Anti-LILRB1 / 2 antibodies and uses thereof

Abstract

The present disclosure relates to anti-LILRB1 (leukocyte immunoglobulin-like receptor B member 1) and / or anti-LILRB2 (leukocyte immunoglobulin-like receptor B subfamily member 2) antibodies, antigen binding fragments and uses thereof.

Description

[0001] This application claims priority to U.S. Provisional Application No. 63 / 316,918, filed on March 4, 2022. Technical Field

[0002] The present disclosure relates to antibodies capable of binding to leukocyte immunoglobulin-like receptor subfamily B member 1 and / or leukocyte immunoglobulin-like receptor subfamily B member 2, and uses thereof. Background Art

[0003] During tumor progression, several immune escape mechanisms are induced. For example, newly transformed cells may lose their antigenicity and / or immunogenicity, thereby acquiring the expression of molecules that inhibit T cell activation, and these inhibitory cytokine secretions may also promote an immunosuppressive microenvironment. Overall, these mechanisms can lead to tumor escape by suppressing and exhausting T cells.

[0004] In cancer treatment, breakthroughs have been made in therapies to control tumor progression and reconstruct immune function. For example, immunotherapy is mainly based on antibodies that target and inhibit T cell activation molecules or their ligands. Continuous clinical results have been achieved by administering these antibodies to restore T cell co-stimulatory signals and reactivate anti-tumor T cell immune responses. Despite the success of these therapies, a considerable number of patients still do not respond. Therefore, it is necessary to continue to develop antibodies for various cancer treatments. Summary of the invention

[0005] The present disclosure relates to anti-LILRB1 / 2 antibodies, antigen-binding fragments thereof, and uses thereof.

[0006] In one aspect, the disclosure relates to an antibody or antigen-binding fragment that binds to LILRB1 (leukocyte immunoglobulin-like receptor subfamily B member 1) and / or LILRB2 (leukocyte immunoglobulin-like receptor subfamily B member 2), comprising: a heavy chain variable region (VH) comprising complementary determining regions (CDRs) 1, 2, and 3, wherein the VH CDR1 region has an amino acid sequence that is at least 80% homologous to a selected VHCDR1, the VH CDR2 region has an amino acid sequence that is at least 80% homologous to a selected VH CDR2, and the VH CDR3 region has an amino acid sequence that is at least 80% homologous to a selected VH CDR3; and a light chain variable region (VL) comprising complementary determining regions (CDRs) 1, 2, and 3, wherein the VL CDR1 region has an amino acid sequence that is at least 80% homologous to a selected VL CDR1, the VL CDR2 region has an amino acid sequence that is at least 80% homologous to a selected VL CDR2, and the VL CDR3 region has an amino acid sequence that is at least 80% homologous to a selected VL CDR3. CDR3 has an amino acid sequence with 80% homology. In a specific implementation, the selected VH CDR1, 2 and 3 amino acid sequences and the selected VL CDR1, 2 and 3 amino acid sequences are one of the following:

[0007] (1) the heavy chain variable region CDR1, 2, and 3 respectively comprise an amino acid sequence selected from SEQ ID NOs: 7, 8, and 9, and the light chain variable region CDR1, 2, and 3 respectively comprise an amino acid sequence selected from SEQ ID NOs: 10, 11, and 12;

[0008] (2) the heavy chain variable region CDR1, 2, and 3 respectively comprise an amino acid sequence selected from SEQ ID NOs: 37, 38, and 39, and the light chain variable region CDR1, 2, and 3 respectively comprise an amino acid sequence selected from SEQ ID NOs: 40, 41, and 42;

[0009] (3) the heavy chain variable region CDR1, 2, and 3 include amino acid sequences selected from SEQ ID NOs: 67, 68, and 69, respectively, and the light chain variable region CDR1, 2, and 3 include amino acid sequences selected from SEQ ID NOs: 70, 71, and 72, respectively;

[0010] (4) the heavy chain variable region CDR1, 2, and 3 respectively comprise an amino acid sequence selected from SEQ ID NOs: 97, 98, and 99, and the light chain variable region CDR1, 2, and 3 respectively comprise an amino acid sequence selected from SEQ ID NOs: 100, 101, and 102;

[0011] (5) the heavy chain variable region CDR1, 2, and 3 include amino acid sequences selected from SEQ ID NOs: 127, 128, and 129, respectively, and the light chain variable region CDR1, 2, and 3 include amino acid sequences selected from SEQ ID NOs: 130, 131, and 132, respectively;

[0012] (6) the heavy chain variable region CDR1, 2, and 3 include amino acid sequences selected from SEQ ID NOs: 157, 158, and 159, respectively, and the light chain variable region CDR1, 2, and 3 include amino acid sequences selected from SEQ ID NOs: 160, 161, and 162, respectively;

[0013] (7) the heavy chain variable region CDR1, 2, and 3 include amino acid sequences selected from SEQ ID NOs: 187, 188, and 189, respectively, and the light chain variable region CDR1, 2, and 3 include amino acid sequences selected from SEQ ID NOs: 190, 191, and 192, respectively;

[0014] (8) the heavy chain variable region CDR1, 2, and 3 include amino acid sequences selected from SEQ ID NOs: 217, 218, and 219, respectively, and the light chain variable region CDR1, 2, and 3 include amino acid sequences selected from SEQ ID NOs: 220, 221, and 222, respectively;

[0015] (9) the heavy chain variable region CDR1, 2, and 3 respectively comprise an amino acid sequence selected from SEQ ID NOs: 247, 248, and 249, and the light chain variable region CDR1, 2, and 3 respectively comprise an amino acid sequence selected from SEQ ID NOs: 250, 251, and 252;

[0016] (10) the heavy chain variable region CDR1, 2, and 3 respectively comprise an amino acid sequence selected from SEQ ID NOs: 277, 278, and 279, and the light chain variable region CDR1, 2, and 3 respectively comprise an amino acid sequence selected from SEQ ID NOs: 280, 281, and 282;

[0017] (11) the heavy chain variable region CDR1, 2, and 3 respectively comprise an amino acid sequence selected from SEQ ID NOs: 307, 308, and 309, and the light chain variable region CDR1, 2, and 3 respectively comprise an amino acid sequence selected from SEQ ID NOs: 310, 311, and 312;

[0018] (12) the heavy chain variable region CDR1, 2, and 3 include amino acid sequences selected from SEQ ID NOs: 337, 338, and 339, respectively, and the light chain variable region CDR1, 2, and 3 include amino acid sequences selected from SEQ ID NOs: 340, 341, and 342, respectively;

[0019] (13) the heavy chain variable region CDR1, 2, and 3 respectively comprise an amino acid sequence selected from SEQ ID NOs: 367, 368, and 369, and the light chain variable region CDR1, 2, and 3 respectively comprise an amino acid sequence selected from SEQ ID NOs: 370, 371, and 372;

[0020] (14) the heavy chain variable region CDR1, 2, and 3 respectively comprise an amino acid sequence selected from SEQ ID NOs: 397, 398, and 399, and the light chain variable region CDR1, 2, and 3 respectively comprise an amino acid sequence selected from SEQ ID NOs: 400, 401, and 402;

[0021] (15) the heavy chain variable region CDR1, 2, and 3 include amino acid sequences selected from SEQ ID NOs: 427, 428, and 429, respectively, and the light chain variable region CDR1, 2, and 3 include amino acid sequences selected from SEQ ID NOs: 430, 431, and 432, respectively;

[0022] (16) the heavy chain variable region CDR1, 2, and 3 include amino acid sequences selected from SEQ ID NOs: 457, 458, and 459, respectively, and the light chain variable region CDR1, 2, and 3 include amino acid sequences selected from SEQ ID NOs: 460, 461, and 462, respectively;

[0023] (17) the heavy chain variable region CDR1, 2, and 3 include amino acid sequences selected from SEQ ID NOs: 487, 488, and 489, respectively, and the light chain variable region CDR1, 2, and 3 include amino acid sequences selected from SEQ ID NOs: 490, 491, and 492, respectively;

[0024] (18) the heavy chain variable region CDR1, 2, and 3 include amino acid sequences selected from SEQ ID NOs: 517, 518, and 519, respectively, and the light chain variable region CDR1, 2, and 3 include amino acid sequences selected from SEQ ID NOs: 520, 521, and 522, respectively;

[0025] (19) the heavy chain variable region CDR1, 2, and 3 include amino acid sequences selected from SEQ ID NOs: 547, 548, and 549, respectively, and the light chain variable region CDR1, 2, and 3 include amino acid sequences selected from SEQ ID NOs: 550, 551, and 552, respectively;

[0026] (20) the heavy chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 577, 578, and 579, respectively, and the light chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 580, 581, and 582, respectively;

[0027] (21) the heavy chain variable region CDR1, 2, and 3 respectively include an amino acid sequence selected from SEQ ID NOs: 607, 608, and 609, and the light chain variable region CDR1, 2, and 3 respectively include an amino acid sequence selected from SEQ ID NOs: 610, 611, and 612;

[0028] (22) the heavy chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 637, 638, and 639, respectively, and the light chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 640, 641, and 642, respectively;

[0029] (23) the heavy chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 667, 668, and 669, respectively, and the light chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 670, 671, and 672, respectively;

[0030] (24) the heavy chain variable region CDR1, 2, and 3 include amino acid sequences selected from SEQ ID NOs: 697, 698, and 699, respectively, and the light chain variable region CDR1, 2, and 3 include amino acid sequences selected from SEQ ID NOs: 700, 701, and 702, respectively;

[0031] (25) the heavy chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 727, 728, and 729, respectively, and the light chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 730, 731, and 732, respectively;

[0032] (26) the heavy chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1069, 1070, and 1071, respectively, and the light chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1072, 1073, and 1074, respectively;

[0033] (27) the heavy chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1093, 1094, and 1095, respectively, and the light chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1096, 1097, and 1098, respectively;

[0034] (28) the heavy chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1117, 1118, and 1119, respectively, and the light chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1120, 1121, and 1122, respectively;

[0035] (29) the heavy chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1141, 1142, and 1143, respectively, and the light chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1144, 1145, and 1146, respectively;

[0036] (30) the heavy chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1165, 1166, and 1167, respectively, and the light chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1168, 1169, and 1170, respectively;

[0037] (31) the heavy chain variable region CDR1, 2, and 3 respectively comprise an amino acid sequence selected from SEQ ID NOs: 1189, 1190, and 1191, and the light chain variable region CDR1, 2, and 3 respectively comprise an amino acid sequence selected from SEQ ID NOs: 1192, 1193, and 1194;

[0038] (32) the heavy chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1213, 1214, and 1215, respectively, and the light chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1216, 1217, and 1218, respectively;

[0039] (33) the heavy chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1237, 1238, and 1239, respectively, and the light chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1240, 1241, and 1242, respectively;

[0040] (34) the heavy chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1261, 1262, and 1263, respectively, and the light chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1264, 1265, and 1266, respectively;

[0041] (35) the heavy chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1285, 1286, and 1287, respectively, and the light chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1288, 1289, and 1290, respectively;

[0042] (36) the heavy chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1309, 1310, and 1311, respectively, and the light chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1312, 1313, and 1314, respectively;

[0043] (37) the heavy chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1333, 1334, and 1335, respectively, and the light chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1336, 1337, and 1338, respectively;

[0044] (38) the heavy chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1357, 1358, and 1359, respectively, and the light chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1360, 1361, and 1362, respectively;

[0045] (39) the heavy chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1381, 1382, and 1383, respectively, and the light chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1384, 1385, and 1386, respectively;

[0046] (40) the heavy chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1405, 1406, and 1407, respectively, and the light chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1408, 1409, and 1410, respectively;

[0047] (41) the heavy chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1429, 1430, and 1431, respectively, and the light chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1432, 1433, and 1434, respectively;

[0048] (42) the heavy chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1453, 1454, and 1455, respectively, and the light chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1456, 1457, and 1458, respectively;

[0049] (43) the heavy chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1477, 1478, and 1479, respectively, and the light chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1480, 1481, and 1482, respectively;

[0050] (44) the heavy chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1501, 1502, and 1503, respectively, and the light chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1504, 1505, and 1506, respectively;

[0051] (45) the heavy chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1525, 1526, and 1527, respectively, and the light chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1528, 1529, and 1530, respectively;

[0052] (46) the heavy chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1549, 1550, and 1551, respectively, and the light chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1552, 1553, and 1554, respectively;

[0053] (47) the heavy chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1573, 1574, and 1575, respectively, and the light chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1576, 1577, and 1578, respectively;

[0054] (48) the heavy chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1597, 1598, and 1599, respectively, and the light chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1600, 1601, and 1602, respectively;

[0055] (49) the heavy chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1621, 1622, and 1623, respectively, and the light chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1624, 1625, and 1626, respectively;

[0056] (50) the heavy chain variable region CDR1, 2, and 3 respectively include an amino acid sequence selected from SEQ ID NOs: 1645, 1646, and 1647, and the light chain variable region CDR1, 2, and 3 respectively include an amino acid sequence selected from SEQ ID NOs: 1648, 1649, and 1650; and

[0057] (51) the heavy chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1669, 1670, and 1671, respectively, and the light chain variable region CDR1, 2, and 3 include an amino acid sequence selected from SEQ ID NOs: 1672, 1673, and 1674, respectively;

[0058] In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 7, 8, 9, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 10, 11, 12, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 37, 38, 39, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 40, 41, 42, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 67, 68, 69, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 70, 71, 72, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 97, 98, 99, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 100, 101, 102, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 127, 128, 129, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 130, 131, 132, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 157, 158, 159, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 160, 161, 162, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 187, 188, 189, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 190, 191, 192, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 217, 218, 219, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 220, 221, 222, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 247, 248, 249, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 250, 251, 252, respectively. In some embodiments, the heavy chain variable region CDR1, 2, and 3 are selected from the amino acid sequences of SEQ ID NOs: 277, 278, and 279, respectively, and the light chain variable region CDR1, 2, and 3 are selected from the amino acid sequences of SEQ ID NOs: 280, 281, and 282, respectively.In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 307, 308, 309, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 310, 311, 312, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 337, 338, 339, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 340, 341, 342, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 367, 368, 369, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 370, 371, 372, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 397, 398, 399, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 400, 401, 402, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 427, 428, 429, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 430, 431, 432, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 457, 458, 459, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 460, 461, 462, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 487, 488, 489, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 490, 491, 492, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 517, 518, 519, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 520, 521, 522, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 547, 548, 549, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 550, 551, 552, respectively.In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 577, 578, 579, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 580, 581, 582, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 607, 608, 609, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 610, 611, 612, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 637, 638, 639, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 640, 641, 642, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 667, 668, 669, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 670, 671, 672, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 697, 698, 699, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 700, 701, 702, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 727, 728, 729, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 730, 731, 732, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1069, 1070, 1071, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1072, 1073, 1074, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1093, 1094, 1095, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1096, 1097, 1098, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1117, 1118, 1119, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1120, 1121, 1122, respectively.In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1141, 1142, 1143, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1144, 1145, 1146, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1165, 1166, 1167, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1168, 1169, 1170, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1189, 1190, 1191, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1192, 1193, 1194, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1213, 1214, 1215, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1216, 1217, 1218, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1237, 1238, 1239, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1240, 1241, 1242, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1261, 1262, 1263, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1264, 1265, 1266, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1285, 1286, 1287, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1288, 1289, 1290, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1309, 1310, 1311, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1312, 1313, 1314, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1333, 1334, 1335, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1336, 1337, 1338, respectively.In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1357, 1358, 1359, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1360, 1361, 1362, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1381, 1382, 1383, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1384, 1385, 1386, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1405, 1406, 1407, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1408, 1409, 1410, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1429, 1430, 1431, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1432, 1433, 1434, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1453, 1454, 1455, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1456, 1457, 1458, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1477, 1478, 1479, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1480, 1481, 1482, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1501, 1502, 1503, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1504, 1505, 1506, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1525, 1526, 1527, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1528, 1529, 1530, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1549, 1550, 1551, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1552, 1553, 1554, respectively.In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1573, 1574, 1575, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1576, 1577, 1578, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1597, 1598, 1599, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1600, 1601, 1602, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1621, 1622, 1623, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1624, 1625, 1626, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1645, 1646, 1647, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1648, 1649, 1650, respectively. In some embodiments, the heavy chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1669, 1670, 1671, respectively, and the light chain variable region CDR1, 2, 3 are selected from the amino acid sequences of SEQ ID NOs: 1672, 1673, 1674, respectively.

[0059] In some embodiments, the antibody or antigen-binding fragment thereof specifically binds to human LILRB1 and / or human LILRB2. In some embodiments, the antibody or antigen-binding fragment thereof specifically binds to monkey LILRB1 and / or monkey LILRB2. In some embodiments, the antibody or antigen-binding fragment thereof can block the interaction between LILRB1 and MHC class I molecules (e.g., human leukocyte antigen-G (HLA-G)), or the interaction between LILRB2 and MHC class I molecules (e.g., HLA-G). In some embodiments, the antibody or antigen-binding fragment thereof is a humanized antibody or antigen-binding fragment. In some embodiments, the antibody or antigen-binding fragment thereof is a single-chain variable fragment (scFV) or a multispecific antibody (e.g., a bispecific antibody). In some embodiments, the antibody or antigen-binding fragment thereof specifically binds to LILRB3 (e.g., human LILRB3).

[0060] In one aspect, the disclosure relates to a nucleic acid comprising a polynucleotide encoding a polypeptide comprising:

[0061] (1) An immunoglobulin heavy chain or a fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 7, 8 and 9, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 752, it can bind to LILRB1 and / or LILRB2;

[0062] (2) an immunoglobulin light chain or a fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 10, 11 and 12, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 751, it can bind to LILRB1 and / or LILRB2;

[0063] (3) an immunoglobulin heavy chain or a fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 37, 38 and 39, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 754, it can bind to LILRB1 and / or LILRB2;

[0064] (4) an immunoglobulin light chain or a fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 40, 41 and 42, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 753, it can bind to LILRB1 and / or LILRB2;

[0065] (5) an immunoglobulin heavy chain or a fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 67, 68 and 69, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 756, it can bind to LILRB1 and / or LILRB2;

[0066] (6) an immunoglobulin light chain or a fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 70, 71 and 72, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 755, it can bind to LILRB1 and / or LILRB2;

[0067] (7) an immunoglobulin heavy chain or a fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 97, 98 and 99, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 758, it can bind to LILRB1 and / or LILRB2;

[0068] (8) an immunoglobulin light chain or a fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 100, 101 and 102, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 757, it can bind to LILRB1 and / or LILRB2;

[0069] (9) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 127, 128 and 129, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 760, it can bind to LILRB1 and / or LILRB2;

[0070] (10) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 130, 131 and 132, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 759, it can bind to LILRB1 and / or LILRB2;

[0071] (11) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 157, 158 and 159, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 762, it can bind to LILRB1 and / or LILRB2;

[0072] (12) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 160, 161 and 162, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 761, it can bind to LILRB1 and / or LILRB2;

[0073] (13) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 187, 188 and 189, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 764, it can bind to LILRB1 and / or LILRB2;

[0074] (14) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 190, 191 and 192, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 763, it can bind to LILRB1 and / or LILRB2;

[0075] (15) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 217, 218 and 219, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 766, it can bind to LILRB1 and / or LILRB2;

[0076] (16) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 220, 221 and 222, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 765, it can bind to LILRB1 and / or LILRB2;

[0077] (17) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 247, 248 and 249, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 768, it can bind to LILRB1 and / or LILRB2;

[0078] (18) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 250, 251 and 252, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 767, it can bind to LILRB1 and / or LILRB2;

[0079] (19) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 277, 278 and 279, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 770, it can bind to LILRB1 and / or LILRB2;

[0080] (20) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 280, 281 and 282, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 769, it can bind to LILRB1 and / or LILRB2;

[0081] (21) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 307, 308 and 309, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 772, it can bind to LILRB1 and / or LILRB2;

[0082] (22) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 310, 311 and 312, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 771, it can bind to LILRB1 and / or LILRB2;

[0083] (23) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 337, 338 and 339, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 774, it can bind to LILRB1 and / or LILRB2;

[0084] (24) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 340, 341 and 342, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 773, it can bind to LILRB1 and / or LILRB2;

[0085] (25) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs 367, 368 and 369, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 776, it can bind to LILRB1 and / or LILRB2;

[0086] (26) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 370, 371 and 372, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 775, it can bind to LILRB1 and / or LILRB2;

[0087] (27) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 397, 398 and 399, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 778, it can bind to LILRB1 and / or LILRB2;

[0088] (28) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 400, 401 and 402, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 777, it can bind to LILRB1 and / or LILRB2;

[0089] (29) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 427, 428 and 429, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 780, it can bind to LILRB1 and / or LILRB2;

[0090] (30) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 430, 431 and 432, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 779, it can bind to LILRB1 and / or LILRB2;

[0091] (31) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 457, 458 and 459, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 782, it can bind to LILRB1 and / or LILRB2;

[0092] (32) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 460, 461 and 462, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 781, it can bind to LILRB1 and / or LILRB2;

[0093] (33) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 487, 488 and 489, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 784, it can bind to LILRB1 and / or LILRB2;

[0094] (34) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 490, 491 and 492, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 783, it can bind to LILRB1 and / or LILRB2;

[0095] (35) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 517, 518 and 519, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 786, it can bind to LILRB1 and / or LILRB2;

[0096] (36) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 520, 521 and 522, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 785, it can bind to LILRB1 and / or LILRB2;

[0097] (37) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 547, 548 and 549, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 788, it can bind to LILRB1 and / or LILRB2;

[0098] (38) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 550, 551 and 552, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 787, it can bind to LILRB1 and / or LILRB2;

[0099] (39) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 577, 578 and 579, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 790, it can bind to LILRB1 and / or LILRB2;

[0100] (40) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 580, 581 and 582, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 789, it can bind to LILRB1 and / or LILRB2;

[0101] (41) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 607, 608 and 609, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 792, it can bind to LILRB1 and / or LILRB2;

[0102] (42) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 610, 611 and 612, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 791, it can bind to LILRB1 and / or LILRB2;

[0103] (43) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 637, 638 and 639, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 794, it can bind to LILRB1 and / or LILRB2;

[0104] (44) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 640, 641 and 642, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 793, it can bind to LILRB1 and / or LILRB2;

[0105] (45) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 667, 668 and 669, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 796, it can bind to LILRB1 and / or LILRB2;

[0106] (46) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 670, 671 and 672, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 795, it can bind to LILRB1 and / or LILRB2;

[0107] (47) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 697, 698 and 699, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 798, it can bind to LILRB1 and / or LILRB2;

[0108] (48) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 700, 701 and 702, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 797, it can bind to LILRB1 and / or LILRB2;

[0109] (49) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 727, 728 and 729, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 800, it can bind to LILRB1 and / or LILRB2;

[0110] (50) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 730, 731 and 732, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 799, it can bind to LILRB1 and / or LILRB2;

[0111] (51) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1069, 1070 and 1071, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 988, it can bind to LILRB1 and / or LILRB2;

[0112] (52) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1072, 1073 and 1074, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 987, it can bind to LILRB1 and / or LILRB2;

[0113] (53) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1093, 1094 and 1095, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 988, it can bind to LILRB1 and / or LILRB2;

[0114] (54) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1096, 1097 and 1098, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 1687, it can bind to LILRB1 and / or LILRB2;

[0115] (55) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1117, 1118 and 1119, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 988, it can bind to LILRB1 and / or LILRB2;

[0116] (56) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1120, 1121 and 1122, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 1688, it can bind to LILRB1 and / or LILRB2;

[0117] (57) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1141, 1142 and 1143, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 989, it can bind to LILRB1 and / or LILRB2;

[0118] (58) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1144, 1145 and 1146, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 987, it can bind to LILRB1 and / or LILRB2;

[0119] (59) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1165, 1166 and 1167, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 990, it can bind to LILRB1 and / or LILRB2;

[0120] (60) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1168, 1169 and 1170, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 987, it can bind to LILRB1 and / or LILRB2;

[0121] (61) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1189, 1190 and 1191, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 991, it can bind to LILRB1 and / or LILRB2;

[0122] (62) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1192, 1193 and 1194, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 987, it can bind to LILRB1 and / or LILRB2;

[0123] (63) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1213, 1214 and 1215, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 992, it can bind to LILRB1 and / or LILRB2;

[0124] (64) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1216, 1217 and 1218, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 987, it can bind to LILRB1 and / or LILRB2;

[0125] (65) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1237, 1238 and 1239, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 1020, it can bind to LILRB1 and / or LILRB2;

[0126] (66) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1240, 1241 and 1242, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 1019, it can bind to LILRB1 and / or LILRB2;

[0127] (67) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1261, 1262 and 1263, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 1022, it can bind to LILRB1 and / or LILRB2;

[0128] (68) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1264, 1265 and 1266, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 1021, it can bind to LILRB1 and / or LILRB2;

[0129] (69) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1285, 1286 and 1287, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 1024, it can bind to LILRB1 and / or LILRB2;

[0130] (70) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1288, 1289 and 1290, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 1023, it can bind to LILRB1 and / or LILRB2;

[0131] (71) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1309, 1310 and 1311, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 1026, it can bind to LILRB1 and / or LILRB2;

[0132] (72) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1312, 1313 and 1314, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 1025, it can bind to LILRB1 and / or LILRB2;

[0133] (73) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1333, 1334 and 1335, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 1028, it can bind to LILRB1 and / or LILRB2;

[0134] (74) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1336, 1337 and 1338, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 1027, it can bind to LILRB1 and / or LILRB2;

[0135] (75) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1357, 1358 and 1359, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 1030, it can bind to LILRB1 and / or LILRB2;

[0136] (76) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1360, 1361 and 1362, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 1029, it can bind to LILRB1 and / or LILRB2;

[0137] (77) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1381, 1382 and 1383, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 1032, it can bind to LILRB1 and / or LILRB2;

[0138] (78) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1384, 1385 and 1386, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 1031, it can bind to LILRB1 and / or LILRB2;

[0139] (79) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1405, 1406 and 1407, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 1034, it can bind to LILRB1 and / or LILRB2;

[0140] (80) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1408, 1409 and 1410, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 1033, it can bind to LILRB1 and / or LILRB2;

[0141] (81) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1429, 1430 and 1431, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 1036, it can bind to LILRB1 and / or LILRB2;

[0142] (82) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1432, 1433 and 1434, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 1035, it can bind to LILRB1 and / or LILRB2;

[0143] (83) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1453, 1454 and 1455, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 1038, it can bind to LILRB1 and / or LILRB2;

[0144] (84) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1456, 1457 and 1458, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 1037, it can bind to LILRB1 and / or LILRB2;

[0145] (85) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1477, 1478 and 1479, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 1040, it can bind to LILRB1 and / or LILRB2;

[0146] (86) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1480, 1481 and 1482, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 1039, it can bind to LILRB1 and / or LILRB2;

[0147] (87) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1501, 1502 and 1503, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 1042, it can bind to LILRB1 and / or LILRB2;

[0148] (88) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs 1504, 1505 and 1506, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 1041, it can bind to LILRB1 and / or LILRB2;

[0149] (89) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1525, 1526 and 1527, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 1044, 1689 or 1690, it can bind to LILRB1 and / or LILRB2;

[0150] (90) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1528, 1529 and 1530, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 1043, it can bind to LILRB1 and / or LILRB2;

[0151] (91) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1549, 1550 and 1551, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 1046, it can bind to LILRB1 and / or LILRB2;

[0152] (92) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1552, 1553 and 1554, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 1045, it can bind to LILRB1 and / or LILRB2;

[0153] (93) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1573, 1574 and 1575, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 1048, it can bind to LILRB1 and / or LILRB2;

[0154] (94) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1576, 1577 and 1578, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 1047, it can bind to LILRB1 and / or LILRB2;

[0155] (95) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1597, 1598 and 1599, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 1050, it can bind to LILRB1 and / or LILRB2;

[0156] (96) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1600, 1601 and 1602, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 1049, it can bind to LILRB1 and / or LILRB2;

[0157] (97) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1621, 1622 and 1623, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 1052, it can bind to LILRB1 and / or LILRB2;

[0158] (98) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1624, 1625 and 1626, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 1051, it can bind to LILRB1 and / or LILRB2;

[0159] (99) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1645, 1646 and 1647, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 1054, it can bind to LILRB1 and / or LILRB2;

[0160] (100) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1648, 1649 and 1650, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 1053, it can bind to LILRB1 and / or LILRB2;

[0161] (101) An immunoglobulin heavy chain or fragment thereof, wherein the heavy chain variable region (VH) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1669, 1670 and 1671, respectively. In certain embodiments, when the VH is paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO: 1056, it can bind to LILRB1 and / or LILRB2; or

[0162] (102) An immunoglobulin light chain or fragment thereof, wherein the light chain variable region (VL) comprises complementarity determining regions (CDRs) 1, 2 and 3 consisting of the amino acid sequences shown in SEQ ID NOs: 1672, 1673 and 1674, respectively. In certain embodiments, when the VL is paired with a heavy chain variable region (VH) comprising the amino acid sequence shown in SEQ ID NO: 1055, it can bind to LILRB1 and / or LILRB2;

[0163] In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 7, 8 and 9, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 10, 11 and 12, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 37, 38 and 39, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 40, 41 and 42, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 67, 68 and 69, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 70, 71 and 72, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 97, 98 and 99, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 100, 101 and 102, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 127, 128 and 129, respectively.In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 130, 131 and 132, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 157, 158 and 159, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 160, 161 and 162, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 187, 188 and 189, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 190, 191 and 192, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 217, 218 and 219, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 220, 221 and 222, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 247, 248 and 249, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 250, 251 and 252, respectively.In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 277, 278 and 279, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 280, 281 and 282, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 307, 308 and 309, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 310, 311 and 312, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 337, 338 and 339, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 340, 341 and 342, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 367, 368 and 369, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 370, 371 and 372, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 397, 398 and 399, respectively.In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 400, 401 and 402, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 427, 428 and 429, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 430, 431 and 432, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 457, 458 and 459, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 460, 461 and 462, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 487, 488 and 489, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 490, 491 and 492, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 517, 518 and 519, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 520, 521 and 522, respectively.In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 547, 548 and 549, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 550, 551 and 552, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 577, 578 and 579, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 580, 581 and 582, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 607, 608 and 609, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 610, 611 and 612, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 637, 638 and 639, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 640, 641 and 642, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 667, 668 and 669, respectively.In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 700, 701 and 702, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 697, 698 and 699, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 700, 701 and 702, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 727, 728 and 729, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 730, 731 and 732, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 1069, 1070 and 1071, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 1072, 1073 and 1074, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 1093, 1094 and 1095, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 1096, 1097 and 1098, respectively.In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 1117, 1118 and 1119, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 1120, 1121 and 1122, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 1141, 1142 and 1143, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 1144, 1145 and 1146, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 1165, 1166 and 1167, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 1168, 1169 and 1170, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 1189, 1190 and 1191, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 1192, 1193 and 1194, respectively.In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 1213, 1214 and 1215, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 1216, 1217 and 1218, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 1237, 1238 and 1239, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 1240, 1241 and 1242, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 1261, 1262 and 1263, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 1264, 1265 and 1266, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 1285, 1286 and 1287, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 1288, 1289 and 1290, respectively.In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 1309, 1310 and 1311, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 1312, 1313 and 1314, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 1333, 1334 and 1335, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 1336, 1337 and 1338, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 1357, 1358 and 1359, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 1360, 1361 and 1362, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 1381, 1382 and 1383, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 1384, 1385 and 1386, respectively.In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 1405, 1406 and 1407, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 1408, 1409 and 1410, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 1429, 1430 and 1431, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 1432, 1433 and 1434, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 1453, 1454 and 1455, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 1456, 1457 and 1458, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 1477, 1478 and 1479, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 1480, 1481 and 1482, respectively.In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 1501, 1502 and 1503, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 1504, 1505 and 1506, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 1525, 1526 and 1527, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 1528, 1529 and 1530, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 1549, 1550 and 1551, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 1552, 1553 and 1554, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 1573, 1574 and 1575, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 1576, 1577 and 1578, respectively.In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 1597, 1598 and 1599, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 1600, 1601 and 1602, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 1621, 1622 and 1623, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 1624, 1625 and 1626, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 1645, 1646 and 1647, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementary determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 1648, 1649 and 1650, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a heavy chain variable region (VH) consisting of the amino acid sequences shown in SEQ ID NOs: 1669, 1670 and 1671, respectively. In certain embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin light chain or a fragment thereof, comprising complementarity determining regions (CDRs) 1, 2 and 3 of a light chain variable region (VL) consisting of the amino acid sequences shown in SEQ ID NOs: 1672, 1673 and 1674, respectively.

[0164] In some embodiments, when VH is paired with VL, it specifically binds to human LILRB1 and / or LILRB2; or when VL is paired with VH, it specifically binds to human LILRB1 and / or LILRB2. In some embodiments, the immunoglobulin heavy chain or fragment thereof is a humanized immunoglobulin heavy chain or fragment thereof, and the immunoglobulin light chain or fragment thereof is a humanized immunoglobulin light chain or fragment thereof. In some embodiments, the nucleic acid encodes a single-chain variable fragment (scFv) or a multispecific antibody (e.g., a bispecific antibody). In some embodiments, the nucleic acid is a cDNA.

[0165] In one aspect, the disclosure relates to a vector comprising one or more nucleic acids described herein. In one aspect, the disclosure relates to a vector comprising two nucleic acids described herein, in some embodiments, the vector encodes a VL region and a VH region that bind to LILRB1 and / or LILRB2 together. In one aspect, the disclosure relates to a pair of vectors, in some embodiments, each vector comprises a nucleic acid described herein, in some embodiments, the pair of vectors together encode a VL region and a VH region that bind to LILRB1 and / or LILRB2.

[0166] In one aspect, the disclosure relates to a cell comprising a vector or vector pair described herein. In some embodiments, the cell is a CHO cell. In one aspect, the disclosure relates to a cell comprising one or more nucleic acids described herein. In one aspect, the disclosure relates to a cell comprising two nucleic acids described herein. In some embodiments, the two nucleic acids together encode a VL region and a VH region that binds to LILRB1 and / or LILRB2.

[0167] In one aspect, the disclosure relates to a method of producing an antibody or an antigen-binding fragment thereof, the method comprising (a) culturing a cell described herein under conditions sufficient for the cell to produce the antibody or antigen-binding fragment; and (b) collecting the antibody or antigen-binding fragment produced by the cell.

[0168] In one aspect, the disclosure relates to an antibody or antigen-binding fragment that binds to LILRB1 and / or LILRB2, the fragment comprising a heavy chain variable region (VH) comprising an amino acid sequence that is at least 90% identical to a selected VH sequence, and a light chain variable region (VL) comprising an amino acid sequence that is at least 90% identical to a selected VL sequence. In some embodiments, the selected VH sequence and the selected VL sequence are one of the following: (1) the selected VH sequence is SEQ ID NO: 751 and the selected VL sequence is SEQ ID NO: 752; (2) the selected VH sequence is SEQ ID NO: 753 and the selected VL sequence is SEQ ID NO: 754; (3) the selected VH sequence is SEQ ID NO: 755 and the selected VL sequence is SEQ ID NO: 756; (4) the selected VH sequence is SEQ ID NO: 757 and the selected VL sequence is SEQ ID NO: 758; (5) the selected VH sequence is SEQ ID NO: ID NO: 759, the selected VL sequence is SEQ ID NO: 760; (6) the selected VH sequence is SEQ ID NO: 761, the selected VL sequence is SEQ ID NO: 762; (7) the selected VH sequence is SEQ ID NO: 763, the selected VL sequence is SEQ ID NO: 764; (8) the selected VH sequence is SEQ ID NO: 765, the selected VL sequence is SEQ ID NO: 766; (9) the selected VH sequence is SEQ ID NO: 767, the selected VL sequence is SEQ ID NO: 768; (10) the selected VH sequence is SEQ ID NO: 769, the selected VL sequence is SEQ ID NO: 770; (11) the selected VH sequence is SEQ ID NO: 771, the selected VL sequence is SEQ ID NO: 772; (12) the selected VH sequence is SEQ ID NO: 773, the selected VL sequence is SEQ ID NO: 774; (13) the selected VH sequence is SEQ ID NO: 775, and the selected VL sequence is SEQ ID NO: 776; (14) the selected VH sequence is SEQ ID NO: 777, and the selected VL sequence is SEQ ID NO: 778; (15) the selected VH sequence is SEQ ID NO: 779, and the selected VL sequence is SEQ ID NO: 780; (16) the selected VH sequence is SEQ ID NO: 781, and the selected VL sequence is SEQ ID NO: 782; (17) the selected VH sequence is SEQ ID NO: 783, and the selected VL sequence is SEQ ID NO: 784;(18) the selected VH sequence is SEQ ID NO: 785, and the selected VL sequence is SEQ ID NO: 786; (19) the selected VH sequence is SEQ ID NO: 787, and the selected VL sequence is SEQ ID NO: 788; (20) the selected VH sequence is SEQ ID NO: 789, and the selected VL sequence is SEQ ID NO: 790; (21) the selected VH sequence is SEQ ID NO: 791, and the selected VL sequence is SEQ ID NO: 792; (22) the selected VH sequence is SEQ ID NO: 793, and the selected VL sequence is SEQ ID NO: 794; (23) the selected VH sequence is SEQ ID NO: 795, and the selected VL sequence is SEQ ID NO: 796; (24) the selected VH sequence is SEQ ID NO: 797, and the selected VL sequence is SEQ ID NO: 798; (25) the selected VH sequence is SEQ ID NO: NO: 799, the selected VL sequence is SEQ ID NO: 800; (26) the selected VH sequence is SEQ ID NO: 841, the selected VL sequence is SEQ ID NO: 842; (27) the selected VH sequence is SEQ ID NO: 843, the selected VL sequence is SEQ ID NO: 844; (28) the selected VH sequence is SEQ ID NO: 845, the selected VL sequence is SEQ ID NO: 846; (29) the selected VH sequence is SEQ ID NO: 847, the selected VL sequence is SEQ ID NO: 848; (30) the selected VH sequence is SEQ ID NO: 849, the selected VL sequence is SEQ ID NO: 850; (31) the selected VH sequence is SEQ ID NO: 851, the selected VL sequence is SEQ ID NO: 852; (32) the selected VH sequence is SEQ ID NO: 853, the selected VL sequence is SEQ ID NO: 854; (33) the selected VH sequence is SEQ ID NO: 855, and the selected VL sequence is SEQ ID NO: 856; (34) the selected VH sequence is SEQ ID NO: 857, and the selected VL sequence is SEQ ID NO: 858; (35) the selected VH sequence is SEQ ID NO: 859, and the selected VL sequence is SEQ ID NO: 860; (36) the selected VH sequence is SEQ ID NO: 861, and the selected VL sequence is SEQ ID NO: 862; (37) the selected VH sequence is SEQ ID NO: 863, and the selected VL sequence is SEQ ID NO: 864;(38) the selected VH sequence is SEQ ID NO: 865, and the selected VL sequence is SEQ ID NO: 866; (39) the selected VH sequence is SEQ ID NO: 867, and the selected VL sequence is SEQ ID NO: 868; (40) the selected VH sequence is SEQ ID NO: 869, and the selected VL sequence is SEQ ID NO: 870; (41) the selected VH sequence is SEQ ID NO: 871, and the selected VL sequence is SEQ ID NO: 872; (42) the selected VH sequence is SEQ ID NO: 873, and the selected VL sequence is SEQ ID NO: 874; (43) the selected VH sequence is SEQ ID NO: 875, and the selected VL sequence is SEQ ID NO: 876; (44) the selected VH sequence is SEQ ID NO: 877, and the selected VL sequence is SEQ ID NO: 878; (45) the selected VH sequence is SEQ ID NO: 879, the selected VL sequence is SEQ ID NO: 880; (46) the selected VH sequence is SEQ ID NO: 881, the selected VL sequence is SEQ ID NO: 882; (47) the selected VH sequence is SEQ ID NO: 883, the selected VL sequence is SEQ ID NO: 884; (48) the selected VH sequence is SEQ ID NO: 885, the selected VL sequence is SEQ ID NO: 886; (49) the selected VH sequence is SEQ ID NO: 887, the selected VL sequence is SEQ ID NO: 888; (50) the selected VH sequence is SEQ ID NO: 889, the selected VL sequence is SEQ ID NO: 890; (51) the selected VH sequence is SEQ ID NO: 891, the selected VL sequence is SEQ ID NO: 892; (52) the selected VH sequence is SEQ ID NO: 893, the selected VL sequence is SEQ ID NO: 894; (53) the selected VH sequence is SEQ ID NO: 895, and the selected VL sequence is SEQ ID NO: 896; (54) the selected VH sequence is SEQ ID NO: 897, and the selected VL sequence is SEQ ID NO: 898; (55) the selected VH sequence is SEQ ID NO: 899, and the selected VL sequence is SEQ ID NO: 900; (56) the selected VH sequence is SEQ ID NO: 901, and the selected VL sequence is SEQ ID NO: 902; (57) the selected VH sequence is SEQ ID NO: 903, and the selected VL sequence is SEQ ID NO: 904;(58) the selected VH sequence is SEQ ID NO: 905, and the selected VL sequence is SEQ ID NO: 906; (59) the selected VH sequence is SEQ ID NO: 907, and the selected VL sequence is SEQ ID NO: 908; (60) the selected VH sequence is SEQ ID NO: 909, and the selected VL sequence is SEQ ID NO: 910; (61) the selected VH sequence is SEQ ID NO: 911, and the selected VL sequence is SEQ ID NO: 912; (62) the selected VH sequence is SEQ ID NO: 913, and the selected VL sequence is SEQ ID NO: 914; (63) the selected VH sequence is SEQ ID NO: 915, and the selected VL sequence is SEQ ID NO: 916; (64) the selected VH sequence is SEQ ID NO: 917, and the selected VL sequence is SEQ ID NO: 918; (65) the selected VH sequence is SEQ ID NO:919, the selected VL sequence is SEQ ID NO:920; (66) the selected VH sequence is SEQ ID NO:921, the selected VL sequence is SEQ ID NO:922; (67) the selected VH sequence is SEQ ID NO:923, the selected VL sequence is SEQ ID NO:924; (68) the selected VH sequence is SEQ ID NO:925, the selected VL sequence is SEQ ID NO:926; (69) the selected VH sequence is SEQ ID NO:927, the selected VL sequence is SEQ ID NO:928; (70) the selected VH sequence is SEQ ID NO:929, the selected VL sequence is SEQ ID NO:930; (71) the selected VH sequence is SEQ ID NO:931, the selected VL sequence is SEQ ID NO:932; (72) the selected VH sequence is SEQ ID NO:933, the selected VL sequence is SEQ ID NO: 934; (73) the selected VH sequence is SEQ ID NO: 935, and the selected VL sequence is SEQ ID NO: 936; (74) the selected VH sequence is SEQ ID NO: 937, and the selected VL sequence is SEQ ID NO: 938; (75) the selected VH sequence is SEQ ID NO: 939, and the selected VL sequence is SEQ ID NO: 940; (76) the selected VH sequence is SEQ ID NO: 941, and the selected VL sequence is SEQ ID NO: 942; (77) the selected VH sequence is SEQ ID NO: 943, and the selected VL sequence is SEQ ID NO: 944;(78) the selected VH sequence is SEQ ID NO: 945, and the selected VL sequence is SEQ ID NO: 946; (79) the selected VH sequence is SEQ ID NO: 947, and the selected VL sequence is SEQ ID NO: 948; (80) the selected VH sequence is SEQ ID NO: 949, and the selected VL sequence is SEQ ID NO: 950; (81) the selected VH sequence is SEQ ID NO: 951, and the selected VL sequence is SEQ ID NO: 952; (82) the selected VH sequence is SEQ ID NO: 953, and the selected VL sequence is SEQ ID NO: 954; (83) the selected VH sequence is SEQ ID NO: 955, and the selected VL sequence is SEQ ID NO: 956; (84) the selected VH sequence is SEQ ID NO: 957, and the selected VL sequence is SEQ ID NO: 958; (85) the selected VH sequence is SEQ ID NO: NO:959, the selected VL sequence is SEQ ID NO:960; (86) the selected VH sequence is SEQ ID NO:961, the selected VL sequence is SEQ ID NO:962; (87) the selected VH sequence is SEQ ID NO:963, the selected VL sequence is SEQ ID NO:964; (88) the selected VH sequence is SEQ ID NO:965, the selected VL sequence is SEQ ID NO:966; (89) the selected VH sequence is SEQ ID NO:967, the selected VL sequence is SEQ ID NO:968; (90) the selected VH sequence is SEQ ID NO:969, the selected VL sequence is SEQ ID NO:970; (91) the selected VH sequence is SEQ ID NO:971, the selected VL sequence is SEQ ID NO:972; (92) the selected VH sequence is SEQ ID NO:973, the selected VL sequence is SEQ ID NO: 974; (93) the selected VH sequence is SEQ ID NO: 975, and the selected VL sequence is SEQ ID NO: 976; (94) the selected VH sequence is SEQ ID NO: 977, and the selected VL sequence is SEQ ID NO: 978; (95) the selected VH sequence is SEQ ID NO: 979, and the selected VL sequence is SEQ ID NO: 980, 981, 982, 983 or 984; (96) the selected VH sequence is SEQ ID NO: 985, and the selected VL sequence is SEQ ID NO: 986; (97) the selected VH sequence is SEQ ID NO: 987, 1687 or 1688, and the selected VL sequence is SEQ ID NO: 988, 989, 990, 991 or 992;(98) the selected VH sequence is SEQ ID NO: 993, and the selected VL sequence is SEQ ID NO: 994; (99) the selected VH sequence is SEQ ID NO: 995, and the selected VL sequence is SEQ ID NO: 996; (100) the selected VH sequence is SEQ ID NO: 997, and the selected VL sequence is SEQ ID NO: 998; (101) the selected VH sequence is SEQ ID NO: 999, and the selected VL sequence is SEQ ID NO: 1000, 1001, 1002, 1003 or 1004; (102) the selected VH sequence is SEQ ID NO: 1005, and the selected VL sequence is SEQ ID NO: 1006; (103) the selected VH sequence is SEQ ID NO: 1007, and the selected VL sequence is SEQ ID NO: 1008, 1009 or 1010; (104) the selected VH sequence is SEQ ID NO: NO: 1011, the selected VL sequence is SEQ ID NO: 1012; (105) the selected VH sequence is SEQ ID NO: 1013, the selected VL sequence is SEQ ID NO: 1014; (106) the selected VH sequence is SEQ ID NO: 1015, the selected VL sequence is SEQ ID NO: 1016; (107) the selected VH sequence is SEQ ID NO: 1017, the selected VL sequence is SEQ ID NO: 1018; (108) the selected VH sequence is SEQ ID NO: 1019, the selected VL sequence is SEQ ID NO: 1020; (109) the selected VH sequence is SEQ ID NO: 1021, the selected VL sequence is SEQ ID NO: 1022; (110) the selected VH sequence is SEQ ID NO: 1023, the selected VL sequence is SEQ ID NO: 1024; (111) the selected VH sequence is SEQ ID NO: 1025, the selected VL sequence is SEQ ID NO: 1026; (112) the selected VH sequence is SEQ ID NO: 1027, the selected VL sequence is SEQ ID NO: 1028; (113) the selected VH sequence is SEQ ID NO: 1029, the selected VL sequence is SEQ ID NO: 1030; (114) the selected VH sequence is SEQ ID NO: 1031, the selected VL sequence is SEQ ID NO: 1032; (115) the selected VH sequence is SEQ ID NO: 1033, the selected VL sequence is SEQ ID NO: 1034; (116) the selected VH sequence is SEQ ID NO: 1035, the selected VL sequence is SEQ ID NO: 1036;(117) the selected VH sequence is SEQ ID NO: 1037, and the selected VL sequence is SEQ ID NO: 1038; (118) the selected VH sequence is SEQ ID NO: 1039, and the selected VL sequence is SEQ ID NO: 1040; (119) the selected VH sequence is SEQ ID NO: 1041, and the selected VL sequence is SEQ ID NO: 1042; (120) the selected VH sequence is SEQ ID NO: 1043, and the selected VL sequence is SEQ ID NO: 1044, 1689 or 1690; (121) the selected VH sequence is SEQ ID NO: 1045, and the selected VL sequence is SEQ ID NO: 1046; (122) the selected VH sequence is SEQ ID NO: 1047, and the selected VL sequence is SEQ ID NO: 1048; (123) the selected VH sequence is SEQ ID NO: NO: 1049, the selected VL sequence is SEQ ID NO: 1050; (124) the selected VH sequence is SEQ ID NO: 1051, the selected VL sequence is SEQ ID NO: 1052; (125) the selected VH sequence is SEQ ID NO: 1053, the selected VL sequence is SEQ ID NO: 1054; (126) the selected VH sequence is SEQ ID NO: 1055, the selected VL sequence is SEQ ID NO: 1056.;

[0169] In some embodiments, the VH comprises the sequence of SEQ ID NO: 751 and the VL comprises the sequence of SEQ ID NO: 752. In some embodiments, the VH comprises the sequence of SEQ ID NO: 753 and the VL comprises the sequence of SEQ ID NO: 754. In some embodiments, the VH comprises the sequence of SEQ ID NO: 755 and the VL comprises the sequence of SEQ ID NO: 756. In some embodiments, the VH comprises the sequence of SEQ ID NO: 757 and the VL comprises the sequence of SEQ ID NO: 758. In some embodiments, the VH comprises the sequence of SEQ ID NO: 759 and the VL comprises the sequence of SEQ ID NO: 760. In some embodiments, the VH comprises the sequence of SEQ ID NO: 761 and the VL comprises the sequence of SEQ ID NO: 762. In some embodiments, the VH comprises the sequence of SEQ ID NO: 763 and the VL comprises the sequence of SEQ ID NO: 764. In some embodiments, the VH comprises the sequence of SEQ ID NO: 765 and the VL comprises the sequence of SEQ ID NO: 766. In some embodiments, the VH comprises the sequence of SEQ ID NO: 767 and the VL comprises the sequence of SEQ ID NO: 768. In some embodiments, the VH comprises the sequence of SEQ ID NO: 769 and the VL comprises the sequence of SEQ ID NO: 770. In some embodiments, the VH comprises the sequence of SEQ ID NO: 771 and the VL comprises the sequence of SEQ ID NO: 772. In some embodiments, the VH comprises the sequence of SEQ ID NO: 773 and the VL comprises the sequence of SEQ ID NO: 774. In some embodiments, the VH comprises the sequence of SEQ ID NO: 775 and the VL comprises the sequence of SEQ ID NO: 776. In some embodiments, the VH comprises the sequence of SEQ ID NO: 777 and the VL comprises the sequence of SEQ ID NO: 778. In some embodiments, the VH comprises the sequence of SEQ ID NO: 779 and the VL comprises the sequence of SEQ ID NO: 780. In some embodiments, the VH comprises the sequence of SEQ ID NO: 781 and the VL comprises the sequence of SEQ ID NO: 782. In some embodiments, VH comprises the sequence of SEQ ID NO: 783 and VL comprises the sequence of SEQ ID NO: 784. In some embodiments, VH comprises the sequence of SEQ ID NO: 785 and VL comprises the sequence of SEQ ID NO: 786. In some embodiments, VH comprises the sequence of SEQ ID NO: 787 and VL comprises the sequence of SEQ ID NO: 788.In some embodiments, the VH comprises the sequence of SEQ ID NO: 789 and the VL comprises the sequence of SEQ ID NO: 790. In some embodiments, the VH comprises the sequence of SEQ ID NO: 791 and the VL comprises the sequence of SEQ ID NO: 792. In some embodiments, the VH comprises the sequence of SEQ ID NO: 793 and the VL comprises the sequence of SEQ ID NO: 794. In some embodiments, the VH comprises the sequence of SEQ ID NO: 795 and the VL comprises the sequence of SEQ ID NO: 796. In some embodiments, the VH comprises the sequence of SEQ ID NO: 797 and the VL comprises the sequence of SEQ ID NO: 798. In some embodiments, the VH comprises the sequence of SEQ ID NO: 799 and the VL comprises the sequence of SEQ ID NO: 800. In some embodiments, the VH comprises the sequence of SEQ ID NO: 841 and the VL comprises the sequence of SEQ ID NO: 842. In some embodiments, the VH comprises the sequence of SEQ ID NO: 843 and the VL comprises the sequence of SEQ ID NO: 844. In some embodiments, the VH comprises the sequence of SEQ ID NO: 845 and the VL comprises the sequence of SEQ ID NO: 846. In some embodiments, the VH comprises the sequence of SEQ ID NO: 847 and the VL comprises the sequence of SEQ ID NO: 848. In some embodiments, the VH comprises the sequence of SEQ ID NO: 849 and the VL comprises the sequence of SEQ ID NO: 850. In some embodiments, the VH comprises the sequence of SEQ ID NO: 851 and the VL comprises the sequence of SEQ ID NO: 852. In some embodiments, the VH comprises the sequence of SEQ ID NO: 853 and the VL comprises the sequence of SEQ ID NO: 854. In some embodiments, the VH comprises the sequence of SEQ ID NO: 855 and the VL comprises the sequence of SEQ ID NO: 856. In some embodiments, the VH comprises the sequence of SEQ ID NO: 857 and the VL comprises the sequence of SEQ ID NO: 858. In some embodiments, the VH comprises the sequence of SEQ ID NO: 859 and the VL comprises the sequence of SEQ ID NO: 860. In some embodiments, VH comprises the sequence of SEQ ID NO: 861 and VL comprises the sequence of SEQ ID NO: 862. In some embodiments, VH comprises the sequence of SEQ ID NO: 863 and VL comprises the sequence of SEQ ID NO: 864. In some embodiments, VH comprises the sequence of SEQ ID NO: 865 and VL comprises the sequence of SEQ ID NO: 866.In some embodiments, the VH comprises the sequence of SEQ ID NO: 867 and the VL comprises the sequence of SEQ ID NO: 868. In some embodiments, the VH comprises the sequence of SEQ ID NO: 869 and the VL comprises the sequence of SEQ ID NO: 870. In some embodiments, the VH comprises the sequence of SEQ ID NO: 871 and the VL comprises the sequence of SEQ ID NO: 872. In some embodiments, the VH comprises the sequence of SEQ ID NO: 873 and the VL comprises the sequence of SEQ ID NO: 874. In some embodiments, the VH comprises the sequence of SEQ ID NO: 875 and the VL comprises the sequence of SEQ ID NO: 876. In some embodiments, the VH comprises the sequence of SEQ ID NO: 877 and the VL comprises the sequence of SEQ ID NO: 878. In some embodiments, the VH comprises the sequence of SEQ ID NO: 879 and the VL comprises the sequence of SEQ ID NO: 880. In some embodiments, the VH comprises the sequence of SEQ ID NO: 881 and the VL comprises the sequence of SEQ ID NO: 882. In some embodiments, the VH comprises the sequence of SEQ ID NO: 883 and the VL comprises the sequence of SEQ ID NO: 884. In some embodiments, the VH comprises the sequence of SEQ ID NO: 885 and the VL comprises the sequence of SEQ ID NO: 886. In some embodiments, the VH comprises the sequence of SEQ ID NO: 887 and the VL comprises the sequence of SEQ ID NO: 888. In some embodiments, the VH comprises the sequence of SEQ ID NO: 889 and the VL comprises the sequence of SEQ ID NO: 890. In some embodiments, the VH comprises the sequence of SEQ ID NO: 891 and the VL comprises the sequence of SEQ ID NO: 892. In some embodiments, the VH comprises the sequence of SEQ ID NO: 893 and the VL comprises the sequence of SEQ ID NO: 894. In some embodiments, the VH comprises the sequence of SEQ ID NO: 895 and the VL comprises the sequence of SEQ ID NO: 896. In some embodiments, the VH comprises the sequence of SEQ ID NO: 897 and the VL comprises the sequence of SEQ ID NO: 898. In some embodiments, VH comprises the sequence of SEQ ID NO: 899 and VL comprises the sequence of SEQ ID NO: 900. In some embodiments, VH comprises the sequence of SEQ ID NO: 901 and VL comprises the sequence of SEQ ID NO: 902. In some embodiments, VH comprises the sequence of SEQ ID NO: 903 and VL comprises the sequence of SEQ ID NO: 904.In some embodiments, the VH comprises the sequence of SEQ ID NO: 905 and the VL comprises the sequence of SEQ ID NO: 906. In some embodiments, the VH comprises the sequence of SEQ ID NO: 907 and the VL comprises the sequence of SEQ ID NO: 908. In some embodiments, the VH comprises the sequence of SEQ ID NO: 909 and the VL comprises the sequence of SEQ ID NO: 910. In some embodiments, the VH comprises the sequence of SEQ ID NO: 911 and the VL comprises the sequence of SEQ ID NO: 912. In some embodiments, the VH comprises the sequence of SEQ ID NO: 913 and the VL comprises the sequence of SEQ ID NO: 914. In some embodiments, the VH comprises the sequence of SEQ ID NO: 915 and the VL comprises the sequence of SEQ ID NO: 916. In some embodiments, the VH comprises the sequence of SEQ ID NO: 917 and the VL comprises the sequence of SEQ ID NO: 918. In some embodiments, the VH comprises the sequence of SEQ ID NO: 919 and the VL comprises the sequence of SEQ ID NO: 920. In some embodiments, the VH comprises the sequence of SEQ ID NO: 921 and the VL comprises the sequence of SEQ ID NO: 922. In some embodiments, the VH comprises the sequence of SEQ ID NO: 923 and the VL comprises the sequence of SEQ ID NO: 924. In some embodiments, the VH comprises the sequence of SEQ ID NO: 925 and the VL comprises the sequence of SEQ ID NO: 926. In some embodiments, the VH comprises the sequence of SEQ ID NO: 927 and the VL comprises the sequence of SEQ ID NO: 928. In some embodiments, the VH comprises the sequence of SEQ ID NO: 929 and the VL comprises the sequence of SEQ ID NO: 930. In some embodiments, the VH comprises the sequence of SEQ ID NO: 931 and the VL comprises the sequence of SEQ ID NO: 932. In some embodiments, the VH comprises the sequence of SEQ ID NO: 933 and the VL comprises the sequence of SEQ ID NO: 934. In some embodiments, the VH comprises the sequence of SEQ ID NO: 935 and the VL comprises the sequence of SEQ ID NO: 936. In some embodiments, VH comprises the sequence of SEQ ID NO: 937 and VL comprises the sequence of SEQ ID NO: 938. In some embodiments, VH comprises the sequence of SEQ ID NO: 939 and VL comprises the sequence of SEQ ID NO: 940. In some embodiments, VH comprises the sequence of SEQ ID NO: 941 and VL comprises the sequence of SEQ ID NO: 942.In some embodiments, the VH comprises the sequence of SEQ ID NO: 943 and the VL comprises the sequence of SEQ ID NO: 944. In some embodiments, the VH comprises the sequence of SEQ ID NO: 945 and the VL comprises the sequence of SEQ ID NO: 946. In some embodiments, the VH comprises the sequence of SEQ ID NO: 947 and the VL comprises the sequence of SEQ ID NO: 948. In some embodiments, the VH comprises the sequence of SEQ ID NO: 949 and the VL comprises the sequence of SEQ ID NO: 950. In some embodiments, the VH comprises the sequence of SEQ ID NO: 951 and the VL comprises the sequence of SEQ ID NO: 952. In some embodiments, the VH comprises the sequence of SEQ ID NO: 953 and the VL comprises the sequence of SEQ ID NO: 954. In some embodiments, the VH comprises the sequence of SEQ ID NO: 955 and the VL comprises the sequence of SEQ ID NO: 956. In some embodiments, the VH comprises the sequence of SEQ ID NO: 957 and the VL comprises the sequence of SEQ ID NO: 958. In some embodiments, the VH comprises the sequence of SEQ ID NO: 959 and the VL comprises the sequence of SEQ ID NO: 960. In some embodiments, the VH comprises the sequence of SEQ ID NO: 961 and the VL comprises the sequence of SEQ ID NO: 962. In some embodiments, the VH comprises the sequence of SEQ ID NO: 963 and the VL comprises the sequence of SEQ ID NO: 964. In some embodiments, the VH comprises the sequence of SEQ ID NO: 965 and the VL comprises the sequence of SEQ ID NO: 966. In some embodiments, the VH comprises the sequence of SEQ ID NO: 967 and the VL comprises the sequence of SEQ ID NO: 968. In some embodiments, the VH comprises the sequence of SEQ ID NO: 969 and the VL comprises the sequence of SEQ ID NO: 970. In some embodiments, the VH comprises the sequence of SEQ ID NO: 971 and the VL comprises the sequence of SEQ ID NO: 972. In some embodiments, the VH comprises the sequence of SEQ ID NO: 973 and the VL comprises the sequence of SEQ ID NO: 974. In some embodiments, the VH comprises the sequence of SEQ ID NO: 975 and the VL comprises the sequence of SEQ ID NO: 976. In some embodiments, the VH comprises the sequence of SEQ ID NO: 977 and the VL comprises the sequence of SEQ ID NO: 978. In some embodiments, the VH comprises the sequence of SEQ ID NO: 979 and the VL comprises the sequence of SEQ ID NO: 980, 981, 982, 983 or 984.In some embodiments, the VH comprises the sequence of SEQ ID NO: 985 and the VL comprises the sequence of SEQ ID NO: 986. In some embodiments, the VH comprises the sequence of SEQ ID NO: 987, 1687 or 1688 and the VL comprises the sequence of SEQ ID NO: 988, 989, 990, 991 or 992. In some embodiments, the VH comprises the sequence of SEQ ID NO: 993 and the VL comprises the sequence of SEQ ID NO: 994. In some embodiments, the VH comprises the sequence of SEQ ID NO: 995 and the VL comprises the sequence of SEQ ID NO: 996. In some embodiments, the VH comprises the sequence of SEQ ID NO: 997 and the VL comprises the sequence of SEQ ID NO: 998. In some embodiments, the VH comprises the sequence of SEQ ID NO: 999 and the VL comprises the sequence of SEQ ID NO: 1000, 1001, 1002, 1003 or 1004. In some embodiments, the VH comprises the sequence of SEQ ID NO: 1005 and the VL comprises the sequence of SEQ ID NO: 1006. In some embodiments, the VH comprises the sequence of SEQ ID NO: 1007 and the VL comprises the sequence of SEQ ID NO: 1008, 1009, 1010. In some embodiments, the VH comprises the sequence of SEQ ID NO: 1011 and the VL comprises the sequence of SEQ ID NO: 1012. In some embodiments, the VH comprises the sequence of SEQ ID NO: 1013 and the VL comprises the sequence of SEQ ID NO: 1014. In some embodiments, the VH comprises the sequence of SEQ ID NO: 1015 and the VL comprises the sequence of SEQ ID NO: 1016. In some embodiments, the VH comprises the sequence of SEQ ID NO: 1017 and the VL comprises the sequence of SEQ ID NO: 1018. In some embodiments, the VH comprises the sequence of SEQ ID NO: 1019 and the VL comprises the sequence of SEQ ID NO: 1020. In some embodiments, the VH comprises the sequence of SEQ ID NO: 1021 and the VL comprises the sequence of SEQ ID NO: 1022. In some embodiments, the VH comprises the sequence of SEQ ID NO: 1023 and the VL comprises the sequence of SEQ ID NO: 1024. In some embodiments, the VH comprises the sequence of SEQ ID NO: 1025 and the VL comprises the sequence of SEQ ID NO: 1026. In some embodiments, the VH comprises the sequence of SEQ ID NO: 1027 and the VL comprises the sequence of SEQ ID NO: 1028. In some embodiments, the VH comprises the sequence of SEQ ID NO: 1029 and the VL comprises the sequence of SEQ ID NO: 1030.In some embodiments, the VH comprises the sequence of SEQ ID NO: 1031 and the VL comprises the sequence of SEQ ID NO: 1032. In some embodiments, the VH comprises the sequence of SEQ ID NO: 1033 and the VL comprises the sequence of SEQ ID NO: 1034. In some embodiments, the VH comprises the sequence of SEQ ID NO: 1035 and the VL comprises the sequence of SEQ ID NO: 1036. In some embodiments, the VH comprises the sequence of SEQ ID NO: 1037 and the VL comprises the sequence of SEQ ID NO: 1038. In some embodiments, the VH comprises the sequence of SEQ ID NO: 1039 and the VL comprises the sequence of SEQ ID NO: 1040. In some embodiments, the VH comprises the sequence of SEQ ID NO: 1041 and the VL comprises the sequence of SEQ ID NO: 1042. In some embodiments, the VH comprises the sequence of SEQ ID NO: 1043 and the VL comprises the sequence of SEQ ID NO: 1044, 1689, or 1690. In some embodiments, the VH comprises the sequence of SEQ ID NO: 1045 and the VL comprises the sequence of SEQ ID NO: 1046. In some embodiments, the VH comprises the sequence of SEQ ID NO: 1047 and the VL comprises the sequence of SEQ ID NO: 1048. In some embodiments, the VH comprises the sequence of SEQ ID NO: 1049 and the VL comprises the sequence of SEQ ID NO: 1050. In some embodiments, the VH comprises the sequence of SEQ ID NO: 1051 and the VL comprises the sequence of SEQ ID NO: 1052. In some embodiments, the VH comprises the sequence of SEQ ID NO: 1053 and the VL comprises the sequence of SEQ ID NO: 1054. In some embodiments, the VH comprises the sequence of SEQ ID NO: 1055 and the VL comprises the sequence of SEQ ID NO: 1056.

[0170] In some embodiments, the antibody or antigen-binding fragment specifically binds to human LILRB1 and / or LILRB2. In some embodiments, the antibody or antigen-binding fragment is a humanized antibody or antigen-binding fragment thereof. In some embodiments, the antibody or antigen-binding fragment is a single-chain variable fragment (scFV) or a multispecific antibody (e.g., a bispecific antibody).

[0171] In one aspect, the disclosure relates to an antibody or antigen-binding fragment thereof comprising an antibody-drug conjugate as described herein, covalently bound to a therapeutic agent. In some embodiments, the therapeutic agent is a cytotoxic or cytostatic agent.

[0172] In one aspect, the disclosure relates to a method for treating a subject with cancer, the method comprising administering to the subject a therapeutically effective amount of a composition comprising the antibody or its antigen-binding fragment, or an antibody-drug conjugate as described herein. In some embodiments, the subject suffers from a solid tumor or a blood cancer. In some embodiments, the cancer is a glioma, thyroid cancer, lung cancer, colorectal cancer, head and neck cancer, gastric cancer, liver cancer, pancreatic cancer, kidney cancer, urothelial cancer, prostate cancer, testicular cancer, breast cancer, cervical cancer, endometrial cancer, ovarian cancer, or melanoma.

[0173] In one aspect, the disclosure relates to a method of reducing tumor growth rate comprising contacting a tumor cell with an effective amount of a composition comprising an antibody or antigen binding fragment or an antibody-drug conjugate described herein.

[0174] In one aspect, the disclosure relates to a method of killing tumor cells, the method comprising contacting the tumor cells with an effective amount of a composition comprising an antibody or antigen-binding fragment, or an antibody-drug conjugate described herein.

[0175] In one aspect, the disclosure relates to a pharmaceutical composition comprising an antibody or antigen-binding fragment thereof and a pharmaceutically acceptable carrier. In one aspect, the disclosure relates to a pharmaceutical composition comprising an antibody drug conjugate as described herein and a pharmaceutically acceptable carrier.

[0176] The term "cancer" as used herein refers to cells with autonomous growth capacity. Examples of such cells include cells with abnormal states or conditions characterized by rapid proliferating cell growth. The term is intended to include cancerous growths, such as tumors; carcinogenic processes, metastatic tissues, and malignantly transformed cells, tissues, or organs, regardless of the histopathological type or invasive stage. Malignant tumors of various organ systems are also included, such as the respiratory system, cardiovascular system, renal system, reproductive system, blood system, nervous system, liver system, gastrointestinal tract, and endocrine system; and adenocarcinomas, including malignant tumors, such as most colon cancers, renal cell carcinomas, prostate cancers, and / or testicular tumors, non-small cell lung cancer, and small intestinal cancer. "Naturally occurring" cancers include any cancer that is not caused by experimentally implanting cancer cells into a subject, including, for example, spontaneously occurring cancers, cancers caused by exposure of patients to carcinogens, cancers caused by insertion of transgenic oncogenes or knockout of tumor suppressor genes, and cancers caused by infection, for example, viral infection. "Cancer" is a recognized term that refers to a malignant tumor of epithelial or endocrine tissue. The term also includes carcinosarcomas, which include malignant tumors composed of carcinoma and sarcomatous tissue. "Adenocarcinoma" refers to a carcinoma that originates from glandular tissue, or a carcinoma in which the tumor cells form a recognizable glandular structure. "Sarcoma" is a recognized term that refers to a malignant tumor of mesenchymal origin. The term "hematopoietic neoplastic disease" includes diseases involving hyperplastic / neoplastic cells of hematopoietic origin. Hematopoietic neoplastic diseases can originate from the myeloid, lymphoid, or erythroid lineages, or their precursor cells.

[0177] The term "antibody" as used herein refers to any antigen binding molecule containing at least one (e.g., one, two, three, four, five or six) complementary determining regions (CDRs) (e.g., any one of the three CDRs from an immunoglobulin light chain or any one of the three CDRs from an immunoglobulin heavy chain) and capable of specifically binding to an epitope. Non-limiting examples of antibodies include: monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), single-chain antibodies, chimeric antibodies, human antibodies, and humanized antibodies. In some embodiments, the antibody may include the Fc region of a human antibody. The term antibody also includes derivatives such as bispecific antibodies, single-chain antibodies, double antibodies, linear antibodies, and multispecific antibodies formed by antibody fragments.

[0178] As used herein, the term "antigen binding fragment" refers to a portion of a full-length antibody, wherein the portion of the antibody is capable of specifically binding to an antigen. In some embodiments, the antigen binding fragment comprises at least one variable domain (e.g., a variable domain of a heavy chain or a variable domain of a light chain). Non-limiting examples of antibody fragments include, for example, Fab, Fab', F(ab')2, and Fv fragments.

[0179] The term "human antibody" as used herein refers to an antibody encoded by endogenous nucleic acids present in humans (e.g., rearranged human immunoglobulin heavy or light chain sites). In some embodiments, human antibodies are collected from humans or produced in human cell cultures (e.g., human hybridoma cells). In some embodiments, human antibodies are produced in non-human cells (e.g., mouse or hamster cell lines). In some embodiments, human antibodies are produced in bacteria or yeast cells. In some embodiments, human antibodies are produced in transgenic non-human animals (e.g., cattle) containing unrearranged or rearranged human immunoglobulin sites (e.g., heavy or light chain human immunoglobulin sites).

[0180] As used herein, the term "chimeric antibody" refers to an antibody containing sequences present in at least two different antibodies (e.g., antibodies from two different mammalian species, such as human antibodies and mouse antibodies). A non-limiting example of a chimeric antibody is an antibody comprising a variable domain sequence (e.g., all or part of a light chain and / or heavy chain variable domain sequence) of a non-human (e.g., mouse) antibody and a constant domain of a human antibody. Other examples of chimeric antibodies are described herein and are known in the art.

[0181] The term "humanized antibody" used herein refers to a non-human antibody, which contains a very small portion of sequences derived from non-human (e.g., mouse) immunoglobulins, and contains sequences derived from human immunoglobulins. In a non-limiting example, a humanized antibody is a human antibody (receptor antibody), wherein the hypervariable (e.g., CDR) region residues of the receptor antibody are replaced by hypervariable (e.g., CDR) region residues from non-human antibodies (e.g., donor antibodies), for example, mouse, rat or rabbit antibodies, with the required specificity, affinity and capacity. In some embodiments, the Fv framework residues of human immunoglobulins are replaced by corresponding non-human (e.g., mouse) immunoglobulin residues. In some embodiments, humanized antibodies may contain residues not found in receptor antibodies or donor antibodies. These modifications can be performed to further improve antibody performance. In some embodiments, humanized antibodies substantially include all the content domains of at least one (usually two) variable domains, wherein all or substantially all of the hypervariable loops (CDRs) correspond to the highly variable loops (CDRs) of non-human (e.g., mouse) immunoglobulins, and all or substantially all of the framework regions are the framework regions of human immunoglobulins. Humanized antibodies can also comprise at least a portion of an immunoglobulin constant region (Fc), typically a portion of a human immunoglobulin. Humanized antibodies can be produced using molecular biology methods known in the art. Non-limiting examples of methods for producing humanized antibodies are described herein.

[0182] The term "single-chain antibody" as used herein refers to a single polypeptide containing at least two immunoglobulin variable domains (eg, variable domains of mammalian immunoglobulin heavy or light chains) capable of specific binding to an antigen. Non-limiting examples of single-chain antibodies are described herein.

[0183] The term "multimeric antibody" as used herein refers to an antibody containing four or more (e.g., six, eight or ten) immunoglobulin variable domains. In some embodiments, the multimeric antibody is capable of cross-linking a target molecule (e.g., LILRB1, LILRB2 or LILRB3) to at least one second target molecule (e.g., LILRB1, LILRB2 or LILRB3) on the surface of a mammalian cell (e.g., a human T cell).

[0184] As used herein, the terms "subject" and "patient" are used interchangeably throughout this article and describe animals, humans or non-humans, to whom treatment is provided according to the methods of the present invention. Veterinary and non-veterinary applications are contemplated by the present invention. Human patients can be adult humans or adolescents (e.g., humans under 18 years of age). In addition to humans, patients include, but are not limited to, mice, rats, hamsters, guinea pigs, rabbits, ferrets, cats, dogs, and primates. For example, non-human primates (e.g., monkeys, chimpanzees, gorillas, etc.), rodents (e.g., rats, mice, gerbils, hamsters, ferrets, rabbits), lake animals, pigs (e.g., pigs, miniature pigs), horses, dogs, felines, cattle and other livestock, farm and zoo animals are included.

[0185] As used herein, the phrases "specifically bind" and "specifically binds" when referring to antibodies means that the antibody interacts better with its target molecule (e.g., LILRB1 and / or LILRB2) than with other molecules because the interaction depends on the presence of a specific structure (i.e., antigenic determinant or epitope) on the target molecule; in other words, the agent is recognizing and binding to molecules containing a specific structure, rather than all molecules in general. Antibodies that specifically bind to a target molecule may be referred to as target-specific antibodies. For example, antibodies that specifically bind to LILRB1 and / or LILRB2 molecules may be referred to as LILRB1 and / or LILRB2-specific antibodies or anti-LILRB1 / 2 antibodies.

[0186] As used herein, the terms "polypeptide," "peptide," and "protein" are used interchangeably to refer to polymers of amino acids of any length of at least two amino acids.

[0187] As used herein, the terms "polynucleotide," "nucleic acid molecule," and "nucleic acid sequence" are used interchangeably herein to refer to nucleotide polymers of any length of at least two nucleotides, and include but are not limited to DNA, RNA, DNA / RNA hybrids, and modifications thereof.

[0188] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by one of ordinary skill in the art to which the invention belongs. Methods and materials for use in the present invention are described herein; otherwise, suitable methods and materials known in the art may also be used. The materials, methods, and examples are provided for illustrative purposes only and are not intended to be limiting. All publications, patent applications, patents, sequences, database entries, and other references mentioned herein are incorporated by reference in their entirety. In the event of a conflict, this specification (including definitions) shall prevail.

[0189] Other features and advantages of the invention will be apparent from the following detailed description and drawings, and from the claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0190] Figures 1A to 1F Figure 1 shows that 19 of the 46 antibodies bind to LILRB1 and LILRB2 and block LILRB1 / HLA-G and LILRB2 / HLA-G interactions. CHO-LILRB1 or CHO-LILRB2 cells were incubated with serial dilutions of anti-LILRB1 / 2 antibodies and then stained with Violet TM 421-labeled anti-human Fc antibody and APC-labeled HLA-G / β2M / peptide trimer tetramer or HLA-G monomer (HLA-G free chain) tetramer were incubated; Violet TM 421 (gMFI) antibody binding signal to LILRB1 or LILRB2, and antibody blocking signal to APC HLA-G; 3C1 and 1E1 (QE) are reference antibodies; IgG1 is an isotype control (IgG); 48 differently numbered graphs representing each antibody, 4 panels for each antibody, with MFI on the vertical Y-axis and antibody concentration on the horizontal X-axis (5, 1, 0.1, and 0 μg / mL); HLA-G binding signal (MFI) was normalized with the signal without antibody blocking (0 μg / mL); the upper left graph shows HLA-G binding to CHO cells expressing RB1; the upper right graph shows HLA-G binding to CHO cells expressing RB2; the lower left graph shows anti-RB1 / 2 binding to CHO cells expressing RB1, and the lower right graph shows anti-RB1 / 2 binding to CHO cells expressing RB2;

[0191] Figure 1G Is a description Figures 1A to 1F A schematic diagram of the information on Figures 1A to 1F Representative figure labels and legends for each sample in;

[0192] Figure 2AThe binding of anti-LILRB1 / 2 antibodies to LILRB1 on CHO-LILRB1 cells is shown. CHO-LILRB1 cells were incubated with serial dilutions of anti-LILRB1 / 2 antibodies and then incubated with Violet TM 421-labeled anti-human Fc antibody and APC-labeled tetrameric HLA-G trimer were incubated together; Violet TM 421 (gMFI) antibody binding signal to LILRB1;

[0193] Figure 2B Anti-LILRB1 / 2 antibodies block LILRB1 / HLA-G interaction. CHO-LILRB1 cells were incubated with serial dilutions of anti-LILRB1 / 2 antibodies and then incubated with Violet TM 421-labeled anti-human Fc antibody and APC-labeled tetrameric HLA-G trimer were incubated together; the antibody blocking signal of APC (gMFI) to HLA-G was measured by flow cytometry;

[0194] Figure 2C The values ​​of blocking efficiency (IC50) and binding efficiency (EC50) are shown;

[0195] Figure 3A Humanized and optimized anti-LILRB1 / 2 antibodies are shown to bind to LILRB1 in Jurkat-LILRB1 cells. Jurkat-LILRB1 cells were incubated with serial dilutions of anti-LILRB1 / 2 antibodies and then incubated with Violet TM 421-labeled anti-human Fc antibody and APC-labeled tetrameric HLA-G trimer (recombinant HLA-G / β2M / peptide) were incubated; Violet TM 421 (gMFI) antibody binding signal to LILRB1;

[0196] Figure 3B Humanized and optimized anti-LILRB1 / 2 antibodies that block LILRB1 / HLA-G interaction are shown. Jurkat-LILRB1 cells were incubated with serial dilutions of anti-LILRB1 / 2 antibodies and then incubated with Violet TM 421-labeled anti-human Fc antibody and APC-labeled tetrameric HLA-G trimer were incubated together; the antibody blocking signal of APC (gMFI) to HLA-G was measured by flow cytometry;

[0197] Figure 3CHumanized and optimized anti-LILRB1 / 2 antibodies are shown to bind to LILRB2 in Jurkat-LILRB2 cells. Jurkat-LILRB2 cells were incubated with serial dilutions of anti-LILRB1 / 2 antibodies and then incubated with Violet TM 421-labeled anti-human Fc antibody and APC-labeled tetrameric HLA-G monomer (free chain HLA-G) were incubated; Violet TM 421 (gMFI) antibody binding signal to LILRB2;

[0198] Figure 3D Humanized and optimized anti-LILRB1 / 2 antibodies were shown to block LILRB2 / HLA-G interaction. Jurkat-LILRB2 cells were incubated with serial dilutions of anti-LILRB1 / 2 antibodies and then incubated with Violet TM 421-labeled anti-human Fc antibody and APC-labeled tetrameric HLA-G monomer were incubated together; the antibody blocking signal of APC (gMFI) to HLA-G was measured by flow cytometry;

[0199] Figure 3E The EC50 binding values ​​to LILRB1 / B2 and the inhibitory efficiency (IC50) of blocking the binding of HLA-G to LILRB1 / B2 are shown;

[0200] Figure 4A Shown through Binding affinity of anti-LILRB1 / 2 antibodies to LILRB1 or LILRB2 measured by LSA;

[0201] Figure 4B-Figure 4C The binding affinities of D2M002-002 to LILRB1 and LILRB2 measured by Gator are shown, respectively;

[0202] Figure 5A Shown through The LSA-measured screening revealed that D2M002-002 and its humanized variant D2M002-103 bind to LILRB1 or LILRB2 in kinetic plots and fits;

[0203] Figure 5B The binding kinetics and fits of the screening discovery D2M002-026 and its humanized and optimized variant D2M002-126 to LILRB1 or LILRB2 as measured by Carterra LSA are shown;

[0204] Figure 5C Shown through Binding affinities of the screened and selected humanized and optimized anti-LILRB1 / 2 to LILRB1 and LILRB2, respectively, as measured by LSA;

[0205] Figure 6 The binding affinities of the screen-discovered and selected humanized and optimized anti-LILRB1 / 2 to human LILRB1, LILRB2, and cynomolgus monkey LILRB2 as measured by Gator are shown;

[0206] FIG. 7A to FIG. 7B Binding of anti-LILRB1 / 2 antibodies to LILRB1 and LILRB2 in CHO cell lines is shown, respectively. CHO-LILRB1 or CHO-LILRB2 cells were incubated with serial dilutions of anti-LILRB1 / 2 antibodies and then incubated with Violet TM 421-labeled anti-human Fc antibody; anti-LILRB1 antibody 3C1 and anti-LILRB2 antibody 1E1 (QE) are reference antibodies; IgG1 is an isotype control (IgG); Violet TM 421 (gMFI) antibody binding signal to LILRB1 and LILRB2;

[0207] Figure 7C is a table showing the maximum MFI values ​​and calculated EC50s of anti-LILRB1 / 2 antibodies binding to CHO cells expressing LILRB1 and LILRB2. 3C1 and 1E1 (QE) are reference antibodies; IgG1 is an isotype control (IgG);

[0208] Fig. 8A The activation of Jurkat T cells under co-culture of C1R-OKT3-HLAG and Jurkat-LILRB1 in the presence of anti-LILRB1 / 2 antibodies is shown. Anti-LILRB1 / 2 antibodies reversed the inhibition of Jurkat cell activation by HLA-G; 3C1 is a reference antibody; IgG1 is an isotype control (IgG); co-culture of C1R-OKT3 is a control without HLA-G inhibitory signal; Luciferase signal (ordinate) is measured based on luciferase luciferin signal (RLU) driven by NFAT under stimulation of membrane-expressed anti-CD3;

[0209] Figure 8BThe activation of Jurkat T cells co-cultured with C1R-OKT3-HLAG and Jurkat-LILRB2 in the presence of anti-LILRB1 / 2 antibodies is shown. Anti-LILRB1 / 2 antibodies reversed the inhibition of Jurkat cell activation by HLA-G; 1E1 (QE) is a reference antibody; IgG1 is an isotype control (IgG); C1R-OKT3 co-culture is a control without HLA-G inhibitory signal; Luciferase signal (ordinate) is measured based on luciferase luciferin signal (RLU) driven by NFAT under the stimulation of membrane-expressed anti-CD3;

[0210] Fig. 9A The activation of Jurkat T cells co-cultured with C1R-OKT3-HLAG and Jurkat-LILRB1 in the presence of serial dilutions of anti-LILRB1 / 2 antibodies is shown. Anti-LILRB1 / 2 antibodies restored the activation of Jurkat cells inhibited by HLA-G; IgG1 is an isotype control (IgG); Luciferase signal (ordinate) is measured as luciferase-luciferin signal (RLU) driven by NFAT in response to membrane-expressed anti-CD3 stimulation;

[0211] Fig. 9B The activation of Jurkat T cells co-cultured with Jurkat-LILRB2 by C1R-OKT3-HLAG in the presence of serial dilutions of anti-LILRB1 / 2 antibodies is shown. Anti-LILRB1 / 2 antibodies reversed the activation of Jurkat cells inhibited by HLA-G; IgG1 is an isotype control (IgG); Luciferase signal (ordinate) is measured based on the luciferase-luciferin signal (RLU) driven by NFAT in response to membrane-expressed anti-CD3 stimulation;

[0212] Fig. 9C The EC50 values ​​of anti-LILRB1 / 2 antibodies for restoring HLA-G-inhibited Jurkat cell activation are summarized;

[0213] Fig. 10A The concentration of TNF-α in the culture supernatant of anti-LILRB1 / 2 antibody-treated PBMCs after LPS stimulation is shown. PBMCs were stimulated with 50 ng / mL LPS in the presence of anti-LILRB1 / 2 antibodies (#2, #8, #11, #22, #26, or #27) or reference antibodies (3C1 or 1E1 (QE)); IgG1 is an isotype control (IgG); TNF-α concentrations were quantified by ELISA;

[0214] Fig. 10BThe concentration of IL-10 in the culture supernatant of PBMCs treated with anti-LILRB1 / 2 antibodies after LPS stimulation is shown. PBMCs were stimulated with 50 ng / mL LPS in the presence of anti-LILRB1 / 2 antibodies (#2, #8, #11, #22, #26, or #27) or reference antibodies (3C1 or 1E1 (QE)); IgG1 is an isotype control (IgG); IL-10 concentrations were quantified by ELISA;

[0215] Fig.11A The results of the measurement of TNF-α concentration in the culture supernatant of PBMCs treated with serial dilutions of anti-LILRB1 / 2 antibodies after LPS stimulation are shown. PBMCs were stimulated with 50 ng / mL LPS in the presence of serial dilutions of anti-LILRB1 / 2 antibodies (D2M002-126) or reference antibodies (Hz73D1.v1); IgG1 is an isotype control (IgG1-LALA); TNF-α concentrations were quantified by ELISA; the figure is a composite of data from three healthy blood donors;

[0216] Fig. 11B The results of measuring IL-10 concentration in the culture supernatant of PBMC treated with serial dilutions of anti-LILRB1 / 2 antibodies after LPS stimulation are shown. PBMCs were stimulated with 50 ng / mL LPS in the presence of anti-LILRB1 / 2 antibodies (D2M002-126) or reference antibodies (Hz73D1.v1); IgG1 is an isotype control (IgG1-LALA); IL-10 concentrations were quantified by ELISA; the figure is a composite of data from three healthy blood donors;

[0217] FIG. 12A to FIG. 12F Expression profiles of phenotypic markers CD14, CD11B, CD86, CD163, CD206, and PD-L1 quantified by flow cytometry are shown, respectively. Macrophages differentiated from human monocytes with M-SCF in the presence of anti-LILRB1 / 2 antibodies (#2, #8, #11, #22, #26, or #27), reference antibodies (3C1 or 1E1 (QE)), or IgG1 isotype control (IgG); each point represents one blood donor; P values ​​were calculated by t-test; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, ns not significant;

[0218] FIG. 13A to FIG. 13DFigure 3 Humanized and optimized anti-LILRB1 / 2 promoted the inflammatory expression profile of CD14, CD11B, CD206, and PD-L1 phenotypic markers, respectively, as quantified by flow cytometry. Macrophages differentiated from human monocytes by M-SCF in the presence of anti-LILRB1 / 2 antibody or IgG1-LALA-PA isotype control or PBS; each dot represents one blood donor; P values ​​were calculated by t-test; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, ns not significant;

[0219] FIG. 14A to FIG. 14C Expression profiles of PD-L1, TNF-α, and IL-10 are shown, respectively. Differentiated macrophages treated with anti-LILRB1 / 2 antibodies (#2, #8, #11, #22, #26, or #27), reference antibodies (3C1 or 1E1 (QE)), or IgG1 isotype control (IgG) were stimulated with LPS (100 ng / mL); the expression of the phenotypic marker PD-L1 was quantified by flow cytometry, and the concentrations of cytokines (TNF-α and IL-10) in the culture supernatant were quantified by ELISA; each point represents one blood donor; P values ​​were calculated by t-test; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, ns not significant;

[0220] FIG. 15A to FIG. 15B Humanized and optimized anti-LILRB1 / 2 induced functional phenotypes represented by the expression of TNF-α and IL-10, respectively, are shown. Differentiated macrophages treated with anti-LILRB1 / 2 antibody or IgG1_LALA-PA isotype control or PBS were stimulated with LPS (100 ng / mL); the concentrations of cytokines (TNF-α and IL-10) in the culture supernatant were quantified by ELISA; each point represents one blood donor; P values ​​were calculated by t-test; *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001, ns not significant;

[0221] FIG. 16A to FIG. 16FExpression profiles of phenotypic markers CD14, CD11B, CD86, CD163, CD206, and PD-L1 quantified by flow cytometry are shown, respectively. Human monocytes were co-cultured with human breast cancer cells MDA-MB-231 to induce TAMs in the presence of anti-LILRB1 / 2 antibodies (#2, #8, #11, #22, #26, or #27), reference antibodies (3C1 or 1E1 (QE)), or IgG1 isotype control (IgG); Each point represents one blood donor; P values ​​were calculated by t-test; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, ns not significant;

[0222] Figure 16G The proportion of tumor cells in the co-culture is shown (%). Human monocytes were co-cultured with human breast cancer cells MDA-MB-231, and TAMs were induced in the presence of anti-LILRB1 / 2 antibodies (#2, #8, #11, #22, #26, or #27), reference antibodies (3C1 or 1E1 (QE)), IgG1 isotype control (IgG), or medium alone (Medium); anti-LILRB1 / 2 antibodies and 1E1 (QE) inhibited tumor cell growth; each point represents a blood donor; P values ​​were calculated by t-test; *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001, ns not significant;

[0223] FIG. 17A to FIG. 17D Humanized and optimized anti-LILRB1 / 2 were shown to promote the inflammatory expression profile of CD14, CD86, CD206 and PD-L1 phenotypic markers, respectively. As quantified by flow cytometry; Human monocytes were co-cultured with human breast cancer cells MDA-MB-231 to induce TAMs in the presence of anti-LILRB1 / 2 antibodies or IgG1LALA-PA isotype control or PBS; Each point represents a single blood donor; P values ​​were calculated by t-test; *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001, ns not significant;

[0224] Fig.17E Humanized and optimized anti-LILRB1 / 2 showed that it inhibited tumor growth in vitro. Human monocytes were co-cultured with human breast cancer cells MDA-MB-231 to induce TAMs in the presence of anti-LILRB1 / 2 antibodies or IgG1-LALA-PA isotype control or PBS; the proportion of tumor cells in the co-culture was measured using FACS; the ordinate is the proportion of tumor cells in the co-culture (%); each point represents a blood donor; P values ​​were calculated by t-test; *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001, ns not significant;

[0225] 18A to 18C Expression profiles of PD-L1, TNF-α, and IL-10 are shown, respectively. TAMs treated with anti-LILRB1 / 2 antibodies (#2, #8, #11, #22, #26, or #27), reference antibodies (3C1 or 1E1 (QE)), IgG1 isotype control (IgG), or medium alone (Medium) were stimulated with LPS (100 ng / mL); the expression of the phenotypic marker PD-L1 was quantified by flow cytometry, and the concentrations of cytokines (TNF-α and IL-10) in the culture supernatant were quantified by ELISA; each point represents one blood donor; P values ​​were calculated by t-test; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, ns not significant;

[0226] FIG. 19A to FIG. 19B The expression profiles of TNF-α and IL-10 are shown, respectively. TAMs treated with anti-LILRB1 / 2 antibody or IgG1_LALA-PA isotype control or PBS were stimulated with LPS (100 ng / mL); the concentrations of cytokines (TNF-α and IL-10) in the culture supernatant were quantified by ELISA; each point represents one blood donor; P values ​​were calculated by t-test; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, ns not significant;

[0227] Fig. 20 IFN-γ concentrations in MLR culture supernatants measured by ELISA are shown. Dendritic cells (DCs) were differentiated from monocytes with GM-CSF / IL4 and matured by LPS stimulation; Mature DCs and allogeneic T cells negatively isolated from human PBMCs were co-cultured in the presence of hMDMs differentiated by anti-LILRB1 / 2 antibodies (#2, #8, #11, #22, #26, or #27) in a mixed lymphocyte reaction (MLR); 3C1 and 1E1 (QE) are reference antibodies; IgG1 is an isotype control (IgG); T cell activation was measured based on the expression of IFN-γ in MLR supernatants; "w / oMac" stands for the absence of macrophages; Each point represents a combination of MLR donor pairs and hMDMs; P values ​​were calculated by t-test; *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001, ns not significant;

[0228] Fig.21Phagocytosis represented by the ratio of GFP+hMDMs in total hMDMs measured by flow cytometry is shown. C1R-HLAG-GFP cells were co-cultured with hMDMs in equal proportions in the presence of anti-LILRB1 / 2 antibodies (#2, #8, #11, #26, or #27); 3C1 and 1E1 (QE) are reference antibodies; IgG1 is an isotype control (IgG); clone #4 can only bind to LILRB1, and clone #44 can only bind to LILRB2; each point represents a blood donor; P values ​​were calculated by t-test; *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001, ns not significant;

[0229] Fig. 22 Figure 2 shows antibody-dependent cellular phagocytosis, or ADCP, represented by the ratio of GFP+hMDMs to total hMDMs measured by flow cytometry; tumor cells labeled with rituximab (anti-CD20) were used for ADCP and co-cultured with hMDMs in equal proportions in the presence of anti-LILRB1 / 2 antibodies (#2, #8, #11, #26, or #27); 3C1 and 1E1 (QE) are reference antibodies; IgG1 is an isotype control (IgG); clone #4 can only bind to LILRB1, and clone #44 can only bind to LILRB2; each point represents one blood donor; P values ​​were calculated by t-test; *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001, ns not significant;

[0230] FIG. 23A to FIG. 23B Antibody-dependent cellular phagocytosis (i.e., ADCP) represented by the ratio of GFP+hMDMs in total hMDMs measured by flow cytometry is shown. A375 tumor cells were labeled with anti-CD47 for ADCP and co-cultured with hMDMs in equal proportions in the presence of anti-LILRB1 / 2 antibodies; 3C1 and 15G8 are anti-LILRB1 reference antibodies; 1E1(QE) and J-19-H1 are anti-LILRB2 reference antibodies; Hz73D1.v1 is an anti-LILRB1 / 2 reference antibody; IgG1-LALA is an isotype control; P values ​​were calculated by t-test; *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001, ns not significant;

[0231] Fig.24AShown are histograms of APC signals after CHO cells expressing cynomolgus LILRB1 or cynomolgus LILRB2 (CHO-cynoLILRB1 or CHO-cynoLILRB2) were incubated with 2 μg / mL anti-LILRB1 / 2 antibodies and then incubated with APC anti-hFc. 3C1 and 1E1 (QE) are reference antibodies; IgG1 is an isotype control (IgG);

[0232] Fig. 24B Binding signals to monkey LILRB2 (cynoLILRB2) measured by flow cytometry are shown. CHO-cynoLILRB2 cells were incubated with serial dilutions of anti-LILRB1 / 2 antibodies and then with APC anti-hFc; IgG1 is an isotype control (IgG);

[0233] Fig.25A The binding signals of anti-LILRB1 / 2 antibodies to LILRB1, LILRB2, LILRB3, LILRB4, and LILRB5 are shown. 293T cells transiently expressing different LILRB proteins were incubated with anti-LILRB1 / 2 antibodies (5 μg / mL) and then incubated with APC anti-human Fc; antibody binding signals were measured by flow cytometry and geometric MFI (gMFI); 3C1 and 1E1 (QE) are reference antibodies; IgG1 is an isotype control (IgG);

[0234] Fig.25B The binding signals of anti-LILRB1 / 2 antibodies to LILRA1, LILRA2, LILRA3, LILRA4, LILRA5, and LILRA6 are shown. 293T cells transiently expressing different LILRB proteins were incubated with anti-LILRB1 / 2 antibodies (5 μg / mL) and then incubated with APC anti-human Fc; antibody binding signals were measured by flow cytometry and geometric MFI (gMFI); 3C1 and 1E1 (QE) are reference antibodies; IgG1 is an isotype control (IgG);

[0235] Fig.25C The binding signals of antibodies to LILRB3 measured by flow cytometry are shown. CHO-LILRB3 cells were incubated with serial dilutions of anti-LILRB1 / 2 antibodies and then incubated with APC anti-hFc; IgG1 is an isotype control (IgG);

[0236] FIG. 26A to FIG. 26FThe binding properties of anti-LILRB1 / 2 antibodies to human LILRB1, LILRB2, LILRB3, cynomolgus monkey LILRB2 (cynoLILRB2), human LILRA1, and LILRA6 in CHO cell lines are shown. CHO-LILRB1, CHO-LILRB2, CHO-LILRB3, CHO-cynoLILRB2, CHO-LILRA1, or CHO-LILRA6 cells were incubated with serial dilutions of anti-LILRB1 / 2 antibodies and then stained with Violet TM 421-labeled anti-human Fc antibody incubation; IgG1 is an isotype control (IgG); Violet TM 421 (gMFI) antibody binding signals to LILRB1, LILRB2, LILRB3, cynoLILRB2, LILRA1, and LILRA6);

[0237] Figure 26G is a table summarizing the maximum MFI and calculated EC50 of anti-LILRB1 / 2 antibodies against LILRB1, LILRB2, LILRB3, cynoLILRB2, LILRA1, and LILRA6. NB means not binding (NOT BIND);

[0238] FIG. 27A to FIG. 27F The anti-LILRB1 / 2 antibody D2M002-126 blocks the interaction of LILRB2 with putative ligands SEMA4A, MAG, CD1C, CD1D, ANGPTL2, and ANGPTL5 reported in the literature. The microplate-coated ligand was incubated with a mixture of biotinylated LILRB2-hFc and serially diluted D2M002-126 or isotype control (IgG1-LALA); the binding signal of the ligand to LILRB2 was detected by streptavidin HRP and substrate TMB;

[0239] Fig.28 Cytotoxicity of RB1-transduced NK cells against A253 tumor cells measured by flow cytometry is shown. Human primary NK cells were transduced with lentiviral particles to express LILRB1 and co-cultured with A253-GFP tumor cells in the presence of anti-LILRB1 / 2 antibody or isotype control or PBS; the proportion of dead tumor cells (GFP+DAPI+) in total tumor cells (GFP+) was quantified by flow cytometry; Hz73D1.v1 is an anti-LILRB1 / 2 reference antibody; IgG1-LALA is an isotype control; P values ​​were calculated by t-test; *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001, ns not significant;

[0240] Fig.29 Cytotoxicity of RB1-transduced CD8+ T cells against C1R tumor cells expressing anti-CD3 scFv and HLA-G measured by flow cytometry is shown. Human primary CD8+ T cells were activated and transduced with lentiviral particles to express LILRB1; CD8+ T cells were co-cultured with C1R-GFP cells expressing anti-CD3 scFv and HLA-G in the presence of anti-LILRB1 / 2 antibodies or isotype controls; the proportion of dead tumor cells (GFP+DAPI+) in total tumor cells (GFP+) was quantified by flow cytometry; 3C1 and 15G8 were anti-LILRB1 reference antibodies; Hz73D1.v1 was an anti-LILRB1 / 2 reference antibody; IgG1-LALA was an isotype control;

[0241] Fig. 30A Figure 2 is a graph showing the cell binding affinity of humanized and optimized anti-LILRB1 / 2 antibodies to CHO-LILRB1 cells treated in human serum or PBS for 1, 2, and 3 weeks at 37°C. CHO-LILRB1 cells were incubated with serial dilutions of anti-LILRB1 / 2 antibodies or against and then treated with Violet TM 421-labeled anti-human Fc antibody incubation; Violet TM 421 (gMFI) antibody binding signal to LILRB1;

[0242] Fig. 30B Figure 2 is a graph showing the cell binding affinity of humanized and optimized anti-LILRB1 / 2 antibodies to CHO-LILRB2 cells treated in human serum or PBS for 1, 2, and 3 weeks at 37°C. CHO-LILRB2 cells were incubated with serial dilutions of anti-LILRB1 / 2 antibodies or against and then stained with Violet TM 421-labeled anti-human Fc antibody incubation; Violet TM 421 (gMFI) antibody binding signal to LILRB2;

[0243] Fig.31 A graph showing the abundance of D2M002-126 in vivo over time is shown. A single dose (10 mg / kg) of D2M002-126 was intravenously injected into C57BL / 6 mice; blood samples were collected at the indicated time points; D2M002-126 was quantified using a sandwich ELISA method using anti-human Fab as a capture reagent and anti-human FC as a detection reagent;

[0244] Fig.32Shown are tumor volumes of NCG mice co-implanted subcutaneously with a mixture of A375 tumor cells and human MDM and treated twice weekly with D2M002-126 and isotype control (IgG-1-LALA-PA) for 3 weeks;

[0245] Fig.33 Figure 2 shows the tumor volume of NCG mice implanted with A375 tumor cells. 3 At 2 s, human MDM were injected intratumorally, and tumor-bearing mice were treated with antibodies and isotype controls twice a week for a total of 3 weeks;

[0246] Fig.34 Tumor volume in NCG mice implanted with A375 tumor cells and reconstituted with human PBMCs is shown. Mice were divided into groups and treated with D2M002-126 and isotype control (IgG1) twice a week for a total of 4 weeks;

[0247] FIG. 35A to FIG. 35B It was shown that the D2M002-002 variant and the D2M026 variant have different binding epitopes. Epitope binning analysis was performed by Gator TM The GatorPrime biolayer interferometry platform was used;

[0248] Fig.35C Competitive binding of D2M002-126 to LILRB1 is shown. D2M002-126 does not compete with the reference anti-LILRB1 antibody 15G8; 15G8 is an anti-LILRB1 reference antibody; Hz73D1.v1 is an anti-LILRB1 / 2 reference antibody;

[0249] Fig.35D Competitive binding of D2M002-126 to LILRB2 is shown. Although D2M002-126 competes with Hz73D1.v1, D2M002-126 does not compete with the anti-LILRB2 reference antibody J-19.H1, while 1E1(QE) and Hz73D1.v1 compete with J-19.H1; H1.1E1(QE) and J19.H1 are anti-LILRB2 reference antibodies; Hz73D1.v1 is an anti-LILRB1 / 2 reference antibody;

[0250] Fig.36The CDR amino acid sequences of the heavy and light chain variable regions of anti-LILRB1 / 2 antibodies defined by the IMGT, Kabat, Chothia or North numbering schemes are listed (D2M002-001, D2M002-002, D2M002-003, D2M002-004, D2M002-008, D2M002-011, D2M002-012, D2M002-016, D2M002-017, D2M002-018, D2M002-020, D2M002-021, D2M002-022, D2M002-023, D2M002-024, D2M002-025, D2M002-026, D2M002-027, D2M002-028, D2M002-029, D2M002-030, D2M002-031, D2M002-032, D2M002-033, D2M002-034, D2M002-035, D2M002-036, D2M002-037, D2M002-038, D2M002-039, D2M002-040, D2M002-041, D2M002-042, D2M002-043, D2M002-044, D2M002-045, D2M002-046, D2M002-047, D2M002-048, D 2M002-020, D2M002-021, D2M002-021, D2M002-022, D2M002-023, D2M002-026, D2M002-027, D2M002-028, D 2M002-029, D2M002-031, D2M002-035, D2M002-036, D2M002-040, D2M002-041, D2M002-044 and D2M002-045);

[0251] Fig.37 The amino acid sequences of the heavy chain variable region and light chain variable region of the anti-LILRB1 / 2 antibody are listed;

[0252] Fig.38 The amino acid sequences of the relevant antibodies or fragments thereof are listed;

[0253] Fig.39 The amino acid sequences of the heavy and light chains of D2M002-002 mouse IgG1 are listed;

[0254] Fig.40 The amino acid sequence of the custom protein is listed;

[0255] Fig.41 The amino acid sequences of other proteins discussed in the disclosure are listed;

[0256] Figure 42 lists the CDR sequences of humanized and optimized variants of the D2M002-002 lineage as defined by the IMGT, Kabat, Chothia or North numbering schemes;

[0257] Figure 43 lists the CDR sequences of humanized and optimized variants of the D2M002-026 lineage as defined by the IMGT, Kabat, Chothia or North numbering schemes;

[0258] FIG44 lists the VH and VL amino acid sequences of humanized and optimized variants of the D2M002-002 lineage;

[0259] FIG45 lists the VH and VL amino acid sequences of humanized and optimized variants of the D2M002-026 lineage;

[0260] Figure 46 lists the heavy and light chain amino acid sequences of the humanized and optimized variants. DETAILED DESCRIPTION

[0261] The present disclosure provides examples of antibodies and antigen-binding fragments thereof that bind to LILRB1 (leukocyte immunoglobulin-like receptor subfamily B member 1; also known as ILT2) and / or LILRB2 (leukocyte immunoglobulin-like receptor subfamily B member 2; also known as ILT4).

[0262] LILRB1, LILRB2 and HLA-G

[0263] The major histocompatibility complex (MHC) plays a key role in the body's immune defense mechanism induced by T cell immune responses by presenting cancer or virus-derived antigenic peptides. Humans have MHC class I and class II genes. The classical class I genes are known as HLA-A, HLA-B, and HLA-C. The minor MHC class I genes in HLA are HLA-E, HLA-F, and HLA-G.

[0264] HLA-G is a nonclassical MHC class I molecule that plays a crucial role in fetal-maternal tolerance. It is an inhibitory molecule that regulates T-cell activation. HLA-G inhibits cytotoxic T cells, natural killer (NK) cells, and B cells, induces T-cell anergy, regulates myeloid cells, and promotes T regulatory cells (Tregs) through the interaction of LILRB1 (ILT2) and LILRB2 (ILT4) receptors. In addition, HLA-G expressed on antigen-presenting cells (APCs), such as myeloid-derived suppressor cells (MDSCs) or tolerogenic dendritic cells (DCs), promotes T-cell hyporesponsiveness and induces Treg differentiation. LILRB1 is expressed on different leukemias and solid tumors. While LILRB1 prevents primary cutaneous T-cell lymphoma cell death and promotes gastric tumor growth, HLA-G / LILRB1 interaction inhibits neoplastic B-cell proliferation. Blockade of LILRB1 on myeloma or lymphoblasts does not prevent NK-mediated lysis. LILRB2 is expressed in various solid tumors, such as clear cell renal carcinoma (ccRCC) and stromal cells in the tumor microenvironment. LILRB2 expression is associated with poor cell differentiation and late metastasis. One potential mechanism is the upregulation of vascular endothelial growth factor (VEGF)-C, a well-characterized and potent growth factor involved in lymphangiogenesis and lymphatic metastasis.

[0265] In immunocompetent mice, tumor cells expressing HLA-G proliferate, whereas in immunodeficient mice, injection of HLA-G-expressing tumor cells results in widespread metastasis, suggesting a role for HLA-G in tumor immune escape. Furthermore, de novo expression of HLA-G is found in the majority of human tumors analyzed but not in surrounding healthy autonomous tissues. These findings are consistent with the involvement of checkpoint HLA-G in tumor progression and invasiveness. Furthermore, HLA-G / LILRB affects a broader range of immune cells than those regulated by cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) / B7 and programmed death (PD)-1 / PD ligand-1; known targets of current IC blockade therapies. Thus, the checkpoint HLA-G / LILRB interaction holds promise as an additional target for cancer immunotherapy.

[0266] LILRs (also known as immunoglobulin-like transcripts (ILTs) or LIRs) are a family of 11 receptors with two to four extracellular Ig-like domains that are classified as inhibitory or activating. Most LILRs are expressed as membrane-bound receptors, with the exception of LILRA3, which is expressed only in a soluble form. Inhibitory receptors (LILRB1 to B5) have long cytoplasmic tails containing ITIMs, whereas activating receptors (LILRA1 to A6, excluding A3) have short cytoplasmic tails and couple to ITAM-bearing FcεRIγ. Individual LILR receptors are classified as members of group 1 (LILRB1, LILRB2, and LILRA1-3) or group 2 (LILRB3-5 and LILRA4-6) based on the conservation of LILRB1 residues that recognize human leukocyte antigen (HLA) class I molecules. Expression of individual LILRs has been documented in a range of immune cells, including neutrophils, eosinophils, macrophages, dendritic cells, NK cells, B cells, T cells, and osteoclasts, as well as non-immune cells such as endothelial cells and neurons. Most LILR genes also encode soluble forms of LILR produced by alternative splicing. The LILR orthologs found in mice are called PIRs; however, there are fundamental differences within human LILRs. For example, PIRs have six Ig-like domains and only two inhibitory receptors, called PIR-B and gp49b1. Human LILRB and PIR-B can regulate the function of ITAM-bearing receptors, such as FcRs, B cell receptors (BCRs), and T cell receptors (TCRs). LILRs also regulate toll-like receptor (TLR) signaling and function. Therefore, LILRs can regulate a wide range of immune functions, including immune cell function, cytokine release, antibody production, and antigen presentation.

[0267] LILRB1 and LILRB2 belong to the B subfamily of LIR receptors and contain two or four extracellular immunoglobulin domains, a transmembrane domain, and two to four cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs). The receptor is expressed on immune cells, binds to MHC class I molecules on antigen-presenting cells, and transduces negative signals that inhibit the stimulation of immune responses. It is thought to control inflammatory responses and cytotoxicity to help focus immune responses and limit autoreactivity. Multiple transcript variants encoding different isoforms have been found. Both LILRB1 and LILRB2 are expressed on a variety of human immune cells. This includes all B cells, monocytes and macrophages, dendritic cells, and subsets of NK cells and T cells. The percentage of LILRB1+ NK cells is significantly higher in patients with advanced prostate and breast cancer than in healthy voluntary donors or patients with localized cancer. Using in vitro models, blocking LILRB1 signaling in immune cells can activate NK cell activity against solid tumors and leukemias, and activate T cell or macrophage activity against solid tumors.

[0268] In addition, LILRB1 was found on the surface of macrophages, where it can bind to a portion of the MHCI class that is widely shared on cancer cells. This binding had the effect of inhibiting macrophages from engulfing and killing cancer cells, both when grown in laboratory dishes and in mice bearing human tumors. Therefore, LILRB1 is considered the second "don't eat me" signal found on cancer cells after the CD47 / SIRPα pathway.

[0269] Since LILRB1 and LILRB2 are promising immunomodulatory targets for cancer immunotherapy, LILRB1 and / or LILRB2-specific antibodies could be designed, for example to block LILRB1 / HLA-G and / or LILRB2 / HLA-G interactions, thereby increasing the immune response. A detailed description of LILRB1, LILRB2 and their role in cancer immunotherapy can be found, for example, in "HLA-G / LILRBs: A Challenge for Cancer Immunotherapy" by Carosella, ED et al. Trends in Cancer 7.5 (2021): 389-392; Chen, H. et al. "Antagonistic LILRB1 monoclonal antibodies modulate the antitumor function of natural killer cells." Journal of Cancer Immunotherapy 8.2 (2020); Lewis M. et al. "Leukocyte immunoglobulin-like receptors (LILRs) on human neutrophils: modulators of infection and immunity." Frontiers in Immunology (2020): 857; Wang, Q. et al. "Structures of four Ig-like domain LILRB2 and four domain LILRB1 in complex with HLA-G1." Cellular and Molecular Immunology 17.9 (2020): 966-975; and Barkal, A. et al. "Inhibitory receptor LILRB1 participates in MHCI class I inhibition of macrophages and is a target for cancer immunotherapy." Nature Immunology 19.1 (2018): 76-84; all incorporated herein by reference.

[0270] The present disclosure provides several anti-LILRB1 / 2 antibodies, antigen-binding fragments thereof, and methods of using these antibodies and antigen-binding fragments to inhibit tumor growth and treat cancer.

[0271] Anti-LILRB1 / 2 Antibodies and Antigen-Binding Fragments

[0272] The present disclosure provides antibodies and antigen-binding fragments thereof that specifically bind to LILRB1 and / or LILRB2. The antibodies and antigen-binding fragments described herein are capable of binding to LILRB1 and / or LILRB2, and can inhibit signaling pathways to increase immune responses. The disclosure provides, for example: mouse anti-LILRB1 / 2 antibodies D2M002-001 ("#1"), D2M002-002 ("#2"), D2M002-003 ("#3"), D2M002-004 ("#4"), D2M002-008 ("#8"), D2M002-011 ("#11"), D2M002-012 ("#12"), D2M002-016 ("#16"), D2M002-017 ("#17"), D2M 002-018("#18"), D2M002-020("#20"), D2M002-021("#21"), D2M002-022("#22"), D2M002-023("#23"), D2M00 2-026("#26"), D2M002-027("#27"), D2M002-028("#28"), D2M002-029("#29"), D2M002-031("#31"), D2M002- 035("#35"), D2M002-036("#36"), D2M002-040("#40"), D2M002-041("#41"), D2M002-044("#44"), D2M002-04 5("#45"), D2M002-002-H12, D2M002-002-H26, D2M002-026-H14, D2M002-026-H25, P215_C06, P215_H02, P212_ E10, P211_E01, P211_B01, P211_G04, P211_C01, P212_C04, P212_F06, P211_B02, P213_C03, P211_C02, P211_C0 9, P212_A03, P212_B07, P213_C05, P213_H11, P211_E07, P213_G10, P212_E03, P212_G10, P215_A01, P211_B05,P215_H01, P212_D01, P215_F02, P212_H04, P212_D04, P211_E02, P213_ F05, P212_B12, P211_H07, P213_C11, P211_D03, P215_F06, P211_C05, P2 11_C06, P212_F11, P211_A06, P211_B10, P212_A12, P213_C02, P211_A03 ,P211_C10,P215_D05,P213_D04,P212_E06,P212_E12,P211_A10,P212_ C01, P212_C08, P211_D12, P211_C07, P215_D06, P211_H09, P213_E05, P 213_H03, P215_C01, P214_A10, P211_G09, P215_C07, P216_E06, P216_H0 1. P215_E11, P215_A07, D2M002-101(P211_A12), D2M002-102(P212_E04 ), D2M002-103(P212_F01), D2M002-104(P212_E01), D2M002-105(P211_ B12), D2M002-106(P213_A03), D2M002-107(P213_H05), D2M002-108(P 211_B09), D2M002-109(P212_D03), D2M002-110(P211_E08), D2M002-11 1. D2M002-112, D2M002-113, D2M002-114, D2M002-115, D2M002-116, D2M 002-117, D2M002-118, D2M002-119, D2M002-120, D2M002-121, D2M002-1 22. D2M002-123, D2M002-124, D2M002-125, D2M002-126, D2M002-1217, D2M002-128, D2M002-129, D2M002-130, D2M002-131, D2M002-132, D2M002-103HV1, D2M002-103HV2, D2M002-103LV1, D2M002-103LV3, D2M002-103LV4, D2M002-103LV5, D2M002-126LV1, D2M002-126LV2, chimeric antibodies thereof, and humanized antibodies thereof.

[0273] The CDR sequences of D2M002-001 and D2M002-001 derived antibodies (e.g., humanized antibodies) include CDRs of the heavy chain variable domain, SEQ ID NOs: 7-9 and CDRs of the light chain variable domain, SEQ ID NOs: 10-12, defined by Kabat numbering. CDRs may also be defined by the Chothia numbering system. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 13-15, and the CDR sequences of the light chain variable domain are listed in SEQ ID NOs: 16-18.

[0274] Likewise, the CDR sequences of D2M002-002 and D2M002-002 derived antibodies include the CDRs of the heavy chain variable domain, SEQ ID NOs: 37-39 and the CDRs of the light chain variable domain, SEQ ID NOs: 40-42, as defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 43-45, and the CDR sequences of the light chain variable domain are listed in SEQ ID NOs: 46-48.

[0275] The CDR sequences of D2M002-003 and D2M002-003 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 67-69 and CDRs of the light chain variable domain, SEQ ID NOs: 70-72, as defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 73-75, and the CDR sequences of the light chain variable domain are listed in SEQ ID NOs: 76-78.

[0276] The CDR sequences of D2M002-004 and D2M002-004 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 97-99 and CDRs of the light chain variable domain, SEQ ID NOs: 100-102, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 103-105, and the CDR sequences of the light chain variable domain are listed in SEQ ID NOs: 106-108.

[0277] The CDR sequences of D2M002-008 and D2M002-008 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 127-129 and CDRs of the light chain variable domain, SEQ ID NOs: 130-132, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 133-135, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 136-138.

[0278] The CDR sequences of D2M002-011 and D2M002-011 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 157-159 and CDRs of the light chain variable domain, SEQ ID NOs: 160-162, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 163-165, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 166-168.

[0279] The CDR sequences of D2M002-012 and D2M002-012 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 187-189, and CDRs of the light chain variable domain, SEQ ID NOs: 190-192, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 193-195, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 196-198.

[0280] The CDR sequences of D2M002-016 and D2M002-016 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 217-219 and CDRs of the light chain variable domain, SEQ ID NOs: 220-222, as defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 223-225, and the CDR sequences of the light chain variable domain are listed in SEQ ID NOs: 226-228.

[0281] The CDR sequences of D2M002-017 and D2M002-017 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 247-249 and CDRs of the light chain variable domain, SEQ ID NOs: 250-252, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 253-255, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 256-258.

[0282] The CDR sequences of D2M002-018 and D2M002-018 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 277-279 and CDRs of the light chain variable domain, SEQ ID NOs: 280-282, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 283-285, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 286-288.

[0283] The CDR sequences of D2M002-020 and D2M002-020 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 307-309 and CDRs of the light chain variable domain, SEQ ID NOs: 310-312, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 313-315, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 316-318.

[0284] The CDR sequences of D2M002-021 and D2M002-021 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 337-339 and CDRs of the light chain variable domain, SEQ ID NOs: 340-342, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 343-345, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 346-348.

[0285] The CDR sequences of D2M002-022 and D2M002-022-derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 367-369 and CDRs of the light chain variable domain, SEQ ID NOs: 370-372, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 373-375, and the CDR sequences of the light chain variable domain are listed in SEQ ID NOs: 376-378.

[0286] The CDR sequences of D2M002-023 and D2M002-023 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 397-399 and CDRs of the light chain variable domain, SEQ ID NOs: 400-402, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 403-405, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 406-408.

[0287] The CDR sequences of D2M002-026 and D2M002-026-derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 427-429 and CDRs of the light chain variable domain, SEQ ID NOs: 430-432, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 433-435, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 436-438.

[0288] The CDR sequences of D2M002-027 and D2M002-027 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 457-459 and CDRs of the light chain variable domain, SEQ ID NOs: 460-462, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 463-465, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 466-468.

[0289] The CDR sequences of D2M002-028 and D2M002-028 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 487-489 and CDRs of the light chain variable domain, SEQ ID NOs: 490-492, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 493-495, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 496-498.

[0290] The CDR sequences of D2M002-029 and D2M002-029 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 517-519 and CDRs of the light chain variable domain, SEQ ID NOs: 520-522, as defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 523-525, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 526-528.

[0291] The CDR sequences of D2M002-031 and D2M002-031 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 547-549 and CDRs of the light chain variable domain, SEQ ID NOs: 550-552, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 553-555, and the CDR sequences of the light chain variable domain are listed in SEQ ID NOs: 556-558.

[0292] The CDR sequences of D2M002-035 and D2M002-035 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 577-579 and CDRs of the light chain variable domain, SEQ ID NOs: 580-582, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 583-585, and the CDR sequences of the light chain variable domain are listed in SEQ ID NOs: 586-588.

[0293] The CDR sequences of D2M002-036 and D2M002-036-derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 607-609 and CDRs of the light chain variable domain, SEQ ID NOs: 610-612, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 613-615, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 616-618.

[0294] The CDR sequences of D2M002-040 and D2M002-040-derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 637-639 and CDRs of the light chain variable domain, SEQ ID NOs: 640-642, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 643-645, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 646-648.

[0295] The CDR sequences of D2M002-041 and D2M002-041 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 667-669 and CDRs of the light chain variable domain, SEQ ID NOs: 670-672, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 673-675, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 676-678.

[0296] The CDR sequences of D2M002-044 and D2M002-044-derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 697-699 and CDRs of the light chain variable domain, SEQ ID NOs: 700-702, as defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 703-705, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 706-708.

[0297] The CDR sequences of D2M002-045 and D2M002-045 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 727-729 and CDRs of the light chain variable domain, SEQ ID NOs: 730-732, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 733-735, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 736-738.

[0298] Figure 14 also provides the CDR sequences of VH and VL of the above antibodies defined by the IMGT, North or Aho numbering systems.

[0299] In some embodiments, the antibodies and antigen-binding fragments described herein can be classified as the D2M002-002 lineage, such as D2M002-002, D2M002-103, D2M002-103HV1, D2M002-103HV2, D2M002-103LV1, D2M002-103LV3, D2M002-103LV4, and D2M002-103LV5. In some embodiments, the antibodies and antigen-binding fragments described herein can be classified as the D2M002-026 lineage, such as. g., D2M002-026, D2M002-114, D2M002-115, D2M002-116, D2M002-117, D2M0 02-118, D2M002-119, D2M002-120, D2M002-121, D2M002-122, D2M002-123, D In some embodiments, the above antibodies or variants have humanized and / or optimized sequences.

[0300] The CDR sequences of D2M002-103 and D2M002-103 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 1069-1071 and CDRs of the light chain variable domain, SEQ ID NOs: 1072-1074, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 1075-1077, and the CDR sequences of the light chain variable domain are listed in SEQ ID NOs: 1078-1080.

[0301] The CDR sequences of D2M002-103HV1 ​​and D2M002-103HV1 ​​derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 1093-1095, and CDRs of the light chain variable domain, SEQ ID NOs: 1096-1098, as defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 1099-1101, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 1102-1104.

[0302] The CDR sequences of D2M002-103HV2 and D2M002-103HV2-derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 1117-1119 and CDRs of the light chain variable domain, SEQ ID NOs: 1120-1122, as defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 1123-1125, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 1126-1128.

[0303] The CDR sequences of D2M002-103LV1 and D2M002-103LV1-derived antibodies include the CDRs of the heavy chain variable domain, SEQ ID NOs: 1141-1143 and the CDRs of the light chain variable domain, SEQ ID NOs: 1144-1146, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 1147-1149, and the CDR sequences of the light chain variable domain are listed in SEQ ID NOs: 1150-1152.

[0304] The CDR sequences of D2M002-103LV3 and D2M002-103LV3-derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 1165-1167 and CDRs of the light chain variable domain, SEQ ID NOs: 1168-1170, as defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 1171-1173, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 1174-1176.

[0305] The CDR sequences of D2M002-103LV4 and D2M002-103LV4-derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 1189-1191 and CDRs of the light chain variable domain, SEQ ID NOs: 1192-1194, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 1195-1197, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 1198-1200.

[0306] The CDR sequences of D2M002-103LV5 and D2M002-103LV5-derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 1213-1215, and CDRs of the light chain variable domain, SEQ ID NOs: 1216-1218, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 1219-1221, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 1222-1224.

[0307] The VH and VL CDR sequences of the above antibodies (e.g., D2M002-002 lineage humanized and / or optimized variants) under IMGT or North numbering are also shown in Figure 42.

[0308] The CDR sequences of D2M002-114 and D2M002-114 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 1237-1239 and CDRs of the light chain variable domain, SEQ ID NOs: 1240-1242, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 1243-1245, and the CDR sequences of the light chain variable domain are listed in SEQ ID NOs: 1246-1248.

[0309] The CDR sequences of D2M002-115 and D2M002-115 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 1261-1263 and CDRs of the light chain variable domain, SEQ ID NOs: 1264-1266, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 1267-1269, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 1270-1272.

[0310] The CDR sequences of D2M002-116 and D2M002-116 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 1285-1287 and CDRs of the light chain variable domain, SEQ ID NOs: 1288-1290, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 1291-1293, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 1294-1296.

[0311] The CDR sequences of D2M002-117 and D2M002-117 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 1309-1311 and CDRs of the light chain variable domain, SEQ ID NOs: 1312-1314, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 1315-1317, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 1318-1320.

[0312] The CDR sequences of D2M002-118 and D2M002-118 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 1333-1335 and CDRs of the light chain variable domain, SEQ ID NOs: 1336-1338, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 1339-1341, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 1342-1344.

[0313] The CDR sequences of D2M002-119 and D2M002-119 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 1357-1359 and CDRs of the light chain variable domain, SEQ ID NOs: 1360-1362, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 1362-1365, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 1366-1368.

[0314] The CDR sequences of D2M002-120 and D2M002-120 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 1381-1383 and CDRs of the light chain variable domain, SEQ ID NOs: 1384-1386, as defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 1387-1389, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 1390-1392.

[0315] The CDR sequences of D2M002-121 and D2M002-121 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 1405-1407, and CDRs of the light chain variable domain, SEQ ID NOs: 1408-1410, as defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 1411-1413, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 1414-1416.

[0316] The CDR sequences of D2M002-122 and D2M002-122-derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 1429-1431 and CDRs of the light chain variable domain, SEQ ID NOs: 1432-1434, as defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 1435-1437, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 1438-1440.

[0317] The CDR sequences of D2M002-123 and D2M002-123 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 1453-1455, and CDRs of the light chain variable domain, SEQ ID NOs: 1456-1458, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 1459-1461, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 1462-1464.

[0318] The CDR sequences of D2M002-124 and D2M002-124-derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 1477-1479, and CDRs of the light chain variable domain, SEQ ID NOs: 1480-1482, as defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 1483-1485, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 1486-1488.

[0319] The CDR sequences of D2M002-125 and D2M002-125 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 1501-1503 and CDRs of the light chain variable domain, SEQ ID NOs: 1504-1506, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 1507-1509, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 1510-1512.

[0320] The CDR sequences of D2M002-126 and D2M002-126-derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 1525-1527 and CDRs of the light chain variable domain, SEQ ID NOs: 1528-1530, as defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 1531-1533, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 1534-1536.

[0321] The CDR sequences of D2M002-127 and D2M002-127 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 1549-1551, and CDRs of the light chain variable domain, SEQ ID NOs: 1552-1554, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 1555-1557, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 1558-1560.

[0322] The CDR sequences of D2M002-128 and D2M002-128 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 1573-1575 and CDRs of the light chain variable domain, SEQ ID NOs: 1576-1578, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 1579-1581, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 1582-1584.

[0323] The CDR sequences of D2M002-129 and D2M002-129 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 1597-1599, and CDRs of the light chain variable domain, SEQ ID NOs: 1600-1602, as defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 1603-1605, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 1606-1608.

[0324] The CDR sequences of D2M002-130 and D2M002-130 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 1621-1623 and CDRs of the light chain variable domain, SEQ ID NOs: 1624-1636, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 1627-1629, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 1630-1632.

[0325] The CDR sequences of D2M002-131 and D2M002-131 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 1645-1647 and CDRs of the light chain variable domain, SEQ ID NOs: 1648-1650, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 1651-1653, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 1654-1656.

[0326] The CDR sequences of D2M002-132 and D2M002-132 derived antibodies include CDRs of the heavy chain variable domain, SEQ ID NOs: 1669-1671 and CDRs of the light chain variable domain, SEQ ID NOs: 1672-1674, defined by Kabat numbering. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are listed in SEQ ID NOs: 1675-1677, and the CDRs of the light chain variable domain are listed in SEQ ID NOs: 1678-1680.

[0327] The VH and VL CDR sequences of the above antibodies (e.g., D2M002-026 lineage humanized and / or optimized variants) under IMGT or North numbering are also shown in Figure 43. The amino acid sequences of the heavy chain variable region and the light chain variable region of the humanized antibodies are also provided. The amino acid sequence of the heavy chain variable region (VH) of D2M002-001 is set forth in SEQ ID NO: 751. The amino acid sequence of the light chain variable region (VL) of D2M002-001 is set forth in SEQ ID NO: 752. The amino acid sequence of the VH of D2M002-002 is set forth in SEQ ID NO: 753. The amino acid sequence of the VL of D2M002-002 is set forth in SEQ ID NO: 754. The amino acid sequence of the VH of D2M002-003 is set forth in SEQ ID NO: 755. The amino acid sequence of the VL of D2M002-003 is set forth in SEQ ID NO: 756. The amino acid sequence of D2M002-004 VH is set forth in SEQ ID NO: 757. The amino acid sequence of D2M002-004 VL is set forth in SEQ ID NO: 758. The amino acid sequence of D2M002-008 VH is set forth in SEQ ID NO: 759. The amino acid sequence of D2M002-008 VL is set forth in SEQ ID NO: 760. The amino acid sequence of D2M002-011 VH is set forth in SEQ ID NO: 761. The amino acid sequence of D2M002-011 VL is set forth in SEQ ID NO: 762. The amino acid sequence of D2M002-012 VH is set forth in SEQ ID NO: 763. The amino acid sequence of D2M002-012 VL is set forth in SEQ ID NO: 764. The amino acid sequence of D2M002-016 VH is set forth in SEQ ID NO: 765. The amino acid sequence of the VL of D2M002-016 is set forth in SEQ ID NO: 766. The amino acid sequence of the VH of D2M002-017 is set forth in SEQ ID NO: 767. The amino acid sequence of the VL of D2M002-017 is set forth in SEQ ID NO: 768. The amino acid sequence of the VH of D2M002-018 is set forth in SEQ ID NO: 769. The amino acid sequence of the VL of D2M002-018 is set forth in SEQ ID NO: 770. The amino acid sequence of the VH of D2M002-020 is set forth in SEQ ID NO: 771. The amino acid sequence of the VL of D2M002-020 is set forth in SEQ ID NO: 772. The amino acid sequence of the VH of D2M002-021 is set forth in SEQ ID NO: 773. The amino acid sequence of the VL of D2M002-021 is set forth in SEQ ID NO: 774.The amino acid sequence of the VH of D2M002-022 is set forth in SEQ ID NO: 775. The amino acid sequence of the VL of D2M002-022 is set forth in SEQ ID NO: 776. The amino acid sequence of the VH of D2M002-023 is set forth in SEQ ID NO: 777. The amino acid sequence of the VL of D2M002-023 is set forth in SEQ ID NO: 778. The amino acid sequence of the VH of D2M002-026 is set forth in SEQ ID NO: 779. The amino acid sequence of the VL of D2M002-026 is set forth in SEQ ID NO: 780. The amino acid sequence of the VH of D2M002-027 is set forth in SEQ ID NO: 781. The amino acid sequence of the VL of D2M002-027 is set forth in SEQ ID NO: 782. The amino acid sequence of the VH of D2M002-028 is set forth in SEQ ID NO: 783. The amino acid sequence of the VL of D2M002-028 is set forth in SEQ ID NO: 784. The amino acid sequence of the VH of D2M002-029 is set forth in SEQ ID NO: 785. The amino acid sequence of the VL of D2M002-029 is set forth in SEQ ID NO: 786. The amino acid sequence of the VH of D2M002-031 is set forth in SEQ ID NO: 787. The amino acid sequence of the VL of D2M002-031 is set forth in SEQ ID NO: 788. The amino acid sequence of the VH of D2M002-035 is set forth in SEQ ID NO: 789. The amino acid sequence of the VL of D2M002-035 is set forth in SEQ ID NO: 790. The amino acid sequence of the VH of D2M002-036 is set forth in SEQ ID NO: 791. The amino acid sequence of the VL of D2M002-036 is set forth in SEQ ID NO: 792. The amino acid sequence of D2M002-040 VH is set forth in SEQ ID NO: 793. The amino acid sequence of the VL of D2M002-040 is set forth in SEQ ID NO: 794. The amino acid sequence of D2M002-041 VH is set forth in SEQ ID NO: 795. The amino acid sequence of the VL of D2M002-041 is set forth in SEQ ID NO: 796. The amino acid sequence of D2M002-044 VH is set forth in SEQ ID NO: 797. The amino acid sequence of the VL of D2M002-044 is set forth in SEQ ID NO: 798. The amino acid sequence of the VH of D2M002-045 is set forth in SEQ ID NO: 799. The amino acid sequence of the VL of D2M002-045 is set forth in SEQ ID NO: 800. The amino acid sequence of D2M002-002-H12 VH is set forth in SEQ ID NO: 841.The amino acid sequence of the VL of D2M002-002-H12 is set forth in SEQ ID NO:842. The amino acid sequence of the VH of D2M002-002-H26 is set forth in SEQ ID NO:843. The amino acid sequence of the VL of D2M002-002-H26 is set forth in SEQ ID NO:844. The amino acid sequence of the VH of D2M002-026-H14 is set forth in SEQ ID NO:845. The amino acid sequence of the VL of D2M002-026-H14 is set forth in SEQ ID NO:846. The amino acid sequence of the VH of D2M002-026-H25 is set forth in SEQ ID NO:847. The amino acid sequence of the VL of D2M002-026-H25 is set forth in SEQ ID NO:848. The amino acid sequence of the VH of P215_C06 is set forth in SEQ ID NO:849. The amino acid sequence of P215_C06 VL is set forth in SEQ ID NO: 850. The amino acid sequence of P215_H02 VH is set forth in SEQ ID NO: 851. The amino acid sequence of P215_H02 VL is set forth in SEQ ID NO: 852. The amino acid sequence of P212_E10 VH is set forth in SEQ ID NO: 853. The amino acid sequence of P212_E10 VL is set forth in SEQ ID NO: 854. The amino acid sequence of P211_E01 VH is set forth in SEQ ID NO: 855. The amino acid sequence of P211_E01 VL is set forth in SEQ ID NO: 856. The amino acid sequence of P211_B01 VH is set forth in SEQ ID NO: 857. The amino acid sequence of P211_B01 VL is set forth in SEQ ID NO: 858. The amino acid sequence of the VH of P211_G04 is set forth in SEQ ID NO:859. The amino acid sequence of the VL of P211_G04 is set forth in SEQ ID NO:860. The amino acid sequence of the VH of P211_C01 is set forth in SEQ ID NO:861. The amino acid sequence of the VL of P211_C01 is set forth in SEQ ID NO:862. The amino acid sequence of the VH of P212_C04 is set forth in SEQ ID NO:863. The amino acid sequence of the VL of P212_C04 is set forth in SEQ ID NO:864. The amino acid sequence of the VH of P212_F06 is set forth in SEQ ID NO:865. The amino acid sequence of the VL of P212_F06 is set forth in SEQ ID NO:866. The amino acid sequence of the VH of P211_B02 is set forth in SEQ ID NO:867. The amino acid sequence of the VL of P211_B02 is set forth in SEQ ID NO:868.The amino acid sequence of the VH of P213_C03 is set forth in SEQ ID NO: 869. The amino acid sequence of the VL of P213_C03 is set forth in SEQ ID NO: 870. The amino acid sequence of the VH of P211_C02 is set forth in SEQ ID NO: 871. The amino acid sequence of the VL of P211_C02 is set forth in SEQ ID NO: 872. The amino acid sequence of the VH of P211_C09 is set forth in SEQ ID NO: 873. The amino acid sequence of the VL of P211_C09 is set forth in SEQ ID NO: 874. The amino acid sequence of the VH of P212_A03 is set forth in SEQ ID NO: 875. The amino acid sequence of the VL of P212_A03 is set forth in SEQ ID NO: 876. The amino acid sequence of the VH of P212_B07 is set forth in SEQ ID NO: 877. The amino acid sequence of the VL of P212_B07 is set forth in SEQ ID NO: 878. The amino acid sequence of the VH of P213_C05 is set forth in SEQ ID NO: 879. The amino acid sequence of the VL of P213_C05 is set forth in SEQ ID NO: 880. The amino acid sequence of the VH of P213_H11 is set forth in SEQ ID NO: 881. The amino acid sequence of the VL of P213_H11 is set forth in SEQ ID NO: 882. The amino acid sequence of the VH of P211_E07 is set forth in SEQ ID NO: 883. The amino acid sequence of the VL of P211_E07 is set forth in SEQ ID NO: 884. The amino acid sequence of the VH of P213_G10 is set forth in SEQ ID NO: 885. The amino acid sequence of the VL of P213_G10 is set forth in SEQ ID NO: 886. The amino acid sequence of the VH of P212_E03 is set forth in SEQ ID NO: 887. The amino acid sequence of the VL of P212_E03 is set forth in SEQ ID NO: 888. The amino acid sequence of the VH of P212_G10 is set forth in SEQ ID NO: 889. The amino acid sequence of the VL of P212_G10 is set forth in SEQ ID NO: 890. The amino acid sequence of the VH of P215_A01 is set forth in SEQ ID NO: 891. The amino acid sequence of the VL of P215_A01 is set forth in SEQ ID NO: 892. The amino acid sequence of the VH of P211_B05 is set forth in SEQ ID NO: 893. The amino acid sequence of the VL of P211_B05 is set forth in SEQ ID NO: 894. The amino acid sequence of the VH of P215_H01 is set forth in SEQ ID NO: 895. The amino acid sequence of the VL of P215_H01 is set forth in SEQ ID NO: 896.The amino acid sequence of the VH of P212_D01 is set forth in SEQ ID NO: 897. The amino acid sequence of the VL of P212_D01 is set forth in SEQ ID NO: 898. The amino acid sequence of the VH of P215_F02 is set forth in SEQ ID NO: 899. The amino acid sequence of the VL of P215_F02 is set forth in SEQ ID NO: 900. The amino acid sequence of the VH of P212_H04 is set forth in SEQ ID NO: 901. The amino acid sequence of the VL of P212_H04 is set forth in SEQ ID NO: 902. The amino acid sequence of the VH of P212_D04 is set forth in SEQ ID NO: 903. The amino acid sequence of the VL of P212_D04 is set forth in SEQ ID NO: 904. The amino acid sequence of the VH of P211_E02 is set forth in SEQ ID NO: 905. The amino acid sequence of the VL of P211_E02 is set forth in SEQ ID NO: 906. The amino acid sequence of the VH of P213_F05 is set forth in SEQ ID NO:907. The amino acid sequence of the VL of P213_F05 is set forth in SEQ ID NO:908. The amino acid sequence of the VH of P212_B12 is set forth in SEQ ID NO:909. The amino acid sequence of the VL of P212_B12 is set forth in SEQ ID NO:910. The amino acid sequence of the VH of P211_H07 is set forth in SEQ ID NO:911. The amino acid sequence of the VL of P211_H07 is set forth in SEQ ID NO:912. The amino acid sequence of the VH of P213_C11 is set forth in SEQ ID NO:913. The amino acid sequence of the VL of P213_C11 is set forth in SEQ ID NO:914. The amino acid sequence of the VH of P211_D03 is set forth in SEQ ID NO:915. The amino acid sequence of the VL of P211_D03 is set forth in SEQ ID NO:916. The amino acid sequence of P215_F06 VH is set forth in SEQ ID NO:917. The amino acid sequence of P215_F06 VL is set forth in SEQ ID NO:918. The amino acid sequence of P211_C05 VH is set forth in SEQ ID NO:919. The amino acid sequence of P211_C05 VL is set forth in SEQ ID NO:920. The amino acid sequence of P211_C06 VH is set forth in SEQ ID NO:921. The amino acid sequence of P211_C06 VL is set forth in SEQ ID NO:922. The amino acid sequence of P212_F11 VH is set forth in SEQ ID NO:923. The amino acid sequence of P212_F11 VL is set forth in SEQ ID NO:924.The amino acid sequence of P211_A06 VH is set forth in SEQ ID NO:925. The amino acid sequence of P211_A06 VL is set forth in SEQ ID NO:926. The amino acid sequence of P211_B10 VH is set forth in SEQ ID NO:927. The amino acid sequence of P211_B10 VL is set forth in SEQ ID NO:928. The amino acid sequence of P212_A12 VH is set forth in SEQ ID NO:929. The amino acid sequence of P212_A12 VL is set forth in SEQ ID NO:930. The amino acid sequence of P213_C02 VH is set forth in SEQ ID NO:931. The amino acid sequence of P213_C02 VL is set forth in SEQ ID NO:932. The amino acid sequence of P211_A03 VH is set forth in SEQ ID NO:933. The amino acid sequence of P211_A03 VL is set forth in SEQ ID NO:934. The amino acid sequence of P211_C10 VH is set forth in SEQ ID NO: 935. The amino acid sequence of P211_C10 VL is set forth in SEQ ID NO: 936. The amino acid sequence of P215_D05 VH is set forth in SEQ ID NO: 937. The amino acid sequence of P215_D05 VL is set forth in SEQ ID NO: 938. The amino acid sequence of P213_D04 VH is set forth in SEQ ID NO: 939. The amino acid sequence of P213_D04 VL is set forth in SEQ ID NO: 940. The amino acid sequence of P212_E06 VH is set forth in SEQ ID NO: 941. The amino acid sequence of P212_E06 VL is set forth in SEQ ID NO: 942. The amino acid sequence of P212_E12 VH is set forth in SEQ ID NO: 943. The amino acid sequence of P212_E12 VL is set forth in SEQ ID NO:944. The amino acid sequence of P211_A10 VH is set forth in SEQ ID NO:945. The amino acid sequence of P211_A10 VL is set forth in SEQ ID NO:946. The amino acid sequence of P212_C01 VH is set forth in SEQ ID NO:947. The amino acid sequence of P212_C01 VL is set forth in SEQ ID NO:948. The amino acid sequence of P212_C08 VH is set forth in SEQ ID NO:949. The amino acid sequence of P212_C08 VL is set forth in SEQ ID NO:950. The amino acid sequence of P211_D12 VH is set forth in SEQ ID NO:951. The amino acid sequence of P211_D12 VL is set forth in SEQ ID NO:952.The amino acid sequence of the VH of P211_C07 is set forth in SEQ ID NO: 953. The amino acid sequence of the VL of P211_C07 is set forth in SEQ ID NO: 954. The amino acid sequence of the VH of P215_D06 is set forth in SEQ ID NO: 955. The amino acid sequence of the VL of P215_D06 is set forth in SEQ ID NO: 956. The amino acid sequence of the VH of P211_H09 is set forth in SEQ ID NO: 957. The amino acid sequence of the VL of P211_H09 is set forth in SEQ ID NO: 958. The amino acid sequence of the VH of P213_E05 is set forth in SEQ ID NO: 959. The amino acid sequence of the VL of P213_E05 is set forth in SEQ ID NO: 960. The amino acid sequence of the VH of P213_H03 is set forth in SEQ ID NO: 961. The amino acid sequence of the VL of P213_H03 is set forth in SEQ ID NO: 962. The amino acid sequence of the VH of P215_C01 is set forth in SEQ ID NO: 963. The amino acid sequence of the VL of P215_C01 is set forth in SEQ ID NO: 964. The amino acid sequence of the VH of P214_A10 is set forth in SEQ ID NO: 965. The amino acid sequence of the VL of P214_A10 is set forth in SEQ ID NO: 966. The amino acid sequence of the VH of P211_G09 is set forth in SEQ ID NO: 967. The amino acid sequence of the VL of P211_G09 is set forth in SEQ ID NO: 968. The amino acid sequence of the VH of P215_C07 is set forth in SEQ ID NO: 969. The amino acid sequence of the VL of P215_C07 is set forth in SEQ ID NO: 970. The amino acid sequence of the VH of P216_E06 is set forth in SEQ ID NO: 971. The amino acid sequence of the VL of P216_E06 is set forth in SEQ ID NO: 972. The amino acid sequence of the VH of P216_H01 is set forth in SEQ ID NO: 973. The amino acid sequence of the VL of P216_H01 is set forth in SEQ ID NO: 974. The amino acid sequence of the VH of P215_E11 is set forth in SEQ ID NO: 975. The amino acid sequence of the VL of P215_E11 is set forth in SEQ ID NO: 976. The amino acid sequence of the VH of P215_A07 is set forth in SEQ ID NO: 977. The amino acid sequence of the VL of P215_A07 is set forth in SEQ ID NO: 978. The amino acid sequence of the VH of D2M002-101 is set forth in SEQ ID NO: 979. The amino acid sequence of the VL of D2M002-101 is set forth in SEQ ID NO: 980.The amino acid sequence of the VH of D2M002-101 is set forth in SEQ ID NO: 979. The amino acid sequence of the VL of D2M002-101 is set forth in SEQ ID NO: 980, 981, 982, 983 or 984. The amino acid sequence of the VH of D2M002-102 is set forth in SEQ ID NO: 985. The amino acid sequence of the VL of D2M002-102 is set forth in SEQ ID NO: 986. The amino acid sequence of the VH of D2M002-103 is set forth in SEQ ID NO: 987. The amino acid sequence of the VL of D2M002-103 is set forth in SEQ ID NO: 988, 989, 990, 991 or 992. The amino acid sequence of the VH of D2M002-104 is set forth in SEQ ID NO: 993. The amino acid sequence of the VL of D2M002-104 is set forth in SEQ ID NO: 994. The amino acid sequence of the VH of D2M002-105 is set forth in SEQ ID NO: 995. The amino acid sequence of the VL of D2M002-105 is set forth in SEQ ID NO: 996. The amino acid sequence of the VH of D2M002-106 is set forth in SEQ ID NO: 997. The amino acid sequence of the VL of D2M002-106 is set forth in SEQ ID NO: 998. The amino acid sequence of the VH of D2M002-107 is set forth in SEQ ID NO: 999. The amino acid sequence of the VL of D2M002-107 is set forth in SEQ ID NO: 1000, 1001, 1002, 1003 or 1004. The amino acid sequence of the VH of D2M002-108 is set forth in SEQ ID NO: 1005. The amino acid sequence of the VL of D2M002-108 is set forth in SEQ ID NO: 1006. The amino acid sequence of the VH of D2M002-109 is set forth in SEQ ID NO: 1007. The amino acid sequence of the VL of D2M002-109 is set forth in SEQ ID NO: 1008, 1009 or 1010.

[0328] The amino acid sequence of the VH of D2M002-110 is set forth in SEQ ID NO: 1011. The amino acid sequence of the VL of D2M002-110 is set forth in SEQ ID NO: 1012. The amino acid sequence of the VH of D2M002-111 is set forth in SEQ ID NO: 1013. The amino acid sequence of the VL of D2M002-111 is set forth in SEQ ID NO: 1014. The amino acid sequence of the VH of D2M002-112 is set forth in SEQ ID NO: 1015. The amino acid sequence of the VL of D2M002-112 is set forth in SEQ ID NO: 1016. The amino acid sequence of the VH of D2M002-113 is set forth in SEQ ID NO: 1017. The amino acid sequence of the VL of D2M002-113 is set forth in SEQ ID NO: 1018. The amino acid sequence of D2M002-114 VH is set forth in SEQ ID NO: 1019. The amino acid sequence of D2M002-114 VL is set forth in SEQ ID NO: 1020. The amino acid sequence of D2M002-115 VH is set forth in SEQ ID NO: 1021. The amino acid sequence of D2M002-115 VL is set forth in SEQ ID NO: 1022. The amino acid sequence of D2M002-116 VH is set forth in SEQ ID NO: 1023. The amino acid sequence of D2M002-116 VL is set forth in SEQ ID NO: 1024. The amino acid sequence of D2M002-117 VH is set forth in SEQ ID NO: 1025. The amino acid sequence of D2M002-117 VL is set forth in SEQ ID NO: 1026. The amino acid sequence of D2M002-118 VH is set forth in SEQ ID NO: 1027. The amino acid sequence of D2M002-118 VL is set forth in SEQ ID NO: 1028. The amino acid sequence of D2M002-119 VH is set forth in SEQ ID NO: 1029. The amino acid sequence of D2M002-119 VL is set forth in SEQ ID NO: 1030. The amino acid sequence of D2M002-120 VH is set forth in SEQ ID NO: 1031. The amino acid sequence of D2M002-120 VL is set forth in SEQ ID NO: 1032. The amino acid sequence of D2M002-121 VH is set forth in SEQ ID NO: 1033. The amino acid sequence of D2M002-121 VL is set forth in SEQ ID NO: 1034. The amino acid sequence of the VH of D2M002-122 is set forth in SEQ ID NO: 1035. The amino acid sequence of the VL of D2M002-122 is set forth in SEQ ID NO:1036.The amino acid sequence of the VH of D2M002-123 is set forth in SEQ ID NO: 1037. The amino acid sequence of the VL of D2M002-123 is set forth in SEQ ID NO: 1038. The amino acid sequence of the VH of D2M002-124 is set forth in SEQ ID NO: 1039. The amino acid sequence of the VL of D2M002-124 is set forth in SEQ ID NO: 1040. The amino acid sequence of the VH of D2M002-125 is set forth in SEQ ID NO: 1041. The amino acid sequence of the VL of D2M002-125 is set forth in SEQ ID NO: 1042. The amino acid sequence of the VH of D2M002-126 is set forth in SEQ ID NO: 1043. The amino acid sequence of the VL of D2M002-126 is set forth in SEQ ID NO: 1044. The amino acid sequence of the VH of D2M002-127 is set forth in SEQ ID NO: 1045. The amino acid sequence of the VL of D2M002-127 is set forth in SEQ ID NO: 1046. The amino acid sequence of the VH of D2M002-128 is set forth in SEQ ID NO: 1047. The amino acid sequence of the VL of D2M002-128 is set forth in SEQ ID NO: 1048. The amino acid sequence of the VH of D2M002-129 is set forth in SEQ ID NO: 1049. The amino acid sequence of the VL of D2M002-129 is set forth in SEQ ID NO: 1050. The amino acid sequence of the VH of D2M002-130 is set forth in SEQ ID NO: 1051. The amino acid sequence of the VL of D2M002-130 is set forth in SEQ ID NO: 1052. The amino acid sequence of the VH of D2M002-131 is set forth in SEQ ID NO: 1053. The amino acid sequence of the VL of D2M002-131 is set forth in SEQ ID NO: 1054. The amino acid sequence of the VH of D2M002-132 is set forth in SEQ ID NO: 1055. The amino acid sequence of the VL of D2M002-132 is set forth in SEQ ID NO: 1056.

[0329] The amino acid sequence of D2M002-103HV1 ​​VH is set forth in SEQ ID NO: 1687. The amino acid sequence of D2M002-103HV1 ​​VL is set forth in SEQ ID NO: 988. The amino acid sequence of D2M002-103HV2 VH is set forth in SEQ ID NO: 1688. The amino acid sequence of D2M002-103HV2 VL is set forth in SEQ ID NO: 988. The amino acid sequence of D2M002-103LV1 VH is set forth in SEQ ID NO: 987. The amino acid sequence of D2M002-103LV1 VL is set forth in SEQ ID NO: 989. The amino acid sequence of D2M002-103LV3 VH is set forth in SEQ ID NO: 987. The amino acid sequence of D2M002-103LV3 VL is set forth in SEQ ID NO: 990. The amino acid sequence of the VH of D2M002-103LV4 is set forth in SEQ ID NO: 987. The amino acid sequence of the VL of D2M002-103LV4 is set forth in SEQ ID NO: 991. The amino acid sequence of the VH of D2M002-103LV5 is set forth in SEQ ID NO: 987. The amino acid sequence of the VL of D2M002-103LV5 is set forth in SEQ ID NO: 992. The amino acid sequence of the VH of D2M002-126LV1 is set forth in SEQ ID NO: 1043. The amino acid sequence of the VL of D2M002-126LV1 is set forth in SEQ ID NO: 1689. The amino acid sequence of the VH of D2M002-126LV2 is set forth in SEQ ID NO: 1043. The amino acid sequence of the VL of D2M002-126LV2 is set forth in SEQ ID NO: 1690.

[0330] Any of these heavy chain variable region sequences (SEQ ID NOs: 751, 753, 755, 757, 759, 761, 763, 765, 767, 769, 771, 773, 775, 777, 779, 781, 783, 785, 787, 789, 791, 793, 795, 797, 799, 841, 843, 845, 847, 849, 851, 853, 855, 857, 859, 861, 863, 865, 867, 869, 871, 873, 875, 877, 879, 881, 883, 885, 887, 889, 891, 893, 895, 897, 899, 901, 903, 905, 907, 909, 911, 913, 915, 917, 919, 921, 923, 925, 927, 929,931,933,935,937,939,941,943,945,947,949,951,953,955,957,959,961,963,965,967,969,971,973,975,977,979,985,987,993,995,997,999,1005,1007,1008 1014, 1016, 1018, 1021, 1023, 1025, 1027, 1029, 1031, 1033, 1035, 1037, 1039, 1041, 1043, 1045, 1047, 1049, 1051, 1053, 1055, 1067 or 1068) can be used with these light chain variable region sequences (SEQ ID NO: 752, 754, 756, 758, 760, 762, 764, 766, 768, 770, 772, 774, 776, 778, 780, 782, 784, 786, 788, 790, 792, 794, 796, 798, 800 , 842, 844, 846, 848, 850, 852, 854, 856, 858, 860, 862, 864, 866, 868, 870, 872, 874, 876, 878, 880, 882, 884, 886, 888, 890, 89 2,894,896,898,900,902,904,906,908,910,912,914,916,918,920,922,924,926,928,930,932,934,936,938,940,942,944,946,948,950,952,954,956,958,960,962,964,966,968,970,972,974,976,978,980,981,982,983,984,986,988,989,990, 991, 992, 994, 996, 998, 1000, 1001, 1002, 1003, 1004, 1006, 1008, 1009, 1010, 1012, 1014, 1016, 1018, 1020, 1022, 1024, 1026, 1028, 1030, 1032, 1034, 1036, 1038, 1040, 1042, 1044, 1046, 1048, 1050, 1052, 1054, 1056, 1689 or 1690).

[0331] In some embodiments, humanization percentage refers to the identity percentage of heavy chain or light chain variable region sequence compared with the human antibody sequence in the International Immunogenetics Information System (IMGT) database.The highest hit rate means that the heavy chain or light chain variable region sequence is closer to a specific species rather than other species.For example, "the highest hit rate to humans" means that the sequence is closer to humans than other species.The highest hit rate to humans and macaques means that the sequence has the same percentage identity as human sequences and macaques, and compared with the sequences of other species, these percentage identities are the highest.In some embodiments, the humanization percentage is greater than 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94% or 95%.A detailed description of how to determine the humanization percentage and how to determine the highest hit rate is known in the art, and as described in "INNs and outs of antibody non-proprietary names" by Jones, Tim D., etc. Monoclonal antibodies. Volume 8. Number 1. Taylor & Francis, 2016, which is incorporated herein by reference in its entirety. A high percentage of humanization generally has various advantages, such as being safer for humans, more effective, more likely to be tolerated by human subjects, and / or less likely to produce side effects.

[0332] In addition, in some embodiments, the antibodies or antigen-binding fragments thereof described herein may further comprise one, two or three heavy chain variable region CDRs selected from the group consisting of SEQ ID NOs: 7-9, SEQ ID NOs: 37-39, SEQ ID NOs: 67-69, SEQ ID NOs: 97-99, SEQ ID NOs: 127-129, SEQ ID NOs: 157-159, SEQ ID NOs: 187-189, SEQ ID NOs: 217-219, SEQ ID NOs: 247-249, SEQ ID NOs: 277-279, SEQ ID NOs: 307-309, SEQ ID NOs: 337-339, SEQ ID NOs: 367-369, SEQ ID NOs: 397-399, SEQ ID NOs: 427-429, SEQ ID NOs: 457-459, SEQ ID NOs: 487-489, SEQ ID NOs: 508-511, 512-513, 514-515, 515-516, 517-518, 519-520, 521-527, 528-529, 530-531 NOs: 517-519, SEQ ID NOs: 547-549, SEQ ID NOs: 577-579, SEQ ID NOs: 607-609, SEQ ID NOs: 637-639, SEQ ID NOs: 667-669, SEQ ID NOs: 697-699, SEQ ID NOs: 727-729, SEQ ID NOs: 1069-1071, SEQ ID NOs: 1093-1095, SEQ ID NOs: 1117-1119, SEQ ID NOs: 1141-1143, SEQ ID NOs: 1165-1167, SEQ ID NOs: 1189-1191, SEQ ID NOs: 1213-1215, SEQ ID NOs: 1237-1239, SEQ ID NOs: 1261-1263, SEQ ID NOs: 1285-1287, SEQ ID NOs: 1309-1311, SEQ ID NOs: 1333-1335, SEQ ID NOs: 1357-1359, SEQ ID NOs: 1381-1383, SEQ ID NOs: 1405-1407, SEQ ID NOs: 1429-1431, SEQ ID NOs: 1453-1455, SEQ ID NOs: 1477-1479, SEQ ID NOs: 1501-1503, SEQ ID NOs: 1525-1527, SEQ ID NOs: 1549-1551, SEQ ID NOs: 1573-1575, SEQ ID NOs: 1597-1599,SEQ ID NOs: 1621-1623, SEQ ID NOs: 1645-1647, SEQ ID NOs: 1669-1671; and / or one, two or three light chain variable region CDRs selected from the following group: 10-12, SEQ ID NOs: 40-42, SEQ ID NOs: 70-72, SEQ ID NOs: 100-102, SEQ ID NOs: 130-132, SEQ ID NOs: 160-162, SEQ ID NOs: 190-192, SEQ ID NOs: 220-222, SEQ ID NOs: 250-252, SEQ ID NOs: 280-282, SEQ ID NOs: 310-312, SEQ ID NOs: 340-342, SEQ ID NOs: 370-372, SEQ ID NOs: 400-402, SEQ ID NOs: 430-432, SEQ ID NOs: 460-462, SEQ ID NOs: 490-492, SEQ ID NOs: 520-522, SEQ ID NOs: 550-552, SEQ ID NOs: 580-582, SEQ ID NOs: 610-612, SEQ ID NOs: 640-642, SEQ ID NOs: 670-672, SEQ ID NOs: 700-702, SEQ ID NOs: 730-732, SEQ ID NOs: 1072-1074, SEQ ID NOs: 1096-1098, SEQ ID NOs: 1120-1122, SEQ ID NOs: 1144-1146, SEQ ID NOs: 1168-1170, SEQ ID NOs: 1192-1194, SEQ ID NOs: 1216-1218, SEQ ID NOs: 1240-1242, SEQ ID NOs: 1264-1266, SEQ ID NOs: 1288-1290, SEQ ID NOs: 1312-1314, SEQ ID NOs: 1336-1338, SEQ ID NOs: 1360-1362, SEQ ID NOs: 1384-1386, SEQ ID NOs: 1408-1410, SEQ ID NOs: 1432-1434, SEQ ID NOs: 1456-1458, SEQ ID NOs: 1480-1482, SEQ ID NOs: 1504-1506, SEQ ID NOs: 1528-1530, SEQID NOs: 1552-1554,SEQ ID NOs: 1576-1578, SEQ ID NOs: 1600-1602, SEQ ID NOs: 1624-1636, SEQ ID NOs: 1648-1650 and SEQ ID NOs: 1672-1674. In some embodiments, the antibodies or antigen-binding fragments thereof described herein may further comprise one, two or three heavy chain variable region CDRs under the Chothia, IMGT, North or Aho numbering schemes as shown in Figures 14, 42 and 43; and / or one, two or three light chain variable region CDRs as shown in Figures 14, 42, 43 using the Chothia, IMGT, North or Aho numbering schemes. ,

[0333] In some embodiments, the antibody can have a heavy chain variable region (VH) comprising complementarity determining regions (CDRs) 1, 2, 3, wherein the CDR1 region comprises or consists of an amino acid sequence that is at least 80%, 85%, 90% or 95% identical to a selected VH CDR1 amino acid sequence, the CDR2 region comprises or consists of an amino acid sequence that is at least 80%, 85%, 90% or 95% identical to a selected VH CDR2 amino acid sequence, and the CDR3 region comprises or consists of an amino acid sequence that is at least 80%, 85%, 90% or 95% identical to a selected VH CDR3 amino acid sequence, and a light chain variable region (VL) comprising CDRs 1, 2, 3, wherein the CDR1 region comprises or consists of an amino acid sequence that is at least 80%, 85%, 90% or 95% identical to a selected VL CDR1 amino acid sequence, the CDR2 region comprises or consists of an amino acid sequence that is at least 80%, 85%, 90% or 95% identical to a selected VL CDR2 amino acid sequence. The CDR2 amino acid sequence is composed of at least 80%, 85%, 90% or 95% identical amino acid sequence, and the CDR3 region comprises or consists of at least 80% amino acid sequence, 85%, 90% or 95% identical to the selected VL CDR3 amino acid sequence. The selected VH CDRs1, 2, 3 amino acid sequences and the selected VL CDRs, 1, 2, 3 amino acid sequences are shown in Figures 14, 42 and 43.

[0334] In some embodiments, the antibodies or antigen-binding fragments described herein may comprise a heavy chain variable domain comprising one, two or three of the VH CDR1s shown in Figures 14, 42 and 43, which have zero, one or two amino acid insertions, deletions or substitutions; any of the VH CDR2s shown in Figure 14, Figures 42 and 43 have zero, one or two amino acid insertions, deletions or substitutions; any of the VH CDR3s shown in Figures 14, 42 and 43 have zero, one or two amino acid insertions, deletions or substitutions. For example, the D2M002-001 antibody or antigen-binding fragment described herein may comprise a heavy chain variable domain comprising one, two or three CDRs of SEQ ID NO: 7 with zero, one or two amino acid insertions, deletions or substitutions; SEQ ID NO: 8 with zero, one or two amino acid insertions, deletions or substitutions; SEQ ID NO: 9 with zero, one or two amino acid insertions, deletions or substitutions.

[0335] In some embodiments, the antibodies or antigen-binding fragments described herein may comprise a light chain variable domain comprising one, two or three of the VL CDR1s shown in Figures 14, 42 and 43, with zero, one or two amino acid insertions, deletions or substitutions; any of the VL CDR2s shown in Figure 14, Figures 42 and 43 with zero, one or two amino acid insertions, deletions or substitutions; any of the VL CDR3s shown in Figures 14, 42 and 43 with zero, one or two amino acid insertions, deletions or substitutions. In some embodiments, the D2M002-001 antibodies or antigen-binding fragments described herein may comprise one, two or three CDRs of SEQ ID NO: 10, with zero, one or two amino acid insertions, deletions or substitutions; SEQ ID NO: 11, with zero, one or two amino acid insertions, deletions or substitutions; SEQ ID NO: 12, with zero, one or two amino acid insertions, deletions or substitutions.

[0336] Insertions, deletions and substitutions may be within the CDR sequence or located at one or both ends of the CDR sequence.

[0337] The present disclosure also provides antibodies or antigen-binding fragments thereof that bind to LILRB1 and / or LILRB2. The antibodies or antigen-binding fragments thereof comprise a heavy chain variable region (VH) that includes or consists of an amino acid sequence that is at least 80%, 85%, 90% or 95% identical to a selected VH sequence, and a light chain variable region (VL) that includes or consists of an amino acid sequence that is at least 80%, 85%, 90% or 95% identical to a selected VL sequence. In some embodiments, the selected VH sequence is SEQ ID NO: 751, 753, 755, 757, 759, 761, 763, 765, 767, 769, 771, 773, 775, 777, 779, 781, 783, 785, 787, 789, 791, 793, 795, 797, 799, 841, 843, 845, 847, 851, 853, 855, 857 ,859,861,863,865,867,869,871,873,875,877,879,881,883,885,887,889,891,893,895,897,899,901,903,905,907,909,911,913,915,917,919,921,923,92 5,927,929,931,933,935,937,939,941,943,945,947,949,951,953,955,957,959,961,963,965,967,969,971,973,975,977,979,985,987,993,995,997,999, 1005, 1007, 1011, 1013, 1015, 1017, 1019, 1021, 1023, 1025, 1027, 1029, 1031, 1033, 1035, 1037, 1039, 1041, 1043, 1045, 1047, 1049, 1051, 1053, 1055, 1067 or 1068.In some embodiments, the selected VL sequence is 752, 754, 756, 758, 760, 762, 764, 766, 768, 770, 772, 774, 776, 778, 780, 782, 784, 786, 788, 790, 792, 794, 796, 798, 800, 842, 844, 846, 848, 850, 852, 854, 856, 858, 8 60, 862, 864, 866, 868, 870, 872, 874, 876, 878, 880, 882, 884, 886, 888, 890, 892, 894, 896, 898, 900, 902, 904, 906, 908, 910, 912, 914, 916, 918, 920, 922, 924, 926, 928, 930, 932, 934, 936, 938,940,942,944,946,948,950,952,954,956,958,960,962,964,966,968,970,972,974,976,978,980,981,982,983,984,986,988,989,990,991,992,994,996,998,1000,1001,1002, In some embodiments, the selected VH sequence is SEQ ID NO: 751 and the selected VL sequence is SEQ ID NO: 752. In some embodiments, the selected VH sequence is SEQ ID NO: 753 and the selected VL sequence is SEQ ID NO: 754. In some embodiments, the selected VH sequence is SEQ ID NO: 755 and the selected VL sequence is SEQ ID NO: 756. In some embodiments, the selected VH sequence is SEQ ID NO: 757 and the selected VL sequence is SEQ ID NO: 758. In some embodiments, the selected VH sequence is SEQ ID NO: 759 and the selected VL sequence is SEQ ID NO: 760. In some embodiments, the selected VH sequence is SEQ ID NO: 761 and the selected VL sequence is SEQ ID NO: 762. In some embodiments, the selected VH sequence is SEQ ID NO: 763 and the selected VL sequence is SEQ ID NO: 764.In some embodiments, the selected VH sequence is SEQ ID NO: 765 and the selected VL sequence is SEQ ID NO: 766. In some embodiments, the selected VH sequence is SEQ ID NO: 767 and the selected VL sequence is SEQ ID NO: 768. In some embodiments, the selected VH sequence is SEQ ID NO: 769 and the selected VL sequence is SEQ ID NO: 770. In some embodiments, the selected VH sequence is SEQ ID NO: 771 and the selected VL sequence is SEQ ID NO: 772. In some embodiments, the selected VH sequence is SEQ ID NO: 773 and the selected VL sequence is SEQ ID NO: 774. In some embodiments, the selected VH sequence is SEQ ID NO: 775 and the selected VL sequence is SEQ ID NO: 776. In some embodiments, the selected VH sequence is SEQ ID NO: 777 and the selected VL sequence is SEQ ID NO: 778. In some embodiments, the selected VH sequence is SEQ ID NO: 779 and the selected VL sequence is SEQ ID NO: 780. In some embodiments, the selected VH sequence is SEQ ID NO: 781 and the selected VL sequence is SEQ ID NO: 782. In some embodiments, the selected VH sequence is SEQ ID NO: 783 and the selected VL sequence is SEQ ID NO: 784. In some embodiments, the selected VH sequence is SEQ ID NO: 785 and the selected VL sequence is SEQ ID NO: 786. In some embodiments, the selected VH sequence is SEQ ID NO: 787 and the selected VL sequence is SEQ ID NO: 788. In some embodiments, the selected VH sequence is SEQ ID NO: 789 and the selected VL sequence is SEQ ID NO: 790. In some embodiments, the selected VH sequence is SEQ ID NO: 791 and the selected VL sequence is SEQ ID NO: 792. In some embodiments, the selected VH sequence is SEQ ID NO: 793 and the selected VL sequence is SEQ ID NO: 794. In some embodiments, the selected VH sequence is SEQ ID NO: 795 and the selected VL sequence is SEQ ID NO: 796. In some embodiments, the selected VH sequence is SEQ ID NO: 797 and the selected VL sequence is SEQ ID NO: 798. In some embodiments, the selected VH sequence is SEQ ID NO: 799 and the selected VL sequence is SEQ ID NO: 800. In some embodiments, the selected VH sequence is SEQ ID NO: 841 and the selected VL sequence is SEQ ID NO: 842.In some embodiments, the selected VH sequence is SEQ ID NO: 843 and the selected VL sequence is SEQ ID NO: 844. In some embodiments, the selected VH sequence is SEQ ID NO: 845 and the selected VL sequence is SEQ ID NO: 846. In some embodiments, the selected VH sequence is SEQ ID NO: 847 and the selected VL sequence is SEQ ID NO: 848. In some embodiments, the selected VH sequence is SEQ ID NO: 849 and the selected VL sequence is SEQ ID NO: 850. In some embodiments, the selected VH sequence is SEQ ID NO: 851 and the selected VL sequence is SEQ ID NO: 852. In some embodiments, the selected VH sequence is SEQ ID NO: 853 and the selected VL sequence is SEQ ID NO: 854. In some embodiments, the selected VH sequence is SEQ ID NO: 855 and the selected VL sequence is SEQ ID NO: 856. In some embodiments, the selected VH sequence is SEQ ID NO: 857 and the selected VL sequence is SEQ ID NO: 858. In some embodiments, the selected VH sequence is SEQ ID NO: 859 and the selected VL sequence is SEQ ID NO: 860. In some embodiments, the selected VH sequence is SEQ ID NO: 861 and the selected VL sequence is SEQ ID NO: 862. In some embodiments, the selected VH sequence is SEQ ID NO: 863 and the selected VL sequence is SEQ ID NO: 864. In some embodiments, the selected VH sequence is SEQ ID NO: 865 and the selected VL sequence is SEQ ID NO: 866. In some embodiments, the selected VH sequence is SEQ ID NO: 867 and the selected VL sequence is SEQ ID NO: 868. In some embodiments, the selected VH sequence is SEQ ID NO: 869 and the selected VL sequence is SEQ ID NO: 870. In some embodiments, the selected VH sequence is SEQ ID NO: 871 and the selected VL sequence is SEQ ID NO: 872. In some embodiments, the selected VH sequence is SEQ ID NO: 873 and the selected VL sequence is SEQ ID NO: 874. In some embodiments, the selected VH sequence is SEQ ID NO: 875 and the selected VL sequence is SEQ ID NO: 876. In some embodiments, the selected VH sequence is SEQ ID NO: 877 and the selected VL sequence is SEQ ID NO: 878. In some embodiments, the selected VH sequence is SEQ ID NO: 879 and the selected VL sequence is SEQ ID NO: 880.In some embodiments, the selected VH sequence is SEQ ID NO: 881 and the selected VL sequence is SEQ ID NO: 882. In some embodiments, the selected VH sequence is SEQ ID NO: 883 and the selected VL sequence is SEQ ID NO: 884. In some embodiments, the selected VH sequence is SEQ ID NO: 885 and the selected VL sequence is SEQ ID NO: 886. In some embodiments, the selected VH sequence is SEQ ID NO: 887 and the selected VL sequence is SEQ ID NO: 888. In some embodiments, the selected VH sequence is SEQ ID NO: 889 and the selected VL sequence is SEQ ID NO: 890. In some embodiments, the selected VH sequence is SEQ ID NO: 891 and the selected VL sequence is SEQ ID NO: 892. In some embodiments, the selected VH sequence is SEQ ID NO: 893 and the selected VL sequence is SEQ ID NO: 894. In some embodiments, the selected VH sequence is SEQ ID NO: 895 and the selected VL sequence is SEQ ID NO: 896. In some embodiments, the selected VH sequence is SEQ ID NO: 897 and the selected VL sequence is SEQ ID NO: 898. In some embodiments, the selected VH sequence is SEQ ID NO: 899 and the selected VL sequence is SEQ ID NO: 900. In some embodiments, the selected VH sequence is SEQ ID NO: 901 and the selected VL sequence is SEQ ID NO: 902. In some embodiments, the selected VH sequence is SEQ ID NO: 903 and the selected VL sequence is SEQ ID NO: 904. In some embodiments, the selected VH sequence is SEQ ID NO: 905 and the selected VL sequence is SEQ ID NO: 906. In some embodiments, the selected VH sequence is SEQ ID NO: 907 and the selected VL sequence is SEQ ID NO: 908. In some embodiments, the selected VH sequence is SEQ ID NO: 909 and the selected VL sequence is SEQ ID NO: 910. In some embodiments, the selected VH sequence is SEQ ID NO: 911 and the selected VL sequence is SEQ ID NO: 912. In some embodiments, the selected VH sequence is SEQ ID NO: 913 and the selected VL sequence is SEQ ID NO: 914. In some embodiments, the selected VH sequence is SEQ ID NO: 915 and the selected VL sequence is SEQ ID NO: 916. In some embodiments, the selected VH sequence is SEQ ID NO: 917 and the selected VL sequence is SEQ ID NO: 918.In some embodiments, the selected VH sequence is SEQ ID NO: 919 and the selected VL sequence is SEQ ID NO: 920. In some embodiments, the selected VH sequence is SEQ ID NO: 921 and the selected VL sequence is SEQ ID NO: 922. In some embodiments, the selected VH sequence is SEQ ID NO: 923 and the selected VL sequence is SEQ ID NO: 924. In some embodiments, the selected VH sequence is SEQ ID NO: 925 and the selected VL sequence is SEQ ID NO: 926. In some embodiments, the selected VH sequence is SEQ ID NO: 927 and the selected VL sequence is SEQ ID NO: 928. In some embodiments, the selected VH sequence is SEQ ID NO: 929 and the selected VL sequence is SEQ ID NO: 930. In some embodiments, the selected VH sequence is SEQ ID NO: 931 and the selected VL sequence is SEQ ID NO: 932. In some embodiments, the selected VH sequence is SEQ ID NO: 933 and the selected VL sequence is SEQ ID NO: 934. In some embodiments, the selected VH sequence is SEQ ID NO: 935 and the selected VL sequence is SEQ ID NO: 936. In some embodiments, the selected VH sequence is SEQ ID NO: 937 and the selected VL sequence is SEQ ID NO: 938. In some embodiments, the selected VH sequence is SEQ ID NO: 939 and the selected VL sequence is SEQ ID NO: 940. In some embodiments, the selected VH sequence is SEQ ID NO: 941 and the selected VL sequence is SEQ ID NO: 942. In some embodiments, the selected VH sequence is SEQ ID NO: 943 and the selected VL sequence is SEQ ID NO: 944. In some embodiments, the selected VH sequence is SEQ ID NO: 945 and the selected VL sequence is SEQ ID NO: 946. In some embodiments, the selected VH sequence is SEQ ID NO: 947 and the selected VL sequence is SEQ ID NO: 948. In some embodiments, the selected VH sequence is SEQ ID NO: 949 and the selected VL sequence is SEQ ID NO: 950. In some embodiments, the selected VH sequence is SEQ ID NO: 951 and the selected VL sequence is SEQ ID NO: 952. In some embodiments, the selected VH sequence is SEQ ID NO: 953 and the selected VL sequence is SEQ ID NO: 954. In some embodiments, the selected VH sequence is SEQ ID NO: 955 and the selected VL sequence is SEQ ID NO: 956.In some embodiments, the selected VH sequence is SEQ ID NO: 957 and the selected VL sequence is SEQ ID NO: 958. In some embodiments, the selected VH sequence is SEQ ID NO: 959 and the selected VL sequence is SEQ ID NO: 960. In some embodiments, the selected VH sequence is SEQ ID NO: 961 and the selected VL sequence is SEQ ID NO: 962. In some embodiments, the selected VH sequence is SEQ ID NO: 963 and the selected VL sequence is SEQ ID NO: 964. In some embodiments, the selected VH sequence is SEQ ID NO: 965 and the selected VL sequence is SEQ ID NO: 966. In some embodiments, the selected VH sequence is SEQ ID NO: 967 and the selected VL sequence is SEQ ID NO: 968. In some embodiments, the selected VH sequence is SEQ ID NO: 969 and the selected VL sequence is SEQ ID NO: 970. In some embodiments, the selected VH sequence is SEQ ID NO: 971 and the selected VL sequence is SEQ ID NO: 972. In some embodiments, the selected VH sequence is SEQ ID NO: 973 and the selected VL sequence is SEQ ID NO: 974. In some embodiments, the selected VH sequence is SEQ ID NO: 975 and the selected VL sequence is SEQ ID NO: 976. In some embodiments, the selected VH sequence is SEQ ID NO: 977 and the selected VL sequence is SEQ ID NO: 978. In some embodiments, the selected VH sequence is SEQ ID NO: 979 and the selected VL sequence is SEQ ID NO: 980, 981, 982, 983 or 984. In some embodiments, the selected VH sequence is SEQ ID NO: 985 and the selected VL sequence is SEQ ID NO: 986. In some embodiments, the selected VH sequence is SEQ ID NO: 987, 1687 or 1688 and the selected VL sequence is SEQ ID NO: 988, 989, 990, 991, 992. In some embodiments, the selected VH sequence is SEQ ID NO: 987 and the selected VL sequence is SEQ ID NO: 988. In some embodiments, the selected VH sequence is SEQ ID NO: 1687 and the selected VL sequence is SEQ ID NO: 988. In some embodiments, the selected VH sequence is SEQ ID NO: 1688 and the selected VL sequence is SEQ ID NO: 988. In some embodiments, the selected VH sequence is SEQ ID NO: 987 and the selected VL sequence is SEQ ID NO: 989.In some embodiments, the selected VH sequence is SEQ ID NO: 987 and the selected VL sequence is SEQ ID NO: 990. In some embodiments, the selected VH sequence is SEQ ID NO: 987 and the selected VL sequence is SEQ ID NO: 991. In some embodiments, the selected VH sequence is SEQ ID NO: 987 and the selected VL sequence is SEQ ID NO: 992. In some embodiments, the selected VH sequence is SEQ ID NO: 993 and the selected VL sequence is SEQ ID NO: 994. In some embodiments, the selected VH sequence is SEQ ID NO: 995 and the selected VL sequence is SEQ ID NO: 996. In some embodiments, the selected VH sequence is SEQ ID NO: 997 and the selected VL sequence is SEQ ID NO: 998. In some embodiments, the selected VH sequence is SEQ ID NO: 999 and the selected VL sequence is SEQ ID NO: 1000, 1001, 1002, 1003, or 1004. In some embodiments, the selected VH sequence is SEQ ID NO: 1005 and the selected VL sequence is SEQ ID NO: 1006. In some embodiments, the selected VH sequence is SEQ ID NO: 1007 and the selected VL sequence is SEQ ID NO: 1008, 1009 or 1010. In some embodiments, the selected VH sequence is SEQ ID NO: 1011 and the selected VL sequence is SEQ ID NO: 1012. In some embodiments, the selected VH sequence is SEQ ID NO: 1013 and the selected VL sequence is SEQ ID NO: 1014. In some embodiments, the selected VH sequence is SEQ ID NO: 1015 and the selected VL sequence is SEQ ID NO: 1016. In some embodiments, the selected VH sequence is SEQ ID NO: 1017 and the selected VL sequence is SEQ ID NO: 1018. In some embodiments, the selected VH sequence is SEQ ID NO: 1019 and the selected VL sequence is SEQ ID NO: 1020. In some embodiments, the selected VH sequence is SEQ ID NO: 1021 and the selected VL sequence is SEQ ID NO: 1022. In some embodiments, the selected VH sequence is SEQ ID NO: 1023 and the selected VL sequence is SEQ ID NO: 1024. In some embodiments, the selected VH sequence is SEQ ID NO: 1025 and the selected VL sequence is SEQ ID NO: 1026. In some embodiments, the selected VH sequence is SEQ ID NO: 1027 and the selected VL sequence is SEQ ID NO: 1028.In some embodiments, the selected VH sequence is SEQ ID NO: 1029 and the selected VL sequence is SEQ ID NO: 1030. In some embodiments, the selected VH sequence is SEQ ID NO: 1031 and the selected VL sequence is SEQ ID NO: 1032. In some embodiments, the selected VH sequence is SEQ ID NO: 1033 and the selected VL sequence is SEQ ID NO: 1034. In some embodiments, the selected VH sequence is SEQ ID NO: 1035 and the selected VL sequence is SEQ ID NO: 1036. In some embodiments, the selected VH sequence is SEQ ID NO: 1037 and the selected VL sequence is SEQ ID NO: 1038. In some embodiments, the selected VH sequence is SEQ ID NO: 1039 and the selected VL sequence is SEQ ID NO: 1040. In some embodiments, the selected VH sequence is SEQ ID NO: 1041 and the selected VL sequence is SEQ ID NO: 1042. In some embodiments, the selected VH sequence is SEQ ID NO: 1043 and the selected VL sequence is SEQ ID NO: 1044, 1689 or 1690. In some embodiments, the selected VH sequence is SEQ ID NO: 1043 and the selected VL sequence is SEQ ID NO: 1044. In some embodiments, the selected VH sequence is SEQ ID NO: 1043 and the selected VL sequence is SEQ ID NO: 1689. In some embodiments, the selected VH sequence is SEQ ID NO: 1043 and the selected VL sequence is SEQ ID NO: 1690. In some embodiments, the selected VH sequence is SEQ ID NO: 1045 and the selected VL sequence is SEQ ID NO: 1046. In some embodiments, the selected VH sequence is SEQ ID NO: 1047 and the selected VL sequence is SEQ ID NO: 1048. In some embodiments, the selected VH sequence is SEQ ID NO: 1049 and the selected VL sequence is SEQ ID NO: 1050. In some embodiments, the selected VH sequence is SEQ ID NO: 1051 and the selected VL sequence is SEQ ID NO: 1052. In some embodiments, the selected VH sequence is SEQ ID NO: 1053 and the selected VL sequence is SEQ ID NO: 1054. In some embodiments, the selected VH sequence is SEQ ID NO: 1055 and the selected VL sequence is SEQ ID NO: 1056.

[0338] The present disclosure also provides antibodies or antigen-binding fragments thereof that bind to LILRB1 and / or LILRB2. The antibody or antigen-binding fragment thereof comprises a heavy chain comprising or consisting of an amino acid sequence that is at least 80%, 85%, 90% or 95% identical to a selected heavy chain sequence, and a light chain comprising or consisting of an amino acid sequence that is at least 80%, 85%, 90% or 95% identical to a selected light chain sequence. In some embodiments, the selected heavy chain is SEQ ID NO: 1691 and the selected light chain is SEQ ID NO: 1692. In some embodiments, the selected heavy chain is SEQ ID NO: 1693 and the selected light chain is SEQ ID NO: 1692. In some embodiments, the selected heavy chain is SEQ ID NO: 1694 and the selected light chain is SEQ ID NO: 1695.

[0339] In order to determine the percentage identity of two amino acid sequences or two nucleic acid sequences, it is necessary to align the sequences for optimal comparison purposes (e.g., gaps can be introduced in one or both of the first and second amino acid or nucleic acid sequences to achieve optimal alignment, and non-homologous sequences can be ignored for comparison). The amino acid residues or nucleotides at the corresponding amino acid positions or nucleotide positions are then compared. When the position in the first sequence is occupied by the same amino acid residue or nucleotide as the corresponding position in the second sequence, the molecules are identical at that position. The percentage identity between the two sequences is a function of the number of identical positions shared by the sequences, taking into account the number of gaps and the length of each gap, and these values ​​need to be introduced to achieve optimal alignment of the two sequences. For purposes of the present disclosure, the comparison of sequences and the determination of the percentage identity between the two sequences can be achieved using the Blossum 62 scoring matrix, with a gap penalty of 12, a gap extension penalty of 4, and a frameshift gap penalty of 5.

[0340] The present disclosure also provides a polynucleotide comprising a polynucleotide, a polypeptide encoding a polypeptide, a nucleic acid comprising an immunoglobulin heavy chain or an immunoglobulin heavy chain. The immunoglobulin heavy chain or the immunoglobulin light chain comprises a CDR (under Kabat, Chothia, IMGT, North or Aho numbering) as shown in Figures 14, 42 and 43, or has a sequence as shown in Figures 15, 44 and 45. When the polypeptide is paired with a corresponding polypeptide (e.g., a corresponding heavy chain variable region or a corresponding light chain variable region), the paired polypeptide binds to LILRB1 (e.g., human LILRB1) and / or LILRB2 (e.g., human LILRB2).

[0341] Anti-LILRB1 / 2 antibodies and antigen-binding fragments may also be antibody variants (including derivatives and conjugates) and multispecific (e.g., bispecific) antibodies or antibody fragments thereof. Additional antibodies provided herein are polyclonal antibodies, monoclonal antibodies, multispecific antibodies (polymers, e.g., bispecific), human antibodies, chimeric antibodies (e.g., human-mouse chimeras), single-chain antibodies, antibodies produced intracellularly (i.e., in vivo antibodies), and antigen-binding fragments thereof. The antibody or antigen-binding fragment thereof may be of any type (e.g., IgG, IgE, IgM, IgD, IgA, and IgY), class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2), or subclass. In some embodiments, the antibody or antigen-binding fragment thereof is an IgG antibody or an antigen-binding fragment thereof.

[0342] As long as antibody fragments maintain the affinity and specificity required for full-length antibodies, they are suitable for use in the provided methods. Thus, antibody fragments that bind to LILRB1 and / or LILRB2 will retain the ability to bind to LILRB1 and / or LILRB2. An Fv fragment is an antibody fragment that contains a complete antigen recognition and binding site. This region consists of a dimer of a tightly associated heavy chain variable domain and a light chain variable domain, which can be covalent in nature, such as in an scFv. It is in this configuration that the three CDRs of each variable domain interact to define an antigen binding site on the surface of the VH-VL dimer. Collectively, these six CDRs or a subset thereof confer antigen binding specificity to the antibody. However, even a single variable domain (or half of an Fv containing only three antigen-specific CDRs) can have the ability to recognize and bind to an antigen, although its affinity is generally lower than that of the entire binding site.

[0343] Single-chain Fv or (scFv) antibody fragments include the VH and VL domains (or regions) of an antibody, wherein these domains are present in a single polypeptide chain. Typically, the scFv polypeptide also includes a polypeptide linker between the VH and VL domains, which enables the scFv to form a desired antigen-binding structure.

[0344] The Fab fragment contains the variable and constant domains of the light chain and the variable domain and the first constant domain (CH1) of the heavy chain. The F(ab')2 antibody fragment consists of a pair of Fab fragments, which are usually covalently linked near their carboxyl termini by a hinge cysteine ​​between them. Other chemical couplings of antibody fragments are known in the art.

[0345] Diabodies are small antibody fragments with two antigen-binding sites that consist of a VH linked to a VL in the same polypeptide chain (VH and VL). By using a linker that is too short to allow pairing between the two domains on the same chain, the domains are forced to pair with the complementary domains of another chain and create two antigen-binding sites.

[0346] Linear antibodies consist of a pair of tandem Fd fragments (VH-CH1-VH-CH1), which together with complementary light chain polypeptides form a pair of antigen binding regions. Linear antibodies can be bispecific or monospecific.

[0347] The antibodies and antibody fragments of the present disclosure may be modified in the Fc region to provide desired effector function or serum half-life.

[0348] The multimerization of antibodies can be achieved by natural aggregation of antibodies or by chemical or recombinant connection techniques known in the art. For example, a certain proportion of purified antibody preparations (e.g., purified IgG1 molecules) spontaneously form protein aggregates containing antibody homodimers and other high-order antibody multimers.

[0349] In addition, antibody homodimers can be formed by chemical bonding techniques known in the art. For example, heterobifunctional cross-linkers include, but are not limited to, SMCC (succinimidyl 4-(maleimidomethyl) cyclohexane-1-carboxylate) and SATA (N-succinimidyl S-ethylthioacetate) can be used to form antibody polymers. Ghetie et al. (Proc. Natl. Acad. Sci. USA 94: 7509-7514, 1997). Antibody homodimers can be converted into Fab'2 homodimers by digestion with pepsin. Another method for forming antibody homodimers is by using Zhao et al. (J. Immunol. 25: 396-404, 2002).

[0350] In some embodiments, multispecific antibodies are bispecific antibodies. Bispecific antibodies can be prepared by designing the interface between a pair of antibody molecules to maximize the percentage of heterodimers recovered from recombinant cell culture. For example, the interface can at least comprise a part of the CH3 domain of the constant domain of the antibody. In this method, one or more small amino acid side chains from the interface of the first antibody molecule are replaced by larger side chains (such as tyrosine or tryptophan). By replacing the large amino acid side chains with smaller amino acid side chains (such as alanine or threonine), a compensatory "cavity" of the same or similar size as the large side chain is formed on the interface of the second antibody molecule. This provides a mechanism that can improve the yield of heterodimers relative to other unwanted end products (such as homodimers). For example, the method is described in WO96 / 27011, which is incorporated by reference in its entirety.

[0351] Bispecific antibodies include cross-linked antibodies or "heteroconjugate" antibodies. For example, one antibody in the heteroconjugate can be coupled to avidin and the other can be coupled to biotin. Heteroconjugate antibodies can also be prepared using any convenient cross-linking method. Suitable cross-linking agents and cross-linking techniques are well known in the art and are disclosed in U.S. Patent No. 4,676,980, which is incorporated herein by reference in its entirety.

[0352] Methods for producing bispecific antibodies from antibody fragments are also known in the art. For example, bispecific antibodies can be prepared using chemical bonds. Brennan et al. (Science 229: 81, 1985) described a process in which intact antibody proteolytic cleavage is performed to produce F(ab')2 fragments. These fragments are reduced in the presence of a dithiol complexing agent, sodium arsenite, to stabilize nearby dithiols and prevent the formation of intermolecular disulfides. The resulting Fab' fragments are then converted into thionitrobenzoate (TNB) derivatives. Then, one of the Fab'TNB derivatives is reconverted into a Fab'thiol by reduction with mercaptoethylamine and mixed with an equimolar amount of another Fab'TNB derivative to form a bispecific antibody.

[0353] Any antibody or antigen-binding fragment described herein can be coupled to a stabilizing molecule (e.g., a molecule that increases the half-life of the antibody or antigen-binding fragment thereof in a subject or solution). Non-limiting examples of stabilizing molecules include: polymers (e.g., polyethylene glycol) or proteins (e.g., serum albumin, such as human serum albumin). The coupling of stabilizing molecules can increase the half-life of the antibody or antigen-binding fragment or extend the biological activity of the antibody or antigen-binding fragment in vitro (e.g., in tissue culture) or in vivo (e.g., in the human body).

[0354] In some embodiments, the antibodies or antigen-binding fragments described herein can be coupled to a therapeutic agent. Antibody-drug conjugates comprising antibodies or antigen-binding fragments thereof can be covalently or non-covalently bound to a therapeutic agent. In some embodiments, the therapeutic agent is a cytotoxic or cytostatic agent (e.g., cytochalasin B, gramicidin D, ethidium bromide, emetine, mitomycin, etoposide, tenotoposide, vincristine, vinblastine, colchicine, doxorubicin, daunorubicin, dihydroxyanthraquinone, maytansine compounds such as DM-1 and DM-4, ​​diketones, mitoxantrone, lindane, actinomycin D, 1-dehydrotestosterone, glucocorticoids, procaine, tetracaine, lidocaine, propranolol, puromycin, epirubicin, cyclophosphamide and the like).

[0355] Antibodies and antigen-binding fragments

[0356] The present disclosure provides anti-LILRB1 / 2 antibodies and antigen-binding fragments thereof. In general, antibodies (also called immunoglobulins) are composed of two types of polypeptide chains, light chains and heavy chains. The non-limiting antibodies of the present disclosure can be complete, four-immunoglobulin chain antibodies comprising two heavy chains and two light chains. The heavy chain of the antibody can be of any isotype, including IgM, IgG, IgE, IgA or IgD, or it can be a subisotype, including IgG1, IgG2, IgG2a, IgG2b, IgG3, IgG4, IgE1, IgE2, etc. The light chain can be a kappa light chain or a lambda light chain. The antibody can contain two identical copies of the light chain and two identical copies of the heavy chain. Each heavy chain contains a variable domain (or variable region, VH) and multiple constant domains (or constant regions), which are bound to each other through disulfide bonds within their constant domains to form the "stem" of the antibody. Each light chain consists of a variable domain (or variable region, VL) and a constant domain (or constant region), and each light chain is bound to a heavy chain through disulfide bonds. The variable region of each light chain is aligned with the variable region of the heavy chain to which it is bound. The variable regions of both light and heavy chains contain three hypervariable regions sandwiched between more conserved framework regions (FR).

[0357] These hypervariable regions are called complementarity determining regions (CDRs) and form loops that constitute the major antigen binding surface of the antibody. The four framework regions primarily adopt a beta-sheet conformation, and the CDRs form loops that connect the beta-sheet structure and in some cases form part of the beta-sheet structure. The CDRs in each chain are tightly bound by the framework regions and, together with the CDRs from the other chain, contribute to the formation of the antigen binding region.

[0358] Methods for identifying the CDR regions of antibodies by analyzing the amino acid sequence of the antibody are well known, and a number of CDR definitions are commonly used. The Kabat definition is based on sequence variability, while the Chothia definition is based on the location of the structural loop regions. These methods and definitions are described, for example, in Martin, "Protein sequence and structural analysis of antibody variable domains," Antibody Engineering, Springer Berlin, Heidelberg, 2001. 422-439; Abhinandan et al., "Analysis and improvement of Kabat and correct numbering of structures of antibody variable domains," Molecular Immunology 45.14 (2008): 3832-3839; Wu, TT and Kabat, EA (1970) J. Exp. Med. 132: 211-250; Martin et al., Methods Enzymol. 203:121-53 (1991); Morea et al., Biophys Chem. 68(1-3):9-16 (October 1997); Morea et al., J Mol Biol. 275(2):269-94 (January 1998); Chothia et al., Nature 342(6252):877-83 (December 1989); Ponomarenko and Bourne, BMC Structural Biology 7:64 (2007); each of which is incorporated herein by reference in its entirety. Unless otherwise specified in this disclosure, Kabat numbering is used by default in this disclosure.

[0359] CDRs are important for recognizing the epitope of an antigen. As used herein, an "epitope" is the smallest portion of a target molecule that is capable of specific binding to the antigen binding domain of an antibody. The minimum size of an epitope may be about three, four, five, six, or seven amino acids, but these amino acids do not have to be in a continuous linear sequence of the primary structure of the antigen, as the epitope may depend on the three-dimensional configuration of the antigen based on the secondary and tertiary structures of the antigen.

[0360] In some embodiments, the antibody is a complete immunoglobulin molecule (e.g., IgG1, IgG2a, IgG2b, IgG3, IgM, IgD, IgE, IgA). IgG subclasses (IgG1, IgG2, IgG3, and IgG4) are highly conserved and differ in their constant regions, particularly in their hinge and upper CH2 domains. The sequences and differences of IgG subclasses are known in the art and are described in Vidarsson et al., "IgG subclasses and allotypes: from structure to effector function." Frontiers in Immunology 5 (2014); Irani et al. "Molecular properties of human IgG subclasses and their implications for the design of therapeutic monoclonal antibodies against infectious diseases." Molecular Immunology 67.2 (2015): 171-182; Shakib, Farouk, ed. Human IgG subclasses: Molecular analysis of structure, function, and regulation. Elsevier, 2016; each of which is incorporated herein by reference in its entirety.

[0361] The antibody may also be an immunoglobulin molecule derived from any species (e.g., humans, rodents, mice, camelids). Antibodies disclosed herein also include, but are not limited to, polyclonal antibodies, monoclonal antibodies, monospecific antibodies, multispecific antibodies, and chimeric antibodies comprising an immunoglobulin binding domain fused to another polypeptide. The term "antigen binding domain" or "antigen binding fragment" is a part of an antibody that retains the specific binding activity of a complete antibody, i.e., any part of an antibody that can specifically bind to an epitope on a complete antibody target molecule. It includes, for example, Fab, Fab', F(ab')2, and variants of these fragments. Therefore, in some embodiments, an antibody or its antigen binding fragment may be, for example, scFv, Fv, Fd, dAb, bispecific antibodies, bispecific scFv, diabody, linear antibodies, single-chain antibody molecules, multispecific antibodies formed by antibody fragments, and any polypeptides comprising homology or homology to the binding domain. Antibody binding domain. Non-limiting examples of antigen binding domains include, e.g., heavy and / or light chain CDRs of an intact antibody, heavy and / or light chain variable regions of an intact antibody, a full length heavy or light chain of an intact antibody, or a single CDR from a heavy or light chain of an intact antibody.

[0362] In some embodiments, the antigen binding fragment may form part of a chimeric antigen receptor (CAR). In some embodiments, the chimeric antigen receptor is a fusion of a single-chain variable fragment (scFv) as described herein, fused to the CD3-zeta transmembrane and internal domains. In some embodiments, the chimeric antigen receptor also includes intracellular signal transduction domains from various costimulatory protein receptors (e.g., CD28, 41BB, ICOS). In some embodiments, the chimeric antigen receptor includes multiple signaling domains, such as CD3z-CD28-41BB or CD3z-CD28-OX40, to increase effectiveness. Therefore, in one aspect, the disclosure further provides cells (e.g., T cells) expressing chimeric antigen receptors as described herein.

[0363] In some embodiments, the scFV has one heavy chain variable domain and one light chain variable domain.

[0364] Antibody characteristics

[0365] The antibodies or antigen-binding fragments thereof described herein can block the binding of LILRB1 and / or LILRB2 to MHC class I molecules (eg, HLA-G).

[0366] LILRB1 and LILRB2 are expressed on immune cells, which bind to MHC class I molecules on antigen presenting cells and transduce negative signals that inhibit the stimulation of immune responses. In some embodiments, by binding to LILRB1 and / or LILRB2, the antibodies described herein can block negative signals that inhibit the stimulation of immune responses, thereby upregulating immune responses. Therefore, in some embodiments, the antibodies or antigen-binding fragments thereof described herein are agonists of LILRB1 and / or LILRB2. In some embodiments, the antibodies or antigen-binding fragments thereof are antagonists of LILRB1 and / or LILRB2.

[0367] In some embodiments, the antibodies or antigen-binding fragments thereof described herein can increase immune response, activity or the number of T cells (e.g., CD8+ and / or CD4+ cells) or cytokines (e.g., TNF-α) by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 2 times, 3 times, 5 times, 10 times, or 20 times. In some embodiments, the antibodies or antigen-binding fragments thereof described herein can reduce the activity or number of Tregs, or the production of cytokines (e.g., IL10) by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 2 times, 3 times, 5 times, 10 times, or 20 times.

[0368] In certain embodiments, the antibody (or antigen-binding fragment thereof) specifically binds to LILRB1 (e.g., human LILRB1, monkey LILRB1, mouse LILRB1 and / or chimeric LILRB1) or LILRB2 (e.g., human LILRB2, monkey LILRB2, mouse LILRB2 and / or chimeric LILRB2) with an off rate (koff) of less than 0.1 s -1 Less than 0.01s -1 , less than 0.001s -1 , less than 0.0001s -1 , or less than 0.0001s -1 In some embodiments, the off-rate (koff) is greater than 0.01 s -1 , greater than 0.001s -1 , greater than 0.0001s -1 , greater than 0.0001s- 1 , or greater than 0.00001s -1 .

[0369] In some embodiments, the kinetic binding ratio (kon) is greater than 1×10 2 / Ms, greater than 1×10 3 / Ms, greater than 1×10 4 / Ms, greater than 1×10 5 / Ms or greater than 1×10 6 / Ms. In certain embodiments, the kinetic binding rate (kon) is less than 1×10 5 / Ms, less than 1×10 6 / Ms, or less than 1×10 7 / Ms.

[0370] Affinity can be derived from the quotient of the kinetic rate constants (KD = koff / kon). In certain embodiments, KD is less than 1×10 -6 M, less than 1×10 -7 M, less than 1×10 -8 M, less than 1×10 -9 M, or less than 1×10 -10 In certain embodiments, the KD is less than 30 nM, 20 nM, 15 nM, 10 nM, 9 nM, 8 nM, 7 nM, 6 nM, 5 nM, 4 nM, 3 nM, 2 nM, or 1 nM. In certain embodiments, the KD is greater than 1×10 -7 M, greater than 1×10 -8 M, greater than 1×10 -9 M, greater than 1×10 -10 M, greater than 1×10 -11 M, or greater than 1×10 -12M

[0371] Common techniques for measuring antibody affinity for an antigen include ELISA, RIA, and surface plasmon resonance (SPR). SPR imaging system or Gator Prime BLI system. In some embodiments, the antibody binds to human LILRB1, monkey LILRB1 (e.g., cynomolgus monkey LILRB1) and / or chimeric LILRB1. In some embodiments, the antibody binds to human LILRB2, monkey LILRB2 (e.g., cynomolgus monkey LILRB2) and / or chimeric LILRB2.

[0372] In some embodiments, the anti-LILRB1 / 2 antibodies or antigen-binding fragments thereof described herein can bind to human LILRB1 and / or LILRB2 with an EC50 value of less than 10 μg / mL, less than 9 μg / mL, less than 8 μg / mL, less than 7 μg / mL, less than 6 μg / mL, less than 5 μg / mL, less than 4 μg / mL, less than 3 μg / mL, less than 2 μg / mL, less than 1 μg / mL, less than 0.9 μg / mL, less than 0.8 μg / mL, less than 0.7 μg / mL, less than 0.6 μg / mL, less than 0.5 μg / mL, less than 0.4 μg / mL, less than 0.3 μg / mL, less than 0.2 μg / mL, or less than 0.1 μg / mL. In some embodiments, the antibodies described herein can block the LILRB1 / HLA-G interaction and / or the LILRB2 / HLA-G interaction with an IC50 value of less than 2 μg / mL, less than 1 μg / mL, less than 0.9 μg / mL, less than 0.8 μg / mL, less than 0.7 μg / mL, less than 0.6 μg / mL, less than 0.5 μg / mL, less than 0.4 μg / mL, less than 0.3 μg / mL, less than 0.2 μg / mL, less than 0.1 μg / mL, less than 0.05 μg / mL, less than 0.04 μg / mL, less than 0.03 μg / mL, less than 0.02 μg / mL or less than 0.01 μg / mL.

[0373] In some embodiments, the anti-LILRB1 / 2 antibodies or antigen-binding fragments thereof described herein can bind to monkey LILRB1 or LILRB2 with an EC50 value of less than 10 μg / mL, less than 9 μg / mL, less than 8 μg / mL, less than 7 μg / mL, less than 6 μg / mL, less than 5 μg / mL, less than 4 μg / mL, less than 3 μg / mL, less than 2 μg / mL, or less than 1 μg / mL. In some embodiments, the antibodies described herein can bind to monkey LILRB1 or LILRB2 with a KD value of less than 1×10-6M, less than 1×10-7M, less than 1×10-8M, less than 1×10-9M, or less than 1×10-10M. In some embodiments, the antibodies described herein do not bind to monkey LILRB1 or LILRB2.

[0374] In some embodiments, the anti-LILRB1 / 2 antibodies or antigen-binding fragments thereof described herein can bind to any of the LILRAB family members, including LILRA family members (e.g., LILRA1, LILRA2, LILRA3, LILRA4, LILRA5 and / or LILRA6) and LILRB family members (e.g., LILRB1, LILRB2, LILRA3, LILRA4 and / or LILRB5). In some embodiments, the antibodies described herein do not bind to any of the LILRAB family members, including LILRA family members (e.g., LILRA1, LILRA2, LILRA3, LILRA4, LILRA5 and / or LILRA6) and LILRB family members (e.g., LILRB1, LILRB2, LILRA3, LILRA4 and / or LILRB5). In some embodiments, the antibodies described herein (e.g., any D2M002-002 and / or D2M002-026 lineage antibodies or variants described herein) can bind to LILRB1 (e.g., human LILRB1), LILRB2 (e.g., human LILRB2) and / or LILRA1 (e.g., human LILRA1) with an EC50 value of less than 10 μg / mL, less than 10 μg / mL, less than 9 μg / mL, less than 8 μg / mL, less than 7 μg / mL, less than 6 μg / mL, less than 5 μg / mL, less than 4 μg / mL, less than 3 μg / mL, less than 2 μg / mL, less than 1 μg / mL, less than 0.5 μg / mL or less than 0.1 μg / mL. In some embodiments, the antibodies described herein (e.g., any D2M002-002 lineage antibody or variant described herein) can bind to LILRB3 (e.g., human LILRB3), LILRA6 (e.g., human LILRA6) and / or LILRB2 (e.g., monkey LILRB2) with an EC50 value of less than 10 μg / mL, less than 10 μg / mL, less than 9 μg / mL, less than 8 μg / mL, less than 7 μg / mL, less than 6 μg / mL, less than 5 μg / mL, less than 4 μg / mL, less than 3 μg / mL, less than 2 μg / mL, less than 1 μg / mL, less than 0.5 μg / mL, or less than 0.1 μg / mL. In some embodiments, the corresponding EC50 value is less than 50 nM, less than 40 nM, less than 30 nM, less than 20 nM, or less than 10 nM.

[0375] In some embodiments, the anti-LILRB1 / 2 antibodies or antigen-binding fragments thereof described herein (e.g., any D2M002-026 lineage antibodies or variants described herein) can block the binding of LILRB2 to its ligands (e.g., SEMA4A, MAG, CD1C, CD1D, ANGPTL2 and / or ANGPTL5).

[0376] In some embodiments, thermal stability is measured. The Tm of antibodies or their antigen-binding fragments described herein may be greater than 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94 or 95°C. Since IgG can be described as a multi-domain protein, the melting curve sometimes shows two transitions, the first denaturation temperature Tm D1 and the second denaturation temperature Tm D2. The presence of these two peaks usually indicates the denaturation of Fc domains (Tm D1) and Fab domains (Tm D2), respectively. When there are two peaks, Tm usually refers to Tm D2.

[0377] Thus, in some embodiments, the antibodies or antigen-binding fragments thereof described herein have a temperature greater than 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, or 95°C. In some embodiments, the antibodies or antigen binding fragments described herein have a temperature of greater than 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, or 95°C.

[0378] In some embodiments, Tm, Tm Dl, Tm D2 is less than 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, or 95 °C.

[0379] In some embodiments, an anti-LILRB1 / 2 antibody or antigen-binding fragment thereof described herein (e.g., any D2M002-026 lineage antibody or variant described herein) can be mixed with fresh human plasma and stored at about 30-40° C. (e.g., about 37° C.) for at least 1 week, 2 weeks, 3 weeks, 4 weeks, or 5 weeks without showing significant loss of activity (e.g., binding to LILRB1 and / or LILRB2).

[0380] In some embodiments, an anti-LILRB1 / 2 antibody or antigen-binding fragment thereof described herein (e.g., any D2M002-026 lineage antibody or variant described herein) can maintain at least 95%, at least 90%, at least 85%, at least 80%, at least 75%, at least 70%, at least 65%, at least 60%, at least 65%, at least 65%, or at least 50% compared to the original in vivo concentration (measured immediately after injection) after about 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, or 10 days after injection into an animal (e.g., a mouse).

[0381] In some embodiments, the tumor growth inhibition percentage (TGI%) of the antibody is greater than 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 110%, 120%, 130%, 140%, 150%, 160%, 170%, 180%, 190% or 200%. In some embodiments, the tumor growth inhibition percentage of the antibody is less than 60%, 70%, 80%, 90%, 100%, 110%, 120%, 130%, 140%, 150%, 160%, 170%, 180%, 190% or 200%. The TGI% can be 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 days after the start of treatment, or 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months after the start of treatment. As used herein, tumor growth inhibition percentage (TGI%) is calculated using the following formula:

[0382] TGI(%)=[1-(Ti-T0) / (Vi-V0)]×100

[0383] Ti is the mean tumor volume on day i of the treatment group. T0 is the mean tumor volume on day 0 of the treatment group. Vi is the mean tumor volume on day i of the control group. V0 is the mean tumor volume on day 0 of the control group.

[0384] In some embodiments, the anti-LILRB1 / LILRB2 antibodies or antigen-binding fragments thereof described herein can be mixed with macrophages (e.g., hMDM) for the treatment of cancer. In some embodiments, the mixture is injected into a subject (e.g., an immunocompromised animal) and the tumor volume is monitored over time. In some embodiments, the mixture is administered by subcutaneous injection or intratumoral injection. In some embodiments, the antibodies can reprogram macrophages and significantly inhibit tumor growth, for example, the TGI is at least 10%, at least 20%, at least 30%, at least 40%, or at least 50% higher than the TGI of the isotype control.

[0385] In some embodiments, the anti-LILRB1 / 2 anti-LILRB1 / LILRB2 antibodies or antigen-binding fragments thereof described herein can be administered to a subject (e.g., an immunocompromised animal) pre-injected with human PBMCs. In some embodiments, the antibodies can significantly inhibit tumor growth in a PBMC reconstituted animal model, e.g., TGI is at least 10%, at least 20%, at least 30%, at least 40%, or at least 50% higher than an isotype control.

[0386] In some embodiments, the anti-LILRB1 / 2 antibodies or antigen-binding fragments thereof described herein have a functional Fc. In some embodiments, the Fc is from human IgG1, human IgG2, human IgG3, or human IgG4. In some embodiments, the effector function of the functional Fc is antibody-dependent cell-mediated cytotoxicity (ADCC). In some embodiments, the effector function of the functional Fc is phagocytosis (e.g., antibody-dependent cellular phagocytosis, or ADCP). In some embodiments, the effector function of the functional Fc is ADCC and phagocytosis. In some embodiments, the antibodies or antigen-binding fragments thereof described herein have an Fc region without effector function. In some embodiments, Fc is human IgG4 Fc. In some embodiments, Fc is human IgG1 Fc. In some embodiments, Fc does not have a functional Fc region. For example, the Fc region has a LALA mutation (L234A and L235A mutations in EU numbering), a LALA-PA mutation (L234A, L235A and P329A) or a LALA-PG mutation (L234A, L235A, P329G mutations in EU numbering). Details of the LALA-PG mutation can be found in PCT Application Publication No. WO2012 / 130831, U.S. Patent No. 8,969,526, U.S. Patent No. 10,093,714; each of which is incorporated herein by reference in its entirety. Detailed information on the LALA-PA mutation can be found, for example, in U.S. Patent Application Publication No. US20210087271A1, which is incorporated herein by reference in its entirety.

[0387] Other references to SALA mutations can be found in Wines, BD et al., “IgGFc contains distinct Fc receptor (FcR) binding sites: the leukocyte receptors FcγRI and FcγRIIa bind to a region in Fc that is distinct from that recognized by the neonatal FcR and protein A. Journal of Immunology 164.10 (2000): 5313-5318; Chappel, MS et al. “Identification of the Fcγ receptor class I binding site in human IgG by using recombinant IgG1 / IgG2 hybrid and point-mutated antibodies.” Proc. Natl. Acad. Sci. USA 88.20 (1991): 9036-9040; Wilkinson, I. et al. “Fc-engineered antibodies with immune effector functions are completely abolished.” PLoS One 16.12 (2021): e0260954; and Lund, J. et al. “Human FcγRI and FcγRII interact with distinct but overlapping sites on human IgG.” "Journal of Immunology (Baltimore, MD: 1950) 147.8 (1991): 2657-2662; each of which is incorporated herein by reference in its entirety. For other references to the P329A mutation, see, for example, U.S. Pat. No. 6,528,624; Sondermann, P. et al., "Degradation of the Human IgG1 Fc Fragment-FcγRIII Complex Crystal structure. " Nature 406.6793 (2000): 267-273; Idusogie, EE et al. "Mapping of the C1q binding site on rituxan, a chimeric antibody with a human IgG1 Fc." Journal of Immunology 164.8 (2000): 4178-4184; and Shields, RL et al. "High-resolution mapping of the binding sites of FcγRI, FcγRII, FcγRIII, and FcRn on human IgG1 and design of IgG1 variants with improved binding to FcγRs. "Journal of Biological Chemistry 276.9 (2001): 6591-6604; each of which is incorporated herein by reference in its entirety. In some embodiments, the Fc region includes an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 95% or 100% identical to SEQ ID NO: 801, 802, 803, 804 or 805. For example, the antibody or antigen-binding fragment is a Fab, Fab', F(ab')2 and Fv fragment.

[0388] In some embodiments, the anti-LILRB1 / 2 antibodies or antigen-binding fragments thereof described herein can only bind to LILRB1 (e.g., #4), and thus can also be named anti-LILRB1 antibodies. In some embodiments, the anti-LILRB1...

Claims

1. An antibody or antigen-binding fragment that binds to LILRB1 (leukocyte immunoglobulin-like receptor subfamily B member 1) and / or LILRB2 (leukocyte immunoglobulin-like receptor subfamily B member 2), comprising: a heavy chain variable region (VH) comprising complementarity determining regions (CDRs) 1, 2, and 3, wherein the VH CDR1 region comprises an amino acid sequence at least 80% identical to a selected VH CDR1 amino acid sequence, the VH CDR2 region comprises an amino acid sequence at least 80% identical to a selected VH CDR2 amino acid sequence, and the VH CDR3 region comprises an amino acid sequence at least 80% identical to a selected VH CDR3 amino acid sequence; and A light chain variable region (VL) comprising CDRs 1, 2 and 3, wherein the VL CDR1 region comprises an amino acid sequence at least 80% identical to a selected VL CDR1 amino acid sequence, the VL CDR2 region comprises an amino acid sequence at least 80% identical to a selected VL CDR2 amino acid sequence, and the VL CDR3 region comprises an amino acid sequence at least 80% identical to a selected VL CDR3 amino acid sequence, The selected VH CDRs are 1, 2, and 3 amino acid sequences, and the selected VL CDRs, 1, 2, and 3 amino acid sequences are one of the following: (1) The amino acid sequences of selected VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 7, 8, and 9, respectively, and the amino acid sequences of selected VLCDRs 1, 2, and 3 are listed in SEQ ID NOs: 10, 11, and 12, respectively; (2) the amino acid sequences of selected VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 37, 38, and 39, respectively, and the amino acid sequences of selected VLCDRs 1, 2, and 3 are listed in SEQ ID NOs: 40, 41, and 42, respectively; (3) the amino acid sequences of selected VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 67, 68, and 69, respectively, and the amino acid sequences of selected VLCDRs 1, 2, and 3 are listed in SEQ ID NOs: 70, 71, and 72, respectively; (4) the amino acid sequences of selected VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 97, 98, and 99, respectively, and the amino acid sequences of selected VLCDRs 1, 2, and 3 are listed in SEQ ID NOs: 100, 101, and 102, respectively; (5) the selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 127, 128, and 129, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 130, 131, and 132, respectively; (6) the selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 157, 158, and 159, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 160, 161, and 162, respectively; (7) the selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 187, 188, and 189, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 190, 191, and 192, respectively; (8) the selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 217, 218, and 219, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 220, 221, and 222, respectively; (9) the selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 247, 248, and 249, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 250, 251, and 252, respectively; (10) the selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 277, 278, and 279, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 280, 281, and 282, respectively; (11) The amino acid sequences of selected VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 307, 308, and 309, respectively, and the amino acid sequences of selected VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 310, 311, and 312, respectively; (12) the selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 337, 338, and 339, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 340, 341, and 342, respectively; (13) the selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 367, 368, and 369, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 370, 371, and 372, respectively; (14) the selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 397, 398, and 399, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 400, 401, and 402, respectively; (15) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 427, 428, and 429, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 430, 431, and 432, respectively; (16) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 457, 458, and 459, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 460, 461, and 462, respectively; (17) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 487, 488, and 489, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 490, 491, and 492, respectively; (18) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 517, 518, and 519, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 520, 521, and 522, respectively; (19) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 547, 548, and 549, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 550, 551, and 552, respectively; (20) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 577, 578, and 579, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 580, 581, and 582, respectively; (21) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 607, 608, and 609, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 610, 611, and 612, respectively; (22) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 637, 638, and 639, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 640, 641, and 642, respectively; (23) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 667, 668, and 669, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 670, 671, and 672, respectively; (24) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 697, 698, and 699, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 700, 701, and 702, respectively; (25) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 727, 728, and 729, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 730, 731, and 732, respectively; (26) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1069, 1070, and 1071, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1072, 1073, and 1074, respectively; (27) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1093, 1094, and 1095, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1096, 1097, and 1098, respectively; (28) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1117, 1118, and 1119, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1120, 1121, and 1122, respectively; (29) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1141, 1142, and 1143, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1144, 1145, and 1146, respectively; (30) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1165, 1166, and 1167, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1168, 1169, and 1170, respectively; (31) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1189, 1190, and 1191, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1192, 1193, and 1194, respectively; (32) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1213, 1214, and 1215, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1216, 1217, and 1218, respectively; (33) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1237, 1238, and 1239, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1240, 1241, and 1242, respectively; (34) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1261, 1262, and 1263, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1264, 1265, and 1266, respectively; (35) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1285, 1286, and 1287, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1288, 1289, and 1290, respectively; (36) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1309, 1310, and 1311, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1312, 1313, and 1314, respectively; (37) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1333, 1334, and 1335, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1336, 1337, and 1338, respectively; (38) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1357, 1358, and 1359, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1360, 1361, and 1362, respectively; (39) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1381, 1382, and 1383, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1384, 1385, and 1386, respectively; (40) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1405, 1406, and 1407, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1408, 1409, and 1410, respectively; (41) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1429, 1430, and 1431, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1432, 1433, and 1434, respectively; (42) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1453, 1454, and 1455, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1456, 1457, and 1458, respectively; (43) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1477, 1478, and 1479, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1480, 1481, and 1482, respectively; (44) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1501, 1502, and 1503, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1504, 1505, and 1506, respectively; (45) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1525, 1526, and 1527, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1528, 1529, and 1530, respectively; (46) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1549, 1550, and 1551, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1552, 1553, and 1554, respectively; (47) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1573, 1574, and 1575, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1576, 1577, and 1578, respectively; (48) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1597, 1598, and 1599, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1600, 1601, and 1602, respectively; (49) The selected amino acid sequences of VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1621, 1622, and 1623, respectively, and the selected amino acid sequences of VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1624, 1625, and 1626, respectively; (50) the selected VH CDRs 1, 2, and 3 amino acid sequences are listed in SEQ ID NOs: 1645, 1646, and 1647, respectively, and the selected VL CDRs 1, 2, and 3 amino acid sequences are listed in SEQ ID NOs: 1648, 1649, and 1650, respectively; and (51) The amino acid sequences of the selected VH CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1669, 1670, and 1671, respectively, and the amino acid sequences of the selected VL CDRs 1, 2, and 3 are listed in SEQ ID NOs: 1672, 1673, and 1674, respectively.

2. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 7, 8, and 9, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 10, 11, and 12, respectively.

3. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 37, 38, and 39, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 40, 41, and 42, respectively.

4. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 67, 68, and 69, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 70, 71, and 72, respectively.

5. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 97, 98, and 99, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 100, 101, and 102, respectively.

6. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 127, 128, and 129, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 130, 131, and 132, respectively.

7. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 157, 158, and 159, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 160, 161, and 162, respectively.

8. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 187, 188, and 189, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 190, 191, and 192, respectively.

9. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 217, 218, and 219, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 220, 221, and 222, respectively.

10. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 247, 248, and 249, respectively, and the VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 250, 251, and 252, respectively.

11. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 277, 278, and 279, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 280, 281, and 282, respectively.

12. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 307, 308, and 309, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 310, 311, and 312, respectively.

13. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 337, 338, and 339, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 340, 341, and 342, respectively.

14. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 367, 368, and 369, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 370, 371, and 372, respectively.

15. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 397, 398, and 399, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 400, 401, and 402, respectively.

16. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 427, 428, and 429, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 430, 431, and 432, respectively.

17. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 457, 458, and 459, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 460, 461, and 462, respectively.

18. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 487, 488, and 489, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 490, 491, and 492, respectively.

19. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 517, 518, and 519, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 520, 521, and 522, respectively.

20. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, 3 and the amino acid sequences shown in SEQ ID NOs: 547, 548 and 549, and VL comprises CDRs 1, 2, 3 and the amino acid sequences shown in SEQ ID NOs: 550, 551 and 552.

21. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 577, 578, and 579, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 580, 581, and 582, respectively.

22. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 607, 608, and 609, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 610, 611, and 612, respectively.

23. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 637, 638, and 639, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 640, 641, and 642, respectively.

24. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 667, 668, and 669, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 670, 671, and 672, respectively.

25. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 697, 698, and 699, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 700, 701, and 702, respectively.

26. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 727, 728, and 729, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 730, 731, and 732, respectively.

27. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1069, 1070, and 1071, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1072, 1073, and 1074, respectively.

28. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1093, 1094, and 1095, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1096, 1097, and 1098, respectively.

29. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1117, 1118, and 1119, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1120, 1121, and 1122, respectively.

30. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1141, 1142, and 1143, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1144, 1145, and 1146, respectively.

31. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1165, 1166, and 1167, respectively, and the VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1168, 1169, and 1170, respectively.

32. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1189, 1190, and 1191, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1192, 1193, and 1194, respectively.

33. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1213, 1214, and 1215, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1216, 1217, and 1218, respectively.

34. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, and their amino acid sequences are SEQ ID NOs: 1237, 1238, and 1239, respectively, and VL comprises CDRs 1, 2, and 3 and their amino acid sequences are shown in SEQ ID NOs: 1240, 1241, and 1242.

35. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1261, 1262, and 1263, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1264, 1265, and 1266, respectively.

36. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1285, 1286, and 1287, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1288, 1289, and 1290, respectively.

37. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1309, 1310, and 1311, respectively, and the VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1312, 1313, and 1314, respectively.

38. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1333, 1334, and 1335, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1336, 1337, and 1338, respectively.

39. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1357, 1358, and 1359, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1360, 1361, and 1362, respectively.

40. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1381, 1382, and 1383, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1384, 1385, and 1386, respectively.

41. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, and their amino acid sequences are SEQ ID NOs: 1405, 1406, and 1407, respectively, and VL comprises CDRs 1, 2, and 3 and their amino acid sequences are shown in SEQ ID NOs: 1408, 1409, and 1410.

42. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1429, 1430, and 1431, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1432, 1433, and 1434, respectively.

43. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, 3 and the amino acid sequences shown in SEQ ID NOs: 1453, 1454 and 1455, respectively, and VL comprises CDRs 1, 2, 3 and the amino acid sequences shown in SEQ ID NOs: 1456, 1457 and 1458.

44. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, and their amino acid sequences are SEQ ID NOs: 1477, 1478, and 1479, respectively, and VL comprises CDRs 1, 2, and 3 and their amino acid sequences are shown in SEQ ID NOs: 1480, 1481, and 1482.

45. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1501, 1502, and 1503, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1504, 1505, and 1506, respectively.

46. ​​The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1525, 1526, and 1527, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1528, 1529, and 1530, respectively.

47. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1549, 1550, and 1551, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1552, 1553, and 1554, respectively.

48. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1573, 1574, and 1575, respectively, and the VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1576, 1577, and 1578, respectively.

49. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, and their amino acid sequences are SEQ ID NOs: 1597, 1598, and 1599, respectively, and the VL comprises CDRs 1, 2, and 3 and their amino acid sequences shown in SEQ ID NOs: 1600, 1601, and 1602.

50. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1621, 1622, and 1623, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1624, 1625, and 1626, respectively.

51. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1645, 1646, and 1647, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1648, 1649, and 1650, respectively.

52. The antibody or antigen-binding fragment of claim 1, wherein VH comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1669, 1670, and 1671, respectively, and VL comprises CDRs 1, 2, and 3, whose amino acid sequences are SEQ ID NOs: 1672, 1673, and 1674, respectively.

53. The antibody or antigen-binding fragment of any one of claims 1-52, wherein the antibody or antigen-binding fragment specifically binds to human LILRB1 and / or human LILRB2.

54. The antibody or antigen-binding fragment of any one of claims 1-53, wherein the antibody or antigen-binding fragment specifically binds to monkey LILRB1 and / or monkey LILRB2.

55. The antibody or antigen-binding fragment of any one of claims 1-54, wherein the antibody or antigen-binding fragment can block the interaction between LILRB1 and MHC class I molecules (such as HLA-G), or the interaction between LILRB2 and MHC class I molecules (such as HLA-G).

56. The antibody or antigen-binding fragment of any one of claims 1-55, wherein the antibody or antigen-binding fragment is a humanized antibody or a humanized antigen-binding fragment.

57. The antibody or antigen-binding fragment of any one of claims 1-56, wherein the antibody or antigen-binding fragment is a single-chain variable fragment (scFV) or a multispecific antibody (eg, a bispecific antibody).

58. The antibody or antigen-binding fragment of any one of claims 1-57, wherein the antibody or antigen-binding fragment specifically binds to LILRB3 (eg, human LILRB3).

59. A nucleic acid, comprising a polynucleotide encoding a polypeptide, comprising: (1) An immunoglobulin heavy chain or a fragment thereof, comprising a heavy chain variable region (VH), including complementarity determining regions (CDRs) 1, 2 and 3, each comprising the amino acid sequence shown in SEQ ID NOs: 7, 8 and 9, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NOs: 752; (2) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 of the amino acid sequences shown in SEQ ID NOs: 10, 11 and 12, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence shown in SEQ ID NO: 751; (3) an immunoglobulin heavy chain or fragment thereof, comprising a VH comprising CDRs 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 37, 38, and 39, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence set forth in SEQ ID NO: 754; (4) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 40, 41, and 42, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO: 753; (5) an immunoglobulin heavy chain or fragment thereof, comprising a VH comprising CDRs 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 67, 68, and 69, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence set forth in SEQ ID NO: 756; (6) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 70, 71, and 72, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO: 755; (7) an immunoglobulin heavy chain or fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 97, 98 and 99, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence set forth in SEQ ID NO: 758; (8) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 100, 101, and 102, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO: 757; (9) an immunoglobulin heavy chain or fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 127, 128 and 129, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 760; (10) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 130, 131 and 132, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO: 759; (11) an immunoglobulin heavy chain or a fragment thereof, comprising a VH including CDRs 1, 2 and 3, comprising the amino acid sequences shown in SEQ ID NOs: 157, 158 and 159, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL including the amino acid sequence shown in SEQ ID NO: 762; (12) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 160, 161 and 162, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO: 761; (13) an immunoglobulin heavy chain or fragment thereof, comprising a VH including CDRs 1, 2 and 3, comprising the amino acid sequences shown in SEQ ID NOs: 187, 188 and 189, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL including the amino acid sequence shown in SEQ ID NO: 764; (14) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 190, 191 and 192, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO: 763; (15) an immunoglobulin heavy chain or a fragment thereof, comprising a VH comprising the amino acid sequences shown in SEQ ID NOs: 217, 218 and 219, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 766; (16) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 220, 221 and 222, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO: 765; (17) an immunoglobulin heavy chain or a fragment thereof, comprising a VH including CDRs 1, 2 and 3, comprising the amino acid sequences shown in SEQ ID NOs: 247, 248 and 249, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL including the amino acid sequence shown in SEQ ID NO: 768; (18) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 250, 251 and 252, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence shown in SEQ ID NO: 767; (19) an immunoglobulin heavy chain or a fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 of the amino acid sequences shown in SEQ ID NOs: 277, 278 and 279, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 770; (20) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 280, 281 and 282, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO: 769; (21) an immunoglobulin heavy chain or fragment thereof, comprising a VH including CDRs 1, 2 and 3, comprising the amino acid sequences shown in SEQ ID NOs: 307, 308 and 309, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL including the amino acid sequence shown in SEQ ID NO: 772; (22) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 310, 311 and 312, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO: 771; (23) an immunoglobulin heavy chain or fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 337, 338 and 339, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 774; (24) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 340, 341 and 342, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence shown in SEQ ID NO: 773; (25) an immunoglobulin heavy chain or fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 367, 368 and 369, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 776; (26) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 370, 371 and 372, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence shown in SEQ ID NO: 775; (27) an immunoglobulin heavy chain or a fragment thereof, comprising a VH comprising the amino acid sequences in SEQ ID NOs: 397, 398 and 399, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 778; (28) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 400, 401 and 402, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence shown in SEQ ID NO: 777; (29) an immunoglobulin heavy chain or a fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 of the amino acid sequences shown in SEQ ID NOs: 427, 428 and 429, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 780; (30) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 430, 431 and 432, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence shown in SEQ ID NO: 779; (31) an immunoglobulin heavy chain or a fragment thereof, comprising a VH including CDRs 1, 2 and 3, comprising the amino acid sequences shown in SEQ ID NOs: 457, 458 and 459, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL including the amino acid sequence shown in SEQ ID NO: 782; (32) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 460, 461 and 462, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence shown in SEQ ID NO: 781; (33) an immunoglobulin heavy chain or fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 487, 488 and 489, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 784; (34) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 490, 491 and 492, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH having the amino acid sequence set forth in SEQ ID NO: 783; (35) an immunoglobulin heavy chain or fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 517, 518 and 519, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 786; (36) an immunoglobulin light chain or a fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 of the amino acid sequences shown in SEQ ID NOs: 520, 521 and 522, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence shown in SEQ ID NO: 785; (37) an immunoglobulin heavy chain or fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 547, 548 and 549, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 788; (38) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 as set forth in SEQ ID NOs: 550, 551 and 552, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence as set forth in SEQ ID NO: 787; (39) an immunoglobulin heavy chain or fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 577, 578 and 579, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 790; (40) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 580, 581 and 582, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence shown in SEQ ID NO: 789; (41) an immunoglobulin heavy chain or a fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 of the amino acid sequences shown in SEQ ID NOs: 607, 608 and 609, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 792; (42) an immunoglobulin light chain or a fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 of the amino acid sequences shown in SEQ ID NOs: 610, 611 and 612, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence shown in SEQ ID NO: 791; (43) an immunoglobulin heavy chain or fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 637, 638 and 639, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 794; (44) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 640, 641 and 642, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO: 793; (45) an immunoglobulin heavy chain or a fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 of the amino acid sequences shown in SEQ ID NOs: 667, 668 and 669, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 796; (46) an immunoglobulin light chain or a fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 of the amino acid sequences shown in SEQ ID NOs: 670, 671 and 672, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence shown in SEQ ID NO: 795; (47) an immunoglobulin heavy chain or a fragment thereof, comprising a VH comprising the amino acid sequences shown in SEQ ID NOs: 697, 698 and 699, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 798; (48) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 700, 701 and 702, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence shown in SEQ ID NO: 797; (49) an immunoglobulin heavy chain or a fragment thereof, comprising a VH comprising the amino acid sequences shown in SEQ ID NOs: 727, 728 and 729, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 800; (50) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 of the amino acid sequences shown in SEQ ID NOs: 730, 731 and 732, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence shown in SEQ ID NO: 799; (51) an immunoglobulin heavy chain or a fragment thereof, comprising a VH including CDRs 1, 2 and 3, comprising the amino acid sequences shown in SEQ ID NOs: 1069, 1070 and 1071, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL including the amino acid sequence shown in SEQ ID NO: 988; (52) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 1072, 1073 and 1074, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO: 987; (53) an immunoglobulin heavy chain or fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 1093, 1094 and 1095, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 988; (54) an immunoglobulin light chain or a fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 of the amino acid sequences shown in SEQ ID NOs: 1096, 1097 and 1098, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence shown in SEQ ID NO: 1687; (55) an immunoglobulin heavy chain or fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 1117, 1118 and 1119, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 988; (56) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 1120, 1121 and 1122, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence shown in SEQ ID NO: 1688; (57) an immunoglobulin heavy chain or a fragment thereof, comprising a VH comprising the amino acid sequences shown in SEQ ID NOs: 1141, 1142 and 1143, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 989; (58) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 1144, 1145 and 1146, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence shown in SEQ ID NO: 987; (59) an immunoglobulin heavy chain or a fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 of the amino acid sequences shown in SEQ ID NOs: 1165, 1166 and 1167, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 990; (60) an immunoglobulin light chain or a fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 of the amino acid sequences shown in SEQ ID NOs: 1168, 1169 and 1170, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence shown in SEQ ID NO: 987; (61) an immunoglobulin heavy chain or a fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 of the amino acid sequences shown in SEQ ID NOs: 1189, 1190 and 1191, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 991; (62) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 1192, 1193 and 1194, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO: 987; (63) an immunoglobulin heavy chain or a fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 of the amino acid sequences shown in SEQ ID NOs: 1213, 1214 and 1215, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 992; (64) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 1216, 1217 and 1218, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO: 987; (65) an immunoglobulin heavy chain or a fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 of the amino acid sequences shown in SEQ ID NOs: 1237, 1238 and 1239, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 1020; (66) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 1240, 1241 and 1242, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence shown in SEQ ID NO: 1019; (67) an immunoglobulin heavy chain or a fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 of the amino acid sequences shown in SEQ ID NOs: 1261, 1262 and 1263, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 1022; (68) an immunoglobulin light chain or a fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 of the amino acid sequences shown in SEQ ID NOs: 1264, 1265 and 1266, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence shown in SEQ ID NO: 1021; (69) an immunoglobulin heavy chain or fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 1285, 1286 and 1287, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 1024; (70) an immunoglobulin light chain or a fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 of the amino acid sequences shown in SEQ ID NOs: 1288, 1289 and 1290, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence shown in SEQ ID NO: 1023; (71) an immunoglobulin heavy chain or a fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 1309, 1310 and 1311, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 1026; (72) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 1312, 1313 and 1314, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO: 1025; (73) an immunoglobulin heavy chain or fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 1333, 1334 and 1335, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 1028; (74) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 of the amino acid sequences shown in SEQ ID NOs: 1336, 1337 and 1338, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence shown in SEQ ID NO: 1027; (75) an immunoglobulin heavy chain or fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 1357, 1358 and 1359, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 1030; (76) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 1360, 1361 and 1362, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO: 1029; (77) an immunoglobulin heavy chain or fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 1381, 1382 and 1383, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 1032; (78) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 1384, 1385 and 1386, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH having the amino acid sequence set forth in SEQ ID NO: 1031; (79) an immunoglobulin heavy chain or a fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 of the amino acid sequences shown in SEQ ID NOs: 1405, 1406 and 1407, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 1034; (80) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 1408, 1409 and 1410, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence shown in SEQ ID NO: 1033; (81) an immunoglobulin heavy chain or a fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 of the amino acid sequences shown in SEQ ID NOs: 1429, 1430 and 1431, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 1036; (82) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 of the amino acid sequences shown in SEQ ID NOs: 1432, 1433 and 1434, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence shown in SEQ ID NO: 1035; (83) an immunoglobulin heavy chain or a fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 of the amino acid sequences shown in SEQ ID NOs: 1453, 1454 and 1455, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 1038; (84) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 1456, 1457 and 1458, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence shown in SEQ ID NO: 1037; (85) an immunoglobulin heavy chain or a fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 of the amino acid sequences shown in SEQ ID NOs: 1477, 1478 and 1479, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 1040; (86) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 1480, 1481 and 1482, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence shown in SEQ ID NO: 1039; (87) an immunoglobulin heavy chain or a fragment thereof, comprising a VH comprising the amino acid sequences in SEQ ID NOs: 1501, 1502, and 1503, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 1042; (88) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 1504, 1505 and 1506, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence shown in SEQ ID NO: 1041; (89) an immunoglobulin heavy chain or fragment thereof, comprising a VH comprising CDRs 1, 2, and 3 comprising the amino acid sequences shown in SEQ ID NOs: 1525, 1526, and 1527, respectively, wherein the VH, when paired with a VL comprising the amino acid sequence shown in SEQ ID NOs: 1044, 1689, or 1690, binds to LILRB1 and / or LILRB2; (90) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 1528, 1529 and 1530, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence shown in SEQ ID NO: 1043; (91) an immunoglobulin heavy chain or a fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 of the amino acid sequences shown in SEQ ID NOs: 1549, 1550 and 1551, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 1046; (92) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 1552, 1553 and 1554, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence shown in SEQ ID NO: 1045; (93) an immunoglobulin heavy chain or fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 1573, 1574 and 1575, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 1048; (94) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 1576, 1577 and 1578, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence shown in SEQ ID NO: 1047; (95) an immunoglobulin heavy chain or fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 1597, 1598 and 1599, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 1050; (96) an immunoglobulin light chain or a fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 of the amino acid sequences shown in SEQ ID NOs: 1600, 1601 and 1602, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence shown in SEQ ID NO: 1049; (97) an immunoglobulin heavy chain or a fragment thereof, comprising a VH comprising CDRs 1, 2 and 3 of the amino acid sequences shown in SEQ ID NOs: 1621, 1622 and 1623, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 1052; (98) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2 and 3 comprising the amino acid sequences shown in SEQ ID NOs: 1624, 1625 and 1626, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence shown in SEQ ID NO: 1051; (99) an immunoglobulin heavy chain or fragment thereof, comprising a VH comprising CDRs 1, 2 and 3, comprising the amino acid sequences shown in SEQ ID NOs: 1645, 1646 and 1647, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 1054; (100) an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDRs 1, 2, and 3 comprising the amino acid sequences shown in SEQ ID NOs: 1648, 1649, and 1650, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH comprising the amino acid sequence shown in SEQ ID NO: 1053; (101) an immunoglobulin heavy chain or a fragment thereof, comprising a VH comprising CDRs 1, 2 and 3, wherein the VH comprises the amino acid sequences shown in SEQ ID NOs: 1669, 1670 and 1671, respectively, wherein the VH binds to LILRB1 and / or LILRB2 when paired with a VL comprising the amino acid sequence shown in SEQ ID NO: 1056; or (102) An immunoglobulin light chain or fragment thereof, comprising a VL including CDRs 1, 2 and 3, comprising the amino acid sequences shown in SEQ ID NOs: 1672, 1673 and 1674, respectively, wherein the VL binds to LILRB1 and / or LILRB2 when paired with a VH including the amino acid sequence shown in SEQ ID NO: 1055.

60. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 7, 8 and 9.

61. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 10, 11 and 12.

62. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 37, 38 and 39.

63. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 40, 41 and 42.

64. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 67, 68 and 69.

65. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs:70, 71 and 72.

66. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs:97, 98 and 99.

67. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 100, 101 and 102.

68. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 127, 128 and 129.

69. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 130, 131 and 132.

70. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 157, 158 and 159.

71. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 160, 161 and 162.

72. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 187, 188 and 189.

73. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 190, 191 and 192.

74. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 217, 218 and 219.

75. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 220, 221 and 222.

76. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 247, 248 and 249.

77. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 250, 251 and 252.

78. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 277, 278 and 279.

79. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 280, 281 and 282.

80. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 307, 308 and 309.

81. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 310, 311 and 312.

82. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 337, 338 and 339.

83. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 340, 341 and 342.

84. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 367, 368 and 369.

85. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 370, 371 and 372.

86. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 397, 398 and 399.

87. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 400, 401 and 402.

88. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 427, 428 and 429.

89. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 430, 431 and 432.

90. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 457, 458 and 459.

91. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 460, 461 and 462.

92. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 487, 488 and 489.

93. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 490, 491 and 492.

94. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 517, 518 and 519.

95. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 520, 521 and 522.

96. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 547, 548 and 549.

97. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 550, 551 and 552.

98. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 577, 578 and 579.

99. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 580, 581 and 582.

100. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 607, 608 and 609.

101. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 610, 611 and 612.

102. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 637, 638 and 639.

103. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 640, 641 and 642.

104. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 667, 668 and 669.

105. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 700, 701 and 702.

106. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 697, 698 and 699.

107. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 700, 701 and 702.

108. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 727, 728 and 729.

109. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 730, 731 and 732.

110. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1069, 1070 and 1071.

111. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1072, 1073 and 1074.

112. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1093, 1094 and 1095.

113. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having the amino acid sequences set forth in SEQ ID NOs 1096, 1097 and 1098.

114. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1117, 1118 and 1119.

115. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1120, 1121 and 1122.

116. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1141, 1142 and 1143.

117. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1144, 1145 and 1146.

118. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1165, 1166 and 1167.

119. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1168, 1169 and 1170.

120. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1189, 1190 and 1191.

121. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1192, 1193 and 1194.

122. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1213, 1214 and 1215.

123. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1216, 1217 and 1218.

124. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having the amino acid sequences set forth in SEQ ID NOs: 1237, 1238 and 1239.

125. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1240, 1241 and 1242.

126. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1261, 1262 and 1263.

127. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1264, 1265 and 1266.

128. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1285, 1286 and 1287.

129. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1288, 1289 and 1290.

130. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1309, 1310 and 1311.

131. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1312, 1313 and 1314.

132. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1333, 1334 and 1335.

133. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1336, 1337 and 1338.

134. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1357, 1358 and 1359.

135. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having the amino acid sequence set forth in SEQ ID Nos 1360, 1361 and 1362.

136. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1381, 1382 and 1383.

137. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1384, 1385 and 1386.

138. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1405, 1406 and 1407.

139. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1408, 1409 and 1410.

140. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1429, 1430 and 1431.

141. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1432, 1433 and 1434.

142. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs 1453, 1454 and 1455.

143. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1456, 1457 and 1458.

144. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1477, 1478 and 1479.

145. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1480, 1481 and 1482.

146. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having the amino acid sequences set forth in SEQ ID NOs: 1501, 1502 and 1503.

147. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1504, 1505 and 1506.

148. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1525, 1526 and 1527.

149. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1528, 1529 and 1530.

150. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1549, 1550 and 1551.

151. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1552, 1553 and 1554.

152. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1573, 1574 and 1575.

153. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1576, 1577 and 1578.

154. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1597, 1598 and 1599.

155. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having the amino acid sequences set forth in SEQ ID NOs: 1600, 1601 and 1602.

156. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1621, 1622 and 1623.

157. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1624, 1625 and 1626.

158. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1645, 1646 and 1647.

159. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1648, 1649 and 1650.

160. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VH having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1669, 1670 and 1671.

161. The nucleic acid of claim 59, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide comprising an immunoglobulin heavy chain or a fragment thereof comprising a VL having CDR1, CDR2 and CDR3 having an amino acid sequence set forth in SEQ ID NOs: 1672, 1673 and 1674.

162. The nucleic acid of any one of claims 59-161, wherein When VH is paired with VL, it specifically binds to human LILRB1 and / or LILRB2; or when VL is paired with VH, it specifically binds to human LILRB1 and / or LILRB2.

163. The nucleic acid of any one of claims 59-162, wherein the immunoglobulin heavy chain or fragment thereof is a humanized immunoglobulin heavy chain or fragment thereof, and the immunoglobulin light chain or fragment thereof is a humanized immunoglobulin light chain or fragment thereof.

164. The nucleic acid of any one of claims 59-163, wherein the nucleic acid encodes a single-chain variable fragment (scFv) or a multispecific antibody (e.g., a bispecific antibody).

165. The nucleic acid of any one of claims 59-164, wherein the nucleic acid is cDNA.

166. A plasmid vector comprising one or more nucleic acids of any one of claims 59-165.

167. A vector comprising two nucleic acids according to any one of claims 59-165, wherein: The vector encodes a VL region and a VH region that jointly bind to LILRB1 and / or LILRB2.

168. A pair of plasmid vectors, each of which comprises one of the nucleic acids of any one of claims 59-165, wherein, The vector pair together encodes a VL region and a VH region that binds to LILRB1 and / or LILRB2.

169. A cell comprising the plasmid vector of claim 166 or 167, or the plasmid vector pair of claim 168.

170. The cell of claim 169, wherein the cell is a CHO cell.

171. A cell comprising one or more nucleic acids of any one of claims 59-165.

172. A cell comprising two nucleic acids of any one of claims 59-165.

173. The cell of claim 172, wherein the two nucleic acids together encode a VL region and a VH region that binds to LILRB1 and / or LILRB2.

174. A method for preparing an antibody or an antigen-binding fragment thereof, the method comprising a) culturing the cell of any one of claims 169-173 under conditions sufficient for the cell to produce the antibody or antigen-binding fragment; and b) collecting the antibodies or antigen-binding fragments produced by the cells.

175. An antibody or antigen-binding fragment that binds to LILRB1 and / or LILRB2, comprising a heavy chain variable region (VH) comprising an amino acid sequence that is at least 90% identical to a selected VH sequence, and a light chain variable region (VL) comprising an amino acid sequence that is at least 90% identical to a selected VL sequence, wherein: The selected VH sequence and the selected VL sequence are one of the following: (1) the selected VH sequence is SEQ ID NO: 751, and the selected VL sequence is SEQ ID NO: 752; (2) the selected VH sequence is SEQ ID NO: 753, and the selected VL sequence is SEQ ID NO: 754; (3) the selected VH sequence is SEQ ID NO: 755, and the selected VL sequence is SEQ ID NO: 756; (4) the selected VH sequence is SEQ ID NO: 757, and the selected VL sequence is SEQ ID NO: 758; (5) the selected VH sequence is SEQ ID NO: 759, and the selected VL sequence is SEQ ID NO: 760; (6) the selected VH sequence is SEQ ID NO: 761, and the selected VL sequence is SEQ ID NO: 762; (7) the selected VH sequence is SEQ ID NO: 763, and the selected VL sequence is SEQ ID NO: 764; (8) the selected VH sequence is SEQ ID NO: 765, and the selected VL sequence is SEQ ID NO: 766; (9) the selected VH sequence is SEQ ID NO: 767, and the selected VL sequence is SEQ ID NO: 768; (10) the selected VH sequence is SEQ ID NO: 769, and the selected VL sequence is SEQ ID NO: 770; (11) the selected VH sequence is SEQ ID NO: 771, and the selected VL sequence is SEQ ID NO: 772; (12) the selected VH sequence is SEQ ID NO: 773, and the selected VL sequence is SEQ ID NO: 774; (13) the selected VH sequence is SEQ ID NO: 775, and the selected VL sequence is SEQ ID NO: 776; (14) the selected VH sequence is SEQ ID NO: 777, and the selected VL sequence is SEQ ID NO: 778; (15) the selected VH sequence is SEQ ID NO: 779, and the selected VL sequence is SEQ ID NO: 780; (16) the selected VH sequence is SEQ ID NO: 781, and the selected VL sequence is SEQ ID NO: 782; (17) the selected VH sequence is SEQ ID NO: 783, and the selected VL sequence is SEQ ID NO: 784; (18) the selected VH sequence is SEQ ID NO: 785, and the selected VL sequence is SEQ ID NO: 786; (19) the selected VH sequence is SEQ ID NO: 787, and the selected VL sequence is SEQ ID NO: 788; (20) the selected VH sequence is SEQ ID NO: 789, and the selected VL sequence is SEQ ID NO: 790; (21) the selected VH sequence is SEQ ID NO: 791, and the selected VL sequence is SEQ ID NO: 792; (22) the selected VH sequence is SEQ ID NO: 793, and the selected VL sequence is SEQ ID NO: 794; (23) The selected VH sequence is SEQ ID NO: 795, and the selected VL sequence is SEQ ID NO: 796; (24) the selected VH sequence is SEQ ID NO: 797, and the selected VL sequence is SEQ ID NO: 798; (25) the selected VH sequence is SEQ ID NO: 799, and the selected VL sequence is SEQ ID NO: 800; (26) The selected VH sequence is SEQ ID NO: 841, and the selected VL sequence is SEQ ID NO: 842; (27) The selected VH sequence is SEQ ID NO: 843, and the selected VL sequence is SEQ ID NO: 844; (28) The selected VH sequence is SEQ ID NO: 845, and the selected VL sequence is SEQ ID NO: 846; (29) The selected VH sequence is SEQ ID NO: 847, and the selected VL sequence is SEQ ID NO: 848; (30) the selected VH sequence is SEQ ID NO: 849, and the selected VL sequence is SEQ ID NO: 850; (31) The selected VH sequence is SEQ ID NO: 851, and the selected VL sequence is SEQ ID NO: 852; (32) The selected VH sequence is SEQ ID NO: 853, and the selected VL sequence is SEQ ID NO: 854; (33) The selected VH sequence is SEQ ID NO: 855, and the selected VL sequence is SEQ ID NO: 856; (34) the selected VH sequence is SEQ ID NO: 857, and the selected VL sequence is SEQ ID NO: 858; (35) The selected VH sequence is SEQ ID NO: 859, and the selected VL sequence is SEQ ID NO: 860; (36) The selected VH sequence is SEQ ID NO: 861, and the selected VL sequence is SEQ ID NO: 862; (37) The selected VH sequence is SEQ ID NO: 863, and the selected VL sequence is SEQ ID NO: 864; (38) The selected VH sequence is SEQ ID NO: 865, and the selected VL sequence is SEQ ID NO: 866; (39) The selected VH sequence is SEQ ID NO: 867, and the selected VL sequence is SEQ ID NO: 868; (40) The selected VH sequence is SEQ ID NO: 869, and the selected VL sequence is SEQ ID NO: 870; (41) The selected VH sequence is SEQ ID NO: 871, and the selected VL sequence is SEQ ID NO: 872; (42) The selected VH sequence is SEQ ID NO: 873, and the selected VL sequence is SEQ ID NO: 874; (43) The selected VH sequence is SEQ ID NO: 875, and the selected VL sequence is SEQ ID NO: 876; (44) The selected VH sequence is SEQ ID NO: 877, and the selected VL sequence is SEQ ID NO: 878; (45) The selected VH sequence is SEQ ID NO: 879, and the selected VL sequence is SEQ ID NO: 880; (46) The selected VH sequence is SEQ ID NO: 881, and the selected VL sequence is SEQ ID NO: 882; (47) The selected VH sequence is SEQ ID NO: 883, and the selected VL sequence is SEQ ID NO: 884; (48) The selected VH sequence is SEQ ID NO: 885, and the selected VL sequence is SEQ ID NO: 886; (49) The selected VH sequence is SEQ ID NO: 887, and the selected VL sequence is SEQ ID NO: 888; (50) The selected VH sequence is SEQ ID NO: 889, and the selected VL sequence is SEQ ID NO: 890; (51) The selected VH sequence is SEQ ID NO: 891, and the selected VL sequence is SEQ ID NO: 892; (52) The selected VH sequence is SEQ ID NO: 893, and the selected VL sequence is SEQ ID NO: 894; (53) The selected VH sequence is SEQ ID NO: 895, and the selected VL sequence is SEQ ID NO: 896; (54) The selected VH sequence is SEQ ID NO: 897, and the selected VL sequence is SEQ ID NO: 898; (55) The selected VH sequence is SEQ ID NO: 899, and the selected VL sequence is SEQ ID NO: 900; (56) The selected VH sequence is SEQ ID NO: 901, and the selected VL sequence is SEQ ID NO: 902; (57) The selected VH sequence is SEQ ID NO: 903, and the selected VL sequence is SEQ ID NO: 904; (58) The selected VH sequence is SEQ ID NO: 905, and the selected VL sequence is SEQ ID NO: 906; (59) The selected VH sequence is SEQ ID NO: 907, and the selected VL sequence is SEQ ID NO: 908; (60) The selected VH sequence is SEQ ID NO: 909, and the selected VL sequence is SEQ ID NO: 910; (61) The selected VH sequence is SEQ ID NO: 911, and the selected VL sequence is SEQ ID NO: 912; (62) The selected VH sequence is SEQ ID NO: 913, and the selected VL sequence is SEQ ID NO: 914; (63) The selected VH sequence is SEQ ID NO: 915, and the selected VL sequence is SEQ ID NO: 916; (64) The selected VH sequence is SEQ ID NO: 917, and the selected VL sequence is SEQ ID NO: 918; (65) The selected VH sequence is SEQ ID NO: 919, and the selected VL sequence is SEQ ID NO: 920; (66) The selected VH sequence is SEQ ID NO: 921, and the selected VL sequence is SEQ ID NO: 922; (67) The selected VH sequence is SEQ ID NO: 923, and the selected VL sequence is SEQ ID NO: 924; (68) The selected VH sequence is SEQ ID NO: 925, and the selected VL sequence is SEQ ID NO: 926; (69) The selected VH sequence is SEQ ID NO: 927, and the selected VL sequence is SEQ ID NO: 928; (70) The selected VH sequence is SEQ ID NO: 929, and the selected VL sequence is SEQ ID NO: 930; (71) The selected VH sequence is SEQ ID NO: 931, and the selected VL sequence is SEQ ID NO: 932; (72) The selected VH sequence is SEQ ID NO: 933, and the selected VL sequence is SEQ ID NO: 934; (73) The selected VH sequence is SEQ ID NO: 935, and the selected VL sequence is SEQ ID NO: 936; (74) The selected VH sequence is SEQ ID NO: 937, and the selected VL sequence is SEQ ID NO: 938; (75) The selected VH sequence is SEQ ID NO: 939, and the selected VL sequence is SEQ ID NO: 940; (76) The selected VH sequence is SEQ ID NO: 941, and the selected VL sequence is SEQ ID NO: 942; (77) The selected VH sequence is SEQ ID NO: 943, and the selected VL sequence is SEQ ID NO: 944; (78) The selected VH sequence is SEQ ID NO: 945, and the selected VL sequence is SEQ ID NO: 946; (79) The selected VH sequence is SEQ ID NO: 947, and the selected VL sequence is SEQ ID NO: 948; (80) The selected VH sequence is SEQ ID NO: 949, and the selected VL sequence is SEQ ID NO: 950; (81) The selected VH sequence is SEQ ID NO: 951, and the selected VL sequence is SEQ ID NO: 952; (82) The selected VH sequence is SEQ ID NO: 953, and the selected VL sequence is SEQ ID NO: 954; (83) The selected VH sequence is SEQ ID NO: 955, and the selected VL sequence is SEQ ID NO: 956; (84) The selected VH sequence is SEQ ID NO: 957, and the selected VL sequence is SEQ ID NO: 958; (85) The selected VH sequence is SEQ ID NO: 959, and the selected VL sequence is SEQ ID NO: 960; (86) The selected VH sequence is SEQ ID NO: 961, and the selected VL sequence is SEQ ID NO: 962; (87) The selected VH sequence is SEQ ID NO: 963, and the selected VL sequence is SEQ ID NO: 964; (88) The selected VH sequence is SEQ ID NO: 965, and the selected VL sequence is SEQ ID NO: 966; (89) The selected VH sequence is SEQ ID NO: 967, and the selected VL sequence is SEQ ID NO: 968; (90) The selected VH sequence is SEQ ID NO: 969, and the selected VL sequence is SEQ ID NO: 970; (91) The selected VH sequence is SEQ ID NO: 971, and the selected VL sequence is SEQ ID NO: 972; (92) The selected VH sequence is SEQ ID NO: 973, and the selected VL sequence is SEQ ID NO: 974; (93) The selected VH sequence is SEQ ID NO: 975, and the selected VL sequence is SEQ ID NO: 976; (94) The selected VH sequence is SEQ ID NO: 977, and the selected VL sequence is SEQ ID NO: 978; (95) the selected VH sequence is SEQ ID NO: 979, and the selected VL sequence is SEQ ID NO: 980, 981, 982, 983 or 984; (96) The selected VH sequence is SEQ ID NO: 985, and the selected VL sequence is SEQ ID NO: 986; (97) the selected VH sequence is SEQ ID NO: 987, 1687 or 1688, and the selected VL sequence is SEQ ID NO: 988, 989, 990, 991 or 992; (98) The selected VH sequence is SEQ ID NO: 993, and the selected VL sequence is SEQ ID NO: 994; (99) The selected VH sequence is SEQ ID NO: 995, and the selected VL sequence is SEQ ID NO: 996; (100) The selected VH sequence is SEQ ID NO: 997, and the selected VL sequence is SEQ ID NO: 998; (101) the selected VH sequence is SEQ ID NO: 999, and the selected VL sequence is SEQ ID NO: 1000, 1001, 1002, 1003 or 1004; (102) The selected VH sequence is SEQ ID NO: 1005, and the selected VL sequence is SEQ ID NO: 1006; (103) the selected VH sequence is SEQ ID NO: 1007, and the selected VL sequence is SEQ ID NO: 1008, 1009 or 1010; (104) The selected VH sequence is SEQ ID NO: 1011, and the selected VL sequence is SEQ ID NO: 1012; (105) The selected VH sequence is SEQ ID NO: 1013, and the selected VL sequence is SEQ ID NO: 1014; (106) The selected VH sequence is SEQ ID NO: 1015, and the selected VL sequence is SEQ ID NO: 1016; (107) The selected VH sequence is SEQ ID NO: 1017, and the selected VL sequence is SEQ ID NO: 1018; (108) The selected VH sequence is SEQ ID NO: 1019, and the selected VL sequence is SEQ ID NO: 1020; (109) The selected VH sequence is SEQ ID NO: 1021, and the selected VL sequence is SEQ ID NO: 1022; (110) The selected VH sequence is SEQ ID NO: 1023, and the selected VL sequence is SEQ ID NO: 1024; (111) The selected VH sequence is SEQ ID NO: 1025, and the selected VL sequence is SEQ ID NO: 1026; (112) The selected VH sequence is SEQ ID NO: 1027, and the selected VL sequence is SEQ ID NO: 1028; (113) The selected VH sequence is SEQ ID NO: 1029, and the selected VL sequence is SEQ ID NO: 1030; (114) The selected VH sequence is SEQ ID NO: 1031, and the selected VL sequence is SEQ ID NO: 1032; (115) The selected VH sequence is SEQ ID NO: 1033, and the selected VL sequence is SEQ ID NO: 1034; (116) The selected VH sequence is SEQ ID NO: 1035, and the selected VL sequence is SEQ ID NO: 1036; (117) The selected VH sequence is SEQ ID NO: 1037, and the selected VL sequence is SEQ ID NO: 1038; (118) The selected VH sequence is SEQ ID NO: 1039, and the selected VL sequence is SEQ ID NO: 1040; (119) The selected VH sequence is SEQ ID NO: 1041, and the selected VL sequence is SEQ ID NO: 1042; (120) the selected VH sequence is SEQ ID NO: 1043, and the selected VL sequence is SEQ ID NO: 1044, 1689 or 1690; (121) The selected VH sequence is SEQ ID NO: 1045, and the selected VL sequence is SEQ ID NO: 1046; (122) The selected VH sequence is SEQ ID NO: 1047, and the selected VL sequence is SEQ ID NO: 1048; (123) The selected VH sequence is SEQ ID NO: 1049, and the selected VL sequence is SEQ ID NO: 1050; (124) The selected VH sequence is SEQ ID NO: 1051, and the selected VL sequence is SEQ ID NO: 1052; (125) the selected VH sequence is SEQ ID NO: 1053, the selected VL sequence is SEQ ID NO: 1054; and (126) The selected VH sequence is SEQ ID NO: 1055, and the selected VL sequence is SEQ ID NO: 1056.

176. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 751 and the VL comprises the sequence of SEQ ID NO:

752.

177. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 753 and the VL comprises the sequence of SEQ ID NO:

754.

178. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 755 and the VL comprises the sequence of SEQ ID NO:

756.

179. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 757 and the VL comprises the sequence of SEQ ID NO:

758.

180. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 759 and VL comprises the sequence of SEQ ID NO:

760.

181. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 761 and the VL comprises the sequence of SEQ ID NO:

762.

182. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 763 and the VL comprises the sequence of SEQ ID NO:

764.

183. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 765 and VL comprises the sequence of SEQ ID NO:

766.

184. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 767 and VL comprises the sequence of SEQ ID NO:

768.

185. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 769 and the VL comprises the sequence of SEQ ID NO:

770.

186. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 771 and the VL comprises the sequence of SEQ ID NO:

772.

187. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 773 and VL comprises the sequence of SEQ ID NO:

774.

188. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 775 and the VL comprises the sequence of SEQ ID NO:

776.

189. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 777 and the VL comprises the sequence of SEQ ID NO:

778.

190. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 779 and the VL comprises the sequence of SEQ ID NO:

780.

191. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 781 and the VL comprises the sequence of SEQ ID NO:

782.

192. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 783 and VL comprises the sequence of SEQ ID NO:

784.

193. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 785 and VL comprises the sequence of SEQ ID NO:

786.

194. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 787 and VL comprises the sequence of SEQ ID NO:

788.

195. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 789 and the VL comprises the sequence of SEQ ID NO:

790.

196. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 791 and VL comprises the sequence of SEQ ID NO:

792.

197. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 793 and the VL comprises the sequence of SEQ ID NO:

794.

198. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 795 and VL comprises the sequence of SEQ ID NO:

796.

199. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 797 and the VL comprises the sequence of SEQ ID NO:

798.

200. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 799 and the VL comprises the sequence of SEQ ID NO:

800.

201. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 841 and the VL comprises the sequence of SEQ ID NO:

842.

202. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 843 and the VL comprises the sequence of SEQ ID NO:

844.

203. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 845 and the VL comprises the sequence of SEQ ID NO:

846.

204. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 847 and the VL comprises the sequence of SEQ ID NO:

848.

205. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 849 and the VL comprises the sequence of SEQ ID NO:

850.

206. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 851 and VL comprises the sequence of SEQ ID NO:

852.

207. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 853 and the VL comprises the sequence of SEQ ID NO:

854.

208. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 855 and the VL comprises the sequence of SEQ ID NO:

856.

209. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 857 and VL comprises the sequence of SEQ ID NO:

858.

210. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 859 and the VL comprises the sequence of SEQ ID NO:

860.

211. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 861 and the VL comprises the sequence of SEQ ID NO:

862.

212. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 863 and the VL comprises the sequence of SEQ ID NO:

864.

213. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 865 and the VL comprises the sequence of SEQ ID NO:

866.

214. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 867 and the VL comprises the sequence of SEQ ID NO:

868.

215. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 869 and the VL comprises the sequence of SEQ ID NO:

870.

216. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 871 and the VL comprises the sequence of SEQ ID NO:

872.

217. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 873 and the VL comprises the sequence of SEQ ID NO:

874.

218. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 875 and the VL comprises the sequence of SEQ ID NO:

876.

219. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 877 and the VL comprises the sequence of SEQ ID NO:

878.

220. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 879 and the VL comprises the sequence of SEQ ID NO:

880.

221. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 881 and the VL comprises the sequence of SEQ ID NO:

882.

222. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 883 and the VL comprises the sequence of SEQ ID NO:

884.

223. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 885 and the VL comprises the sequence of SEQ ID NO:

886.

224. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 887 and the VL comprises the sequence of SEQ ID NO:

888.

225. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 889 and the VL comprises the sequence of SEQ ID NO:

890.

226. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 891 and the VL comprises the sequence of SEQ ID NO:

892.

227. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 893 and the VL comprises the sequence of SEQ ID NO:

894.

228. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 895 and the VL comprises the sequence of SEQ ID NO:

896.

229. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 897 and VL comprises the sequence of SEQ ID NO:

898.

230. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 899 and the VL comprises the sequence of SEQ ID NO:

900.

231. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:901 and the VL comprises the sequence of SEQ ID NO:

902.

232. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 903 and the VL comprises the sequence of SEQ ID NO:

904.

233. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:905 and the VL comprises the sequence of SEQ ID NO:

906.

234. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:907 and the VL comprises the sequence of SEQ ID NO:

908.

235. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:909 and the VL comprises the sequence of SEQ ID NO:

910.

236. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:911 and VL comprises the sequence of SEQ ID NO:

912.

237. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:913 and the VL comprises the sequence of SEQ ID NO:

914.

238. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:915 and the VL comprises the sequence of SEQ ID NO:

916.

239. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:917 and the VL comprises the sequence of SEQ ID NO:

918.

240. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:919 and the VL comprises the sequence of SEQ ID NO:

920.

241. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:921 and the VL comprises the sequence of SEQ ID NO:

922.

242. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 923 and VL comprises the sequence of SEQ ID NO:

924.

243. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:925 and the VL comprises the sequence of SEQ ID NO:

926.

244. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:927 and the VL comprises the sequence of SEQ ID NO:

928.

245. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:929 and the VL comprises the sequence of SEQ ID NO:

930.

246. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:931 and VL comprises the sequence of SEQ ID NO:

932.

247. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:933 and the VL comprises the sequence of SEQ ID NO:

934.

248. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:935 and the VL comprises the sequence of SEQ ID NO:

936.

249. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:937 and the VL comprises the sequence of SEQ ID NO:

938.

250. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:939 and the VL comprises the sequence of SEQ ID NO:

940.

251. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:941 and the VL comprises the sequence of SEQ ID NO:

942.

252. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 943 and the VL comprises the sequence of SEQ ID NO:

944.

253. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:945 and VL comprises the sequence of SEQ ID NO:

946.

254. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:947 and VL comprises the sequence of SEQ ID NO:

948.

255. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:949 and the VL comprises the sequence of SEQ ID NO:

950.

256. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:951 and VL comprises the sequence of SEQ ID NO:

952.

257. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:953 and the VL comprises the sequence of SEQ ID NO:

954.

258. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:955 and the VL comprises the sequence of SEQ ID NO:

956.

259. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:957 and VL comprises the sequence of SEQ ID NO:

958.

260. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:959 and the VL comprises the sequence of SEQ ID NO:

960.

261. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:961 and the VL comprises the sequence of SEQ ID NO:

962.

262. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 963 and the VL comprises the sequence of SEQ ID NO:

964.

263. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:965 and the VL comprises the sequence of SEQ ID NO:

966.

264. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:967 and the VL comprises the sequence of SEQ ID NO:

968.

265. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:969 and the VL comprises the sequence of SEQ ID NO:

970.

266. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:971 and VL comprises the sequence of SEQ ID NO:

972.

267. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 973 and VL comprises the sequence of SEQ ID NO:

974.

268. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:975 and VL comprises the sequence of SEQ ID NO:

976.

269. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 977 and the VL comprises the sequence of SEQ ID NO:

978.

270. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 979 and the VL comprises the sequence of SEQ ID NO: 980, 981, 982, 983 or 984.

271. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:985 and VL comprises the sequence of SEQ ID NO:

986.

272. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 987, 1687 or 1688, and VL comprises the sequence of SEQ ID NO: 988, 989, 990, 991 or 992.

273. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 993 and the VL comprises the sequence of SEQ ID NO:

994.

274. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO:995 and the VL comprises the sequence of SEQ ID NO:

996.

275. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 997 and VL comprises the sequence of SEQ ID NO:

998.

276. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 999 and the VL comprises the sequence of SEQ ID NO: 1000, 1001, 1002, 1003 or 1004.

277. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 1005 and the VL comprises the sequence of SEQ ID NO: 1006.

278. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 1007 and the VL comprises the sequence of SEQ ID NO: 1008, 1009, 1010.

279. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 1011 and the VL comprises the sequence of SEQ ID NO: 1012.

280. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 1013 and VL comprises the sequence of SEQ ID NO: 1014.

281. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 1015 and the VL comprises the sequence of SEQ ID NO: 1016.

282. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 1017 and the VL comprises the sequence of SEQ ID NO: 1018.

283. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 1019 and the VL comprises the sequence of SEQ ID NO: 1020.

284. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 1021 and the VL comprises the sequence of SEQ ID NO: 1022.

285. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 1023 and the VL comprises the sequence of SEQ ID NO: 1024.

286. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 1025 and the VL comprises the sequence of SEQ ID NO: 1026.

287. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 1027 and the VL comprises the sequence of SEQ ID NO: 1028.

288. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 1029 and the VL comprises the sequence of SEQ ID NO: 1030.

289. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 1031 and the VL comprises the sequence of SEQ ID NO: 1032.

290. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 1033 and the VL comprises the sequence of SEQ ID NO: 1034.

291. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 1035 and the VL comprises the sequence of SEQ ID NO: 1036.

292. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 1037 and the VL comprises the sequence of SEQ ID NO: 1038.

293. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 1039 and the VL comprises the sequence of SEQ ID NO: 1040.

294. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 1041 and the VL comprises the sequence of SEQ ID NO: 1042.

295. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 1043 and the VL comprises the sequence of SEQ ID NO: 1044, 1689 or 1690.

296. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 1045 and the VL comprises the sequence of SEQ ID NO: 1046.

297. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 1047 and the VL comprises the sequence of SEQ ID NO: 1048.

298. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 1049 and the VL comprises the sequence of SEQ ID NO: 1050.

299. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 1051 and VL comprises the sequence of SEQ ID NO: 1052.

300. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 1053 and the VL comprises the sequence of SEQ ID NO: 1054.

301. The antibody or antigen-binding fragment of claim 175, wherein VH comprises the sequence of SEQ ID NO: 1055 and VL comprises the sequence of SEQ ID NO: 1056.

302. The antibody or antigen-binding fragment of any one of claims 175-301, wherein the antibody or antigen-binding fragment specifically binds to human LILRB1 and / or LILRB2.

303. The antibody or antigen-binding fragment of any one of claims 175-302, wherein the antibody or antigen-binding fragment is a humanized antibody or antigen-binding fragment thereof.

304. The antibody or antigen-binding fragment of any one of claims 175-303, wherein the antibody or antigen-binding fragment is a single-chain variable fragment (scFV) or a multispecific antibody (e.g., a bispecific antibody).

305. An antibody-drug conjugate comprising the antibody or antigen-binding fragment thereof of any one of claims 1-58 and 175-304 covalently bound to a therapeutic agent.

306. The antibody drug conjugate of claim 305, wherein the therapeutic agent is a cytotoxic or cytostatic agent.

307. A method of treating a subject having cancer, the method comprising administering to the subject a therapeutically effective amount of a composition comprising the antibody or antigen-binding fragment of any one of claims 1-58 and 175-304, or the antibody-drug conjugate of claim 227 or 228.

308. The method of claim 307, wherein the subject has a solid tumor or a hematological cancer.

309. The method of claim 307, wherein the cancer is glioma, thyroid cancer, lung cancer, colorectal cancer, head and neck cancer, gastric cancer, liver cancer, pancreatic cancer, kidney cancer, urothelial cancer, prostate cancer, testicular cancer, breast cancer, cervical cancer, endometrial cancer, ovarian cancer or melanoma.

310. A method for reducing tumor growth rate, the method comprising The tumor cells are contacted with an effective amount of a composition comprising the antibody or antigen-binding fragment of any one of claims 1-58 and 175-304, or the antibody-drug conjugate of claim 305 or 306.

311. A method for killing tumor cells, the method comprising The tumor cells are contacted with an effective amount of a composition comprising the antibody or antigen-binding fragment of any one of claims 1-58 and 175-304, or the antibody-drug conjugate of claim 305 or 306.

312. A pharmaceutical composition comprising the antibody or antigen-binding fragment of any one of claims 1-58 and 175-304, and a pharmaceutically acceptable carrier.

313. A pharmaceutical composition comprising the antibody-drug conjugate of claim 305 or 306, and a pharmaceutically acceptable carrier.

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