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 78; and V L , comprising the amino acid sequence of SEQ ID NO: 97 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 97; (viii) V H , comprising the amino acid sequence of SEQ ID NO: 73 or a variant thereof, wherein the variant has at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 73; and V L , comprising the amino acid sequence of SEQ ID NO: 98 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 98; (ix) V H , comprising the amino acid sequence of SEQ ID NO: 74 or a variant thereof, wherein the variant has at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 74; and V L , comprising the amino acid sequence of SEQ ID NO: 98 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 98; (x) V H , comprising the amino acid sequence of SEQ ID NO: 75 or a variant thereof, wherein the variant has at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 75; and V L , comprising the amino acid sequence of SEQ ID NO: 98 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 98; (xi) V H , comprising the amino acid sequence of SEQ ID NO: 76 or a variant thereof, wherein the variant has at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 76; and V L , comprising the amino acid sequence of SEQ ID NO: 98 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 98; (xii) V H , comprising the amino acid sequence of SEQ ID NO: 77 or a variant thereof, wherein the variant has at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 77; and V L , comprising the amino acid sequence of SEQ ID NO: 98 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 98; (xiii) V H , comprising the amino acid sequence of SEQ ID NO: 78 or a variant thereof, wherein the variant has at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 78; and V L , comprising the amino acid sequence of SEQ ID NO: 98 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 98; (xiv) V H , comprising the amino acid sequence of SEQ ID NO: 78 or a variant thereof, wherein the variant has at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 78; and V L , comprising the amino acid sequence of SEQ ID NO: 99 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 99; (xv) V H , comprising the amino acid sequence of SEQ ID NO: 78 or a variant thereof, wherein the variant has at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 78; and V L , comprising the amino acid sequence of SEQ ID NO: 100 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 100; (xvi) V H , comprising the amino acid sequence of SEQ ID NO: 79 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 79; and V L , comprising the amino acid sequence of SEQ ID NO: 100 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 100; (xvii) V H , comprising the amino acid sequence of SEQ ID NO: 80 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 80; and V L , comprising the amino acid sequence of SEQ ID NO: 100 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 100; (xviii) V H , comprising the amino acid sequence of SEQ ID NO: 81 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 81; and V L , comprising the amino acid sequence of SEQ ID NO: 99 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 99; (xix) V H , comprising the amino acid sequence of SEQ ID NO: 82 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 82; and V L , comprising the amino acid sequence of SEQ ID NO: 99 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 99; (xx) V H , comprising the amino acid sequence of SEQ ID NO: 83 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 83; and V L , comprising the amino acid sequence of SEQ ID NO: 99 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 99; (xxi) V H , comprising the amino acid sequence of SEQ ID NO: 84 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 84; and V L , comprising the amino acid sequence of SEQ ID NO: 99 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 99; (xxii) V H , comprising the amino acid sequence of SEQ ID NO: 79 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 79; and V L , comprising the amino acid sequence of SEQ ID NO: 99 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 99; (xxiii) V H , comprising the amino acid sequence of SEQ ID NO: 80 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 80; and V L , which comprises the amino acid sequence of SEQ ID NO:99 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:99; or (xxiv) V H , comprising the amino acid sequence of SEQ ID NO: 78 or a variant thereof, wherein the variant has at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 78; and V L , which comprises the amino acid sequence of SEQ ID NO:101 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:

101. An isolated anti-NKG2A antibody comprising: (i) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:35, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:45, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:51; (ii) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 17, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 26; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:36, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:46, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:58; (iii) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 18, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 27; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 37, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 47, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 59; (iv) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 4, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 19, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 28; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 38, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 48, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 60; (v) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 5, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 20, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 29; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 39, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 61; (vi) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 6, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 30; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:40, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:49, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:62; (vii) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 7, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 31; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:41, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:44, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:63; or (viii) V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 8, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 23, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 32; and V L , the V L It comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:42, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:50, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:

64. The isolated anti-NKG2A antibody according to claim 7, comprising: (i) V H , which comprises the amino acid sequence shown in SEQ ID NO:68 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:68; and V L , which comprises the amino acid sequence shown in SEQ ID NO: 102 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 102; (ii) V H , which comprises the amino acid sequence shown in SEQ ID NO:85 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:85; and V L , which comprises the amino acid sequence shown in SEQ ID NO: 103 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 103; (iii) V H , comprising the amino acid sequence shown in SEQ ID NO:86 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:86; and V L , which comprises the amino acid sequence shown in SEQ ID NO: 104 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 104; (iv) V H , comprising the amino acid sequence shown in SEQ ID NO:87 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:87; and V L , which comprises the amino acid sequence shown in SEQ ID NO: 105 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 105; (v) V H , comprising the amino acid sequence shown in SEQ ID NO:88 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:88; and V L , which comprises the amino acid sequence shown in SEQ ID NO: 106 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 106; (vi) V H , comprising the amino acid sequence shown in SEQ ID NO:89 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:89; and V L , which comprises the amino acid sequence shown in SEQ ID NO: 107 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 107; (vii) V H , comprising the amino acid sequence shown in SEQ ID NO:90 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:90; and V L , which comprises the amino acid sequence shown in SEQ ID NO: 108 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 108; or (viii) V H , comprising the amino acid sequence shown in SEQ ID NO:91 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:91; and V L , which comprises the amino acid sequence shown in SEQ ID NO:109 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:

109. The isolated anti-NKG2A antibody according to any one of claims 1-8, wherein the anti-NKG2A antibody binds to human NKG2A with a Kd value of about 0.1 pM to about 10 nM. The isolated anti-NKG2A antibody according to any one of claims 1 to 9, wherein the anti-NKG2A antibody comprises an Fc fragment. The isolated anti-NKG2A antibody according to claim 10, wherein the anti-NKG2A antibody is a full-length IgA, IgD, IgE, IgG or IgM antibody. The isolated anti-NKG2A antibody according to claim 11, wherein the anti-NKG2A antibody is a full-length IgG1, IgG2, IgG3 or IgG4 antibody. The isolated anti-NKG2A antibody according to any one of claims 1 to 12, wherein the anti-NKG2A antibody is a chimeric, human or humanized antibody. The isolated anti-NKG2A antibody according to any one of claims 1 to 9, wherein the anti-NKG2A antibody is an antigen-binding fragment selected from the group consisting of Fab, Fab', F(ab)'2, Fab'-SH, single-chain Fv (scFv), Fv fragment, dAb, Fd, nanobody, diabody and linear antibody. An isolated nucleic acid molecule encoding the anti-NKG2A antibody according to any one of claims 1-14. A vector comprising the nucleic acid molecule of claim 15. An isolated host cell comprising the anti-NKG2A antibody according to any one of claims 1 to 14, the nucleic acid molecule according to claim 15 or the vector according to claim 16. A method for preparing an anti-NKG2A antibody, comprising: a) culturing the host cell of claim 17 under conditions that can effectively express the anti-NKG2A antibody; and b) obtaining the expressed anti-NKG2A antibody from the host cell. A pharmaceutical composition comprising the anti-NKG2A antibody according to any one of claims 1 to 14, the nucleic acid molecule according to claim 15, the vector according to claim 16, the isolated host cell according to claim 17 or the antibody prepared by the method according to claim 18, and a pharmaceutically acceptable carrier. Use of the antibody of any one of claims 1 to 14, the nucleic acid molecule of claim 15, the vector of claim 16, the host cell of claim 17, the antibody prepared by the method of claim 18, or the pharmaceutical composition of claim 19 in the preparation of a medicament for treating a disease or condition in an individual in need thereof. The use according to claim 20, wherein the disease or condition is a disease and / or condition caused by dysregulation of the NKG2A signaling pathway, such as cancer, viral disease, autoimmune disease and / or inflammatory disease. The use according to claim 21, wherein the disease or condition is selected from cancer, such as renal cancer, bladder cancer, breast cancer, colon cancer, liver cancer, lung cancer, ovarian cancer, prostate cancer, pancreatic cancer, stomach cancer, uterine cancer, thyroid cancer, skin cancer, melanoma, xeroderma pigmentosum, keratoacanthoma, seminoma, follicular thyroid cancer, teratoma, squamous cell carcinoma, leukemia, acute lymphocytic leukemia, chronic lymphocytic leukemia, acute lymphoblastic leukemia, B cell lymphoma, T cell lymphoma, Hodgkin's Lymphoma, non-Hodgkin's lymphoma, hairy cell lymphoma, Burketts lymphoma, multiple myeloma, acute and chronic myeloid leukemia, promyelocytic leukemia, myelodysplastic syndrome; viral diseases, such as hepatitis A, hepatitis B, hepatitis C, influenza, chickenpox, adenovirus, herpes simplex type I (HSV-1), herpes simplex type II (HSV-2), rinderpest, rhinovirus, echovirus, rotavirus, respiratory syncytial virus, papillomavirus, cytomegalovirus, echinovirus rus, arboviruses, hantaviruses, coxsackieviruses, mumps virus, measles virus, rubella virus, poliovirus, human immunodeficiency virus type 1 or 2 (HIV-1, HIV-2); autoimmune diseases such as hemolytic anemia, pernicious anemia, polyarteritis nodosa, systemic lupus erythematosus, Wegener's granulomatosis, autoimmune hepatitis, Behcet's disease, Crohn's disease, primary biliary cirrhosis, scleroderma, ulcerative colitis, Sjogren's syndrome, type 1 diabetes, Uveitis, Graves' disease, Alzheimer's disease, thyroiditis; inflammatory diseases, such as conjunctivitis, cystitis, dermatitis, diverticulitis, encephalitis, endocarditis, esophagitis, eustachianitis, fibrositis, folliculitis, gastritis, gastroenteritis, gingivitis, glossitis, hepatosplenomegaly, keratitis, otitis interna, laryngitis, lymphangitis, mastitis, otitis media, meningitis, metritis, mucositis, myocarditis, myositis, tympanitis, nephritis, neuritis, orchitis, osteochondritis, otitis, pericarditis, tenosynovitis, peritonitis, pharyngitis, phlebitis, etc.

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