Antigen-binding protein construct and use of the same

Abstract

To provide an antigen-binding protein construct and use of the same.SOLUTION: The disclosure relates to a field of biotechnology, more detail, relates to antigen-binding molecules. The invention is based on a concept in which, an antigen-binding protein construct which exhibits improvement of efficiency (for example, one or more of increase of toxin discharge (detectable increase) in target mammalian cell, increase (for example, detectable increase) of killing of target mammalian cell, and increase (for example, detectable increase) of endo lysosome), may be generated.SELECTED DRAWING: None

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 62 / 910,935, filed October 4, 2019, the contents of which are incorporated herein by reference in their entirety.

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

[0003] 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. Summary of the Invention [Means for solving the problem]

[0004] The present invention is based on the concept that antigen binding protein constructs can be generated that exhibit improved efficacy (e.g., one or more of increased (e.g., detectable increase) toxin release in target mammalian cells, increased (e.g., detectable increase) killing of target mammalian cells, and increased (e.g., detectable increase) endolysosomal delivery).

[0005] Provided herein is a pharmaceutical composition comprising an effective amount of an antigen-binding protein construct (ABPC), the composition 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, or (b) the dissociation constant (K) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is greater than the dissociation rate at a pH of about 7.0 to about 8.0. D ) at pH 7.0 to 8.0 DThe pharmaceutical composition is provided in a form greater than or equal to 1000 mg / kg.

[0006] In some embodiments of the pharmaceutical compositions described herein, ABPC is degraded in the target mammalian cells following internalization of ABPC by the target mammalian cells.

[0007] In some embodiments of the pharmaceutical compositions described herein, the ABPC comprises a conjugated toxin, radioisotope, drug, or small molecule.

[0008] Also provided herein is a pharmaceutical composition comprising an effective amount of an antigen-binding protein construct (ABPC), the composition 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, or the dissociation constant (K) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is greater than the dissociation rate at a pH of about 7.0 to about 8.0. D ) is K at pH 7.0 to 8.0 D and (b) the composition provides one or more of: increased toxin release in target mammalian cells compared to a composition comprising the same amount of control ABPC; increased killing of target mammalian cells compared to a composition comprising the same amount of control ABPC; and increased endolysosomal delivery in target mammalian cells compared to a composition comprising the same amount of control ABPC.

[0009] In some embodiments of the pharmaceutical compositions described herein, the first antigen-binding domain comprises one of the following (a) to (d): (a) a heavy chain variable domain of samrotamab wherein one or more amino acids are substituted with histidine, said heavy chain variable domain comprising SEQ ID NO: 1; and / or a light chain variable domain of samrotamab wherein one or more amino acids are substituted with histidine, said light chain variable domain comprising SEQ ID NO: 2; (b) a heavy chain variable domain of hu139.10 wherein one or more amino acids are substituted with histidine, said heavy chain variable domain comprising SEQ ID NO: 84; and / or a light chain variable domain of hu139.10 wherein one or more amino acids are substituted with histidine, said hu139.10 comprising SEQ ID NO: 85. (c) a heavy chain variable domain of huAD208.4.1 wherein one or more amino acids are substituted with histidine, said heavy chain variable domain comprising SEQ ID NO: 178; and / or a light chain variable domain of huAD208.4.1 wherein one or more amino acids are substituted with histidine, said light chain variable domain comprising SEQ ID NO: 179; and (d) a heavy chain variable domain of huAD208.12.1 wherein one or more amino acids are substituted with histidine, said heavy chain variable domain comprising SEQ ID NO: 272; and / or a light chain variable domain of huAD208.12.1 wherein one or more amino acids are substituted with histidine, said heavy chain variable domain comprising SEQ ID NO: 273.

[0010] In some embodiments of the pharmaceutical compositions described herein, the first LRRC15-binding domain comprises one of (a) to (d): (a) a heavy chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 3 to 5, respectively, collectively, in which one or more amino acid positions in SEQ ID NOs: 3 to 5 are substituted with histidine; and / or a light chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 6 to 8, respectively, collectively, in which one or more amino acid positions in SEQ ID NOs: 6 to 8 are substituted with histidine; (b) a heavy chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 86 to 88, respectively, collectively, in which one or more amino acid positions in SEQ ID NOs: 86 to 88 are substituted with histidine; and / or CDR1, CDR2, and CDR3 of SEQ ID NOs: 89 to 91, respectively, collectively, in which one or more amino acid positions in SEQ ID NOs: 89 to 91 are substituted with histidine. (c) a heavy chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 180 to 182, respectively, in which a total of one or more amino acid positions of SEQ ID NOs: 180 to 182 are substituted with histidine; and / or a light chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 183 to 185, respectively, in which a total of one or more amino acid positions of SEQ ID NOs: 183 to 185 are substituted with histidine; and (d) a heavy chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 274 to 276, respectively, in which a total of one or more amino acid positions of SEQ ID NOs: 274 to 276 are substituted with histidine; and / or a light chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 277 to 279, respectively, in which a total of one or more amino acid positions of SEQ ID NOs: 277 to 279 are substituted with histidine.

[0011] In some embodiments of the pharmaceutical compositions described herein, the first antigen-binding domain comprises one of the following (a)-(d): (a) a heavy chain variable domain at least 90% identical to SEQ ID NO: 1, comprising a histidine at one or more positions in 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 at least 90% identical to SEQ ID NO: 2, comprising a histidine at one or more positions in SEQ ID NO: 2 selected from the group consisting of 32, 34, 50, 51, 89, 90, 92, 93, 94, and 96; (b) a heavy chain variable domain that is at least 90% identical to SEQ ID NO: 84, comprising 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 that is 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; (c) a heavy chain variable domain that is at least 90% identical to SEQ ID NO: 178, comprising 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 (d) 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.

[0012] In some embodiments of the pharmaceutical compositions described herein, 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 light 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: a heavy chain variable domain of 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 is selected from the group consisting of (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 that is not one of SEQ ID NOs: 20, 21, 23, 25, 30, 32, 43, 45, 46, 50-52, or 80-83; or (iii) a heavy chain variable domain of SEQ ID NO: 1 and a heavy chain variable domain of SEQ ID NO: (b) does not contain a light chain variable domain other than one of SEQ ID NO: 84, 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, a light chain variable domain of SEQ ID NO:175, SEQ ID NO:176, or SEQ ID NO:177, and / or a heavy chain variable domain of SEQ ID NO:85, 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; and / or (c) 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 is selected from the group consisting of: (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 heavy 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. does not comprise a light chain variable domain; 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.

[0013] In some embodiments of the pharmaceutical compositions described herein, the composition provides increased toxin release in target mammalian cells compared to a composition comprising the same amount of control ABPC, and / or increased killing of target mammalian cells compared to a composition comprising the same amount of control ABPC.

[0014] In some embodiments of the pharmaceutical compositions described herein, the compositions provide increased endolysosomal delivery in target mammalian cells compared to a composition comprising an equivalent amount of control ABPC.

[0015] In some embodiments of the pharmaceutical compositions described herein, the composition does not cause a significant decrease in the level of LRRC15 present on the surface of target mammalian cells, or does not result in a detectable decrease in the level of LRRC15 present on the surface of target mammalian cells, compared to a composition comprising an equivalent amount of control ABPC.

[0016] In some embodiments of the pharmaceutical compositions described herein, target mammalian cells are cancer cells.In some embodiments of the pharmaceutical compositions described herein, ABPC is cytotoxic or cytostatic to target mammalian cells.In some embodiments of the pharmaceutical compositions described herein, ABPC is cross-reactive with non-human primate LRRC15 and human LRRC15, or cross-reactive with one or both of non-human primate LRRC15, human LRRC15, and rat LRRC15 and mouse LRRC15.

[0017] In some embodiments of the pharmaceutical compositions described herein, the ABPC comprises a single polypeptide. In some embodiments of the pharmaceutical compositions described herein, the antigen-binding domain is selected from the group consisting of a VH domain, a VHH domain, a VNAR domain, and an scFv. In some embodiments of the pharmaceutical compositions described herein, the ABPC comprises two or more polypeptides. In some embodiments of the pharmaceutical compositions described herein, the ABPC is an antibody.

[0018] In some embodiments of the pharmaceutical compositions described herein, the half-life of ABPC in vivo is decreased compared to the half-life of control ABPC in vivo.

[0019] In some embodiments of the pharmaceutical compositions described herein, the ABPC comprises a second antigen-binding domain.

[0020] Provided herein is an antigen-binding protein construct (ABPC), 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, or (b) the dissociation constant (K D ) at pH 7.0 to 8.0 D Antigen binding protein constructs (ABPCs) are provided that are larger than

[0021] In some embodiments of the ABPC described herein, the ABPC is degraded in the target mammalian cells following internalization of the ABPC by the target mammalian cells.

[0022] In some embodiments of the ABPC described herein, the ABPC comprises a conjugated toxin, radioisotope, drug, or small molecule.

[0023] Also provided herein is an antigen-binding protein construct (ABPC), 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, 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 ) is K at pH 7.0 to 8.0 D and (b) the composition provides one or more of: increased toxin release in target mammalian cells compared to a composition comprising the same amount of control ABPC; increased killing of target mammalian cells compared to a composition comprising the same amount of control ABPC; and increased endolysosomal delivery in target mammalian cells compared to a composition comprising the same amount of control ABPC.

[0024] In some embodiments of the ABPC described herein, the first antigen-binding domain comprises one of the following (a) to (d): (a) a heavy chain variable domain of samrotamab wherein one or more amino acids are substituted with histidine, said heavy chain variable domain comprising SEQ ID NO: 1; and / or a light chain variable domain of samrotamab wherein one or more amino acids are substituted with histidine, said light chain variable domain comprising SEQ ID NO: 2; (b) a heavy chain variable domain of hu139.10 wherein one or more amino acids are substituted with histidine, said heavy chain variable domain comprising SEQ ID NO: 84; and / or a light chain variable domain of hu139.10 wherein one or more amino acids are substituted with histidine, said hu139.10 comprising SEQ ID NO: 85. (c) a heavy chain variable domain of huAD208.4.1 wherein one or more amino acids are substituted with histidine, said heavy chain variable domain comprising SEQ ID NO: 178; and / or a light chain variable domain of huAD208.4.1 wherein one or more amino acids are substituted with histidine, said light chain variable domain comprising SEQ ID NO: 179; and (d) a heavy chain variable domain of huAD208.12.1 wherein one or more amino acids are substituted with histidine, said heavy chain variable domain comprising SEQ ID NO: 272; and / or a light chain variable domain of huAD208.12.1 wherein one or more amino acids are substituted with histidine, said heavy chain variable domain comprising SEQ ID NO: 273.

[0025] In some embodiments of the ABPC described herein, the first LRRC15-binding domain comprises one of the following (a) to (d): (a) a heavy chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 3 to 5, respectively, collectively, in which one or more amino acid positions in SEQ ID NOs: 3 to 5 have been substituted with histidine; and / or a light chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 6 to 8, respectively, collectively, in which one or more amino acid positions in SEQ ID NOs: 6 to 8 have been substituted with histidine; (b) a heavy chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 86 to 88, respectively, collectively, in which one or more amino acid positions in SEQ ID NOs: 86 to 88 have been substituted with histidine; and / or a light chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 89 to 91, respectively, collectively, in which one or more amino acid positions in SEQ ID NOs: 89 to 91 have been substituted with histidine. (c) a heavy chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 180 to 182, respectively, in which a total of one or more amino acid positions of SEQ ID NOs: 180 to 182 have been substituted with histidine; and / or a light chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 183 to 185, respectively, in which a total of one or more amino acid positions of SEQ ID NOs: 183 to 185 have been substituted with histidine; and (d) a heavy chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 274 to 276, respectively, in which a total of one or more amino acid positions of SEQ ID NOs: 274 to 276 have been substituted with histidine; and / or a light chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 277 to 279, respectively, in which a total of one or more amino acid positions of SEQ ID NOs: 277 to 279 have been substituted with histidine.

[0026] In some embodiments of the ABPC described herein, the first antigen-binding domain comprises one of the following (a)-(d): (a) a heavy chain variable domain at least 90% identical to SEQ ID NO: 1, comprising a histidine at one or more positions in 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 heavy chain variable domain at least 90% identical to SEQ ID NO: 2 selected from the group consisting of 32, 34, 50, 51, 89, 90, 92, 93, 94, and 96. (b) a light chain variable domain at least 90% identical to SEQ ID NO: 2, comprising a histidine at one or more positions in SEQ ID NO: 2 selected from the group consisting of 27, 29, 32, 50, 54, 58, 99, 100, 102, 104, and 105; and / or a heavy chain variable domain at least 90% identical to SEQ ID NO: 84, comprising a histidine at one or more positions in SEQ ID NO: 84 selected from the group consisting of 29, 31, 32, 34, 36, 37, 38, 40, 56, 60, 61, 95, 96, 97, and 100. (c) a light chain variable domain at least 90% identical to SEQ ID NO: 85 comprising a histidine at one or more positions 33, 52, 56, 57, and 106 of SEQ ID NO: 178; and / or a heavy chain variable domain at least 90% identical to SEQ ID NO: 178 comprising a histidine at one or more positions 25, 26, 28, 29, 31, 36, 37, 57, 59, 94, 95, 96, and 100 of SEQ ID NO: 179. and (d) 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 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.

[0027] In some embodiments of the ABPC described herein, 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 light 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: a heavy chain variable domain of 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 is selected from the group consisting of (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 that is not one of SEQ ID NOs: 20, 21, 23, 25, 30, 32, 43, 45, 46, 50-52, or 80-83; or (iii) a heavy chain variable domain of SEQ ID NO: 1 and a heavy chain variable domain of SEQ ID NO: (b) does not contain a light chain variable domain other than one of SEQ ID NO: 84, 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, a light chain variable domain of SEQ ID NO:175, SEQ ID NO:176, or SEQ ID NO:177, and / or a heavy chain variable domain of SEQ ID NO:85, 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; and / or (c) 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 is selected from the group consisting of: (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 heavy 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. does not comprise a light chain variable domain; 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.

[0028] In some embodiments of the ABPC described herein, a composition comprising ABPC provides increased toxin release in target mammalian cells compared to a composition comprising an equivalent amount of control ABPC, and / or increased killing of target mammalian cells compared to a composition comprising an equivalent amount of control ABPC.

[0029] In some embodiments of ABPC described herein, a composition comprising ABPC provides increased endolysosomal delivery in target mammalian cells compared to a composition comprising an equivalent amount of control ABPC.

[0030] In some embodiments of the ABPC described herein, a composition comprising ABPC does not result in a significant decrease in the level of LRRC15 present on the surface of target mammalian cells, or does not result in a detectable decrease in the level of LRRC15 present on the surface of target mammalian cells, compared to a composition comprising an equivalent amount of control ABPC.

[0031] In some embodiments of the ABPC described herein, the target mammalian cell is cancer cell.In some embodiments of the ABPC described herein, ABPC is cytotoxic or cytostatic to target mammalian cell.In some embodiments of the ABPC described herein, ABPC is cross-reactive with non-human primate LRRC15 and human LRRC15, or cross-reactive with one or both of non-human primate LRRC15, human LRRC15, and rat LRRC15 and mouse LRRC15.

[0032] In some embodiments of the ABPC described herein, the ABPC comprises a single polypeptide. In some embodiments of the ABPC described herein, the antigen-binding domain is selected from the group consisting of a VH domain, a VHH domain, a VNAR domain, and an scFv. In some embodiments of the ABPC described herein, the ABPC comprises two or more polypeptides. In some embodiments of the ABPC described herein, the ABPC is an antibody.

[0033] In some embodiments of the ABPC described herein, the half-life of the ABPC in vivo is decreased compared to the half-life of a control ABPC in vivo.

[0034] In some embodiments of the ABPCs described herein, the ABPC comprises a second antigen-binding domain.

[0035] Also provided herein are kits that include any of the pharmaceutical compositions described herein or at least one dose of any of the ABPCs described herein.

[0036] Also provided herein is a method for treating a cancer characterized by having a population of cancer cells that have LRRC15 or an epitope of LRRC15 present on their surface, the method comprising administering a therapeutically effective amount of any one of the pharmaceutical compositions described herein or any of the ABPCs described herein to a subject identified as having a cancer characterized by having the above-mentioned population of cancer cells.

[0037] 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 have LRRC15 or an epitope of LRRC15 present on their surface, the method comprising administering a therapeutically effective amount of any of the pharmaceutical compositions described herein or any one of the ABPCs described herein to a subject identified as having a cancer characterized by having the above-mentioned population of cancer cells.

[0038] Also provided herein is a method for inducing cell death of cancer cells in a subject, wherein the cancer cells have LRRC15 or an epitope of LRRC15 present on their surface, the method comprising administering a therapeutically effective amount of any one of the pharmaceutical compositions described herein or any one of the ABPCs described herein to a subject identified as having a cancer characterized by having a population of the above cancer cells.

[0039] Also provided herein is a method for reducing the risk of developing metastases or reducing the risk of developing further metastases in a subject having cancer characterized by having a population of cancer cells that have LRRC15 or an epitope of LRRC15 present on their surface, the method comprising administering a therapeutically effective amount of any one of the pharmaceutical compositions described herein or any one of the ABPCs described herein to a subject identified as having a cancer characterized by having the above-mentioned population of cancer cells.

[0040] 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.

[0041] 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 embodiments, 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.

[0042] 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.

[0043] 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.

[0044] 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 are sorted for internalization via cell-mediated internalization processes, such as pinocytosis, micropinocytosis, receptor-mediated endocytosis, and / or phagocytosis.

[0045] Once endosomes in the endosomal / lysosomal pathway have been purified or isolated, assays for the target protein (e.g., the antigen-binding protein constructs described herein) can be performed using methods known in the art (e.g., ELISA, Western blot, immunofluorescence, and immunoprecipitation followed by assays of 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 (e.g., a fluorescently, dye-, or GFP-labeled antibody, e.g., CellLight™ Early Endosome-GFP) that specifically binds to a characteristic protein present in endosomes (e.g., EEA1 in early endosomes) and a fluorescently labeled antibody (e.g., an antigen-binding protein construct) that specifically binds to the protein of interest, and the level of the target protein in the endosomes can be determined by quantifying the overlap of the fluorescence emissions of the two different antibodies.

[0046] 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).

[0047] 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.

[0048] Exemplary assays for measuring endolysosomal delivery of any of the ABPCs described herein include assays involving labeling ABPC with a fluorescent dye, followed by incubation of the labeled ABPC with cells, and measuring cellular fluorescence as an indicator of endolysosomal delivery of ABPC (see, e.g., generally, Wustner, Traffic, 7(6):699-715, 2006). Alternatively, a pH-sensitive dye that is preferentially fluorescent at acidic pH but not at neutral pH can be used to label any of the ABPCs described herein, which can then be incubated with cells and cellular fluorescence measured as an indication of delivery of the ABPC to acidic endolysosomal compartments.

[0049] 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.

[0050] 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).

[0051] 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).

[0052] "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.

[0053] 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.

[0054] 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.

[0055] 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.

[0056] 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.

[0057] 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.

[0058] The phrase "control ABPC" or "control antigen-binding protein construct" refers to an ABPC that (i) is 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 wherein 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 a pH of about 4.0 to about 6.5 (e.g., any of the subranges of this range described herein); or 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.

[0059] 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.

[0060] The term "endolysosomal space" refers to the fluid enclosed by the vesicles and organelles that make up the endosomal / lysosomal pathway in mammalian cells.

[0061] 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.

[0062] 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 drug concentration, by the drug's IC50 (i.e., the drug concentration 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 described herein are compared with those of a control ABPC (as defined herein), and optionally demonstrate that the ABPC described herein has a higher cell killing ability than the control ABPC.

[0063] 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.

[0064] The phrases "target cell" or "target mammalian cell" or "mammalian target cell" refer to a mammalian cell having at least one LRRC15 molecule present on its surface. In some embodiments, the mammalian target cell can be a cancer cell. In some embodiments of the target mammalian cell, the total number of molecules present on the plasma membrane of the target mammalian cell is 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, about 1 to about 600,000, about 1 to about 4 00,000 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 60,000 pieces, about 1 to about 5 5,000 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 10,00 0 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 10 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 10 to about 100,000 pieces, Approx. 10 to approx. 80,000 pieces, approx. 10 to approx. 80,000 pieces, approx. 10 to approx. 75,000 pieces, approx. 10 to approx. 70,000 pieces, approx. 10 to approx. 65,000 pieces, approx.000, approximately 10 to approximately 40,000, approximately 10 to approximately 35,000, approximately 10 to approximately 30,000, approximately 10 to approximately 25,000, approximately 10 to approximately 20,000, approximately 10 to approximately 15,000, approximately 10 to approximately 10,000, approximately 10 to approximately 7,500, approximately 10 to approximately 5,000, approximately 10~ Approximately 4,000, approximately 10 to approximately 3,000, approximately 10 to approximately 2,000, approximately 10 to approximately 1,000, approximately 10 to approximately 500, approximately 10 to approximately 100, approximately 10 to approximately 50, approximately 50 to approximately 10,000,000, approximately 50 to approximately 9,000,000, approximately 50 to approximately 8,000,000, approximately 50 Approximately 7,000,000; approximately 50 to approximately 6,000,000; approximately 50 to approximately 5,000,000; approximately 50 to approximately 4,000,000; approximately 50 to approximately 3,000,000; approximately 50 to approximately 2,000,000; approximately 50 to approximately 1,000,000; approximately 50 to approximately 800,000; approximately 50~approximately 600,000, approximately 50~approximately 400,000, approximately 50~approximately 200,000, approximately 50~approximately 100,000, approximately 50~approximately 80,000, approximately 50~approximately 80,000, approximately 50~approximately 75,000, approximately 50~approximately 70,000, approximately 50~approximately 65,000, approximately 50~approximately 60,000, approximately 50 to approximately 55,000, approximately 50 to approximately 50,000, approximately 50 to approximately 45,000, approximately 50 to approximately 40,000, approximately 50 to approximately 35,000, approximately 50 to approximately 30,000, approximately 50 to approximately 25,000, approximately 50 to approximately 20,000, approximately 50 to approximately 15,000 Approximately 50 to 10,000, approximately 50 to 7,500, approximately 50 to 5,000, approximately 50 to 4,000, approximately 50 to 3,000, approximately 50 to 2,000, approximately 50 to 1,000, approximately 50 to 500, approximately 50 to 100, approximately 100 to 10,000,000, approximately 100 to approximately 9,000,000, approximately 100 to approximately 8,000,000, approximately 100 to approximately 7,000,000, approximately 100 to approximately 6,000,000, approximately 100 to approximately 5,000,000, approximately 100 to approximately 4,000,000, approximately 100 to approximately 3,000,000, approximately 100 to approximately 2 ,000,000, approximately 100 to approximately 1,000,000, approximately 100 to approximately 800,000, approximately 100 to approximately 600,000, approximately 100 to approximately 400,000, approximately 100 to approximately 200,000, approximately 100 to approximately 100,000, approximately 100 to approximately 80,000, approximately 100 to approximately 75,000, approximately 100 to approximately 70,000, approximately 100 to approximately 65,000, approximately 100 to approximately 60,000, approximately 100 to approximately 55,000, approximately 100 to approximately 50,000, approximately 100 to approximately 45,000, approximately 100 to approximately 40,000, approximately 100 to approximately 35,000, approximately 100 to approximately 3 0,000, approximately 100 to approximately 25,000, approximately 100 to approximately 20,000, approximately 100 to approximately 15,000, approximately 100 to approximately 10,000, approximately 100 to approximately 7,500, approximately 100 to approximately 5,000, approximately 100 to approximately 4,000, approximately 100 to approximately 3,000, approximately 100 to approximately 2,000 0, approximately 100 to approximately 1,000, approximately 100 to approximately 500, approximately 500 to approximately 10,000,000, approximately 500 to approximately 9,000,000, approximately 500 to approximately 8,000,000, approximately 500 to approximately 7,000,000, approximately 500 to approximately 6,000,000, approximately 500 to approximately 5,000 ,000, approximately 500 to approximately 4,000,000, approximately 500 to approximately 3,000,000, approximately 500 to approximately 2,000,000, approximately 500 to approximately 1,000,000, approximately 500 to approximately 800,000, approximately 500 to approximately 600,000, approximately 500 to approximately 400,000, approximately 500 to approximately 200,000, approximately 500 to 100,000, approximately 500 to 80,000, approximately 500 to 75,000, approximately 500 to 70,000, approximately 500 to 65,000, approximately 500 to 60,000, approximately 500 to 55,000, approximately 500 to 50,000, approximately 5 00~approximately 45,000, approximately 500~approximately 40,000, approximately 500~approximately 35,000, approximately 500~approximately 30,000, approximately 500~approximately 25,000, approximately 500~approximately 20,000, approximately 500~approximately 15,000, approximately 500~approximately 10,000, approximately 500~approximately 7,500, approximately 5 00~approximately 5,000, approximately 500~approximately 4,000, approximately 500~approximately 3,000, approximately 500~approximately 2,000, approximately 500~approximately 1,000, approximately 1,000~approximately 10,000,000, approximately 1,000~approximately 9,000,000, approximately 1,000~approximately 8,000,000, approximately 1, 000~approximately 7,000,000, approximately 1,000~approximately 6,000,000, approximately 1,000~approximately 5,000,000, approximately 1,000~approximately 4,000,000, approximately 1,000~approximately 3,000,000, approximately 1,000~approximately 2,000,000, approximately 1,000~approximately 1,000000, approximately 1,000 to approximately 800,000, approximately 1,000 to approximately 600,000, approximately 1,000 to approximately 400,000, approximately 1,000 to approximately 200,000, approximately 1,000 to approximately 100,000, approximately 1,000 to approximately 80,000, approximately 1,000 to approximately 75,000, approximately 1 ,000~approximately 70,000, approximately 1,000~approximately 65,000, approximately 1,000~approximately 60,000, approximately 1,000~approximately 55,000, approximately 1,000~approximately 50,000, approximately 1,000~approximately 45,000, approximately 1,000~approximately 40,000, approximately 1,000~approximately 35,000 Approximately 1,000 to 30,000; approximately 1,000 to 25,000; approximately 1,000 to 20,000; approximately 1,000 to 15,000; approximately 1,000 to 10,000; approximately 1,000 to 7,500; approximately 1,000 to 5,000; approximately 1,000 to 4,000 Approximately 1,000 to 3,000, approximately 1,000 to 2,000, approximately 2,000 to 10,000,000, approximately 2,000 to 9,000,000, approximately 2,000 to 8,000,000, approximately 2,000 to 7,000,000, approximately 2,000 to 6,000,000 0, approximately 2,000 to approximately 5,000,000, approximately 2,000 to approximately 4,000,000, approximately 2,000 to approximately 3,000,000, approximately 2,000 to approximately 2,000,000, approximately 2,000 to approximately 1,000,000, approximately 2,000 to approximately 800,000, approximately 2,000 to approximately 6 00,000, approximately 2,000 to approximately 400,000, approximately 2,000 to approximately 200,000, approximately 2,000 to approximately 100,000, approximately 2,000 to approximately 80,000, approximately 2,000 to approximately 75,000, approximately 2,000 to approximately 70,000, approximately 2,000 to approximately 65,000, approximately 2 ,000~approximately 60,000, approximately 2,000~approximately 55,000, approximately 2,000~approximately 50,000, approximately 2,000~approximately 45,000, approximately 2,000~approximately 40,000, approximately 2,000~approximately 35,000, approximately 2,000~approximately 30,000, approximately 2,000~approximately 25,000 Approximately 2,000 to 20,000, approximately 2,000 to 15,000, approximately 2,000 to 10,000, approximately 2,000 to 7,500, approximately 2,000 to 5,000, approximately 2,000 to 4,000, approximately 2,000 to 3,000, approximately 3,000 to 10,000000, approximately 3,000 to approximately 9,000,000, approximately 3,000 to approximately 8,000,000, approximately 3,000 to approximately 7,000,000, approximately 3,000 to approximately 6,000,000, approximately 3,000 to approximately 5,000,000, approximately 3,000 to approximately 4,000,000, approximately 3,000 Approximately 3,000,000; approximately 3,000 to approximately 2,000,000; approximately 3,000 to approximately 1,000,000; approximately 3,000 to approximately 800,000; approximately 3,000 to approximately 600,000; approximately 3,000 to approximately 400,000; approximately 3,000 to approximately 200,000; approximately 3,000 ~ Approximately 100,000, approximately 3,000~ Approximately 80,000, approximately 3,000~ Approximately 75,000, approximately 3,000~ Approximately 70,000, approximately 3,000~ Approximately 65,000, approximately 3,000~ Approximately 60,000, approximately 3,000~ Approximately 55,000, approximately 3,000~ Approximately 50,000, approximately 3 ,000~approximately 45,000, approximately 3,000~approximately 40,000, approximately 3,000~approximately 35,000, approximately 3,000~approximately 30,000, approximately 3,000~approximately 25,000, approximately 3,000~approximately 20,000, approximately 3,000~approximately 15,000, approximately 3,000~approximately 10,000 Approximately 3,000 to 7,500; approximately 3,000 to 5,000; approximately 3,000 to 4,000; approximately 4,000 to 10,000,000; approximately 4,000 to 9,000,000; approximately 4,000 to 8,000,000; approximately 4,000 to 7,000,000; approximately 4 ,000~approximately 6,000,000, approximately 4,000~approximately 5,000,000, approximately 4,000~approximately 4,000,000, approximately 4,000~approximately 3,000,000, approximately 4,000~approximately 2,000,000, approximately 4,000~approximately 1,000,000, approximately 4,000~approximately 800,000 00, approximately 4,000 to approximately 600,000, approximately 4,000 to approximately 400,000, approximately 4,000 to approximately 200,000, approximately 4,000 to approximately 100,000, approximately 4,000 to approximately 80,000, approximately 4,000 to approximately 75,000, approximately 4,000 to approximately 70,000, approximately 4,000 0~approximately 65,000, approximately 4,000~approximately 60,000, approximately 4,000~approximately 55,000, approximately 4,000~approximately 50,000, approximately 4,000~approximately 45,000, approximately 4,000~approximately 40,000, approximately 4,000~approximately 35,000, approximately 4,000~approximately 30,000, approximately 4,000~approximately 25,000, approximately 4,000~approximately 20,000, approximately 4,000~approximately 15,000, approximately 4,000~approximately 10,000, approximately 4,000~approximately 7,500, approximately 4,000~approximately 5,000, Approximately 5,000 to 10,000,000; approximately 5,000 to 9,000,000; approximately 5,000 to 8,000,000; approximately 5,000 to 7,000,000; approximately 5,000 to 6,000,000; approximately 5,000 to 5,000,000; approximately 5,000 to 4 ,000,000, approximately 5,000 to approximately 3,000,000, approximately 5,000 to approximately 2,000,000, approximately 5,000 to approximately 1,000,000, approximately 5,000 to approximately 800,000, approximately 5,000 to approximately 600,000, approximately 5,000 to approximately 400,000, approximately 5,000 Approximately 200,000; approximately 5,000 to approximately 100,000; approximately 5,000 to approximately 80,000; approximately 5,000 to approximately 75,000; approximately 5,000 to approximately 70,000; approximately 5,000 to approximately 65,000; approximately 5,000 to approximately 60,000; approximately 5,000 to approximately 55,000. Approximately 5,000 to 50,000, approximately 5,000 to 45,000, approximately 5,000 to 40,000, approximately 5,000 to 35,000, approximately 5,000 to 30,000, approximately 5,000 to 25,000, approximately 5,000 to 20,000, approximately 5,000 to 15,000 0, approximately 5,000 to 10,000, approximately 5,000 to 7,500, approximately 7,500 to 10,000,000, approximately 7,500 to 9,000,000, approximately 7,500 to 8,000,000, approximately 7,500 to 7,000,000, approximately 7,500 to 6,000 ,000, approximately 7,500 to approximately 5,000,000, approximately 7,500 to approximately 4,000,000, approximately 7,500 to approximately 3,000,000, approximately 7,500 to approximately 2,000,000, approximately 7,500 to approximately 1,000,000, approximately 7,500 to approximately 800,000, approximately 7,500 Approximately 600,000, approximately 7,500 to approximately 400,000, approximately 7,500 to approximately 200,000, approximately 7,500 to approximately 100,000, approximately 7,500 to approximately 80,000, approximately 7,500 to approximately 75,000, approximately 7,500 to approximately 70,000, approximately 7,500 to approximately 65,000 Approximately 7,500 to 60,000, approximately 7,500 to 55,000, approximately 7,500 to 50,000, approximately 7,500 to 45,000, approximately 7,500 to 40,000, approximately 7,500 to 35,000, approximately 7,500 to 30,000, approximately 7,500 to 25,000, approximately 7,500 to approximately 20,000, approximately 7,500 to approximately 15,000, approximately 7,500 to approximately 10,000, approximately 10,000 to approximately 10,000,000, approximately 10,000 to approximately 9,000,000, approximately 10,000 to approximately 8,000,000, approximately 10,000 to approximately 7 ,000,000, approximately 10,000 to approximately 6,000,000, approximately 10,000 to approximately 5,000,000, approximately 10,000 to approximately 4,000,000, approximately 10,000 to approximately 3,000,000, approximately 10,000 to approximately 2,000,000, approximately 10,000 to approximately 1,000 000, approximately 10,000 to approximately 800,000, approximately 10,000 to approximately 600,000, approximately 10,000 to approximately 400,000, approximately 10,000 to approximately 200,000, approximately 10,000 to approximately 100,000, approximately 10,000 to approximately 80,000, approximately 10,000 to approximately 75, 000, approximately 10,000 to approximately 70,000, approximately 10,000 to approximately 65,000, approximately 10,000 to approximately 60,000, approximately 10,000 to approximately 55,000, approximately 10,000 to approximately 50,000, approximately 10,000 to approximately 45,000, approximately 10,000 to approximately 40,000, approximately 10,000 to approximately 35,000, approximately 10,000 to approximately 30,000, approximately 10,000 to approximately 25,000, approximately 10,000 to approximately 20,000, approximately 10,000 to approximately 15,000, approximately 15,000 to approximately 10,000,000, approximately 15,000 to approximately 9,000,000 Approximately 15,000 to 8,000,000; approximately 15,000 to 7,000,000; approximately 15,000 to 6,000,000; approximately 15,000 to 5,000,000; approximately 15,000 to 4,000,000; approximately 15,000 to 3,000,000; approximately 15, 000~approximately 2,000,000, approximately 15,000~approximately 1,000,000, approximately 15,000~approximately 800,000, approximately 15,000~approximately 600,000, approximately 15,000~approximately 400,000, approximately 15,000~approximately 200,000, approximately 15,000~approximately 100,000 Approximately 15,000 to 80,000, approximately 15,000 to 75,000, approximately 15,000 to 70,000, approximately 15,000 to 65,000, approximately 15,000 to 60,000, approximately 15,000 to 55,000, approximately 15,000 to 50,000, approximately 15,000~approximately 45,000, approximately 15,000~approximately 40,000, approximately 15,000~approximately 35,000, approximately 15,000~approximately 30,000, approximately 15,000~approximately 25,000, approximately 15,000~approximately 20,000, approximately 20,000~approximately 10,000,000, approximately 20,000 00~approximately 9,000,000, approximately 20,000~approximately 8,000,000, approximately 20,000~approximately 7,000,000, approximately 20,000~approximately 6,000,000, approximately 20,000~approximately 5,000,000, approximately 20,000~approximately 4,000,000, approximately 20,000~approximately 3 ,000,000, approximately 20,000 to approximately 2,000,000, approximately 20,000 to approximately 1,000,000, approximately 20,000 to approximately 800,000, approximately 20,000 to approximately 600,000, approximately 20,000 to approximately 400,000, approximately 20,000 to approximately 200,000, approximately 20 ,000~approximately 100,000, approximately 20,000~approximately 80,000, approximately 20,000~approximately 75,000, approximately 20,000~approximately 70,000, approximately 20,000~approximately 65,000, approximately 210,000~approximately 60,000, approximately 20,000~approximately 55,000, approximately 20,000 Approximately 50,000, approximately 20,000 to approximately 45,000, approximately 20,000 to approximately 40,000, approximately 20,000 to approximately 35,000, approximately 20,000 to approximately 30,000, approximately 20,000 to approximately 25,000, approximately 25,000 to approximately 10,000,000, approximately 25,000 to approximately 9,000,000; approximately 25,000 to approximately 8,000,000; approximately 25,000 to approximately 7,000,000; approximately 25,000 to approximately 6,000,000; approximately 25,000 to approximately 5,000,000; approximately 25,000 to approximately 4,000,000; approximately 25,000 to approximately 3,000 ,000, approximately 25,000 to approximately 2,000,000, approximately 25,000 to approximately 1,000,000, approximately 25,000 to approximately 800,000, approximately 25,000 to approximately 600,000, approximately 25,000 to approximately 400,000, approximately 25,000 to approximately 200,000, approximately 25,000 ~approximately 100,000, approximately 25,000~approximately 80,000, approximately 25,000~approximately 75,000, approximately 25,000~approximately 70,000, approximately 25,000~approximately 65,000, approximately 25,000~approximately 60,000, approximately 25,000~approximately 55,000, approximately 25,000~approximately 50,000000, approximately 25,000 to approximately 45,000, approximately 25,000 to approximately 40,000, approximately 25,000 to approximately 35,000, approximately 25,000 to approximately 30,000, approximately 30,000 to approximately 10,000,000, approximately 30,000 to approximately 9,000,000, approximately 30,000 to approximately 8 ,000,000, approximately 30,000 to approximately 7,000,000, approximately 30,000 to approximately 6,000,000, approximately 30,000 to approximately 5,000,000, approximately 30,000 to approximately 4,000,000, approximately 30,000 to approximately 3,000,000, approximately 30,000 to approximately 2,000 ,000, approximately 30,000 to approximately 1,000,000, approximately 30,000 to approximately 800,000, approximately 30,000 to approximately 600,000, approximately 30,000 to approximately 400,000, approximately 30,000 to approximately 200,000, approximately 30,000 to approximately 100,000, approximately 30,000~ Approximately 80,000; approximately 30,000 to approximately 75,000; approximately 30,000 to approximately 70,000; approximately 30,000 to approximately 65,000; approximately 30,000 to approximately 60,000; approximately 30,000 to approximately 55,000; approximately 30,000 to approximately 50,000; approximately 30,000 to approximately 45,000 0, approximately 30,000 to approximately 40,000, approximately 30,000 to approximately 35,000, approximately 35,000 to approximately 10,000,000, approximately 35,000 to approximately 9,000,000, approximately 35,000 to approximately 8,000,000, approximately 35,000 to approximately 7,000,000, approximately 35,000 0~approx. 6,000,000, approximately 35,000~approx. 5,000,000, approximately 35,000~approx. 4,000,000, approximately 35,000~approx. 3,000,000, approximately 35,000~approx. 2,000,000, approximately 35,000~approx. 1,000,000, approximately 35,000~approx. 8 00,000, approximately 35,000 to approximately 600,000, approximately 35,000 to approximately 400,000, approximately 35,000 to approximately 200,000, approximately 35,000 to approximately 100,000, approximately 35,000 to approximately 80,000, approximately 35,000 to approximately 75,000, approximately 35,000 to approximately 7 0,000, approximately 35,000 to approximately 65,000, approximately 35,000 to approximately 60,000, approximately 35,000 to approximately 55,000, approximately 35,000 to approximately 50,000, approximately 35,000 to approximately 45,000, approximately 35,000 to approximately 40,000, approximately 40,000 to approximately 10,000000, approximately 40,000 to approximately 9,000,000, approximately 40,000 to approximately 8,000,000, approximately 40,000 to approximately 7,000,000, approximately 40,000 to approximately 6,000,000, approximately 40,000 to approximately 5,000,000, approximately 40,000 to approximately 4,000,000, approximately 40,000 to approximately 3,000,000, approximately 40,000 to approximately 2,000,000, approximately 40,000 to approximately 1,000,000, approximately 40,000 to approximately 800,000, approximately 40 ,000~approximately 600,000, approximately 40,000~approximately 400,000, approximately 40,000~approximately 200,000, approximately 40,000~approximately 100,000, approximately 40,000~approximately 80,000, approximately 40,000~approximately 75,000, approximately 40,000~approximately 70,000, approximately 40,000~approximately 65,000, approximately 40,000~approximately 60,000, approximately 40,000~approximately 55,000, approximately 40,000~approximately 50,000, approximately 40,000~approximately 45,000 Approximately 45,000 to 10,000,000; approximately 45,000 to 9,000,000; approximately 45,000 to 8,000,000; approximately 45,000 to 7,000,000; approximately 45,000 to 6,000,000; approximately 45,000 to 5,000,000; approximately 45 ,000~approximately 4,000,000, approximately 45,000~approximately 3,000,000, approximately 45,000~approximately 2,000,000, approximately 45,000~approximately 1,000,000, approximately 45,000~approximately 800,000, approximately 45,000~approximately 600,000, approximately 45,000~approximately 400 ,000, approximately 45,000 to approximately 200,000, approximately 45,000 to approximately 100,000, approximately 45,000 to approximately 80,000, approximately 45,000 to approximately 75,000, approximately 45,000 to approximately 70,000, approximately 45,000 to approximately 65,000, approximately 45,000 to approximately 60,000 Approximately 45,000 to 55,000; approximately 45,000 to 50,000; approximately 50,000 to 10,000,000; approximately 50,000 to 9,000,000; approximately 50,000 to 8,000,000; approximately 50,000 to 7,000,000; approximately 50,000~ Approximately 6,000,000; approximately 50,000 to approximately 5,000,000; approximately 50,000 to approximately 4,000,000; approximately 50,000 to approximately 3,000,000; approximately 50,000 to approximately 2,000,000; approximately 50,000 to approximately 1,000,000; approximately 50,000 to approximately 800. 000, approximately 50,000 to 600,000, approximately 50,000 to 400,000, approximately 50,000 to 200,000, approximately 50,000 to 100,000, approximately 50,000 to 80,000, approximately 50,000 to 75,000, approximately 50,000 to 70,000 0, approximately 50,000 to approximately 65,000, approximately 50,000 to approximately 60,000, approximately 50,000 to approximately 55,000, approximately 55,000 to approximately 10,000,000, approximately 55,000 to approximately 9,000,000, approximately 55,000 to approximately 8,000,000, approximately 55,000 to approximately 7 ,000,000, approximately 55,000 to 6,000,000, approximately 55,000 to 5,000,000, approximately 55,000 to 4,000,000, approximately 55,000 to 3,000,000, approximately 55,000 to 2,000,000, approximately 55,000 to 1,000000, approximately 55,000 to approximately 800,000, approximately 55,000 to approximately 600,000, approximately 55,000 to approximately 400,000, approximately 55,000 to approximately 200,000, approximately 55,000 to approximately 100,000, approximately 55,000 to approximately 80,000, approximately 55,000 to approximately 75, 000, approximately 55,000 to 70,000, approximately 55,000 to 65,000, approximately 55,000 to 60,000, approximately 60,000 to 10,000,000, approximately 60,000 to 9,000,000, approximately 60,000 to 8,000,000, approximately 60,000~ Approximately 7,000,000; approximately 60,000 to approximately 6,000,000; approximately 60,000 to approximately 5,000,000; approximately 60,000 to approximately 4,000,000; approximately 60,000 to approximately 3,000,000; approximately 60,000 to approximately 2,000,000; approximately 60,000 to approximately 1,000. 00,000, approximately 60,000 to approximately 800,000, approximately 60,000 to approximately 600,000, approximately 60,000 to approximately 400,000, approximately 60,000 to approximately 200,000, approximately 60,000 to approximately 100,000, approximately 60,000 to approximately 80,000, approximately 60,000 to approximately 7 5,000, approximately 60,000 to 70,000, approximately 60,000 to 65,000, approximately 65,000 to 10,000,000, approximately 65,000 to 9,000,000, approximately 65,000 to 8,000,000, approximately 65,000 to 7,000,000, approximately 6 5,000 to approximately 6,000,000; approximately 65,000 to approximately 5,000,000; approximately 65,000 to approximately 4,000,000; approximately 65,000 to approximately 3,000,000; approximately 65,000 to approximately 2,000,000; approximately 65,000 to approximately 1,000,000; approximately 65,000 ~approximately 800,000, approximately 65,000~approximately 600,000, approximately 65,000~approximately 400,000, approximately 65,000~approximately 200,000, approximately 65,000~approximately 100,000, approximately 65,000~approximately 80,000, approximately 65,000~approximately 75,000, approximately 65,000~ Approximately 70,000; approximately 70,000 to approximately 10,000,000; approximately 70,000 to approximately 9,000,000; approximately 70,000 to approximately 8,000,000; approximately 70,000 to approximately 7,000,000; approximately 70,000 to approximately 6,000,000; approximately 70,000 to approximately 5,000.000, approximately 70,000 to approximately 4,000,000, approximately 70,000 to approximately 3,000,000, approximately 70,000 to approximately 2,000,000, approximately 70,000 to approximately 1,000,000, approximately 70,000 to approximately 800,000, approximately 70,000 to approximately 600,000, approximately 70 ,000~approximately 400,000, approximately 70,000~approximately 200,000, approximately 70,000~approximately 100,000, approximately 70,000~approximately 90,000, approximately 70,000~approximately 80,000, approximately 80,000~approximately 10,000,000, approximately 80,000~approximately 9,000,000 Approximately 80,000 to 8,000,000; approximately 80,000 to 7,000,000; approximately 80,000 to 6,000,000; approximately 80,000 to 5,000,000; approximately 80,000 to 4,000,000; approximately 80,000 to 3,000,000; approximately 8 0,000~approx. 2,000,000, approximately 80,000~approx. 1,000,000, approximately 80,000~approx. 800,000, approximately 80,000~approx. 600,000, approximately 80,000~approx. 400,000, approximately 80,000~approx. 200,000, approximately 80,000~approx. 100,000 00, approximately 80,000 to approximately 90,000, approximately 90,000 to approximately 10,000,000, approximately 90,000 to approximately 9,000,000, approximately 90,000 to approximately 8,000,000, approximately 90,000 to approximately 7,000,000, approximately 90,000 to approximately 6,000,000, approximately 9 0,000~approx. 5,000,000, approximately 90,000~approx. 4,000,000, approximately 90,000~approx. 3,000,000, approximately 90,000~approx. 2,000,000, approximately 90,000~approx. 1,000,000, approximately 90,000~approx. 800,000, approximately 90,000~ Approximately 600,000; approximately 90,000 to approximately 400,000; approximately 90,000 to approximately 200,000; approximately 90,000 to approximately 100,000; approximately 100,000 to approximately 10,000,000; approximately 100,000 to approximately 9,000,000; approximately 100,000 to approximately 8,000,000. 00, approximately 100,000 to approximately 7,000,000, approximately 100,000 to approximately 6,000,000, approximately 100,000 to approximately 5,000,000, approximately 100,000 to approximately 4,000,000, approximately 100,000 to approximately 3,000,000, approximately 100,000 to approximately 2,000000, approximately 100,000 to approximately 1,000,000, approximately 100,000 to approximately 800,000, approximately 100,000 to approximately 600,000, approximately 100,000 to approximately 400,000, approximately 100,000 to approximately 200,000, approximately 200,000 to approximately 10,000,000 Approximately 200,000 to approximately 9,000,000; approximately 200,000 to approximately 8,000,000; approximately 200,000 to approximately 7,000,000; approximately 200,000 to approximately 6,000,000; approximately 200,000 to approximately 5,000,000; approximately 200,000 to approximately 4,000,000 Approximately 200,000 to 3,000,000; approximately 200,000 to 2,000,000; approximately 200,000 to 1,000,000; approximately 200,000 to 800,000; approximately 200,000 to 600,000; approximately 200,000 to 400,000; approximately 4 00,000~approximately 10,000,000; approximately 400,000~approximately 9,000,000; approximately 400,000~approximately 8,000,000; approximately 400,000~approximately 7,000,000; approximately 400,000~approximately 6,000,000; approximately 400,000~approximately 5,000,000 Approximately 400,000 to 4,000,000; approximately 400,000 to 3,000,000; approximately 400,000 to 2,000,000; approximately 400,000 to 1,000,000; approximately 400,000 to 800,000; approximately 400,000 to 600,000; approximately 600,000 to approximately 10,000,000; approximately 600,000 to approximately 9,000,000; approximately 600,000 to approximately 8,000,000; approximately 600,000 to approximately 7,000,000; approximately 600,000 to approximately 6,000,000; approximately 600,000 to approximately 5,000,000 Approximately 600,000 to 4,000,000; approximately 600,000 to 3,000,000; approximately 600,000 to 2,000,000; approximately 600,000 to 1,000,000; approximately 600,000 to 800,000; approximately 800,000 to 10,000,000 0, approximately 800,000 to approximately 9,000,000, approximately 800,000 to approximately 8,000,000, approximately 800,000 to approximately 7,000,000, approximately 800,000 to approximately 6,000,000, approximately 800,000 to approximately 5,000,000, approximately 800,000 to approximately 4,000000, approximately 800,000 to approximately 3,000,000, approximately 800,000 to approximately 2,000,000, approximately 800,000 to approximately 1,000,000, approximately 1,000,000 to approximately 10,000,000, approximately 1,000,000 to approximately 9,000,000, approximately 1,000,000 0 to approximately 8,000,000, approximately 1,000,000 to approximately 7,000,000, approximately 1,000,000 to approximately 6,000,000, approximately 1,000,000 to approximately 5,000,000, approximately 1,000,000 to approximately 4,000,000, approximately 1,000,000 to approximately 3,000,000 00, approximately 1,000,000 to approximately 2,000,000, approximately 2,000,000 to approximately 10,000,000, approximately 2,000,000 to approximately 9,000,000, approximately 2,000,000 to approximately 8,000,000, approximately 2,000,000 to approximately 7,000,000, approximately 2,000 0,000~approximately 6,000,000; approximately 2,000,000~approximately 5,000,000; approximately 2,000,000~approximately 4,000,000; approximately 2,000,000~approximately 3,000,000; approximately 3,000,000~approximately 10,000,000; approximately 3,000,000~approximately 9, 000,000, approximately 3,000,000 to approximately 8,000,000, approximately 3,000,000 to approximately 7,000,000, approximately 3,000,000 to approximately 6,000,000, approximately 3,000,000 to approximately 5,000,000, approximately 3,000,000 to approximately 4,000,000 Approximately 4,000,000 to approximately 10,000,000; approximately 4,000,000 to approximately 9,000,000; approximately 4,000,000 to approximately 8,000,000; approximately 4,000,000 to approximately 7,000,000; approximately 4,000,000 to approximately 6,000,000; approximately 4,000,000 0 to approximately 5,000,000; approximately 5,000,000 to approximately 10,000,000; approximately 5,000,000 to approximately 9,000,000; approximately 5,000,000 to approximately 8,000,000; approximately 5,000,000 to approximately 7,000,000; approximately 5,000,000 to approximately 6,000. 000, approximately 6,000,000 to approximately 10,000,000, approximately 6,000,000 to approximately 9,000,000, approximately 6,000,000 to approximately 8,000,000, approximately 6,000,000 to approximately 7,000,000, approximately 7,000,000 to approximately 10,000,000, approximately 7,The LRRC15 has 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 LRRC15s.

[0065] 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).

[0066] 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.

[0067] 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.

[0068] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill 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.

[0069] Other features and advantages of the invention will become apparent from the following detailed description and figures, and from the claims. In certain embodiments, for example, the following items are provided: (Item 1) 1. A pharmaceutical composition comprising an effective amount of an antigen binding protein construct (ABPC), a first antigen-binding domain capable of specifically binding to LRRC15 or an epitope of LRRC15 displayed on the surface of a target mammalian cell; (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; or (b) the dissociation constant (K D ) at pH 7.0 to 8.0 D 10. A pharmaceutical composition comprising said effective amount of an antigen binding protein construct (ABPC), wherein said effective amount is greater than or equal to: (Item 2) 2. The pharmaceutical composition according to item 1, wherein the ABPC is degraded in the target mammalian cells after internalization of the ABPC by the target mammalian cells. (Item 3) 3. The pharmaceutical composition of item 1 or 2, wherein the ABPC further comprises a conjugated toxin, radioisotope, drug, or small molecule. (Item 4) 1. A pharmaceutical composition comprising an effective amount of an antigen binding protein construct (ABPC), 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 Conjugated toxins, radioisotopes, drugs, or small molecules, (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; or The dissociation constant (K D ) at pH 7.0 to 8.0 D Larger; and (b) the composition comprises: an increase in toxin release in said target mammalian cells compared to a composition containing an equal amount of control ABPC; increased killing of target mammalian cells compared to a composition containing an equivalent amount of control ABPC; and a pharmaceutical composition comprising an effective amount of an antigen-binding protein construct (ABPC) that results in one or more of: increased endolysosomal delivery in said target mammalian cells compared to a composition comprising an equivalent amount of a control ABPC. (Item 5) The first antigen-binding domain is one of the following (a) to (d): (a) a heavy chain variable domain of samrotamab comprising SEQ ID NO: 1, wherein one or more amino acids are substituted with histidine; and / or a light chain variable domain of samrotamab in which one or more amino acids are substituted with histidine, the light chain variable domain of samrotamab comprising SEQ ID NO: 2; (b) a heavy chain variable domain of hu139.10 in which one or more amino acids are substituted with histidine, wherein the heavy chain variable domain of hu139.10 comprises SEQ ID NO: 84; and / or a light chain variable domain of hu139.10 wherein one or more amino acids are substituted with histidine, wherein the light chain variable domain of hu139.10 comprises SEQ ID NO: 85; (c) a heavy chain variable domain of huAD208.4.1 comprising SEQ ID NO: 178, wherein one or more amino acids are substituted with histidine; and / or a light chain variable domain of huAD208.4.1 comprising SEQ ID NO: 179, wherein one or more amino acids are substituted with histidine; and (d) a heavy chain variable domain of huAD208.12.1, wherein one or more amino acids are substituted with histidine; a heavy chain variable domain; and / or 5. The pharmaceutical composition of paragraph 1 or 4, comprising a light chain variable domain of huAD208.12.1, wherein one or more amino acids are substituted with histidine, wherein the light chain variable domain of huAD208.12.1 comprises SEQ ID NO: 273. (Item 6) the first LRRC15-binding domain is one of the following (a) to (d): (a) a heavy chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 3-5, respectively, collectively substituted with histidine at one or more amino acid positions in SEQ ID NOs: 3-5; and / or A light chain variable domain comprising CDR1, CDR2 and CDR3 of SEQ ID NOs: 6-8, respectively, collectively substituted with histidine at one or more amino acid positions in total of SEQ ID NOs: 6-8: (b) a heavy chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 86-88, respectively, collectively substituted with histidine at one or more amino acid positions in SEQ ID NOs: 86-88; and / or a light chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 89-91, respectively, collectively in total, with one or more amino acid positions of SEQ ID NOs: 89-91 substituted with histidine; (c) a heavy chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 180-182, respectively, collectively substituted with histidine at one or more amino acid positions in SEQ ID NOs: 180-182; and / or a light chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 183-185, respectively, and collectively substituted with histidine at one or more amino acid positions in SEQ ID NOs: 183-185; and (d) a heavy chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 274-276, respectively, wherein one or more amino acid positions collectively totaling SEQ ID NOs: 274-276 are substituted with histidine; and / or 5. The pharmaceutical composition according to items 1 to 4, comprising a light chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 277 to 279, respectively, and collectively, one or more amino acid positions of SEQ ID NOs: 277 to 279 substituted with histidine. (Item 7) The first antigen-binding domain is one of the following (a) to (d): (a) a heavy chain variable domain at least 90% identical to SEQ ID NO: 1, wherein the heavy chain variable domain comprises a histidine at one or more positions in 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 at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at one or more positions in SEQ ID NO:2 selected from the group consisting of 32, 34, 50, 51, 89, 90, 92, 93, 94, and 96; (b) a heavy chain variable domain at least 90% identical to SEQ ID NO: 84, comprising 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; (c) a heavy chain variable domain at least 90% identical to SEQ ID NO: 178, comprising 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 (d) 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 7. The pharmaceutical composition of any one of items 1 and 4 to 6, comprising a light chain variable domain that is at least 90% identical to SEQ ID NO: 273, and that comprises 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. (Item 8) The first antigen-binding domain is 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; the first antigen-binding domain is a light chain variable domain and / or a heavy chain variable domain that does not include: (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 that is not 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 that is not one of SEQ ID NOs: 61, 63 to 65, 71, 72, 74 to 76, or 78; (b) a light chain variable domain of SEQ ID NO:84, 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:85, 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; the first antigen-binding domain does not comprise: (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) 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 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; the first antigen-binding domain is a light chain variable domain and / or a heavy chain variable domain that does not (i) comprise a light chain variable domain of SEQ ID NO: 179 and a heavy chain variable domain of SEQ ID NO: 178, (ii) comprise 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 to 261, or (iii) comprise 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 to 253, 257, 263, 264, or 268 to 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; 5. The pharmaceutical composition of items 1 to 4, wherein the first antigen-binding domain comprises a light chain variable domain and / or a heavy chain variable domain that does not include: (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 that is not 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 that is not one of SEQ ID NOs: 327 to 329, 331, 332, 342, 345, or 346. (Item 9) The composition comprises: an increase in toxin release in said target mammalian cells compared to a composition containing an equivalent amount of control ABPC; and / or 9. The pharmaceutical composition of any one of items 1 to 8, which provides increased target mammalian cell killing compared to a composition containing the same amount of control ABPC. (Item 10) 10. The pharmaceutical composition according to any one of items 1 to 9, wherein the composition provides increased endolysosomal delivery in the target mammalian cells compared to a composition comprising the same amount of control ABPC. (Item 11) The composition comprises: a lesser reduction in the level of LRRC15 displayed on the surface of said target mammalian cells compared to a composition containing said same amount of control ABPC; or 11. The pharmaceutical composition according to any one of items 1 to 10, which does not result in a detectable decrease in the level of LRRC15 displayed on the surface of the target mammalian cells. (Item 12) 12. The pharmaceutical composition according to any one of items 1 to 11, wherein the target mammalian cells are cancer cells. (Item 13) 13. The pharmaceutical composition according to any one of items 1 to 12, wherein said ABPC is cytotoxic or cytostatic to said target mammalian cells. (Item 14) The ABPC is is cross-reactive with non-human primate LRRC15 and human LRRC15; or Any one of items 1 to 13, which is cross-reactive with non-human primate LRRC15, human LRRC15, and one or both of rat LRRC15 and mouse LRRC15. The pharmaceutical composition described in (Item 15) 15. The pharmaceutical composition according to any one of items 1 to 14, wherein the ABPC comprises a single polypeptide. (Item 16) 16. The pharmaceutical composition of item 15, wherein the antigen-binding domain is selected from the group consisting of a VH domain, a VHH domain, a VNAR domain, and an scFv. (Item 17) 15. The pharmaceutical composition according to any one of items 1 to 14, wherein the ABPC comprises two or more polypeptides. (Item 18) 18. The pharmaceutical composition of item 17, wherein the ABPC is an antibody. (Item 19) 19. The pharmaceutical composition of any one of items 1 to 18, wherein the half-life of the ABPC in vivo is reduced compared to the half-life of a control ABPC in vivo. (Item 20) 20. The pharmaceutical composition according to any one of items 1 to 19, wherein the ABPC further comprises a second antigen-binding domain. (Item 21) An antigen binding protein construct (ABPC), comprising: a first antigen-binding domain capable of specifically binding to LRRC15 or an epitope of LRRC15 displayed on the surface of a target mammalian cell; (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; or (b) the dissociation constant (K D ) at pH 7.0 to 8.0 D antigen-binding protein constructs (ABPCs), which are larger than (Item 22) 22. The ABPC according to item 21, wherein the ABPC is degraded in the target mammalian cells after internalization of the ABPC by the target mammalian cells. (Item 23) 23. The ABPC of item 21 or 22, wherein the ABPC further comprises a conjugated toxin, radioisotope, drug, or small molecule. (Item 24) An antigen binding protein construct (ABPC), 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 Conjugated toxins, radioisotopes, drugs, or small molecules, (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; or The dissociation constant (K D ) at pH 7.0 to 8.0 D Larger; and (b) the composition comprises: an increase in toxin release in said target mammalian cells compared to a composition containing an equal amount of control ABPC; increased killing of target mammalian cells compared to a composition containing an equivalent amount of control ABPC; and and increased endolysosomal delivery in said target mammalian cells compared to a composition comprising an equivalent amount of control ABPC. (Item 25) The first antigen-binding domain is one of the following (a) to (d): (a) a heavy chain variable domain of samrotamab comprising SEQ ID NO: 1, wherein one or more amino acids are substituted with histidine; and / or a light chain variable domain of samrotamab in which one or more amino acids are substituted with histidine, the light chain variable domain of samrotamab comprising SEQ ID NO: 2; (b) a heavy chain variable domain of hu139.10 in which one or more amino acids are substituted with histidine, wherein the heavy chain variable domain of hu139.10 comprises SEQ ID NO: 84; and / or a light chain variable domain of hu139.10 wherein one or more amino acids are substituted with histidine, wherein the light chain variable domain of hu139.10 comprises SEQ ID NO: 85; (c) a heavy chain variable domain of huAD208.4.1 comprising SEQ ID NO: 178, wherein one or more amino acids are substituted with histidine; and / or a light chain variable domain of huAD208.4.1 comprising SEQ ID NO: 179, wherein one or more amino acids are substituted with histidine; and (d) a heavy chain variable domain of huAD208.12.1 wherein one or more amino acids are substituted with histidine, wherein the heavy chain variable domain comprises SEQ ID NO: 272; and / or 25. The ABPC of paragraph 21 or 24, comprising a light chain variable domain of huAD208.12.1 wherein one or more amino acids are substituted with histidine, wherein the light chain variable domain of huAD208.12.1 comprises SEQ ID NO: 273. (Item 26) the first LRRC15-binding domain is one of the following (a) to (d): (a) a heavy chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 3-5, respectively, collectively substituted with histidine at one or more amino acid positions in SEQ ID NOs: 3-5; and / or A light chain variable domain comprising CDR1, CDR2 and CDR3 of SEQ ID NOs: 6-8, respectively, collectively substituted with histidine at one or more amino acid positions in total of SEQ ID NOs: 6-8: (b) a heavy chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 86-88, respectively, collectively substituted with histidine at one or more amino acid positions in SEQ ID NOs: 86-88; and / or a light chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 89-91, respectively, collectively in total, with one or more amino acid positions of SEQ ID NOs: 89-91 substituted with histidine; (c) a heavy chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 180-182, respectively, collectively substituted with histidine at one or more amino acid positions in SEQ ID NOs: 180-182; and / or a light chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 183-185, respectively, and collectively substituted with histidine at one or more amino acid positions in SEQ ID NOs: 183-185; and (d) a heavy chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 274-276, respectively, wherein one or more amino acid positions collectively totaling SEQ ID NOs: 274-276 are substituted with histidine; and / or 25. The ABPC according to items 21 to 24, comprising a light chain variable domain comprising CDR1, CDR2 and CDR3 of SEQ ID NOs: 277 to 279, respectively, and collectively, one or more amino acid positions in total of SEQ ID NOs: 277 to 279 substituted with histidine. (Item 27) The first antigen-binding domain is one of the following (a) to (d): (a) a heavy chain variable domain at least 90% identical to SEQ ID NO: 1, wherein the heavy chain variable domain comprises a histidine at one or more positions in 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 at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at one or more positions in SEQ ID NO:2 selected from the group consisting of 32, 34, 50, 51, 89, 90, 92, 93, 94, and 96; (b) a heavy chain variable domain at least 90% identical to SEQ ID NO: 84, comprising 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; (c) a heavy chain variable domain at least 90% identical to SEQ ID NO: 178, comprising 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 (d) 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 27. The ABPC of any one of items 21 and 24 to 26, comprising a light chain variable domain that is at least 90% identical to SEQ ID NO: 273, and that comprises 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. (Item 28) The first antigen-binding domain is 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; the first antigen-binding domain is a light chain variable domain and / or a heavy chain variable domain that does not include: (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 that is not 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 that is not one of SEQ ID NOs: 61, 63 to 65, 71, 72, 74 to 76, or 78; (b) SEQ ID NO:84, 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 the sequence a light chain variable domain of SEQ ID NO: 177, and / or a heavy chain variable domain of SEQ ID NO:85, 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; the first antigen-binding domain does not comprise: (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) 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; the first antigen-binding domain is a light chain variable domain and / or a heavy chain variable domain that does not (i) comprise a light chain variable domain of SEQ ID NO: 179 and a heavy chain variable domain of SEQ ID NO: 178, (ii) comprise 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 to 261, or (iii) comprise 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 to 253, 257, 263, 264, or 268 to 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; 25. The ABPC of item 21 or 24, 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 that is not one of SEQ ID NOs: 281, 284, 286, 305, 306, 311, or 321; or (iii) a light chain variable domain and / or a heavy chain variable domain that does not comprise a heavy chain variable domain of SEQ ID NO: 272 and a light chain variable domain that is not one of SEQ ID NOs: 327 to 329, 331, 332, 342, 345, or 346. (Item 29) The composition comprising ABPC is an increase in toxin release in said target mammalian cells compared to a composition containing an equivalent amount of control ABPC; and / or 29. The ABPC of any one of items 21 to 28, which provides increased killing of target mammalian cells compared to a composition comprising an equivalent amount of control ABPC. (Item 30) The composition containing ABPC inhibits the activity of the target protein compared to a composition containing the same amount of control ABPC. 30. The ABPC of any one of items 21 to 29, which provides increased endolysosomal delivery in mammalian cells. (Item 31) The composition comprising ABPC is a lesser reduction in the level of LRRC15 displayed on the surface of said target mammalian cells compared to a composition containing said same amount of control ABPC; or 31. The ABPC of any one of items 21 to 30, which does not result in a detectable decrease in the level of LRRC15 displayed on the surface of the target mammalian cells. (Item 32) 32. The ABPC according to any one of items 21 to 31, wherein the target mammalian cells are cancer cells. (Item 33) 33. The ABPC according to any one of items 21 to 32, wherein the ABPC is cytotoxic or cytostatic to the target mammalian cells. (Item 34) The ABPC is is cross-reactive with non-human primate LRRC15 and human LRRC15; or 34. The ABPC of any one of items 21 to 33, which is cross-reactive with non-human primate LRRC15, human LRRC15, and one or both of rat LRRC15 and mouse LRRC15. (Item 35) 35. The ABPC according to any one of items 21 to 34, wherein the ABPC comprises a single polypeptide. (Item 36) 36. The ABPC of item 35, wherein the antigen-binding domain is selected from the group consisting of a VH domain, a VHH domain, a VNAR domain, and an scFv. (Item 37) 35. The ABPC according to any one of items 21 to 34, wherein the ABPC comprises two or more polypeptides. (Item 38) 38. The ABPC of item 37, wherein the ABPC is an antibody. (Item 39) 39. The ABPC of any one of items 21 to 38, wherein the half-life of said ABPC in vivo is decreased compared to the half-life of a control ABPC in vivo. (Item 40) 40. The ABPC according to any one of items 21 to 39, wherein the ABPC further comprises a second antigen-binding domain. (Item 41) A kit comprising at least one dose of the pharmaceutical composition according to any one of items 1 to 20 or the ABPC according to any one of items 21 to 40. (Item 42) 1. A method of treating a cancer characterized by having a population of cancer cells that display LRRC15 or an epitope of LRRC15 on their surface, said method comprising: A method comprising administering a therapeutically effective amount of the pharmaceutical composition according to any one of items 1 to 20 or the ABPC according to any one of items 21 to 40 to a subject identified as having a cancer characterized by having the population of cancer cells. (Item 43) A method of 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: A method comprising administering a therapeutically effective amount of the pharmaceutical composition according to any one of items 1 to 20 or the ABPC according to any one of items 21 to 40 to a subject identified as having a cancer characterized by having the population of cancer cells. (Item 44) 1. A method of inducing cell death of cancer cells in a subject, the cancer cells having LRRC15 or an epitope of LRRC15 displayed on their surface, the method comprising: A method comprising administering a therapeutically effective amount of the pharmaceutical composition according to any one of items 1 to 20 or the ABPC according to any one of items 21 to 40 to a subject identified as having a cancer characterized by having the population of cancer cells. (Item 45) 1. A method of reducing the risk of developing metastases or reducing the risk of developing further metastases in a subject having cancer, wherein the cancer is characterized by having a population of cancer cells that have LRRC15 or an epitope of LRRC15 present on their surface, the method comprising: A method comprising administering a therapeutically effective amount of the pharmaceutical composition according to any one of items 1 to 20 or the ABPC according to any one of items 21 to 40 to a subject identified as having a cancer characterized by having the population of cancer cells. [Brief explanation of the drawings]

[0070] [Figure 1] Figure 1 shows SDS-PAGE analysis of histidine-scanning and alanine-scanning SAMROTAMAB. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of SAMROTAMAB 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 SAMROTAMAB, and the remaining lanes (MYT0964-MYT1003) represent histidine-scanning and alanine-scanning variants of the heavy chain of SAMROTAMAB. [Figure 2A] Figures 2a-2ao show the 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] Figure 3 is a table of 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] Figure 4 shows SDS-PAGE analysis of histidine-scanning and alanine-scanning variants of SAMROTAMAB. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of SAMROTAMAB 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 SAMROTAMAB. [Figure 5A] Figures 5a-5aa show the binding of SAMROTAMAB starting ABPC and histidine-scanning and alanine-scanning variants to LRRC15 by biolayer interferometry. The 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] Figure 6 is a table of construct identifiers 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] Figure 7 shows SDS-PAGE analysis of histidine-scanning and alanine-scanning variants of SAMROTAMAB. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of SAMROTAMAB 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 SAMROTAMAB. [Figure 8A]Figures 8a-8d show the binding of histidine-scanning and alanine-scanning variants of SAMROTAMAB to LRRC15 by biolayer interferometry. Histidine-scanning and alanine-scanning variants of SAMROTAMAB heavy chain combinations, 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 figures. [Figure 8B] Same as above. [Figure 8C] Same as above. [Figure 8D] Same as above. [Figure 9] Figure 9 is a table of construct identifiers to SEQ ID NOs. Construct 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] Figure 10 shows 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] Figures 11a-11ao show 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 in the figure. [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] Figure 12 is a table of 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] Figure 13 shows 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] Figures 14a-14af show binding of the 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 figures. [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] Figure 15 is a table of construct identifiers 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]Figure 16 shows 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] Figures 17a-17d show the 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 in the figure. [Figure 17B] Same as above. [Figure 17C] Same as above. [Figure 17D] Same as above. [Figure 18] Figure 18 is a table of construct identifiers to SEQ ID NOs. Construct 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] Figure 19 shows 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. MYT4165 to MYT4174 are histidine-scanning and alanine-scanning variants of the hu139.10 light chain combination. [Figure 20A]Figures 20a-20j show the 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 in the figures. [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] Figure 21 is a table of construct identifiers to 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] Figure 22 shows 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. 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]Figures 23a-23aq show 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] Figure 24 is a table of 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] Figure 25 shows 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]Figures 26a-26ad show 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 specified 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] Figure 27 is a table of construct identifiers 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 to the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 28] Figure 28 shows 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 to MYT4388 are histidine-scanning and alanine-scanning variants of the heavy chain combination of huAD208.4.1. [Figure 29A] Figures 29a-29d show binding of histidine-scanning and alanine-scanning variants of huAD208.4.1 to LRRC15 by biolayer interferometry. Histidine-scanning and alanine-scanning variants of huAD208.4.1 heavy chain combinations, 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] Figure 30 is a table of construct identifiers to 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]Figure 31 shows 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 to MYT4399 are histidine-scanning and alanine-scanning variants of the huAD208.4.1 light chain combination. [Figure 32A] Figures 32a-32j show binding of histidine-scanning and alanine-scanning variants of huAD208.4.1 to LRRC15 by biolayer interferometry. Histidine-scanning and alanine-scanning variants of huAD208.4.1 light chain combinations, 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] Figure 33 is a table of construct identifiers to 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]Figure 34 shows 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. 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] Figures 35a-35as show the binding of huAD208.12.1 starting ABPC and histidine-scanning and alanine-scanning variants to LRRC15 by biolayer interferometry. MYT3179 (huAD208.12.1) and MYT4090-MYT4133 heavy chain histidine-scanning and alanine-scanning variants were captured on an anti-human Fc biosensor and allowed to bind to LRRC15 at pH 7.4, as indicated in the figure. Dissociation was 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] Figure 36 is a table of 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] Figure 37 shows 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] Figures 38a-38aa show 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 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, as specified in the figure. 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] Figure 39 is a table corresponding construct identifiers to SEQ ID NOs. Construct light chain histidine-scanning and alanine-scanning variants 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] Figures 40a-40b show the binding affinity characterization 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] Figures 41a-41g show the internalization of anti-LRRC15 mAbs in cells. Anti-LRRC15 pH-engineered antibody variants, the corresponding starting ABPC antibody, a control IgG1 isotype control (BP0297, Bioxcell), and the vehicle control specified in Figure 41 were assayed for internalization 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 42 shows the 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. The melting temperatures (Tm) were calculated as the maximum values ​​of the graph and are tabulated. [Figure 43] Figure 43 shows an SDS PAGE of MYT0766. Purified MYT0766 was loaded onto a non-reducing (NR) and reducing (R) SDS PAGE gel to confirm size and purity. The theoretical molecular weight of intact MYT0766 is approximately 109 kDa. DETAILED DESCRIPTION OF THE INVENTION

[0071] Provided herein is an antigen-binding protein construct (ABPC) 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 internalization of the ABPC by the target mammalian cell. Some embodiments of any of the ABPCs described herein may further include a conjugated toxin, radioisotope, drug, or small molecule (e.g., a fluorophore or dye).

[0072] Also provided is an antigen-binding protein construct (ABPC) 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 greater than or equal to 1. 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.

[0073] 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., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) 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., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) 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., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) amino acids have been substituted with histidine, and a light chain variable domain of samrotamab in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) 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.

[0074] In some embodiments of any of the ABPCs 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 to 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 to 8 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 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) 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, 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: 6 to 8 have been substituted with histidine.

[0075] In some embodiments of any of the ABPCs 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 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., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) amino acids 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.

[0076] In some embodiments of any of the ABPCs 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. [Table 1-1] [Table 1-2]

[0077] In some embodiments of any of the ABPCs 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. [Table 2]

[0078] In some embodiments of any of the ABPCs 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 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, 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:2 listed in Table 2.

[0079] In some embodiments of any of the ABPCs 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., two, three, four, five, six, seven, eight, nine, or ten) amino acid positions of SEQ ID NO:1 listed in Table 1.

[0080] 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% 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.

[0081] 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% 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.

[0082] 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% 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.

[0083] 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% identical to SEQ ID NO:2, where 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, where the heavy chain variable domain comprises a histidine at any specific combination of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0084] 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% 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.

[0085] 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% 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.

[0086] 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% 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.

[0087] 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% identical to SEQ ID NO:2, where 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, where the heavy chain variable domain comprises a histidine at any specific combination of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0088] 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% identical to SEQ ID NO:2, where 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, where the heavy chain variable domain comprises a histidine at any specific combination of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0089] 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% identical to SEQ ID NO:2, where 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, where the heavy chain variable domain comprises a histidine at any specific combination of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0090] 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., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) histidines have been substituted with alanine. 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., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) histidines have been substituted with alanine. 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., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) histidines have been substituted with alanine, and a light chain variable domain of samrotamab in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) histidines have been substituted with alanine. 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.

[0091] In some embodiments of any of the ABPCs 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 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 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 to 5 have been substituted with alanine; 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, 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 to 8 have been substituted with alanine.

[0092] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises 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.

[0093] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises 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.

[0094] In some embodiments of any of the ABPCs 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.

[0095] In some embodiments of any of the ABPCs 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.

[0096] In some embodiments of any of the ABPCs 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.

[0097] In some embodiments of any of the ABPCs 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.

[0098] In some embodiments of any of the ABPCs 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.

[0099] In some embodiments of any of the ABPCs 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.

[0100] In some embodiments of any of the ABPCs 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.

[0101] In some embodiments of any of the ABPCs 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.

[0102] In some embodiments of any of the ABPCs 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.

[0103] In some embodiments of any of the ABPCs 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.

[0104] In some embodiments of any of the ABPCs 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.

[0105] In some embodiments of any of the ABPCs 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.

[0106] In some embodiments of any of the ABPCs 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.

[0107] In some embodiments of any of the ABPCs 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.

[0108] In some embodiments of any of the ABPCs 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.

[0109] In some embodiments of any of the ABPCs 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.

[0110] In some embodiments of any of the ABPCs 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.

[0111] In some embodiments of any of the ABPCs 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.

[0112] In some embodiments of any of the ABPCs 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.

[0113] In some embodiments of any of the ABPCs 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.

[0114] In some embodiments of any of the ABPCs 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.

[0115] In some embodiments of any of the ABPCs 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.

[0116] In some embodiments of any of the ABPCs 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.

[0117] In some embodiments of any of the ABPCs 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.

[0118] In some embodiments of any of the ABPCs 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.

[0119] In some embodiments of any of the ABPCs 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.

[0120] In some embodiments of any of the ABPCs 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.

[0121] In some embodiments of any of the ABPCs 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.

[0122] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain of SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, or SEQ ID NO:83.

[0123] In some embodiments of any of the ABPCs 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.

[0124] In some embodiments of any of the ABPCs 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.

[0125] In some embodiments of any of the ABPCs 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.

[0126] In some embodiments of any of the ABPCs 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.

[0127] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain of hu139.10 in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) 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 hu139.10 in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) 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 hu139.10 in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) amino acids have been substituted with histidine, and a light chain variable domain of hu139.10 in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) amino acids have been substituted with histidine. In some embodiments of any of the ABPCs described herein, the heavy chain variable domain of hu139.10 comprises SEQ ID NO: 84. In some embodiments of any of the ABPCs described herein, the light chain variable domain of hu139.10 comprises SEQ ID NO: 85.

[0128] In some embodiments of any of the ABPCs 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, 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: 86 to 88 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 set forth in SEQ ID NO: 89, SEQ ID NO: 90, and SEQ ID NO: 91, 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: 89 to 91 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 comprising CDR1, CDR2, and CDR3 which are 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., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs: 89 to 91 have been substituted with histidine; and a light chain variable domain comprising CDR1, CDR2, and CDR3 which are 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., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs: 89 to 91 have been substituted with histidine.

[0129] In some embodiments of any of the ABPCs 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 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 consisting 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 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 histidine amino acid residue at one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) amino acid positions of SEQ ID NO: 85 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., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) amino acid positions of SEQ ID NO: 84 selected from the group consisting of 29, 31, 32, 34, 36, 37, 38, 40, 56, 60, 61, 95, 96, 97, or 100.

[0130] In some embodiments of any of the ABPCs 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.

[0131] In some embodiments of any of the ABPCs 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.

[0132] In some embodiments of any of the ABPCs 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.

[0133] In some embodiments of any of the ABPCs 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%, at least 99%, or 100%) identical to SEQ ID NO: 85. and a light chain variable domain that is 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 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.

[0134] In some embodiments of any of the ABPCs 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%, at least 99%, or 100%) identical to SEQ ID NO: 85. and a light chain variable domain that is 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 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.

[0135] In some embodiments of any of the ABPCs 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., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) 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 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 or an alanine at position 98; 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., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) 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.

[0136] In some embodiments of any of the ABPCs 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 98 of SEQ ID NO: 84. [Table 3]

[0137] In some embodiments of any of the ABPCs 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]

[0138] In some embodiments of any of the ABPCs 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.

[0139] In some embodiments of any of the ABPCs 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 particular combination of one or more amino acids located in 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 particular combination of one or more amino acids located in SEQ ID NO: 84 listed in Table 4.

[0140] In some embodiments of any of the ABPCs 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 specific combination of one or more amino acids located in 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 specific combination of one or more amino acids located in SEQ ID NO: 84 listed in Table 4.

[0141] In some embodiments of any of the ABPCs 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., two, three, four, five, six, seven, eight, nine, or ten) amino acid positions of SEQ ID NO: 84 listed in Table 3.

[0142] 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% 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.

[0143] 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% 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.

[0144] 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% 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.

[0145] 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% 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.

[0146] 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% 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.

[0147] 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% 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.

[0148] 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% 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.

[0149] 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% 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.

[0150] 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% 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.

[0151] 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% 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.

[0152] 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% 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.

[0153] 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% 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.

[0154] 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% 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.

[0155] 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% 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.

[0156] 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% 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.

[0157] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain of hu139.10 in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) histidines have been substituted with alanine. In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain of hu139.10 in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) histidines have been substituted with alanine. In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain of hu139.10 in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) histidines have been substituted with alanine, and a light chain variable domain of hu139.10 in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) histidines have been substituted with alanine. In some embodiments of any of the ABPCs described herein, the heavy chain variable domain of hu139.10 comprises SEQ ID NO: 84. In some embodiments of any of the ABPCs described herein, the light chain variable domain of hu139.10 comprises SEQ ID NO: 85.

[0158] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NO: 86, SEQ ID NO: 87, and SEQ ID NO: 88, respectively, collectively 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. In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NO: 89, SEQ ID NO: 90, and SEQ ID NO: 91, respectively, in which 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 collectively substituted with alanine. In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NO: 86, SEQ ID NO: 87, and SEQ ID NO: 88, respectively, in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines of SEQ ID NO: 86-88 have been collectively replaced with alanine; and a light chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NO: 89, SEQ ID NO: 90, and SEQ ID NO: 91, in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines of SEQ ID NO: 89-91 have been collectively replaced with alanine.

[0159] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain of 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.

[0160] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain of 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.

[0161] In some embodiments of any of the ABPCs 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.

[0162] In some embodiments of any of the ABPCs 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.

[0163] In some embodiments of any of the ABPCs 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.

[0164] In some embodiments of any of the ABPCs 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.

[0165] In some embodiments of any of the ABPCs 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.

[0166] In some embodiments of any of the ABPCs 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.

[0167] In some embodiments of any of the ABPCs 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.

[0168] In some embodiments of any of the ABPCs 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.

[0169] In some embodiments of any of the ABPCs 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.

[0170] In some embodiments of any of the ABPCs 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.

[0171] In some embodiments of any of the ABPCs 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.

[0172] In some embodiments of any of the ABPCs 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.

[0173] In some embodiments of any of the ABPCs 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.

[0174] In some embodiments of any of the ABPCs 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.

[0175] In some embodiments of any of the ABPCs 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.

[0176] In some embodiments of any of the ABPCs 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.

[0177] In some embodiments of any of the ABPCs 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.

[0178] In some embodiments of any of the ABPCs 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.

[0179] In some embodiments of any of the ABPCs 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.

[0180] In some embodiments of any of the ABPCs 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.

[0181] In some embodiments of any of the ABPCs 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.

[0182] In some embodiments of any of the ABPCs 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.

[0183] In some embodiments of any of the ABPCs 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.

[0184] In some embodiments of any of the ABPCs 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.

[0185] In some embodiments of any of the ABPCs 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.

[0186] In some embodiments of any of the ABPCs 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.

[0187] In some embodiments of any of the ABPCs 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.

[0188] In some embodiments of any of the ABPCs 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.

[0189] In some embodiments of any of the ABPCs 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.

[0190] In some embodiments of any of the ABPCs 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.

[0191] In some embodiments of any of the ABPCs 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.

[0192] In some embodiments of any of the ABPCs 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.

[0193] In some embodiments of any of the ABPCs 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.

[0194] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain of SEQ ID NO:164, SEQ ID NO:165, SEQ ID NO:166, or SEQ ID NO:167.

[0195] In some embodiments of any of the ABPCs 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.

[0196] In some embodiments of any of the ABPCs 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.

[0197] In some embodiments of any of the ABPCs 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.

[0198] In some embodiments of any of the ABPCs 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.

[0199] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain of 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.

[0200] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 168 and a light 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, and a heavy chain variable domain comprising 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.

[0201] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 169 and a light 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, and a heavy chain variable domain comprising 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.

[0202] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 170 and a light 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, and a heavy chain variable domain comprising 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.

[0203] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 171 and a light 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, and a heavy chain variable domain comprising 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.

[0204] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 172 and a light 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, and a heavy chain variable domain comprising 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.

[0205] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 173 and a light 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, and a heavy chain variable domain comprising 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.

[0206] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 174 and a light 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, and a heavy chain variable domain comprising 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.

[0207] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 175 and a light 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, and a heavy chain variable domain comprising 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.

[0208] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 176 and a light 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, and a heavy chain variable domain comprising 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.

[0209] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 177 and a light 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, and a heavy chain variable domain comprising 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.

[0210] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain of huAD208.4.1 in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) 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 huAD208.4.1 in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) 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 huAD208.4.1 in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) amino acids have been substituted with histidine, and a light chain variable domain of huAD208.4.1 in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) amino acids have been substituted with histidine. In some embodiments of any of the ABPCs described herein, the heavy chain variable domain of huAD208.4.1 comprises SEQ ID NO: 178. In some embodiments of any of the ABPCs described herein, the light chain variable domain of huAD208.4.1 comprises SEQ ID NO: 179.

[0211] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NO: 180, SEQ ID NO: 181, and SEQ ID NO: 182, respectively, in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) entire amino acid positions of SEQ ID NOs: 180-182 have been collectively substituted with histidine. In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NO: 183, SEQ ID NO: 184, and SEQ ID NO: 185, respectively, in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) entire amino acid positions of SEQ ID NOs: 183-185 have been collectively substituted with histidine. In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NO: 180, SEQ ID NO: 181, and SEQ ID NO: 182, respectively, in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) entire amino acid positions of SEQ ID NOs: 180-182 have been collectively substituted with histidine, and a light chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NO: 183, SEQ ID NO: 184, and SEQ ID NO: 185, respectively, in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) entire amino acid positions of SEQ ID NOs: 183-185 have been collectively substituted with histidine.

[0212] In some embodiments of any of the ABPCs 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, 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: 178 selected from the group consisting of 33, 52, 56, 57, or 106. 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: 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 consisting of 25, 26, 28, 29, 31, 36, 37, 57, 59, 94, 95, 96, or 100.In some embodiments of any of the ABPCs 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 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. 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., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) 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.

[0213] In some embodiments of any of the ABPCs 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. [Table 5]

[0214] In some embodiments of any of the ABPCs 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. [Table 6-1] [Table 6-2]

[0215] In some embodiments of any of the ABPCs 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 and that includes a histidine at any of the specific combinations of one or more amino acids located in SEQ ID NO: 178 listed in Table 5; 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 includes a histidine at any of the specific combinations of one or more amino acid positions in SEQ ID NO: 179 listed in Table 6.

[0216] In some embodiments of any of the ABPCs 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., two, three, four, five, six, seven, eight, nine, ten) amino acid positions of SEQ ID NO: 178 listed in Table 5.

[0217] 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% 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.

[0218] 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% 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.

[0219] 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% 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.

[0220] 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% 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.

[0221] 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% 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.

[0222] 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% 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.

[0223] 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% 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.

[0224] 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% 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.

[0225] 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% 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.

[0226] 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% 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.

[0227] 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% 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.

[0228] 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% 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.

[0229] 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% 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.

[0230] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain of huAD208.4.1 in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) histidines have been substituted with alanine. In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain of huAD208.4.1 in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) histidines have been substituted with alanine. In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain of huAD208.4.1 in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) histidines have been substituted with alanine, and a light chain variable domain of huAD208.4.1 in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) histidines have been substituted with alanine. In some embodiments of any of the ABPCs described herein, the heavy chain variable domain of huAD208.4.1 comprises SEQ ID NO: 178. In some embodiments of any of the ABPCs described herein, the light chain variable domain of huAD208.4.1 comprises SEQ ID NO: 179.

[0231] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NO: 180, SEQ ID NO: 181, and SEQ ID NO: 182, respectively, in which 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 collectively substituted with alanine. In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NO: 183, SEQ ID NO: 184, and SEQ ID NO: 185, respectively, in which 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 collectively substituted with alanine. In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NO: 180, SEQ ID NO: 181, and SEQ ID NO: 182, respectively, in which 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 collectively substituted with alanine, and a light chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NO: 183, SEQ ID NO: 184, and SEQ ID NO: 185, respectively, in which 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 collectively substituted with alanine.

[0232] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain of 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.

[0233] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain of 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.

[0234] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 179 and a light 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, and a heavy chain variable domain comprising 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.

[0235] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:228, and a light 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: 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.

[0236] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:229 and a light 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.

[0237] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:230 and a light 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.

[0238] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:231 and a light 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.

[0239] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:232 and a light 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.

[0240] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:233 and a light 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.

[0241] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:234 ​​and a light 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.

[0242] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:235, and a light 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: 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.

[0243] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:236 and a light 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.

[0244] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:237 and a light 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.

[0245] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:238 and a light 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.

[0246] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:239 and a light 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.

[0247] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:240 and a light 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.

[0248] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:241 and a light 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.

[0249] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:242 and a light 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.

[0250] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:243 and a light 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.

[0251] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:244 and a light 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.

[0252] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:245 and a light 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.

[0253] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:246 and a light 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 described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:247 and a light 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 described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:248 and a light 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 described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:249 and a light 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 described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:250 and a light 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, SE...

Claims

1. 1. A pharmaceutical composition for treating a disease characterized by having a population of cells that display LRRC15 or an epitope of LRRC15 on their surface, comprising an antigen binding protein construct (ABPC), wherein the disease is not cancer, and the composition is administered to a subject identified as having the disease, the ABPC comprising: a first antigen-binding domain capable of specifically binding to LRRC15 or an epitope of LRRC15 displayed on the surface of a target mammalian cell; the first antigen-binding domain (a) a heavy chain variable domain comprising heavy chain CDRs of SEQ ID NO: 1, wherein the heavy chain variable domain comprises a histidine at one position of SEQ ID NO: 1 selected from the group consisting of 33, 34, 50, 52, 57, 59, 100, 102, 103, 107, 108 and 109, a histidine at two positions of SEQ ID NO: 1 selected from the group consisting of 34, 59, 103, or a histidine at positions 34, 59 and 103 of SEQ ID NO: 1; and a light chain variable domain comprising light chain CDRs of SEQ ID NO: 2, wherein the light chain variable domain comprises a histidine at one position of SEQ ID NO: 2 selected from the group consisting of 32, 34, 50, 51, 89, 90, 92, 93, 94 and 96 of SEQ ID NO: 2; a heavy chain variable domain comprising heavy chain CDRs of SEQ ID NO: 1, wherein the heavy chain variable domain comprises a histidine at one position of SEQ ID NO: 1 selected from the group consisting of 33, 34, 50, 52, 57, 59, 100, 102, 103, 107, 108 and 109, a histidine at two positions of SEQ ID NO: 1 selected from the group consisting of 34, 59 and 103, or histidines at positions 34, 59 and 103 of SEQ ID NO: 1, and a light chain variable domain comprising light chain CDRs of SEQ ID NO: 2; or a heavy chain variable domain comprising the heavy chain CDRs of SEQ ID NO: 1 and a light chain variable domain comprising the light chain CDRs of SEQ ID NO: 2, wherein the light chain variable domain comprises a histidine at one position of SEQ ID NO: 2 selected from the group consisting of 32, 34, 50, 51, 89, 90, 92, 93, 94 and 96; (b) a heavy chain variable domain comprising a heavy chain CDR of SEQ ID NO: 84, wherein the heavy chain variable domain comprises a histidine at one position of SEQ ID NO: 84 selected from the group consisting of 27, 29, 32, 50, 54, 58, 99, 100, 102, 104 and 105, or an alanine at position 98 and a histidine at position 104 of SEQ ID NO: 84, and a light chain variable domain comprising a light chain CDR of SEQ ID NO: 85, wherein the light chain variable domain comprises a histidine at one position 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, a histidine at two positions of SEQ ID NO: 84 selected from the group consisting of 40, 56, 61 and 100, or a histidine at three positions of SEQ ID NO: 84 selected from the group consisting of 40, 56, 61 and 100; a heavy chain variable domain comprising the heavy chain CDRs of SEQ ID NO: 84, wherein the heavy chain variable domain comprises a histidine at one position of SEQ ID NO: 84 selected from the group consisting of 27, 29, 32, 50, 54, 58, 99, 100, 102, 104 and 105, or an alanine at position 98 and a histidine at position 104 of SEQ ID NO: 84, and a light chain variable domain comprising the light chain CDRs of SEQ ID NO: 85; or a heavy chain variable domain comprising the heavy chain CDRs of SEQ ID NO: 84, and a light chain variable domain comprising the light chain CDRs of SEQ ID NO: 85, wherein the light chain variable domain comprises a histidine at one position 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, a histidine at two positions of SEQ ID NO: 84 selected from the group consisting of 40, 56, 61 and 100, or a histidine at three positions of SEQ ID NO: 84 selected from the group consisting of 40, 56, 61 and 100; (c) a heavy chain variable domain comprising a heavy chain CDR of SEQ ID NO: 178, wherein the heavy chain variable domain comprises a histidine at one position of SEQ ID NO: 178 selected from the group consisting of 33, 52, 56, 57 or 106, a histidine at two positions of SEQ ID NO: 178 selected from the group consisting of 33, 103 and 106, or a histidine at positions 33, 103 and 106 of SEQ ID NO: 178; and a light chain variable domain comprising a light chain CDR of SEQ ID NO: 179, wherein the light chain variable domain comprises a histidine at one position 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, a histidine at two positions of SEQ ID NO: 179 selected from the group consisting of 25, 31 and 36, or a histidine at three positions of SEQ ID NO: 179 selected from the group consisting of 25, 26, 31 and 36; a heavy chain variable domain comprising the heavy chain CDRs of SEQ ID NO: 178, wherein the heavy chain variable domain comprises a histidine at one position of SEQ ID NO: 178 selected from the group consisting of 33, 52, 56, 57 or 106, a histidine at two positions of SEQ ID NO: 178 selected from the group consisting of 33, 103 and 106, or a histidine at positions 33, 103 and 106 of SEQ ID NO: 178, and a light chain variable domain comprising the light chain CDRs of SEQ ID NO: 179; or a heavy chain variable domain comprising the heavy chain CDRs of SEQ ID NO: 178, and a light chain variable domain comprising the light chain CDRs of SEQ ID NO: 179, wherein the light chain variable domain comprises a histidine at one position 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, a histidine at two positions of SEQ ID NO: 179 selected from the group consisting of 25, 31, and 36, or a histidine at three positions of SEQ ID NO: 179 selected from the group consisting of 25, 26, 31, and 36; or (d) a heavy chain variable domain comprising the heavy chain CDRs of SEQ ID NO: 272, wherein the heavy chain variable domain comprises a histidine at one position in SEQ ID NO: 272 selected from the group consisting of 24, 27, 29, 62, 63, 98, and 108, and a light chain variable domain comprising the light chain CDRs of SEQ ID NO: 273, wherein the light chain variable domain comprises a histidine at one position in SEQ ID NO: 273 selected from the group consisting of 27, 28, 29, 31, 32, 89, 92, and 93; a heavy chain variable domain comprising the heavy chain CDRs of SEQ ID NO:272, wherein the heavy chain variable domain comprises a histidine at one position of SEQ ID NO:272 selected from the group consisting of 24, 27, 29, 62, 63, 98 and 108, and a light chain variable domain comprising the light chain CDRs of SEQ ID NO:273; or a heavy chain variable domain comprising the heavy chain CDRs of SEQ ID NO:272, and a light chain variable domain comprising the light chain CDRs of SEQ ID NO:273, wherein the light chain variable domain comprises a histidine at one position of SEQ ID NO:273 selected from the group consisting of 27, 28, 29, 31, 32, 89, 92, and 93. Including, (i) the dissociation rate of the first antigen-binding domain at pH 5.4 is faster than the dissociation rate at pH 7.4; or (ii) the dissociation constant (K) of the first antigen-binding domain at pH 5.4 Ｄ ) is K at pH 7.4 Ｄ The pharmaceutical composition is greater than or equal to 1000 mg / kg.

2. The pharmaceutical composition described in claim 1, wherein the ABPC is degraded in the target mammalian cells after intracellular translocation of the ABPC by the target mammalian cells.

3. The pharmaceutical composition of claim 1 or 2, wherein the ABPC further comprises a conjugated toxin, radioisotope, drug, or small molecule.

4. The pharmaceutical composition, an increase in toxin release in said target mammalian cells compared to a composition containing an equal amount of a control ABPC; increased killing of target mammalian cells compared to a composition containing an equivalent amount of a control ABPC; and Increased endolysosomal delivery in said target mammalian cells compared to a composition containing an equivalent amount of a control ABPC. The pharmaceutical composition of claim 3, wherein the pharmaceutical composition provides one or more of the following:

5. The method of claim 1, wherein the first antigen-binding domain comprises: a heavy chain variable domain comprising heavy chain CDRs of SEQ ID NO: 1, wherein the heavy chain variable domain comprises a histidine at one position of SEQ ID NO: 1 selected from the group consisting of 33, 34, 50, 52, 57, 59, 100, 102, 103, 107, 108 and 109, a histidine at two positions of SEQ ID NO: 1 selected from the group consisting of 34, 59, 103, or a histidine at positions 34, 59 and 103 of SEQ ID NO: 1; and a light chain variable domain comprising light chain CDRs of SEQ ID NO: 2, wherein the light chain variable domain comprises a histidine at one position of SEQ ID NO: 2 selected from the group consisting of 32, 34, 50, 51, 89, 90, 92, 93, 94 and 96 of SEQ ID NO: 2; a heavy chain variable domain comprising heavy chain CDRs of SEQ ID NO: 1, wherein the heavy chain variable domain comprises a histidine at one position of SEQ ID NO: 1 selected from the group consisting of 33, 34, 50, 52, 57, 59, 100, 102, 103, 107, 108 and 109, a histidine at two positions of SEQ ID NO: 1 selected from the group consisting of 34, 59 and 103, or histidines at positions 34, 59 and 103 of SEQ ID NO: 1, and a light chain variable domain comprising light chain CDRs of SEQ ID NO: 2; or a heavy chain variable domain comprising the heavy chain CDRs of SEQ ID NO: 1 and a light chain variable domain comprising the light chain CDRs of SEQ ID NO: 2, wherein the light chain variable domain comprises a histidine at one position of SEQ ID NO: 2 selected from the group consisting of 32, 34, 50, 51, 89, 90, 92, 93, 94 and 96. The pharmaceutical composition according to any one of claims 1 to 4, comprising:

6. The first antigen-binding domain 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 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 Including, the first antigen-binding domain does not comprise a light chain variable domain of SEQ ID NO: 2 and a heavy chain variable domain of SEQ ID NO: 1; The pharmaceutical composition according to claim 5.

7. The method of claim 1, wherein the first antigen-binding domain comprises: a heavy chain variable domain comprising a heavy chain CDR of SEQ ID NO: 84, wherein the heavy chain variable domain comprises a histidine at one position of SEQ ID NO: 84 selected from the group consisting of 27, 29, 32, 50, 54, 58, 99, 100, 102, 104 and 105, or an alanine at position 98 and a histidine at position 104 of SEQ ID NO: 84; and a light chain variable domain comprising a light chain CDR of SEQ ID NO: 85, wherein the light chain variable domain comprises a histidine at one position 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, a histidine at two positions of SEQ ID NO: 84 selected from the group consisting of 40, 56, 61 and 100, or a histidine at three positions of SEQ ID NO: 84 selected from the group consisting of 40, 56, 61 and 100; a heavy chain variable domain comprising the heavy chain CDRs of SEQ ID NO: 84, wherein the heavy chain variable domain comprises a histidine at one position of SEQ ID NO: 84 selected from the group consisting of 27, 29, 32, 50, 54, 58, 99, 100, 102, 104 and 105, or an alanine at position 98 and a histidine at position 104 of SEQ ID NO: 84, and a light chain variable domain comprising the light chain CDRs of SEQ ID NO: 85; or a heavy chain variable domain comprising the heavy chain CDRs of SEQ ID NO: 84, and a light chain variable domain comprising the light chain CDRs of SEQ ID NO: 85, wherein the light chain variable domain comprises a histidine at one position 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, a histidine at two positions of SEQ ID NO: 84 selected from the group consisting of 40, 56, 61, and 100, or a histidine at three positions of SEQ ID NO: 84 selected from the group consisting of 40, 56, 61, and 100. The pharmaceutical composition according to any one of claims 1 to 4, comprising:

8. The method of claim 1, wherein the first antigen-binding domain comprises: a light 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 The heavy chain variable domain of SEQ ID NO:84, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:98, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, 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 Including, the first antigen-binding domain does not comprise a light chain variable domain of SEQ ID NO: 85 and a heavy chain variable domain of SEQ ID NO: 84; The pharmaceutical composition of claim 7.

9. The method of claim 8, wherein the first antigen-binding domain comprises: a heavy chain variable domain comprising a heavy chain CDR of SEQ ID NO: 178, wherein the heavy chain variable domain comprises a histidine at one position of SEQ ID NO: 178 selected from the group consisting of 33, 52, 56, 57 or 106, a histidine at two positions of SEQ ID NO: 178 selected from the group consisting of 33, 103 and 106, or a histidine at positions 33, 103 and 106 of SEQ ID NO: 178; and a light chain variable domain comprising a light chain CDR of SEQ ID NO: 179, wherein the light chain variable domain comprises a histidine at one position 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, a histidine at two positions of SEQ ID NO: 179 selected from the group consisting of 25, 31 and 36, or a histidine at three positions of SEQ ID NO: 179 selected from the group consisting of 25, 26, 31 and 36; a heavy chain variable domain comprising the heavy chain CDRs of SEQ ID NO: 178, wherein the heavy chain variable domain comprises a histidine at one position of SEQ ID NO: 178 selected from the group consisting of 33, 52, 56, 57 or 106, a histidine at two positions of SEQ ID NO: 178 selected from the group consisting of 33, 103 and 106, or a histidine at positions 33, 103 and 106 of SEQ ID NO: 178, and a light chain variable domain comprising the light chain CDRs of SEQ ID NO: 179; or a heavy chain variable domain comprising the heavy chain CDRs of SEQ ID NO: 178, and a light chain variable domain comprising the light chain CDRs of SEQ ID NO: 179, wherein the light chain variable domain comprises a histidine at one position 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, a histidine at two positions of SEQ ID NO: 179 selected from the group consisting of 25, 31, and 36, or a histidine at three positions of SEQ ID NO: 179 selected from the group consisting of 25, 26, 31, and 36. The pharmaceutical composition according to any one of claims 1 to 4, comprising:

10. The first antigen-binding domain, 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 The 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 Including, the first antigen-binding domain does not comprise a light chain variable domain of SEQ ID NO: 179 and a heavy chain variable domain of SEQ ID NO: 178; The pharmaceutical composition of claim 9.

11. The first antigen-binding domain, a heavy chain variable domain comprising the heavy chain CDRs of SEQ ID NO:272, wherein the heavy chain variable domain comprises a histidine at one position of SEQ ID NO:272 selected from the group consisting of 24, 27, 29, 62, 63, 98 and 108, and a light chain variable domain comprising the light chain CDRs of SEQ ID NO:273, wherein the light chain variable domain comprises a histidine at one position of SEQ ID NO:273 selected from the group consisting of 27, 28, 29, 31, 32, 89, 92 and 93; a heavy chain variable domain comprising the heavy chain CDRs of SEQ ID NO:272, wherein the heavy chain variable domain comprises a histidine at one position of SEQ ID NO:272 selected from the group consisting of 24, 27, 29, 62, 63, 98 and 108, and a light chain variable domain comprising the light chain CDRs of SEQ ID NO:273; or a heavy chain variable domain comprising the heavy chain CDRs of SEQ ID NO:272, and a light chain variable domain comprising the light chain CDRs of SEQ ID NO:273, wherein the light chain variable domain comprises a histidine at one position of SEQ ID NO:273 selected from the group consisting of 27, 28, 29, 31, 32, 89, 92, and 93. The pharmaceutical composition according to any one of claims 1 to 4, comprising:

12. The first antigen-binding domain, 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 The 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 Including, the first antigen-binding domain does not comprise a light chain variable domain of SEQ ID NO: 273 and a heavy chain variable domain of SEQ ID NO: 272; The pharmaceutical composition of claim 11.

13. The pharmaceutical composition comprising: a lesser reduction in the level of LRRC15 displayed on the surface of said target mammalian cells compared to a composition comprising an equivalent amount of a control ABPC; or does not result in a detectable decrease in the level of LRRC15 displayed on the surface of said target mammalian cells; The pharmaceutical composition according to any one of claims 1 to 12.

14. The ABPC, 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; The pharmaceutical composition according to any one of claims 1 to 13.

15. A pharmaceutical composition described in any one of claims 1 to 14, wherein the ABPC comprises a single polypeptide.

16. The pharmaceutical composition described in claim 15, wherein the antigen-binding domain is an scFv.

17. A pharmaceutical composition described in any one of claims 1 to 14, wherein the ABPC comprises two or more polypeptides.

18. The pharmaceutical composition described in claim 14, wherein the ABPC is an antibody.

19. A pharmaceutical composition described in any one of claims 1 to 18, wherein the ABPC further comprises a second antigen-binding domain.

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