Antigen-binding protein constructs and antibodies and uses thereof

Abstract

Provided herein are antigen binding protein constructs and antibodies, and uses thereof.

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims priority to U.S. Provisional Patent Application No. 63 / 171,705, filed April 7, 2021, the entire contents of which are incorporated herein by reference.

[0002] The present disclosure relates to the field of biotechnology, and more particularly to antigen-binding molecules.

[0003] This application contains a Sequence Listing that has been submitted electronically as an ASCII text file named 45395-0045WO_SL.txt. The size of the ASCII text file, created on April 4, 2022, is 515 kilobytes. The material in the ASCII text file is incorporated herein by reference in its entirety. [Background technology]

[0004] Antibody-drug conjugates have been designed to address a variety of diseases. One particular advantage of this approach is the ability of antibody-drug conjugates to have cytostatic or cytotoxic effects. Despite many years of development, improvements in antibody-drug conjugates are desirable. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] U.S. Patent No. 7,612,181 [Patent Document 2] U.S. Patent No. 8,258,268 [Patent Document 3] U.S. Patent No. 8,586,714 [Patent Document 4] U.S. Patent No. 8,716,450 [Patent Document 5] U.S. Patent No. 8,722,855 [Patent Document 6] U.S. Patent No. 8,735,546

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Non-licensed literature

[0006] [Non-licensed document 1] Wustner,Traffic7(6):699-715,2006 [Non-licensed document 2] Purcell et al(2018) "LRRC15 Is a Novel Mesenchymal Protein and Stromal Target for Antibody-Drug Conjugates" Cancer Res.78(14):4059-4072 [Non-licensed document 3] Cromie et al.,Curr.Top.Med.Chem.15:2543-2557,2016

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[0007] The present invention is based on the concept that antigen binding protein constructs and antibodies can be generated that exhibit improved efficacy (e.g., one or more of increased (e.g., a detectable increase) in toxin release in target mammalian cells, increased (e.g., a detectable increase) in target mammalian cell killing, and increased (e.g., a detectable increase) in endolysosomal delivery).

[0008] Antibodies are provided herein, the antibodies comprising: (a) a heavy chain variable domain and a light chain variable domain selected from the group consisting of: (i) a heavy chain variable domain that is at least 90% identical to SEQ ID NO: 1, comprising a histidine at one or more positions of SEQ ID NO: 1 selected from the group consisting of 33, 34, 50, 52, 57, 59, 100, 102, 103, 107, 108, and 109; and / or one or more of SEQ ID NO: 2 selected from the group consisting of 32, 34, 50, 51, 89, 90, 92, 93, 94, and 96. (ii) a light chain variable domain that is at least 90% identical to SEQ ID NO: 2, comprising a histidine at one or more positions of SEQ ID NO: 84 selected from the group consisting of 27, 29, 32, 50, 54, 58, 99, 100, 102, 104, and 105; and / or one or more of SEQ ID NO: 85 selected from the group consisting of 29, 31, 32, 34, 36, 37, 38, 40, 56, 60, 61, 95, 96, 97, and 100. (iii) a light chain variable domain at least 90% identical to SEQ ID NO: 85, wherein the variable domain comprises a histidine at one or more positions of SEQ ID NO: 178 selected from the group consisting of 33, 52, 56, 57, or 106; and / or a heavy chain variable domain at least 90% identical to SEQ ID NO: 178, wherein the variable domain comprises a histidine at one or more positions of SEQ ID NO: 179 selected from the group consisting of 25, 26, 28, 29, 31, 36, 37, 57, 59, 94, 95, 96, and 100. 179; and (iv) a heavy chain variable domain at least 90% identical to SEQ ID NO: 272 comprising a histidine at one or more positions in SEQ ID NO: 272 selected from the group consisting of 24, 27, 29, 62, 63, 98, and 108; and / or a light chain variable domain at least 90% identical to SEQ ID NO: 273 comprising a histidine at one or more positions in SEQ ID NO: 273 selected from the group consisting of 27, 28, 29, 31, 32, 89, 92, and 93;(b) a heavy chain CH1-CH2-CH3 sequence of SEQ ID NO: 351 or SEQ ID NO: 352, comprising one or more of the following: (i) a methionine to tyrosine substitution at amino acid position 135, a serine to threonine substitution at amino acid position 137, and a threonine to glutamic acid substitution at amino acid position 139, (ii) a methionine to leucine substitution at amino acid position 311 and an asparagine to serine substitution at amino acid position 317, and (iii) a light chain C of SEQ ID NO: 353, comprising an alanine to cysteine ​​substitution at amino acid position 1 and / or a valine to cysteine ​​substitution at amino acid position 98; L Contains arrays.

[0009] In some embodiments, the heavy chain CH1-CH2-CH3 sequence of SEQ ID NO:351 or SEQ ID NO:352 comprises a methionine to leucine substitution at amino acid position 311 and an asparagine to serine substitution at amino acid position 317. In some embodiments, the antibody comprises heavy and light chain sequences selected from the group of: (i) SEQ ID NO:354 and SEQ ID NO:2, respectively; (ii) SEQ ID NO:360 and SEQ ID NO:85, respectively; (iii) SEQ ID NO:366 and SEQ ID NO:179, respectively; and (iv) SEQ ID NO:372 and SEQ ID NO:273, respectively.

[0010] In some embodiments, the heavy chain CH1-CH2-CH3 sequence of SEQ ID NO:351 or SEQ ID NO:352 comprises a methionine to tyrosine substitution at amino acid position 135, a serine to threonine substitution at amino acid position 137, and a threonine to glutamic acid substitution at amino acid position 139. In some embodiments, the antibody comprises heavy and light chain sequences selected from the group of: (i) SEQ ID NO:355 and SEQ ID NO:2, respectively; (ii) SEQ ID NO:361 and SEQ ID NO:85, respectively; (iii) SEQ ID NO:366 and SEQ ID NO:179, respectively; and (iv) SEQ ID NO:373 and SEQ ID NO:273, respectively.

[0011] In some embodiments, the antibody comprises a light chain C of SEQ ID NO: 353. Land a valine to cysteine ​​substitution at amino acid position 98. In some embodiments, the antibody comprises heavy and light chain sequences selected from the group of: (i) SEQ ID NO: 1 and SEQ ID NO: 359, respectively; (ii) SEQ ID NO: 84 and SEQ ID NO: 365, respectively; (iii) SEQ ID NO: 178 and SEQ ID NO: 371, respectively; and (iv) SEQ ID NO: 272 and SEQ ID NO: 377, respectively.

[0012] In some embodiments, the heavy chain CH1-CH2-CH3 sequence of SEQ ID NO: 351 or SEQ ID NO: 352 contains a methionine to leucine substitution at amino acid position 311 and an asparagine to serine substitution at amino acid position 317, and the light chain C L The sequences comprise a valine to cysteine ​​substitution at amino acid position 98. In some embodiments, the antibody comprises heavy and light chain sequences selected from the group of: (i) SEQ ID NO:354 and SEQ ID NO:359, respectively; (ii) SEQ ID NO:360 and SEQ ID NO:365, respectively; (iii) SEQ ID NO:366 and SEQ ID NO:371, respectively; and (iv) SEQ ID NO:372 and SEQ ID NO:377, respectively.

[0013] In some embodiments, the heavy chain CH1-CH2-CH3 sequence of SEQ ID NO: 351 or SEQ ID NO: 352 comprises a methionine to tyrosine substitution at amino acid position 135, a serine to threonine substitution at amino acid position 137, and a threonine to glutamic acid substitution at amino acid position 139, and the light chain C L The sequences comprise a valine to cysteine ​​substitution at amino acid position 98. In some embodiments, the antibody comprises heavy and light chain sequences selected from the group of: (i) SEQ ID NO:355 and SEQ ID NO:359, respectively; (ii) SEQ ID NO:361 and SEQ ID NO:365, respectively; (iii) SEQ ID NO:367 and SEQ ID NO:371, respectively; and (iv) SEQ ID NO:373 and SEQ ID NO:377, respectively.

[0014] In some embodiments, the heavy chain CH1-CH2-CH3 sequence of SEQ ID NO: 351 or SEQ ID NO: 352 comprises an alanine to cysteine ​​substitution at amino acid position 1. In some embodiments, the antibody comprises heavy and light chain sequences selected from the group of: (i) SEQ ID NO: 356 and SEQ ID NO: 2, respectively; (ii) SEQ ID NO: 362 and SEQ ID NO: 85, respectively; (iii) SEQ ID NO: 368 and SEQ ID NO: 179, respectively; and (iv) SEQ ID NO: 374 and SEQ ID NO: 273, respectively.

[0015] In some embodiments, the heavy chain CH1-CH2-CH3 sequence of SEQ ID NO:351 or SEQ ID NO:352 comprises a methionine to leucine substitution at amino acid position 311, an asparagine to serine substitution at amino acid position 317, and an alanine to cysteine ​​substitution at amino acid position 1. In some embodiments, the antibody comprises heavy and light chain sequences selected from the group of: (i) SEQ ID NO:357 and SEQ ID NO:2, respectively; (ii) SEQ ID NO:363 and SEQ ID NO:85, respectively; (iii) SEQ ID NO:369 and SEQ ID NO:179, respectively; and (iv) SEQ ID NO:375 and SEQ ID NO:273, respectively.

[0016] In some embodiments, the heavy chain CH1-CH2-CH3 sequence of SEQ ID NO:351 or SEQ ID NO:352 comprises a methionine to tyrosine substitution at amino acid position 135, a serine to threonine substitution at amino acid position 137, a threonine to glutamic acid substitution at amino acid position 139, and an alanine to cysteine ​​substitution at amino acid position 1. In some embodiments, the antibody comprises heavy and light chain sequences selected from the group of: (i) SEQ ID NO:358 and SEQ ID NO:2, respectively; (ii) SEQ ID NO:364 and SEQ ID NO:85, respectively; (iii) SEQ ID NO:370 and SEQ ID NO:179, respectively; and (iv) SEQ ID NO:376 and SEQ ID NO:273, respectively.

[0017] In some embodiments, the antibody comprises a cytotoxic agent conjugated to one or more of: (a) the heavy chain CH1-CH2-CH3 of SEQ ID NO: 351 or SEQ ID NO: 352, which comprises one or more of: (i) a cysteine ​​at amino acid position 103, (ii) a cysteine ​​at amino acid position 109, (iii) a cysteine ​​at amino acid position 112; and / or (b) a cysteine ​​at amino acid position 107 of SEQ ID NO: 353.

[0018] In some embodiments, the antibody comprises a cytotoxic or cytostatic agent, which is conjugated to the cysteine ​​at position 98 of SEQ ID NO: 353. In some embodiments, the antibody comprises a cytotoxic or cytostatic agent, which is conjugated to the cysteine ​​at position 1 of SEQ ID NO: 351 or SEQ ID NO: 352. In some embodiments, the cytotoxic or cytostatic agent is a conjugated toxin, radioisotope, drug, or small molecule.

[0019] In some embodiments, (a) the dissociation rate of the antibody at a pH of about 4.0 to about 6.5 is faster than the dissociation rate at a pH of about 7.0 to about 8.0; or (b) the dissociation constant (K D ) is the K at pH 7.0 to 8.0. D is greater than.

[0020] In some embodiments, a composition comprising the antibody results in one or more of: increased toxin release in target mammalian cells compared to a composition comprising an equivalent amount of a control antibody; increased killing of target mammalian cells compared to a composition comprising an equivalent amount of the control antibody; and increased endolysosomal delivery in target mammalian cells compared to a composition comprising an equivalent amount of the control antibody.

[0021] In some embodiments, a composition comprising the antibody does not result in a significant or detectable decrease in the level of LRRC15 present on the surface of target mammalian cells compared to a composition comprising an equivalent amount of a control antibody.

[0022] In some embodiments, the antibody is degraded in the target mammalian cell after intracellular uptake of the antibody by the target mammalian cell. In some embodiments, the target mammalian cell is a cancer cell. In some embodiments, the antibody is cytotoxic or cytostatic to the target mammalian cell. In some embodiments, the antibody has an avidity that confers higher selectivity for cancer cells over non-cancer cells.

[0023] In some embodiments, the antibody is cross-reactive with non-human primate LRRC15 and human LRRC15, or cross-reactive with non-human primate LRRC15, human LRRC15, and one or both of rat LRRC15 and mouse LRRC15.

[0024] In some embodiments, the half-life of the antibody in vivo is increased compared to the half-life of a control antibody in vivo.

[0025] Also provided herein is a pharmaceutical composition comprising an effective amount of any one of the antibodies described herein, wherein the first antigen-binding domain comprises one of the following (a) to (d): (a) a light chain variable domain of SEQ ID NO:2, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, or SEQ ID NO:78, and / or a heavy chain variable domain of SEQ ID NO:1, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, or SEQ ID NO:83, wherein the first antigen-binding domain comprises: (i) a light chain variable domain of SEQ ID NO:2 and a heavy chain variable domain of SEQ ID NO:1; (ii) a light chain variable domain of SEQ ID NO: 2 and a heavy chain variable domain other than one of SEQ ID NOs: 20, 21, 23, 25, 30, 32, 43, 45, 46, 50 to 52, or 80 to 83; or (iii) a heavy chain variable domain of SEQ ID NO: 1 and a light chain variable domain other than one of SEQ ID NOs: 61, 63 to 65, 71, 72, 74 to 76, or 78; (b) does not contain a heavy chain variable domain of SEQ ID NO: 85, SEQ ID NO: 137, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 142, SEQ ID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 148, SEQ ID NO: 149, SEQ ID NO: 153, SEQ ID NO: 154, SEQ ID NO: 156, SEQ ID NO: 157, SEQ ID NO: 158, SEQ ID NO: 161, SEQ ID NO: 169, SEQ ID NO: 170, SEQ ID NO: 171, SEQ ID NO: 172, SEQ ID NO: 173, SEQ ID NO: 174, SEQ ID NO: 175, SEQ ID NO: 176, or SEQ ID NO: 177, and / or a heavy chain variable domain of SEQ ID NO: 84, SEQ ID NO: 93, SEQ ID NO: 95, SEQ ID NO: 98, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 106, SEQ ID NO: 110, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 124, SEQ ID NO: 126, SEQ ID NO: 127, or SEQ ID NO: 166, wherein the first antigen-binding domain comprises: (i) a light chain variable domain of SEQ ID NO: 85 and a heavy chain variable domain of SEQ ID NO: 84;(ii) a light chain variable domain of SEQ ID NO: 85 and a heavy chain variable domain that is not one of SEQ ID NOs: 93, 95, 98, 101, 102, 106, 110, 120 to 122, 124, 126, 127, or 166; or (iii) a heavy chain variable domain of SEQ ID NO: 84 and a light chain variable domain that is not one of SEQ ID NOs: 137, 139, 140, 142, 144 to 146, 148, 149, 153, 154, 156 to 158, 161, or 169 to 177; (c) does not contain a light chain variable domain of SEQ ID NO: 179, SEQ ID NO: 229, SEQ ID NO: 230, SEQ ID NO: 232, SEQ ID NO: 233, SEQ ID NO: 235, SEQ ID NO: 240, SEQ ID NO: 241, SEQ ID NO: 246, SEQ ID NO: 248, SEQ ID NO: 251, SEQ ID NO: 252, SEQ ID NO: 253, SEQ ID NO: 257, SEQ ID NO: 263, SEQ ID NO: 264, SEQ ID NO: 268, SEQ ID NO: 269, SEQ ID NO: 270, or SEQ ID NO: 271, and / or a heavy chain variable domain of SEQ ID NO: 178, SEQ ID NO: 196, SEQ ID NO: 201, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 225, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260, or SEQ ID NO: 261, wherein the first antigen-binding domain comprises (i) a light chain variable domain of SEQ ID NO: 179 and a heavy chain variable domain of SEQ ID NO: 178; (ii) a light chain variable domain of SEQ ID NO: 179 and a heavy chain variable domain that is not one of SEQ ID NOs: 196, 201, 205, 206, 225, or 258-261; or (iii) a heavy chain variable domain of SEQ ID NO: 178 and a light chain variable domain that is not one of SEQ ID NOs: 229, 230, 232, 233, 235, 240, 241, 246, 248, 251-253, 257, 263, 264, or 268-271;and (d) a light chain variable domain of SEQ ID NO:273, SEQ ID NO:327, SEQ ID NO:328, SEQ ID NO:329, SEQ ID NO:331, SEQ ID NO:332, SEQ ID NO:342, SEQ ID NO:345, or SEQ ID NO:346, and / or a heavy chain variable domain of SEQ ID NO:272, SEQ ID NO:281, SEQ ID NO:284, SEQ ID NO:286, SEQ ID NO:305, SEQ ID NO:306, SEQ ID NO:311, or SEQ ID NO:321, wherein the first antigen-binding domain comprises (i) a light chain variable domain of SEQ ID NO:273 and a heavy chain variable domain of SEQ ID NO:272; (ii) a light chain variable domain of SEQ ID NO: 273 and a heavy chain variable domain other than one of SEQ ID NOs: 281, 284, 286, 305, 306, 311, or 321; or (iii) a heavy chain variable domain of SEQ ID NO: 272 and a light chain variable domain other than one of SEQ ID NOs: 327-329, 331, 332, 342, 345, or 346.

[0026] Also provided herein are kits comprising at least one dose of any of the antibodies described herein or any of the pharmaceutical compositions described herein.

[0027] Also provided herein is a method for treating a cancer characterized by having a population of cancer cells that display LRRC15 or an epitope of LRRC15 on their surface, comprising administering a therapeutically effective amount of any one of the antibodies described herein or any one of the pharmaceutical compositions described herein to a subject identified as having a cancer characterized by having the above-mentioned population of cancer cells.

[0028] Also provided herein is a method for reducing tumor volume in a subject, wherein the tumor is characterized by having a population of cancer cells that display LRRC15 or an epitope of LRRC15 on their surface, the method comprising administering a therapeutically effective amount of any one of the antibodies described herein or any of the pharmaceutical compositions described herein to a subject identified as having a cancer characterized by having the above population of cancer cells.

[0029] Also provided herein is a method for inducing cell death of cancer cells in a subject, wherein the cancer cells display LRRC15 or an epitope of LRRC15 on their surface, the method comprising administering a therapeutically effective amount of any one of the antibodies described herein or any one of the pharmaceutical compositions described herein to a subject identified as having a cancer characterized by having a population of the cancer cells.

[0030] Also provided herein is a method for reducing the risk of developing metastases or reducing the risk of further metastases in a subject having cancer, wherein the cancer is characterized by having a population of cancer cells that display LRRC15 or an epitope of LRRC15 on their surface, the method comprising administering a therapeutically effective amount of any one of the antibodies described herein or any one of the pharmaceutical compositions described herein to a subject identified as having a cancer characterized by having the above population of cancer cells.

[0031] Also herein, an antibody may comprise (a) a heavy chain variable domain and a light chain variable domain selected from the group consisting of: (i) SEQ ID NO: 1 and SEQ ID NO: 2, respectively; (ii) SEQ ID NO: 84 and SEQ ID NO: 85, respectively; (iii) SEQ ID NO: 178 and SEQ ID NO: 179, respectively; and (iv) SEQ ID NO: 272 and SEQ ID NO: 273, respectively; and (b) a heavy chain CH1-CH2-CH3 sequence of SEQ ID NO: 351 or SEQ ID NO: 352 that includes one or more of the following substitutions: (i) a methionine to tyrosine substitution at amino acid position 135, a serine to threonine substitution at amino acid position 137, and a threonine to glutamic acid substitution at amino acid position 139; (ii) a methionine to leucine substitution at amino acid position 311 and an asparagine to serine substitution at amino acid position 317; (iii) an alanine to cysteine ​​substitution at amino acid position 1; and / or a light chain CH1-CH2-CH3 sequence of SEQ ID NO: 353 that includes a valine to cysteine ​​substitution at position 98.L Also provided are antibodies comprising the sequence:

[0032] In some embodiments, the heavy chain CH1-CH2-CH3 sequence of SEQ ID NO:351 or SEQ ID NO:352 comprises a methionine to leucine substitution at amino acid position 311 and an asparagine to serine substitution at amino acid position 317. In some embodiments, the antibody comprises heavy and light chain sequences selected from the group of: (i) SEQ ID NO:354 and SEQ ID NO:2, respectively; (ii) SEQ ID NO:360 and SEQ ID NO:85, respectively; (iii) SEQ ID NO:366 and SEQ ID NO:179, respectively; and (iv) SEQ ID NO:372 and SEQ ID NO:273, respectively.

[0033] In some embodiments, the heavy chain CH1-CH2-CH3 sequence of SEQ ID NO:351 or SEQ ID NO:352 comprises a methionine to tyrosine substitution at amino acid position 135, a serine to threonine substitution at amino acid position 137, and a threonine to glutamic acid substitution at amino acid position 139. In some embodiments, the antibody comprises heavy and light chain sequences selected from the group of: (i) SEQ ID NO:355 and SEQ ID NO:2, respectively; (ii) SEQ ID NO:361 and SEQ ID NO:85, respectively; (iii) SEQ ID NO:366 and SEQ ID NO:179, respectively; and (iv) SEQ ID NO:373 and SEQ ID NO:273, respectively.

[0034] In some embodiments, the light chain C of SEQ ID NO: 353 L The sequences comprise a valine to cysteine ​​substitution at amino acid position 98. In some embodiments, the antibody comprises heavy and light chain sequences selected from the group of: (i) SEQ ID NO:1 and SEQ ID NO:359, respectively; (ii) SEQ ID NO:84 and SEQ ID NO:365, respectively; (iii) SEQ ID NO:178 and SEQ ID NO:371, respectively; and (iv) SEQ ID NO:272 and SEQ ID NO:377, respectively.

[0035] In some embodiments, the heavy chain CH1-CH2-CH3 sequence of SEQ ID NO: 351 or SEQ ID NO: 352 contains a methionine to leucine substitution at amino acid position 311 and an asparagine to serine substitution at amino acid position 317, and the light chain C L The sequence contains a valine to cysteine ​​substitution at amino acid position 98.

[0036] In some embodiments, the antibody comprises heavy and light chain sequences selected from the group of: (i) SEQ ID NO: 354 and SEQ ID NO: 359, respectively; (ii) SEQ ID NO: 360 and SEQ ID NO: 365, respectively; (iii) SEQ ID NO: 366 and SEQ ID NO: 371, respectively; and (iv) SEQ ID NO: 372 and SEQ ID NO: 377, respectively.

[0037] In some embodiments, the heavy chain CH1-CH2-CH3 sequence of SEQ ID NO: 351 or SEQ ID NO: 352 comprises a methionine to tyrosine substitution at amino acid position 135, a serine to threonine substitution at amino acid position 137, and a threonine to glutamic acid substitution at amino acid position 139, and the light chain C L The sequences comprise a valine to cysteine ​​substitution at amino acid position 98. In some embodiments, the antibody comprises heavy and light chain sequences selected from the group of: (i) SEQ ID NO:355 and SEQ ID NO:359, respectively; (ii) SEQ ID NO:361 and SEQ ID NO:365, respectively; (iii) SEQ ID NO:367 and SEQ ID NO:371, respectively; and (iv) SEQ ID NO:373 and SEQ ID NO:377, respectively.

[0038] In some embodiments, the heavy chain CH1-CH2-CH3 sequence of SEQ ID NO: 351 or SEQ ID NO: 352 comprises an alanine to cysteine ​​substitution at amino acid position 1. In some embodiments, the antibody comprises heavy and light chain sequences selected from the group of: (i) SEQ ID NO: 356 and SEQ ID NO: 2, respectively; (ii) SEQ ID NO: 362 and SEQ ID NO: 85, respectively; (iii) SEQ ID NO: 368 and SEQ ID NO: 179, respectively; and (iv) SEQ ID NO: 374 and SEQ ID NO: 273, respectively.

[0039] In some embodiments, the heavy chain CH1-CH2-CH3 sequence of SEQ ID NO:351 or SEQ ID NO:352 comprises a methionine to leucine substitution at amino acid position 311, an asparagine to serine substitution at amino acid position 317, and an alanine to cysteine ​​substitution at amino acid position 1. In some embodiments, the antibody comprises heavy and light chain sequences selected from the group of: (i) SEQ ID NO:357 and SEQ ID NO:2, respectively; (ii) SEQ ID NO:363 and SEQ ID NO:85, respectively; (iii) SEQ ID NO:369 and SEQ ID NO:179, respectively; and (iv) SEQ ID NO:375 and SEQ ID NO:273, respectively.

[0040] In some embodiments, the heavy chain CH1-CH2-CH3 sequence of SEQ ID NO:351 or SEQ ID NO:352 comprises a methionine to tyrosine substitution at amino acid position 135, a serine to threonine substitution at amino acid position 137, a threonine to glutamic acid substitution at amino acid position 139, and an alanine to cysteine ​​substitution at amino acid position 1. In some embodiments, the antibody comprises heavy and light chain sequences selected from the group of: (i) SEQ ID NO:358 and SEQ ID NO:2, respectively; (ii) SEQ ID NO:364 and SEQ ID NO:85, respectively; (iii) SEQ ID NO:370 and SEQ ID NO:179, respectively; and (iv) SEQ ID NO:376 and SEQ ID NO:273, respectively.

[0041] In some embodiments, the antibody comprises a cytotoxic agent conjugated to one or more of: (a) the heavy chain CH1-CH2-CH3 of SEQ ID NO: 351 or SEQ ID NO: 352, which comprises one or more of: (i) a cysteine ​​at amino acid position 103, (ii) a cysteine ​​at amino acid position 109, and (iii) a cysteine ​​at amino acid position 112; and / or (b) a cysteine ​​at amino acid position 107 of SEQ ID NO: 353.

[0042] In some embodiments, the antibody comprises a cytotoxic or cytostatic agent, which is conjugated to the cysteine ​​at position 98 of SEQ ID NO:353.

[0043] In some embodiments, the antibody comprises a cytotoxic or cytostatic agent, which is conjugated to cysteine ​​at position 1 of SEQ ID NO:351 or SEQ ID NO:352.

[0044] In some embodiments, the cytostatic or cytotoxic agent is a conjugated toxin, radioisotope, drug, or small molecule. In some embodiments, the antibody is cytotoxic or cytostatic to the target mammalian cell. In some embodiments, the antibody is degraded in the target mammalian cell after intracellular uptake of the antibody by the target mammalian cell. In some embodiments, the target mammalian cell is a cancer cell. In some embodiments, the antibody has an avidity that confers higher selectivity for cancer cells over non-cancerous cells.

[0045] In some embodiments, the antibody is cross-reactive with non-human primate LRRC15 and human LRRC15, or cross-reactive with non-human primate LRRC15, human LRRC15, and one or both of rat LRRC15 and mouse LRRC15.

[0046] In some embodiments, the half-life of the antibody in vivo is increased compared to the half-life of a control antibody in vivo.

[0047] In some embodiments, the target mammalian cell is a cancer cell. Also provided herein are pharmaceutical compositions comprising an effective amount of any one of the antibodies described herein.

[0048] Also provided herein are kits comprising at least one dose of any one of the antibodies described herein or any one of the pharmaceutical compositions described herein.

[0049] Also provided herein is a method for treating a cancer characterized by having a population of cancer cells that display LRRC15 or an epitope of LRRC15 on their surface, comprising administering a therapeutically effective amount of any one of the antibodies described herein or any one of the pharmaceutical compositions described herein to a subject identified as having a cancer characterized by having the above-mentioned population of cancer cells.

[0050] Also provided herein is a method for reducing tumor volume in a subject, wherein the tumor is characterized by having a population of cancer cells that display LRRC15 or an epitope of LRRC15 on their surface, the method comprising administering a therapeutically effective amount of any one of the antibodies described herein or any one of the pharmaceutical compositions described herein to a subject identified as having a cancer characterized by having the above population of cancer cells.

[0051] Also provided herein is a method for inducing cell death of cancer cells in a subject, wherein the cancer cells display LRRC15 or an epitope of LRRC15 on their surface, the method comprising administering a therapeutically effective amount of any one of the antibodies described herein or any one of the pharmaceutical compositions described herein to a subject identified as having a cancer characterized by having a population of the above cancer cells.

[0052] Also provided herein is a method for reducing the risk of developing metastases or reducing the risk of further metastases in a subject having cancer, wherein the cancer is characterized by having a population of cancer cells that display LRRC15 or an epitope of LRRC15 on their surface, the method comprising administering a therapeutically effective amount of any one of the antibodies described herein or any one of the pharmaceutical compositions described herein to a subject identified as having a cancer characterized by having the above-mentioned population of cancer cells.

[0053] As used herein, the term "antigen-binding protein construct" refers to (i) a single polypeptide comprising at least one antigen-binding domain, or (ii) a complex of two or more polypeptides (e.g., the same or different polypeptides) that together form at least one antigen-binding domain. Non-limiting examples and embodiments of antigen-binding protein constructs are described herein. Further examples and embodiments of antigen-binding protein constructs are known in the art.

[0054] A "multispecific antigen-binding protein construct" is an antigen-binding protein construct comprising two or more different antigen-binding domains that collectively specifically bind two or more different epitopes. The two or more different epitopes can be epitopes on the same antigen (e.g., a single polypeptide present on the surface of a cell) or on different antigens (e.g., different proteins present on the surface of the same cell or on the surface of different cells). In some aspects, the antigens are present on the surface of a cell. In some aspects, the multispecific antigen-binding protein construct binds to two different epitopes (i.e., a "bispecific antigen-binding protein construct"). In some aspects, the multispecific antigen-binding protein construct binds to three different epitopes (i.e., a "trispecific antigen-binding protein construct"). In some aspects, the multispecific antigen-binding protein construct binds to four different epitopes (i.e., a "tetraspecific antigen-binding protein construct"). In some aspects, the multispecific antigen-binding protein construct binds to five different epitopes (i.e., a "pentaspecific antigen-binding protein construct"). Each binding specificity may be present in any suitable valency. Non-limiting examples of multispecific antigen-binding protein constructs are described herein.

[0055] An "antigen-binding domain" is one or more protein domains (e.g., formed from amino acids from a single polypeptide or formed from amino acids from two or more polypeptides (e.g., the same or different polypeptides) that can specifically bind to one or more different antigens). In some examples, an antigen-binding domain can bind to an antigen or epitope with specificity and affinity similar to that of a naturally occurring antibody. In some embodiments, an antigen-binding domain may be an antibody or fragment thereof. In some embodiments, an antigen-binding domain may comprise an alternative scaffold. Non-limiting examples of antigen-binding domains are described herein. Further examples of antigen-binding domains are known in the art. In some examples, an antigen-binding domain may bind to a single antigen.

[0056] The term "antibody" is used herein in its broadest sense and includes a specific type of immunoglobulin molecule that contains one or more antigen-binding domains that specifically bind to an antigen or epitope. Antibodies include, for example, intact antibodies (e.g., intact immunoglobulins, such as human IgG (e.g., human IgG1, human IgG2, human IgG3, human IgG4)), antibody fragments, and multispecific antibodies, among others. One example of an antigen-binding domain is the antigen-binding domain formed by a VH-VL dimer. Further examples of antibodies are described herein. Further examples of antibodies are known in the art.

[0057] The phrase "endosomal / lysosomal pathway" refers to the network of endosomes (early endosomes, multivesicular bodies, late endosomes, and lysosomes) in the cytoplasm of mammalian cells, where molecules internalized via cell-mediated internalization processes, such as pinocytosis, micropinocytosis, receptor-mediated endocytosis, and / or phagocytosis, are sorted.

[0058] Once endosomes in the endosomal / lysosomal pathway have been purified or isolated, assays for the target protein (e.g., an antigen-binding protein construct described herein) can be performed using methods known in the art (e.g., ELISA, Western blot, immunofluorescence, and immunoprecipitation followed by assays for protein concentration) and can be used to determine the concentration or relative levels of the target protein in the endosomes. Alternatively, endosomes in the endosomal / lysosomal pathway can be imaged by immunofluorescence microscopy using a detectably labeled antibody, an antibody that specifically binds to a characteristic protein present in endosomes (e.g., EEA1 in early endosomes) (e.g., a fluorescently-, dye-, or GFP-labeled antibody, e.g., CellLight™ Early Endosome-GFP), and a fluorescently-labeled antibody that specifically binds to the protein of interest (e.g., an antigen-binding protein construct), and the level of the target protein in the endosome can be determined by quantifying the overlap of the fluorescence emissions of the two different antibodies.

[0059] The phrase "endolysosomal delivery" refers to the rate of accumulation over time or the total amount accumulated at a particular time point of an antigen binding protein construct (e.g., any of the antigen binding protein constructs described herein) in the endosomal / lysosomal pathway in a mammalian cell (e.g., any of the exemplary target mammalian cells described herein).

[0060] An exemplary method for calculating the increased endolysosomal delivery of a pH-engineered ABPC variant compared to the corresponding starting ABPC from cytofluorescence data is to measure the ratio of the mean fluorescence intensity of the variant minus the mean fluorescence intensity of the non-binding IgG control, and then divide the total by the mean fluorescence intensity of the variant's corresponding starting ABPC minus the mean fluorescence intensity of the IgG control.

[0061] An exemplary assay for measuring endolysosomal delivery of any of the ABPCs described herein involves labeling ABPC with a fluorescent dye, followed by incubating the labeled ABPC with cells and measuring cellular fluorescence as an indicator of endolysosomal delivery of ABPC (as generally described, for example, in (Non-Patent Document 1)). Alternatively, any of the ABPCs described herein can be labeled with a pH-sensitive dye that is preferentially fluorescent at acidic pH but not at neutral pH, which can then be incubated with cells and cellular fluorescence measured as an indicator of delivery of ABPC to the acidic endolysosomal compartment.

[0062] When the term "population" is used before a noun, it means two or more of that particular noun. For example, the phrase "population of cancer cells" means "two or more cancer cells." Non-limiting examples of cancer cells are described herein.

[0063] The phrase "cytostatic to a cell" refers to a direct or indirect reduction in proliferation (cell division) of the cell (e.g., a cancer cell) in vivo or in vitro. When a therapeutic agent is cytostatic to a cell, the therapeutic agent may, for example, directly or indirectly cause cell cycle arrest of the cell (e.g., a cancer cell). In some examples, a therapeutic agent that is cytostatic to a cell can reduce the number of cells in a population of cells that are in S phase (compared to the number of cells in that population of cells that are in S phase prior to contact with the therapeutic agent). In some examples, a therapeutic agent that is cytostatic to a cell can reduce the percentage of cells in S phase by at least 20%, at least 40%, at least 60%, or at least 80% (e.g., compared to the percentage of cells in a population of cells that are in S phase prior to contact with the therapeutic agent).

[0064] The phrase "cytotoxic to a cell" refers to directly or indirectly inducing death (eg, necrosis or apoptosis) of the cell (eg, a mammalian cell, eg, a cancer cell) of interest.

[0065] "Affinity" refers to the strength of the sum total of non-covalent interactions between an antigen-binding site and its binding partner (e.g., antigen or epitope). Unless otherwise indicated, as used herein, "affinity" refers to the intrinsic binding affinity, which reflects a 1:1 interaction between a member of the antigen-binding domain and the antigen or epitope. The affinity of a molecule X for its partner Y is determined by the dissociation equilibrium constant (K D ). Affinity can be measured by common methods known in the art, including those described herein. Affinity can be determined, for example, using surface plasmon resonance (SPR) technology (e.g., BIACORE®) or biolayer interferometry (e.g., FORTEBIO®). Additional methods for determining the affinity of an antigen-binding domain to its corresponding antigen or epitope are known in the art.

[0066] The term "epitope" refers to a portion of an antigen that is specifically bound by an antigen-binding domain through a series of physical interactions between: (i) all monomers (e.g., individual amino acid residues, sugar side chains, post-translationally modified amino acid residues) on the portion of the antigen-binding domain that specifically binds to the antigen, and (ii) all monomers (e.g., individual amino acid residues, sugar side chains, post-translationally modified amino acid residues) on the portion of the antigen that is specifically bound by the antigen-binding domain. Epitopes may consist of, for example, surface-accessible amino acid residues, sugar side chains, phosphorylated amino acid residues, methylated amino acid residues, and / or acetylated amino acid residues, and may have specific three-dimensional structural characteristics as well as specific charge characteristics. Conformational and nonconformational epitopes are distinguished in that binding to the former, but not the latter, can be lost in the presence of denaturing solvents. In some embodiments, an epitope is defined by a linear amino acid sequence of at least about 3-6 amino acids, or about 10-15 amino acids. In some embodiments, an epitope refers to a portion of a full-length protein or a portion thereof defined by three-dimensional structure (e.g., protein folding). In some embodiments, an epitope is defined by discontinuous amino acid sequences held together through protein folding. In some embodiments, an epitope is defined by discontinuous amino acid sequences held together by quaternary structure (e.g., a cleft formed by the interaction of two different polypeptide chains). The amino acid sequence between the residues defining the epitope may not be important to the three-dimensional structure of the epitope. Conformational epitopes can be determined and screened using assays comparing the binding of antigen-binding protein constructs to denatured versions of the antigen of interest, so that linear epitopes are generated. Epitopes can include amino acid residues directly involved in binding and other amino acid residues not directly involved in binding.

[0067] Methods for identifying the epitope to which an antigen-binding domain specifically binds are known in the art, such as structural-based analyses (e.g., X-ray crystallography, NMR, and / or electron microscopy) (e.g., of the antigen and / or antigen-antigen binding domain complex), and / or mutagenesis-based analyses in which variants are measured in binding assays with binding partners (e.g., alanine scanning mutagenesis, glycine scanning mutagenesis, and homology scanning mutagenesis), many of which are known in the art.

[0068] The term "paratope" refers to a portion of an antigen-binding domain that specifically binds to an antigen through a series of physical interactions between: (i) all monomers (e.g., individual amino acid residues, sugar side chains, post-translationally modified amino acid residues) on the portion of the antigen-binding domain that specifically binds to the antigen, and (ii) all monomers (e.g., individual amino acid residues, sugar side chains, post-translationally modified amino acid residues) on the portion of the antigen that is specifically bound by the antigen-binding domain. A paratope can consist of, for example, surface-accessible amino acid residues and can have specific three-dimensional structural characteristics as well as specific charge characteristics. In some embodiments, a paratope refers to a portion of a full-length antigen-binding domain or a portion thereof that is defined by a three-dimensional structure (e.g., protein folding). In some embodiments, a paratope is defined by discontinuous amino acid sequences held together through protein folding. In some embodiments, an epitope is defined by discontinuous amino acid sequences held together by a quaternary structure (e.g., a cleft formed by the interaction of two different polypeptide chains). The amino acid sequence between the residues that define the paratope may not be important to the three-dimensional structure of the paratope. The paratope can include amino acid residues that are directly involved in binding and other amino acid residues that are not directly involved in binding.

[0069] Methods for identifying the paratope to which an antigen-binding domain specifically binds are known in the art, such as structural-based analyses (e.g., X-ray crystallography, NMR, and / or electron microscopy) (e.g., of the antigen-binding domain and / or antigen-binding domain-antigen complex), and / or mutagenesis-based analyses in which variants are measured in binding assays with binding partners (e.g., alanine scanning mutagenesis, glycine scanning mutagenesis, and homology scanning mutagenesis), many of which are known in the art.

[0070] The phrase "present on the surface of a mammalian cell" refers to (1) an antigen that is physically associated with or at least partially incorporated into the plasma membrane of a mammalian cell (e.g., a transmembrane protein, a peripheral membrane protein, a lipid-binding protein (e.g., a GPI anchor), an N-myristolyated protein, or an S-palmitoylated protein), or (2) an antigen stably bound to its cognate receptor that is physically associated with the plasma membrane of a mammalian cell (e.g., a ligand bound to its cognate receptor, which physically attaches the cognate receptor to the plasma membrane). Non-limiting methods for determining the presence of an antigen on the surface of a mammalian cell include fluorescence-activated cell sorting (FACS), immunohistochemistry, cell fractionation assays, and Western blot.

[0071] The phrase "control ABPC" or "control antigen-binding protein construct" refers to an ABPC that is (i) capable of specifically binding to LRRC15 or an epitope of LRRC15 present on the surface of a mammalian cell (e.g., a target mammalian cell), and in which one or both of the following are true: (a) the dissociation rate of the first antigen-binding domain at a pH of about 4.0 to about 6.5 (e.g., any subrange of this range described herein) is greater than or equal to about 7.0 to about 8.0 (e.g., any subrange of this range described herein). or (b) the dissociation constant (K) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 (e.g., 2.8-fold or less, 2.6-fold or less, 2.5-fold or less, 2.4-fold or less, 2.2-fold or less, 2.0-fold or less, 1.8-fold or less, 1.6-fold or less, 1.5-fold or less, 1.4-fold or less, 1.2-fold or less, 1.0-fold or less, 0.8-fold or less, 0.6-fold or less, 0.5-fold or less, 0.4-fold or less, 0.3-fold or less, 0.2-fold or less, or 0.1-fold or less) faster than the dissociation rate at pH 6.5; or (b) the dissociation constant (K) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 (e.g., any of the subranges of this range described herein). D ) at a pH of about 7.0 to about 8.0 (e.g., any of the subranges of this range described herein). D (ii) samrotamab; (iii) hu139.10; (iv) huAD208.4.1 and / or (v) huAD208.12.1, which are 3-fold or less (e.g., 2.8-fold or less, 2.6-fold or less, 2.5-fold or less, 2.4-fold or less, 2.2-fold or less, 2.0-fold or less, 1.8-fold or less, 1.6-fold or less, 1.5-fold or less, 1.4-fold or less, 1.2-fold or less, 1.0-fold or less, 0.8-fold or less, 0.6-fold or less, 0.5-fold or less, 0.4-fold or less, 0.3-fold or less, 0.2-fold or less, or 0.1-fold or less) greater than ABPC; (ii) samrotamab; (iii) hu139.10; (iv) huAD208.4.1 and / or (v) huAD208.12.1.

[0072] The term "extracellular space" refers to the fluid outside the plasma membrane of a mammalian cell. When the mammalian cell is in vitro, the extracellular space can be liquid culture medium. When the mammalian cell is in vivo, the extracellular space can be, for example, plasma, serum, blood, interstitial fluid, or lymph.

[0073] The term "endolysosomal space" refers to the fluid enclosed by the vesicles and organelles that make up the endosomal / lysosomal pathway in mammalian cells.

[0074] The phrase "reduced level" or "decreased level" can be a reduction or decrease that is a reduction of at least 1% (e.g., at least 2%, at least 4%, at least 6%, at least 8%, at least 10%, at least 12%, at least 14%, at least 16%, at least 18%, at least 20%, at least 22%, at least 24%, at least 26%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99%) as compared to a reference level or value.

[0075] The term "cell killing ability" refers to the ability of a drug (e.g., any ABPC described herein) to directly or indirectly induce apoptosis and / or necrosis in mammalian cells (e.g., cancer cells), measured as a rate over time or at relevant time points. Methods for determining the cell killing ability of a cell are known in the art (e.g., trypan blue staining, microscopy, fluorescence-assisted cell sorting, and assays detecting apoptosis markers (e.g., Annexin V)). In non-limiting examples, cell killing ability can be measured, for example, by cell killing at a single concentration of the drug, by the IC50 of the drug (i.e., the concentration of the drug that achieves half of the maximum cell killing ability), or by the ratio of the drug's dissociation constant KD in mammalian cells divided by its IC50. In some non-limiting examples, the IC50 and / or KD ratio of the ABPC described herein is compared to that of a control ABPC (as defined herein), and optionally demonstrates that the ABPC described herein has a higher cell killing ability than the control ABPC.

[0076] The term "toxin release" refers to the ability of mammalian cells (e.g., non-cancerous mammalian cells or cancer cells) to internalize (e.g., via pinocytosis and / or receptor-mediated endocytosis) any of the ABPCs described herein (e.g., any of the ABPCs described herein or control ABPCs) conjugated to a toxin, and then release the toxin conjugated to the ABPC, measured as a percentage over time or at specific time points. Toxin release can be assessed using a variety of different exemplary assays, such as ELISA, immunofluorescence, cell killing assays, cell cycle arrest assays, DNA damage assays, mass spectrometry, HPLC, and / or isotope-labeled toxins.

[0077] The phrases "target cell" or "target mammalian cell" or "mammalian target cell" refer to mammalian cells having at least one LRRC15 present on their surface. In some examples, the mammalian target cell can be a cancer cell. In some embodiments, the target mammalian cell has a total of about 1 to about 10,000,000, about 1 to about 9,000,000, about 1 to about 8,000,000, about 1 to about 7,000,000, about 1 to about 6,000,000, about 1 to about 5,000,000, about 1 to about 4,000,000, about 1 to about 3,000,000, about 1 to about 2,000,000, about 1 to about 1,000,000, about 1 to about 800,000, or about 1 to about 600,000 LRRC15 present on the plasma membrane of the target mammalian cell. 00 pieces, about 1 to about 400,000 pieces, about 1 to about 200,000 pieces, about 1 to about 100,000 pieces, about 1 to about 80,000 pieces, about 1 to about 80,000 pieces, about 1 to about 75,000 pieces, about 1 to about 70,000 pieces, about 1 to about 65,000 pieces, about 1 to about 60,0 00 pieces, about 1 to about 55,000 pieces, about 1 to about 50,000 pieces, about 1 to about 45,000 pieces, about 1 to about 40,000 pieces, about 1 to about 35,000 pieces, about 1 to about 30,000 pieces, about 1 to about 25,000 pieces, about 1 to about 20,000 pieces, about 1 to about 15,000 pieces , about 1 to about 10,000 pieces, about 1 to about 7,500 pieces, about 1 to about 5,000 pieces, about 1 to about 4,000 pieces, about 1 to about 3,000 pieces, about 1 to about 2,000 pieces, about 1 to about 1,000 pieces, about 1 to about 500 pieces, about 1 to about 100 pieces, about 1 to about 50 pieces, about 1 to about 1 0 pieces, about 10 to about 10,000,000 pieces, about 10 to about 9,000,000 pieces, about 10 to about 8,000,000 pieces, about 10 to about 7,000,000 pieces, about 10 to about 6,000,000 pieces, about 10 to about 5,000,000 pieces, about 10 to about 4,000, 000 pieces, about 10 to about 3,000,000 pieces, about 10 to about 2,000,000 pieces, about 10 to about 1,000,000 pieces, about 10 to about 800,000 pieces, about 10 to about 600,000 pieces, about 10 to about 400,000 pieces, about 10 to about 200,000 pieces, about 1 0 to about 100,000 pieces, about 10 to about 80,000 pieces, about 10 to about 80,000 pieces, about 10 to about 75,000 pieces, about 10 to about 70,000 pieces, about 10 to about 65,000 pieces, about 10 to about 60,000 pieces, about 10 to about 55,000 pieces, about 10 to about 50,000, about 10 to about 45,000, about 10 to about 40,000, about 10 to about 35,000, about 10 to about 30,000, about 10 to about 25,000, about 10 to about 20,000, about 10 to about 15,000, about 10 to about 10,000, about 10 to about 7,500, about 10 to about 5,000, about 10 to about 4,000, about 10 to about 3,000, about 10 to about 2,000, about 10 to about 1,000, about 10 to about 500, about 10 to about 100, about 10 to about 50, about 50 to about 10,000,000, about 50 to about 9,000,000, about 50 to about 8 ,000,000, about 50 to about 7,000,000, about 50 to about 6,000,000, about 50 to about 5,000,000, about 50 to about 4,000,000, about 50 to about 3,000,000, about 50 to about 2,000,000, about 50 to about 1,000,000, about 5 0 to about 800,000, about 50 to about 600,000, about 50 to about 400,000, about 50 to about 200,000, about 50 to about 100,000, about 50 to about 80,000, about 50 to about 80,000, about 50 to about 75,000, about 50 to about 70,000, about 50 to about 65,000, about 50 to about 60,000, about 50 to about 55,000, about 50 to about 50,000, about 50 to about 45,000, about 50 to about 40,000, about 50 to about 35,000, about 50 to about 30,000, about 50 to about 25,000, about 50 to about 20,000 , about 50 to about 15,000, about 50 to about 10,000, about 50 to about 7,500, about 50 to about 5,000, about 50 to about 4,000, about 50 to about 3,000, about 50 to about 2,000, about 50 to about 1,000, about 50 to about 500, about 50 to about 100, about 100 to about 10,000,000, about 100 to about 9,000,000, about 100 to about 8,000,000, about 100 to about 7,000,000, about 100 to about 6,000,000, about 100 to about 5,000,000, about 100 to about 4,000,000, about 100 to about 3,000 0,000, about 100 to about 2,000,000, about 100 to about 1,000,000, about 100 to about 800,000, about 100 to about 600,000, about 100 to about 400,000, about 100 to about 200,000, about 100 to about 100,000, about 100 to about 80,000, about 100 to about 75,000, about 100 to about 70,000, about 100 to about 65,000, about 100 to about 60,000, about 100 to about 55,000, about 100 to about 50,000, about 100 to about 45,000, about 100 to about 40,000, about 100 to about 3 5,000, about 100 to about 30,000, about 100 to about 25,000, about 100 to about 20,000, about 100 to about 15,000, about 100 to about 10,000, about 100 to about 7,500, about 100 to about 5,000, about 100 to about 4,000, about 100 to about 3,0 00, about 100 to about 2,000, about 100 to about 1,000, about 100 to about 500, about 500 to about 10,000,000, about 500 to about 9,000,000, about 500 to about 8,000,000, about 500 to about 7,000,000, about 500 to about 6,000,000 , about 500 to about 5,000,000, about 500 to about 4,000,000, about 500 to about 3,000,000, about 500 to about 2,000,000, about 500 to about 1,000,000, about 500 to about 800,000, about 500 to about 600,000, about 500 to about 40 0,000, about 500 to about 200,000, about 500 to about 100,000, about 500 to about 80,000, about 500 to about 75,000, about 500 to about 70,000, about 500 to about 65,000, about 500 to about 60,000, about 500 to about 55,000, about 500 to about 50,000, about 500 to about 45,000, about 500 to about 40,000, about 500 to about 35,000, about 500 to about 30,000, about 500 to about 25,000, about 500 to about 20,000, about 500 to about 15,000, about 500 to about 10,000, about 50 0 to about 7,500, about 500 to about 5,000, about 500 to about 4,000, about 500 to about 3,000, about 500 to about 2,000, about 500 to about 1,000, about 1,000 to about 10,000,000, about 1,000 to about 9,000,000, about 1,000 to about 8,000 00,000, about 1,000 to about 7,000,000, about 1,000 to about 6,000,000, about 1,000 to about 5,000,000, about 1,000 to about 4,000,000, about 1,000 to about 3,000,000, about 1,000 to about 2,000,000, about 1,000 to about 1,000,000, about 1,000 to about 800,000, about 1,000 to about 600,000, about 1,000 to about 400,000, about 1,000 to about 200,000, about 1,000 to about 100,000, about 1,000 to about 80,000, about 1,000 to About 75,000, about 1,000 to about 70,000, about 1,000 to about 65,000, about 1,000 to about 60,000, about 1,000 to about 55,000, about 1,000 to about 50,000, about 1,000 to about 45,000, about 1,000 to about 40,000, about 1, 000 to about 35,000, about 1,000 to about 30,000, about 1,000 to about 25,000, about 1,000 to about 20,000, about 1,000 to about 15,000, about 1,000 to about 10,000, about 1,000 to about 7,500, about 1,000 to about 5,000, about 1,000 to about 4,000, about 1,000 to about 3,000, about 1,000 to about 2,000, about 2,000 to about 10,000,000, about 2,000 to about 9,000,000, about 2,000 to about 8,000,000, about 2,000 to about 7,000,000, about 2,000 to about 8,000,000 00 to about 6,000,000, about 2,000 to about 5,000,000, about 2,000 to about 4,000,000, about 2,000 to about 3,000,000, about 2,000 to about 2,000,000, about 2,000 to about 1,000,000, about 2,000 to about 800,000 0, about 2,000 to about 600,000, about 2,000 to about 400,000, about 2,000 to about 200,000, about 2,000 to about 100,000, about 2,000 to about 80,000, about 2,000 to about 75,000, about 2,000 to about 70,000, about 2,000 ~ about 65,000, about 2,000 to about 60,000, about 2,000 to about 55,000, about 2,000 to about 50,000, about 2,000 to about 45,000, about 2,000 to about 40,000, about 2,000 to about 35,000, about 2,000 to about 30,000, about 2 ,000 to about 25,000, about 2,000 to about 20,000, about 2,000 to about 15,000, about 2,000 to about 10,000, about 2,000 to about 7,500, about 2,000 to about 5,000, about 2,000 to about 4,000, about 2,000 to about 3,000, about 3,000 to about 10,000,000, about 3,000 to about 9,000,000, about 3,000 to about 8,000,000, about 3,000 to about 7,000,000, about 3,000 to about 6,000,000, about 3,000 to about 5,000,000, about 3,000 to about 4,000 0,000, about 3,000 to about 3,000,000, about 3,000 to about 2,000,000, about 3,000 to about 1,000,000, about 3,000 to about 800,000, about 3,000 to about 600,000, about 3,000 to about 400,000, about 3,000 to about 20 0,000, about 3,000 to about 100,000, about 3,000 to about 80,000, about 3,000 to about 75,000, about 3,000 to about 70,000, about 3,000 to about 65,000, about 3,000 to about 60,000, about 3,000 to about 55,000, about 3,0 00~about 50,000, about 3,000~about 45,000, about 3,000~about 40,000, about 3,000~about 35,000, about 3,000~about 30,000, about 3,000~about 25,000, about 3,000~about 20,000, about 3,000~about 15,000, about 3,000 to about 10,000, about 3,000 to about 7,500, about 3,000 to about 5,000, about 3,000 to about 4,000, about 4,000 to about 10,000,000, about 4,000 to about 9,000,000, about 4,000 to about 8,000,000, about 4,000 to about 7,000,000, about 4,000 to about 6,000,000, about 4,000 to about 5,000,000, about 4,000 to about 4,000,000, about 4,000 to about 3,000,000, about 4,000 to about 2,000,000, about 4,000 to about 1,000,000 , about 4,000 to about 800,000, about 4,000 to about 600,000, about 4,000 to about 400,000, about 4,000 to about 200,000, about 4,000 to about 100,000, about 4,000 to about 80,000, about 4,000 to about 75,000, about 4,000 ~ about 70,000, about 4,000 to about 65,000, about 4,000 to about 60,000, about 4,000 to about 55,000, about 4,000 to about 50,000, about 4,000 to about 45,000, about 4,000 to about 40,000, about 4,000 to about 35,000, about 4,000 to about 30,000, about 4,000 to about 25,000, about 4,000 to about 20,000, about 4,000 to about 15,000, about 4,000 to about 10,000, about 4,000 to about 7,500, about 4,000 to about 5,000, about 5,000 to about 10,000,000, about 5,000 to about 9,000,000, about 5,000 to about 8,000,000, about 5,000 to about 7,000,000, about 5,000 to about 6,000,000, about 5,000 to about 5,000,000 00, about 5,000 to about 4,000,000, about 5,000 to about 3,000,000, about 5,000 to about 2,000,000, about 5,000 to about 1,000,000, about 5,000 to about 800,000, about 5,000 to about 600,000, about 5,000 to about 400,000, about 5,000 to about 200,000, about 5,000 to about 100,000, about 5,000 to about 80,000, about 5,000 to about 75,000, about 5,000 to about 70,000, about 5,000, 00~about 65,000, about 5,000~about 60,000, about 5,000~about 55,000, about 5,000~about 50,000, about 5,000~about 45,000, about 5,000~about 40,000, about 5,000~about 35,000, about 5,000~about 30,000, About 5,000 to about 25,000, about 5,000 to about 20,000, about 5,000 to about 15,000, about 5,000 to about 10,000, about 5,000 to about 7,500, about 7,500 to about 10,000,000, about 7,500 to about 9,000,000, about 7,500 to about 8,000,000, about 7,500 to about 7,000,000, about 7,500 to about 6,000,000, about 7,500 to about 5,000,000, about 7,500 to about 4,000,000, about 7,500 to about 3,000,000, about 7,500 to about 2,000,000 0, about 7,500 to about 1,000,000, about 7,500 to about 800,000, about 7,500 to about 600,000, about 7,500 to about 400,000, about 7,500 to about 200,000, about 7,500 to about 100,000, about 7,500 to about 80,000, about 7 ,500~about 75,000, about 7,500~about 70,000, about 7,500~about 65,000, about 7,500~about 60,000, about 7,500~about 55,000, about 7,500~about 50,000, about 7,500~about 45,000, about 7,500~about 40,000 , about 7,500 to about 35,000, about 7,500 to about 30,000, about 7,500 to about 25,000, about 7,500 to about 20,000, about 7,500 to about 15,000, about 7,500 to about 10,000, about 10,000 to about 10,000,000, about 10,000 to about 9,000,000, about 10,000 to about 8,000,000, about 10,000 to about 7,000,000, about 10,000 to about 6,000,000, about 10,000 to about 5,000,000, about 10,000 to about 4,000,000, about 10,000 to about 3, 000,000, about 10,000 to about 2,000,000, about 10,000 to about 1,000,000, about 10,000 to about 800,000, about 10,000 to about 600,000, about 10,000 to about 400,000, about 10,000 to about 200,000, about 10,000 to about 100,000, about 10,000 to about 80,000, about 10,000 to about 75,000, about 10,000 to about 70,000, about 10,000 to about 65,000, about 10,000 to about 60,000, about 10,000 to about 55,000, about 10,000 to About 50,000, about 10,000 to about 45,000, about 10,000 to about 40,000, about 10,000 to about 35,000, about 10,000 to about 30,000, about 10,000 to about 25,000, about 10,000 to about 20,000, about 10,000 to about 15,000 0, about 15,000 to about 10,000,000, about 15,000 to about 9,000,000, about 15,000 to about 8,000,000, about 15,000 to about 7,000,000, about 15,000 to about 6,000,000, about 15,000 to about 5,000,000, About 15,000 to about 4,000,000, about 15,000 to about 3,000,000, about 15,000 to about 2,000,000, about 15,000 to about 1,000,000, about 15,000 to about 800,000, about 15,000 to about 600,000, about 15,000 to about 400,000, about 15,000 to about 200,000, about 15,000 to about 100,000, about 15,000 to about 80,000, about 15,000 to about 75,000, about 15,000 to about 70,000, about 15,000 to about 65,000, about 15,000 to about 60 ,000, about 15,000 to about 55,000, about 15,000 to about 50,000, about 15,000 to about 45,000, about 15,000 to about 40,000, about 15,000 to about 35,000, about 15,000 to about 30,000, about 15,000 to about 25,000, About 15,000 to about 20,000, about 20,000 to about 10,000,000, about 20,000 to about 9,000,000, about 20,000 to about 8,000,000, about 20,000 to about 7,000,000, about 20,000 to about 6,000,000, about 20,000 0 to about 5,000,000, about 20,000 to about 4,000,000, about 20,000 to about 3,000,000, about 20,000 to about 2,000,000, about 20,000 to about 1,000,000, about 20,000 to about 800,000, about 20,000 to about 600,000, about 20,000 to about 400,000, about 20,000 to about 200,000, about 20,000 to about 100,000, about 20,000 to about 80,000, about 20,000 to about 75,000, about 20,000 to about 70,000, about 20,000 to about 65,000 , about 210,000 to about 60,000, about 20,000 to about 55,000, about 20,000 to about 50,000, about 20,000 to about 45,000, about 20,000 to about 40,000, about 20,000 to about 35,000, about 20,000 to about 30,000, about 20 ,000 to about 25,000, about 25,000 to about 10,000,000, about 25,000 to about 9,000,000, about 25,000 to about 8,000,000, about 25,000 to about 7,000,000, about 25,000 to about 6,000,000, about 25,000 to about 5 ,000,000, about 25,000 to about 4,000,000, about 25,000 to about 3,000,000, about 25,000 to about 2,000,000, about 25,000 to about 1,000,000, about 25,000 to about 800,000, about 25,000 to about 600,000 , about 25,000 to about 400,000, about 25,000 to about 200,000, about 25,000 to about 100,000, about 25,000 to about 80,000, about 25,000 to about 75,000, about 25,000 to about 70,000, about 25,000 to about 65,000, about 2 5,000 to about 60,000, about 25,000 to about 55,000, about 25,000 to about 50,000, about 25,000 to about 45,000, about 25,000 to about 40,000, about 25,000 to about 35,000, about 25,000 to about 30,000, about 30,000 to About 10,000,000, about 30,000 to about 9,000,000, about 30,000 to about 8,000,000, about 30,000 to about 7,000,000, about 30,000 to about 6,000,000, about 30,000 to about 5,000,000, about 30,000 to about 4,0 00,000, about 30,000 to about 3,000,000, about 30,000 to about 2,000,000, about 30,000 to about 1,000,000, about 30,000 to about 800,000, about 30,000 to about 600,000, about 30,000 to about 400,000, about 30,000 to about 300,000, about 30,000 to about 200,000, about 30,000 to about 100,000, about 30,000 to about 80,000, about 30,000 to about 75,000, about 30,000 to about 70,000, about 30,000 to about 65,000, about 30,000 0 to about 60,000, about 30,000 to about 55,000, about 30,000 to about 50,000, about 30,000 to about 45,000, about 30,000 to about 40,000, about 30,000 to about 35,000, about 35,000 to about 10,000,000, about 35,000 to about 9,000,000, about 35,000 to about 8,000,000, about 35,000 to about 7,000,000, about 35,000 to about 6,000,000, about 35,000 to about 5,000,000, about 35,000 to about 4,000,000, about 35,000 to about 3, 000,000, about 35,000 to about 2,000,000, about 35,000 to about 1,000,000, about 35,000 to about 800,000, about 35,000 to about 600,000, about 35,000 to about 400,000, about 35,000 to about 300,000, about 35, 000 to about 200,000, about 35,000 to about 100,000, about 35,000 to about 80,000, about 35,000 to about 75,000, about 35,000 to about 70,000, about 35,000 to about 65,000, about 35,000 to about 60,000, about 35,000 ~ about 55,000, about 35,000 to about 50,000, about 35,000 to about 45,000, about 35,000 to about 40,000, about 40,000 to about 10,000,000, about 40,000 to about 9,000,000, about 40,000 to about 8,000,000, about 4 0,000 to about 7,000,000, about 40,000 to about 6,000,000, about 40,000 to about 5,000,000, about 40,000 to about 4,000,000, about 40,000 to about 3,000,000, about 40,000 to about 2,000,000, about 40,000 0 to about 1,000,000, about 40,000 to about 800,000, about 40,000 to about 600,000, about 40,000 to about 400,000, about 40,000 to about 200,000, about 40,000 to about 100,000, about 40,000 to about 80,000, about 40,000 to about 75,000, about 40,000 to about 70,000, about 40,000 to about 65,000, about 40,000 to about 60,000, about 40,000 to about 55,000, about 40,000 to about 50,000, about 40,000 to about 45,000, about 45,000 to about 10,000,000, about 45,000 to about 9,000,000, about 45,000 to about 8,000,000, about 45,000 to about 7,000,000, about 45,000 to about 6,000,000, about 45,000 to about 5,000,000, about 45,000 to about 4,0 00,000, about 45,000 to about 3,000,000, about 45,000 to about 2,000,000, about 45,000 to about 1,000,000, about 45,000 to about 800,000, about 45,000 to about 600,000, about 45,000 to about 400,000, about 4 5,000 to about 200,000, about 45,000 to about 100,000, about 45,000 to about 80,000, about 45,000 to about 75,000, about 45,000 to about 70,000, about 45,000 to about 65,000, about 45,000 to about 60,000, about 45,000 00 to about 55,000, about 45,000 to about 50,000, about 50,000 to about 10,000,000, about 50,000 to about 9,000,000, about 50,000 to about 8,000,000, about 50,000 to about 7,000,000, about 50,000 to about 6,000 ,000, about 50,000 to about 5,000,000, about 50,000 to about 4,000,000, about 50,000 to about 3,000,000, about 50,000 to about 2,000,000, about 50,000 to about 1,000,000, about 50,000 to about 800,000, About 50,000 to about 600,000, about 50,000 to about 400,000, about 50,000 to about 200,000, about 50,000 to about 100,000, about 50,000 to about 80,000, about 50,000 to about 75,000, about 50,000 to about 70,000, about 50,000 to about 65,000, about 50,000 to about 60,000, about 50,000 to about 55,000, about 55,000 to 10,000,000, about 55,000 to about 9,000,000, about 55,000 to about 8,000,000, about 55,000 to about 7,000,000, about 55,000 to about 6,000,000, about 55,000 to about 5,000,000, about 55,000 to about 4,000,000, about 55,000 to about 3,000,000, about 55,000 to about 2,000,000, about 55,000 to about 1,000,000, About 55,000 to about 800,000, about 55,000 to about 600,000, about 55,000 to about 400,000, about 55,000 to about 200,000, about 55,000 to about 100,000, about 55,000 to about 80,000, about 55,000 to about 75,000, about 5 5,000 to about 70,000, about 55,000 to about 65,000, about 55,000 to about 60,000, about 60,000 to about 10,000,000, about 60,000 to about 9,000,000, about 60,000 to about 8,000,000, about 60,000 to about 7,000, 000, about 60,000 to about 6,000,000, about 60,000 to about 5,000,000, about 60,000 to about 4,000,000, about 60,000 to about 3,000,000, about 60,000 to about 2,000,000, about 60,000 to about 1,000,000, About 60,000 to about 800,000, about 60,000 to about 600,000, about 60,000 to about 400,000, about 60,000 to about 200,000, about 60,000 to about 100,000, about 60,000 to about 80,000, about 60,000 to about 75,000, about 60,000 to about 70,000, about 60,000 to about 65,000, about 65,000 to about 10,000,000, about 65,000 to about 9,000,000, about 65,000 to about 8,000,000, about 65,000 to about 7,000,000, about 65,000 to about 6, 000,000, about 65,000 to about 5,000,000, about 65,000 to about 4,000,000, about 65,000 to about 3,000,000, about 65,000 to about 2,000,000, about 65,000 to about 1,000,000, about 65,000 to about 800,000 , about 65,000 to about 600,000, about 65,000 to about 400,000, about 65,000 to about 200,000, about 65,000 to about 100,000, about 65,000 to about 80,000, about 65,000 to about 75,000, about 65,000 to about 70,000, About 70,000 to about 10,000,000, about 70,000 to about 9,000,000, about 70,000 to about 8,000,000, about 70,000 to about 7,000,000, about 70,000 to about 6,000,000, about 70,000 to about 5,000,000, about 70, 000 to about 4,000,000, about 70,000 to about 3,000,000, about 70,000 to about 2,000,000, about 70,000 to about 1,000,000, about 70,000 to about 800,000, about 70,000 to about 600,000, about 70,000 to about 400, 000, about 70,000 to about 200,000, about 70,000 to about 100,000, about 70,000 to about 90,000, about 70,000 to about 80,000, about 80,000 to about 10,000,000, about 80,000 to about 9,000,000, about 80,000 to about 8,000,000, about 80,000 to about 7,000,000, about 80,000 to about 6,000,000, about 80,000 to about 5,000,000, about 80,000 to about 4,000,000, about 80,000 to about 3,000,000, about 80,000 to about 2,000,000, about 80,000 to about 1,000,000, about 80,000 to about 800,000, about 80,000 to about 600,000, about 80,000 to about 400,000, about 80,000 to about 200,000, about 80,000 to about 100,000, about 80,000 to about 90,000, about 90,000 to about 10,000,000, about 90,000 to about 9,000,000, about 90,000 to about 8,000,000, about 90,000 to about 7,000,000, about 90,000 to about 6,000,000, about 90,000 to about 5,000, 000, about 90,000 to about 4,000,000, about 90,000 to about 3,000,000, about 90,000 to about 2,000,000, about 90,000 to about 1,000,000, about 90,000 to about 800,000, about 90,000 to about 600,000, about 90 ,000 to about 400,000, about 90,000 to about 200,000, about 90,000 to about 100,000, about 100,000 to about 10,000,000, about 100,000 to about 9,000,000, about 100,000 to about 8,000,000, about 100,000 to about 7,000,000, about 100,000 to about 6,000,000, about 100,000 to about 5,000,000, about 100,000 to about 4,000,000, about 100,000 to about 3,000,000, about 100,000 to about 2,000,000, about 100,000 to about 1,000,000, about 100,000 to about 800,000, about 100,000 to about 600,000, about 100,000 to about 400,000, about 100,000 to about 200,000, about 200,000 to about 10,000,000, about 200,000 to about 9,000 0,000, about 200,000 to about 8,000,000, about 200,000 to about 7,000,000, about 200,000 to about 6,000,000, about 200,000 to about 5,000,000, about 200,000 to about 4,000,000, about 200,000 to about 3, 000,000, about 200,000 to about 2,000,000, about 200,000 to about 1,000,000, about 200,000 to about 800,000, about 200,000 to about 600,000, about 200,000 to about 400,000, about 400,000 to about 10,000,000, about 400,000 to about 9,000,000, about 400,000 to about 8,000,000, about 400,000 to about 7,000,000, about 400,000 to about 6,000,000, about 400,000 to about 5,000,000, about 400,000 to about 4,000 ,000, about 400,000 to about 3,000,000, about 400,000 to about 2,000,000, about 400,000 to about 1,000,000, about 400,000 to about 800,000, about 400,000 to about 600,000, about 600,000 to about 10,000,0 00, about 600,000 to about 9,000,000, about 600,000 to about 8,000,000, about 600,000 to about 7,000,000, about 600,000 to about 6,000,000, about 600,000 to about 5,000,000, about 600,000 to about 4,000, 000, about 600,000 to about 3,000,000, about 600,000 to about 2,000,000, about 600,000 to about 1,000,000, about 600,000 to about 800,000, about 800,000 to about 10,000,000, about 800,000 to about 9,000, 000, about 800,000 to about 8,000,000, about 800,000 to about 7,000,000, about 800,000 to about 6,000,000, about 800,000 to about 5,000,000, about 800,000 to about 4,000,000, about 800,000 to about 3,000 ,000, about 800,000 to about 2,000,000, about 800,000 to about 1,000,000, about 1,000,000 to about 10,000,000, about 1,000,000 to about 9,000,000, about 1,000,000 to about 8,000,000, about 1,000, 000 to about 7,000,000, about 1,000,000 to about 6,000,000, about 1,000,000 to about 5,000,000, about 1,000,000 to about 4,000,000, about 1,000,000 to about 3,000,000, about 1,000,000 to about 2,000 ,000, about 2,000,000 to about 10,000,000, about 2,000,000 to about 9,000,000, about 2,000,000 to about 8,000,000, about 2,000,000 to about 7,000,000, about 2,000,000 to about 6,000,000, about 2,000,000 to about 5,000,000 pieces, about 2,000,000 to about 4,000,000 pieces, about 2,000,000 to about 3,000,000 pieces, about 3,000,000 to about 10,000,000 pieces, about 3,0 00,000 to about 9,000,000 pieces, about 3,000,000 to about 8,000,000 pieces, about 3,000,000 to about 7,000,000 pieces, about 3,000,000 to about 6,000,000 pieces, about 3,000, 000 to about 5,000,000 pieces, about 3,000,000 to about 4,000,000, about 4,000,000 to about 10,000,000 pieces, about 4,000,000 to about 9,000,000 pieces, about 4,000,000 ~about 8,000,000 pieces, about 4,000,000~about 7,000,000 pieces, about 4,000,000~about 6,000,000 pieces, about 4,000,000~about 5,000,000 pieces, about 5,000,000~approx. 10,000,000 pieces, about 5,000,000 to about 9,000,000 pieces, about 5,000,000 to about 8,000,000 pieces, about 5,000,000 to about 7,000,000 pieces, about 5,00 0,000~6,000,000 pieces, 6,000,000~10,000,000 pieces, 6,000,000~9,000,000 pieces, 6,000,000~8,000,000 pieces , about 6,000,000 to about 7,000,000, about 7,000,000 to about 10,000,000, about 7,000,000 to about 9,000,000, about 7,000,000 to about 8,000,000, about 8,000,000 to about 10,000,000, about 8,000,000 to about 9,000,000, or about 9,000,000 to about 10,000,000.

[0078] The phrase "antigen density" refers to the number of LRRC15 present on the surface of a target mammalian cell, or the average number of LRRC15 on the surface of a population of target mammalian cells of a particular type, which can be measured, for example, using a Quantibright bead kit or radiolabeling (e.g., BD Biosciences PE Phycoerythrin Fluorescence Quantitation Kit, catalog number 340495).

[0079] The phrase "amino acid substituted with histidine" refers to the substitution of a non-histidine amino acid residue in a reference polypeptide sequence with histidine. Non-limiting methods for substituting an amino acid residue in a reference polypeptide with histidine are described herein. Additional methods for substituting an amino acid residue in a reference polypeptide with histidine are known in the art.

[0080] The phrase "amino acid substituted with alanine" refers to the substitution of an amino acid residue that is a histidine in a reference polypeptide sequence with alanine. Non-limiting methods for substituting alanine for histidine in a reference polypeptide are described herein. Additional methods for substituting alanine for a histidine in a reference polypeptide are known in the art.

[0081] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this invention belongs. Methods and materials for use in the present invention are described herein; other suitable methods and materials known in the art may also be used. The materials, methods, and examples are illustrative only and are not intended to be limiting. All publications, patent applications, patents, sequences, database entries, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. [Effects of the Invention]

[0082] Other features and advantages of the invention will become apparent from the following detailed description and figures, and from the claims. [Brief explanation of the drawings]

[0083] [Figure 1]SDS-PAGE analysis of histidine-scanning and alanine-scanning variants of samuratamab. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of samuratamab and its histidine-scanning and alanine-scanning variants. The arrows indicate the size corresponding to IgG on the non-reducing SDS-PAGE gel. MYT0963 represents samuratamab, and the remaining lanes (MYT0964-MYT1003) represent histidine-scanning and alanine-scanning variants of the heavy chain of samuratamab. [Figure 2A] Binding of SAMROTAMAB-starting ABPC and histidine-scanning and alanine-scanning variants to LRRC15 by biolayer interferometry. MYT0963 (SAMROTAMAB) and MYT0964-MYT1003 heavy chain histidine-scanning and alanine-scanning variants were captured on an anti-human Fc biosensor and allowed to bind to LRRC15 at low or high pH, ​​as indicated in the figure. [Figure 2B] Same as above [Figure 2C] Same as above [Figure 2D] Same as above [Figure 2E] Same as above [Figure 2F] Same as above [Figure 2G] Same as above [Figure 2H] Same as above [Figure 2I] Same as above [Figure 2J] Same as above [Figure 2K] Same as above [Figure 2L] Same as above [Figure 2M] Same as above [Figure 2N] Same as above [Figure 2O] Same as above [Figure 2P] Same as above [Figure 2Q] Same as above [Figure 2R] Same as above [Figure 2S] Same as above [Figure 2T] Same as above [Figure 2U] Same as above [Figure 2V] Same as above [Figure 2W] Same as above [Figure 2X] Same as above [Figure 2Y] Same as above [Figure 2Z] Same as above [Figure 2AA] Same as above [Figure 2AB] Same as above [Figure 2AC] Same as above [Figure 2AD] Same as above [Figure 2AE] Same as above [Figure 2AF] Same as above [Figure 2AG] Same as above [Figure 2AH] Same as above [Figure 2AI] Same as above [Figure 2AJ] Same as above [Figure 2AK] Same as above [Figure 2AL] Same as above [Figure 2AM] Same as above [Figure 2AN] Same as above [Figure 2AO] Same as above [Figure 3] 1 is a table corresponding construct identifiers to SEQ ID NOs. Construct heavy chain histidine-scanning and alanine-scanning variants are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 4]SDS-PAGE analysis of histidine-scanning and alanine-scanning variants of samarotamab. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of samarotamab and its histidine-scanning and alanine-scanning variants. The arrows indicate the size corresponding to IgG on the non-reducing SDS-PAGE gel. MYT2726 to MYT2752 are histidine-scanning and alanine-scanning variants of the light chain of samarotamab. [Figure 5A] Binding of SAMROTAMAB starting ABPC and histidine-scanning and alanine-scanning variants to LRRC15 by biolayer interferometry. Light chain histidine-scanning and alanine-scanning variants of SAMROTAMAB, MYT2726-MYT2752, were captured on an anti-human Fc biosensor and allowed to bind to LRRC15 at low or high pH, ​​as indicated in the figure. [Figure 5B] Same as above [Figure 5C] Same as above [Figure 5D] Same as above [Figure 5E] Same as above [Figure 5F] Same as above [Figure 5G] Same as above [Figure 5H] Same as above [Figure 5I] Same as above [Figure 5J] Same as above [Figure 5K] Same as above [Figure 5L] Same as above [Figure 5M] Same as above [Figure 5N] Same as above [Figure 5O] Same as above [Figure 5P] Same as above [Figure 5Q] Same as above [Figure 5R] Same as above [Figure 5S] Same as above [Figure 5T] Same as above [Figure 5U] Same as above [Figure 5V] Same as above [Figure 5W] Same as above [Figure 5X] Same as above [Figure 5Y] Same as above [Figure 5Z] Same as above [Figure 5AA] Same as above [Figure 6] 1 is a table of construct identifiers corresponding to SEQ ID NOs. Constructs, histidine-scanning and alanine-scanning variants of the light chain, are listed in the first column of the table, with SEQ ID NOs listed and corresponding for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 7] SDS-PAGE analysis of histidine-scanning and alanine-scanning variants of samarotamab. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of samarotamab histidine-scanning and alanine-scanning variants. The arrows indicate the size corresponding to IgG on the non-reducing SDS-PAGE gel. MYT2722 to MYT2725 are histidine-scanning and alanine-scanning variants of the heavy chain combination of samarotamab. [Figure 8A] Binding of histidine-scanning and alanine-scanning variants of SAMROTAMAB to LRRC15 by biolayer interferometry. Histidine-scanning and alanine-scanning variants of the heavy chain combination of SAMROTAMAB, MYT2722-MYT2725, were captured on an anti-human Fc biosensor and allowed to bind to LRRC15 at low or high pH, ​​as indicated in the figure. [Figure 8B] Same as above [Figure 8C] Same as above [Figure 8D] Same as above [Figure 9]1 is a table corresponding to construct identifiers with SEQ ID NOs. Constructs, histidine-scanning and alanine-scanning variants of heavy chain combinations are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 10] SDS-PAGE of hu139.10 histidine-scanning and alanine-scanning variants. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of hu139.10 and its histidine-scanning and alanine-scanning variants. The arrows indicate the size corresponding to the IgG on the non-reducing SDS-PAGE gel. MYT3252 represents hu139.10, and the remaining lanes (MYT3253-MYT3292) represent hu139.10 heavy chain histidine-scanning and alanine-scanning variants. [Figure 11A] Binding of hu139.10 starting ABPC and histidine-scanning and alanine-scanning variants to LRRC15 by biolayer interferometry. MYT3252 (hu139.10) and MYT3253-MYT3292, histidine-scanning and alanine-scanning variants of the heavy chain of hu139.10, were captured on an anti-human Fc biosensor and allowed to bind to LRRC15 at low or high pH, ​​as indicated. [Figure 11B] Same as above [Figure 11C] Same as above [Figure 11D] Same as above [Figure 11E] Same as above [Figure 11F] Same as above [Figure 11G] Same as above [Figure 11H] Same as above [Figure 11I] Same as above [Figure 11J] Same as above [Figure 11K] Same as above [Figure 11L] Same as above [Figure 11M] Same as above [Figure 11N] Same as above [Figure 11O] Same as above [Figure 11P] Same as above [Figure 11Q] Same as above [Figure 11R] Same as above [Figure 11S] Same as above [Figure 11T] Same as above [Figure 11U] Same as above [Figure 11V] Same as above [Figure 11W] Same as above [Figure 11X] Same as above [Figure 11Y] Same as above [Figure 11Z] Same as above [Figure 11AA] Same as above [Figure 11AB] Same as above [Figure 11AC] Same as above [Figure 11AD] Same as above [Figure 11AE] Same as above [Figure 11AF] Same as above [Figure 11AG] Same as above [Figure 11AH] Same as above [Figure 11AI] Same as above [Figure 11AJ] Same as above [Figure 11AK] Same as above [Figure 11AL] Same as above [Figure 11AM] Same as above [Figure 11AN] Same as above [Figure 11AO] Same as above [Figure 12] 1 is a table corresponding construct identifiers to SEQ ID NOs. Construct heavy chain histidine-scanning and alanine-scanning variants are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 13]SDS-PAGE of hu139.10 histidine-scanning and alanine-scanning variants. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of hu139.10 and its histidine-scanning and alanine-scanning variants. Arrows indicate the size corresponding to IgG on the non-reducing SDS-PAGE gel. MYT3293 to MYT3324 are hu139.10 light chain histidine-scanning and alanine-scanning variants. [Figure 14A] Binding of hu139.10 starting ABPC and histidine-scanning and alanine-scanning variants to LRRC15 by biolayer interferometry. Histidine-scanning and alanine-scanning variants of the light chain of hu139.10, MYT3293-MYT3324, were captured on an anti-human Fc biosensor and allowed to bind to LRRC15 at low or high pH, ​​as indicated in the figure. [Figure 14B] Same as above [Figure 14C] Same as above [Figure 14D] Same as above [Figure 14E] Same as above [Figure 14F] Same as above [Figure 14G] Same as above [Figure 14H] Same as above [Figure 14I] Same as above [Figure 14J] Same as above [Figure 14K] Same as above [Figure 14L] Same as above [Figure 14M] Same as above [Figure 14N] Same as above [Figure 14O] Same as above [Figure 14P] Same as above [Figure 14Q] Same as above [Figure 14R] Same as above [Figure 14S] Same as above [Figure 14T] Same as above [Figure 14U] Same as above [Figure 14V] Same as above [Figure 14W] Same as above [Figure 14X] Same as above [Figure 14Y] Same as above [Figure 14Z] Same as above [Figure 14AA] Same as above [Figure 14AB] Same as above [Figure 14AC] Same as above [Figure 14AD] Same as above [Figure 14AE] Same as above [Figure 14AF] Same as above [Figure 15] 1 is a table of construct identifiers corresponding to SEQ ID NOs. Constructs, histidine-scanning and alanine-scanning variants of the light chain, are listed in the first column of the table, with SEQ ID NOs listed and corresponding for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 16] SDS-PAGE of hu139.10 histidine-scanning and alanine-scanning variants. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of hu139.10 histidine-scanning and alanine-scanning variants. The arrows indicate the size corresponding to the IgG on the non-reducing SDS-PAGE gel. MYT4161 to MYT4164 are histidine-scanning and alanine-scanning variants of the hu139.10 heavy chain combination. [Figure 17A] Binding of histidine-scanning and alanine-scanning variants of hu139.10 to LRRC15 by biolayer interferometry. Histidine-scanning and alanine-scanning variants of heavy chain combinations MYT4161-MYT4164 were captured on an anti-human Fc biosensor and allowed to bind to LRRC15 at low or high pH, ​​as indicated. [Figure 17B] Same as above [Figure 17C] Same as above [Figure 17D] Same as above [Figure 18] 1 is a table corresponding to construct identifiers with SEQ ID NOs. Constructs, histidine-scanning and alanine-scanning variants of heavy chain combinations are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 19] SDS-PAGE of hu139.10 histidine-scanning and alanine-scanning variants. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of hu139.10 histidine-scanning and alanine-scanning variants. The arrows indicate the size corresponding to IgG on the non-reducing SDS-PAGE gel. MYT4165–MYT4174 are histidine-scanning and alanine-scanning variants of the hu139.10 light chain combination. [Figure 20A] Binding of histidine-scanning and alanine-scanning variants of hu139.10 to LRRC15 by biolayer interferometry. Histidine-scanning and alanine-scanning variants of the light chain combinations MYT4165-MYT4174 were captured on an anti-human Fc biosensor and allowed to bind to LRRC15 at low or high pH, ​​as indicated. [Figure 20B] Same as above [Figure 20C] Same as above [Figure 20D] Same as above [Figure 20E] Same as above [Figure 20F] Same as above [Figure 20G] Same as above [Figure 20H] Same as above [Figure 20I] Same as above [Figure 20J] Same as above [Figure 21]1 is a table corresponding to construct identifiers with SEQ ID NOs. Constructs, histidine-scanning and alanine-scanning variants of light chain combinations are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 22] SDS-PAGE of huAD208.4.1 histidine-scanning and alanine-scanning variants. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of huAD208.4.1 and its histidine-scanning and alanine-scanning variants. The arrows indicate the size corresponding to the IgG on the non-reducing SDS-PAGE gel. MYT3325 represents huAD208.4.1, and the remaining lanes (MYT3326-MYT3367) represent huAD208.4.1 heavy chain histidine-scanning and alanine-scanning variants. [Figure 23A] Binding of huAD208.4.1 starting ABPC and histidine-scanning and alanine-scanning variants to LRRC15 by biolayer interferometry. MYT3325 (huAD208.4.1) and MYT3326-MYT3367 heavy chain histidine-scanning and alanine-scanning variants were captured on an anti-human Fc biosensor and allowed to bind to LRRC15 at low or high pH, ​​as indicated in the figure. [Figure 23B] Same as above [Figure 23C] Same as above [Figure 23D] Same as above [Figure 23E] Same as above [Figure 23F] Same as above [Figure 23G] Same as above [Figure 23H] Same as above [Figure 23I] Same as above [Figure 23J] Same as above [Figure 23K] Same as above [Figure 23L] Same as above [Figure 23M] Same as above [Figure 23N] Same as above [Figure 23O] Same as above [Figure 23P] Same as above [Figure 23Q] Same as above [Figure 23R] Same as above [Figure 23S] Same as above [Figure 23T] Same as above [Figure 23U] Same as above [Figure 23V] Same as above [Figure 23W] Same as above [Figure 23X] Same as above [Figure 23Y] Same as above [Figure 23Z] Same as above [Figure 23AA] Same as above [Figure 23AB] Same as above [Figure 23AC] Same as above [Figure 23AD] Same as above [Figure 23AE] Same as above [Figure 23AF] Same as above [Figure 23AG] Same as above [Figure 23AH] Same as above [Figure 23AI] Same as above [Figure 23AJ] Same as above [Figure 23AK] Same as above [Figure 23AL] Same as above [Figure 23AM] Same as above [Figure 23AN] Same as above [Figure 23AO] Same as above [Figure 23AP] Same as above [Figure 23AQ] Same as above [Figure 24] 1 is a table corresponding construct identifiers to SEQ ID NOs. Construct heavy chain histidine-scanning and alanine-scanning variants are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 25] SDS-PAGE of huAD208.4.1 histidine-scanning and alanine-scanning variants. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of huAD208.4.1 and its histidine-scanning and alanine-scanning variants. Arrows indicate the size corresponding to IgG on the non-reducing SDS-PAGE gel. MYT3369 to MYT3398 are huAD208.4.1 light chain histidine-scanning and alanine-scanning variants. [Figure 26A] Binding of huAD208.4.1 starting ABPC and histidine-scanning and alanine-scanning variants to LRRC15 by biolayer interferometry. Histidine-scanning and alanine-scanning variants of the light chain of huAD208.4.1, MYT3369-MYT3398, were captured on an anti-human Fc biosensor and allowed to bind to LRRC15 at low or high pH, ​​as indicated in the figure. [Figure 26B] Same as above [Figure 26C] Same as above [Figure 26D] Same as above [Figure 26E] Same as above [Figure 26F] Same as above [Figure 26G] Same as above [Figure 26H] Same as above [Figure 26I] Same as above [Figure 26J] Same as above [Figure 26K] Same as above [Figure 26L] Same as above [Figure 26M] Same as above [Figure 26N] Same as above [Figure 26O] Same as above [Figure 26P] Same as above [Figure 26Q] Same as above [Figure 26R] Same as above [Figure 26S] Same as above [Figure 26T] Same as above [Figure 26U] Same as above [Figure 26V] Same as above [Figure 26W] Same as above [Figure 26X] Same as above [Figure 26Y] Same as above [Figure 26Z] Same as above [Figure 26AA] Same as above [Figure 26AB] Same as above [Figure 26AC] Same as above [Figure 26AD] Same as above [Figure 27] 1 is a table of construct identifiers corresponding to SEQ ID NOs. Constructs, histidine-scanning and alanine-scanning variants of the light chain, are listed in the first column of the table, with SEQ ID NOs listed and corresponding for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 28] SDS-PAGE of huAD208.4.1 histidine-scanning and alanine-scanning variants. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of huAD208.4.1 histidine-scanning and alanine-scanning variants. The arrows indicate the size corresponding to the IgG on the non-reducing SDS-PAGE gel. MYT4385 and MYT4388 are histidine-scanning and alanine-scanning variants of the huAD208.4.1 heavy chain combination. [Figure 29A] Binding of histidine-scanning and alanine-scanning variants of huAD208.4.1 to LRRC15 by biolayer interferometry. Histidine-scanning and alanine-scanning variants of the huAD208.4.1 heavy chain combination, MYT4385-MYT4388, were captured on an anti-human Fc biosensor and allowed to bind to LRRC15 at low or high pH, ​​as indicated in the figure. [Figure 29B] Same as above [Figure 29C] Same as above [Figure 29D] Same as above [Figure 30] 1 is a table corresponding to construct identifiers with SEQ ID NOs. Constructs, histidine-scanning and alanine-scanning variants of heavy chain combinations are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 31] SDS-PAGE of huAD208.4.1 histidine-scanning and alanine-scanning variants. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of huAD208.4.1 histidine-scanning and alanine-scanning variants. The arrows indicate the size corresponding to IgG on the non-reducing SDS-PAGE gel. MYT4390–MYT4399 are histidine-scanning and alanine-scanning variants of the huAD208.4.1 light chain combination. [Figure 32A] Binding of histidine-scanning and alanine-scanning variants of huAD208.4.1 to LRRC15 by biolayer interferometry. Histidine-scanning and alanine-scanning variants of the huAD208.4.1 light chain combination, MYT4390-MYT4399, were captured on an anti-human Fc biosensor and allowed to bind to LRRC15 at low or high pH, ​​as indicated in the figure. [Figure 32B] Same as above [Figure 32C] Same as above [Figure 32D] Same as above [Figure 32E] Same as above [Figure 32F] Same as above [Figure 32G] Same as above [Figure 32H] Same as above [Figure 32I] Same as above [Figure 32J] Same as above [Figure 33]1 is a table corresponding to construct identifiers with SEQ ID NOs. Constructs, histidine-scanning and alanine-scanning variants of light chain combinations are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 34] SDS-PAGE of huAD208.12.1 histidine-scanning and alanine-scanning variants. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of huAD208.12.1 and its histidine-scanning and alanine-scanning variants. The arrows indicate the size corresponding to the IgG on the non-reducing SDS-PAGE gel. MYT3179 represents huAD208.12.1, and the remaining lanes (MYT4090-MYT4133) represent huAD208.12.1 heavy chain histidine-scanning and alanine-scanning variants. [Figure 35A] Binding of the huAD208.12.1 starting ABPC and histidine-scanning and alanine-scanning variants to LRRC15 by biolayer interferometry. Histidine-scanning and alanine-scanning variants of the heavy chain, MYT3179 (huAD208.12.1) and MYT4090-MYT4133, were captured on an anti-human Fc biosensor and allowed to bind to LRRC15 at pH 7.4. Dissociation occurred at pH 7.4 (black trace) or pH 5.4 (gray trace). [Figure 35B] Same as above [Figure 35C] Same as above [Figure 35D] Same as above [Figure 35E] Same as above [Figure 35F] Same as above [Figure 35G] Same as above [Figure 35H] Same as above [Figure 35I] Same as above [Figure 35J] Same as above [Figure 35K] Same as above [Figure 35L]Same as above [Figure 35M] Same as above [Figure 35N] Same as above [Figure 35O] Same as above [Figure 35P] Same as above [Figure 35Q] Same as above [Figure 35R] Same as above [Figure 35S] Same as above [Figure 35T] Same as above [Figure 35U] Same as above [Figure 35V] Same as above [Figure 35W] Same as above [Figure 35X] Same as above [Figure 35Y] Same as above [Figure 35Z] Same as above [Figure 35AA] Same as above [Figure 35AB] Same as above [Figure 35AC] Same as above [Figure 35AD] Same as above [Figure 35AE] Same as above [Figure 35AF] Same as above [Figure 35AG] Same as above [Figure 35AH] Same as above [Figure 35AI] Same as above [Figure 35AJ] Same as above [Figure 35AK] Same as above [Figure 35AL] Same as above [Figure 35AM] Same as above [Figure 35AN] Same as above [Figure 35AO] Same as above [Figure 35AP] Same as above [Figure 35AQ] Same as above [Figure 35AR] Same as above [Figure 35AS] Same as above [Figure 36]1 is a table corresponding construct identifiers to SEQ ID NOs. Construct heavy chain histidine-scanning and alanine-scanning variants are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 37] SDS-PAGE of huAD208.12.1 histidine-scanning and alanine-scanning variants. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of huAD208.12.1 and its histidine-scanning and alanine-scanning variants. Arrows indicate the size corresponding to IgG on the non-reducing SDS-PAGE gel. MYT4134 to MYT4160 are huAD208.12.1 light chain histidine-scanning and alanine-scanning variants. [Figure 38A] Binding of huAD208.12.1 starting ABPC and histidine-scanning and alanine-scanning variants to LRRC15 by biolayer interferometry. Histidine-scanning and alanine-scanning variants of the light chain of huAD208.12.1, MYT4134-MYT4160, were captured on an anti-human Fc biosensor and allowed to bind to LRRC15 at pH 7.4. Dissociation was at pH 7.4 (black trace) or pH 5.4 (gray trace). [Figure 38B] Same as above [Figure 38C] Same as above [Figure 38D] Same as above [Figure 38E] Same as above [Figure 38F] Same as above [Figure 38G] Same as above [Figure 38H] Same as above [Figure 38I] Same as above [Figure 38J] Same as above [Figure 38K] Same as above [Figure 38L] Same as above [Figure 38M] Same as above [Figure 38N] Same as above [Figure 38O] Same as above [Figure 38P] Same as above [Figure 38Q] Same as above [Figure 38R] Same as above [Figure 38S] Same as above [Figure 38T] Same as above [Figure 38U] Same as above [Figure 38V] Same as above [Figure 38W] Same as above [Figure 38X] Same as above [Figure 38Y] Same as above [Figure 38Z] Same as above [Figure 38AA] Same as above [Figure 39] 1 is a table of construct identifiers corresponding to SEQ ID NOs. Constructs, histidine-scanning and alanine-scanning variants of the light chain, are listed in the first column of the table, with SEQ ID NOs listed and corresponding for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 40A] Figure 40a shows the binding affinity of anti-LRRC15 mAbs. Anti-LRRC15 mAbs were assayed for their binding to U-87 MG (LRRC15+) cells. Figure 40a shows MYT0963 (samrotamab) with an IC50 of 0.228 nM, and Figure 40b shows MYT0971 with an IC50 of 0.484 nM. [Figure 40B] Same as above [Figure 41A] Intracellular uptake of anti-LRRC15 mAb in cells. Anti-LRRC15 pH-engineered antibody variants, the corresponding starting ABPC antibody, a control IgG1 isotype control (BPO297, Bioxcell), and the vehicle control specified in Figure 41 were assayed for intracellular uptake and endolysosomal delivery as measured by mean fluorescence intensity on cells at 25 nM after 24 hours. Error bars, if present, represent standard deviation. Each number above the bar represents the fold change relative to the corresponding starting ABPC. [Figure 41B] Same as above [Figure 41C] Same as above [Figure 41D] Same as above [Figure 41E] Same as above [Figure 41F] Same as above [Figure 41G] Same as above [Figure 42] Figure 1 Melting temperatures of selected anti-LRRC15 mAbs. Selected anti-LRRC15 mAbs were assayed for melting temperatures by differential scanning fluorimetry (DSF), and the resulting Sypro Orange signal was plotted as its first derivative. Melting temperatures (Tm) were calculated as the maximum of this graph and are shown in the table. [Figure 43] SDS PAGE of MYT0766. Purified MYT0766 was loaded onto non-reducing (NR) and reducing (R) SDS PAGE gels to confirm size and purity. The theoretical molecular weight of intact MYT0766 is approximately 109 kDa. DETAILED DESCRIPTION OF THE INVENTION

[0084] Provided herein are antigen-binding protein constructs (ABPCs) and antibodies comprising a first antigen-binding domain capable of specifically binding to LRRC15 or an epitope of LRRC15 present on the surface of a target mammalian cell, wherein (a) the dissociation rate of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is faster than the dissociation rate at a pH of about 7.0 to about 8.0, and / or (b) the dissociation constant (K D ) at pH 7.0 to 8.0 D The antigen binding protein constructs (ABPCs) are provided, which are larger than or equal to 1. In some embodiments of these ABPCs, the ABPC is degraded in the target mammalian cell after intracellular uptake of the ABPC by the target mammalian cell. Some embodiments of any of the ABPCs described herein may further comprise a conjugated toxin, radioisotope, drug, or small molecule (e.g., a fluorophore or dye).

[0085] Also provided are antigen binding protein constructs (ABPCs) and antibodies comprising a first antigen-binding domain capable of specifically binding to LRRC15 or an epitope of LRRC15 present on the surface of a target mammalian cell; and a conjugated toxin, radioisotope, drug, or small molecule, wherein (a) the dissociation rate of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is faster than the dissociation rate at a pH of about 7.0 to about 8.0, and / or the dissociation constant (K) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is faster than the dissociation rate at a pH of about 7.0 to about 8.0. D ) at pH 7.0 to 8.0 D and (b) a composition comprising the ABPC results in one or more (e.g., two or three) of: increased (e.g., a detectable increase) in toxin release in target mammalian cells compared to a composition comprising the same amount of control ABPC; increased (e.g., a detectable increase) in killing of target mammalian cells compared to a composition comprising the same amount of control ABPC; and increased (e.g., a detectable increase) in endolysosomal delivery in target mammalian cells compared to a composition comprising the same amount of control ABPC.

[0086] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain of samrotamab in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acids have been substituted with histidine. In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain of samrotamab in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acids have been substituted with histidine. In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain of samrotamab in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acids have been substituted with histidine, and a light chain variable domain of samrotamab in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acids have been substituted with histidine. In some embodiments of any of the ABPCs described herein, the heavy chain variable domain of samrotamab comprises SEQ ID NO: 1. In some embodiments of any of the ABPCs described herein, the light chain variable domain of samrotamab comprises SEQ ID NO:2.

[0087] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain including CDR1, CDR2, and CDR3 which are set forth in SEQ ID NO:3, SEQ ID NO:4, and SEQ ID NO:5, respectively, whereby a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs:3-5 have been substituted with histidine. In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain including CDR1, CDR2, and CDR3 which are set forth in SEQ ID NO:6, SEQ ID NO:7, and SEQ ID NO:8, respectively, whereby a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs:6-8 have been substituted with histidine. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising CDR1, CDR2, and CDR3 which are set forth in SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5, respectively, whereby a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs: 3 to 5 have been substituted with histidine; and a light chain variable domain comprising CDR1, CDR2, and CDR3 which are set forth in SEQ ID NO: 6, SEQ ID NO: 7, and SEQ ID NO: 8, respectively, whereby a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs: 6 to 8 have been substituted with histidine.

[0088] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acid positions of SEQ ID NO:1 selected from the group consisting of 33, 34, 50, 52, 57, 59, 100, 102, 103, 107, 108, or 109. In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 2, and the light chain variable domain comprises a histidine at one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acid positions of SEQ ID NO: 2 selected from the group consisting of 32, 34, 50, 51, 89, 90, 92, 93, 94, or 96.In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain is a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 1, and includes one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) antigens of SEQ ID NO: 1 selected from the group consisting of: 33, 34, 50, 52, 57, 59, 100, 102, 103, 107, 108, or 109. and a light chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acid positions of SEQ ID NO:2 selected from the group consisting of 32, 34, 50, 51, 89, 90, 92, 93, 94, or 96.

[0089] In some embodiments of any of the ABPCs and antibodies described herein, the heavy chain variable domain comprises a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, and the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0090] [Table 1-1] [Table 1-2]

[0091] In some embodiments of any of the ABPCs and antibodies described herein, the light chain variable domain comprises a light chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:2, and the light chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:2 listed in Table 2.

[0092] [Table 2]

[0093] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, and that includes a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:1 listed in Table 1; and a light chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:2, and that includes a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:2 listed in Table 2.

[0094] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:2 and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, and that includes a histidine at any of the specific combinations of one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10) amino acid positions of SEQ ID NO:1 listed in Table 1.

[0095] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 32 of SEQ ID NO:2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0096] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 34 of SEQ ID NO:2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0097] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 50 of SEQ ID NO:2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0098] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 51 of SEQ ID NO:2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0099] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 89 of SEQ ID NO:2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0100] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 90 of SEQ ID NO:2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0101] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 92 of SEQ ID NO:2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0102] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 93 of SEQ ID NO:2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0103] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 94 of SEQ ID NO:2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0104] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 96 of SEQ ID NO:2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0105] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain of samrotamab in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) histidines have been substituted with alanine. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain of samrotamab in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) histidines have been substituted with alanine. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain of samrotamab in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) histidines have been substituted with alanine, and a light chain variable domain of samrotamab in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) histidines have been substituted with alanine. In some embodiments of any of the ABPCs and antibodies described herein, the heavy chain variable domain of samrotamab comprises SEQ ID NO: 1. In some embodiments of any of the ABPCs and antibodies described herein, the light chain variable domain of samrotamab comprises SEQ ID NO: 2.

[0106] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising CDR1, CDR2, and CDR3 which are set forth in SEQ ID NO:3, SEQ ID NO:4, and SEQ ID NO:5, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NOs:3-5 have been substituted with alanine. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising CDR1, CDR2, and CDR3 which are set forth in SEQ ID NO:6, SEQ ID NO:7, and SEQ ID NO:8, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NOs:6-8 have been substituted with alanine. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising CDR1, CDR2, and CDR3 having SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5, respectively, in which a total of one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) histidines in SEQ ID NOs: 3-5 have been substituted with alanine, and a light chain variable domain comprising CDR1, CDR2, and CDR3 having SEQ ID NO: 6, SEQ ID NO: 7, and SEQ ID NO: 8, respectively, in which a total of one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) histidines in SEQ ID NOs: 6-8 have been substituted with alanine.

[0107] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises the following heavy chain variable domain: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.

[0108] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises the following light chain variable domain: SEQ ID NO:2, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, or SEQ ID NO:79.

[0109] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:2, and a heavy chain variable domain comprising: SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.

[0110] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:53, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.

[0111] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:54, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.

[0112] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:55, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.

[0113] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:56, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.

[0114] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:57, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.

[0115] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:58, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.

[0116] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:59, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.

[0117] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:60, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.

[0118] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:61, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.

[0119] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:62, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.

[0120] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:63, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.

[0121] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:64, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.

[0122] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:65, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.

[0123] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:66, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.

[0124] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:67, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.

[0125] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:68, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.

[0126] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:69, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.

[0127] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:70, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.

[0128] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:71, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.

[0129] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:72, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.

[0130] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:73, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.

[0131] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:74, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.

[0132] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:75, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.

[0133] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:76, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.

[0134] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:77, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.

[0135] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:78, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.

[0136] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:79, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.

[0137] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises the following heavy chain variable domain: SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, or SEQ ID NO:83.

[0138] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:80, and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, or SEQ ID NO:79.

[0139] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:81, and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, or SEQ ID NO:79.

[0140] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:82, and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, or SEQ ID NO:79.

[0141] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:83, and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, or SEQ ID NO:79.

[0142] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain of hu139.10 in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acids have been substituted with histidine. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain of hu139.10 in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acids have been substituted with histidine. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain of hu139.10 in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acids have been substituted with histidine, and a light chain variable domain of hu139.10 in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acids have been substituted with histidine. In some embodiments of any of the ABPCs and antibodies described herein, the heavy chain variable domain of hu139.10 comprises SEQ ID NO: 84. In some embodiments of any of the ABPCs and antibodies described herein, the light chain variable domain of hu139.10 comprises SEQ ID NO: 85.

[0143] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain including CDR1, CDR2, and CDR3 set forth in SEQ ID NO: 86, SEQ ID NO: 87, and SEQ ID NO: 88, respectively, wherein a total of one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) amino acid positions in SEQ ID NOs: 86-88 have been substituted with histidine. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain including CDR1, CDR2, and CDR3 set forth in SEQ ID NO: 89, SEQ ID NO: 90, and SEQ ID NO: 91, respectively, wherein a total of one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) amino acid positions in SEQ ID NOs: 89-91 have been substituted with histidine. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising CDR1, CDR2, and CDR3 having SEQ ID NO: 86, SEQ ID NO: 87, and SEQ ID NO: 88, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs: 89-91 have been substituted with histidine; and a light chain variable domain comprising CDR1, CDR2, and CDR3 having SEQ ID NO: 89, SEQ ID NO: 90, and SEQ ID NO: 91, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs: 89-91 have been substituted with histidine.

[0144] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 84, and the heavy chain variable domain comprises a histidine at one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acid positions of SEQ ID NO: 84 selected from the group consisting of 27, 29, 32, 50, 54, 58, 99, 100, 102, 104, or 105. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 85, and the light chain variable domain comprises a histidine at one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acid positions of SEQ ID NO: 85 selected from the group of 29, 31, 32, 34, 36, 37, 38, 40, 56, 60, 61, 95, 96, 97, or 100.In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain is a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 84 and contains a His residue at one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acid positions of SEQ ID NO: 84 selected from the group consisting of 27, 29, 32, 50, 54, 58, 99, 100, 102, 104, and 105. and a light chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 85 and that comprises a histidine at one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acid positions of SEQ ID NO: 85 selected from the group consisting of 29, 31, 32, 34, 36, 37, 38, 40, 56, 60, 61, 95, 96, 97, or 100.

[0145] In some embodiments of any of the ABPCs and antibodies described herein, the heavy chain variable domain comprises a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, and the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:84 listed in Table 3.

[0146] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 84, and the heavy chain variable domain comprises an alanine at position 35 of SEQ ID NO: 84.

[0147] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 84, and the heavy chain variable domain comprises an alanine at position 98 of SEQ ID NO: 84.

[0148] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 84, and that comprises an alanine at position 35 of SEQ ID NO: 84; and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, and a light chain variable domain at least 99%, or 100%) identical to SEQ ID NO: 85 and comprising a histidine at one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acid positions in SEQ ID NO: 85 selected from the group consisting of 29, 31, 32, 34, 36, 37, 38, 40, 56, 60, 61, 95, 96, 97, or 100.

[0149] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 84, and that comprises an alanine at position 98 of SEQ ID NO: 84; and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, and a light chain variable domain at least 99%, or 100%) identical to SEQ ID NO: 85 and comprising a histidine at one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acid positions in SEQ ID NO: 85 selected from the group consisting of 29, 31, 32, 34, 36, 37, 38, 40, 56, 60, 61, 95, 96, 97, or 100.

[0150] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 84, wherein the heavy chain variable domain comprises a histidine at one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acid positions of SEQ ID NO: 84 selected from the group consisting of 27, 29, 32, 50, 54, 58, 99, 100, 102, 104, or 105, and the heavy chain variable domain comprises an alanine at position 35 and / or 98 of SEQ ID NO: 84. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain is a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 84 and comprises a histidine at one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acid positions of SEQ ID NO: 84 selected from the group consisting of 27, 29, 32, 50, 54, 58, 99, 100, 102, 104, or 105, and and a light chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 85, wherein the light chain variable domain comprises a histidine at one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acid positions of SEQ ID NO: 85 selected from the group consisting of 29, 31, 32, 34, 36, 37, 38, 40, 56, 60, 61, 95, 96, 97, or 100.

[0151] In some embodiments of any of the ABPCs and antibodies described herein, the heavy chain variable domain comprises a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 84, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 84 listed in Table 1, and wherein the heavy chain variable domain comprises an alanine at position 35 and / or position 98 of SEQ ID NO: 84.

[0152] [Table 3-1] [Table 3-2]

[0153] In some embodiments of any of the ABPCs and antibodies described herein, the light chain variable domain comprises a light chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 85, and the light chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 85 listed in Table 4. [Table 4-1] [Table 4-2] [Table 4-3]

[0154] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 84 and that includes a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 84 listed in Table 3; and a light chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 85 and that includes a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 85 listed in Table 4.

[0155] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 84, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 84 listed in Table 3 and an alanine at position 35 of SEQ ID NO: 84; and a light chain variable domain at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 85, wherein the light chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 84 listed in Table 4.

[0156] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 84, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 84 listed in Table 3 and an alanine at position 98 of SEQ ID NO: 84; and a light chain variable domain at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 85, wherein the light chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 84 listed in Table 4.

[0157] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 85 and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 84, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10) amino acid positions of SEQ ID NO: 84 listed in Table 3.

[0158] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO: 85, wherein the light chain variable domain comprises a histidine at position 29 of SEQ ID NO: 85, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 84, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 84 listed in Table 3.

[0159] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO: 85, wherein the light chain variable domain comprises a histidine at position 31 of SEQ ID NO: 85, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 84, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 84 listed in Table 3.

[0160] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO: 85, wherein the light chain variable domain comprises a histidine at position 32 of SEQ ID NO: 85, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 84, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 84 listed in Table 3.

[0161] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO: 85, wherein the light chain variable domain comprises a histidine at position 34 of SEQ ID NO: 85, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 84, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 84 listed in Table 3.

[0162] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO: 85, wherein the light chain variable domain comprises a histidine at position 36 of SEQ ID NO: 85, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 84, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 84 listed in Table 3.

[0163] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO: 85, wherein the light chain variable domain comprises a histidine at position 37 of SEQ ID NO: 85, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 84, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 84 listed in Table 3.

[0164] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO: 85, wherein the light chain variable domain comprises a histidine at position 38 of SEQ ID NO: 85, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 84, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 84 listed in Table 3.

[0165] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO: 85, wherein the light chain variable domain comprises a histidine at position 40 of SEQ ID NO: 85, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 84, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 84 listed in Table 3.

[0166] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO: 85, wherein the light chain variable domain comprises a histidine at position 56 of SEQ ID NO: 85, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 84, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 84 listed in Table 3.

[0167] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO: 85, wherein the light chain variable domain comprises a histidine at position 60 of SEQ ID NO: 85, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 84, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 84 listed in Table 3.

[0168] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO: 85, wherein the light chain variable domain comprises a histidine at position 61 of SEQ ID NO: 85, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 84, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 84 listed in Table 3.

[0169] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO: 85, wherein the light chain variable domain comprises a histidine at position 95 of SEQ ID NO: 85, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 84, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 84 listed in Table 3.

[0170] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO: 85, wherein the light chain variable domain comprises a histidine at position 96 of SEQ ID NO: 85, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 84, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 84 listed in Table 3.

[0171] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO: 85, wherein the light chain variable domain comprises a histidine at position 97 of SEQ ID NO: 85, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 84, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 84 listed in Table 3.

[0172] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO: 85, wherein the light chain variable domain comprises a histidine at position 100 of SEQ ID NO: 85, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 84, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 84 listed in Table 3.

[0173] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain of hu139.10 in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) histidines have been substituted with alanine. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain of hu139.10 in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) histidines have been substituted with alanine. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain of hu139.10 in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) histidines have been substituted with alanine, and a light chain variable domain of hu139.10 in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) histidines have been substituted with alanine. In some embodiments of any of the ABPCs and antibodies described herein, the heavy chain variable domain of hu139.10 comprises SEQ ID NO: 84. In some embodiments of any of the ABPCs and antibodies described herein, the light chain variable domain of hu139.10 comprises SEQ ID NO: 85.

[0174] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain including CDR1, CDR2, and CDR3 set forth in SEQ ID NO: 86, SEQ ID NO: 87, and SEQ ID NO: 88, respectively, in which a total of one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) histidines in SEQ ID NOs: 86-88 have been substituted with alanine. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain including CDR1, CDR2, and CDR3 set forth in SEQ ID NO: 89, SEQ ID NO: 90, and SEQ ID NO: 91, respectively, in which a total of one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) histidines in SEQ ID NOs: 89-91 have been substituted with alanine. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising CDR1, CDR2, and CDR3 having SEQ ID NO: 86, SEQ ID NO: 87, and SEQ ID NO: 88, respectively, in which a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NOs: 86-88 have been substituted with alanine; and a light chain variable domain comprising CDR1, CDR2, and CDR3 having SEQ ID NO: 89, SEQ ID NO: 90, and SEQ ID NO: 91, respectively, in which a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NOs: 89-91 have been substituted with alanine.

[0175] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises the following heavy chain variable domain: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0176] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises the following light chain variable domain: SEQ ID NO:85, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137, SEQ ID NO:138, SEQ ID NO:139, SEQ ID NO:140, SEQ ID NO:141, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO:144, SEQ ID NO:145, SEQ ID NO:146, SEQ ID NO:147, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:150, SEQ ID NO:151, SEQ ID NO:152, SEQ ID NO:153, SEQ ID NO:154, SEQ ID NO:155, SEQ ID NO:156, SEQ ID NO:157, SEQ ID NO:158, SEQ ID NO:159, SEQ ID NO:160, SEQ ID NO:161, SEQ ID NO:162, or SEQ ID NO:163.

[0177] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:85, and a heavy chain variable domain comprising: SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0178] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:132, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0179] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:133, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0180] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:134, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0181] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:135, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0182] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:136, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0183] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:137, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0184] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:138, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0185] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:139, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0186] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:140, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0187] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:141, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0188] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:142, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0189] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:143, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0190] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:144, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0191] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:145, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0192] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:146, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0193] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:147, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0194] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:148, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0195] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:149, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0196] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:150, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0197] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:151, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0198] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:152, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0199] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:153, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0200] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:154, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0201] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:155, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0202] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:156, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0203] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:157, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0204] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:158, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0205] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:159, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0206] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:160, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0207] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:161, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0208] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:162, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0209] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:163, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 131.

[0210] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises the following heavy chain variable domain: SEQ ID NO: 164, SEQ ID NO: 165, SEQ ID NO: 166, or SEQ ID NO: 167.

[0211] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:164, and a light chain variable domain comprising: SEQ ID NO:85, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137, SEQ ID NO:138, SEQ ID NO:139, SEQ ID NO:140, SEQ ID NO:141, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO:144, SEQ ID NO:145, SEQ ID NO:146, SEQ ID NO:147, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:150, SEQ ID NO:151, SEQ ID NO:152, SEQ ID NO:153, SEQ ID NO:154, SEQ ID NO:155, SEQ ID NO:156, SEQ ID NO:157, SEQ ID NO:158, SEQ ID NO:159, SEQ ID NO:160, SEQ ID NO:161, SEQ ID NO:162, or SEQ ID NO:163.

[0212] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:165, and a light chain variable domain comprising: SEQ ID NO:85, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137, SEQ ID NO:138, SEQ ID NO:139, SEQ ID NO:140, SEQ ID NO:141, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO:144, SEQ ID NO:145, SEQ ID NO:146, SEQ ID NO:147, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:150, SEQ ID NO:151, SEQ ID NO:152, SEQ ID NO:153, SEQ ID NO:154, SEQ ID NO:155, SEQ ID NO:156, SEQ ID NO:157, SEQ ID NO:158, SEQ ID NO:159, SEQ ID NO:160, SEQ ID NO:161, SEQ ID NO:162, or SEQ ID NO:163.

[0213] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:166, and a light chain variable domain comprising: SEQ ID NO:85, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137, SEQ ID NO:138, SEQ ID NO:139, SEQ ID NO:140, SEQ ID NO:141, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO:144, SEQ ID NO:145, SEQ ID NO:146, SEQ ID NO:147, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:150, SEQ ID NO:151, SEQ ID NO:152, SEQ ID NO:153, SEQ ID NO:154, SEQ ID NO:155, SEQ ID NO:156, SEQ ID NO:157, SEQ ID NO:158, SEQ ID NO:159, SEQ ID NO:160, SEQ ID NO:161, SEQ ID NO:162, or SEQ ID NO:163.

[0214] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:167, and a light chain variable domain comprising: SEQ ID NO:85, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137, SEQ ID NO:138, SEQ ID NO:139, SEQ ID NO:140, SEQ ID NO:141, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO:144, SEQ ID NO:145, SEQ ID NO:146, SEQ ID NO:147, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:150, SEQ ID NO:151, SEQ ID NO:152, SEQ ID NO:153, SEQ ID NO:154, SEQ ID NO:155, SEQ ID NO:156, SEQ ID NO:157, SEQ ID NO:158, SEQ ID NO:159, SEQ ID NO:160, SEQ ID NO:161, SEQ ID NO:162, or SEQ ID NO:163.

[0215] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises the following heavy chain variable domain: SEQ ID NO: 168, SEQ ID NO: 169, SEQ ID NO: 170, SEQ ID NO: 171, SEQ ID NO: 172, SEQ ID NO: 173, SEQ ID NO: 174, SEQ ID NO: 175, SEQ ID NO: 176, or SEQ ID NO: 177.

[0216] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:168, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 164, SEQ ID NO: 165, SEQ ID NO: 166, or SEQ ID NO: 167.

[0217] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:169, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 164, SEQ ID NO: 165, SEQ ID NO: 166, or SEQ ID NO: 167.

[0218] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:170, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 164, SEQ ID NO: 165, SEQ ID NO: 166, or SEQ ID NO: 167.

[0219] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:171, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 164, SEQ ID NO: 165, SEQ ID NO: 166, or SEQ ID NO: 167.

[0220] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:172, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 164, SEQ ID NO: 165, SEQ ID NO: 166, or SEQ ID NO: 167.

[0221] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:173, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 164, SEQ ID NO: 165, SEQ ID NO: 166, or SEQ ID NO: 167.

[0222] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:174, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 164, SEQ ID NO: 165, SEQ ID NO: 166, or SEQ ID NO: 167.

[0223] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:175, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 164, SEQ ID NO: 165, SEQ ID NO: 166, or SEQ ID NO: 167.

[0224] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:176, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 164, SEQ ID NO: 165, SEQ ID NO: 166, or SEQ ID NO: 167.

[0225] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:177, and a heavy chain variable domain comprising: SEQ ID NO:84, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 164, SEQ ID NO: 165, SEQ ID NO: 166, or SEQ ID NO: 167.

[0226] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain of huAD208.4.1 in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acids have been substituted with histidine. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain of huAD208.4.1 in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acids have been substituted with histidine. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain of huAD208.4.1 in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acids have been substituted with histidine, and a light chain variable domain of huAD208.4.1 in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acids have been substituted with histidine. In some embodiments of any of the ABPCs and antibodies described herein, the heavy chain variable domain of huAD208.4.1 comprises SEQ ID NO: 178. In some embodiments of any of the ABPCs and antibodies described herein, the light chain variable domain of huAD208.4.1 comprises SEQ ID NO: 179.

[0227] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain including CDR1, CDR2, and CDR3 set forth in SEQ ID NO: 180, SEQ ID NO: 181, and SEQ ID NO: 182, respectively, wherein a total of one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) amino acid positions in SEQ ID NOs: 180-182 are substituted with histidine. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain including CDR1, CDR2, and CDR3 set forth in SEQ ID NO: 183, SEQ ID NO: 184, and SEQ ID NO: 185, respectively, wherein a total of one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) amino acid positions in SEQ ID NOs: 183-185 are substituted with histidine. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising CDR1, CDR2, and CDR3 set forth in SEQ ID NOs: 180, 181, and 182, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs: 180 to 182 have been substituted with histidine; and a light chain variable domain comprising CDR1, CDR2, and CDR3 set forth in SEQ ID NOs: 183, 184, and 185, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs: 183 to 185 have been substituted with histidine.

[0228] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 178, wherein the heavy chain variable domain comprises a histidine at one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acid positions of SEQ ID NO: 178 selected from the group consisting of 33, 52, 56, 57, or 106. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 179, and the light chain variable domain comprises a histidine at one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acid positions of SEQ ID NO: 179 selected from the group of 25, 26, 28, 29, 31, 36, 37, 57, 59, 94, 95, 96, or 100.In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain is a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 178 and includes a histidine at one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acid positions of SEQ ID NO: 178 selected from the group consisting of 33, 52, 56, 57, or 106. and a light chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 179 and that comprises a histidine at one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acid positions of SEQ ID NO: 179 selected from the group consisting of 25, 26, 28, 29, 31, 36, 37, 57, 59, 94, 95, 96, or 100.

[0229] In some embodiments of any of the ABPCs and antibodies described herein, the heavy chain variable domain comprises a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 178, and the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 178 listed in Table 5.

[0230] [Table 5]

[0231] In some embodiments of any of the ABPCs and antibodies described herein, the light chain variable domain comprises a light chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 179, and the light chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 179 listed in Table 6.

[0232] [Table 6-1] [Table 6-2]

[0233] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 178, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 178 listed in Table 5, and a light chain variable domain at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 179, wherein the light chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 179 listed in Table 6.

[0234] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 179 and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 178 and that includes a histidine at any of the specific combinations of one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10) amino acid positions of SEQ ID NO: 178 listed in Table 5.

[0235] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO: 179, wherein the light chain variable domain comprises a histidine at position 25 of SEQ ID NO: 2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 178, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 178 listed in Table 5.

[0236] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO: 179, wherein the light chain variable domain comprises a histidine at position 26 of SEQ ID NO: 2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 178, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 178 listed in Table 5.

[0237] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO: 179, wherein the light chain variable domain comprises a histidine at position 28 of SEQ ID NO: 2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 178, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 178 listed in Table 5.

[0238] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO: 179, wherein the light chain variable domain comprises a histidine at position 29 of SEQ ID NO: 2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 178, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 178 listed in Table 5.

[0239] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO: 179, wherein the light chain variable domain comprises a histidine at position 31 of SEQ ID NO: 2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 178, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 178 listed in Table 5.

[0240] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO: 179, wherein the light chain variable domain comprises a histidine at position 36 of SEQ ID NO: 2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 178, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 178 listed in Table 5.

[0241] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO: 179, wherein the light chain variable domain comprises a histidine at position 37 of SEQ ID NO: 2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 178, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 178 listed in Table 5.

[0242] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO: 179, wherein the light chain variable domain comprises a histidine at position 57 of SEQ ID NO: 2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 178, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 178 listed in Table 5.

[0243] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO: 179, wherein the light chain variable domain comprises a histidine at position 59 of SEQ ID NO: 2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 178, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 178 listed in Table 5.

[0244] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO: 179, wherein the light chain variable domain comprises a histidine at position 94 of SEQ ID NO: 2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 178, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 178 listed in Table 5.

[0245] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO: 179, wherein the light chain variable domain comprises a histidine at position 95 of SEQ ID NO: 2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 178, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 178 listed in Table 5.

[0246] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO: 179, wherein the light chain variable domain comprises a histidine at position 96 of SEQ ID NO: 2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 178, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 178 listed in Table 5.

[0247] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO: 179, wherein the light chain variable domain comprises a histidine at position 100 of SEQ ID NO: 2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 178, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 178 listed in Table 5.

[0248] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain of huAD208.4.1 in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) histidines have been substituted with alanine. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain of huAD208.4.1 in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) histidines have been substituted with alanine. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain of huAD208.4.1 in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) histidines have been substituted with alanine, and a light chain variable domain of huAD208.4.1 in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) histidines have been substituted with alanine. In some embodiments of any of the ABPCs and antibodies described herein, the heavy chain variable domain of huAD208.4.1 comprises SEQ ID NO: 178. In some embodiments of any of the ABPCs and antibodies described herein, the light chain variable domain of huAD208.4.1 comprises SEQ ID NO: 179.

[0249] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain including CDR1, CDR2, and CDR3 set forth in SEQ ID NO: 180, SEQ ID NO: 181, and SEQ ID NO: 182, respectively, in which a total of one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) histidines in SEQ ID NOs: 180-182 have been substituted with alanine. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain including CDR1, CDR2, and CDR3 set forth in SEQ ID NO: 183, SEQ ID NO: 184, and SEQ ID NO: 185, respectively, in which a total of one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) histidines in SEQ ID NOs: 183-185 have been substituted with alanine. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising CDR1, CDR2, and CDR3 having SEQ ID NO: 180, SEQ ID NO: 181, and SEQ ID NO: 182, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NOs: 180-182 have been substituted with alanine; and a light chain variable domain comprising CDR1, CDR2, and CDR3 having SEQ ID NO: 183, SEQ ID NO: 184, and SEQ ID NO: 185, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NOs: 183-185 have been substituted with alanine.

[0250] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises the following heavy chain variable domains: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO:219, SEQ ID NO:220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0251] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises the following light chain variable domain: SEQ ID NO: 179, SEQ ID NO: 228, SEQ ID NO: 229, SEQ ID NO: 230, SEQ ID NO: 231, SEQ ID NO: 232, SEQ ID NO: 233, SEQ ID NO: 234, SEQ ID NO: 235, SEQ ID NO: 236, SEQ ID NO: 237, SEQ ID NO: 238, SEQ ID NO: 239, SEQ ID NO: 240, SEQ ID NO: 241, SEQ ID NO: 242, SEQ ID NO: 243, SEQ ID NO: 244, SEQ ID NO: 245, SEQ ID NO: 246, SEQ ID NO: 247, SEQ ID NO: 248, SEQ ID NO: 249, SEQ ID NO: 250, SEQ ID NO: 251, SEQ ID NO: 252, SEQ ID NO: 253, SEQ ID NO: 254, SEQ ID NO: 255, SEQ ID NO: 256, or SEQ ID NO: 257.

[0252] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:179, and a heavy chain variable domain comprising: SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO:219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0253] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:228, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0254] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:229, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0255] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:230, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0256] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:231, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0257] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:232, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0258] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:233, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0259] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:234, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0260] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:235, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0261] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:236, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0262] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:237, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0263] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:238, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0264] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:239, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0265] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:240, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0266] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:241, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0267] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:242, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0268] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:243, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0269] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:244, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0270] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:245, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0271] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:246, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0272] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:247, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0273] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:248, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0274] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:249, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0275] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:250, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0276] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:251, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0277] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:252, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0278] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:253, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0279] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:254, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0280] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:255, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0281] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:256, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0282] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:257, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0283] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises the following heavy chain variable domain: SEQ ID NO:258, SEQ ID NO:259, SEQ ID NO:260, or SEQ ID NO:261.

[0284] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:258, and a light chain variable domain comprising: SEQ ID NO:179, SEQ ID NO:228, SEQ ID NO:229, SEQ ID NO:230, SEQ ID NO:231, SEQ ID NO:232, SEQ ID NO:233, SEQ ID NO:234, SEQ ID NO:235, SEQ ID NO:236, SEQ ID NO:237, SEQ ID NO:238, SEQ ID NO:239, SEQ ID NO:240, SEQ ID NO:241, SEQ ID NO:242, SEQ ID NO:243, SEQ ID NO:244, SEQ ID NO:245, SEQ ID NO:246, SEQ ID NO:247, SEQ ID NO:248, SEQ ID NO:249, SEQ ID NO:250, SEQ ID NO:251, SEQ ID NO:252, SEQ ID NO:253, SEQ ID NO:254, SEQ ID NO:255, SEQ ID NO:256, or SEQ ID NO:257.

[0285] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:259, and a light chain variable domain comprising: SEQ ID NO:179, SEQ ID NO:228, SEQ ID NO:229, SEQ ID NO:230, SEQ ID NO:231, SEQ ID NO:232, SEQ ID NO:233, SEQ ID NO:234, SEQ ID NO:235, SEQ ID NO:236, SEQ ID NO:237, SEQ ID NO:238, SEQ ID NO:239, SEQ ID NO:240, SEQ ID NO:241, SEQ ID NO:242, SEQ ID NO:243, SEQ ID NO:244, SEQ ID NO:245, SEQ ID NO:246, SEQ ID NO:247, SEQ ID NO:248, SEQ ID NO:249, SEQ ID NO:250, SEQ ID NO:251, SEQ ID NO:252, SEQ ID NO:253, SEQ ID NO:254, SEQ ID NO:255, SEQ ID NO:256, or SEQ ID NO:257.

[0286] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:260, and a light chain variable domain comprising: SEQ ID NO:179, SEQ ID NO:228, SEQ ID NO:229, SEQ ID NO:230, SEQ ID NO:231, SEQ ID NO:232, SEQ ID NO:233, SEQ ID NO:234, SEQ ID NO:235, SEQ ID NO:236, SEQ ID NO:237, SEQ ID NO:238, SEQ ID NO:239, SEQ ID NO:240, SEQ ID NO:241, SEQ ID NO:242, SEQ ID NO:243, SEQ ID NO:244, SEQ ID NO:245, SEQ ID NO:246, SEQ ID NO:247, SEQ ID NO:248, SEQ ID NO:249, SEQ ID NO:250, SEQ ID NO:251, SEQ ID NO:252, SEQ ID NO:253, SEQ ID NO:254, SEQ ID NO:255, SEQ ID NO:256, or SEQ ID NO:257.

[0287] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:261, and a light chain variable domain comprising: SEQ ID NO:179, SEQ ID NO:228, SEQ ID NO:229, SEQ ID NO:230, SEQ ID NO:231, SEQ ID NO:232, SEQ ID NO:233, SEQ ID NO:234, SEQ ID NO:235, SEQ ID NO:236, SEQ ID NO:237, SEQ ID NO:238, SEQ ID NO:239, SEQ ID NO:240, SEQ ID NO:241, SEQ ID NO:242, SEQ ID NO:243, SEQ ID NO:244, SEQ ID NO:245, SEQ ID NO:246, SEQ ID NO:247, SEQ ID NO:248, SEQ ID NO:249, SEQ ID NO:250, SEQ ID NO:251, SEQ ID NO:252, SEQ ID NO:253, SEQ ID NO:254, SEQ ID NO:255, SEQ ID NO:256, or SEQ ID NO:257.

[0288] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises the following light chain variable domain: SEQ ID NO: 262, SEQ ID NO: 263, SEQ ID NO: 264, SEQ ID NO: 265, SEQ ID NO: 266, SEQ ID NO: 267, SEQ ID NO: 268, SEQ ID NO: 269, SEQ ID NO: 270, or SEQ ID NO: 271.

[0289] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:262, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260, or SEQ ID NO: 261.

[0290] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:263, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260, or SEQ ID NO: 261.

[0291] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:264, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260, or SEQ ID NO: 261.

[0292] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:265, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260, or SEQ ID NO: 261.

[0293] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:266, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260, or SEQ ID NO: 261.

[0294] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:267, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260, or SEQ ID NO: 261.

[0295] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:268, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260, or SEQ ID NO: 261.

[0296] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:269, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260, or SEQ ID NO: 261.

[0297] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:270, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260, or SEQ ID NO: 261.

[0298] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:271, and a heavy chain variable domain comprising: SEQ ID NO:178, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260, or SEQ ID NO: 261.

[0299] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain of huAD208.12.1 in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acids have been substituted with histidine. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain of huAD208.12.1 in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acids have been substituted with histidine. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain of huAD208.12.1 in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acids have been substituted with histidine, and a light chain variable domain of huAD208.12.1 in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acids have been substituted with histidine. In some embodiments of any of the ABPCs and antibodies described herein, the heavy chain variable domain of huAD208.12.1 comprises SEQ ID NO: 272. In some embodiments of any of the ABPCs and antibodies described herein, the light chain variable domain of huAD208.12.1 comprises SEQ ID NO: 273.

[0300] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain including CDR1, CDR2, and CDR3 set forth in SEQ ID NO: 274, SEQ ID NO: 275, and SEQ ID NO: 276, respectively, wherein a total of one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) amino acid positions in SEQ ID NOs: 274-276 have been substituted with histidine. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain including CDR1, CDR2, and CDR3 set forth in SEQ ID NO: 277, SEQ ID NO: 278, and SEQ ID NO: 279, respectively, wherein a total of one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) amino acid positions in SEQ ID NOs: 277-279 are substituted with histidine. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising CDR1, CDR2, and CDR3 set forth in SEQ ID NOs: 274, 275, and 276, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs: 274 to 276 have been substituted with histidine; and a light chain variable domain comprising CDR1, CDR2, and CDR3 set forth in SEQ ID NOs: 277, 278, and 279, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs: 277 to 279 have been substituted with histidine.

[0301] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 272, wherein the heavy chain variable domain comprises a histidine at one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acid positions of SEQ ID NO: 272 selected from the group consisting of 24, 27, 29, 62, 63, 98, or 108. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 273, and the light chain variable domain comprises a histidine at one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acid positions of SEQ ID NO: 273 selected from the group of 27, 28, 29, 31, 32, 89, 92, or 93.In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain is a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 272 and contains a human nucleotide sequence at one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acid positions of SEQ ID NO: 272 selected from the group consisting of 24, 27, 29, 62, 63, 98, or 108. and a light chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 273, and that comprises a histidine at one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acid positions of SEQ ID NO: 273 selected from the group consisting of 27, 28, 29, 31, 32, 89, 92, or 93.

[0302] In some embodiments of any of the ABPCs and antibodies described herein, the heavy chain variable domain comprises a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 272, and the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 272 listed in Table 7.

[0303] [Table 7]

[0304] In some embodiments of any of the ABPCs and antibodies described herein, the light chain variable domain comprises a light chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 273, and the light chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO: 273 listed in Table 8.

[0305] [Table 8]

[0306] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:272, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:272 listed in Table 7, and a light chain variable domain at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:273, wherein the light chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions located in SEQ ID NO:273 listed in Table 8.

[0307] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:273 and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:272 and includes a histidine at any of the specific combinations of one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10) amino acid positions of SEQ ID NO:272 listed in Table 7.

[0308] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain at least 90% identical to SEQ ID NO:273, wherein the light chain variable domain comprises a histidine at position 27 of SEQ ID NO:273, and a heavy chain variable domain at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:272, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:272 listed in Table 7.

[0309] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain at least 90% identical to SEQ ID NO:273, wherein the light chain variable domain comprises a histidine at position 28 of SEQ ID NO:273, and a heavy chain variable domain at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:272, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:272 listed in Table 7.

[0310] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain at least 90% identical to SEQ ID NO:273, wherein the light chain variable domain comprises a histidine at position 29 of SEQ ID NO:273, and a heavy chain variable domain at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:272, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:272 listed in Table 7.

[0311] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain at least 90% identical to SEQ ID NO:273, wherein the light chain variable domain comprises a histidine at position 31 of SEQ ID NO:273, and a heavy chain variable domain at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:272, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:272 listed in Table 7.

[0312] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain at least 90% identical to SEQ ID NO:273, wherein the light chain variable domain comprises a histidine at position 32 of SEQ ID NO:273, and a heavy chain variable domain at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:272, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:272 listed in Table 7.

[0313] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain at least 90% identical to SEQ ID NO:273, wherein the light chain variable domain comprises a histidine at position 89 of SEQ ID NO:273, and a heavy chain variable domain at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:272, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:272 listed in Table 7.

[0314] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain at least 90% identical to SEQ ID NO:273, wherein the light chain variable domain comprises a histidine at position 92 of SEQ ID NO:273, and a heavy chain variable domain at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:272, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:272 listed in Table 7.

[0315] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain at least 90% identical to SEQ ID NO:273, wherein the light chain variable domain comprises a histidine at position 93 of SEQ ID NO:273, and a heavy chain variable domain at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:272, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:272 listed in Table 7.

[0316] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain of huAD208.12.1 in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) histidines have been substituted with alanine. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain of huAD208.12.1 in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) histidines have been substituted with alanine. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain of huAD208.12.1 in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) histidines have been substituted with alanine, and a light chain variable domain of huAD208.12.1 in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) histidines have been substituted with alanine. In some embodiments of any of the ABPCs and antibodies described herein, the heavy chain variable domain of huAD208.12.1 comprises SEQ ID NO: 272. In some embodiments of any of the ABPCs and antibodies described herein, the light chain variable domain of huAD208.12.1 comprises SEQ ID NO: 273.

[0317] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain including CDR1, CDR2, and CDR3 set forth in SEQ ID NO: 274, SEQ ID NO: 275, and SEQ ID NO: 276, respectively, in which a total of one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) histidines in SEQ ID NOs: 274-276 have been substituted with alanine. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain including CDR1, CDR2, and CDR3 set forth in SEQ ID NO: 277, SEQ ID NO: 278, and SEQ ID NO: 279, respectively, in which a total of one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) histidines in SEQ ID NOs: 277-279 have been substituted with alanine. In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising CDR1, CDR2, and CDR3 having SEQ ID NO: 274, SEQ ID NO: 275, and SEQ ID NO: 276, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NOs: 274-276 have been substituted with alanine; and a light chain variable domain comprising CDR1, CDR2, and CDR3 having SEQ ID NO: 277, SEQ ID NO: 278, and SEQ ID NO: 279, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NOs: 277-279 have been substituted with alanine.

[0318] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises the following heavy chain variable domain: SEQ ID NO:272, SEQ ID NO:280, SEQ ID NO:281, SEQ ID NO:282, SEQ ID NO:283, SEQ ID NO:284, SEQ ID NO:285, SEQ ID NO:286, SEQ ID NO:287, SEQ ID NO:288, SEQ ID NO:289, SEQ ID NO:290, SEQ ID NO:291, SEQ ID NO:292, SEQ ID NO:293, SEQ ID NO:294, SEQ ID NO:295, SEQ ID NO:296, SEQ ID NO:297, SEQ ID NO:298, SEQ ID NO:299, SEQ ID NO:300, SEQ ID NO:301, SEQ ID NO:302, SEQ ID NO:303, SEQ ID NO:304, SEQ ID NO:305, SEQ ID NO:306, SEQ ID NO:307, SEQ ID NO:308, SEQ ID NO:309, SEQ ID NO:310, SEQ ID NO:311, SEQ ID NO:312, SEQ ID NO:313, SEQ ID NO:314, SEQ ID NO: 315, SEQ ID NO: 316, SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 320, SEQ ID NO: 321, SEQ ID NO: 322, or SEQ ID NO: 323.

[0319] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises the following light chain variable domain: SEQ ID NO: 273, SEQ ID NO: 324, SEQ ID NO: 325, SEQ ID NO: 326, SEQ ID NO: 327, SEQ ID NO: 328, SEQ ID NO: 329, SEQ ID NO: 330, SEQ ID NO: 331, SEQ ID NO: 332, SEQ ID NO: 333, SEQ ID NO: 334, SEQ ID NO: 335, SEQ ID NO: 336, SEQ ID NO: 337, SEQ ID NO: 338, SEQ ID NO: 339, SEQ ID NO: 340, SEQ ID NO: 341, SEQ ID NO: 342, SEQ ID NO: 343, SEQ ID NO: 344, SEQ ID NO: 345, SEQ ID NO: 346, SEQ ID NO: 347, SEQ ID NO: 348, SEQ ID NO: 349, or SEQ ID NO: 350.

[0320] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:273, and a heavy chain variable domain comprising: SEQ ID NO:280, SEQ ID NO:281, SEQ ID NO:282, SEQ ID NO:283, SEQ ID NO:284, SEQ ID NO:285, SEQ ID NO:286, SEQ ID NO:287, SEQ ID NO:288, SEQ ID NO:289, SEQ ID NO:290, SEQ ID NO:291, SEQ ID NO:292, SEQ ID NO:293, SEQ ID NO:294, SEQ ID NO:295, SEQ ID NO:296, SEQ ID NO:297, SEQ ID NO:298, SEQ ID NO:299, SEQ ID NO:300, SEQ ID NO:301, SEQ ID NO:302, SEQ ID NO:303, SEQ ID NO:304, SEQ ID NO:305, SEQ ID NO:306, SEQ ID NO:307, SEQ ID NO:308, SEQ ID NO:309, SEQ ID NO:310, SEQ ID NO:311, SEQ ID NO:312, SEQ ID NO:313, SEQ ID NO: 314, SEQ ID NO: 315, SEQ ID NO: 316, SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 320, SEQ ID NO: 321, SEQ ID NO: 322, or SEQ ID NO: 323.

[0321] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:324, and a heavy chain variable domain comprising: SEQ ID NO:272, SEQ ID NO:280, SEQ ID NO:281, SEQ ID NO:282, SEQ ID NO:283, SEQ ID NO:284, SEQ ID NO:285, SEQ ID NO:286, SEQ ID NO:287, SEQ ID NO:288, SEQ ID NO:289, SEQ ID NO:290, SEQ ID NO:291, SEQ ID NO:292, SEQ ID NO:293, SEQ ID NO:294, SEQ ID NO:295, SEQ ID NO:296, SEQ ID NO:297, SEQ ID NO:298, SEQ ID NO:299, SEQ ID NO:300, SEQ ID NO:301, SEQ ID NO:302, SEQ ID NO:303, SEQ ID NO:304, SEQ ID NO:305, SEQ ID NO:306, SEQ ID NO:307, SEQ ID NO:308, SEQ ID NO:309, SEQ ID NO:310, SEQ ID NO:311, SEQ ID NO:312, SEQ ID NO: 313, SEQ ID NO: 314, SEQ ID NO: 315, SEQ ID NO: 316, SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 320, SEQ ID NO: 321, SEQ ID NO: 322, or SEQ ID NO: 323.

[0322] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:325, and a heavy chain variable domain comprising: SEQ ID NO:272, SEQ ID NO:280, SEQ ID NO:281, SEQ ID NO:282, SEQ ID NO:283, SEQ ID NO:284, SEQ ID NO:285, SEQ ID NO:286, SEQ ID NO:287, SEQ ID NO:288, SEQ ID NO:289, SEQ ID NO:290, SEQ ID NO:291, SEQ ID NO:292, SEQ ID NO:293, SEQ ID NO:294, SEQ ID NO:295, SEQ ID NO:296, SEQ ID NO:297, SEQ ID NO:298, SEQ ID NO:299, SEQ ID NO:300, SEQ ID NO:301, SEQ ID NO:302, SEQ ID NO:303, SEQ ID NO:304, SEQ ID NO:305, SEQ ID NO:306, SEQ ID NO:307, SEQ ID NO:308, SEQ ID NO:309, SEQ ID NO:310, SEQ ID NO:311, SEQ ID NO:312, SEQ ID NO: 313, SEQ ID NO: 314, SEQ ID NO: 315, SEQ ID NO: 316, SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 320, SEQ ID NO: 321, SEQ ID NO: 322, or SEQ ID NO: 323.

[0323] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:326, and a heavy chain variable domain comprising: SEQ ID NO:272, SEQ ID NO:280, SEQ ID NO:281, SEQ ID NO:282, SEQ ID NO:283, SEQ ID NO:284, SEQ ID NO:285, SEQ ID NO:286, SEQ ID NO:287, SEQ ID NO:288, SEQ ID NO:289, SEQ ID NO:290, SEQ ID NO:291, SEQ ID NO:292, SEQ ID NO:293, SEQ ID NO:294, SEQ ID NO:295, SEQ ID NO:296, SEQ ID NO:297, SEQ ID NO:298, SEQ ID NO:299, SEQ ID NO:300, SEQ ID NO:301, SEQ ID NO:302, SEQ ID NO:303, SEQ ID NO:304, SEQ ID NO:305, SEQ ID NO:306, SEQ ID NO:307, SEQ ID NO:308, SEQ ID NO:309, SEQ ID NO:310, SEQ ID NO:311, SEQ ID NO:312, SEQ ID NO: 313, SEQ ID NO: 314, SEQ ID NO: 315, SEQ ID NO: 316, SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 320, SEQ ID NO: 321, SEQ ID NO: 322, or SEQ ID NO: 323.

[0324] In some embodiments of any of the ABPCs and antibodies described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:327, and a heavy chain variable domain comprising: SEQ ID NO:272, SEQ ID NO:280, SEQ ID NO:281, SEQ ID NO:282, SEQ ID NO:283, SEQ ID NO:284, SEQ ID NO:285, SEQ ID NO:286, SEQ ID NO:287, SEQ ID NO:288, SEQ ID NO:289, SEQ ID NO:290, SEQ ID NO:291, SEQ ID NO:292, SEQ ID NO:293, SEQ ID NO:294, SEQ ID NO:295, SEQ ID NO:296, SEQ ID NO:297, SEQ ID NO:298, SEQ ID NO:299, SEQ ID NO:300, SEQ ID NO:301, SEQ ID NO:302, SEQ ID NO:303, SEQ ID NO:304, SEQ ID NO:305, SEQ ID NO:306, SEQ ID NO:307, SEQ ID NO:308, SEQ ID NO:309, SEQ ID NO:310, SEQ ID NO:311, SEQ ID NO:312, SEQ ID NO: 313, SEQ ID NO: 314, SEQ ID NO: 315, SEQ ID NO: 316, SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO:...

Claims

1. An antibody, comprising: A heavy chain variable domain and a light chain variable domain, a heavy chain variable domain which is at least 90% identical to SEQ ID NO:1 and which comprises a histidine at one or more positions of SEQ ID NO:1 selected from the group consisting of 33, 34, 50, 52, 57, 59, 100, 102, 103, 107, 108, and 109; and / or a light chain variable domain that is at least 90% identical to SEQ ID NO:2 and comprises a histidine at one or more positions of SEQ ID NO:2 selected from the group consisting of 32, 34, 50, 51, 89, 90, 92, 93, 94, and 96; and / or a heavy chain variable domain which is at least 90% identical to SEQ ID NO: 84 and which comprises a histidine at one or more positions in SEQ ID NO: 84 selected from the group consisting of 27, 29, 32, 50, 54, 58, 99, 100, 102, 104, and 105; and / or a light chain variable domain at least 90% identical to SEQ ID NO: 85, comprising a histidine at one or more positions in SEQ ID NO: 85 selected from the group consisting of 29, 31, 32, 34, 36, 37, 38, 40, 56, 60, 61, 95, 96, 97, and 100; and and / or a heavy chain variable domain which is at least 90% identical to SEQ ID NO: 178 and which comprises a histidine at one or more positions in SEQ ID NO: 178 selected from the group consisting of 33, 52, 56, 57, or 106; and / or a light chain variable domain at least 90% identical to SEQ ID NO: 179, comprising a histidine at one or more positions in SEQ ID NO: 179 selected from the group consisting of 25, 26, 28, 29, 31, 36, 37, 57, 59, 94, 95, 96, and 100; and and / or a heavy chain variable domain which is at least 90% identical to SEQ ID NO: 272 and which comprises a histidine at one or more positions in SEQ ID NO: 272 selected from the group consisting of 24, 27, 29, 62, 63, 98, and 108; and / or a light chain variable domain at least 90% identical to SEQ ID NO:273, comprising a histidine at one or more positions of SEQ ID NO:273 selected from the group consisting of: 27, 28, 29, 31, 32, 89, 92, and 93; 3. The heavy chain CH1-CH2-CH3 sequence of SEQ ID NO: 351 or SEQ ID NO: 352, (i) a methionine to tyrosine substitution at amino acid position 135, a serine to threonine substitution at amino acid position 137, and a threonine to glutamic acid substitution at amino acid position 139; (ii) a methionine to leucine substitution at amino acid position 311 and an asparagine to serine substitution at amino acid position 317, and (iii) an alanine to cysteine ​​substitution at amino acid position 1; and / or Light chain C of SEQ ID NO: 353, comprising a valine to cysteine ​​substitution at amino acid position 98 Ｌ An antibody comprising the sequence

2. the heavy chain CH1-CH2-CH3 sequence of SEQ ID NO: 351 or SEQ ID NO: 352 2. The antibody of claim 1, comprising a methionine to leucine substitution at amino acid position 311 and an asparagine to serine substitution at amino acid position 317.

3. The antibody, (i) SEQ ID NO: 354 and SEQ ID NO: 2, respectively; (ii) SEQ ID NO: 360 and SEQ ID NO: 85, respectively; (iii) SEQ ID NO: 366 and SEQ ID NO: 179, respectively; (iv) The antibody of claim 2, comprising a heavy chain sequence and a light chain sequence selected from the group of SEQ ID NO: 372 and SEQ ID NO: 273, respectively.

4. the heavy chain CH1-CH2-CH3 sequence of SEQ ID NO: 351 or SEQ ID NO: 352 2. The antibody of claim 1, comprising a methionine to tyrosine substitution at amino acid position 135, a serine to threonine substitution at amino acid position 137, and a threonine to glutamic acid substitution at amino acid position 139.

5. The antibody, (i) SEQ ID NO: 355 and SEQ ID NO: 2, respectively; (ii) SEQ ID NO: 361 and SEQ ID NO: 85, respectively; (iii) SEQ ID NO: 367 and SEQ ID NO: 179, respectively; (iv) The antibody of claim 4, comprising a heavy chain sequence and a light chain sequence selected from the group of SEQ ID NO: 373 and SEQ ID NO: 273, respectively.

6. The antibody, Light chain C of SEQ ID NO: 353 Ｌ 2. The antibody of claim 1, wherein the sequence includes a valine to cysteine ​​substitution at amino acid position 98.

7. The antibody, (i) SEQ ID NO: 1 and SEQ ID NO: 359, respectively; (ii) SEQ ID NO: 84 and SEQ ID NO: 365, respectively; (iii) SEQ ID NO: 178 and SEQ ID NO: 371, respectively; (iv) The antibody of claim 6, comprising a heavy chain sequence and a light chain sequence selected from the group of SEQ ID NO: 272 and SEQ ID NO: 377, respectively.

8. the heavy chain CH1-CH2-CH3 sequence of SEQ ID NO: 351 or SEQ ID NO: 352 a methionine to leucine substitution at amino acid position 311, and an asparagine to serine substitution at amino acid position 317; The light chain C of SEQ ID NO: 353 Ｌ 2. The antibody of claim 1, wherein the sequence includes a valine to cysteine ​​substitution at amino acid position 98.

9. The antibody, (i) SEQ ID NO: 354 and SEQ ID NO: 359, respectively; (ii) SEQ ID NO: 360 and SEQ ID NO: 365, respectively; (iii) SEQ ID NO: 366 and SEQ ID NO: 371, respectively; (iv) The antibody of claim 8, comprising a heavy chain sequence and a light chain sequence selected from the group of SEQ ID NO: 372 and SEQ ID NO: 377, respectively.

10. the heavy chain CH1-CH2-CH3 sequence of SEQ ID NO: 351 or SEQ ID NO: 352 a methionine to tyrosine substitution at amino acid position 135, a serine to threonine substitution at amino acid position 137, and a threonine to glutamic acid substitution at amino acid position 139; The light chain C of SEQ ID NO: 353 Ｌ 2. The antibody of claim 1, wherein the sequence includes a valine to cysteine ​​substitution at amino acid position 98.

11. The antibody, (i) SEQ ID NO: 355 and SEQ ID NO: 359, respectively; (ii) SEQ ID NO: 361 and SEQ ID NO: 365, respectively; (iii) SEQ ID NO: 367 and SEQ ID NO: 371, respectively; (iv) The antibody of claim 10, comprising a heavy chain sequence and a light chain sequence selected from the group of SEQ ID NO: 373 and SEQ ID NO: 377, respectively.

12. the heavy chain CH1-CH2-CH3 sequence of SEQ ID NO: 351 or SEQ ID NO: 352 2. The antibody of claim 1, comprising an alanine to cysteine ​​substitution at amino acid position 1.

13. The antibody, (i) SEQ ID NO: 356 and SEQ ID NO: 2, respectively; (ii) SEQ ID NO: 362 and SEQ ID NO: 85, respectively; (iii) SEQ ID NO: 368 and SEQ ID NO: 179, respectively; (iv) The antibody of claim 12, comprising a heavy chain sequence and a light chain sequence selected from the group of SEQ ID NO: 374 and SEQ ID NO: 273, respectively.

14. the heavy chain CH1-CH2-CH3 sequence of SEQ ID NO: 351 or SEQ ID NO: 352 a methionine to leucine substitution at amino acid position 311 and an asparagine to serine substitution at amino acid position 317; and 2. The antibody of claim 1, comprising an alanine to cysteine ​​substitution at amino acid position 1.

15. The antibody, (i) SEQ ID NO: 357 and SEQ ID NO: 2, respectively; (ii) SEQ ID NO: 363 and SEQ ID NO: 85, respectively; (iii) SEQ ID NO: 369 and SEQ ID NO: 179, respectively; (iv) The antibody of claim 16, comprising a heavy chain sequence and a light chain sequence selected from the group of SEQ ID NO: 375 and SEQ ID NO: 273, respectively.

16. the heavy chain CH1-CH2-CH3 sequence of SEQ ID NO: 351 or SEQ ID NO: 352 a methionine to tyrosine substitution at amino acid position 135, a serine to threonine substitution at amino acid position 137, and a threonine to glutamic acid substitution at amino acid position 139; 2. The antibody of claim 1, comprising an alanine to cysteine ​​substitution at amino acid position 1.

17. The antibody, (i) SEQ ID NO: 358 and SEQ ID NO: 2, respectively; (ii) SEQ ID NO: 364 and SEQ ID NO: 85, respectively; (iii) SEQ ID NO: 370 and SEQ ID NO: 179, respectively; (iv) The antibody of claim 18, comprising a heavy chain sequence and a light chain sequence selected from the group of SEQ ID NO: 376 and SEQ ID NO: 273, respectively.

18. The antibody is conjugated to a cytotoxic drug, the antibody comprising: (a) the heavy chain CH1-CH2-CH3 sequence of SEQ ID NO: 351 or SEQ ID NO: 352 comprising amino acid substitutions as defined in any one of claims 1 to 17, wherein the cytotoxic agent is (i) a cysteine ​​at amino acid position 103, (ii) a cysteine ​​at amino acid position 109, (iii) a cysteine ​​at amino acid position 112 and / or the heavy chain CH1-CH2-CH3 sequence of SEQ ID NO: 351 or SEQ ID NO: 352, which is conjugated to one or more of (b) the light chain C L sequence of SEQ ID NO: 353, in which the cytotoxic agent is conjugated to the cysteine ​​at amino acid position 107; and / or (c) the light chain C L sequence of SEQ ID NO: 353, comprising a valine to cysteine ​​substitution at amino acid position 98, wherein the cytotoxic agent is conjugated to the cysteine ​​of the valine to cysteine ​​substitution at amino acid position 98. The antibody of any one of claims 1 to 17, comprising:

19. The antibody of any one of claims 6 to 11 and claim 18, wherein the antibody further comprises a cytotoxic or cytostatic agent conjugated to the cysteine ​​of the valine to cysteine ​​substitution at position 98 of SEQ ID NO:

353.

20. A pharmaceutical composition comprising an effective amount of any one of the antibodies described in claims 1 to 19.

21. A kit comprising at least one dose of the antibody of any one of claims 1 to 19, or the pharmaceutical composition of claim 20.

22. The pharmaceutical composition of claim 20 for use in a method for treating cancer in a subject, wherein the cancer is characterized by having a population of cancer cells that display LRRC15 or an epitope of LRRC15 on their surface, and the subject has been identified as having a cancer characterized by having the population of cancer cells.

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