Anti-CEACAM5 antibody

Abstract

This specification discloses antibodies that bind to CEACAM5, their antigen-binding fragments, and their uses, nucleic acids encoding these antibodies and antigen-binding fragments, vectors containing these nucleic acids, and host cells containing these nucleic acids or vectors. This specification further discloses pharmaceutical compositions and conjugates containing these antibodies, and methods of treatment by administration of these antibodies.

Description

[Technical Field] 【0001】 This invention relates to an antibody that binds to CEACAM5, its antigen-binding fragment, and its uses. [Background technology] 【0002】 Carcinoembryonic antigens (CEAs) are glycoproteins involved in cell adhesion. CEAs were first identified in 1965 as proteins normally expressed in the fetal intestinal tract during the first six months of pregnancy (Gold and Freedman, J Exp Med [Journal of Experimental Medicine], 121, 439, 1965), and were found in pancreatic cancer, liver cancer, and colon cancer. The CEA family belongs to the immunoglobulin superfamily. The CEA family consists of 18 genes and is subdivided into two protein subgroups: the carcinoembryonic antigen-associated cell adhesion molecule (CEACAM) subgroup and the pregnancy-specific glycoprotein subgroup (Kammerer and Zimmermann, BMC Biology [BMC Biology] 2010, 8:12). In humans, the CEACAM subgroup consists of seven members: CEACAM1, CEACAM3, CEACAM4, CEACAM5, CEACAM6, CEACAM7, and CEACAM8. 【0003】 CEACAM5 (Carcinoembryonic Antigen-Related Cell Adhesion Molecule 5), also known as CEA or CD66e, is a well-known tumor-associated antigen that has been used for many years as a biomarker for cancer diagnosis. CEACAM5 expression is strongly associated with several cancers. It is upregulated in colorectal cancer, rectal cancer, lung cancer, pancreatic cancer, and gastric cancer, and is hundreds of times more altered than in normal tissue. Due to its distribution characteristics, CEACAM5 is a good target for therapeutic agents such as antibodies and ADCs (antibody-drug conjugates). For example, Sanofi's SAR408701 (tusamitamab ravtansine) contains the anti-CEACAM5 antibody SAR408377 (tusamitamab, also known as huMab2-3) which covalently binds to the cytotoxic drug DM4 (effective tubulin-destabilized maytansine) via an N-succinimidyl 4-(2-pyridyldithio)butyrate (SPDB) linker. 【0004】 Therefore, the development of antibodies targeting CEACAM5 is important in tumor immunotherapy. [Overview of the project] 【0005】 The present invention provides antibodies that bind to CEACAM5 and antigen-binding fragments thereof, and includes monoclonal antibodies that target CEACAM5. 【0006】 The monoclonal antibodies targeting CEACAM5 of the present invention are naturally occurring antibodies that have binding activity to both human and cynomolgus monkey CEACAM5. These antibodies are specific to CEACAM5 but do not cross-react with other CEA family members (i.e., CEACAM1, CEACAM3, and CEACAM8). Due to the high homology among CEA family members and the relatively low homology with cynomolgus monkey CEACAM5, it is extremely difficult to produce antibodies that specifically target CEACAM5 and cross-react with cynomolgus monkey CEACAM5. These antibodies also possess good internalization activity, making them potential antibody molecules suitable for the development of ADC drugs. 【0007】 In a first aspect, the present invention provides an antibody or antigen-binding fragment thereof that binds to CEACAM5, wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), and further, (1) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 7, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 8. (2) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 55, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 56. (3) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 16, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 17. (4) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO:24, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:25. (5) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO:30, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:31. (6) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 40, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 41. (7) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 49, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 50. (8) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 59, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 60. (9) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 65, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 66. (10) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 72, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 73. (11) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 82, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 83. (12) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO:91, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:92. (13) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO:96, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:97. (14) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 102, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 103. (15) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 108, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 109. (16) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 114, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 115. (17) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 120, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 121. (18) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 124, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 125. (19) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 128, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 129. (20) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 135, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 136. (21) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 140, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 141. (22) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 146, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 147. (23) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 152, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 153. (24) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 158, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 159. (25) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 164, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 165. (26) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 102, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 168. (27) The VH contains the HCDR 1-3 of VH having the amino acid sequence shown in SEQ ID NO: 171, and the VL contains the LCDR 1-3 of VL having the amino acid sequence shown in SEQ ID NO: 172. (28) The VH contains the HCDR 1-3 of VH having the amino acid sequence shown in SEQ ID NO: 176, and the VL contains the LCDR 1-3 of VL having the amino acid sequence shown in SEQ ID NO: 177. (29) The VH contains the HCDR 1-3 of VH having the amino acid sequence shown in SEQ ID NO: 181, and the VL contains the LCDR 1-3 of VL having the amino acid sequence shown in SEQ ID NO: 182. (30) The VH contains the HCDR 1-3 of VH having the amino acid sequence shown in SEQ ID NO: 186, and the VL contains the LCDR 1-3 of VL having the amino acid sequence shown in SEQ ID NO: 187. (31) The VH contains the HCDR 1-3 of VH having the amino acid sequence shown in SEQ ID NO: 191, and the VL contains the LCDR 1-3 of VL having the amino acid sequence shown in SEQ ID NO: 192. (32) The VH contains the HCDR 1-3 of VH having the amino acid sequence shown in SEQ ID NO: 196, and the VL contains the LCDR 1-3 of VL having the amino acid sequence shown in SEQ ID NO: 197. (33) The VH contains the HCDR 1-3 of VH having the amino acid sequence shown in SEQ ID NO: 201, and the VL contains the LCDR 1-3 of VL having the amino acid sequence shown in SEQ ID NO: 202, or (34) The VH contains the HCDR 1-3 of VH having the amino acid sequence shown in SEQ ID NO: 102, and the VL contains the LCDR 1-3 of VL having the amino acid sequence shown in SEQ ID NO: 206. 【0008】 In some embodiments, the present invention provides an antibody or an antigen-binding fragment thereof that binds to CEACAM5, wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), and wherein (1) The VH comprises HCDR 1 to 3, each containing the amino acid sequences shown in SEQ ID NO: 1, 2, and 3, respectively, and the VL comprises LCDR 1 to 3, each containing the amino acid sequences shown in SEQ ID NO: 4, 5, and 6, (2) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 44, 53 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 54, 38 and 39, respectively. (3) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 11, 12 and 13, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 4, 14 and 15, respectively. (4) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 20, 21 and 22, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 4, 5 and 23, respectively. (5) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 28, 21 and 29, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 4, 5 and 6, respectively. (6) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 34, 35 and 36, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 37, 38 and 39, respectively. (7) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 44, 45 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 47, 38 and 48, respectively. (8) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 44, 53 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 63, 64 and 39, respectively. (9) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 69, 70, and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 71, 38, and 39, respectively. (10) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 76, 77, and 78, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 79, 80, and 81, respectively. (11) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 86, 87, and 88, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 89, 80, and 90, respectively. (12) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 86, 87, and 95, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 89, 80, and 90, respectively. (13) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 34, 100 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 37, 38 and 101, respectively. (14) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 106, 100, and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 107, 38, and 39, respectively. (15) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 44, 112 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 113, 38 and 39, respectively. (16) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 44, 118 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 119, 38 and 39, respectively. (17) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 106, 118 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 113, 38 and 39, respectively. (18) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 34, 100 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 71, 38 and 39, respectively. (19) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 44, 132 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 133, 38 and 134, respectively. (20) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 69, 100 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 139, 38 and 39, respectively. (21) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 144, 77, and 95, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 89, 80, and 145, respectively. (22) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 150, 77 and 151, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 89, 80 and 90, respectively. (23) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 34, 118 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 156, 38 and 157, respectively. (24) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 69, 100 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 162, 163 and 48, respectively. (25) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 34, 100 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 37, 38 and 39, respectively. (26) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 44, 100 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 162, 38 and 39, respectively. (27) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 175, 77, and 95, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 89, 80, and 145, respectively. (28) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 44, 132 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 37, 38 and 180, respectively. (29) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 69, 100 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 185, 38 and 157, respectively. (30) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 44, 190 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 162, 38 and 48, respectively. (31) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 106, 112 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 195, 38 and 39, respectively. (32) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 34, 112, and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 200, 64, and 39, respectively, or (33) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 34, 100, and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 133, 205, and 39, respectively. 【0009】 In some embodiments, the present invention provides an antibody or antigen-binding fragment thereof that binds to CEACAM5, wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), and furthermore, (1) The VH contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:7, and the VL contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:8, (2) The VH contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 55, and the VL contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 56. (3) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:16, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:17. (4) The VH contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:24, and the VL contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:25. (5) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:30, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:31. (6) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:40, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:41. (7) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 49, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 50, (8) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 59, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 60, (9) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 65, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 66, (10) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:72, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:73, (11) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:82, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:83, (12) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:91, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:92, (13) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:96, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:97, (14) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:102, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:103, (15) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:108, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:109. (16) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:114, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:115. (17) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:120, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:121. (18) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:124, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:125. (19) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:128, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:129, (20) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:135, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:136. (21) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:140, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:141. (22) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:146, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:147. (23) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:152, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:153. (24) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:158, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:159. (25) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:164, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:165. (26) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:102, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:168. (27) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:171, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:172. (28) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:176, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:177. (29) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:181, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:182. (30) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:186, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:187. (31) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:191, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:192. (32) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:196, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:197. (33) The VH contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:201, and the VL contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:202, or (34) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:102, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:206. 【0010】 In preferred embodiments, the present invention provides an antibody or antigen-binding fragment thereof that binds to CEACAM5, wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), and further, (1) The VH contains the amino acid sequence shown in SEQ ID NO:7, and the VL contains the amino acid sequence shown in SEQ ID NO:8. (2) The VH contains the amino acid sequence shown in SEQ ID NO: 55, and the VL contains the amino acid sequence shown in SEQ ID NO: 56. (3) The VH contains the amino acid sequence shown in SEQ ID NO:16, and the VL contains the amino acid sequence shown in SEQ ID NO:17. (4) The VH contains the amino acid sequence shown in SEQ ID NO:24, and the VL contains the amino acid sequence shown in SEQ ID NO:25. (5) The VH contains the amino acid sequence shown in SEQ ID NO:30, and the VL contains the amino acid sequence shown in SEQ ID NO:31. (6) The VH comprises the amino acid sequence shown in SEQ ID NO:40, and the VL comprises the amino acid sequence shown in SEQ ID NO:41. (7) The VH contains the amino acid sequence shown in SEQ ID NO:49, and the VL contains the amino acid sequence shown in SEQ ID NO:50. (8) The VH contains the amino acid sequence shown in SEQ ID NO: 59, and the VL contains the amino acid sequence shown in SEQ ID NO: 60. (9) The VH contains the amino acid sequence shown in SEQ ID NO:65, and the VL contains the amino acid sequence shown in SEQ ID NO:66. (10) The VH comprises the amino acid sequence shown in SEQ ID NO:72, and the VL comprises the amino acid sequence shown in SEQ ID NO:73. (11) The VH comprises the amino acid sequence shown in SEQ ID NO:82, and the VL comprises the amino acid sequence shown in SEQ ID NO:83. (12) The VH comprises the amino acid sequence shown in SEQ ID NO:91, and the VL comprises the amino acid sequence shown in SEQ ID NO:92. (13) The VH comprises the amino acid sequence shown in SEQ ID NO:96, and the VL comprises the amino acid sequence shown in SEQ ID NO:97. (14) The VH comprises the amino acid sequence shown in SEQ ID NO:102, and the VL comprises the amino acid sequence shown in SEQ ID NO:103. (15) The VH comprises the amino acid sequence shown in SEQ ID NO:108, and the VL comprises the amino acid sequence shown in SEQ ID NO:109. (16) The VH comprises the amino acid sequence shown in SEQ ID NO:114, and the VL comprises the amino acid sequence shown in SEQ ID NO:115. (17) The VH comprises the amino acid sequence shown in SEQ ID NO:120, and the VL comprises the amino acid sequence shown in SEQ ID NO:121. (18) The VH comprises the amino acid sequence shown in SEQ ID NO:124, and the VL comprises the amino acid sequence shown in SEQ ID NO:125. (19) The VH comprises the amino acid sequence shown in SEQ ID NO:128, and the VL comprises the amino acid sequence shown in SEQ ID NO:129. (20) The VH comprises the amino acid sequence shown in SEQ ID NO:135, and the VL comprises the amino acid sequence shown in SEQ ID NO:136. (21) The VH comprises the amino acid sequence shown in SEQ ID NO:140, and the VL comprises the amino acid sequence shown in SEQ ID NO:141. (22) The VH comprises the amino acid sequence shown in SEQ ID NO:146, and the VL comprises the amino acid sequence shown in SEQ ID NO:147. (23) The VH comprises the amino acid sequence shown in SEQ ID NO:152, and the VL comprises the amino acid sequence shown in SEQ ID NO:153. (24) The VH comprises the amino acid sequence shown in SEQ ID NO:158, and the VL comprises the amino acid sequence shown in SEQ ID NO:159. (25) The VH comprises the amino acid sequence shown in SEQ ID NO:164, and the VL comprises the amino acid sequence shown in SEQ ID NO:165. (26) The VH comprises the amino acid sequence shown in SEQ ID NO:102, and the VL comprises the amino acid sequence shown in SEQ ID NO:168. (27) The VH comprises the amino acid sequence shown in SEQ ID NO:171, and the VL comprises the amino acid sequence shown in SEQ ID NO:172. (28) The VH comprises the amino acid sequence shown in SEQ ID NO:176, and the VL comprises the amino acid sequence shown in SEQ ID NO:177. (29) The VH comprises the amino acid sequence shown in SEQ ID NO:181, and the VL comprises the amino acid sequence shown in SEQ ID NO:182. (30) The VH comprises the amino acid sequence shown in SEQ ID NO:186, and the VL comprises the amino acid sequence shown in SEQ ID NO:187. (31) The VH comprises the amino acid sequence shown in SEQ ID NO:191, and the VL comprises the amino acid sequence shown in SEQ ID NO:192. (32) The VH comprises the amino acid sequence shown in SEQ ID NO:196, and the VL comprises the amino acid sequence shown in SEQ ID NO:197. (33) The VH contains the amino acid sequence shown in SEQ ID NO:201, and the VL contains the amino acid sequence shown in SEQ ID NO:202, or (34) The VH contains the amino acid sequence shown in SEQ ID NO:102, and the VL contains the amino acid sequence shown in SEQ ID NO:206. 【0011】 In some examples, the antibody comprises a heavy chain (HC) and a light chain (LC), where, (1) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:9, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:10. (2) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 57, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 58. (3) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:18, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:19. (4) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:26, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:27. (5) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:32, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:33. (6) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:42, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:43. (7) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 51, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 52. (8) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:61, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:62. (9) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 67, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 68. (10) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:74, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:75, (11) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:84, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:85, (12) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:93, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:94. (13) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:98, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:99, (14) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:104, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:105. (15) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:110, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:111. (16) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:116, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:117. (17) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:122, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:123, (18) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:126, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:127, (19) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:130, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:131, (20) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:137, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:138. (21) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:142, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:143. (22) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:148, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:149. (23) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:154, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:155. (24) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:160, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:161. (25) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:166, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:167. (26) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:169, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:170. (27) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:173, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:174. (28) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:178, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:179. (29) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:183, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:184. (30) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:188, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:189, (31) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:193, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:194. (32) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:198, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:199. (33) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:203, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:204, or (34) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:207, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:208. 【0012】 In preferred embodiments, the antibody comprises a heavy chain (HC) and a light chain (LC), where, (1) The HC contains the amino acid sequence shown in SEQ ID NO:9, and the LC contains the amino acid sequence shown in SEQ ID NO:10. (2) The HC contains the amino acid sequence shown in SEQ ID NO: 57, and the LC contains the amino acid sequence shown in SEQ ID NO: 58. (3) The HC contains the amino acid sequence shown in SEQ ID NO:18, and the LC contains the amino acid sequence shown in SEQ ID NO:19. (4) The HC contains the amino acid sequence shown in SEQ ID NO:26, and the LC contains the amino acid sequence shown in SEQ ID NO:27. (5) The HC contains the amino acid sequence shown in SEQ ID NO:32, and the LC contains the amino acid sequence shown in SEQ ID NO:33. (6) The HC comprises the amino acid sequence shown in SEQ ID NO:42, and the LC comprises the amino acid sequence shown in SEQ ID NO:43. (7) The HC contains the amino acid sequence shown in SEQ ID NO: 51, and the LC contains the amino acid sequence shown in SEQ ID NO: 52. (8) The HC contains the amino acid sequence shown in SEQ ID NO:61, and the LC contains the amino acid sequence shown in SEQ ID NO:62. (9) The HC contains the amino acid sequence shown in SEQ ID NO:67, and the LC contains the amino acid sequence shown in SEQ ID NO:68. (10) The HC comprises the amino acid sequence shown in SEQ ID NO:74, and the LC comprises the amino acid sequence shown in SEQ ID NO:75. (11) The HC comprises the amino acid sequence shown in SEQ ID NO:84, and the LC comprises the amino acid sequence shown in SEQ ID NO:85. (12) The HC comprises the amino acid sequence shown in SEQ ID NO:93, and the LC comprises the amino acid sequence shown in SEQ ID NO:94. (13) The HC comprises the amino acid sequence shown in SEQ ID NO:98, and the LC comprises the amino acid sequence shown in SEQ ID NO:99. (14) The HC comprises the amino acid sequence shown in SEQ ID NO:104, and the LC comprises the amino acid sequence shown in SEQ ID NO:105. (15) The HC comprises the amino acid sequence shown in SEQ ID NO:110, and the LC comprises the amino acid sequence shown in SEQ ID NO:111. (16) The HC comprises the amino acid sequence shown in SEQ ID NO:116, and the LC comprises the amino acid sequence shown in SEQ ID NO:117. (17) The HC comprises the amino acid sequence shown in SEQ ID NO:122, and the LC comprises the amino acid sequence shown in SEQ ID NO:123. (18) The HC comprises the amino acid sequence shown in SEQ ID NO:126, and the LC comprises the amino acid sequence shown in SEQ ID NO:127. (19) The HC comprises the amino acid sequence shown in SEQ ID NO:130, and the LC comprises the amino acid sequence shown in SEQ ID NO:131. (20) The HC comprises the amino acid sequence shown in SEQ ID NO:137, and the LC comprises the amino acid sequence shown in SEQ ID NO:138. (21) The HC comprises the amino acid sequence shown in SEQ ID NO:142, and the LC comprises the amino acid sequence shown in SEQ ID NO:143. (22) The HC comprises the amino acid sequence shown in SEQ ID NO:148, and the LC comprises the amino acid sequence shown in SEQ ID NO:149. (23) The HC comprises the amino acid sequence shown in SEQ ID NO:154, and the LC comprises the amino acid sequence shown in SEQ ID NO:155. (24) The HC comprises the amino acid sequence shown in SEQ ID NO:160, and the LC comprises the amino acid sequence shown in SEQ ID NO:161. (25) The HC contains the amino acid sequence shown in SEQ ID NO:166, and the LC contains the amino acid sequence shown in SEQ ID NO:167, or (26) The HC comprises the amino acid sequence shown in SEQ ID NO:169, and the LC comprises the amino acid sequence shown in SEQ ID NO:170. (27) The HC comprises the amino acid sequence shown in SEQ ID NO:173, and the LC comprises the amino acid sequence shown in SEQ ID NO:174. (28) The HC comprises the amino acid sequence shown in SEQ ID NO:178, and the LC comprises the amino acid sequence shown in SEQ ID NO:179. (29) The HC comprises the amino acid sequence shown in SEQ ID NO:183, and the LC comprises the amino acid sequence shown in SEQ ID NO:184. (30) The HC comprises the amino acid sequence shown in SEQ ID NO:188, and the LC comprises the amino acid sequence shown in SEQ ID NO:189. (31) The HC comprises the amino acid sequence shown in SEQ ID NO:193, and the LC comprises the amino acid sequence shown in SEQ ID NO:194. (32) The HC comprises the amino acid sequence shown in SEQ ID NO:198, and the LC comprises the amino acid sequence shown in SEQ ID NO:199. (33) The HC contains the amino acid sequence shown in SEQ ID NO:203, and the LC contains the amino acid sequence shown in SEQ ID NO:204, or (34) The HC contains the amino acid sequence shown in SEQ ID NO:207, and the LC contains the amino acid sequence shown in SEQ ID NO:208. 【0013】 In some examples, the antibody is a mouse antibody, a chimeric antibody, a humanized antibody, or a human antibody. 【0014】 In some examples, the antibody is an isotype selected from the group consisting of IgG, IgA, IgM, IgE, and IgD. 【0015】 In some examples, the antibody is a subtype selected from the group consisting of IgG1, IgG2, IgG3, and IgG4. 【0016】 In some examples, the antigen-binding fragment is selected from the group consisting of Fab, Fab', F(ab')2, Fd, Fd', Fv, scFv, ds-scFv, and dAb. 【0017】 In some examples, the antibody is a monoclonal antibody, a bispecific antibody, or a multispecific antibody. 【0018】 In some examples, the antibodies are monovalent, bivalent, or polyvalent. 【0019】 In some examples, the antibody or antigen-binding fragment is fluorescently labeled, radiolabeled, or linked to a drug moiety. 【0020】 In some examples, an antibody or antigen-binding fragment is linked to a drug moiety, and the drug moiety is selected from the group consisting of microtubule inhibitors, antibiotics, DNA synthesis inhibitors, topoisomerase inhibitors, RNA polymerase II inhibitors, and RNA spliceosome inhibitors. 【0021】 In preferred embodiments, the drug portion is selected from the group consisting of MMAE, MMAF, duocalmycin, DM1, DM4, SN-38, Dxd, calichemycin, doxorubicin, and PBD (benzodiazepine drugs). 【0022】 In some examples, the antibody or antigen-binding fragment is linked to the drug moiety via a linker. 【0023】 In some embodiments, the linker includes a severable linker or an inseverable linker. 【0024】 In some examples, the cleavable linker is selected from the group consisting of acid-unstable linkers, hydrophilic linkers, protease-sensitive linkers, photo-unstable linkers, hydrazone linkers, dimethyl linkers, and disulfide-containing linkers. 【0025】 In preferred examples, the linker is selected from the group consisting of MC (6-maleimidocaproyl), Val-Cit (valine-citrulline), PABC (p-aminobenzyloxycarbonyl), DMEA (dimethylethylamine), Val-Cit-PABC, MC-Val-Cit-PABC, MC-Val-Cit-PABC-DMEA, GGFG (glycine-glycine-phenylalanine-glycine), MC-GGFG-aminomethyl, AcBut (4-(4-acetylphenoxy)-butyric acid), and AcBut-dimethylhydrazine, and is preferably MC-Val-Cit-PABC. 【0026】 In a second aspect, the present invention provides a bispecific antibody comprising an antibody according to the first aspect of the present invention or an antigen-binding fragment thereof, and a second antigen-binding region that specifically binds to a tumor-associated antigen, an immune cell antigen, or an immune checkpoint molecule. 【0027】 In a third aspect, the present invention provides a nucleic acid comprising a nucleotide sequence encoding an antibody or antigen-binding fragment thereof according to a first aspect of the present invention, or a bispecific antibody according to a second aspect of the present invention. 【0028】 In a fourth aspect, the present invention provides a vector comprising nucleic acid according to a third aspect of the present invention. 【0029】 In a fifth aspect, the present invention provides a host cell comprising a nucleic acid according to a third aspect of the present invention or a vector according to a fourth aspect of the present invention. 【0030】 In a sixth aspect, the present invention provides an antibody-drug conjugate (ADC), the ADC comprising an antibody or antigen-binding fragment thereof according to a first aspect of the present invention or a bispecific antibody according to a second aspect of the present invention, and a drug moiety conjugated thereto via a linker. 【0031】 In some examples, the drug portion is selected from the group consisting of microtubule inhibitors, antibiotics, DNA synthesis inhibitors, topoisomerase inhibitors, RNA polymerase II inhibitors, and RNA spliceosome inhibitors. 【0032】 In preferred embodiments, the drug portion is selected from the group consisting of MMAE, MMAF, duocalmycin, DM1, DM4, SN-38, Dxd, calichemycin, doxorubicin, and PBD (benzodiazepine drugs). 【0033】 In some embodiments, the linker includes a severable linker or an inseverable linker. 【0034】 In some examples, the cleavable linker is selected from the group consisting of acid-unstable linkers, hydrophilic linkers, protease-sensitive linkers, photo-unstable linkers, hydrazone linkers, dimethyl linkers, and disulfide-containing linkers. 【0035】 In preferred examples, the linker is selected from the group consisting of MC (6-maleimidocaproyl), Val-Cit (valine-citrulline), PABC (p-aminobenzyloxycarbonyl), DMEA (dimethylethylamine), Val-Cit-PABC, MC-Val-Cit-PABC, MC-Val-Cit-PABC-DMEA, GGFG (glycine-glycine-phenylalanine-glycine), MC-GGFG-aminomethyl, AcBut (4-(4-acetylphenoxy)-butyric acid), and AcBut-dimethylhydrazine, and is preferably MC-Val-Cit-PABC. 【0036】 In a seventh aspect, the present invention provides a pharmaceutical composition comprising (i) an antibody or antigen-binding fragment thereof according to a first aspect of the present invention, or a bispecific antibody according to a second aspect of the present invention, or a nucleic acid according to a third aspect of the present invention, or a vector according to a fourth aspect of the present invention, or a host cell according to a fifth aspect of the present invention, or an antibody-drug conjugate according to a sixth aspect of the present invention, and optionally (ii) a pharmaceutically acceptable carrier or excipient. 【0037】 In some embodiments, the composition further comprises a second therapeutic agent. Preferably, the second therapeutic agent is selected from the group consisting of antibodies, chemotherapeutic agents, siRNA, antisense oligonucleotides, polypeptides, and small molecule drugs. 【0038】 In an eighth aspect, the present invention provides a method for treating cancer in a subject, the method comprising administering an effective amount of the antibody or antigen-binding fragment thereof, a bispecific antibody, a nucleic acid, a vector, a host cell, an antibody-drug conjugate, or a pharmaceutical composition to the subject. 【0039】 In some specific embodiments, the cancer is a cancer associated with CEACAM5 expression. In preferred embodiments, the cancer is selected from the group consisting of small intestine cancer, colorectal cancer, gastric cancer, lung cancer, cervical cancer, pancreatic cancer, esophageal cancer, ovarian cancer, thyroid cancer, bladder cancer, endometrial cancer, breast cancer, liver cancer, prostate cancer, and skin cancer. 【0040】 In some embodiments, the method further comprises administering a second therapeutic agent to a subject. Preferably, the second therapeutic agent is selected from antibodies, chemotherapeutic agents, siRNA, antisense oligonucleotides, polypeptides, and small molecule drugs. 【0041】 In a ninth aspect, the present invention provides applications for the antibodies or antigen-binding fragments thereof, bispecific antibodies, nucleic acids, vectors, host cells, antibody-drug conjugates, or pharmaceutical compositions of the present invention in the manufacture of drugs for treating cancer in a subject. 【0042】 In some embodiments, the cancer is a cancer associated with CEACAM5 expression. In preferred embodiments, the cancer is selected from the group consisting of small intestine cancer, colorectal cancer, gastric cancer, lung cancer, cervical cancer, pancreatic cancer, esophageal cancer, ovarian cancer, thyroid cancer, bladder cancer, endometrial cancer, breast cancer, liver cancer, prostate cancer, and skin cancer. 【0043】 In some embodiments, the drug further comprises a second therapeutic agent. Preferably, the second therapeutic agent is selected from antibodies, chemotherapeutic agents, siRNAs, antisense oligonucleotides, polypeptides, and small molecule drugs. 【0044】 In some examples, the drug and the second therapeutic agent are administered in combination. Preferably, the second therapeutic agent is selected from antibodies, chemotherapeutic agents, siRNA, antisense oligonucleotides, polypeptides, and small molecule drugs. 【0045】 In a tenth aspect, the present invention provides the use of the antibody or its antigen-binding fragment, bispecific antibody, nucleic acid, vector, host cell, antibody-drug conjugate, or pharmaceutical composition in a method for treating cancer in a subject. 【0046】 In some embodiments, the cancer is a cancer associated with CEACAM5 expression. In preferred embodiments, the cancer is selected from the group consisting of small intestine cancer, colorectal cancer, gastric cancer, lung cancer, cervical cancer, pancreatic cancer, esophageal cancer, ovarian cancer, thyroid cancer, bladder cancer, endometrial cancer, breast cancer, liver cancer, prostate cancer, and skin cancer. 【0047】 In some examples, a second therapeutic agent is further administered to the subject. Preferably, the second therapeutic agent is selected from antibodies, chemotherapeutic agents, siRNA, antisense oligonucleotides, polypeptides, and small molecule drugs. 【0048】 In the eleventh aspect, the present invention provides a method for detecting the presence or level of CEACAM5 in a sample, the method being: (a) Contacting the sample with the antibody or antigen-binding fragment thereof described in any one of claims 1 to 10, (b) Determining the presence or level of CEACAM5 in the sample by detecting the binding of the antibody to the sample. 【0049】 In preferred embodiments, the method is used for non-diagnostic purposes. 【0050】 In a twelfth aspect, the present invention provides a method for diagnosing cancer associated with CEACAM5 expression in a subject, the method being: (a) Obtaining a biological sample from the subject, (b) Contacting the sample with the antibody of the present invention or its antigen-binding fragment, (c) detecting the binding of the antibody to the sample, Here, the binding of the antibody or its antigen-binding fragment to the sample is increased compared to the binding of the antibody or its antigen-binding fragment to the control sample, thereby identifying the subject as having cancer. 【0051】 In a thirteenth aspect, the present invention provides a method for imaging cancers associated with CEACAM5 expression in a subject, the method being: (a) Administering the antibody of the present invention or an antigen-binding fragment thereof to the subject, wherein the antibody is conjugated with a detectable marker, (b) including detecting the presence of the marker. 【0052】 In some embodiments, the detectable markers are: 111 In, and preferably, the marker is detected by single-photon emission computed tomography. In other embodiments, the detectable marker is 89 The marker is Zr, and preferably, it is detected by positron emission tomography. [Brief explanation of the drawing] 【0053】 [Figure 1] This document describes the procedure for immunization and single B cell cloning to produce anti-CEACAM5 antibodies. [Figure 2] This explains the binding of the anti-CEACAM5 H2L2 antibody to the human CEACAM5 protein. [Figure 3] This explains the binding of the anti-CEACAM5 H2L2 antibody to the cyno-CEACAM5 protein. [Figure 4] This explains why the anti-CEACAM5 H2L2 antibody does not bind to the human CEACAM6 protein. [Figure 5] This explains why the anti-CEACAM5 H2L2 antibody does not bind to the human CEACAM1 protein. [Figure 6] This explains why the anti-CEACAM5 H2L2 antibody does not bind to the human CEACAM3 protein. [Figure 7] This explains why the anti-CEACAM5 H2L2 antibody does not bind to the human CEACAM8 protein. [Figure 8] This paper describes the binding of an anti-CEACAM5 H2L2 antibody to 293T cells that overexpress human CEACAM5. [Figure 9] This paper describes the binding of the anti-CEACAM5 H2L2 antibody to CHOK1 cells that overexpress CEACAM5 in cynomolgus monkeys. [Figure 10] This paper describes the binding of the anti-CEACAM5 H2L2 antibody to the cancer cell line LS 174T (colon cancer). [Figure 11] This paper describes the binding of the anti-CEACAM5 H2L2 antibody to the cancer cell line BxPC3 (pancreatic cancer). [Figure 12] This paper describes the internalization of anti-CEACAM5 H2L2 antibody in 293T cell lines and LS174T colon cancer cell lines that overexpress human CEACAM5. 【0054】 The present invention's anti-CEACAM5 antibodies (PR304296, PR304303, PR304717, PR304718, PR304569, PR304688, PR304689, PR304692, PR304693, PR304697, PR304840, PR304870, PR304873, PR307076, PR307077, PR307078, PR307079, PR307080, PR307081, PR307082, PR307083, PR30 The amino acid sequences (based on the Kabat-Chothia combination system) of the CDR, heavy chain variable region (VH), light chain variable region (VL), heavy chain (HC), and light chain (LC) of 7084, PR307085, PR307088, PR307089, PR307091, PR307094, PR307097, PR307098, PR307099, PR307100, PR307101, PR307102, and PR307103) are shown in Table 1. The amino acid sequences (calculated using a combination of Kabat and Chothia systems) of the CDR, heavy chain variable region (VH), light chain variable region (VL), heavy chain (HC), and light chain (LC) of the anti-CEACAM5 reference antibody PR303561 (tusamitamab) and the anti-CEACAM6 reference antibody PR303563 (tinurilimab) are shown in Table 2. 【0055】 [Table 1-1] 【0056】 [Table 1-2] 【0057】 [Table 1-3] 【0058】 [Table 1-4] 【0059】 Table 1-5 【0060】 Table 1-6 【0061】 Table 1-7 【0062】 Table 1-8 【0063】 Table 1-9 【0064】 Table 1-10 【0065】 Table 1-11 【0066】 Table 1-12 【0067】 Table 1-13 【0068】 Table 1-14 【0069】 Table 1-15 【0070】 Table 1-16 【0071】 Table 1-17 【0072】 Table 1-18 【0073】 Table 1-19 【0074】 Table 1-20 【0075】 Table 1-21 【0076】 Table 1-22 【0077】 Table 1-23 【0078】 Table 1-24 【0079】 Table 1-25 【0080】 [Table 1-26] 【0081】 [Table 1-27] 【0082】 [Table 1-28] 【0083】 [Table 1-29] 【0084】 [Table 1-30] 【0085】 [Table 2-1] 【0086】 [Table 2-2] [Modes for carrying out the invention] 【0087】 The following embodiments will be described in detail with accompanying drawings, and the above features and advantages of the present invention, as well as other features and advantages thereof, will be understood more clearly below. 【0088】 The embodiments described herein with reference to the drawings are for interpretation and explanation purposes only and are used to understand the invention in general. The embodiments should not be understood as limiting the scope of the invention. Throughout the specification, elements that are the same or similar, and elements having the same or similar functions, are denoted by similar reference numerals. 【0089】 Unless otherwise specified or defined, all terms used have their general meaning in the art, which will be apparent to those skilled in the art. For example, see the standard manual, e.g., Leuenberger, HGW, Nagel, B. and Klbl, H., eds., "A multilingual glossary of biotechnological terms: (IUPAC Recommendations)", Helvetica Chimica Acta (1995), CH-4010 Basel, Switzerland; Sambrook et al., "Molecular Cloning: A Laboratory Manual" (2nd edition), Volumes 1-3, Cold Spring Laboratory Press (1989); F. Ausubel et al., eds., "Current protocols in molecular biology", Green Publishing and Wiley See InterScience, New York (1987), Roitt et al., "Immunology (6th edition)," Mosby / Elsevier, Edinburgh (2001), and Janeway et al., "Immunobiology (6th edition)," Garland Science Publishing / Churchill Livingstone, New York (2005), and the general background fields referenced above. 【0090】 As used herein, the singular forms "a / an" and "the" refer to multiple objects unless specifically indicated otherwise in the context. Therefore, for example, when referring to "antibodies," it refers to multiple antibodies. 【0091】 Unless otherwise specified or defined, the terms “comprise” and its variations, e.g., “comprises” and “comprising,” should be understood to include the aforementioned elements or steps or sets of elements or steps, but not to exclude any other elements or steps or sets of elements or steps. The term “comprising” covers “including” and “consisting,” for example, a composition “comprises” X may consist entirely of X, or it may include other items, e.g., X + Y. 【0092】 The term "approximately," which is related to the numerical value x, is optional and can refer to, for example, x ± 10% or x ± 5%. 【0093】 As used herein, the term “antibody” refers to an immunoglobulin molecule that has the ability to specifically bind to a particular antigen. Antibodies typically contain a variable region and a constant region in both the heavy chain and the light chain. The variable regions of the antibody heavy chain and light chain contain binding domains that interact with the antigen. The constant region of the antibody can mediate the binding of the immunoglobulin to host tissues or factors, which include various cells of the immune system (e.g., effector cells) and components of the complement system (e.g., C1q, which is the first component in the classical pathway of complement activation). The vast majority of antibodies contain a heavy chain variable region (VH) and a light chain variable region (VL), which together form the antigen-binding portion in the antibody. 【0094】 The "light chain variable region" (VL) or "heavy chain variable region" (VH) consists of four "framework" regions separated by three "complementarity-determining regions" or "CDRs." The role of the framework regions is to arrange the CDRs and specifically bind to the antigen epitope. The CDRs mainly contain amino acid residues of the antibody that are responsible for antigen binding. From the amino terminus to the carboxyl terminus, both the VL and VH domains contain framework (FR) regions and CDR regions, namely FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4. CDRs 1, 2, and 3 of the VL domain are also referred to herein as LCDR1, LCDR2, and LCDR3, respectively, and CDRs 1, 2, and 3 of the VH domain are also referred to herein as HCDR1, HCDR2, and HCDR3, respectively. 【0095】 The distribution of amino acids to each VL and VH domain is according to any general definition of CDR. General definitions include the Kabat definition (Kabat, Sequences of Proteins of Immunological Interest (National Institutes of Health, Bethesda, Maryland, 1987 and 1991)), the Chothia definition (Chothia and Lesk, J.Mol.Biol (Molecular Biology Journal), 196:901-917, 1987; Chothia et al., Nature, 342:878-883, 1989), the Chothia-Kabat CDR complex (also called a Chothia-Kabat combination CDR), where each CDR is a complex of Chothia and Kabat CDRs, and the Oxford This includes AbM definitions used in Molecular's antibody modeling software, and contact definitions from Martin et al. (worldwide web bioinfo.org.uk / abs). Kabat provides a widely used numbering system (Kabat numbering system) in which the same number is assigned to corresponding residues between different heavy chains or between different light chains. 【0096】 This disclosure relates to a CDR defined based on any one of these numbering systems, but a preferred embodiment relates to a CDR defined by a combination of Chothia and Kabat. 【0097】 [Table 3] 【0098】 In Table 3, Laa-Lbb may refer to the amino acid sequence from position aa (according to the Chothia numbering system) to position bb (according to the Chothia numbering system) from the N-terminus of the antibody light chain, and Haa-Hbb may refer to the amino acid sequence from position aa (according to the Chothia numbering system) to position bb (according to the Chothia numbering system) from the N-terminus of the antibody heavy chain. For example, L24-L34 may refer to the amino acid sequence from position 24-34 (according to the Chothia numbering system) from the N-terminus of the antibody light chain, and H26-H32 may refer to the amino acid sequence from position 26-32 (according to the Chothia numbering system) from the N-terminus of the antibody heavy chain. 【0099】 As used herein, the term “antibody” should be understood in its broadest sense and include monoclonal antibodies (full-length monoclonal antibodies), polyclonal antibodies, antibody fragments, and multispecific antibodies (e.g., bispecific antibodies) containing at least two different antigen-binding regions. Antibodies may contain other modifications, such as unnaturally occurring amino acids, mutations in the Fc region, and mutations in the glycosylation site. Antibodies may further include post-translationally modified antibodies, fusion proteins containing antigen-determining clusters of the antibody, and any other modified immunoglobulin molecules containing antigen-recognition sites, provided that these antibodies exhibit the desired biological activity. 【0100】 As used herein, the term “antigen-binding fragment” of an antibody refers to one or more fragments of an antibody that retain the ability to specifically bind to an antigen (e.g., CEACAM5). It has been shown that the antigen-binding function of an antibody can be performed by fragments of a full-length antibody. 【0101】 Examples of antibody antigen-binding fragments include (i) Fab fragments, which are monovalent fragments consisting of VL, VH, CL, and CH1 domains; (ii) F(ab')2 fragments, which are bivalent fragments containing two Fab fragments linked via disulfide bonds in a hinge region; and (iii) Fab' fragments, which are essentially Fab fragments with a partial hinge region. (FUNDAMENTALIMMUNOLOGY [Basic Immunology] (Paul ed., 3.sup.rd) (See ed.1993) and (iv) an Fd fragment consisting of VH and CH1 domains, (v) an Fd' fragment having VH and CH1 domains and one or more cysteine ​​residues at the C-terminus of the CH1 domain, (vi) an Fv fragment consisting of VL and VH domains of a single antibody arm, (vii) a dAb fragment consisting of a VH domain (Ward et al., (1989) Nature 341:544-546), (viii) an isolated complementarity-determining region (CDR), and (ix) a heavy chain variable region containing a nanoantibody, a single variable domain, and two constant domains. Although the two domains VL and VH of the Fv fragment are encoded by separate genes, they can be linked via a synthetic linker using recombination methods, thereby allowing the VL and VH regions to pair up and form a single protein chain that forms a monovalent molecule (called a single-chain Fv (scFv), e.g., Bird et al. (1988) Science 242:423-426, and Huston et al. (1988) Proc. Natl. Acad. Sci. USA 85:5879-5883). Such single-chain antibodies are also intended to be covered by the antibody term "antigen-binding fragment." This term further includes "linear antibodies" of a pair of serial Fd fragments (VH-CH1-VH-CH1) that form an antigen-binding region together with a complementary light chain polypeptide, and modified forms of any of the above fragments that retain antigen-binding activity. 【0102】 These antigen-binding fragments can be obtained by conventional techniques known to those skilled in the art, and the fragments can be screened for utility in the same manner as intact antibodies. 【0103】 As used herein, the terms "bind" or "specifically bind" refer to a non-random binding reaction between two molecules, such as between an antibody and its target antigen. The binding specificity of an antibody may be determined based on affinity and / or avidity. Affinity is represented by the dissociation equilibrium constant (KD) of the antigen and the antibody, and is a scale of the binding strength between the antigen determinant cluster (epitope) and the antigen-binding site on the antibody. The smaller the KD value, the stronger the binding strength between the antigen determinant cluster (epitope) and the antibody. Alternatively, affinity may be represented as the association constant (KA), i.e., 1 / KD. 【0104】 Avidity is a scale of the binding strength between an antibody and a related antigen. Avidity is related to the affinity between the antigen determinant cluster (epitope) and the antigen-binding site on the antibody and the number of related binding sites present on the antibody. Generally, an antibody has a dissociation constant (KD) of 10 -5 ~10 -12 M or less, preferably 10 -7 ~10 -12 M or less, more preferably 10 -8 ~10 -12 M, and / or a binding affinity of at least 10 7 M -1 , preferably at least 10 8 M -1 , more preferably at least 10 9 M -1 , for example at least 10 12 M -1 . It binds with a binding affinity of 10 -4 M or greater for any K DThe value is generally considered to represent nonspecific binding. Specific binding of an antibody to an antigen or antigen-determining cluster may be determined by any suitable method known in itself, which includes, for example, Scatchard analysis and / or competitive binding assays, such as radioimmunoassay (RIA), enzyme immunoassay (EIA), biolayer interference assay (BLI), and sandwich competitive assay, and different variations thereof known in the art. 【0105】 The term "epitope" refers to the site on an antigen to which an antibody binds. Epitopes may be formed from a sequence of amino acids or a sequence of discontinuous amino acids juxtaposed by the tertiary folding of one or more proteins. Epitopes formed from sequence of amino acids (also called linear epitopes) are usually retained when exposed to denaturing solvents, while epitopes formed by tertiary folding (also called conformational epitopes) are usually lost during treatment with denaturing solvents. Epitopes typically contain at least three, and usually at least five or eight to ten, amino acids in a unique conformation. Epitopes are specific targets for antibodies or their antigen-binding fragments because they define the minimal binding site of an antibody. 【0106】 As used herein, the term “sequence identity” refers to the degree to which two sequences (amino acids) have the same residues at the same positions in alignment. For example, “an amino acid sequence is X% identical to SEQ ID NO:Y” refers to the percentage of identity between the amino acid sequence and SEQ ID NO:Y, and states that X% of the residues in the amino acid sequence are identical to the sequence residues disclosed in SEQ ID NO:Y. Typically, computer programs are used for such calculations. Exemplary programs for comparing and aligning sequence pairs include ALIGN (Myers and Miller, 1988), FASTA (Pearson and Lipman, 1988; Pearson, 1990), and GAP BLAST (Altschul et al., 1997), BLASTP, BLASTN, or GCG (Devereux et al., 1984). 【0107】 Furthermore, when determining the degree of sequence identity between two amino acid sequences, those skilled in the art may consider so-called "conservative" amino acid substitutions, which are usually described as amino acid substitutions in which one amino acid residue is replaced by another amino acid residue, the other amino acid residue having a similar chemical structure and having little or no effect on the function, activity or other biological properties of the polypeptide. 【0108】 Such conservative substitutions are preferably those in which one amino acid in the following groups (a) to (e) is replaced by another amino acid residue in the same group: (a) small aliphatic, nonpolar or weakly polar residues: Ala, Ser, Thr, Pro and Gly; (b) negatively charged polar residues and their (uncharged) amides: Asp, Asn, Glu and Gln; (c) positively charged polar residues: His, Arg and Lys; (d) large aliphatic nonpolar residues: Met, Leu, Ile, Val and Cys; and (e) aromatic residues: Phe, Tyr and Trp. 【0109】 The following are particularly preferred conservative substitutions: Ala is replaced with Gly or Ser, Arg is replaced with Lys, Asn is replaced with Gln or His, Asp is replaced with Glu, Cys is replaced with Ser, Gln is replaced with Asn, Glu is replaced with Asp, Gly is replaced with Ala or Pro, His is replaced with Asn or Gln, Ile is replaced with Leu or Val, Leu is replaced with Ile or Val, Lys is replaced with Arg, Gln or Glu, Met is replaced with Leu, Tyr or Ile, Phe is replaced with Met, Leu or Tyr, Ser is replaced with Thr, Thr is replaced with Ser, Trp is replaced with Tyr, Tyr is replaced with Trp, and / or Phe is replaced with Val, Ile or Leu. 【0110】 As used herein, the term “monoclonal antibody” refers to an antibody obtained from a substantially homogeneous antibody population; that is, each antibody constituting the population is identical except for a very small number of spontaneously occurring mutations. Monoclonal antibodies are highly specific and target a single antigen. The term “monoclonal antibody” as used herein is not limited to antibodies produced by hybridoma technology, nor should it be interpreted as requiring any specific method for antibody production. 【0111】 In the context of this invention, the term "bispecific antibody" is understood to mean an antibody having two distinct antigen-binding regions defined by different antibody sequences. This can be understood as binding to different targets, but also includes binding to different epitopes within a single target. 【0112】 As used herein, the term “tumor-associated antigen” refers to an antigen that is differentially expressed in cancer cells compared to normal cells, and therefore can be used to target cancer cells. 【0113】 As used herein, the term “vector” refers to a nucleic acid molecule capable of transporting another nucleic acid to which it is ligated. 【0114】 As used herein, the term “host cell” refers to a cell into which an expression vector has been introduced. 【0115】 The term "pharmaceutically acceptable" means that the carrier or adjuvant is compatible with the other components of the composition, does not cause substantial harm to the recipient, and / or is approved or can be approved for inclusion in a pharmaceutical composition for parenteral administration to humans. 【0116】 As used herein, the term “treatment / treating” refers to administering a drug or performing a procedure to obtain an effect. The effect may be preventive in that it completely or partially prevents a disease or its symptoms, and / or therapeutic in that it results in a partial or complete cure of the disease and / or its symptoms. As used herein, “treatment” may include treatment for a disease or condition (e.g., cancer) in mammals, particularly humans, and includes (a) preventing the onset of the disease or its symptoms in a subject who is susceptible to the disease but has not yet been diagnosed with the disease (e.g., including diseases associated with or caused by a primary disease), (b) inhibiting the disease, i.e., preventing its progression, and (c) alleviating the disease, i.e., causing the disease to subside. Treatment may refer to any indicator of success in the treatment, improvement, or prevention of cancer, and may include objective or subjective parameters such as reduction, alleviation, decrease in symptoms or making the patient more tolerable to the disease, slowing the rate of regression or decline, or reducing the lethality of the final stages of regression. Treatment or improvement of symptoms is based on one or more objective or subjective parameters, including the results of a physician's examination. Therefore, the term “treatment” includes administering any antibody, composition, or conjugate disclosed herein to prevent, delay, reduce, block, or inhibit the progression of symptoms or symptoms associated with a disease (e.g., cancer). The term “therapeutic effect” means reducing, eliminating, or preventing the disease, disease symptoms, or side effects of the disease in a subject. 【0117】 As used herein, the term “effective dose” means an amount sufficient to produce a cure for a disease when administered to a subject for the treatment of that disease. 【0118】 As used herein, the term “subject” refers to any mammalian subject requiring diagnosis, treatment, or therapy. “Mammal” for therapeutic purposes refers to any animal classified as a mammal, including humans, livestock and farm animals, and laboratory animals, zoo animals, exercise animals or pet animals, such as dogs, horses, cats, cattle, sheep, goats, pigs, mice, rats, rabbits, guinea pigs, monkeys, etc. 【0119】 The terms “cyno CEACAM5,” “cynomolgus CEACAM5,” and “Cynomolgus macaques CEACAM5” are interchangeable in this specification and refer to cynomolgus CEACAM5. These terms include any CEACAM5 variant, subtype, and species homolog spontaneously expressed by cynomolgus macaques cells, or those expressed on cells transfected with a gene or cDNA encoding cynomolgus CEACAM5, which are spontaneously expressed on cynomolgus macaques cells. Anti-CEACAM5 antibody 【0120】 In a first aspect, the present invention provides an antibody or antigen-binding fragment thereof that binds to CEACAM5, wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), and further, (1) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 7, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 8. (2) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 55, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 56. (3) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 16, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 17. (4) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO:24, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:25. (5) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO:30, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:31. (6) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 40, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 41. (7) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 49, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 50. (8) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 59, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 60. (9) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 65, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 66. (10) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 72, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 73. (11) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 82, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 83. (12) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO:91, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:92. (13) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO:96, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:97. (14) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 102, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 103. (15) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 108, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 109. (16) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 114, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 115. (17) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 120, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 121. (18) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 124, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 125. (19) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 128, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 129. (20) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 135, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 136. (21) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 140, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 141. (22) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 146, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 147. (23) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 152, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 153. (24) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 158, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 159. (25) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 164, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 165. (26) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 102, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 168. (27) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 171, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 172. (28) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 176, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 177. (29) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 181, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 182. (30) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 186, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 187. (31) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 191, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 192. (32) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 196, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 197. (33) The VH comprises HCDR 1-3 of VH having the amino acid sequence shown in SEQ ID NO:201, and the VL comprises LCDR 1-3 of VL having the amino acid sequence shown in SEQ ID NO:202, or (34) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 102, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 206. 【0121】 In some embodiments, LCDR 1-3 and HCDR 1-3 are defined by the EU Kabat definition / numbering system. In some embodiments, LCDR 1-3 and HCDR 1-3 are defined by the Chothia definition / numbering system. In some embodiments, LCDR 1-3 and HCDR 1-3 are defined by the AbM definition / numbering system. In some preferred embodiments, LCDR 1-3 and HCDR 1-3 are defined by a combined Kabat and Chothia numbering system. 【0122】 In some embodiments, the present invention provides an antibody or antigen-binding fragment thereof that binds to CEACAM5, wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), and furthermore, (1) The VH comprises HCDR 1 to 3, each containing the amino acid sequences shown in SEQ ID NO: 1, 2, and 3, respectively, and the VL comprises LCDR 1 to 3, each containing the amino acid sequences shown in SEQ ID NO: 4, 5, and 6, (2) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 44, 53 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 54, 38 and 39, respectively. (3) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 11, 12 and 13, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 4, 14 and 15, respectively. (4) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 20, 21 and 22, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 4, 5 and 23, respectively. (5) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 28, 21 and 29, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 4, 5 and 6, respectively. (6) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 34, 35 and 36, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 37, 38 and 39, respectively. (7) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 44, 45 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 47, 38 and 48, respectively. (8) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 44, 53 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 63, 64 and 39, respectively. (9) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 69, 70, and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 71, 38, and 39, respectively. (10) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 76, 77, and 78, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 79, 80, and 81, respectively. (11) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 86, 87, and 88, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 89, 80, and 90, respectively. (12) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 86, 87, and 95, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 89, 80, and 90, respectively. (13) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 34, 100 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 37, 38 and 101, respectively. (14) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 106, 100, and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 107, 38, and 39, respectively. (15) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 44, 112 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 113, 38 and 39, respectively. (16) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 44, 118 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 119, 38 and 39, respectively. (17) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 106, 118 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 113, 38 and 39, respectively. (18) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 34, 100 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 71, 38 and 39, respectively. (19) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 44, 132 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 133, 38 and 134, respectively. (20) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 69, 100 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 139, 38 and 39, respectively. (21) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 144, 77, and 95, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 89, 80, and 145, respectively. (22) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 150, 77 and 151, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 89, 80 and 90, respectively. (23) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 34, 118 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 156, 38 and 157, respectively. (24) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 69, 100 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 162, 163 and 48, respectively. (25) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 34, 100 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 37, 38 and 39, respectively. (26) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 44, 100 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 162, 38 and 39, respectively. (27) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 175, 77, and 95, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 89, 80, and 145, respectively. (28) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 44, 132 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 37, 38 and 180, respectively. (29) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 69, 100 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 185, 38 and 157, respectively. (30) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 44, 190 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 162, 38 and 48, respectively. (31) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 106, 112 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 195, 38 and 39, respectively. (32) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 34, 112, and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 200, 64, and 39, respectively, or (33) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 34, 100, and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 133, 205, and 39, respectively. 【0123】 In some embodiments, the CDR is determined by a combination system of Kabat and Chothia. 【0124】 In some embodiments, the present invention provides an antibody or antigen-binding fragment thereof that binds to CEACAM5, wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), and furthermore, (1) The VH contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:7, and the VL contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:8, (2) The VH contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 55, and the VL contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 56. (3) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:16, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:17. (4) The VH contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:24, and the VL contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:25. (5) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:30, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:31. (6) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:40, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:41. (7) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 49, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 50, (8) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 59, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 60, (9) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 65, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 66, (10) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:72, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:73, (11) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:82, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:83, (12) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:91, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:92, (13) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:96, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:97, (14) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:102, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:103, (15) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:108, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:109. (16) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:114, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:115. (17) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:120, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:121. (18) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:124, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:125. (19) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:128, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:129, (20) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:135, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:136. (21) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:140, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:141. (22) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:146, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:147. (23) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:152, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:153. (24) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:158, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:159. (25) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:164, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:165. (26) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:102, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:168. (27) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:171, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:172. (28) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:176, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:177. (29) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:181, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:182. (30) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:186, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:187. (31) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:191, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:192. (32) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:196, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:197. (33) The VH contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:201, and the VL contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:202, or (34) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:102, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:206. 【0125】 In some examples, VH contains a functional variant of the amino acid sequence represented by one of the following SEQ ID NOs: 7, 55, 16, 24, 30, 40, 49, 59, 65, 72, 82, 91, 96, 102, 108, 114, 120, 124, 128, 135, 140, 146, 152, 158, 164, 171, 176, 181, 186, 191, 196, and 201, formed by the insertion, deletion, and / or substitution of one or more amino acids, provided that the antibody containing VH containing the functional variant retains its ability to bind to CEACAM5. In some examples, VL contains a functional variant of the amino acid sequence represented by one of the following SEQ ID NOs: 8, 56, 17, 25, 31, 41, 50, 60, 66, 73, 83, 92, 97, 103, 109, 115, 121, 125, 129, 136, 141, 147, 153, 159, 165, 168, 172, 177, 182, 187, 192, 197, 202, and 206, formed by the insertion, deletion, and / or substitution of one or more amino acids, provided that the antibody containing VL containing the functional variant retains its ability to bind to CEACAM5. 【0126】 Functional variants include or consist of amino acid sequences having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, or at least 99.9% sequence identity with the amino acid sequence of the parent polypeptide. 【0127】 In the context of functional variants, the number of amino acids inserted, deleted and / or substituted is preferably 40% or less, more preferably 35% or less, more preferably 1% to 33%, more preferably 5% to 30%, more preferably 10% to 25%, more preferably 15% to 20% of the total number of amino acids in the parental amino acid sequence. For example, the number of amino acids inserted, deleted and / or substituted may be 1 to 20, preferably 1 to 10, more preferably 1 to 7, even more preferably 1 to 5, and most preferably 1 to 2. In preferred embodiments, the number of amino acids inserted, deleted and / or substituted is 1, 2, 3, 4, 5, 6 or 7. 【0128】 In some embodiments, the insertion, deletion and / or substitution may be carried out in a framework (FR) region, such as FR1, FR2, FR3 and / or FR4. 【0129】 In some embodiments, the substitution of one or more amino acids may be a conservative substitution of one or more amino acids. Such conservative substitutions are preferably substitutions in which one amino acid in one of the following groups (a) to (e) is replaced by another amino acid residue in the same group. (a) Small aliphatic, nonpolar or weakly polar residues: Ala, Ser, Thr, Pro and Gly, (b) Negatively charged polar residues and their (uncharged) amides: Asp, Asn, Glu and Gln, (c) Positively charged polar residues: His, Arg and Lys, (d) Large aliphatic nonpolar residues: Met, Leu, Ile, Val and Cys, and (e) Aromatic residues: Phe, Tyr and Trp. 【0130】 Particularly preferred conservative substitutions are as follows. Ala is substituted with Gly or Ser, Arg is substituted with Lys, Asn is substituted with Gln or His, Asp is substituted with Glu, Cys is substituted with Ser, Gln is substituted with Asn, Glu is substituted with Asp, Gly is substituted with Ala or Pro, His is substituted with Asn or Gln, Ile is substituted with Leu or Val, Leu is substituted with Ile or Val, Lys is substituted with Arg, Gln or Glu, Met is substituted with Leu, Tyr or Ile, Phe is substituted with Met, Leu or Tyr, Ser is substituted with Thr, Thr is substituted with Ser, Trp is substituted with Tyr, Tyr is substituted with Trp, and / or Phe is substituted with Val, Ile or Leu. 【0131】 In a preferred embodiment, the present invention provides an antibody or an antigen-binding fragment thereof that binds to CEACAM5, wherein the antibody comprises a heavy-chain variable region (VH) and a light-chain variable region (VL), and wherein (1) the VH comprises the amino acid sequence shown in SEQ ID NO:7, and the VL comprises the amino acid sequence shown in SEQ ID NO:8, (2) the VH comprises the amino acid sequence shown in SEQ ID NO:55, and the VL comprises the amino acid sequence shown in SEQ ID NO:56, (3) the VH comprises the amino acid sequence shown in SEQ ID NO:16, and the VL comprises the amino acid sequence shown in SEQ ID NO:17, (4) the VH comprises the amino acid sequence shown in SEQ ID NO:24, and the VL comprises the amino acid sequence shown in SEQ ID NO:25, (5) the VH comprises the amino acid sequence shown in SEQ ID NO:30, and the VL comprises the amino acid sequence shown in SEQ ID NO:31, (6) the VH comprises the amino acid sequence shown in SEQ ID NO:40, and the VL comprises the amino acid sequence shown in SEQ ID NO:41, (7) The VH contains the amino acid sequence shown in SEQ ID NO:49, and the VL contains the amino acid sequence shown in SEQ ID NO:50. (8) The VH contains the amino acid sequence shown in SEQ ID NO:59, and the VL contains the amino acid sequence shown in SEQ ID NO:60. (9) The VH contains the amino acid sequence shown in SEQ ID NO:65, and the VL contains the amino acid sequence shown in SEQ ID NO:66. (10) The VH comprises the amino acid sequence shown in SEQ ID NO:72, and the VL comprises the amino acid sequence shown in SEQ ID NO:73. (11) The VH comprises the amino acid sequence shown in SEQ ID NO:82, and the VL comprises the amino acid sequence shown in SEQ ID NO:83. (12) The VH comprises the amino acid sequence shown in SEQ ID NO:91, and the VL comprises the amino acid sequence shown in SEQ ID NO:92. (13) The VH comprises the amino acid sequence shown in SEQ ID NO:96, and the VL comprises the amino acid sequence shown in SEQ ID NO:97. (14) The VH comprises the amino acid sequence shown in SEQ ID NO:102, and the VL comprises the amino acid sequence shown in SEQ ID NO:103. (15) The VH comprises the amino acid sequence shown in SEQ ID NO:108, and the VL comprises the amino acid sequence shown in SEQ ID NO:109. (16) The VH comprises the amino acid sequence shown in SEQ ID NO:114, and the VL comprises the amino acid sequence shown in SEQ ID NO:115. (17) The VH comprises the amino acid sequence shown in SEQ ID NO:120, and the VL comprises the amino acid sequence shown in SEQ ID NO:121. (18) The VH comprises the amino acid sequence shown in SEQ ID NO:124, and the VL comprises the amino acid sequence shown in SEQ ID NO:125. (19) The VH comprises the amino acid sequence shown in SEQ ID NO:128, and the VL comprises the amino acid sequence shown in SEQ ID NO:129. (20) The VH comprises the amino acid sequence shown in SEQ ID NO:135, and the VL comprises the amino acid sequence shown in SEQ ID NO:136. (21) The VH comprises the amino acid sequence shown in SEQ ID NO:140, and the VL comprises the amino acid sequence shown in SEQ ID NO:141. (22) The VH comprises the amino acid sequence shown in SEQ ID NO:146, and the VL comprises the amino acid sequence shown in SEQ ID NO:147. (23) The VH comprises the amino acid sequence shown in SEQ ID NO:152, and the VL comprises the amino acid sequence shown in SEQ ID NO:153. (24) The VH comprises the amino acid sequence shown in SEQ ID NO:158, and the VL comprises the amino acid sequence shown in SEQ ID NO:159. (25) The VH contains the amino acid sequence shown in SEQ ID NO:164, and the VL contains the amino acid sequence shown in SEQ ID NO:165, or (26) The VH comprises the amino acid sequence shown in SEQ ID NO:102, and the VL comprises the amino acid sequence shown in SEQ ID NO:168. (27) The VH comprises the amino acid sequence shown in SEQ ID NO:171, and the VL comprises the amino acid sequence shown in SEQ ID NO:172. (28) The VH comprises the amino acid sequence shown in SEQ ID NO:176, and the VL comprises the amino acid sequence shown in SEQ ID NO:177. (29) The VH comprises the amino acid sequence shown in SEQ ID NO:181, and the VL comprises the amino acid sequence shown in SEQ ID NO:182. (30) The VH comprises the amino acid sequence shown in SEQ ID NO:186, and the VL comprises the amino acid sequence shown in SEQ ID NO:187. (31) The VH comprises the amino acid sequence shown in SEQ ID NO:191, and the VL comprises the amino acid sequence shown in SEQ ID NO:192. (32) The VH comprises the amino acid sequence shown in SEQ ID NO:196, and the VL comprises the amino acid sequence shown in SEQ ID NO:197. (33) The VH contains the amino acid sequence shown in SEQ ID NO:201, and the VL contains the amino acid sequence shown in SEQ ID NO:202, or (34) The VH contains the amino acid sequence shown in SEQ ID NO:102, and the VL contains the amino acid sequence shown in SEQ ID NO:206. 【0132】 In some examples, the antibody comprises a heavy chain (HC) and a light chain (LC), where, (1) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:9, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:10. (2) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 57, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 58. (3) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:18, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:19. (4) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:26, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:27. (5) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:32, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:33. (6) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:42, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:43. (7) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 51, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 52. (8) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:61, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:62. (9) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 67, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 68. (10) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:74, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:75, (11) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:84, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:85, (12) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:93, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:94. (13) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:98, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:99, (14) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:104, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:105. (15) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:110, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:111. (16) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:116, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:117. (17) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:122, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:123, (18) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:126, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:127, (19) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:130, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:131, (20) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:137, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:138. (21) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:142, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:143. (22) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:148, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:149. (23) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:154, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:155. (24) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% sequence identity with SEQ ID NO: 160, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% sequence identity with SEQ ID NO: 161. (25) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% sequence identity with SEQ ID NO: 166, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% sequence identity with SEQ ID NO: 167. (26) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% sequence identity with SEQ ID NO: 169, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% sequence identity with SEQ ID NO: 170. (27) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% sequence identity with SEQ ID NO: 173, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% sequence identity with SEQ ID NO: 174. (28) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:178, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:179. (29) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:183, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:184. (30) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:188, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:189, (31) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:193, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:194. (32) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:198, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:199. (33) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:203, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:204, or (34) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:207, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:208. 【0133】 In some examples, the heavy chain contains a functional variant of the amino acid sequence shown in one of the following SEQ ID NOs: 9, 57, 18, 26, 32, 42, 51, 61, 67, 74, 84, 93, 98, 104, 110, 116, 122, 126, 130, 137, 142, 148, 154, 160, 166, 169, 173, 178, 183, 188, 193, 198, 203, and 207, formed by the insertion, deletion, and / or substitution of one or more amino acids, provided that the antibody containing the heavy chain containing the functional variant retains its ability to bind to CEACAM5. In some examples, the light chain contains a functional variant of the amino acid sequence shown in one of the following SEQ ID NOs: 10, 58, 19, 27, 33, 43, 52, 62, 68, 75, 85, 94, 99, 105, 111, 117, 123, 127, 131, 138, 143, 149, 155, 161, 167, 170, 174, 179, 184, 189, 194, 199, 204, and 208, formed by the insertion, deletion, and / or substitution of one or more amino acids, provided that the antibody containing the light chain containing the functional variant retains its ability to bind to CEACAM5. 【0134】 Functional variants include or consist of amino acid sequences having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, or at least 99.9% sequence identity with the amino acid sequence of the parent polypeptide. 【0135】 In some embodiments, the number of amino acids inserted, deleted, and / or substituted is preferably 40% or less of the total number of amino acids in the parent amino acid sequence, more preferably 35% or less, more preferably 1% to 33%, more preferably 5% to 30%, more preferably 10% to 25%, and more preferably 15% to 20%. For example, the number of amino acids inserted, deleted, and / or substituted may be 1 to 50, preferably 1 to 20, more preferably 1 to 10, and even more preferably 1 to 5. In preferred embodiments, the number of amino acids inserted, deleted, and / or substituted is 1, 2, 3, 4, 5, 6, or 7. 【0136】 In some embodiments, insertions, deletions, and / or substitutions may be performed in framework (FR) regions, e.g., FR1, FR2, FR3, and / or FR4, and / or steady-state regions, e.g., CL, CH1, CH2, and / or CH3. 【0137】 In some examples, the substitution of one or more amino acids may be a conservative substitution of one or more amino acids. Examples of conservative substitutions are as described above. 【0138】 In preferred embodiments, the antibody comprises a heavy chain (HC) and a light chain (LC), where, (1) The HC contains the amino acid sequence shown in SEQ ID NO:9, and the LC contains the amino acid sequence shown in SEQ ID NO:10. (2) The HC contains the amino acid sequence shown in SEQ ID NO: 57, and the LC contains the amino acid sequence shown in SEQ ID NO: 58. (3) The HC contains the amino acid sequence shown in SEQ ID NO:18, and the LC contains the amino acid sequence shown in SEQ ID NO:19. (4) The HC contains the amino acid sequence shown in SEQ ID NO:26, and the LC contains the amino acid sequence shown in SEQ ID NO:27. (5) The HC contains the amino acid sequence shown in SEQ ID NO:32, and the LC contains the amino acid sequence shown in SEQ ID NO:33. (6) The HC comprises the amino acid sequence shown in SEQ ID NO:42, and the LC comprises the amino acid sequence shown in SEQ ID NO:43. (7) The HC contains the amino acid sequence shown in SEQ ID NO: 51, and the LC contains the amino acid sequence shown in SEQ ID NO: 52. (8) The HC contains the amino acid sequence shown in SEQ ID NO:61, and the LC contains the amino acid sequence shown in SEQ ID NO:62. (9) The HC contains the amino acid sequence shown in SEQ ID NO:67, and the LC contains the amino acid sequence shown in SEQ ID NO:68. (10) The HC comprises the amino acid sequence shown in SEQ ID NO:74, and the LC comprises the amino acid sequence shown in SEQ ID NO:75. (11) The HC comprises the amino acid sequence shown in SEQ ID NO:84, and the LC comprises the amino acid sequence shown in SEQ ID NO:85. (12) The HC comprises the amino acid sequence shown in SEQ ID NO:93, and the LC comprises the amino acid sequence shown in SEQ ID NO:94. (13) The HC comprises the amino acid sequence shown in SEQ ID NO:98, and the LC comprises the amino acid sequence shown in SEQ ID NO:99. (14) The HC comprises the amino acid sequence shown in SEQ ID NO:104, and the LC comprises the amino acid sequence shown in SEQ ID NO:105. (15) The HC comprises the amino acid sequence shown in SEQ ID NO:110, and the LC comprises the amino acid sequence shown in SEQ ID NO:111. (16) The HC comprises the amino acid sequence shown in SEQ ID NO:116, and the LC comprises the amino acid sequence shown in SEQ ID NO:117. (17) The HC comprises the amino acid sequence shown in SEQ ID NO:122, and the LC comprises the amino acid sequence shown in SEQ ID NO:123. (18) The HC comprises the amino acid sequence shown in SEQ ID NO:126, and the LC comprises the amino acid sequence shown in SEQ ID NO:127. (19) The HC comprises the amino acid sequence shown in SEQ ID NO:130, and the LC comprises the amino acid sequence shown in SEQ ID NO:131. (20) The HC comprises the amino acid sequence shown in SEQ ID NO:137, and the LC comprises the amino acid sequence shown in SEQ ID NO:138. (21) The HC comprises the amino acid sequence shown in SEQ ID NO:142, and the LC comprises the amino acid sequence shown in SEQ ID NO:143. (22) The HC comprises the amino acid sequence shown in SEQ ID NO:148, and the LC comprises the amino acid sequence shown in SEQ ID NO:149. (23) The HC comprises the amino acid sequence shown in SEQ ID NO:154, and the LC comprises the amino acid sequence shown in SEQ ID NO:155. (24) The HC comprises the amino acid sequence shown in SEQ ID NO:160, and the LC comprises the amino acid sequence shown in SEQ ID NO:161. (25) The HC contains the amino acid sequence shown in SEQ ID NO:166, and the LC contains the amino acid sequence shown in SEQ ID NO:167, or (26) The HC comprises the amino acid sequence shown in SEQ ID NO:169, and the LC comprises the amino acid sequence shown in SEQ ID NO:170. (27) The HC comprises the amino acid sequence shown in SEQ ID NO:173, and the LC comprises the amino acid sequence shown in SEQ ID NO:174. (28) The HC comprises the amino acid sequence shown in SEQ ID NO:178, and the LC comprises the amino acid sequence shown in SEQ ID NO:179. (29) The HC comprises the amino acid sequence shown in SEQ ID NO:183, and the LC comprises the amino acid sequence shown in SEQ ID NO:184. (30) The HC comprises the amino acid sequence shown in SEQ ID NO:188, and the LC comprises the amino acid sequence shown in SEQ ID NO:189. (31) The HC comprises the amino acid sequence shown in SEQ ID NO:193, and the LC comprises the amino acid sequence shown in SEQ ID NO:194. (32) The HC comprises the amino acid sequence shown in SEQ ID NO:198, and the LC comprises the amino acid sequence shown in SEQ ID NO:199. (33) The HC contains the amino acid sequence shown in SEQ ID NO:203, and the LC contains the amino acid sequence shown in SEQ ID NO:204, or (34) The HC contains the amino acid sequence shown in SEQ ID NO:207, and the LC contains the amino acid sequence shown in SEQ ID NO:208. 【0139】 In some examples, the antibody is a mouse antibody, a chimeric antibody, a humanized antibody, or a human antibody. 【0140】 Based on the amino acid sequence of the constant region of the antibody heavy chain, immunoglobulin molecules may be divided into five types (isotypes): IgA, IgD, IgE, IgG, and IgM, and further divided into different subtypes, such as IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, etc. Based on the amino acid sequence of the light chain, the light chain of the antibody may be divided into λ (lambda) chains or κ (kappa) chains. The antibodies disclosed herein may be any of the above classes or subtypes. 【0141】 In some examples, the antibody may be an isotype selected from the group consisting of IgG, IgA, IgM, IgE, and IgD. In some examples, the antibody may be a subtype selected from the group consisting of IgG1, IgG2, IgG3, and IgG4. In preferred examples, the antibody is an IgG1 antibody. 【0142】 The antibodies disclosed herein may be complete antibodies or their antigen-binding fragments. The antigen-binding fragments may be any antibody fragments that retain the ability to bind to CEACAM5. Examples of antigen-binding fragments include, but are not limited to, Fab fragments, F(ab')2 fragments, Fab' fragments, Fd fragments, Fd' fragments, Fv fragments, scFv fragments, dAb fragments, isolated complementarity-determining regions (CDRs), nanoantibodies, linear antibodies comprising a pair of serial Fd fragments (VH-CH1-VH-CH1), and modified forms of any of the above fragments that retain antigen-binding activity. 【0143】 In some examples, the antigen-binding fragment may be selected from the group consisting of Fab, Fab', F(ab')2, Fv, scFv, and ds-scFv. In preferred examples, the antigen-binding fragment is Fab or scFv. 【0144】 In some examples, the antibody includes an Fc region. In some examples, the Fc region may be any isotype and may include, but not be limited to, IgG1, IgG2, IgG3, and IgG4, and may include one or more mutations or modifications. In one example, the Fc region is or is derived from the IgG1 isotype and optionally has one or more mutations or modifications. In one example, the Fc region is human IgG1 Fc. 【0145】 In one embodiment, the Fc region lacks effector function. For example, the Fc region may be an IgG1 isotype or a non-IgG1 type, such as IgG2, IgG3, or IgG4, and the mutation reduces or eliminates its ability to mediate effector function (e.g., ADCC). These mutations are described, for example, in Dall'Acqua WF et al., J Immunol. [Journal of Immunology] 177(2):1129-1138 (2006) and Hezareh M, J Virol. [Journal of Virology] 75(24):12161-12168 (2001). In several embodiments, the antibody Fc region contains wild-type IgG1 Fc with L234A, L235A, and G237A mutations. 【0146】 In some examples, the antibody undergoes mutations at one or more post-translational modification sites. In one example, the Fc region includes a mutation that removes the Asn-linked glycosylated receptor site, or is manipulated to remove the effector function of the antibody. 【0147】 Post-translational modifications (PTMs) are widely observed in proteins expressed in mammalian cells. In addition to conserved PTM sites in antibodies, such as the conserved N-glycosylation site on the CH2 domain of the IgG1 antibody, other PTM sites occurring within the antigen-binding site (i.e., the CDR region) of the antibody can lead to reduced antigen-binding activity or reduced chemical stability. For example, deamidation or isomerization can lead to molecular destabilization and heterogeneity. To reduce sequence risks, PTM motifs may be removed by mutation. VH or VL sequences are scanned for the presence of PTM motifs, such as isomerization motifs (e.g., DG). Then, the "hotspot" residue (e.g., D or G in the DG motif) is mutated to the corresponding residue in the germline sequence or another residue with similar biophysical properties. 【0148】 In some examples, the antibody is a monoclonal antibody, a bispecific antibody, or a multispecific antibody. In some examples, the antibody is monovalent, bivalent, or polyvalent. bispecific antibody 【0149】 In a second aspect, the application provides a bispecific or multispecific antibody. In some examples, the antibody is a bispecific antibody, further comprising a second antigen-binding region that binds to a second antigen. In some examples, the second antigen may be a tumor-associated antigen, an immune checkpoint molecule, or an immune cell antigen. 【0150】 In this field, many tumor-associated antigens have already been identified that are associated with specific cancers. In some embodiments, tumor-associated antigens are antigens that can potentially stimulate a clear tumor-specific immune response. Here, some antigens are encoded by normal cells, but not necessarily expressed by normal cells. These antigens can be characterized as those that are normally silent (i.e., not expressed) in normal cells, those that are expressed only at certain stages of differentiation, and those that are expressed over time, such as embryonic and fetal antigens. Other cancer antigens are encoded by mutant cell genes, such as oncogenes (e.g., activated ras oncogene), inhibitory genes (e.g., mutant p53), and fusion proteins resulting from internal deletions or chromosomal translocations. Other cancer antigens may be encoded by viral genes, such as viral genes carried by RNA and DNA oncoviruses. Many other tumor-associated antigens and antibodies against them are known and / or commercially available and may be produced by those skilled in the art. 【0151】 Examples of tumor-associated antigens include, but are not limited to, 5T4, α-fetoprotein, CA-125, mesothelin, CD19, CD20, CD22, CD23, CD30, CD33, CD40, CD56, CD79, CD78, CD123, CD138, c-Met, CSPG4, IgM, type C lectin-like molecule 1 (CLL-1), EGFR, EGFRvIII, epithelial tumor antigens, ERBB2, FLT3, folate-binding proteins, GD2, GD3, HIV-1 envelope glycoprotein gp41, HIV-1 envelope glycoprotein gpl20, melanoma-associated antigens, CD200R1, MUC-1, mutated p53, mutated ras, ROR1, VEGFR2, and combinations thereof. 【0152】 In some examples, the second antigen is a T cell antigen. In some examples, the T cell antigen may be selected from the group consisting of the T cell receptor (TCR), CD3, CD4, CD8, CD16, CD25, CD28, CD44, CD62L, CD69, ICOS, 41-BB (CD137), and NKG2D, or any combination thereof. 【0153】 In some examples, the second antigen is an immune checkpoint molecule. In some examples, the immune checkpoint molecule may be selected from the group consisting of PD-1, PD-L1, CTLA-4, and the like. 【0154】 In some examples, the bispecific antibody comprises one polypeptide chain or multiple polypeptide chains (e.g., two or four) comprising a first antigen-binding region, a second antigen-binding region, and an optional Fc region. 【0155】 The Fc region may be any isotype and may include, but not be limited to, IgG1, IgG2, IgG3, and IgG4, and may contain one or more mutations or modifications. In one embodiment, the Fc region is or is derived from the IgG1 isotype and optionally has one or more mutations or modifications. In one embodiment, the Fc region is human IgG1 Fc. 【0156】 In one embodiment, the Fc region lacks effector function. For example, the Fc region may be an IgG1 isotype or a non-IgG1 type, such as IgG2, IgG3, or IgG4, and the mutation reduces or even eliminates its ability to mediate effector function (e.g., ADCC). These mutations are described, for example, in Dall'Acqua WF et al., J Immunol. [Journal of Immunology] 177(2):1129-1138 (2006) and Hezareh M, J Virol. [Journal of Virology] 75(24):12161-12168 (2001). 【0157】 In one embodiment, the Fc region includes a mutation that removes an Asn-linked glycosylation receptor site, or is otherwise manipulated to alter its glycosylation properties. For example, in the IgG1 Fc region, the N297Q mutation may be used to remove an Asn-linked glycosylation site. Therefore, in a special embodiment, the Fc region includes an IgG1 wild-type sequence having the N297Q mutation. For example, in the IgG1 Fc region, the N297Q mutation may be used to remove an Asn-linked glycosylation site. Therefore, in a special embodiment, the Fc region includes an IgG1 wild-type sequence having the N297Q mutation. 【0158】 In further examples, the Fc region is genetically engineered to reduce fucose, thereby enhancing ADCC, for example, by adding the compound to the culture medium during the antibody production process, as described, for example, US2009317869 or van Berkel et al. (2010) Biotechnol.Bioeng.105:350, or by using FUT8 knockout cells, as described, for example, Yamane-Ohnuki et al. (2004) Biotechnol.Bioeng.87:614. Alternatively, ADCC may be optimized by the method described by Umana et al. (1999) Nature Biotech.17:176. In further examples, the Fc region has already been engineered to enhance complement activation, as described, for example, Natsume et al. (2009) Cancer Sci.100:2411. nucleic acid 【0159】 In a third aspect, the present invention provides a nucleic acid comprising a nucleotide sequence encoding an anti-CEACAM5 antibody or its antigen-binding fragment as disclosed herein, or a bispecific antibody or its antigen-binding fragment as disclosed herein. 【0160】 "Polynucleotide" or "nucleic acid" includes single-stranded and double-stranded nucleotide polymers. Nucleotides containing nucleic acids may be ribonucleotides or deoxyribonucleotides or modified forms of either type of nucleotide. Such modifications include base modifications such as bromouridine and inosine derivatives, ribose modifications such as 2',3'-dideoxyribose, and internucleotide bond modifications such as thiophosphate, dithiophosphate, seleniumphosphate, diseleniumphosphate, thioanilinephosphate, anilinephosphate, and aminophosphate. 【0161】 For example, the present invention provides a nucleic acid molecule encoding any one of the heavy chain variable region sequences disclosed herein. The present invention further provides a nucleic acid molecule that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the nucleic acid encoding any one of the heavy chain variable region sequences disclosed herein. 【0162】 For example, the present invention provides a nucleic acid molecule encoding any one of the light chain variable region sequences disclosed herein. The present invention further provides a nucleic acid molecule that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the nucleic acid encoding any one of the light chain variable region sequences disclosed herein. 【0163】 For example, the present invention provides a nucleic acid molecule that encodes (i) any one heavy chain variable region sequence disclosed herein and (ii) any one light chain variable region sequence disclosed herein. The present invention further provides a nucleic acid molecule that is at least 90%, at least 95%, at least 98%, or at least 99% identical to a nucleic acid encoding (i) any one heavy chain variable region sequence disclosed herein and (ii) any one light chain variable region sequence disclosed herein. 【0164】 For example, the present invention provides a nucleic acid molecule encoding a heavy chain variable region sequence, the heavy chain variable region sequence comprising a CDR sequence of any one of the heavy chain variable region sequences disclosed herein. 【0165】 For example, the present invention provides a nucleic acid molecule encoding a heavy chain variable region sequence, the heavy chain variable region sequence comprising one of the three CDR sequences disclosed herein. 【0166】 The present invention further provides nucleic acid molecules encoding heavy chain variable region sequences, the heavy chain variable region sequences comprising CDR sequences that are at least 90%, at least 95%, at least 98%, or at least 99% identical to the CDR sequences of any one of the heavy chain variable region sequences disclosed herein. 【0167】 In some embodiments, the present invention provides nucleic acid molecules encoding heavy chain variable region sequences, the heavy chain variable region sequences comprising CDR1, CDR2, and CDR3 sequences that are at least 90%, at least 95%, at least 98%, or at least 99% identical to any one of the three CDR sequences disclosed herein. 【0168】 For example, the present invention provides a nucleic acid molecule encoding a light chain variable region sequence, the light chain variable region sequence comprising a CDR sequence of any one of the light chain variable region sequences disclosed herein. 【0169】 In some embodiments, the present invention provides nucleic acid molecules encoding a light chain variable region sequence, the light chain variable region sequence comprising one of the three CDR sequences disclosed herein. 【0170】 The present invention further provides nucleic acid molecules encoding a light chain variable region sequence, wherein the light chain variable region sequence includes a CDR sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the CDR sequence of any one of the light chain variable region sequences disclosed herein. 【0171】 In some embodiments, the present invention provides nucleic acid molecules encoding light chain variable region sequences, each comprising CDR1, CDR2, and CDR3 sequences that are at least 90%, at least 95%, at least 98%, or at least 99% identical to one of the three CDR sequences disclosed herein. 【0172】 For example, the present invention provides a nucleic acid molecule that encodes (i) a heavy chain variable region sequence comprising a CDR sequence of any one of the heavy chain variable region sequences disclosed herein, and (ii) a light chain variable region sequence comprising a CDR sequence of any one of the light chain variable region sequences disclosed herein. In some embodiments, the present invention provides a nucleic acid molecule that encodes (i) a heavy chain variable region sequence comprising any one of the three CDR sequences disclosed herein, and (ii) a light chain variable region sequence comprising any one of the three CDR sequences disclosed herein. The present invention further provides a nucleic acid molecule that encodes (i) a heavy chain variable region sequence comprising a CDR sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the CDR sequence of any one of the heavy chain variable region sequences disclosed herein, and (ii) a light chain variable region sequence comprising a CDR sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the CDR sequence of any one of the light chain variable region sequences disclosed herein. In some embodiments, the present invention provides a nucleic acid molecule that encodes (i) a heavy chain variable region sequence comprising CDR1, CDR2, and CDR3 sequences which are at least 90%, at least 95%, at least 98%, or at least 99% identical to any one of the three CDR sequences disclosed herein, and (ii) a light chain variable region sequence comprising CDR1, CDR2, and CDR3 sequences which are at least 90%, at least 95%, at least 98%, or at least 99% identical to any one of the three CDR sequences disclosed herein. 【0173】 In some embodiments, the nucleic acid is ribonucleic acid (RNA) or deoxyribonucleic acid (DNA). In some embodiments, the present invention provides ribonucleic acid (RNA) comprising a nucleotide sequence encoding an anti-CEACAM5 antibody or its antigen-binding fragment as disclosed herein, or a bispecific antibody or its antigen-binding fragment as disclosed herein. In some embodiments, the present invention provides deoxyribonucleic acid (DNA) comprising a deoxyribonucleic acid sequence encoding an anti-CEACAM5 antibody or its antigen-binding fragment as disclosed herein, or a bispecific antibody or its antigen-binding fragment as disclosed herein. 【0174】 In some embodiments, deoxyribonucleic acid (DNA) may be introduced into human cells in vivo. In some embodiments, the deoxyribonucleic acid (DNA) of the present invention is contained in a vector or delivery agent. In some embodiments, the deoxyribonucleic acid (DNA) of the present invention is incorporated into the genome of a cell. 【0175】 In some embodiments, ribonucleic acid (RNA) may be introduced into human cells in vivo. In some embodiments, the ribonucleic acid (RNA) of the present invention is included in a vector or delivery agent. 【0176】 In some specific embodiments, the ribonucleic acid (RNA) comprising a nucleotide sequence encoding the anti-CEACAM5 antibody or its antigen-binding fragment disclosed herein, or the bispecific antibody or its antigen-binding fragment disclosed herein, is mRNA. In some embodiments, the mRNA of the present invention is contained in a vector or delivery system (e.g., liposome). In some embodiments, the mRNA can be introduced into human cells in vivo by the vector or delivery system (e.g., liposome) to express the CEACAM5 antibody of the present invention in vivo. vector 【0177】 In a fourth aspect, the present invention provides a vector comprising a nucleic acid, the nucleic acid comprising a nucleotide sequence encoding an anti-CEACAM5 antibody or its antigen-binding fragment as disclosed herein, or a bispecific antibody or its antigen-binding fragment as disclosed herein. 【0178】 In some examples, the vector is a recombinant expression vector capable of expressing a polypeptide containing the heavy chain or light chain variable region of an anti-CEACAM5 antibody. For example, the present invention provides a recombinant expression vector containing any of the above nucleic acid molecules. 【0179】 Any vector may be applicable to this disclosure. In some examples, the vector is a viral vector. In some examples, the vector is a retroviral vector, a DNA vector, a mouse leukemia virus vector, an SFG vector, a plasmid, an RNA vector, an adenovirus vector, a baculovirus vector, an EB (Epstein-Barr) virus vector, a papovavirus vector, a vaccinia virus vector, a herpes simplex virus vector, an adenovirus-associated vector (AAV), a lentiviral vector, or any combination thereof. Suitable exemplary vectors include, for example, pGAR, pBABE-puro, pBABE-neo largeTcDNA, pBABE-hygro-hTERT, pMKO.1 GFP, MSCV-IRES-GFP, pMSCV PIG (Puro IRES GFP empty plasmid), pMSCV-loxp-dsRed-loxp-eGFP-Puro-WPRE, MSCV IRES luciferase, pMIG, MDH1-PGK-GFP_2.0, TtRMPVIR, pMSCV-IRES-mCherry FP, pRetroX GFP T2A Cre, pRXTN, pLncEXP, and pLXIN-Luc. 【0180】 The recombinant expression vector may be any suitable recombinant expression vector. Suitable vectors include, for example, plasmids and viruses, that are designed to be used for proliferation and amplification or expression or both. For example, vectors may be selected from the pUC series (Fermentas Life Sciences, Glen Burnie, Md.), the pBluescript series (Stratagene, La Jolla, California), the pET series (Novagen, Madison, Wisconsin), the pGEX series (Pharmacia Biotech, Uppsala, Sweden), and the pEX series (Clontech, Palo Alto, California). Phage vectors, such as λGT10, λGT11, λZapII (Stratagene), λEMBL4, and λNM1149, may also be used. Examples of plant expression vectors useful in the context of this disclosure include pBI01, pBI101.2, pBI101.3, pBI121, and pBIN19 (Clontech). Examples of animal expression vectors useful in the context of this disclosure include pcDNA, pEUK-Cl, pMAM, and pMAMneo (Clontech). 【0181】 Recombinant expression vectors may be prepared using standard recombinant DNA techniques as described, for example, in Sambrook et al., Molecular Cloning: A Laboratory Manual, 3rd Edition, Cold Spring Press, Cold Spring, New York, 2001, and Ausubel et al., Current Protocols in Molecular Biology, Greene Publishing Associates and John Wiley & Sons, New York, 1994. Circular or linear expression vector constructs may be prepared to include a replication system that functions within a prokaryotic or eukaryotic host cell. The replication system may be derived from, for example, ColEl, 2μ plasmid, λ, SV40, bovine papillomavirus, etc. 【0182】 The vector of the present invention may be introduced into cells. In some examples, the vector of the present invention may be introduced into in vitro or ex vivo cells. Optionally, the cells into which the vector has been introduced may then be administered into the subject. In some examples, the vector of the present invention may be introduced into in vivo cells. 【0183】 For example, the vector may be an adenovirus vector comprising a nucleotide sequence encoding the anti-CEACAM5 antibody or its antigen-binding fragment disclosed herein, or the bispecific antibody or its antigen-binding fragment disclosed herein. The vector may be administered intracellularly to a subject, and in vivo into the subject's cells, thereby incorporating the anti-CEACAM5 antibody or its antigen-binding fragment disclosed herein, or the nucleotide sequence encoding the bispecific antibody or its antigen-binding fragment disclosed herein, into the cell's genome, and subsequently, the cell expresses the anti-CEACAM5 antibody or its antigen-binding fragment disclosed herein. host cell 【0184】 In a fifth aspect, the present invention further provides a host cell comprising a nucleic acid or a vector disclosed herein. 【0185】 Any cell may be used as a host cell for the nucleic acids or vectors of this disclosure. In some examples, the cell may be a prokaryotic cell, a fungal cell, a yeast cell, or a higher eukaryotic cell, such as a mammalian cell. Suitable prokaryotic cells include, but are not limited to, bacteria, such as Gram-negative or Gram-positive organisms, such as Enterobacteriaceae, such as Escherichia, such as Escherichia coli, Enterobacter, Erwinia, Klebsiella, Proteus, Salmonella, such as Salmonella tiphyllum, Serratia, such as Serratia marcescens and Sigella, Bacillus, such as Bacillus subtilis and Bacillus licheniformis, Pseudomonas, such as Pseudomonas aeruginosa, and Streptomyces. In some examples, the cell is a human cell. In some examples, the cell is an immune cell. In some examples, the host cells include, for example, CHO cells, such as CHOS cells and CHOK1 cells, or HEK293 cells, such as HEK293A, HEK293T, and HEK293FS. 【0186】 The host cells of the present invention are prepared by introducing the vectors or nucleic acids disclosed herein in vitro or ex vivo. The host cells of the present invention may be administered into a subject, and the host cells treat the diseases disclosed herein by expressing the anti-CEACAM5 antibody or its antigen-binding fragment disclosed herein in vivo. 【0187】 The present invention further provides host cells into which any of the above vectors have been introduced. The present invention further provides a method for producing antibodies and antibody fragments of the present invention by culturing host cells under conditions that allow for the production of antibodies or antibody fragments, and recovering the antibodies and antibody fragments produced thereby. Conjugates and Antibody-Drug Conjugates 【0188】 The antibody or antigen-binding fragment of the present invention can be linked to a chemical moiety to form a conjugate. 【0189】 In the context of this disclosure, “conjugate” is an antibody or antibody fragment (e.g., an antigen-binding fragment) that covalently binds to a chemical moiety. The chemical moiety may be, for example, a drug, a toxin, a therapeutic agent, a detectable label, a protein, a nucleic acid, a lipid, a nanoparticle, a carbohydrate, or a recombinant virus. Antibody conjugates are commonly referred to as “immunoconjugates.” If the conjugate includes an antibody linked to a drug (e.g., a cytotoxic drug), the conjugate is commonly referred to as an “antibody-drug conjugate” or “ADC.” 【0190】 The terms "conjugate" or "link" may refer to the preparation of two polypeptides into a single continuous polypeptide molecule. In one example, an antibody is linked to a chemical moiety. In another example, the antibody linked to the chemical moiety is linked to a protein or peptide together with a lipid or other molecule to increase its in vivo half-life. Such linking may be carried out chemically or recombinantly. In one example, the linking is chemical, where the reaction between the antibody moiety and the chemical moiety produces a covalent bond between the two molecules to form a single molecule. A peptide linker (short peptide sequence) may optionally be included between the antibody and the chemical moiety. 【0191】 The chemical moiety may be linked to the antibody of the present invention by any number of means known to those skilled in the art. Covalent and non-covalent linking means may be used. The procedure for linking the chemical moiety to the antibody varies depending on the chemical structure of the chemical moiety. Polypeptides typically contain various functional groups, such as carboxylic acid (COOH), free amine (-NH2), or mercapto (-SH) groups, which may be used to react with appropriate functional groups in the antibody to induce linking of the chemical moiety. Alternatively, the antibody may be derivatized to expose or link another reactive functional group. Derivatization may involve linking to any one of many known linker molecules. The linker may be any molecule for linking the antibody to the chemical moiety. The linker can form a covalent bond with the antibody and the chemical moiety. Suitable linkers are well known to those skilled in the art and include, but are not limited to, linear or branched carbon linkers, heterocyclic carbon linkers, or peptide linkers. When the antibody and its chemical moiety are polypeptides, the linker can be linked to the constituent amino acids via their pendant groups (e.g., via disulfide bonds with cysteine), or to the α-carbon amino group and carboxyl group of the terminal amino acids. 【0192】 In some cases, the release of a chemical moiety from the antibody is desired when the immunoconjugate reaches its target site. Therefore, in these cases, the immunoconjugate contains ligatures that can be cleaved near the target site. 【0193】 The release of chemical portions from antibodies through linker cleavage may be facilitated by enzyme activity or conditions under which the immunoconjugate is located within or near the target cell. 【0194】 Given that numerous methods have been reported for linking a large number of radiodiagnostic compounds, radiotherapeutic compounds, labels (e.g., enzymes or fluorescent molecules), drugs, toxins, and other reagents to antibodies, those skilled in the art can determine a suitable method for linking a given reagent to an antibody or other polypeptide. 【0195】 The antibodies disclosed herein may be derivatized or linked to another molecule (e.g., another peptide or protein). Typically, the antibody or a portion thereof is derivatized to prevent adverse effects of derivatization or labeling on binding to a target antigen. For example, the antibody may be linked functionally (by chemical coupling, gene fusion, non-covalent association or other means) to one or more other molecular entities, such as another antibody (e.g., a bispecific antibody or diabody), a detection reagent, a drug reagent, and / or a protein or peptide that can mediate the association of the antibody or antibody portion with another molecule (e.g., a streptavidin core region or polyhistidine tag). 【0196】 A type of derivatized antibody is produced by crosslinking two or more antibodies (of the same or different types). Suitable crosslinkers include heterobifunctional (e.g., m-maleimidobenzoyl-N-hydroxysuccinimidyl) or homobifunctional (e.g., disuccinimidyl suberate) crosslinkers having two apparent reactive groups separated by a suitable spacer. Such linkers are commercially available. 【0197】 In some examples of the conjugates disclosed herein, the chemical portion is selected from the group consisting of a therapeutic agent, a detectable portion, and an immunostimulatory molecule. In some examples, the therapeutic agent includes, but is not limited to, immunomodulators, radiocompounds, enzymes (e.g., perforin), chemotherapeutic agents (e.g., cisplatin), or toxins. In some examples, the therapeutic agent may be, for example, meitansine, geldanamycin, microtubule inhibitors (e.g., tubulin binders, e.g., auristatin), or minor groove binders (e.g., calichemycin). 【0198】 Other suitable therapeutic agents include, for example, small molecular weight cytotoxic agents, i.e., compounds with a molecular weight less than 700 daltons that have the ability to kill mammalian cells. These compounds may also contain toxic metals with cytotoxic effects. It should be understood that these small molecular weight cytotoxic agents may further include prodrugs, i.e., compounds that disintegrate or transform under physiological conditions to release cytotoxic agents. Examples of such drugs include cisplatin, meitansine derivatives, rachelmycin, calichemycin, docetaxel, etoposide, gemcitabine, isocyclophosphamide, irinotecan, melphalan, mitoxantrone, porfimer sodium photofrin II, temozolomide, topotecan, glucuronide trimethrexate, auristatin E vincristine and doxorubicin, and mammalian enzymes such as lysine, diphtheria toxin, pseudomonas exotoxin A, DNA enzymes and RNA enzymes. Peptide cytotoxins, which are proteins or fragments thereof that have the ability to kill cells, include radionuclides that are unstable isotopes of elements that decay with the simultaneous emission of one or more alpha particles, beta particles, or gamma rays, such as iodine-131, rhenium-186, indium-111, yttrium-90, bismuth-210, bismuth-213, actinium-225, and astatine-213, and chelating agents can be used to promote the association of these radionuclides with molecules or their polymers. 【0199】 In some examples, the detectable portion may be selected from the group consisting of biotin, streptavidin, enzymes or their catalytically activated fragments, radionuclides, nanoparticles, paramagnetic metal ions, or fluorescent, phosphorescent, or chemiluminescent molecules. Detectable portions for diagnostic purposes include, for example, fluorescent labels, radiolabels, enzymes, nucleic acid probes, and contrast agents. 【0200】 Antibodies can be conjugated with detectable markers, such as those detectable by ELISA, spectrophotometry, flow cytometry, microscopy, or diagnostic imaging techniques (e.g., computed tomography (CT), computed axial tomography (CAT) scanning, magnetic resonance imaging (MRI), nuclear magnetic resonance imaging (NMRI), magnetic resonance imaging (MTR), ultrasound, fiber optics, and laparoscopy). Specific non-limiting examples of detectable markers include fluorophores, chemiluminescent agents, enzyme conjugates, radioisotopes, and heavy metals or compounds (e.g., superparamagnetic iron oxide nanocrystals for MRI detection). For example, useful detectable markers include fluorescent compounds such as fluorescein, fluorescein isothiocyanate, rhodamine, 5-dimethylamine-l-naphthalenesulfonyl chloride, phycoerythrin, and lanthanide phosphors. Bioluminescent markers, such as luciferase, green fluorescent protein (GFP), and yellow fluorescent protein (YFP), are also useful. 【0201】 Antibodies or antigen-binding fragments can be further conjugated with enzymes available for detection, such as horseradish peroxidase, β-galactosidase, luciferase, alkaline phosphatase, and glucose oxidase. When a bispecific antibody or antigen-binding fragment is conjugated with a detectable enzyme, it can be detected by adding other reagents that add the enzyme to produce a recognizable reaction product. For example, if a horseradish peroxidase reagent is present, adding hydrogen peroxide and diaminobenzidine will produce a visible colored reaction product. Bispecific antibodies or antigen-binding fragments can also be conjugated with biotin and detected by indirect measurement of avidin or streptavidin binding. Note that avidin itself can be conjugated with enzymes or fluorescent labels. 【0202】 Antibodies can be fused to self-labeled protein tags (e.g., HaloTag). For example, the protein tag may be cloned at the end of the constant region. HaloTag is a self-labeled protein tag derived from a bacterial enzyme (haloalkane dehalogenase) designed to covalently bind to a synthetic ligand. In some cases, the synthetic ligand includes a chloroalkane linker linked to a fluorophore (e.g., near-infrared fluorophore) (Los et al. (2008) ACS Chem Biol [ACS Chemical Biology]. 3(6):373-82). Antibodies may be labeled with magnetic reagents (e.g., gadolinium). Antibodies may also be labeled with lanthanide elements (e.g., europium and dysprosium) and manganese. 【0203】 Paramagnetic particles (e.g., superparamagnetic iron oxide) may also be used as tags. The bispecific antibody may be labeled with a predetermined polypeptide epitope recognized by a secondary reporter (e.g., a leucine zipper pair sequence, a secondary antibody binding site, a metal-binding domain, or an epitope tag). In some examples, the tags are linked via spacer arms of varying lengths to reduce potential steric hindrance. 【0204】 Antibodies may be labeled with radiolabeled amino acids. Radiolabeling is available for diagnostic and therapeutic purposes. For example, radiolabeling can be used to detect the expression of a target antigen through X-rays, synchrotron radiation spectra, or other diagnostic techniques. Examples of polypeptide labeling include: 3 H, 14 C, 15 N, 35 S, 90 Y, 99 Tc, 111 In, 125 I, 131 It contains, but is not limited to, the radioactive isotope or radioactive nucleotide I. 【0205】 In some embodiments, the immunostimulatory molecule is an immune effector molecule that stimulates an immune response. For example, the immunostimulatory molecule may be a cytokine, e.g., IL-2 and IFN-γ; a chemokine, e.g., IL-8; platelet factor 4; melanoma growth-stimulating protein; complement activator; viral / bacterial protein domain; or viral / bacterial peptide. 【0206】 In some embodiments, the antibody or antigen-binding fragment of the present invention is fluorescently labeled, radioactively labeled, or linked to a drug moiety. In some embodiments, the antibody or antigen-binding fragment of the present invention is linked to a drug moiety to form an antibody-drug conjugate (ADC). 【0207】 Therefore, in a sixth aspect, the present invention provides an antibody-drug conjugate (ADC), wherein the ADC comprises an antibody or antigen-binding fragment thereof according to a first aspect of the present invention or a bispecific antibody according to a second aspect of the present invention, and a drug portion conjugated thereto via a linker. 【0208】 The terms “drug portion,” “drug payload,” “therapeutic molecule,” “therapeutic payload,” “therapeutic agent,” and “therapeutic portion,” which are interchangeable terms used herein, refer to the chemical or biological portion that conjugates with an antibody or its antigen-binding fragment that binds to CEACAM5. 【0209】 Below, we provide examples of drugs usable in ADCs, i.e., drugs that can be conjugated with antibodies, including antibiotics, DNA synthesis inhibitors, RNA polymerase II inhibitors and RNA spliceosome inhibitors, microtubule inhibitors, antitumor antibiotics, immunomodulators, gene therapy vectors, alkylating agents, angiogenesis inhibitors, antimetabolites, boron-containing drugs, chemoprotective agents, hormonal drugs, glucocorticoids, photoactivators, oligonucleotides, radioisotopes, radiosensitizers, topoisomerase inhibitors (e.g., topoisomerase I inhibitors), tyrosine kinase inhibitors, and combinations thereof. 【0210】 In some examples, the drug portion is selected from the group consisting of microtubule inhibitors, antibiotics, DNA synthesis inhibitors, topoisomerase inhibitors, RNA polymerase II inhibitors, and RNA spliceosome inhibitors. 【0211】 In some examples, the drug portion is a microtubule inhibitor. In some special examples, the drug portion is auristatin. In some special examples, the drug portion is maytansine. In some special examples, the drug portion is tubulicine. In some special examples, the drug portion is a macrolide. In some special examples, the drug portion is rhizoxin. 【0212】 In some embodiments, the drug portion is an antibiotic. In some special embodiments, the drug portion is calichemycin. In some special embodiments, the drug portion is doxorubicin. In some special embodiments, the drug portion is an anthracycline. 【0213】 In some examples, the drug portion is a DNA synthesis inhibitor. In some special examples, the drug portion is duocalmycin. In some special examples, the drug portion is PBD (pyrrolobenzodiazepine). In some special examples, the drug portion is IGN (indolinobenzodiazepine). 【0214】 In some embodiments, the drug moiety is a topoisomerase inhibitor. In some specific embodiments, the drug moiety is a camptothecin analog. 【0215】 In some embodiments, the drug portion is an RNA polymerase II inhibitor. In some special embodiments, the drug portion is amanitin. 【0216】 In some examples, the drug portion is an RNA spliceosome inhibitor selected from the group consisting of spliceostatins and tylanstatins. 【0217】 In some examples, meitansine compounds (DM1, DM2, DM3, DM4, meitansine, and anthamitocin) and their analogues are preferred. 【0218】 In some examples, auristatin (MMAE, MMAF, MMAD, and anthamitocin) and its analogues are preferred. 【0219】 In some examples, PBD (pyrrolobenzodiazepine, or pyrrolo[2,lc][l,4]-benzodiazepine, e.g., SG3199) is preferred. PBD is a sequence-selective DNA alkylating antibiotic with significant antitumor properties. PBD has the ability to recognize and bind to specific sequences in DNA, one such sequence being PuGPu (purine-guanine-purine). PBD may bind to PuGPy (purine-guanine-pyrimidine) or PyGPu sequences without binding to PyGPy sequences. 【0220】 In some examples, the PBD drug portion is SG3199, which is a cytotoxic DNA minor groove interstrand crosslinked pyrrolobenzodiazepine (PBD) dimer. 【0221】 In several embodiments, camptothecin analogs are preferred. Camptothecin analogs are DNA topoisomerase I inhibitors. Unlike monomethyl auristatin E, camptothecin-based therapy does not clinically cause peripheral neuropathy, which suggests that SGN-CD30C may have the potential to avoid one of the most common adverse events associated with BV. 【0222】 In some specific embodiments, the camptothecin drug portion is 7-ethyl-10-hydroxycamptothecin (also known as SN38). 【0223】 In some specific embodiments, the camptothecin drug portion is Dxd, an effective topoisomerase I inhibitor, or an analog or derivative thereof. 【0224】 In some specific embodiments, the camptothecin drug portion is exatecan (also known as DX-8951). 【0225】 In some examples, calicheamicin is preferred, as it is an antitumor antibiotic and a cytotoxic agent that causes double-strand DNA breaks. N-acetylcalicheamicin is a derivative of calicheamicin and is an effective enediyne-based antitumor antibiotic. In other examples, the drug moiety is doxorubicin or its analogues or derivatives. 【0226】 One or more drug moieties (e.g., therapeutic and / or diagnostic agents) may be indirectly conjugated to an anti-CEACAM5 antibody (e.g., via a linker having direct covalent or non-covalent interactions). The linker may be a chemical linker, such as a homobifunctional or heterobifunctional crosslinker available from many commercial sources. 【0227】 In some embodiments, the linker includes a severable linker or an inseverable linker. 【0228】 Under conditions in which a compound or antibody retains its activity, the linker is susceptible to cleavage (cleavable linker), such as acid-inducible cleavage, photo-inducible cleavage, peptidase-inducible cleavage, esterase-inducible cleavage, and disulfide bond cleavage. Alternatively, the linker can be substantially cleavable (e.g., stable linker or cleavable linker). 【0229】 In some examples, the linker is an acid-unstable linker. In some examples, the linker is a photo-unstable linker. In some examples, the linker is a protease-sensitive linker. In some examples, the linker is a hydrazone linker. In some examples, the linker is an esterase-cleavable linker. In some examples, the linker is a dimethyl linker. In some examples, the linker is a disulfide-containing linker. In some examples, the linker is a hydrophilic linker. In some examples, the linker is a pre-charged linker. In some examples, the linker is an acidic linker. 【0230】 In some examples, the linker includes an acid-unstable linker. In some examples, the linker includes a hydrophilic linker. In some examples, the linker includes a protease-sensitive linker. In some examples, the linker includes a photo-unstable linker. In some examples, the linker includes a hydrazone linker. In some examples, the linker includes a dimethyl linker. In some examples, the linker includes a disulfide-containing linker. 【0231】 In some examples, the linker may contain amino acid units. In one such example, the amino acid units facilitate drug release from the antibody-drug conjugate when exposed to intracellular proteases, such as lysosomal enzymes, by allowing cleavage of the linker by proteases. Exemplary amino acid units include, but are not limited to, dipeptides, tripeptides, tetrapeptides, and pentapeptides. Exemplary dipeptides include valine-citrulline (vc or val-cit), alanine-phenylalanine (af or ala-phe), phenylalanine-lysine (fk or phe-lys), or N-methyl-valine-citrulline (Me-valcit). Exemplary tripeptides include glycine-valine-citrulline (gly-val-cit) and glycine-glycine-glycine (gly-gly-gly). In some examples, linkers containing vc (valine-citrulline) units are preferred. The selectivity for enzymatic cleavage of amino acid units by specific enzymes (e.g., tumor-associated proteases, cathepsins B, C, and D, or plasmin proteases) may be designed and optimized. 【0232】 In one embodiment, the linker used in this disclosure is a crosslinking agent, such as MC (6-maleimidocaproyl), Val-Cit (valine-citrulline), PABC (p-aminobenzyloxycarbonyl), DMEA (dimethylethylamine), Val-Cit-PABC, MC-Val-Cit-PABC, MC-Val-Cit-PABC-DMEA, CL2A, Mal-PEG8-Val-Ala-PABC, GGFG (glycine-glycine-phenylalanine-glycine), MC-GGFG-aminomethyl, AcBut (4-(4-acetylphenoxy)-butyric acid), dimethyl Hydrazine (3-methyl-3-mercaptobutyrate hydrazide), AcBut-dimethylhydrazine, SPDP (N-succinimidyl-3-(2-pyridyldithio)propionate), SPP (4-(2-pyridyldithio)pentanoate N-succinimidyl), SPDB (4-(2-pyridyldithio)butyrate N-succinimidyl), sulfo-SPDB (N-succinimidyl-4-(2-pyridyldithio)-2-sulfobutyrate), SIA (N-succinimidyliodoacetate), SIAB ((4-iodoacetyl)aminobenzoate N-succinimidyl), maleimide PEG It is derived from NHS, SMCC (4-(maleimidomethyl)cyclohexanecarboxylic acid N-succinimidyl), sulfo-SMCC (4-(maleimidomethyl)cyclohexanecarboxylic acid N-sulfosuccinimidyl), or 17-(2,5-dioxo-2,5-dihydro-1H-pyrrole-1-yl)-5,8,11,14-tetraoxo-4,7,10,13-tetraazaheptadecan-1-acid 2,5-dioxopyrrolidine-1-yl (CX1-1). 【0233】 In another embodiment, the linker used in this disclosure is derived from a crosslinking reagent, such as sulfo-SPDB (N-succinimidyl-4-(2-pyridyldithio)-2-sulfo-butyrate), mc (6-maleimidocaproyl), Val-Cit (valine-citrulline), PABC (p-aminobenzyl alcohol), Val-Cit-PABC, mc-Val-Cit-PABC, CL2A, mal-PEG8-Val-Ala-PABC, GGFG (glycine-glycine-phenylalanine-glycine), mc-GGFG-aminomethyl, AcBut (4-(4-acetylphenoxy)-butyric acid), dimethylhydrazine (3-methyl-3-mercaptobutyrate hydrazide), AcBut-dimethylhydrazine, or SMCC (4-(maleimidomethyl)cyclohexanecarboxylic acid N-succinimidyl). 【0234】 In preferred examples, the linker is selected from the group consisting of MC (6-maleimidocaproyl), Val-Cit (valine-citrulline), PABC (p-aminobenzyloxycarbonyl), DMEA (dimethylethylamine), Val-Cit-PABC, MC-Val-Cit-PABC, MC-Val-Cit-PABC-DMEA, GGFG (glycine-glycine-phenylalanine-glycine), MC-GGFG-aminomethyl, AcBut (4-(4-acetylphenoxy)-butyric acid), and AcBut-dimethylhydrazine. In one more preferred example, the linker is MC-Val-Cit-PABC. Pharmaceutical composition 【0235】 In a seventh aspect, the present invention provides a pharmaceutical composition comprising (i) an antibody or antigen-binding fragment thereof according to a first aspect of the present invention, or a bispecific antibody according to a second aspect of the present invention, or a nucleic acid according to a third aspect of the present invention, or a vector according to a fourth aspect of the present invention, or a host cell according to a fifth aspect of the present invention, or an ADC according to a sixth aspect of the present invention, and optionally (ii) a pharmaceutically acceptable carrier or excipient. 【0236】 The present invention provides pharmaceutical compositions comprising the antibody of the present invention. In some embodiments, the pharmaceutical composition further comprises a pharmaceutically acceptable carrier agent. The term "pharmaceutically acceptable carrier agent" includes any and all solvents, buffers, dispersion media, coatings, antimicrobial and antifungal agents, isotonic agents and absorption retarders of physiological compatibility. Preferably, the carrier agent is applied to intravenous, intramuscular, subcutaneous, parenteral, spinal, or epidermal administration (e.g., by injection or infusion). For example, in some embodiments, the composition used for intravenous administration is typically a solution in a sterile isotonic aqueous buffer. 【0237】 The antibodies or reagents of the present invention (also referred to herein as “active compounds”) and their derivatives, fragments, analogs, and homologs may be doped into pharmaceutical compositions suitable for administration. Such compositions typically comprise the antibody or reagent and a pharmaceutically acceptable carrier. As used herein, the term “pharmaceutically acceptable carrier” is intended to include any and all solvents, dispersion media, coatings, antimicrobial and antifungal agents, isotonic agents, and absorption retarders that are compatible with the administration of the drug. Suitable carriers are described in the latest edition of Remington's Pharmaceutical Sciences, a standard reference document in the art, which is incorporated herein by reference. Preferred examples of such carriers or diluents include, but are not limited to, water, saline solution, Ringer's solution, glucose solution, and 5% human serum albumin. Liposomes and non-aqueous media, such as fixing oils, may also be used. The use of such media and reagents with pharmacoactive substances is well known in the art. Consider using any conventional media or reagents in the composition unless they are unsuitable for the active compound. Supplemental active compounds may be doped into the composition. 【0238】 The pharmaceutical compositions of the present invention are prepared to suit the desired route of administration. Examples of routes of administration include parenteral administration, e.g., intravenous, intradermal, subcutaneous, oral administration (e.g., inhalation), transdermal (i.e., topical), transmucosal, and rectal administration. Solutions or suspensions for parenteral, intradermal, or subcutaneous administration may contain components such as sterile diluents such as water for injection, aqueous saline solutions, fixative oils, polyethylene glycol, glycerin, propylene glycol, or other synthetic solvents; antimicrobial agents such as benzyl alcohol or methyl p-hydroxybenzoate; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethylenediaminetetraacetic acid (EDTA); buffers such as acetates, citrates, or phosphates; and reagents for adjusting tension, such as sodium chloride or glucose. The pH may be adjusted with an acid or base, e.g., hydrochloric acid or sodium hydroxide. Parenteral formulations can be sealed in ampoules, disposable syringes, or multi-dose vials made of glass or plastic. 【0239】 Pharmaceutical compositions suitable for injection include sterile aqueous solutions (water-soluble) or dispersions, and sterile powders for the temporary preparation of sterile injection solutions or dispersions. For intravenous administration, suitable carriers include physiological saline, bacteriostatic water, and Cremophor EL. (商標)The composition contains either BASF (Parsippany, New Jersey) or phosphate-buffered saline (PBS). Under all circumstances, the composition must be sterile and have sufficient fluidity for easy injection. It must maintain stability under manufacturing and storage conditions and prevent contamination by microorganisms such as bacteria and fungi. The carrier may be a solvent or dispersion medium containing, for example, water, ethanol, polyols (e.g., glycerin, propylene glycol, and liquid polyethylene glycol), and suitable mixtures thereof. Adequate fluidity may be maintained by the use of a coating (e.g., lecithin), by maintaining a desired particle size in the case of a dispersion, and by the use of a surfactant. Microbial action can be prevented by various antimicrobial and antifungal agents (e.g., parahydroxybenzoate, chlorobutanol, phenol, ascorbic acid, thimerosal, etc.). Often, the composition preferably contains isotonic agents, such as sugars, polyols, such as mannitol, sorbitol, and sodium chloride. Sustained absorption of an injectable composition can be achieved by including reagents that delay absorption, such as aluminum monostearate and gelatin, in the composition. 【0240】 Sterile injectable solutions can be prepared by doping the required amount of the active compound with one or more of the above components (as needed) in a suitable solvent and then sterilizing by filtration. Typically, dispersions are prepared by doping the active compound in a sterile medium, which contains a basic dispersion medium and other desired components from those listed above. In the case of sterile powders for the preparation of sterile injectable solutions, the preparation method is vacuum drying and freeze-drying, which produce powders of the active component and any other desired components from the previously sterile filtered solution. 【0241】 Oral compositions typically contain an inert diluent or a food carrier. Oral compositions may be encapsulated in gelatin capsules or compressed into tablets. For oral therapeutic administration, the active compound may be doped with excipients and used in the form of tablets, lozenges, or capsules. Oral compositions may also be prepared using a liquid carrier used as a mouthwash, where the compound in the fluid carrier is gargled and then expelled or swallowed. Pharmaceutically compatible binders and / or adjuvant materials may be included as part of the composition. Tablets, pills, capsules, lozenges, etc., may contain any ingredient or compounds of similar properties, such as adhesives, e.g., microcrystalline cellulose, tragacanth, or gelatin; excipients, e.g., starch, or lactose; disintegrants, e.g., alginic acid, Primogel, or corn starch; lubricants, e.g., magnesium stearate or Sterotes; fluidity enhancers, e.g., colloidal silica; sweeteners, e.g., sucrose or saccharin; or flavoring agents, e.g., mint, methyl salicylate, or orange-flavored flavoring agents. 【0242】 For inhalation administration, the compound is delivered in the form of an aerosol spray from a pressurized container, dispenser, or nebulizer containing a suitable propellant (e.g., a gas such as carbon dioxide). 【0243】 Systemic administration may be carried out via mucosal or transdermal methods. In the case of mucosal or transdermal administration, a penetrating agent suitable for penetration into the target barrier is used in the formulation. Such penetrating agents are those commonly known in the art and include, for example, cleansing agents, bile acids, and fusidic acid derivatives for mucosal administration. Mucosal administration may be carried out using nasal sprays or suppositories. In the case of transdermal administration, the active compound is prepared in the form of ointments, plasters, gels, or creams that are commonly known in the art. 【0244】 The compound may be prepared in the form of a suppository (for example, using a conventional suppository matrix, such as cocoa butter and other glycerides) or a retained enema for rectal administration. 【0245】 In one embodiment, the active compound is prepared together with a carrier agent, which protects the compound from rapid elimination from the body and is a sustained-release formulation, for example, including implants and microencapsulation delivery systems. Biodegradable and biocompatible polymers, such as ethylene vinyl acetate, polyacid anhydride, polyglycolic acid, collagen, polyorthoesters, and polylactic acid may be used. Methods for preparing such formulations are obvious to those skilled in the art. The materials are also commercially available from Alza Corporation and Nova Pharmaceuticals, Inc. Liposome suspensions (containing liposomes targeting infected cells, which have monoclonal antibodies against viral antigens) may be used as pharmaceutically acceptable carrier agents. These may be prepared based on methods known to those skilled in the art, for example, those described in U.S. Patent No. 4,522,811. 【0246】 Preparing oral or parenteral compositions in dose-unit form is particularly advantageous in terms of ease of administration and dose uniformity. As used herein, dose-unit form refers to a physical discrete unit suitable as a single dose for a subject to be treated, each unit containing a predetermined amount of the active compound, which, by calculation, yields the required therapeutic effect associated with the required drug carrier. The specifications of the dose-unit form of the present invention are determined and directly depend on the unique characteristics of the active compound, the specific therapeutic effect to be achieved, and the limitations inherent in the field of complex use of such active compounds in a subject to be treated. 【0247】 The pharmaceutical composition may be contained in a container, packaging, or dispenser along with the instructions for administration. 【0248】 This invention provides a therapeutic composition comprising the anti-CEACAM5 antibody or its antigen-binding fragment. The therapeutic composition according to the present invention, when administered with a suitable carrier, excipient, and other reagents doped into the formulation, provides improved transfer, delivery, resistance, etc. Many suitable formulations can be found in the formulary known to all pharmacochemists. (Remington's Pharmaceutical Sciences, Mack Publishing Company, Easton, Pennsylvania). These formulations include, for example, powders, pastes, ointments, jellies, waxes, oils, lipids, and lipid (cationic or anionic)-containing vesicles (e.g., LIPOFECTIN). (商標) This includes DNA conjugates, anhydrous absorbent pastes, oil-in-water and water-in-oil emulsions, carbowax emulsions (polyethylene glycol of various molecular weights), semi-solid gels, and carbowax-containing semi-solid mixtures. See also Powell et al., "Compendium of excipients for parenteral formulations," PDA (1998) J Pharm Sci Technol [Journal of Pharmaceutical Sciences and Technology] 52:238-311. Production method 【0249】 Monoclonal antibodies may be prepared by hybridoma methods, for example, as described in Kohler and Milstein, Nature, 256:495 (1975). In hybridoma methods, mice, hamsters, or other suitable host animals are typically immunized with an immunizer to induce lymphocytes that produce or are capable of producing antibodies, and these antibodies specifically bind to the immunizer. Alternatively, lymphocytes may be immunized in vitro. 【0250】 Immunotherapeutic agents typically contain protein antigens, their fragments, or fusion proteins. Peripheral blood lymphocytes are usually used when human-derived cells are required, or spleen cells or lymph node cells are used when non-human mammalian sources are required. The lymphocytes are then fused with immortalized cell lines using a suitable fusion agent (e.g., polyethylene glycol) to form hybridoma cells (Goding, Monoclonal Antibodies: Principles and Practice, Academic Press, (1986), pp. 59-103). Immortalized cell lines are typically transformed mammalian cells, particularly rodent, bovine, and human myeloma cells. Rat or mouse myeloma cell lines are usually used. Hybridoma cells may be cultured in a suitable medium, which preferably contains one or more substances that inhibit the proliferation or survival of unfused immortalized cells. For example, if the parent cells lack the enzyme hypoxanthine guanine phosphoribosyltransferase (HGPRT or HPRT), the culture medium for hybridomas typically contains hypoxanthine, methotrexate, and thymidine (HAT medium) to prevent the proliferation of HGPRT-deficient cells. 【0251】 A preferred immortalized cell line is one that effectively fuses, supports stable high-level expression of antibodies by selected antibody-producing cells, and is sensitive to culture media (e.g., HAT medium). A more preferred immortalized cell line is the mouse myeloma cell line, which is available, for example, from the Salk Institute Cell Distribution Center in San Diego, California, and the American Type Culture Collection in Manassas, Virginia. Human myeloma and mouse-human xenomyeloma cell lines have also been described for the production of human monoclonal antibodies. (See Kozbor, J. Immunol. [Journal of Immunology], 133:3001 (1984), Brodeur et al., Monoclonal Antibody Production Techniques and Applications, Marcel Dekker, Inc., New York, (1987), pp. 51-63). 【0252】 Furthermore, the presence or absence of monoclonal antibodies against the antigen may be measured in the culture medium for hybridoma cells. Preferably, the binding specificity of monoclonal antibodies produced by hybridoma cells is determined by immunoprecipitation or in vitro binding assays, such as radioimmunoassay (RIA) or enzyme-linked immunosorbent assay (ELISA). Such techniques and assays are well known in the art. The binding affinity of monoclonal antibodies can be determined, for example, by scatchard analysis as described in Munson and Pollard, Anal. Biochem. [Journal of Analytical Biochemistry], 107:220 (1980). It should be noted that in the therapeutic application of monoclonal antibodies, the identification of antibodies with high specificity and high binding affinity to the target antigen is important. 【0253】 After identifying the required hybridoma cells, clones can be subcloned using limiting dilution procedures and propagated using standard methods (see Goding, Monoclonal Antibodies: Principles and Practice, Academic Press, (1986), pp. 59-103). Suitable media for this purpose include, for example, Dulbecco's Modified Eagle's Medium and RPMI-1640 medium. Alternatively, hybridoma cells can be grown as ascites in mammals. 【0254】 Monoclonal antibodies secreted by subclones may be isolated or purified from culture media or ascites fluid by common immunoglobulin purification procedures (e.g., protein A-agarose chromatography, hydroxyl apatite chromatography, gel electrophoresis, dialysis, or affinity chromatography). 【0255】 Monoclonal antibodies may be prepared by recombinant DNA methods, for example, those described in U.S. Patent No. 4,816,567. Using common procedures (e.g., by using oligonucleotide probes that can specifically bind to the heavy and light chain genes encoding the mouse antibody), the DNA encoding the monoclonal antibody of the present invention can be readily isolated and sequenced. Hybridoma cells of the present invention are used as a preferred source of such DNA. Once isolated, the DNA can be placed into an expression vector, and these vectors can be transfected into host cells that do not additionally produce immunoglobulins (e.g., monkey COS cells, Chinese hamster ovary (CHO) cells, or myeloma cells) to obtain the synthesis of the monoclonal antibody in the recombinant host cell. Furthermore, DNA may be modified, for example, by substituting homologous mouse sequences with coding sequences for human heavy and light chain constant domains (see U.S. Patent No. 4,816,567, Morrison, Nature 368,812-13 (1994)), or by covalently linking all or part of the coding sequences of a non-immunoglobulin polypeptide to an immunoglobulin coding sequence. Such non-immunoglobulin polypeptides can be used to produce chimeric bivalent antibodies by substituting a constant domain of the antibody of the present invention or by substituting a variable domain of one antigen-binding site of the antibody of the present invention. 【0256】 Fully human antibodies are antibody molecules in which the entire sequence of both the light and heavy chains (including the CDR) is derived from human genes. Such antibodies are referred to herein as "humanized antibodies," "human antibodies," or "fully human antibodies." Human monoclonal antibodies may be prepared by trioma technology, human B-cell hybridoma technology (Kozbor, et al., 1983 Immunol Today 4:72), and EBV hybridoma technology that produces human monoclonal antibodies (Cole, et al., 1985: MONOCLONAL ANTIBODIES AND CANCER THERAPY, Alan R. Liss, Inc., pp. 77-96). Human monoclonal antibodies may be used, and the cells may also be produced using human hybridomas (Cote, et al., 1983. Proc Natl Acad Sci USA [Proceedings of the National Academy of Sciences] 80:2026-2030) or by transforming human B cells with EB virus in vitro (Cole, et al., 1985: MONOCLONAL ANTIBODIES AND CANCER THERAPY [Monoclonal Antibodies and Cancer Therapy], Alan R. Liss, Inc., pp. 77-96). 【0257】 Humanized antibodies may be produced in transgenic plants as a low-cost alternative to existing mammalian systems. For example, the transgenic plants may be tobacco plants, namely tobacco benthamiana and Nicotiana tabacum. The antibodies are purified from the leaves of the plants. Stable transformation of the plants may be achieved by Agrobacterium tumefaciens or particle bombardment. For example, a nucleic acid expression vector containing at least heavy and light chain sequences is expressed in a bacterial culture (i.e., Agrobacterium tumefaciens BLA4404) by transformation. Infiltration into the plants may be achieved by injection. Soluble leaf extracts may be prepared by grinding leaf tissue in a mortar and centrifugation. The isolation and purification of antibodies can be easily carried out by many methods known to those skilled in the art. Other methods for producing antibodies in plants are described, for example, in Fischer et al., Vaccine, 2003, 21:820-5, and in Ko et al., Current Topics in Microbiology and Immunology, Vol. 332, 2009, pp. 55-78. Therefore, the present invention further provides any cell or plant comprising a vector that encodes or produces the antibody of the present invention. 【0258】 Furthermore, it is possible to produce (human) antibodies of interest in fungi. For example, the fungus may be a thermophilic filamentous fungus (e.g., thermophilic filamentous fungal strain C1, Visser et al. (2011) Industrial Biotechnology 7(3):214-223). Other examples include the genera Aspergillus (e.g., Aspergillus niger (Huynh et al. (2020) Fungal Biology and Biotechnology 7:7), Aspergillus niger (Ward et al. (2004) Environ. Microbiol 70:2567-76), or Aspergillus luteus (Joosten et al. (2003) Microb. Cell Fact 2:1)) and Trichoderma (e.g., Trichoderma lysey (Nyyssonen et al. (1993) Biotechnology 11:591-595)). In other cases, the fungus may be a yeast, such as budding yeast, Candida boidini, Hanzenula polymorpha, Pichia metanolica, Pichia yeast, Yarowia liporitica, Kluiveromyces lactis, or methanol-inducible yeast (Joosten et al. (2003), Suzuki et al. (2017) J Biosci Bioeng [Journal of Biological Sciences and Biotechnology]. 124:156-63). 【0259】 Human antibodies may also be produced using other techniques (including phage display libraries). (See Hoogenboom and Winter, J.Mol.Biol.[Molecular Biology Journal], 227:381 (1991); Marks et al., J.Mol.Biol.[Molecular Biology Journal], 222:581 (1991)). Similarly, human antibodies may be prepared by introducing human immunoglobulin loci into transgenic animals, such as mice in which the endogenous immunoglobulin gene has been partially or completely inactivated. After induction, the production of human antibodies is observed, which is remarkably similar to the phenomenon observed in humans in all aspects, including gene rearrangement, assembly, and antibody repertoire. For example, WO2006 / 008548, WO2007 / 096779, WO2010 / 109165, WO2010 / 070263, WO2014 / 141189, and WO2014 / 141192 describe this method. 【0260】 A method for producing an antibody of interest (e.g., a human antibody) is disclosed in U.S. Patent No. 5,916,771. The method involves introducing an expression vector containing a nucleotide sequence encoding a heavy chain into one mammalian host cell in culture, introducing an expression vector containing a nucleotide sequence encoding a light chain into another mammalian host cell, and fusing these two cells to form a hybrid cell. The hybrid cell expresses an antibody containing both a heavy chain and a light chain. 【0261】 Further improvements to this procedure are disclosed in PCT Publication WO99 / 53049, which describes a method for identifying clinically relevant epitopes on immunogens and a related method for selecting antibodies that bind immunospecifically to the relevant epitopes with high affinity. 【0262】 The antibody may be expressed by a vector containing a DNA fragment encoding the single-strand antibody described above. 【0263】 These may include vectors, liposomes, naked DNA, adjuvant-assisted DNA, gene guns, catheters, etc. Vectors include chemical conjugates containing a target portion (e.g., a ligand for a cell surface receptor) and a nucleic acid-binding portion (e.g., polylysine), such as those described in WO93 / 64701; viral vectors (e.g., DNA or RNA viral vectors); fusion proteins containing a target portion (e.g., a cell-specific antibody) and a nucleic acid-binding portion (e.g., protamine), such as those described in PCT / US95 / 02140 (WO95 / 22618), such as plasmids and phages. Vectors may be chromosomal, non-chromosomal, or synthetic vectors. 【0264】 Preferred vectors include viral vectors, fusion proteins, and chemical conjugates. Retroviral vectors include Moloney mouse leukemia virus. DNA viral vectors are preferred. These vectors include pox vectors, such as orthopox or avipox vectors, herpesvirus vectors, such as herpes simplex virus type 1 (HSV) vectors (see Geller, AI et al., J. Neurochem, 64:487 (1995), Lim, F., et al., DNA Cloning: Mammalian Systems, D. Glover, Ed. (Oxford University Press, Oxford, UK) (1995), Geller, AI et al., Proc Natl. Acad. Sci.: USA [Proceedings of the National Academy of Sciences] 90:7603 (1993), Geller, AI et al., Proc Natl. Acad. Sci USA [Proceedings of the National Academy of Sciences] 87:1149 (1990)), and adenovirus vectors (LeGal This includes LaSalle et al., Science, 259:988 (1993), Davidson et al., Nat. Genet 3:219 (1993), and Yang et al., J. Virol 69:2004 (1995), as well as adeno-associated virus vectors (see Kaplitt, MG et al., Nat. Genet 8:148 (1994)). 【0265】 Poxvirus vectors introduce genes into the cytoplasm. Avipoxvirus vectors induce only transient expression of nucleic acids. Adenovirus vectors, adeno-associated virus vectors, and herpes simplex virus (HSV) vectors are preferably used to introduce nucleic acids into nerve cells. Adenovirus vectors induce a shorter expression period (about 2 months) than adeno-associated virus (about 4 months), but adeno-associated virus has a shorter expression period than HSV vectors. The specific vector selected depends on the target cells and the disease being treated. It may be introduced by standard techniques, such as infection, transfection, transduction, or transformation. Examples of gene transfer modes include, for example, naked DNA, CaPO4 precipitation, DEAE dextran, electroporation, protoplast fusion, lipofection, intracellular microinjection, and viral vectors. 【0266】 Vectors can be used to target virtually any desired target cell. For example, stereotactic injection can be used to deliver vectors (e.g., adenovirus, HSV) to the required location. Particles can also be delivered by intraventricular (icv) injection using a micropump infusion system (e.g., the SynchroMed infusion system). Macroscopic flow (known as convection)-based methods have also been demonstrated to be effective in delivering macromolecules to broad areas of the brain and can be used for vector delivery to target cells. (See Bobo et al., Proc. Natl. Acad. Sci. USA [Proceedings of the National Academy of Sciences] 91:2076-2080 (1994), Morrison et al., Am. J. Physiol [Journal of Physiology] 266:292-305 (1994)). Other available methods include catheterization, intravenous injection, parenteral injection, intraperitoneal and subcutaneous injection, and oral administration or other known routes of administration. Treatment method 【0267】 The antibodies described herein may be administered to mitigate or inhibit the progression of cancer associated with CEACAM5 expression. In these applications, a therapeutically effective dose of the composition is administered to a subject, the amount being sufficient to inhibit the proliferation, replication, or metastasis of cancer cells or to inhibit the signs or symptoms of cancer. Suitable subjects may include subjects diagnosed with cancers expressing CEACAM5, such as small intestine cancer, colorectal cancer, gastric cancer, lung cancer, cervical cancer, pancreatic cancer, esophageal cancer, ovarian cancer, thyroid cancer, bladder cancer, endometrial cancer, breast cancer, liver cancer, prostate cancer, and skin cancer. 【0268】 This specification provides a method for treating cancers associated with CEACAM5 expression in a subject by administering a therapeutically effective dose of the antibody described herein to the subject. In some examples, the cancers are small intestine cancer, colorectal cancer, gastric cancer, lung cancer, cervical cancer, pancreatic cancer, esophageal cancer, ovarian cancer, thyroid cancer, bladder cancer, endometrial cancer, breast cancer, liver cancer, prostate cancer, and skin cancer. 【0269】 The administration of antibodies disclosed herein may be further combined with the administration of other anticancer agents or therapeutic procedures (e.g., surgical resection of tumors). Any suitable anticancer agent may be administered in combination with the antibodies disclosed herein. Exemplary anticancer agents include, but are not limited to, chemotherapeutic agents, such as mitotic inhibitors, alkylating agents, antimetabolites, insert antibiotics, growth factor inhibitors, cell cycle inhibitors, enzymes, topoisomerase inhibitors, antisurvivators, bioresponse modifiers, antihormone agents (e.g., antiandrogens), and angiogenesis inhibitors. Other anticancer therapies include radiotherapy and other antibodies that specifically target cancer cells. 【0270】 Another common treatment for some types of cancer is surgical treatment, such as surgical removal of metastatic tumors. Another example of treatment is radiotherapy, which involves administering radioactive material or energy (e.g., external beam radiation therapy) to the tumor site before surgical removal to help eradicate or shrink the tumor. Diagnosis and detection methods 【0271】 This specification provides a method for detecting the CEACAM5 protein in vitro or in vivo. In some cases, CEACAM5 expression is detected in a biological sample. The sample may include, but is not limited to, any sample including, blood samples, biopsy tissues, autopsy and pathological specimens. The biological sample further includes tissue sections, e.g., frozen sections for histological purposes. The biological sample further includes body fluids, e.g., blood, serum, plasma, sputum, spinal fluid, or urine. The biological sample is obtained from a mammal, e.g., a human or a non-human primate. In preferred embodiments, the method is used for non-diagnostic purposes. 【0272】 This specification provides a method for determining whether a subject has cancer associated with CEACAM5 expression by contacting a sample of the subject with an anti-CEACAM5 monoclonal antibody disclosed herein and detecting the binding of the antibody to the sample. Increased binding of the antibody to the sample compared to binding of the antibody to a control sample identifies the subject as having cancer. 【0273】 In another embodiment, a method is provided to confirm the diagnosis of CEACAM5 expression-related cancer in a subject by contacting a sample of a subject diagnosed with CEACAM5 expression-related cancer with an anti-CEACAM5 monoclonal antibody disclosed herein and detecting the binding of the antibody to the sample. Compared to the binding of the antibody to a control sample, the binding of the antibody to the sample was increased, thereby confirming the diagnosis of cancer in the subject. 【0274】 In some examples of the disclosed methods, the monoclonal antibody is directly labeled. 【0275】 In other examples, the method further includes contacting a second antibody of a specificity-binding monoclonal antibody with a sample and detecting the binding of the second antibody. The binding of the second antibody to the sample is increased compared to the binding of the second antibody to the control sample, thereby detecting cancer associated with CEACAM5 expression in the subject or confirming the diagnosis of cancer associated with CEACAM5 expression in the subject. 【0276】 In some cases, cancer is small intestine cancer, colorectal cancer, stomach cancer, lung cancer, cervical cancer, pancreatic cancer, esophageal cancer, ovarian cancer, thyroid cancer, bladder cancer, endometrial cancer, breast cancer, liver cancer, prostate cancer, and skin cancer. 【0277】 In some cases, the control sample is a sample from a subject who does not have cancer. In certain cases, the sample is a blood or tissue sample. 【0278】 In some embodiments of the diagnostic and detection methods, the anti-CEACAM5 antibody is directly labeled with a detectable label. In another embodiment, the anti-CEACAM5 antibody (first antibody) is unlabeled, and the second antibody or other molecule capable of binding to the first antibody is labeled. As is well known to those skilled in the art, a specific type and class of second antibody capable of specifically binding to the first antibody is selected. For example, if the first antibody is human IgG, the second antibody may be anti-human IgG. Other molecules capable of binding to the antibody include, but are not limited to, protein A and protein G, both of which are commercially available. 【0279】 Suitable labels for antibodies or secondary antibodies include a variety of enzymes, prosthetic groups, fluorescent materials, luminescent materials, magnetic reagents, and radioactive materials. Non-limiting examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, β-galactosidase, or acetylcholinesterase. Non-limiting examples of suitable prosthetic group complexes include streptavidin / biotin and avidin / biotin. Non-limiting examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinamide fluorescein, dansilchloride, or phycoerythrin. Non-limiting exemplary luminescent materials include luminol, non-limiting exemplary magnetic reagents include gadolinium, and non-limiting exemplary radioactive labels include 125 I, 131 I, 35 S or 3 Includes H. 【0280】 In one alternative embodiment, CEACAM5 may be measured in a biological sample by a competitive immunoassay using a CEACAM5 protein standard labeled with a detectable substance and an unlabeled anti-CEACAM5 antibody. In this assay, the biological sample, the labeled CEACAM5 protein standard, and the anti-CEACAM5 antibody are combined, and the amount of the labeled CEACAM5 protein standard bound to the unlabeled antibody is measured. The amount of CEACAM5 in the biological sample is inversely proportional to the amount of the labeled CEACAM5 protein standard bound to the anti-CEACAM5 antibody. 【0281】 The immunoassays and methods disclosed herein are applicable to multiple purposes. In one example, an anti-CEACAM5 antibody may be used to detect the production of CEACAM5 in cells in cell culture. In another example, the antibody may be used to detect the amount of CEACAM5 in a biological sample, such as a tissue sample, or a blood or serum sample. In some examples, CEACAM5 is cell surface CEACAM5. In other examples, the CEACAM5 protein is soluble (e.g., in cell culture supernatant or body fluid samples, such as blood or serum samples). 【0282】 In one embodiment, a kit is provided for detecting CEACAM5 in a biological sample (e.g., a blood sample or a tissue sample). For example, a biopsy can be performed to confirm a cancer diagnosis in a subject, and a tissue sample can be obtained for histological examination. The kit for detecting polypeptides typically includes a monoclonal anti-CEACAM5 antibody, such as any monoclonal antibody disclosed herein. In further embodiments, the antibody is labeled (e.g., by fluorescent labeling, radiolabeling, or enzymatic labeling). 【0283】 In one embodiment, the kit includes explanatory materials that disclose how to use the anti-CEACAM5 antibody. The explanatory materials can be written in electronic format (e.g., on a computer floppy disk or optical disk) or in visual format (e.g., a video file). The kit may further include other components to facilitate the design of a particular application that the kit aims to realize. For example, the kit may further include means for detecting the label (e.g., an enzyme substrate for enzyme labeling, a filter set for fluorescent label detection, a suitable second label, e.g., a second antibody). The kit may also typically further include buffers and other reagents for practicing a particular method. Such kits and suitable contents are well known to those skilled in the art. 【0284】 In one embodiment, the diagnostic kit includes an immunoassay. While the details of the immunoassay may vary depending on the specific form employed, a method for detecting CEACAM5 in a biological sample typically involves contacting the biological sample with an anti-CEACAM5 antibody. This allows the antibody to specifically bind under immunoreaction conditions to form an immune complex, and the presence of the immune complex (bound antibody) is detected directly or indirectly. 【0285】 The antibodies disclosed herein may also be used in immunoassays, for example, radioimmunoassays (RIA), ELISA, or immunohistochemical assays. The antibodies may further be used in fluorescence-activated cell sorting (FACS). FACS employs multiple color channels, low-angle and wide-angle scattered light detection channels and impedance channels, and other more complex detection levels to separate or classify cells (see U.S. Patent No. 5,061,620). Any monoclonal antibody that binds to CEACAM5 as disclosed herein is usable in these assays. Therefore, the antibodies may be used in common immunoassays, including but not limited to ELISA, RIA, FACS, tissue immunohistochemistry, Western blotting, or immunoprecipitation. example 【0286】 The present invention will be further illustrated by the following examples, which are not intended to limit the invention. In the following examples, experimental procedures where specific conditions are not specified were carried out in accordance with general procedures and conditions or instructions for use. Example 1. Immunotherapy strategies for anti-CEACAM5 antibodies and single B-cell cloning screening. immunization 【0287】 Recombinant human CEACAM5 (Uniprot P06731) Fc-tagged protein, human CEACAM5 A3B3 His-tagged fragment, or CHO-K1-huCEACAM5 overexpressing cell lines were used as immunogens to produce anti-CEACAM5 antibodies (WO2010 / 070263A1) in Harbour H2L2 mice. The immunization schedule is listed in Table 4. 【0288】 [Table 4] 【0289】 For protein immunization, each mouse received an initial booster immunization with 50 μg of protein along with an adjuvant (Sigma, S6322) via sc and ip, followed by a subsequent booster immunization with 25 μg. This immunization was performed a total of five times, every two weeks. For cell immunization, each mouse received 1 x 10⁶ doses in PBS. 7 The cells were administered a total of five times, every three weeks. Final immunization was performed using an immunogen diluted in PBS via ip. Serum titers were tested using recombinant human CEACAM5 His tag, recombinant cyno CEACAM5 (XP_005589491.1) His tag, and recombinant human CEACAM1 (Uniprot P13688) His tag (internal) proteins using ELISA and FACS. Mice exhibiting high serum titers for human CEACAM5 and cyno CEACAM5 and low titers for human CEACAM1 were selected for subsequent single B cell cloning screening. Single B-cell cloning screening Single B-cell screening based on the Beacon® Optofluidic (single-cell optofidics) system. 【0290】 The Beacon® Optofluidic (single-cell optofidics) system uses photoelectrolocation (OEP™) technology to move single cells. Beacon optofluidic systems are automated bioinstruments and instruments that can simultaneously perform biofunctional testing, experimental analysis, positive clone selection, and other operations under cell culture conditions. The Beacon platform has been able to perform these tasks in a large-scale, parallel, and automated manner on thousands of cells. 【0291】 In this application, a plasma cell discovery workflow was used. In each experiment, up to 14k single plasma cells were screened to select antigen-specific antibodies secreted by positive plasma cells. The plasma cells secreting specific antibodies were then exported to a 96-well plate containing cell lysates and used for subsequent single B cell sequencing to identify the heavy and light chains of antibodies produced by single B cells (monoclonals). The overall screening strategy and progress are shown in Figure 1. Single B-cell sequencing 【0292】 Antibody heavy and light chain sequences were recovered from single plasma cells using a single B-cell sequencing method. Single B-cell sequencing has already become a powerful tool for obtaining antibody sequences. The general procedure includes purification of RNA from single plasma cell lysates, reverse transcription and synthesis of cDNA, amplification and purification of cDNA, amplification of heavy and light chains, cloning and transfecting, and Sanger sequencing. Uniqueness and cluster analysis were performed on the obtained sequences, and pairs of heavy and light chain DNA sequences were synthesized. Example 2. Production and purification of anti-CEACAM5 antibody 【0293】 Recombinant plasmids encoding target antibodies were transiently co-transfected into HEK293-6E or 293-F cell cultures using PEI (Polyscience, 24885). After transfection, cells were incubated at 37°C in 5% CO2 and shaken at 120 rpm. Cell culture supernatant collected on days 6-7 was used for purification. Monoclonal antibodies were purified using protein A magnetic beads (AmMag protein A magnetic beads, Genscript, L00695). 【0294】 Antibody purity was detected by SEC-HPLC (Agilent 1260 Infinity II HPLC, Welch Xtimate SEC-300 column, 1X PBS pH 7.4 mobile phase) and SDS-PAGE (SurePAGE, Bis-Tris, 10x8, 4-12%, 12 wells, Genscript, M00653). 34 recombinant antibodies (PR304296, PR304303, PR304717, PR304718, PR304569, PR304688, PR304689, PR304692, PR304693, PR304697, PR304840, PR304870, PR304873, PR307076, PR307077, PR307078, PR307079, PR307080) were analyzed. The antibodies (referred to as PR307081, PR307082, PR307083, PR307084, PR307085, PR307088, PR307089, PR307091, PR307094, PR307097, PR307098, PR307099, PR307100, PR307101, PR307102, and PR307103) were successfully expressed and purified and used for characterization. The amino acid sequences of the 34 antibodies are listed in Table 1. 【0295】 Simultaneously, the anti-CEACAM5 antibody tusamitamab (SAR408377) was also produced according to the above procedure, and its sequence information is from SAR408377, Proposed INN List 123, Vol. 34, No. 2, 2020. Similarly, the anti-CEACAM6 antibody tinuririmab (BAY-1834942) was also produced according to the above procedure, and its sequence information is from Proposed INN List 83, Vol. 34, No. 1, 2020. These antibodies were used as controls, and were assigned the codes PR003561 (against tusamitamab) and PR303563 (against tinuririmab), respectively. The amino acid sequences of these antibodies are listed in Table 2. Example 3. Characterization of anti-CEACAM5 antibody binding properties. Binding of human and cynomolgus monkey CEACAM5 and human CEACAM 6, 1, 3, and 8 proteins. 【0296】 ELISA was used to detect the binding of recombinant anti-CEACAM5 monoclonal antibodies to human and cynomolgus monkey CEACAM5, human CEACAM6 (Uniprot P40199), human CEACAM 1, 3 (NP_001806.2, Beijing Yiqiao Shenzhou Technology Co., Ltd. (Sino Biological) 11933-H08H), and 8 (NP_001807.2, Beijing Baipusais Biotechnology Co., Ltd. (Acro Bio) CE8-H5224). The anti-CEACAM5 antibodies were sequentially diluted in staining buffer (PBS containing 2% FBS). The anti-CEACAM5 antibody PR003561 (tusamitamab), anti-CEACAM6 antibody PR303563 (tinuririmab), anti-CEACAM1 antibody CEACAM1PC (Beijing Yiqiao Shenzhou Technology Co., Ltd. (SinoBiological), Cat:10822-MM02, mouse monoclonal), anti-CEACAM3 antibody CEACAM3PC (Beijing Yiqiao Shenzhou Technology Co., Ltd. (SinoBiological), Cat:11933-MM03, mouse monoclonal), and anti-CEACAM8 antibody CEACAM8PC (Beijing Yiqiao Shenzhou Technology Co., Ltd. (SinoBiological), Cat:11729-MM04, mouse monoclonal) were used as controls. ELISA was used to test the binding of the supernatant containing the antibodies or the purified antibodies to the antigens. In short, the antigen was coated onto a 96-well high-binding plate at 4°C and left overnight. The plate was washed three times with PBST, incubated with blocking buffer (2% bovine serum albumin) at 37°C for 1 hour, washed three times with PBST, and incubated at 37°C for 1 hour with the supernatant containing the antibody or purified antibody at the desired dilution or concentration. A second antibody, anti-human Fc-HRP (Jackson Laboratory, 109-035-097), was used to detect the target antibody. The HRP signal was detected using TMB and stop solution. The HRP signal was read using a SPECTRAMAX plate reader. EC50 was determined based on the ELISA test results (see Table 5 and Figures 2-7). 【0297】 As shown in Table 5 and Figures 2-7, the anti-CEACAM5 antibodies PR304296, PR304303, PR304717, PR304688, PR304689, PR304693, PR304697, PR304840, PR304870, PR304873, PR307076, PR307077, PR307078, PR307079, PR307083, PR307084, PR307085, and PR307097 showed good binding activity to human and cyno-CEACAM5 proteins, but did not bind to other CEA paralogs, such as CEACAM1, CEACAM3, CEACAM6, and CEACAM8. 【0298】 In addition to CEACAM1, CEACAM3, CEACAM6, and CEACAM8, the anti-CEACAM5 antibodies PR304569, PR307080, PR307081, PR307082, PR307088, and PR307103 also did not show binding to cyno-CEACAM5 and bound only to human CEACAM5. 【0299】 Compared to binding to other CEA paralogs, such as huCEACAM6, huCEACAM1, huCEACAM3, or huCEACAM8, the anti-CEACAM5 antibodies PR304718, PR304692, PR307089, PR307094, PR307098, PR307099, PR307100, PR307101, and PR307102 showed relatively better binding activity to the human CEACAM5 protein. 【0300】 [Table 5] Conjugation to human or cynomolgus monkey CEACAM5 stable cell lines 【0301】 The binding of recombinant anti-CEACAM5 antibody to human or cynomolgus monkey CEACAM5 stable cells was detected by flow cytometry. The stable cell lines included 293T cell lines already transfected and overexpressing human CEACAM5 (293T-huCEACAM5 cells) or CEACAM6 (293T-huCEACAM6 cells) on their surface, and CHO-K1 cell lines already transfected and overexpressing cynomolgus monkey CEACAM5 on their surface (CHOK1-cyno CEACAM5 cells). Anti-CEACAM5 antibody was incubated with the stable cell lines. The anti-CEACAM5 antibody was sequentially diluted in staining buffer (PBS containing 2% FBS). 50 μL of diluted antibody solution was then subjected to 1-2 × 10⁻⁶ dilutions. 5 The cells were added to a 50 μL cell suspension containing individual cells and incubated at 4°C for 1 hour. The cells were washed twice with staining buffer, and 100 μL / well of a 1:1000 dilution of fluorescently labeled anti-human IgG antibody (Alexa Fluor® 488 AffiniPure goat anti-human IgG (H+L), Jackson Cat 109-545-088) was added. After incubation at 4°C for 1 hour, the cells were washed twice and run under flow cytometry. PR303561 and unrelated IgG isotype controls (Crownbio, hIgG1) were used as positive and negative controls, respectively. The results are shown in Figures 8-9 and Table 6 below. 【0302】 As shown in Figures 8-9 and Table 6, the anti-CEACAM5 antibodies PR304296, PR304303, PR304718, PR304569, PR304689, PR304693, PR304873, PR307076, PR307077, PR307079, PR307085, PR307094, PR307097, PR307099, and PR307100 exhibited very good binding activity to human and cynomolgus monkey CEACAM5 on the cell membrane. 【0303】 [Table 6] Conjugation of endogenous cell line LS174T and BxPC3 expressing CEACAM5 【0304】 Following a similar procedure as described above, only the stable cell lines were replaced with LS 174T (ATCC CL-188) and BxPC3 (ATCC CRL-1687) cell lines, which simultaneously expressed different levels of membrane-bound endogenous CEACAM5. The binding results are shown in Figures 10-11 and Table 6 above. 【0305】 Figures 10-11 and Table 6 show the good binding ability of antibodies to membrane-bound endogenous human CEACAM5 on LS 174T and BxPC3 cell lines. Most antibodies showed higher saturated binding ability than the positive control PR303561, but antibodies PR304296 and PR304718 showed better EC50 in one or two cell lines. Example 4. Measurement of the binding affinity between anti-CEACAM5 antibody and soluble CEACAM5 using Octet. 【0306】 The binding kinetics of recombinant anti-CEACAM5 antibody to human CEACAM5 and cyno-CEACAM5 were analyzed using Octet. In Octet analysis, recombinant human CEACAM5 His-tagged protein (#Uniprot P06731) was sequentially diluted with 1× dynamic buffer (Fortebio). The anti-CEACAM5 antibody was diluted to 5 μg / mL. The diluted antibody, antigen, and regeneration buffer (10 mM glycine, pH 1.75) were then added to a 96-well plate (Greiner). The rate constants of association and dissociation were measured using an AHC sensor (Fortebio). After each binding experiment, the sensor surface was regenerated with regeneration buffer. Traces were processed using ForteBio data analysis software (version 8.0, Pall ForteBio, California, USA). 【0307】 The KD values ​​of the anti-CEACAM5 antibody are summarized in Table 7. 【0308】 [Table 7] Example 5. Characterization of the binding domain of a CEACAM5 monoclonal antibody. 【0309】 The CEACAM5 protein consists of seven immunoglobulin-like domains, including one IgV-like N-terminal domain and six IgC-like domains, namely A1, B2, A2, B2, A3, and B3. The antibody binding domain on the CEACAM5 protein was determined. Three CEACAM5 cleavage fragments containing IgV-B1, A2B2, and A3B3 were synthesized. The ELISA binding test followed the same procedure as shown in Example 3. As shown in Table 8, the antibodies showed different binding domains, with more than half binding to A3B3, some to A2B2 and A3B3, and a few to A2B2 only. 【0310】 [Table 8] Example 6. Epitope binning of anti-CEACAM5 antibody using Octet. 【0311】 In epitope binning analysis using Octet, antibodies were tested in pairs with other antibodies to determine whether they blocked each other's binding to the antigen epitope. The first and second antibodies were diluted to the same concentration, which was sufficient to saturate the binding of the immobilized antigen. Recombinant CEACAM5-his protein was biotinylated and used as the antigen, immobilized on an SA sensor. The first antibody associated with the antigen, and then with the second antibody. Data were analyzed using ForteBio data analysis software (version 8.0, Pall ForteBio). The ratio of RU values ​​between the antibody with the same second antibody and the antibody with the same first antibody was calculated as the co-binding rate between the antibody and the other antibody. Generally, ratios >50% and close to 100% indicate that the two antibodies bind to different epitope bins, while a ratio <20% represents overlapping bins for the two evaluated antibodies. The co-binding rates are shown in Table 9. 【0312】 As shown in Table 9, the results indicated that the epitopes in these anti-CEACAM5 antibodies were highly diverse, divided into a total of six bins, all of which were distinct from the positive control PR303561. 【0313】 [Table 9] Example 7. Internalization of antibodies on 293T-huCEACAM5 and LS 174T using pHAb amine-reactive dyes. 【0314】 The pHAb amine-reactive dye (Promega, Cat# G9841) was used to measure the internalization of antigen-based anti-CEACAM5 antibodies on 293T-huCEACAM5 and LS 174T. 【0315】 pHAb dyes are pH-sensing dyes that exhibit very low fluorescence at pH > 7, and their fluorescence increases significantly as the pH of the solution becomes more acidic. In such cases, when antibodies labeled with pHAb dye bind to the extracellular environment under neutral pH, no fluorescence is detected or the fluorescence is very low. After internalization, the fluorescence becomes stronger in the low pH environment of endosomes and lysosomes. 【0316】 Antibodies were labeled with a pHAb dye, and the DAR was calculated according to the kit instructions. The labeled antibodies were incubated with 293T-huCEACAM5 and LS 174T at 4°C (theoretically, this temperature is used as a background control because it exhibits very low internalization activity) or 37°C for 6 hours. Fluorescence with a maximum excitation value (Ex) at 532 nm and a maximum emission value (Em) at 560 nm was detected. The final normalized result was obtained by subtracting the background at 4°C from the fluorescence intensity at 37°C, and then dividing by the DAR of the antibody with the pHAb dye. A higher value indicated higher internalization activity. 【0317】 The internalization results are shown in Figure 12. 【0318】 As shown in Figure 12, the majority of antibodies showed internalization equivalent to the reference marker PR303561 on 293T cell lines and LS174T cells overexpressing CEACAM5, while mAbs PR307084, PR307085, and PR307097 showed better internalization than the reference marker on 293T cell lines and LS174T cells overexpressing CEACAM5. Good internalization is useful because most ADCs require internalization to release toxins, thus improving the efficacy of antibodies used for ADCs, and it may also be useful for antibody drugs as it can help reduce the number of CEACAM5 on the cell membrane. Example 8. In vitro cytotoxicity of ADCs conjugated with anti-CEACAM5 antibody-MMAE. 【0319】 In vitro cytotoxicity studies were performed on LS 174T and BxPC3 cells. Anti-CEACAM5 antibody was conjugated with MC-Val-Cit-PABC-MMAE to form ADCs with a DAR of approximately 4. MC-Val-Cit-PABC-MMAE is commercially available (MedChemExpress, HY-15575), and conjugation was performed as follows: The sample buffer containing the antibody was adjusted to the required pH by dialyzing overnight at 4°C and adjusted to a concentration of 5 mg / ml. A relative equivalent of TCEP (compared to protein) was added to the sample buffer, shaken, and incubated at room temperature for 3 hours. A relative equivalent of MC-Val-Cit-PABC-MMAE (compared to protein), dissolved in DMSO, was directly added to the reaction sample and incubated at room temperature for 2-6 hours. The reaction was then quenched by adding 10 equivalents of cysteine ​​(compared to protein) to the reaction sample. Excess low molecular weight cells were removed by dialysis to obtain ADCs containing anti-CEACAM5 antibody conjugated with MC-Val-Cit-PABC-MMAE. For cytotoxicity experiments, cells were incubated with sequentially diluted ADCs for 6 days. Viability was measured using the CellTiter-Glo kit (Promega, G7572). Data were analyzed in GraphPad Prism to obtain IC50 values ​​for different ADCs. 【0320】 As shown in the results in Table 10, ADCs based on PR304296 and PR304689 showed better or equivalent in vitro cytotoxicity than ADCs based on PR303561. 【0321】 [Table 10]

Claims

[Claim 1] An antibody or antigen-binding fragment thereof that binds to CEACAM5, wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), and wherein, (1) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 7, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:

8. (2) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 55, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:

56. (3) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 16, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:

17. (4) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 24, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:

25. (5) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 30, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:

31. (6) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 40, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:

41. (7) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 49, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:

50. (8) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 59, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:

60. (9) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 65, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:

66. (10) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 72, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:

73. (11) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 82, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:

83. (12) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 91, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:

92. (13) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 96, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:

97. (14) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 102, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:

103. (15) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 108, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:

109. (16) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 114, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:

115. (17) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 120, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:

121. (18) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 124, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:

125. (19) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 128, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:

129. (20) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 135, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:

136. (21) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 140, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:

141. (22) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 146, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:

147. (23) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 152, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:

153. (24) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 158, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:

159. (25) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 164, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:

165. (26) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 102, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:

168. (27) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 171, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:

172. (28) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 176, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:

177. (29) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 181, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:

182. (30) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 186, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:

187. (31) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 191, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:

192. (32) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 196, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO:

197. (33) The VH comprises HCDR 1 to 3 of VH having the amino acid sequence shown in SEQ ID NO: 201, and the VL comprises LCDR 1 to 3 of VL having the amino acid sequence shown in SEQ ID NO: 202, or (34) An antibody or antigen-binding fragment thereof that binds to CEACAM5, wherein the VH comprises HCDR 1 to 3 of the VH having the amino acid sequence shown in SEQ ID NO: 102, and the VL comprises LCDR 1 to 3 of the VL having the amino acid sequence shown in SEQ ID NO:

206. [Claim 2] (1) The VH comprises HCDR 1 to 3, each containing the amino acid sequences shown in SEQ ID NO: 1, 2, and 3, and the VL comprises LCDR 1 to 3, each containing the amino acid sequences shown in SEQ ID NO: 4, 5, and 6. (2) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 44, 53 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 54, 38 and 39, respectively. (3) The VH comprises HCDR 1 to 3, each containing the amino acid sequences shown in SEQ ID NO: 11, 12, and 13, and the VL comprises LCDR 1 to 3, each containing the amino acid sequences shown in SEQ ID NO: 4, 14, and 15. (4) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 20, 21 and 22, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 4, 5 and 23, respectively. (5) The VH comprises HCDR 1 to 3, each containing the amino acid sequences shown in SEQ ID NO: 28, 21, and 29, and the VL comprises LCDR 1 to 3, each containing the amino acid sequences shown in SEQ ID NO: 4, 5, and 6. (6) The VH comprises HCDR 1 to 3, each containing the amino acid sequences shown in SEQ ID NO: 34, 35, and 36, and the VL comprises LCDR 1 to 3, each containing the amino acid sequences shown in SEQ ID NO: 37, 38, and 39. (7) The VH comprises HCDR 1 to 3, each containing the amino acid sequences shown in SEQ ID NO: 44, 45, and 46, and the VL comprises LCDR 1 to 3, each containing the amino acid sequences shown in SEQ ID NO: 47, 38, and 48. (8) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 44, 53 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 63, 64 and 39, respectively. (9) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 69, 70, and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 71, 38, and 39, respectively. (10) The VH comprises HCDR 1 to 3, each containing the amino acid sequences shown in SEQ ID NO: 76, 77, and 78, and the VL comprises LCDR 1 to 3, each containing the amino acid sequences shown in SEQ ID NO: 79, 80, and 81. (11) The VH comprises HCDR 1 to 3, each containing the amino acid sequences shown in SEQ ID NO: 86, 87, and 88, and the VL comprises LCDR 1 to 3, each containing the amino acid sequences shown in SEQ ID NO: 89, 80, and 90, (12) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 86, 87, and 95, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 89, 80, and 90, respectively. (13) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 34, 100 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 37, 38 and 101, respectively. (14) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 106, 100, and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 107, 38, and 39, respectively. (15) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 44, 112 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 113, 38 and 39, respectively. (16) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 44, 118 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 119, 38 and 39, respectively. (17) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 106, 118 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 113, 38 and 39, respectively. (18) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 34, 100 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 71, 38 and 39, respectively. (19) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 44, 132 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 133, 38 and 134, respectively. (20) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 69, 100 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 139, 38 and 39, respectively. (21) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 144, 77, and 95, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 89, 80, and 145, respectively. (22) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 150, 77 and 151, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 89, 80 and 90, respectively. (23) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 34, 118 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 156, 38 and 157, respectively. (24) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 69, 100 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 162, 163 and 48, respectively. (25) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 34, 100 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 37, 38 and 39, respectively. (26) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 44, 100 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 162, 38 and 39, respectively. (27) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 175, 77, and 95, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 89, 80, and 145, respectively. (28) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 44, 132 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 37, 38 and 180, respectively. (29) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 69, 100 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 185, 38 and 157, respectively. (30) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 44, 190 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 162, 38 and 48, respectively. (31) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 106, 112 and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 195, 38 and 39, respectively. (32) The VH comprises HCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 34, 112, and 46, respectively, and the VL comprises LCDR 1 to 3 containing the amino acid sequences shown in SEQ ID NO: 200, 64, and 39, respectively, or (33) The antibody or antigen-binding fragment thereof according to claim 1, wherein the VH comprises HCDR 1 to 3 each containing the amino acid sequences shown in SEQ ID NO: 34, 100, and 46, and the VL comprises LCDR 1 to 3 each containing the amino acid sequences shown in SEQ ID NO: 133, 205, and 39. [Claim 3] (1) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 7, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 8, (2) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 55, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

56. (3) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 16, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

17. (4) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 24, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

25. (5) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 30, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

31. (6) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 40, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

41. (7) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 49, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 50, (8) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 59, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 60, (9) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 65, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 66, (10) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 72, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 73, (11) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 82, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 83, (12) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 91, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 92, (13) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 96, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 97, (14) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 102, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 103, (15) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 108, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 109, (16) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 114, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 115, (17) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 120, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

121. (18) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 124, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

125. (19) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 128, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 129, (20) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 135, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 136, (21) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 140, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

141. (22) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 146, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 147, (23) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 152, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 153, (24) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 158, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

159. (25) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 164, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

165. (26) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 102, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 168, (27) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 171, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 172, (28) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 176, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 177, (29) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 181, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 182, (30) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 186, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

187. (31) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 191, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 192, (32) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 196, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 197, (33) The VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 201, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 202, or (34) The antibody or antigen-binding fragment thereof according to claim 1 or 2, wherein the VH comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 102, and the VL comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

206. [Claim 4] The antibody comprises a heavy chain (HC) and a light chain (LC), and here, (1) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 9, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

10. (2) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 57, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

58. (3) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 18, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

19. (4) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 26, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

27. (5) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 32, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

33. (6) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 42, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

43. (7) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 51, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

52. (8) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 61, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

62. (9) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 67, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

68. (10) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 74, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

75. (11) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 84, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

85. (12) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 93, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

94. (13) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 98, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

99. (14) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 104, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

105. (15) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 110, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

111. (16) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 116, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 117, (17) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 122, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 123, (18) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 126, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 127, (19) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 130, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

131. (20) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 137, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

138. (21) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 142, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

143. (22) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 148, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

149. (23) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 154, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

155. (24) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 160, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

161. (25) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 166, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

167. (26) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 169, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 170, (27) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 173, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

174. (28) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 178, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

179. (29) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 183, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

184. (30) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 188, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

189. (31) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 193, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

194. (32) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 198, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

199. (33) The HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 203, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 204, or (34) The antibody or antigen-binding fragment thereof according to any one of claims 1 to 3, wherein the HC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO: 207, and the LC comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with SEQ ID NO:

208. [Claim 5] The antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, wherein the antibody is a mouse antibody, a chimeric antibody, a humanized antibody, or a human antibody. [Claim 6] The antibody or antigen-binding fragment thereof according to any one of claims 1 to 5, wherein the antibody is an isotype selected from the group consisting of IgG, IgA, IgM, IgE, and IgD. [Claim 7] The antibody or antigen-binding fragment thereof according to any one of claims 1 to 6, wherein the antibody is a subtype selected from the group consisting of IgG1, IgG2, IgG3, and IgG4. [Claim 8] The antigen-binding fragment is Fab, Fab', F(ab') ２ An antibody or antigen-binding fragment thereof according to any one of claims 1 to 7, selected from the group consisting of Fd, Fd', Fv, scFv, ds-scFv, and dAb. [Claim 9] The antibody or antigen-binding fragment thereof according to any one of claims 1 to 8, wherein the antibody is a monoclonal antibody, a bispecific antibody, or a multispecific antibody. [Claim 10] The antibody or antigen-binding fragment thereof according to any one of claims 1 to 9, wherein the antibody is monovalent, bivalent, or polyvalent. [Claim 11] The antibody or antigen-binding fragment according to any one of claims 1 to 10, wherein the antibody or antigen-binding fragment is fluorescently labeled, radioactively labeled, or linked to a drug moiety. [Claim 12] The antibody or antigen-binding fragment according to claim 11, wherein the antibody or antigen-binding fragment is linked to a drug portion, and the drug portion is selected from the group consisting of microtubule inhibitors, antibiotics, DNA synthesis inhibitors, topoisomerase inhibitors, RNA polymerase II inhibitors, and RNA spliceosome inhibitors. [Claim 13] The antibody or antigen-binding fragment thereof according to claim 12, wherein the drug portion is selected from the group consisting of MMAE, MMAF, duocalmycin, DM1, DM4, SN-38, Dxd, calichemycin, doxorubicin, and PBD (benzodiazepine drugs). [Claim 14] The antibody or antigen-binding fragment according to claim 11 or 12, wherein the antibody or antigen-binding fragment is linked to the drug portion via a linker. [Claim 15] The antibody or antigen-binding fragment thereof according to claim 14, wherein the linker comprises a cleavable linker or an incleavable linker. [Claim 16] The antibody or antigen-binding fragment thereof according to claim 15, wherein the cleavable linker is selected from the group consisting of an acid-unstable linker, a hydrophilic linker, a protease-sensitive linker, a photo-unstable linker, a hydrazone linker, a dimethyl linker, and a disulfide-containing linker. [Claim 17] The antibody or antigen-binding fragment thereof according to claim 15, wherein the linker is selected from the group consisting of MC (6-maleimidocaproyl), Val-Cit (valine-citrulline), PABC (p-aminobenzyloxycarbonyl), DMEA (dimethylethylamine), Val-Cit-PABC, MC-Val-Cit-PABC, MC-Val-Cit-PABC-DMEA, GGFG (glycine-glycine-phenylalanine-glycine), MC-GGFG-aminomethyl, AcBut (4-(4-acetylphenoxy)-butyric acid), and AcBut-dimethylhydrazine, and preferably MC-Val-Cit-PABC. [Claim 18] A bispecific antibody comprising an antibody or antigen-binding fragment thereof according to any one of claims 1 to 10, and a second antigen-binding region that specifically binds to a tumor-associated antigen, an immune cell antigen, or an immune checkpoint molecule. [Claim 19] A nucleic acid comprising an antibody or antigen-binding fragment thereof according to any one of claims 1 to 10, or a nucleotide sequence encoding a bispecific antibody according to claim 18. [Claim 20] A vector comprising the nucleic acid described in claim 19. [Claim 21] A host cell comprising the nucleic acid described in claim 19 or the vector described in claim 20. [Claim 22] An antibody-drug conjugate (ADC) comprising an antibody or antigen-binding fragment thereof according to any one of claims 1 to 10, or a bispecific antibody according to claim 18, and a drug moiety conjugated thereto via a linker. [Claim 23] The antibody-drug conjugate according to claim 22, wherein the drug portion is selected from the group consisting of microtubule inhibitors, antibiotics, DNA synthesis inhibitors, topoisomerase inhibitors, RNA polymerase II inhibitors, and RNA spliceosome inhibitors. [Claim 24] The antibody-drug conjugate according to claim 23, wherein the drug portion is selected from the group consisting of MMAE, MMAF, duocalmycin, DM1, DM4, SN-38, Dxd, calichemycin, doxorubicin, and PBD (benzodiazepine drugs). [Claim 25] The antibody-drug conjugate according to any one of claims 22 to 24, wherein the linker comprises a cleavable linker or an incleavable linker. [Claim 26] The antibody-drug conjugate according to claim 25, wherein the cleavable linker is selected from the group consisting of an acid-unstable linker, a hydrophilic linker, a protease-sensitive linker, a photo-unstable linker, a hydrazone linker, a dimethyl linker, and a disulfide-containing linker. [Claim 27] The antibody-drug conjugate according to claim 25, wherein the linker is selected from the group consisting of MC (6-maleimidocaproyl), Val-Cit (valine-citrulline), PABC (p-aminobenzyloxycarbonyl), DMEA (dimethylethylamine), Val-Cit-PABC, MC-Val-Cit-PABC, MC-Val-Cit-PABC-DMEA, GGFG (glycine-glycine-phenylalanine-glycine), MC-GGFG-aminomethyl, AcBut (4-(4-acetylphenoxy)-butyric acid), and AcBut-dimethylhydrazine, and preferably MC-Val-Cit-PABC. [Claim 28] A pharmaceutical composition comprising an antibody or antigen-binding fragment thereof according to any one of claims 1 to 17, or a bispecific antibody according to claim 18, or a nucleic acid according to claim 19, or a vector according to claim 20, or a host cell according to claim 21, or an antibody-drug conjugate according to any one of claims 22 to 27, and optionally a pharmaceutically acceptable carrier or excipient. [Claim 29] The pharmaceutical composition according to claim 28, further comprising a second therapeutic agent, preferably selected from the group consisting of antibodies, chemotherapeutic agents, siRNA, antisense oligonucleotides, polypeptides, and low molecular weight drugs. [Claim 30] A method for treating cancer in a subject, the method comprising administering to the subject an effective amount of an antibody or antigen-binding fragment thereof according to any one of claims 1 to 17, or a bispecific antibody according to claim 18, or a nucleic acid according to claim 19, or a vector according to claim 20, or a host cell according to claim 21, or an antibody-drug conjugate according to any one of claims 22 to 27, or a pharmaceutical composition according to claim 28 or 29. [Claim 31] The method according to claim 30, wherein the cancer is a cancer associated with CEACAM5 expression. [Claim 32] The method according to claim 31, wherein the cancer is selected from the group consisting of small intestine cancer, colorectal cancer, stomach cancer, lung cancer, cervical cancer, pancreatic cancer, esophageal cancer, ovarian cancer, thyroid cancer, bladder cancer, endometrial cancer, breast cancer, liver cancer, prostate cancer, and skin cancer. [Claim 33] The method according to any one of claims 30 to 32, further comprising administering a second therapeutic agent to the subject. [Claim 34] The method according to claim 33, wherein the second therapeutic agent is selected from antibodies, chemotherapeutic agents, siRNA, antisense oligonucleotides, polypeptides, and small molecule drugs. [Claim 35] Uses of an antibody or antigen-binding fragment thereof according to any one of claims 1 to 17, or a bispecific antibody according to claim 18, or a nucleic acid according to claim 19, or a vector according to claim 20, or a host cell according to claim 21, or an antibody-drug conjugate according to any one of claims 22 to 27, or a pharmaceutical composition according to claim 28 or 29, in the manufacture of a drug for treating cancer in a subject. [Claim 36] The use according to claim 35, wherein the cancer is a cancer associated with CEACAM5 expression, and preferably the cancer is selected from the group consisting of small intestine cancer, colorectal cancer, gastric cancer, lung cancer, cervical cancer, pancreatic cancer, esophageal cancer, ovarian cancer, thyroid cancer, bladder cancer, endometrial cancer, breast cancer, liver cancer, prostate cancer, and skin cancer. [Claim 37] The drug further comprises a second therapeutic agent, preferably selected from antibodies, chemotherapeutic agents, siRNA, antisense oligonucleotides, polypeptides, and small molecule drugs, for the use according to claim 35 or 36. [Claim 38] The drug and the second therapeutic agent are administered in combination, preferably the second therapeutic agent is selected from antibodies, chemotherapeutic agents, siRNA, antisense oligonucleotides, polypeptides, and small molecule drugs, as per claim 35 or 36. [Claim 39] Use of an antibody or antigen-binding fragment thereof according to any one of claims 1 to 17, or a bispecific antibody according to claim 18, or a nucleic acid according to claim 19, or a vector according to claim 20, or a host cell according to claim 21, or an antibody-drug conjugate according to any one of claims 22 to 27, or a pharmaceutical composition according to claim 28 or 29, in the treatment of cancer in a subject. [Claim 40] The use of the antibody or antigen-binding fragment thereof, bispecific antibody, nucleic acid, vector, host cell, antibody-drug conjugate, or pharmaceutical composition according to claim 39, wherein the cancer is a cancer associated with CEACAM5 expression, and preferably the cancer is selected from the group consisting of small intestine cancer, colorectal cancer, gastric cancer, lung cancer, cervical cancer, pancreatic cancer, esophageal cancer, ovarian cancer, thyroid cancer, bladder cancer, endometrial cancer, breast cancer, liver cancer, prostate cancer, and skin cancer. [Claim 41] The use of an antibody or antigen-binding fragment thereof, a bispecific antibody, a nucleic acid, a vector, a host cell, an antibody-drug conjugate, or a pharmaceutical composition according to claim 39 or 40, further comprising administering a second therapeutic agent to the subject, preferably the second therapeutic agent being selected from antibodies, chemotherapeutic agents, siRNA, antisense oligonucleotides, polypeptides, and small molecule drugs. [Claim 42] A method for detecting the presence or level of CEACAM5 in a sample, the method being (a) Contacting the sample with the antibody or antigen-binding fragment thereof described in any one of claims 1 to 10, (b) A method comprising determining the presence or level of CEACAM5 in a sample by detecting the binding of the antibody to the sample. [Claim 43] A method for diagnosing cancer associated with CEACAM5 expression in a subject, wherein the method is (a) Obtaining a biological sample from the subject, (b) Contacting the sample with the antibody or antigen-binding fragment thereof described in any one of claims 1 to 10, (c) detecting the binding of the antibody to the sample, A method for identifying a subject as having cancer, wherein the binding of the antibody or its antigen-binding fragment to a sample is increased compared to the binding of the antibody or its antigen-binding fragment to a control sample. [Claim 44] A method for imaging cancer associated with CEACAM5 expression in a subject, wherein the method is (a) Administering to the subject an antibody or antigen-binding fragment thereof according to any one of claims 1 to 10, wherein the antibody is conjugated with a detectable marker, (b) A method comprising detecting the presence of the marker. [Claim 45] (a) The detectable marker is １１１ In, and preferably, the marker is detected by single-photon emission computed tomography, (b) The detectable marker is ８９ The method according to claim 44, wherein the marker is Zr and preferably detected by positron emission tomography.

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