Antigen-binding protein constructs and uses thereof

Abstract

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 presented on the surface of a target mammalian cell, 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 first antigen binding domain has a dissociation constant (KD) at a pH of about 4.0 to about 6.5 greater than a KD at a pH of about 7.0 to about 8.0.

Description

[0001] This application is a divisional application of a Chinese patent application with an application date of October 2, 2020, an application number of 202080081551.9, and an invention title of "Antigen-binding Protein Constructs and Their Use". Technical Field

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

[0003] Antibody-drug conjugates have been designed to combat various diseases. A particular advantage of this approach is that antibody-drug conjugates can have cytostatic or cytotoxic effects. Despite years of development, improved antibody-drug conjugates are needed. Summary of the Invention

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

[0005] Provided herein are pharmaceutical compositions comprising an effective amount of an antigen-binding protein construct (ABPC) that comprises: a first antigen-binding domain that is capable of specifically binding to LRRC15 or an epitope of LRRC15 presented 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 ) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is larger than the K D at a pH of about 7.0 to about 8.0.

[0006] In some embodiments of the pharmaceutical compositions described herein, the ABPC is degraded in the target mammalian cell after the ABPC is internalized by the target mammalian cell.

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

[0008] The present invention also provides a pharmaceutical composition comprising an effective amount of an antigen-binding protein construct (ABPC), said ABPC comprising: a first antigen-binding domain capable of specifically binding to LRRC15 or an epitope of LRRC15 presented 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 D ) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is greater than the K D at a pH of about 7.0 to about 8.0; and (b) the composition provides one or more of the following: an increase in toxin release in the target mammalian cells as compared to a composition comprising the same amount of a control ABPC; an increase in target mammalian cell killing as compared to a composition comprising the same amount of a control ABPC; and an increase in endolysosomal delivery in the target mammalian cells as compared to a composition comprising the same amount of a control ABPC.

[0009] In some embodiments of the pharmaceutical compositions described herein, the first antigen-binding domain comprises one of (a) to (d): (a) the heavy-chain variable domain of samrotamab in which one or more amino acids are replaced by histidine, wherein the heavy-chain variable domain of samrotamab comprises SEQ ID NO:1; and / or the light-chain variable domain of samrotamab in which one or more amino acids are replaced by histidine, wherein the light-chain variable domain of samrotamab comprises SEQ ID NO:2; (b) the heavy-chain variable domain of hu139.10 in which one or more amino acids are replaced by histidine, wherein the heavy-chain variable domain of hu139.10 comprises SEQ ID NO:84; and / or the light-chain variable domain of hu139.10 in which one or more amino acids are replaced by histidine, wherein the light-chain variable domain of hu139.10 comprises SEQ ID NO:85; (c) the heavy-chain variable domain of huAD208.4.1 in which one or more amino acids are replaced by histidine, wherein the heavy-chain variable domain of huAD208.4.1 comprises SEQ ID NO:178; and / or the light-chain variable domain of huAD208.4.1 in which one or more amino acids are replaced by histidine, wherein the light-chain variable domain of huAD208.4.1 comprises SEQ ID NO:179; and (d) the heavy-chain variable domain of huAD208.12.1 in which one or more amino acids are replaced by histidine, wherein the heavy-chain variable domain of huAD208.12.1 comprises SEQ ID NO:272; and / or the light-chain variable domain of huAD208.12.1 in which one or more amino acids are replaced by histidine, wherein the light-chain variable domain of huAD208.12.1 comprises 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: 3-5, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 3-5 are collectively substituted with histidine; and / or a light-chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 6-8, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 6-8 are collectively substituted with histidine; (b) a heavy-chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 86-88, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 86-88 are collectively substituted with histidine; and / or a light-chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 89-91, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 89-91 are collectively substituted with histidine; (c) a heavy-chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 180-182, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 180-182 are collectively substituted with histidine; and / or a light-chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 183-185, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 183-185 are collectively substituted with histidine; and (d) a heavy-chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 274-276, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 274-276 are collectively substituted with histidine; and / or a light-chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 277-279, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 277-279 are collectively substituted with histidine.

[0011] In some embodiments of the pharmaceutical compositions described herein, the first antigen-binding domain comprises one of (a) to (d): (a) a heavy chain variable domain that is at least 90% identical to SEQ ID NO:1, wherein the heavy chain variable domain comprises histidine at one or more positions selected from the group consisting of: 33, 34, 50, 52, 57, 59, 100, 102, 103, 107, 108, and 109 in SEQ ID NO:1; and / or a light chain variable domain that is at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises histidine at one or more positions selected from the group consisting of: 32, 34, 50, 51, 89, 90, 92, 93, 94, and 96 in SEQ ID NO:2; (b) a heavy chain variable domain that is at least 90% identical to SEQ ID NO:84, wherein the heavy chain variable domain comprises histidine at one or more positions selected from the group consisting of: 27, 29, 32, 50, 54, 58, 99, 100, 102, 104, and 105 in SEQ ID NO:84; and / or a light chain variable domain that is at least 90% identical to SEQ ID NO:85, wherein the light chain variable domain comprises histidine at one or more positions selected from the group consisting of: 29, 31, 32, 34, 36, 37, 38, 40, 56, 60, 61, 95, 96, 97, and 100 in SEQ ID NO:85; (c) a heavy chain variable domain that is at least 90% identical to SEQ ID NO:178, wherein the heavy chain variable domain comprises histidine at one or more positions selected from the group consisting of: 33, 52, 56, 57, or 106 in SEQ ID NO:178; and / or a light chain variable domain that is at least 90% identical to SEQ ID NO:179, wherein the light chain variable domain comprises histidine at one or more positions selected from the group consisting of: 25, 26, 28, 29, 31, 36, 37, 57, 59, 94, 95, 96, and 100 in SEQ ID NO:179; and (d) a heavy chain variable domain that is at least 90% identical to SEQ ID NO:272, wherein the heavy chain variable domain comprises histidine at one or more positions selected from the group consisting of: 24, 27, 29, 62, 63, 98, and 108 in SEQ ID NO:272; and / or a light chain variable domain that is at least 90% identical to SEQ ID NO:273, wherein the light chain variable domain comprises histidine at one or more positions selected from the group consisting of: 27, 28, 29, 31, 32, 89, 92, and 93 in SEQ ID NO:273.

[0012] In some embodiments of the pharmaceutical composition described herein, the first antigen-binding domain comprises one of (a) to (d): (a) a light chain variable domain of: SEQ ID NO:2, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76 or SEQ ID NO:78; and / or a heavy chain variable domain of: SEQ ID NO:1, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82 or SEQ ID NO:83, wherein the first antigen-binding domain does not include: (i) the light chain variable domain of SEQ ID NO:2 and the heavy chain variable domain of SEQ ID NO:1; (ii) the light chain variable domain of SEQ ID NO:2 and a heavy chain variable domain other than one of SEQ ID NO:20, 21, 23, 25, 30, 32, 43, 45, 46, 50 - 52 or 80 - 83; or (iii) the heavy chain variable domain of SEQ ID NO:1 and a light chain variable domain other than one of SEQ ID NO:61, 63 - 65, 71, 72, 74 - 76 or 78;(b) The following light chain variable domains: 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 the following heavy chain variable domains: 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 does not include: (i) the light chain variable domain of SEQ ID NO:85 and the heavy chain variable domain of SEQ ID NO:84; (ii) the light chain variable domain of SEQ ID NO:85 and a heavy chain variable domain that is not one of the following: SEQ ID NO:93, 95, 98, 101, 102, 106, 110, 120-122, 124, 126, 127 or 166; or (iii) the heavy chain variable domain of SEQ ID NO:84 and a light chain variable domain that is not one of the following: SEQ ID NO:137, 139, 140, 142, 144-146, 148, 149, 153, 154, 156-158, 161 or 169-177;(c) The following light chain variable domains: 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 the following heavy chain variable domains: 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 does not include: (i) the light chain variable domain of SEQ ID NO:179 and the heavy chain variable domain of SEQ ID NO:178; (ii) the light chain variable domain of SEQ ID NO:179 and a heavy chain variable domain other than one of the following: SEQ ID NO:196, 201, 205, 206, 225 or 258 - 261; or (iii) the heavy chain variable domain of SEQ ID NO:178 and a light chain variable domain other than one of the following: SEQ ID NO:229, 230, 232, 233, 235, 240, 241, 246, 248, 251 - 253, 257, 263, 264 or 268 - 271; and (d) the following light chain variable domains: 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 the following heavy chain variable domains: 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 does not include: (i) the light chain variable domain of SEQ ID NO:273 and the heavy chain variable domain of SEQ ID NO:272; (ii) the light chain variable domain of SEQ ID NO:273 and a heavy chain variable domain that is not one of the following: SEQ ID NO:281, 284, 286, 305, 306, 311 or 321; or (iii) the heavy chain variable domain of SEQ ID NO:272 and a light chain variable domain that is not one of the following: SEQ ID NO:327 - 329, 331, 332, 342, 345 or 346.;

[0013] In some embodiments of the pharmaceutical compositions described herein, the compositions provide the following: an increase in toxin release in the target mammalian cells as compared to a composition comprising the same amount of control ABPC; and / or an increase in target mammalian cell killing as compared to a composition comprising the same amount of control ABPC.

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

[0015] In some embodiments of the pharmaceutical compositions described herein, the compositions: result in less of a decrease in the level of LRRC15 presented on the surface of the target mammalian cells as compared to a composition comprising the same amount of control ABPC; or do not cause a detectable decrease in the level of LRRC15 presented on the surface of the target mammalian cells.

[0016] In some embodiments of the pharmaceutical compositions described herein, the target mammalian cells are cancer cells. In some embodiments of the pharmaceutical compositions described herein, the ABPC is cytotoxic or cytostatic to the target mammalian cells. In some embodiments of the pharmaceutical compositions described herein, the ABPC: is cross-reactive with non-human primate LRRC15 and human LRRC15; or is cross-reactive with non-human primate LRRC15, human LRRC15 and one or both of 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: VH domain, VHH domain, VNAR domain, and 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 the ABPC in vivo is decreased compared to the half-life of a control ABPC in vivo.

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

[0020] The present disclosure also provides an antigen-binding protein construct (ABPC) comprising: a first antigen-binding domain that is capable of specifically binding to LRRC15 or an epitope of LRRC15 presented 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 ) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is greater than the K D at a pH of about 7.0 to about 8.0.

[0021] In some embodiments of the ABPCs described herein, after the ABPC is internalized by the target mammalian cell, the ABPC is degraded in the target mammalian cell.

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

[0023] The present disclosure also provides an antigen-binding protein construct (ABPC) comprising: a first antigen-binding domain that is capable of specifically binding to LRRC15 or an epitope of LRRC15 presented 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 D ) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is greater than the K Dlarge; and (b) the composition provides one or more of the following: an increase in toxin release in the target mammalian cells as compared to a composition comprising the same amount of control ABPC; an increase in target mammalian cell killing as compared to a composition comprising the same amount of control ABPC; and an increase in endolysosomal delivery in the target mammalian cells as compared to a composition comprising the same amount of control ABPC.

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

[0025] In some embodiments of ABPC 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: 3-5, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 3-5 are jointly substituted with histidine; and / or a light chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 6-8, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 6-8 are jointly substituted with histidine; (b) a heavy chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 86-88, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 86-88 are jointly substituted with histidine; and / or a light chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 89-91, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 89-91 are jointly substituted with histidine; (c) a heavy chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 180-182, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 180-182 are jointly substituted with histidine; and / or a light chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 183-185, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 183-185 are jointly substituted with histidine; and (d) a heavy chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 274-276, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 274-276 are jointly substituted with histidine; and / or a light chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 277-279, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 277-279 are jointly substituted with histidine.

[0026] In some embodiments of the ABPCs described herein, the first antigen-binding domain comprises one of (a) to (d): (a) a heavy chain variable domain that is at least 90% identical to SEQ ID NO:1, wherein the heavy chain variable domain comprises histidine at one or more positions selected from the group consisting of: 33, 34, 50, 52, 57, 59, 100, 102, 103, 107, 108, and 109 in SEQ ID NO:1; and / or a light chain variable domain that is at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises histidine at one or more positions selected from the group consisting of: 32, 34, 50, 51, 89, 90, 92, 93, 94, and 96 in SEQ ID NO:2; (b) a heavy chain variable domain that is at least 90% identical to SEQ ID NO:84, wherein the heavy chain variable domain comprises histidine at one or more positions selected from the group consisting of: 27, 29, 32, 50, 54, 58, 99, 100, 102, 104, and 105 in SEQ ID NO:84; and / or a light chain variable domain that is at least 90% identical to SEQ ID NO:85, wherein the light chain variable domain comprises histidine at one or more positions selected from the group consisting of: 29, 31, 32, 34, 36, 37, 38, 40, 56, 60, 61, 95, 96, 97, and 100 in SEQ ID NO:85; (c) a heavy chain variable domain that is at least 90% identical to SEQ ID NO:178, wherein the heavy chain variable domain comprises histidine at one or more positions selected from the group consisting of: 33, 52, 56, 57, or 106 in SEQ ID NO:178; and / or a light chain variable domain that is at least 90% identical to SEQ ID NO:179, wherein the light chain variable domain comprises histidine at one or more positions selected from the group consisting of: 25, 26, 28, 29, 31, 36, 37, 57, 59, 94, 95, 96, and 100 in SEQ ID NO:179; and (d) a heavy chain variable domain that is at least 90% identical to SEQ ID NO:272, wherein the heavy chain variable domain comprises histidine at one or more positions selected from the group consisting of: 24, 27, 29, 62, 63, 98, and 108 in SEQ ID NO:272; and / or a light chain variable domain that is at least 90% identical to SEQ ID NO:273, wherein the light chain variable domain comprises histidine at one or more positions selected from the group consisting of: 27, 28, 29, 31, 32, 89, 92, and 93 in SEQ ID NO:273.

[0027] In some embodiments of the ABPC described herein, the first antigen-binding domain comprises one of (a) to (d): (a) a light chain variable domain of: SEQ ID NO:2, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76 or SEQ ID NO:78, and / or a heavy chain variable domain of: SEQ ID NO:1, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82 or SEQ ID NO:83, wherein the first antigen-binding domain does not include: (i) the light chain variable domain of SEQ ID NO:2 and the heavy chain variable domain of SEQ ID NO:1; (ii) the light chain variable domain of SEQ ID NO:2 and a heavy chain variable domain that is not one of: SEQ ID NO:20, 21, 23, 25, 30, 32, 43, 45, 46, 50 - 52 or 80 - 83; or (iii) the heavy chain variable domain of SEQ ID NO:1 and a light chain variable domain that is not one of: SEQ ID NO:61, 63 - 65, 71, 72, 74 - 76 or 78;(b) The following light chain variable domains: 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 the following heavy chain variable domains: 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 does not include: (i) the light chain variable domain of SEQ ID NO:85 and the heavy chain variable domain of SEQ ID NO:84; (ii) the light chain variable domain of SEQ ID NO:85 and a heavy chain variable domain that is not one of the following: SEQ ID NO:93, 95, 98, 101, 102, 106, 110, 120-122, 124, 126, 127 or 166; or (iii) the heavy chain variable domain of SEQ ID NO:84 and a light chain variable domain that is not one of the following: SEQ ID NO:137, 139, 140, 142, 144-146, 148, 149, 153, 154, 156-158, 161 or 169-177;(c) The following light chain variable domains: 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 the following heavy chain variable domains: 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 does not include: (i) the light chain variable domain of SEQ ID NO:179 and the heavy chain variable domain of SEQ ID NO:178; (ii) the light chain variable domain of SEQ ID NO:179 and a heavy chain variable domain other than one of the following: SEQ ID NO:196, 201, 205, 206, 225 or 258 - 261; or (iii) the heavy chain variable domain of SEQ ID NO:178 and a light chain variable domain other than one of the following: SEQ ID NO:229, 230, 232, 233, 235, 240, 241, 246, 248, 251 - 253, 257, 263, 264 or 268 - 271; and (d) the following light chain variable domains: 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 the following heavy chain variable domains: 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 does not include: (i) the light chain variable domain of SEQ ID NO:273 and the heavy chain variable domain of SEQ ID NO:272; (ii) the light chain variable domain of SEQ ID NO:273 and a heavy chain variable domain that is not one of the following: SEQ ID NO:281, 284, 286, 305, 306, 311 or 321; or (iii) the heavy chain variable domain of SEQ ID NO:272 and a light chain variable domain that is not one of the following: SEQ ID NO:327-329, 331, 332, 342, 345 or 346.;

[0028] In some embodiments of the ABPCs described herein, a composition comprising the ABPC provides the following: an increase in the release of toxin in the target mammalian cells as compared to a composition comprising the same amount of a control ABPC; and / or an increase in the killing of target mammalian cells as compared to a composition comprising the same amount of a control ABPC.

[0029] In some embodiments of the ABPCs described herein, a composition comprising the ABPC provides an increase in endolysosomal delivery in the target mammalian cells as compared to a composition comprising the same amount of a control ABPC.

[0030] In some embodiments of the ABPCs described herein, a composition comprising the ABPC: results in less of a decrease in the level of LRRC15 presented on the surface of the target mammalian cells as compared to a composition comprising the same amount of a control ABPC; or does not cause a detectable decrease in the level of LRRC15 presented on the surface of the target mammalian cells.

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

[0032] In some embodiments of the ABPCs described herein, the ABPCs comprise a single polypeptide. In some embodiments of the ABPCs described herein, the antigen-binding domain is selected from the group consisting of: VH domain, VHH domain, VNAR domain, and scFv. In some embodiments of the ABPCs described herein, the ABPCs comprise two or more polypeptides. In some embodiments of the ABPCs described herein, the ABPCs are antibodies.

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

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

[0035] The present disclosure also provides a kit comprising at least one dose of any of the pharmaceutical compositions described herein and any of the ABPCs described herein.

[0036] The present disclosure also provides a method of treating cancer characterized by a population of cancer cells having LRRC15 or an epitope of LRRC15 presented on the surface of the cancer cells, the method comprising: administering to a subject identified as having cancer a therapeutically effective amount of any of the pharmaceutical compositions described herein or any of the ABPCs described herein, the cancer being characterized by the population of cancer cells.

[0037] The present disclosure also provides a method of reducing the volume of a tumor in a subject, wherein the tumor is characterized by a population of cancer cells having LRRC15 or an epitope of LRRC15 presented on the surface of the cancer cells, the method comprising: administering to a subject identified as having cancer a therapeutically effective amount of any of the pharmaceutical compositions described herein or any of the ABPCs described herein, the cancer being characterized by the population of cancer cells.

[0038] The present disclosure also provides a method of inducing cell death in cancer cells of a subject, wherein the cancer cells have LRRC15 or an epitope of LRRC15 presented on the surface of the cancer cells, the method comprising: administering to a subject identified as having cancer a therapeutically effective amount of any of the pharmaceutical compositions described herein or any of the ABPCs described herein, the cancer being characterized by the population of cancer cells.

[0039] The present disclosure also provides methods for reducing the risk of metastasis in a subject having cancer or reducing the risk of additional metastasis in the subject, wherein the cancer is characterized by a population of cancer cells having LRRC15 or an epitope of LRRC15 presented on the surface of the cancer cells, the method comprising: administering to a subject identified as having cancer a therapeutically effective amount of any of the pharmaceutical compositions described herein or any of the ABPCs described herein, the cancer being characterized by a population of the cancer cells.

[0040] As used herein, the term “antigen-binding protein construct” is: (i) a single polypeptide comprising at least one antigen-binding domain; or (ii) a complex of two or more polypeptides (e.g., the same polypeptide or different polypeptides) that together form at least one antigen-binding domain. Non-limiting examples and aspects of antigen-binding protein constructs are described herein. Additional examples and aspects of antigen-binding protein constructs are known in the art.

[0041] A “multispecific antigen-binding protein construct” is an antigen-binding protein construct that comprises two or more different antigen-binding domains that specifically bind jointly to 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 cell surface) or different antigens (e.g., different proteins present on the same cell surface or on different cell surfaces). In some aspects, the antigen is present on the cell surface. In some aspects, the multispecific antigen-binding protein construct binds two different epitopes (i.e., a “bispecific antigen-binding protein construct”). In some aspects, the multispecific antigen-binding protein construct binds three different epitopes (i.e., a “trispecific antigen-binding protein construct”). In some aspects, the multispecific antigen-binding protein construct binds four different epitopes (i.e., a “tetraspecific antigen-binding protein construct”). In some aspects, the multispecific antigen-binding protein construct binds five different epitopes (i.e., a “pentaspecific antigen-binding protein construct”). Each binding specificity can be present in any suitable valence. Non-limiting examples of multispecific antigen-binding protein constructs are described herein.

[0042] "Antigen-binding domain" refers to one or more protein domains that are capable of specifically binding to one or more different antigens (e.g., formed from amino acids of a single polypeptide or from amino acids of two or more polypeptides (e.g., the same or different polypeptides)). In some instances, an antigen-binding domain may bind to an antigen or epitope with a specificity and affinity similar to that of a naturally occurring antibody. In some embodiments, the antigen-binding domain can be an antibody or a fragment thereof. In some embodiments, the antigen-binding domain can comprise an alternative scaffold. Non-limiting examples of antigen-binding domains are described herein. Additional examples of antigen-binding domains are known in the art. In some instances, an antigen-binding domain can bind to a single antigen.

[0043] The term "antibody" is used herein in its broadest sense and includes certain types of immunoglobulin molecules that comprise one or more antigen-binding domains that specifically bind to an antigen or epitope. Antibodies specifically include, for example, intact antibodies (e.g., intact immunoglobulins, e.g., human IgG (e.g., human IgG1, human IgG2, human IgG3, human IgG4)), antibody fragments, and multispecific antibodies. An example of an antigen-binding domain is an antigen-binding domain formed by a VH-VL dimer. Additional examples of antibodies are described herein. Additional 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 internalized by cell-mediated endocytic processes (e.g., pinocytosis, micropinocytosis, receptor-mediated endocytosis, and / or phagocytosis) are sorted.

[0045] Once endosomes in the endosomal / lysosomal pathway are purified or isolated, methods known in the art (ELISA, Western blot, immunofluorescence, and immunoprecipitation, followed by determination of protein concentration) can be used to assay for a target protein (e.g., an antigen-binding protein construct as described herein), and can be used to determine the concentration or relative level of the target protein in the endosomes. Alternatively, immunofluorescence microscopy can be used, using a detectable-labeled antibody (e.g., a fluorophore-labeled antibody, a dye-labeled antibody, or a GFP-labeled antibody, e.g., CellLight TM Early Endosome-GFP) that specifically binds to a characteristic protein present in the endosome (e.g., EEA1 of early endosomes) and a fluorophore-labeled antibody that specifically binds to the target protein (e.g., an antigen-binding protein construct) to image endosomes in the endosomal / lysosomal pathway, and the level of the target protein in the endosomes can be determined by quantifying the overlap in the fluorescence emission of the two different antibodies.

[0046] The phrase "endolysosomal delivery" refers to the rate of accumulation over time or the total accumulation at a specific time point of an antigen-binding protein construct (e.g., any antigen-binding protein construct described herein) in the endosomal / lysosomal pathway of a mammalian cell (e.g., any exemplary target mammalian cell described herein).

[0047] An exemplary method for calculating the increase in endolysosomal delivery of a pH-engineered ABPC variant compared to its corresponding starting ABPC from cell fluorescence 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 whole by the mean fluorescence intensity of the corresponding starting ABPC of the variant minus the mean fluorescence intensity of the IgG control.

[0048] Exemplary assays for measuring endosomal delivery of any ABPC described herein include those involving: labeling the ABPC with a fluorescent dye, then incubating the labeled ABPC with cells and measuring cell fluorescence as an indicator of ABPC endolysosomal delivery (e.g., as generally described in Wustner, Traffic 7(6):699-715, 2006). Alternatively, a pH-sensitive dye that fluoresces preferentially at acidic pH rather than neutral pH can be used to label any ABPC described herein, and then the ABPC can be incubated with cells and cell fluorescence can be measured as an indicator of ABPC delivery to acidic endolysosomal compartments.

[0049] When the term "population" is used in front of a noun, it means two or more specific nouns. For example, the phrase "a 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 the proliferation (cell division) of a cell (e.g., a cancer cell) in vivo or in vitro. When an agent is cytostatic to a cell, the agent can, for example, directly or indirectly cause cell cycle arrest in the cell (e.g., a cancer cell). In some instances, an agent that is cytostatic to a cell can reduce the number of cells in the S phase in a cell population (compared to the number of cells in the S phase in the cell population before contact with the agent). In some instances, an agent that is cytostatic to a cell can reduce the percentage of cells in the 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 the S phase in the cell population before contact with the agent).

[0051] The phrase "cytotoxic to a cell" refers to directly or indirectly inducing the death (e.g., necrosis or apoptosis) of a cell (e.g., a mammalian cell, e.g., a cancer cell).

[0052] "Affinity" refers to the overall strength of the non-covalent interactions between an antigen-binding site and its binding partner (e.g., an antigen or an epitope). Unless otherwise stated, as used herein, "affinity" refers to the intrinsic binding affinity, which reflects the 1:1 interaction between an antigen-binding domain and a member of an antigen or an epitope. The affinity of molecule X for its partner Y can be expressed by the dissociation equilibrium constant (K D ). Affinity can be measured by conventional methods known in the art (including those described herein). Affinity can be determined, for example, using surface plasmon resonance (SPR) technology (e.g., ) or biolayer interferometry (e.g., ). Additional methods for determining the affinity of an antigen-binding domain and its corresponding antigen or epitope are known in the art.

[0053] The term "epitope" means a part of an antigen that is specifically bound by an antigen-binding domain through a set of physical interactions between: (i) all monomers on the part of the antigen-binding domain that specifically binds the antigen (e.g., individual amino acid residues, sugar side chains, and post-translationally modified amino acid residues), and (ii) all monomers on the part of the antigen that is specifically bound by the antigen-binding domain (e.g., individual amino acid residues, sugar side chains, post-translationally modified amino acid residues). An epitope can, for example, consist of surface-accessible amino acid residues, sugar side chains, phosphorylated amino acid residues, methylated amino acid residues, and / or acetylated amino acid residues and can have specific three-dimensional structural features as well as specific charge features. The difference between a conformational epitope and a non-conformational epitope is that binding to the former, but not the latter, may be lost in the presence of a denaturing solvent. In some embodiments, an epitope is defined by a linear amino acid sequence of at least about 3 to 6 amino acids or about 10 to 15 amino acids. In some embodiments, an epitope refers to a part of a full-length protein or a part thereof defined by a three-dimensional structure (e.g., a protein fold). In some embodiments, an epitope is defined by a discontinuous amino acid sequence that is brought together via protein folding. In some embodiments, an epitope is defined by a discontinuous amino acid sequence that is brought 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 an epitope may not be critical for the three-dimensional structure of the epitope. Assays that compare the binding of an antigen-binding protein construct to a denatured form of an antigen can be used to identify and screen conformational epitopes in order to generate linear epitopes. An epitope can contain amino acid residues directly involved in binding and other amino acid residues not directly involved in binding.

[0054] Methods for identifying epitopes to which an antigen-binding domain specifically binds are known in the art, such as structure-based analysis (e.g., X-ray crystallography, NMR, and / or electron microscopy) (e.g., based on the antigen and / or antigen-antigen-binding domain complex), and / or mutagenesis-based analysis (e.g., alanine-scanning mutagenesis, glycine-scanning mutagenesis, and homologous-scanning mutagenesis), where mutants are measured with a binding partner in a binding assay, and many of the mutants are known in the art.

[0055] The term "complementary site" means a part of an antigen-binding domain that specifically binds to an antigen through a set of physical interactions between: (i) all monomers on the part of the antigen-binding domain that specifically binds the antigen (e.g., individual amino acid residues, sugar side chains, post-translationally modified amino acid residues), and (ii) all monomers on the part of the antigen that is specifically bound by the antigen-binding domain (e.g., individual amino acid residues, sugar side chains, post-translationally modified amino acid residues). The complementary site can, for example, consist of surface-accessible amino acid residues and can have specific three-dimensional structural features as well as specific charge features. In some embodiments, the complementary site refers to a part of the full-length antigen-binding domain defined by a three-dimensional structure (e.g., a protein fold) or a part thereof. In some embodiments, the complementary site is defined by discontinuous amino acid sequences that are brought together by protein folding. In some embodiments, the epitope is defined by discontinuous amino acid sequences that are brought 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 complementary site may not be critical for the three-dimensional structure of the complementary site. The complementary site can include amino acid residues directly involved in binding and other amino acid residues not directly involved in binding.

[0056] Methods for identifying complementary sites to which an antigen-binding domain specifically binds are known in the art, such as structure-based analysis (e.g., X-ray crystallography, NMR, and / or electron microscopy) (e.g., based on the antigen-binding domain, and / or antigen-binding domain-antigen complex), and / or mutagenesis-based analysis (e.g., alanine-scanning mutagenesis, glycine-scanning mutagenesis, and homologous-scanning mutagenesis), where mutants are measured with a binding partner in a binding assay, and many of the mutants are known in the art.

[0057] The phrase "present on the surface of mammalian cells" means (1) an antigen that is physically attached to or at least partially embedded in the plasma membrane of a mammalian cell (e.g., a transmembrane protein, a peripheral membrane protein, a lipid-anchored protein (e.g., a GPI-anchor), an N-myristoylated protein, or an S-palmitoylated protein) or (2) an antigen that stably binds to its cognate receptor, where the cognate receptor is physically attached to the plasma membrane of a mammalian cell (e.g., a ligand that binds to its cognate receptor, where the cognate receptor is physically attached to the plasma membrane). Non-limiting methods for determining the presence of an antigen on the surface of mammalian cells include fluorescence-activated cell sorting (FACS), immunohistochemistry, cell fractionation assays, and Western blotting.

[0058] The phrase "control ABPC" or "control antigen-binding protein construct" means (i) an ABPC that is capable of specifically binding to LRRC15 or an epitope of LRRC15 presented on the surface of a mammalian cell (e.g., a target mammalian cell), where one or both of the following are true: (a) the dissociation rate of the first antigen-binding domain at a pH of from about 4.0 to about 6.5 (e.g., any subrange within this range described herein) is no more than 3-fold (e.g., no more than 2.8-fold, no more than 2.6-fold, no more than 2.5-fold, no more than 2.4-fold, no more than 2.2-fold, no more than 2.0-fold, no more than 1.8-fold, no more than 1.6-fold, no more than 1.5-fold, no more than 1.4-fold, no more than 1.2-fold, no more than 1.0-fold, no more than 0.8-fold, no more than 0.6-fold, no more than 0.5-fold, no more than 0.4-fold, no more than 0.3-fold, no more than 0.2-fold, or no more than 0.1-fold) of the dissociation rate at a pH of from about 7.0 to about 8.0 (e.g., any subrange within this range described herein); or (b) the dissociation constant (K D ) of the first antigen-binding domain at a pH of from about 4.0 to about 6.5 (e.g., any subrange within this range described herein) is no more than 3-fold (e.g., no more than 2.8-fold, no more than 2.6-fold, no more than 2.5-fold, no more than 2.4-fold, no more than 2.2-fold, no more than 2.0-fold, no more than 1.8-fold, no more than 1.6-fold, no more than 1.5-fold, no more than 1.4-fold, no more than 1.2-fold, no more than 1.0-fold, no more than 0.8-fold, no more than 0.6-fold, no more than 0.5-fold, no more than 0.4-fold, no more than 0.3-fold, no more than 0.2-fold, or no more than 0.1-fold) of the K D at a pH of from about 7.0 to about 8.0 (e.g., any subrange within this range described herein); (ii) sarilumab; (iii) hu139.10; (iv) huAD208.4.1 and / or (v) huAD208.12.1.

[0059] The term "extracellular space" means the fluid outside the plasma membrane of a mammalian cell. When a mammalian cell is in vitro, the extracellular space can be the liquid culture medium. When a mammalian cell is in vivo, the extracellular space can be, for example, plasma, serum, blood, interstitial fluid, or lymph.

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

[0061] The phrase "reduced level" or "decreased level" can be a reduction or decrease 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%) compared to a reference level or reference value.

[0062] The term "cytotoxic efficacy" refers to the ability of an agent (e.g., any ABPC described herein) to directly or indirectly induce apoptosis and / or necrosis in mammalian cells (e.g., cancer cells) as measured by the rate over time or at relevant time points. Methods for determining the cytotoxic efficacy of cells are known in the art (e.g., trypan blue staining, microscopy, fluorescence-activated cell sorting, and assays for detecting apoptotic markers (e.g., annexin V)). In non-limiting examples, cytotoxic efficacy can be measured, for example, by cell killing at a single concentration of the agent, by the IC50 of the agent (i.e., the concentration of the agent that achieves half of the maximum cytotoxic efficacy), or by the ratio of the dissociation constant KD of the agent on mammalian cells divided by its IC50. In some non-limiting examples, the ratio of the IC50 and / or KD ratio described herein to that of a control ABPC (as defined herein) is compared, and optionally it is demonstrated that the ABPC described herein has a higher cytotoxic efficacy compared to 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 conjugated to a toxin (e.g., any of the ABPCs described herein or control ABPCs) and subsequently release the toxin conjugated to the ABPC, as measured by the rate over time or at a specific time point. Toxin release can be evaluated 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 isotopically labeled toxins.

[0064] The phrase "target cell" or "target mammalian cell" or "mammalian target cell" means a mammalian cell having at least one LRRC15 present on its surface. In some instances, the mammalian target cell can be a cancer cell. In some embodiments of the target mammalian cell, there can be a total of about 1 to about 10,000,000, about 1 to about 9,000,000, about 1 to about 8,000,000, about 1 to about 7,000,000, about 1 to about 6,000,000, about 1 to about 5,000,000, about 1 to about 4,000,000, about 1 to about 3,000,000, about 1 to about 2,000,000, about 1 to about 1,000,000, about 1 to about 800,000, about 1 to about 600,000, about 1 to about 400,000, about 1 to about 200,000, about 1 to about 100,000, about 1 to about 80,000, about 1 to about 80,000, about 1 to about 75,000, about 1 to about 70,000, about 1 to about 65,000, about 1 to about 60,000, about 1 to about 55,000, about 1 to about 50,000, about 1 to about 45,000, about 1 to about 40,000, about 1 to about 35,000, about 1 to about 30,000, about 1 to about 25,000, about 1 to about 20,000, about 1 to about 15,000, about 1 to about 10,000, about 1 to about 7,500, about 1 to about 5,000, about 1 to about 4,000, about 1 to about 3,000, about 1 to about 2,000, about 1 to about 1,000, about 1 to about 500, about 1 to about 100, about 1 to about 50, about 1 to about 10, about 10 to about 10,000,000, about 10 to about 9,000,000, about 10 to about 8,000,000, about 10 to about 7,000,000, about 10 to about 6,000,000, about 10 to about 5,000,000, about 10 to about 4,000,000, about 10 to about 3,000,000, about 10 to about 2,000,000, about 10 to about 1,000,000, about 10 to about 800,000, about 10 to about 600,000, about 10 to about 400,000, about 10 to about 200,000, about 10 to about 100,000, about 10 to about 80,000, about 10 to about 80,000, about 10 to about 75,000, about 10 to about 70,000, about 10 to about 65,000, about 10 to about 60,000, about 10 to about 55,000, about 10 to about 50,0, about 10 to about 45,000, about 10 to about 40,000, about 10 to about 35,000, about 10 to about 30,000, about 10 to about 25,000, about 10 to about 20,000, about 10 to about 15,000, about 10 to about 10,000, about 10 to about 7,500, about 10 to about 5,000, about 10 to about 4,000, about 10 to about 3,000, about 10 to about 2,000, about 10 to about 1,000, about 10 to about 500, about 10 to about 100, about 10 to about 50, about 50 to about 10,000,000, about 50 to about 9,000,000, about 50 to about 8,000,000, about 50 to about 7,000,000, about 50 to about 6,000,000, about 50 to about 5,000,000, about 50 to about 4,000,000, about 50 to about 3,000,000, about 50 to about 2,000,000, about 50 to about 1,000,000, about 50 to about 800,000, about 50 to about 600,000, about 50 to about 400,000, about 50 to about 200,000, about 50 to about 100,000, about 50 to about 80,000, about 50 to about 80,000, about 50 to about 75,000, about 50 to about 70,000, about 50 to about 65,000, about 50 to about 60,000, about 50 to about 55,000, about 50 to about 50,000, about 50 to about 45,000, about 50 to about 40,000, about 50 to about 35,000, about 50 to about 30,000, about 50 to about 25,000, about 50 to about 20,000, about 50 to about 15,000, about 50 to about 10,000, about 50 to about 7,500, about 50 to about 5,000, about 50 to about 4,000, about 50 to about 3,000, about 50 to about 2,000, about 50 to about 1,000, about 50 to about 500, about 50 to about 100, about 100 to about 10,000,000, about 100 to about 9,000,000, about 100 to about 8,000,000, about 100 to about 7,000,000, about 100 to about 6,000,000, about 100 to about 5,000,000, about 100 to about 4,000,000, about 100 to about 3,000,000, about 100 to about 2,000,000, about 100 to about 1,000,000, about 100 to about 800,0, about 100 to about 600,000, about 100 to about 400,000, about 100 to about 200,000, about 100 to about 100,000, about 100 to about 80,000, about 100 to about 75,000, about 100 to about 70,000, about 100 to about 65,000, about 100 to about 60,000, about 100 to about 55,000, about 100 to about 50,000, about 100 to about 45,000, about 100 to about 40,000, about 100 to about 35,000, about 100 to about 30,000, about 100 to about 25,000, about 100 to about 20,000, about 100 to about 15,000, about 100 to about 10,000, about 100 to about 7,500, about 100 to about 5,000, about 100 to about 4,000, about 100 to about 3,000, about 100 to about 2,000, about 100 to about 1,000, about 100 to about 500, about 500 to about 10,000,000, about 500 to about 9,000,000, about 500 to about 8,000,000, about 500 to about 7,000,000, about 500 to about 6,000,000, about 500 to about 5,000,000, about 500 to about 4,000,000, about 500 to about 3,000,000, about 500 to about 2,000,000, about 500 to about 1,000,000, about 500 to about 800,000, about 500 to about 600,000, about 500 to about 400,000, about 500 to about 200,000, about 500 to about 100,000, about 500 to about 80,000, about 500 to about 75,000, about 500 to about 70,000, about 500 to about 65,000, about 500 to about 60,000, about 500 to about 55,000, about 500 to about 50,000, about 500 to about 45,000, about 500 to about 40,000, about 500 to about 35,000, about 500 to about 30,000, about 500 to about 25,000, about 500 to about 20,000, about 500 to about 15,000, about 500 to about 10,000, about 500 to about 7,500, about 500 to about 5,000, about 500 to about 4,000, about 500 to about 3,000, about 500 to about 2,000, about 500 to about 1,000, about 1,000 to about 10,000,000, about 1,000 to about 9,000,0, about 1,000 to about 8,000,000, about 1,000 to about 7,000,000, about 1,000 to about 6,000,000, about 1,000 to about 5,000,000, about 1,000 to about 4,000,000, about 1,000 to about 3,000,000, about 1,000 to about 2,000,000, about 1,000 to about 1,000,000, about 1,000 to about 800,000, about 1,000 to about 600,000, about 1,000 to about 400,000, about 1,000 to about 200,000, about 1,000 to about 100,000, about 1,000 to about 80,000, about 1,000 to about 75,000, about 1,000 to about 70,000, about 1,000 to about 65,000, about 1,000 to about 60,000, about 1,000 to about 55,000, about 1,000 to about 50,000, about 1,000 to about 45,000, about 1,000 to about 40,000, about 1,000 to about 35,000, about 1,000 to about 30,000, about 1,000 to about 25,000, about 1,000 to about 20,000, about 1,000 to about 15,000, about 1,000 to about 10,000, about 1,000 to about 7,500, about 1,000 to about 5,000, about 1,000 to about 4,000, about 1,000 to about 3,000, about 1,000 to about 2,000, about 2,000 to about 10,000,000, about 2,000 to about 9,000,000, about 2,000 to about 8,000,000, about 2,000 to about 7,000,000, about 2,000 to about 6,000,000, about 2,000 to about 5,000,000, about 2,000 to about 4,000,000, about 2,000 to about 3,000,000, about 2,000 to about 2,000,000, about 2,000 to about 1,000,000, about 2,000 to about 800,000, about 2,000 to about 600,000, about 2,000 to about 400,000, about 2,000 to about 200,000, about 2,000 to about 100,000, about 2,000 to about 80,000, about 2,000 to about 75,000, about 2,000 to about 70,000, about 2,000 to about 65,000, about 2,000 to about 60,000, about 2,000 to about 55,000, about 2,000 to about 50,0, about 2,000 to about 45,000, about 2,000 to about 40,000, about 2,000 to about 35,000, about 2,000 to about 30,000, about 2,000 to about 25,000, about 2,000 to about 20,000, about 2,000 to about 15,000, about 2,000 to about 10,000, about 2,000 to about 7,500, about 2,000 to about 5,000, about 2,000 to about 4,000, about 2,000 to about 3,000, about 3,000 to about 10,000,000, about 3,000 to about 9,000,000, about 3,000 to about 8,000,000, about 3,000 to about 7,000,000, about 3,000 to about 6,000,000, about 3,000 to about 5,000,000, about 3,000 to about 4,000,000, about 3,000 to about 3,000,000, about 3,000 to about 2,000,000, about 3,000 to about 1,000,000, about 3,000 to about 800,000, about 3,000 to about 600,000, about 3,000 to about 400,000, about 3,000 to about 200,000, about 3,000 to about 100,000, about 3,000 to about 80,000, about 3,000 to about 75,000, about 3,000 to about 70,000, about 3,000 to about 65,000, about 3,000 to about 60,000, about 3,000 to about 55,000, about 3,000 to about 50,000, about 3,000 to about 45,000, about 3,000 to about 40,000, about 3,000 to about 35,000, about 3,000 to about 30,000, about 3,000 to about 25,000, about 3,000 to about 20,000, about 3,000 to about 15,000, about 3,000 to about 10,000, about 3,000 to about 7,500, about 3,000 to about 5,000, about 3,000 to about 4,000, about 4,000 to about 10,000,000, about 4,000 to about 9,000,000, about 4,000 to about 8,000,000, about 4,000 to about 7,000,000, about 4,000 to about 6,000,000, about 4,000 to about 5,000,000, about 4,000 to about 4,000,000, about 4,000 to about 3,000,000, about 4,000 to about 2,000,000, about 4,000 to about 1,000,0, about 4,000 to about 800,000, about 4,000 to about 600,000, about 4,000 to about 400,000, about 4,000 to about 200,000, about 4,000 to about 100,000, about 4,000 to about 80,000, about 4,000 to about 75,000, about 4,000 to about 70,000, about 4,000 to about 65,000, about 4,000 to about 60,000, about 4,000 to about 55,000, about 4,000 to about 50,000, about 4,000 to about 45,000, about 4,000 to about 40,000, about 4,000 to about 35,000, about 4,000 to about 30,000, about 4,000 to about 25,000, about 4,000 to about 20,000, about 4,000 to about 15,000, about 4,000 to about 10,000, about 4,000 to about 7,500, about 4,000 to about 5,000, about 5,000 to about 10,000,000, about 5,000 to about 9,000,000, about 5,000 to about 8,000,000, about 5,000 to about 7,000,000, about 5,000 to about 6,000,000, about 5,000 to about 5,000,000, about 5,000 to about 4,000,000, about 5,000 to about 3,000,000, about 5,000 to about 2,000,000, about 5,000 to about 1,000,000, about 5,000 to about 800,000, about 5,000 to about 600,000, about 5,000 to about 400,000, about 5,000 to about 200,000, about 5,000 to about 100,000, about 5,000 to about 80,000, about 5,000 to about 75,000, about 5,000 to about 70,000, about 5,000 to about 65,000, about 5,000 to about 60,000, about 5,000 to about 55,000, about 5,000 to about 50,000, about 5,000 to about 45,000, about 5,000 to about 40,000, about 5,000 to about 35,000, about 5,000 to about 30,000, about 5,000 to about 25,000, about 5,000 to about 20,000, about 5,000 to about 15,000, about 5,000 to about 10,000, about 5,000 to about 7,500, about 7,500 to about 10,000,000, about 7,500 to about 9,000,000, about 7,500 to about 8,000,0, about 7,500 to about 7,000,000, about 7,500 to about 6,000,000, about 7,500 to about 5,000,000, about 7,500 to about 4,000,000, about 7,500 to about 3,000,000, about 7,500 to about 2,000,000, about 7,500 to about 1,000,000, about 7,500 to about 800,000, about 7,500 to about 600,000, about 7,500 to about 400,000, about 7,500 to about 200,000, about 7,500 to about 100,000, about 7,500 to about 80,000, about 7,500 to about 75,000, about 7,500 to about 70,000, about 7,500 to about 65,000, about 7,500 to about 60,000, about 7,500 to about 55,000, about 7,500 to about 50,000, about 7,500 to about 45,000, about 7,500 to about 40,000, about 7,500 to about 35,000, about 7,500 to about 30,000, about 7,500 to about 25,000, about 7,500 to about 20,000, about 7,500 to about 15,000, about 7,500 to about 10,000, about 10,000 to about 10,000,000, about 10,000 to about 9,000,000, about 10,000 to about 8,000,000, about 10,000 to about 7,000,000, about 10,000 to about 6,000,000, about 10,000 to about 5,000,000, about 10,000 to about 4,000,000, about 10,000 to about 3,000,000, about 10,000 to about 2,000,000, about 10,000 to about 1,000,000, about 10,000 to about 800,000, about 10,000 to about 600,000, about 10,000 to about 400,000, about 10,000 to about 200,000, about 10,000 to about 100,000, about 10,000 to about 80,000, about 10,000 to about 75,000, about 10,000 to about 70,000, about 10,000 to about 65,000, about 10,000 to about 60,000, about 10,000 to about 55,000, about 10,000 to about 50,000, about 10,000 to about 45,000, about 10,000 to about 40,000, about 10,000 to about 35,000, about 10,000 to about 30,000, about 10,0 to about 25,000, about 10,000 to about 20,000, about 10,000 to about 15,000, about 15,000 to about 10,000,000, about 15,000 to about 9,000,000, about 15,000 to about 8,000,000, about 15,000 to about 7,000,000, about 15,000 to about 6,000,000, about 15,000 to about 5,000,000, about 15,000 to about 4,000,000, about 15,000 to about 3,000,000, about 15,000 to about 2,000,000, about 15,000 to about 1,000,000, about 15,000 to about 800,000, about 15,000 to about 600,000, about 15,000 to about 400,000, about 15,000 to about 200,000, about 15,000 to about 100,000, about 15,000 to about 80,000, about 15,000 to about 75,000, about 15,000 to about 70,000, about 15,000 to about 65,000, about 15,000 to about 60,000, about 15,000 to about 55,000, about 15,000 to about 50,000, about 15,000 to about 45,000, about 15,000 to about 40,000, about 15,000 to about 35,000, about 15,000 to about 30,000, about 15,000 to about 25,000, about 15,000 to about 20,000, about 20,000 to about 10,000,000, about 20,000 to about 9,000,000, about 20,000 to about 8,000,000, about 20,000 to about 7,000,000, about 20,000 to about 6,000,000, about 20,000 to about 5,000,000, about 20,000 to about 4,000,000, about 20,000 to about 3,000,000, about 20,000 to about 2,000,000, about 20,000 to about 1,000,000, about 20,000 to about 800,000, about 20,000 to about 600,000, about 20,000 to about 400,000, about 20,000 to about 200,000, about 20,000 to about 100,000, about 20,000 to about 80,000, about 20,000 to about 75,000, about 20,000 to about 70,000, about 20,000 to about 65,000, about 210,000 to about 60,000, about 20,000 to about 55,0, about 20,000 to about 50,000, about 20,000 to about 45,000, about 20,000 to about 40,000, about 20,000 to about 35,000, about 20,000 to about 30,000, about 20,000 to about 25,000, about 25,000 to about 10,000,000, about 25,000 to about 9,000,000, about 25,000 to about 8,000,000, about 25,000 to about 7,000,000, about 25,000 to about 6,000,000, about 25,000 to about 5,000,000, about 25,000 to about 4,000,000, about 25,000 to about 3,000,000, about 25,000 to about 2,000,000, about 25,000 to about 1,000,000, about 25,000 to about 800,000, about 25,000 to about 600,000, about 25,000 to about 400,000, about 25,000 to about 200,000, about 25,000 to about 100,000, about 25,000 to about 80,000, about 25,000 to about 75,000, about 25,000 to about 70,000, about 25,000 to about 65,000, about 25,000 to about 60,000, about 25,000 to about 55,000, about 25,000 to about 50,000, about 25,000 to about 45,000, about 25,000 to about 40,000, about 25,000 to about 35,000, about 25,000 to about 30,000, about 30,000 to about 10,000,000, about 30,000 to about 9,000,000, about 30,000 to about 8,000,000, about 30,000 to about 7,000,000, about 30,000 to about 6,000,000, about 30,000 to about 5,000,000, about 30,000 to about 4,000,000, about 30,000 to about 3,000,000, about 30,000 to about 2,000,000, about 30,000 to about 1,000,000, about 30,000 to about 800,000, about 30,000 to about 600,000, about 30,000 to about 400,000, about 30,000 to about 200,000, about 30,000 to about 100,000, about 30,000 to about 80,000, about 30,000 to about 75,000, about 30,000 to about 70,000, about 30,000 to about 65,000, about 30,from about 0 to about 60,000, from about 30,000 to about 55,000, from about 30,000 to about 50,000, from about 30,000 to about 45,000, from about 30,000 to about 40,000, from about 30,000 to about 35,000, from about 35,000 to about 10,000,000, from about 35,000 to about 9,000,000, from about 35,000 to about 8,000,000, from about 35,000 to about 7,000,000, from about 35,000 to about 6,000,000, from about 35,000 to about 5,000,000, from about 35,000 to about 4,000,000, from about 35,000 to about 3,000,000, from about 35,000 to about 2,000,000, from about 35,000 to about 1,000,000, from about 35,000 to about 800,000, from about 35,000 to about 600,000, from about 35,000 to about 400,000, from about 35,000 to about 200,000, from about 35,000 to about 100,000, from about 35,000 to about 80,000, from about 35,000 to about 75,000, from about 35,000 to about 70,000, from about 35,000 to about 65,000, from about 35,000 to about 60,000, from about 35,000 to about 55,000, from about 35,000 to about 50,000, from about 35,000 to about 45,000, from about 35,000 to about 40,000, from about 40,000 to about 10,000,000, from about 40,000 to about 9,000,000, from about 40,000 to about 8,000,000, from about 40,000 to about 7,000,000, from about 40,000 to about 6,000,000, from about 40,000 to about 5,000,000, from about 40,000 to about 4,000,000, from about 40,000 to about 3,000,000, from about 40,000 to about 2,000,000, from about 40,000 to about 1,000,000, from about 40,000 to about 800,000, from about 40,000 to about 600,000, from about 40,000 to about 400,000, from about 40,000 to about 200,000, from about 40,000 to about 100,000, from about 40,000 to about 80,000, from about 40,000 to about 75,000, from about 40,000 to about 70,000, from about 40,000 to about 65,000, from about 40,000 to about 60,000, from about 40,000 to about 55,000, from about 40,000 to about 50,0, about 40,000 to about 45,000, about 45,000 to about 10,000,000, about 45,000 to about 9,000,000, about 45,000 to about 8,000,000, about 45,000 to about 7,000,000, about 45,000 to about 6,000,000, about 45,000 to about 5,000,000, about 45,000 to about 4,000,000, about 45,000 to about 3,000,000, about 45,000 to about 2,000,000, about 45,000 to about 1,000,000, about 45,000 to about 800,000, about 45,000 to about 600,000, about 45,000 to about 400,000, about 45,000 to about 200,000, about 45,000 to about 100,000, about 45,000 to about 80,000, about 45,000 to about 75,000, about 45,000 to about 70,000, about 45,000 to about 65,000, about 45,000 to about 60,000, about 45,000 to about 55,000, about 45,000 to about 50,000, about 50,000 to about 10,000,000, about 50,000 to about 9,000,000, about 50,000 to about 8,000,000, about 50,000 to about 7,000,000, about 50,000 to about 6,000,000, about 50,000 to about 5,000,000, about 50,000 to about 4,000,000, about 50,000 to about 3,000,000, about 50,000 to about 2,000,000, about 50,000 to about 1,000,000, about 50,000 to about 800,000, about 50,000 to about 600,000, about 50,000 to about 400,000, about 50,000 to about 200,000, about 50,000 to about 100,000, about 50,000 to about 80,000, about 50,000 to about 75,000, about 50,000 to about 70,000, about 50,000 to about 65,000, about 50,000 to about 60,000, about 50,000 to about 55,000, about 55,000 to about 10,000,000, about 55,000 to about 9,000,000, about 55,000 to about 8,000,000, about 55,000 to about 7,000,000, about 55,000 to about 6,000,000, about 55,000 to about 5,000,000, about 55,0 to approximately 4,000,000, approximately 55,000 to approximately 3,000,000, approximately 55,000 to approximately 2,000,000, approximately 55,000 to approximately 1,000,000, 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 approximately 70,000, approximately 55,000 to approximately 65,000, approximately 55,000 to approximately 60,000, approximately 60,000 to approximately 10,000,000, approximately 60,000 to approximately 9,000,000, approximately 60,000 to approximately 8,000,000, approximately 60,000 to 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 1,000,000, 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 75,000, approximately 60,000 to approximately 70,000, approximately 60,000 to approximately 65,000, approximately 65,000 to approximately 10,000,000, approximately 65,000 to approximately 9,000,000, approximately 65,000 to approximately 8,000,000, approximately 65,000 to approximately 7,000,000, approximately 65,000 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 to approximately 800,000, approximately 65,000 to approximately 600,000, approximately 65,000 to approximately 400,000, approximately 65,000 to approximately 200,000, approximately 65,000 to approximately 100,000, approximately 65,000 to approximately 80,000, approximately 65,000 to approximately 75,000, approximately 65,000 to approximately 70,0, about 70,000 to about 10,000,000, about 70,000 to about 9,000,000, about 70,000 to about 8,000,000, about 70,000 to about 7,000,000, about 70,000 to about 6,000,000, about 70,000 to about 5,000,000, about 70,000 to about 4,000,000, about 70,000 to about 3,000,000, about 70,000 to about 2,000,000, about 70,000 to about 1,000,000, about 70,000 to about 800,000, about 70,000 to about 600,000, about 70,000 to about 400,000, about 70,000 to about 200,000, about 70,000 to about 100,000, about 70,000 to about 90,000, about 70,000 to about 80,000, about 80,000 to about 10,000,000, about 80,000 to about 9,000,000, about 80,000 to about 8,000,000, about 80,000 to about 7,000,000, about 80,000 to about 6,000,000, about 80,000 to about 5,000,000, about 80,000 to about 4,000,000, about 80,000 to about 3,000,000, about 80,000 to about 2,000,000, about 80,000 to about 1,000,000, about 80,000 to about 800,000, about 80,000 to about 600,000, about 80,000 to about 400,000, about 80,000 to about 200,000, about 80,000 to about 100,000, about 80,000 to about 90,000, about 90,000 to about 10,000,000, about 90,000 to about 9,000,000, about 90,000 to about 8,000,000, about 90,000 to about 7,000,000, about 90,000 to about 6,000,000, about 90,000 to about 5,000,000, about 90,000 to about 4,000,000, about 90,000 to about 3,000,000, about 90,000 to about 2,000,000, about 90,000 to about 1,000,000, about 90,000 to about 800,000, about 90,000 to about 600,000, about 90,000 to about 400,000, about 90,000 to about 200,000, about 90,000 to about 100,000, about 100,000 to about 10,000,0, about 100,000 to about 9,000,000, about 100,000 to about 8,000,000, about 100,000 to about 7,000,000, about 100,000 to about 6,000,000, about 100,000 to about 5,000,000, about 100,000 to about 4,000,000, about 100,000 to about 3,000,000, about 100,000 to about 2,000,000, about 100,000 to about 1,000,000, about 100,000 to about 800,000, about 100,000 to about 600,000, about 100,000 to about 400,000, about 100,000 to about 200,000, about 200,000 to about 10,000,000, about 200,000 to about 9,000,000, about 200,000 to about 8,000,000, about 200,000 to about 7,000,000, about 200,000 to about 6,000,000, about 200,000 to about 5,000,000, about 200,000 to about 4,000,000, about 200,000 to about 3,000,000, about 200,000 to about 2,000,000, about 200,000 to about 1,000,000, about 200,000 to about 800,000, about 200,000 to about 600,000, about 200,000 to about 400,000, about 400,000 to about 10,000,000, about 400,000 to about 9,000,000, about 400,000 to about 8,000,000, about 400,000 to about 7,000,000, about 400,000 to about 6,000,000, about 400,000 to about 5,000,000, about 400,000 to about 4,000,000, about 400,000 to about 3,000,000, about 400,000 to about 2,000,000, about 400,000 to about 1,000,000, about 400,000 to about 800,000, about 400,000 to about 600,000, about 600,000 to about 10,000,000, about 600,000 to about 9,000,000, about 600,000 to about 8,000,000, about 600,000 to about 7,000,000, about 600,000 to about 6,000,000, about 600,000 to about 5,000,000, about 600,000 to about 4,000,000, about 600,000 to about 3,000,0, about 600,000 to about 2,000,000, about 600,000 to about 1,000,000, about 600,000 to about 800,000, about 800,000 to about 10,000,000, about 800,000 to about 9,000,000, about 800,000 to about 8,000,000, about 800,000 to about 7,000,000, about 800,000 to about 6,000,000, about 800,000 to about 5,000,000, about 800,000 to about 4,000,000, about 800,000 to about 3,000,000, about 800,000 to about 2,000,000, about 800,000 to about 1,000,000, about 1,000,000 to about 10,000,000, about 1,000,000 to about 9,000,000, about 1,000,000 to about 8,000,000, about 1,000,000 to about 7,000,000, about 1,000,000 to about 6,000,000, about 1,000,000 to about 5,000,000, about 1,000,000 to about 4,000,000, about 1,000,000 to about 3,000,000, about 1,000,000 to about 2,000,000, about 2,000,000 to about 10,000,000, about 2,000,000 to about 9,000,000, about 2,000,000 to about 8,000,000, about 2,000,000 to about 7,000,000, about 2,000,000 to about 6,000,000, about 2,000,000 to about 5,000,000, about 2,000,000 to about 4,000,000, about 2,000,000 to about 3,000,000, about 3,000,000 to about 10,000,000, about 3,000,000 to about 9,000,000, about 3,000,000 to about 8,000,000, about 3,000,000 to about 7,000,000, about 3,000,000 to about 6,000,000, about 3,000,000 to about 5,000,000, about 3,000,000 to about 4,000,000, about 4,000,000 to about 10,000,000, about 4,000,000 to about 9,000,000, about 4,000,000 to about 8,000,000, about 4,000,000 to about 7,000,000, about 4,000,000 to about 6,000,000, about 4,000,From about 0 to about 5,000,000, from about 5,000,000 to about 10,000,000, from about 5,000,000 to about 9,000,000, from about 5,000,000 to about 8,000,000, from about 5,000,000 to about 7,000,000, from about 5,000,000 to about 6,000,000, from about 6,000,000 to about 10,000,000, from about 6,000,000 to about 9,000,000, from about 6,000,000 to about 8,000,000, from about 6,000,000 to about 7,000,000, from about 7,000,000 to about 10,000,000, from about 7,000,000 to about 9,000,000, from about 7,000,000 to about 8,000,000, from about 8,000,000 to about 10,000,000, from about 8,000,000 to about 9,000,000 or from about 9,000,000 to about 10,000,000 LRRC15 present on the plasma membrane of the target mammalian cell.,

[0065] The phrase "antigen density" means 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 a particular type of target mammalian cell. "Antigen density" can be measured using, for example, the Quantibright bead kit or a radiolabel (e.g., BD Biosciences PE Phycoerythrin Fluorescence Quantitation Kit, catalog number 340495).

[0066] The phrase "an amino acid is replaced by histidine" means that an amino acid residue that is not histidine in a reference polypeptide sequence is replaced by histidine. Non-limiting methods for replacing an amino acid residue in a reference polypeptide with histidine are described herein. Additional methods for replacing an amino acid residue in a reference polypeptide with histidine are known in the art.

[0067] The phrase "histidine is replaced by alanine" means that an amino acid residue that is histidine in a reference polypeptide sequence is replaced by alanine. Non-limiting methods for replacing histidine in a reference polypeptide with alanine are described herein. Additional methods for replacing histidine in a reference polypeptide with alanine 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 are described herein for use in the present invention; other suitable methods and materials known in the art may also be used. The materials, methods, and examples are illustrative only and not intended to be limiting. All publications, patent applications, patents, sequences, database entries, and other references mentioned herein are hereby incorporated by reference in their entirety. In case of conflict, the present specification (including definitions) shall prevail.

[0069] Other features and advantages of the present invention will be apparent from the following detailed description and figures, as well as from the claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0070] Figure 1 : SDS PAGE for shamalizumab histidine scanning and alanine scanning. The harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS PAGE gel to confirm the expression of shamalizumab and histidine scanning and alanine scanning variants. The arrows indicate the corresponding sizes of IgG on the non-reducing SDS PAGE gel. MYT0963 is shamalizumab, and the remaining lanes (MYT0964 - MYT1003) are shamalizumab heavy chain histidine scanning and alanine scanning variants.

[0071] Figures 2A to 2AO : Binding of shamalizumab starting ABPC and histidine scanning and alanine scanning variants to LRRC15 by biolayer interferometry. MYT0963 (shamalizumab) and MYT0964 - MYT1003 (i.e., heavy chain histidine scanning and alanine scanning variants) were captured on an anti-human Fc biosensor and associated with LRRC15 at low pH or high pH as specified in the figures.

[0072] Figure 3 : Table of construct identifiers corresponding to SEQ ID NOs. The constructs, i.e., heavy chain histidine scanning and alanine scanning variants, are listed in the first column of the table, and the SEQ ID NOs are listed and correspond to the constructs on the left and the appropriate heavy chain and / or light chain classes along the top.

[0073] Figure 4: SDS-PAGE for histidine scanning and alanine scanning of sabatolimab. The harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of sabatolimab and its histidine-scanned and alanine-scanned variants. The arrows indicate the corresponding sizes of IgG on the non-reducing SDS-PAGE gel. MYT2726-MYT2752 are the histidine-scanned and alanine-scanned variants of the sabatolimab light chain.

[0074] Figures 5A to 5AA : Binding of sabatolimab starting ABPC and its histidine-scanned and alanine-scanned variants to LRRC15 by biolayer interferometry. MYT2726-MYT2752, the histidine-scanned and alanine-scanned variants of the sabatolimab light chain, were captured on an anti-human Fc biosensor and associated with LRRC15 at low or high pH as specified in the figures.

[0075] Figure 6 : Table of construct identifiers corresponding to SEQ ID NO. The constructs, which are the histidine-scanned and alanine-scanned variants of the light chain, are listed in the first column of the table, and the SEQ ID NO are listed and correspond to the constructs on the left and the appropriate heavy chain and / or light chain classes along the top.

[0076] Figure 7 : SDS-PAGE for histidine scanning and alanine scanning of sabatolimab. The harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of the histidine-scanned and alanine-scanned variants of sabatolimab. The arrows indicate the corresponding sizes of IgG on the non-reducing SDS-PAGE gel. MYT2722-MYT2725 are the histidine-scanned and alanine-scanned variants of the sabatolimab heavy chain combination.

[0077] Figures 8A to 8D : Binding of the histidine-scanned and alanine-scanned variants of sabatolimab to LRRC15 by biolayer interferometry. MYT2722-MYT2725, the histidine-scanned and alanine-scanned variants of the sabatolimab heavy chain combination, were captured on an anti-human Fc biosensor and associated with LRRC15 at low or high pH as specified in the figures.

[0078] Figure 9 : Table of construct identifiers corresponding to SEQ ID NO. The constructs, which are the histidine-scanned and alanine-scanned variants of the heavy chain combination, are listed in the first column of the table, and the SEQ ID NO are listed and correspond to the constructs on the left and the appropriate heavy chain and / or light chain classes along the top.

[0079] Figure 10: SDS-PAGE for hu139.10 histidine scanning and alanine scanning. The harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of hu139.10 and histidine-scanning and alanine-scanning variants. The arrow indicates the corresponding size of IgG on the non-reducing SDS-PAGE gel. MYT3252 is hu139.10, and the remaining lanes (MYT3253 - MYT3292) are hu139.10 heavy-chain histidine-scanning and alanine-scanning variants.

[0080] Figures 11A to 11AO : Binding of hu139.10 starting ABPC and histidine-scanning and alanine-scanning variants to LRRC15 by biolayer interferometry. MYT3252 (hu139.10) and MYT3253 - MYT3292 (i.e., hu139.10 heavy-chain histidine-scanning and alanine-scanning variants) were captured on an anti-human Fc biosensor and associated with LRRC15 at low pH or high pH as specified in the figures.

[0081] Figure 12 : Construct identifier and SEQ ID NO correspondence table. The constructs, i.e., heavy-chain histidine-scanning and alanine-scanning variants, are listed in the first column of the table, and the SEQ ID NOs are listed and correspond to the constructs on the left and the appropriate heavy-chain and / or light-chain classes along the top.

[0082] Figure 13 : SDS-PAGE for hu139.10 histidine scanning and alanine scanning. The harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of hu139.10 and histidine-scanning and alanine-scanning variants. The arrow indicates the corresponding size of IgG on the non-reducing SDS-PAGE gel. MYT3293 - MYT3324 are hu139.10 light-chain histidine-scanning and alanine-scanning variants.

[0083] Figures 14A to 14AF : Binding of hu139.10 starting ABPC and histidine-scanning and alanine-scanning variants to LRRC15 by biolayer interferometry. MYT3293 - MYT3324, i.e., hu139.10 light-chain histidine-scanning and alanine-scanning variants, were captured on an anti-human Fc biosensor and associated with LRRC15 at low pH or high pH as specified in the figures.

[0084] Figure 15: Construct identifier and SEQ ID NO correspondence table. The constructs, namely the light chain histidine scan and alanine scan variants, are listed in the first column of the table, and the SEQ ID NOs are listed and correspond to the constructs on the left and the appropriate heavy chain and / or light chain classes along the top.

[0085] Figure 16 : SDS PAGE for histidine scan and alanine scan of hu139.10. The harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS PAGE gel to confirm the expression of the hu139.10 histidine scan and alanine scan variants. The arrows indicate the corresponding sizes of IgG on the non-reducing SDS PAGE gel. MYT4161 - MYT4164 are the hu139.10 heavy chain combination histidine scan and alanine scan variants.

[0086] Figures 17A to 17D : Binding of histidine scan and alanine scan variants of hu139.10 to LRRC15 by biolayer interferometry. MYT4161 - MYT4164, the heavy chain combination histidine scan and alanine scan variants, were captured on an anti-human Fc biosensor and associated with LRRC15 at low pH or high pH as specified in the figures.

[0087] Figure 18 : Construct identifier and SEQ ID NO correspondence table. The constructs, namely the heavy chain combination histidine scan and alanine scan variants, are listed in the first column of the table, and the SEQ ID NOs are listed and correspond to the constructs on the left and the appropriate heavy chain and / or light chain classes along the top.

[0088] Figure 19 : SDS PAGE for histidine scan and alanine scan of hu139.10. The harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS PAGE gel to confirm the expression of the hu139.10 histidine scan and alanine scan variants. The arrows indicate the corresponding sizes of IgG on the non-reducing SDS PAGE gel. MYT4165 - MYT4174 are the hu139.10 light chain combination histidine scan and alanine scan variants.

[0089] Figures 20A to 20J : Binding of histidine scan and alanine scan variants of hu139.10 to LRRC15 by biolayer interferometry. MYT4165 - MYT4174, the light chain combination histidine scan and alanine scan variants, were captured on an anti-human Fc biosensor and associated with LRRC15 at low pH or high pH as specified in the figures.

[0090] Figure 21: Construct identifier and SEQ ID NO correspondence table. The constructs, namely the light chain combined histidine scan and alanine scan variants, are listed in the first column of the table, and the SEQ ID NOs are listed and correspond to the constructs on the left and the appropriate heavy chain and / or light chain classes along the top.

[0091] Figure 22 : SDS PAGE for huAD208.4.1 histidine scan and alanine scan. The harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS PAGE gel to confirm the expression of huAD208.4.1 and the histidine scan and alanine scan variants. The arrows indicate the corresponding sizes of IgG on the non-reducing SDS PAGE gel. MYT3325 is huAD208.4.1, and the rest of the lanes (MYT3326 - MYT3367) are huAD208.4.1 heavy chain histidine scan and alanine scan variants.

[0092] Figures 23A to 23AQ : Binding of huAD208.4.1 starting ABPC and histidine scan and alanine scan variants to LRRC15 by biolayer interferometry. MYT3325 (huAD208.4.1) and MYT3326 - MYT3367 (i.e., heavy chain histidine scan and alanine scan variants) were captured on an anti-human Fc biosensor and associated with LRRC15 at low pH or high pH as specified in the figure.

[0093] Figure 24 : Construct identifier and SEQ ID NO correspondence table. The constructs, namely the heavy chain histidine scan and alanine scan variants, are listed in the first column of the table, and the SEQ ID NOs are listed and correspond to the constructs on the left and the appropriate heavy chain and / or light chain classes along the top.

[0094] Figure 25 : SDS PAGE for huAD208.4.1 histidine scan and alanine scan. The harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS PAGE gel to confirm the expression of huAD208.4.1 and the histidine scan and alanine scan variants. The arrows indicate the corresponding sizes of IgG on the non-reducing SDS PAGE gel. MYT3369 - MYT3398 are huAD208.4.1 light chain histidine scan and alanine scan variants.

[0095] Figures 26A to 26AD: Binding of huAD208.4.1 starting ABPC and histidine and alanine scan variants to LRRC15 by biolayer interferometry. MYT3369 - MYT3398, the light chain histidine and alanine scan variants of huAD208.4.1, were captured on an anti - human Fc biosensor and associated with LRRC15 at low or high pH as specified in the figures.

[0096] Figure 27 : Construct identifier to SEQ ID NO correspondence table. Constructs, namely the light chain histidine and alanine scan variants, are listed in the first column of the table, and the SEQ ID NOs are listed and correspond to the constructs on the left and the appropriate heavy chain and / or light chain classes along the top.

[0097] Figure 28 : SDS - PAGE for histidine and alanine scans of huAD208.4.1. The harvested Expi293 cell culture supernatant was loaded onto a non - reducing SDS - PAGE gel to confirm the expression of the histidine and alanine scan variants of huAD208.4.1. The arrows indicate the corresponding sizes of IgG on the non - reducing SDS - PAGE gel. MYT4385 - MYT4388 are the heavy chain combined histidine and alanine scan variants of huAD208.4.1.

[0098] Figures 29A to 29D : Binding of histidine and alanine scan variants of huAD208.4.1 to LRRC15 by biolayer interferometry. MYT4385 - MYT4388, the heavy chain combined histidine and alanine scan variants of huAD208.4.1, were captured on an anti - human Fc biosensor and associated with LRRC15 at low or high pH as specified in the figures.

[0099] Figure 30 : Construct identifier to SEQ ID NO correspondence table. Constructs, namely the heavy chain combined histidine and alanine scan variants, are listed in the first column of the table, and the SEQ ID NOs are listed and correspond to the constructs on the left and the appropriate heavy chain and / or light chain classes along the top.

[0100] Figure 31: SDS-PAGE for histidine scanning and alanine scanning of huAD208.4.1. The harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of the histidine-scanning and alanine-scanning variants of huAD208.4.1. The arrow indicates the corresponding size of IgG on the non-reducing SDS-PAGE gel. MYT4390-MYT4399 are the light-chain combined histidine-scanning and alanine-scanning variants of huAD208.4.1.

[0101] Figures 32A to 32J : Binding of histidine-scanning and alanine-scanning variants of huAD208.4.1 to LRRC15 by biolayer interferometry. MYT4390-MYT4399, the light-chain combined histidine-scanning and alanine-scanning variants of huAD208.4.1, were captured on an anti-human Fc biosensor and associated with LRRC15 at low pH or high pH as specified in the figure.

[0102] Figure 33 : Table of construct identifiers corresponding to SEQ ID NO. Constructs, namely light-chain combined histidine-scanning and alanine-scanning variants, are listed in the first column of the table, and SEQ ID NO is listed and corresponds to the construct on the left and the appropriate heavy-chain and / or light-chain classes along the top.

[0103] Figure 34 : SDS-PAGE for histidine scanning and alanine scanning of huAD208.12.1. The harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of huAD208.12.1 and its histidine-scanning and alanine-scanning variants. The arrow indicates the corresponding size of IgG on the non-reducing SDS-PAGE gel. MYT3179 is huAD208.12.1, and the rest of the lanes (MYT4090-MYT4133) are the heavy-chain histidine-scanning and alanine-scanning variants of huAD208.12.1.

[0104] Figures 35A to 35AS : Binding of huAD208.12.1 starting ABPC and its histidine-scanning and alanine-scanning variants to LRRC15 by biolayer interferometry. MYT3179 (huAD208.12.1) and MYT4090-MYT4133 (i.e., heavy-chain histidine-scanning and alanine-scanning variants) were captured on an anti-human Fc biosensor and associated with LRRC15 at pH 7.4. Dissociation was carried out at pH 7.4 (black trace) or pH 5.4 (gray trace).

[0105] Figure 36: Table of construct identifiers corresponding to SEQ ID NOs. The constructs, namely the heavy chain histidine scan and alanine scan variants, are listed in the first column of the table, and the SEQ ID NOs are listed and correspond to the constructs on the left and the appropriate heavy chain and / or light chain classes along the top.

[0106] Figure 37 : SDS PAGE for histidine scan and alanine scan of huAD208.12.1. The harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS PAGE gel to confirm the expression of huAD208.12.1 and the histidine scan and alanine scan variants. The arrows indicate the corresponding sizes of IgG on the non-reducing SDS PAGE gel. MYT4134-MYT4160 are the light chain histidine scan and alanine scan variants of huAD208.12.1.

[0107] Figures 38A to 38AA : Binding of huAD208.12.1 starting ABPC and histidine scan and alanine scan variants to LRRC15 by biolayer interferometry. MYT4134-MYT4160 (i.e., the light chain histidine scan and alanine scan variants of huAD208.12.1) were captured on an anti-human Fc biosensor and associated with LRRC15 at pH 7.4. Dissociation was carried out at pH 7.4 (black trace) or pH 5.4 (gray trace).

[0108] Figure 39 : Table of construct identifiers corresponding to SEQ ID NOs. The constructs, namely the light chain histidine scan and alanine scan variants, are listed in the first column of the table, and the SEQ ID NOs are listed and correspond to the constructs on the left and the appropriate heavy chain and / or light chain classes along the top.

[0109] Figures 40A - 40B : Characterization of the binding affinity of anti-LRRC15 mAb. The binding of anti-LRRC15 mAb to U-87MG (LRRC15+) cells was assayed. Figure 40A shows MYT0963 (sarmatumab) with an IC50 of 0.228 nM, and Figure 40B shows MYT0971 with an IC50 of 0.484 nM.

[0110] Figures 41A - 41G: Internalization of anti-LRRC15 mAb in cells. Internalization and endolysosomal delivery of anti-LRRC15 pH-engineered antibody variants, corresponding starting ABPC antibodies, control IgG1 isotype control (BP0297, Bioxcell) along with vehicle control were assayed against internalization and endolysosomal delivery measured as mean fluorescence density on the cell surface at 25 nM after 24 hours as designated in Figure 41. Error bars represent standard deviation (where present). Numbers on the bars represent fold change relative to the corresponding starting ABPC.

[0111] Figure 42 : Melting temperature of anti-LRRC15 mAb. The melting temperature of the selected anti-LRRC15 mAb listed in the table was determined by differential scanning fluorimetry (DSF), and the resulting Sypro Orange signal was plotted as its first derivative. The melting temperature (Tm) was calculated as the local maximum of the plot and is shown in the table.

[0112] Figure 43 : SDS PAGE for MYT0766. Purified MYT0766 was loaded onto an SDS PAGE gel in non-reducing (NR) and reducing (R) forms to confirm size and purity. The theoretical molecular weight of full-length MYT0766 is approximately 109 kDa. Detailed Description

[0113] Provided herein are antigen-binding protein constructs (ABPCs) that comprise: a first antigen-binding domain that is capable of specifically binding to LRRC15 or an epitope of LRRC15 presented on the surface of a target mammalian cell, wherein: (a) the first antigen-binding domain has a faster dissociation rate at a pH of from about 4.0 to about 6.5 than at a pH of from about 7.0 to about 8.0; and / or (b) the first antigen-binding domain has a dissociation constant (K D ) at a pH of from about 4.0 to about 6.5 that is greater than the K D at a pH of from about 7.0 to about 8.0. In some instances of these ABPCs, after the ABPC is internalized by the target mammalian cell, the ABPC is degraded in the target mammalian cell. Some instances of any ABPC described herein may further comprise a conjugated toxin, radioisotope, drug, or small molecule (e.g., fluorophore or dye).

[0114] An antigen-binding protein construct (ABPC) is also provided, which comprises: a first antigen-binding domain capable of specifically binding to LRRC15 or an epitope of LRRC15 presented 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 D ) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is greater than the K D at a pH of about 7.0 to about 8.0; and (b) a composition comprising the ABPC provides one or more (e.g., two or three) of the following: an increase (e.g., a detectable increase) in toxin release in the target mammalian cells as compared to a composition comprising the same amount of a control ABPC; an increase (e.g., a detectable increase) in target mammalian cell killing as compared to a composition comprising the same amount of a control ABPC; and an increase (e.g., a detectable increase) in endolysosomal delivery in the target mammalian cells as compared to a composition comprising the same amount of a control ABPC.

[0115] In some instances of any ABPCs described herein, the first antigen-binding domain comprises the heavy-chain variable domain of sacituzumab 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 are replaced with histidine. In some instances of any ABPCs described herein, the first antigen-binding domain comprises the light-chain variable domain of sacituzumab 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 are replaced with histidine. In some instances of any ABPCs described herein, the first antigen-binding domain comprises: the heavy-chain variable domain of sacituzumab 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 are replaced with histidine; and the light-chain variable domain of sacituzumab 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 are replaced with histidine. In some instances of any ABPCs described herein, the heavy-chain variable domain of sacituzumab comprises SEQ ID NO:1. In some instances of any ABPCs described herein, the light-chain variable domain of sacituzumab comprises SEQ ID NO:2.

[0116] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy-chain variable domain comprising CDR1, CDR2, and CDR3 that respectively comprise SEQ ID NO:3, SEQ ID NO:4, and SEQ ID NO:5, 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: 3-5 are jointly replaced with histidine. In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light-chain variable domain comprising CDR1, CDR2, and CDR3 that respectively comprise SEQ ID NO:6, SEQ ID NO:7, and SEQ ID NO:8, 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: 6-8 are jointly replaced with histidine. In some instances of any ABPCs described herein, the first antigen-binding domain comprises: a heavy-chain variable domain comprising CDR1, CDR2, and CDR3 that respectively comprise SEQ ID NO:3, SEQ ID NO:4, and SEQ ID NO:5, 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: 3-5 are jointly replaced with histidine; and a light-chain variable domain comprising CDR1, CDR2, and CDR3 that respectively comprise SEQ ID NO:6, SEQ ID NO:7, and SEQ ID NO:8, 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: 6-8 are jointly replaced with histidine.

[0117] In some instances of any 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 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 selected from the group consisting of: 33, 34, 50, 52, 57, 59, 100, 102, 103, 107, 108 or 109 of SEQ ID NO:1. In some instances of any 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, wherein the light chain variable domain comprises 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 selected from the group consisting of: 32, 34, 50, 51, 89, 90, 92, 93, 94 or 96 of SEQ ID NO:2.In some instances of any 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 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 selected from the group consisting of: 33, 34, 50, 52, 57, 59, 100, 102, 103, 107, 108 or 109 of SEQ ID NO: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 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 selected from the group consisting of: 32, 34, 50, 51, 89, 90, 92, 93, 94 or 96 of SEQ ID NO:2.

[0118] In some instances of any 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, wherein the heavy-chain variable domain comprises histidine at any combination of one or more amino acid positions listed in Table 1 of SEQ ID NO:1.

[0119] Table 1. Exemplary combinations of amino acid positions in SEQ ID NO:1 that can be substituted with histidine.

[0120]

[0121]

[0122] In some instances of any 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, wherein the light-chain variable domain comprises histidine at any combination of one or more amino acid positions listed in Table 2 of SEQ ID NO:2.

[0123] Table 2. Exemplary combinations of amino acid positions in SEQ ID NO:2 that can be substituted with histidine

[0124]

[0125] In some instances of any 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 histidine at any combination of one or more of the specific combinations of amino acid positions listed in Table 1 of SEQ ID NO: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 histidine at any combination of one or more of the specific combinations of amino acid positions listed in Table 2 of SEQ ID NO:2.

[0126] In some instances of any 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, wherein the heavy chain variable domain comprises histidine at any combination of one or more (e.g., two, three, four, five, six, seven, eight, nine or ten) of the specific combinations of amino acid positions listed in Table 1 of SEQ ID NO:1.

[0127] In some instances of any 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 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 histidine at any combination of one or more of the specific combinations of amino acid positions listed in Table 1 of SEQ ID NO:1.

[0128] In some instances of any 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 histidine at position 34 in 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 histidine at any combination of one or more of the amino acid positions listed in Table 1 of SEQ ID NO:1.

[0129] In some instances of any 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 histidine at position 50 in 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 histidine at any combination of one or more of the amino acid positions listed in Table 1 of SEQ ID NO:1.

[0130] In some instances of any 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 histidine at position 51 in 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 histidine at any combination of one or more of the amino acid positions listed in Table 1 of SEQ ID NO:1.

[0131] In some instances of any 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 histidine at position 89 in 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 histidine at any combination of one or more of the amino acid positions listed in Table 1 of SEQ ID NO:1.

[0132] In some instances of any 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 histidine at position 90 in 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 histidine at any combination of one or more of the amino acid positions listed in Table 1 of SEQ ID NO:1.

[0133] In some instances of any 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 histidine at position 92 in 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 histidine at any combination of one or more of the amino acid positions listed in Table 1 of SEQ ID NO:1.

[0134] In some instances of any 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 histidine at position 93 in 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 histidine at any combination of one or more of the amino acid positions listed in Table 1 of SEQ ID NO:1.

[0135] In some instances of any 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 histidine at position 94 in 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 histidine at any combination of one or more of the amino acid positions listed in Table 1 of SEQ ID NO:1.

[0136] In some instances of any 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 histidine at position 96 in 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 histidine at any combination of one or more amino acid positions listed in Table 1 of SEQ ID NO:1.

[0137] In some instances of any ABPCs described herein, the first antigen-binding domain comprises the heavy chain variable domain of sacituzumab 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 are replaced with alanine. In some instances of any ABPCs described herein, the first antigen-binding domain comprises the light chain variable domain of sacituzumab 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 are replaced with alanine. In some instances of any ABPCs described herein, the first antigen-binding domain comprises: the heavy chain variable domain of sacituzumab 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 are replaced with alanine; and the light chain variable domain of sacituzumab 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 are replaced with alanine. In some instances of any ABPCs described herein, the heavy chain variable domain of sacituzumab comprises SEQ ID NO:1. In some instances of any ABPCs described herein, the light chain variable domain of sacituzumab comprises SEQ ID NO:2.

[0138] In some instances of any ABPC described herein, the first antigen-binding domain comprises a heavy-chain variable domain comprising CDR1, CDR2, and CDR3 that respectively comprise SEQ ID NO:3, SEQ ID NO:4, and SEQ ID NO:5, 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 are collectively replaced with alanine. In some instances of any ABPC described herein, the first antigen-binding domain comprises a light-chain variable domain comprising CDR1, CDR2, and CDR3 that respectively comprise SEQ ID NO:6, SEQ ID NO:7, and SEQ ID NO:8, 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 are collectively replaced with alanine. In some instances of any ABPC described herein, the first antigen-binding domain comprises: a heavy-chain variable domain comprising CDR1, CDR2, and CDR3 that respectively comprise SEQ ID NO:3, SEQ ID NO:4, and SEQ ID NO:5, 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 are collectively replaced with alanine; and a light-chain variable domain comprising CDR1, CDR2, and CDR3 that respectively comprise SEQ ID NO:6, SEQ ID NO:7, and SEQ ID NO:8, 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 are collectively replaced with alanine.

[0139] In some instances of any ABPC described herein, the first antigen-binding domain comprises a heavy chain variable domain of any of the following: 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.

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

[0141] In some instances of any 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.

[0142] In some instances of any 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.

[0143] In some instances of any 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.

[0144] In some instances of any 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.

[0145] In some instances of any 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.

[0146] In some instances of any 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.

[0147] In some instances of any ABPC 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.

[0148] In some instances of any 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.

[0149] In some instances of any ABPC 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.

[0150] In some instances of any 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.

[0151] In some instances of any ABPC 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.

[0152] In some instances of any 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.

[0153] In some instances of any ABPC 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.

[0154] In some instances of any 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.

[0155] In some instances of any 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.

[0156] In some instances of any 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.

[0157] In some instances of any ABPC 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.

[0158] In some instances of any ABPC 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.

[0159] In some instances of any 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.

[0160] In some instances of any ABPC 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.

[0161] In some instances of any 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.

[0162] In some instances of any ABPC 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.

[0163] In some instances of any 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.

[0164] In some instances of any 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.

[0165] In some instances of any 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.

[0166] In some instances of any 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.

[0167] In some instances of any 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.

[0168] In some instances of any 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.

[0169] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising: SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82 or SEQ ID NO:83.

[0170] In some instances of any 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.

[0171] In some instances of any 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.

[0172] In some instances of any 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.

[0173] In some instances of any 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.

[0174] In some instances of any ABPCs described herein, the first antigen-binding domain comprises the 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 are replaced with histidine. In some instances of any ABPCs described herein, the first antigen-binding domain comprises the 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 are replaced with histidine. In some instances of any ABPCs described herein, the first antigen-binding domain comprises: the 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 are replaced with histidine; and the 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 are replaced with histidine. In some instances of any ABPCs described herein, the heavy-chain variable domain of hu139.10 comprises SEQ ID NO:84. In some instances of any ABPCs described herein, the light-chain variable domain of hu139.10 comprises SEQ ID NO:85.

[0175] In some instances of any ABPC described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising CDR1, CDR2, and CDR3 that respectively comprise SEQ ID NO: 86, SEQ ID NO: 87, and SEQ ID NO: 88, 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: 86-88 are jointly substituted with histidine. In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising CDR1, CDR2, and CDR3 that respectively comprise SEQ ID NO: 89, SEQ ID NO: 90, and SEQ ID NO: 91, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs: 89-91 are jointly substituted with histidine. In some instances of any ABPC described herein, the first antigen-binding domain comprises: a heavy chain variable domain comprising CDR1, CDR2, and CDR3 that respectively comprise SEQ ID NO: 86, SEQ ID NO: 87, and SEQ ID NO: 88, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs: 89-91 are jointly substituted with histidine; and a light chain variable domain comprising CDR1, CDR2, and CDR3 that respectively comprise SEQ ID NO: 89, SEQ ID NO: 90, and SEQ ID NO: 91, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs: 89-91 are jointly substituted with histidine.

[0176] In some instances of any 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 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 selected from the group consisting of: 27, 29, 32, 50, 54, 58, 99, 100, 102, 104, or 105 of SEQ ID NO: 84. In some instances of any 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, wherein the light-chain variable domain comprises 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 selected from the group consisting of: 29, 31, 32, 34, 36, 37, 38, 40, 56, 60, 61, 95, 96, 97, or 100 of SEQ ID NO: 85.In some instances of any 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 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 selected from the group consisting of: 27, 29, 32, 50, 54, 58, 99, 100, 102, 104, and 105 of SEQ ID NO: 84; 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 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 selected from the group consisting of: 29, 31, 32, 34, 36, 37, 38, 40, 56, 60, 61, 95, 96, 97, or 100 of SEQ ID NO: 85.

[0177] In some instances of any 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, wherein the heavy-chain variable domain comprises histidine at any combination of one or more of the amino acid positions listed in Table 3 of SEQ ID NO: 84.

[0178] In some instances of any 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 alanine at position 35 of SEQ ID NO: 84.

[0179] In some instances of any 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 alanine at position 98 in SEQ ID NO: 84.

[0180] In some instances of any 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 alanine at position 35 in SEQ ID NO: 84; 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 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 selected from the group consisting of: 29, 31, 32, 34, 36, 37, 38, 40, 56, 60, 61, 95, 96, 97, or 100 in SEQ ID NO: 85.

[0181] In some instances of any 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 alanine at position 98 in SEQ ID NO: 84; 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 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 selected from the group consisting of: 29, 31, 32, 34, 36, 37, 38, 40, 56, 60, 61, 95, 96, 97, or 100 in SEQ ID NO: 85.

[0182] In some instances of any 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 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 selected from the group consisting of: 27, 29, 32, 50, 54, 58, 99, 100, 102, 104 or 105 of SEQ ID NO: 84, and wherein the heavy chain variable domain comprises alanine at position 35 and / or 98 of SEQ ID NO: 84. In some instances of any 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 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 selected from the group consisting of: 27, 29, 32, 50, 54, 58, 99, 100, 102, 104 or 105 of SEQ ID NO: 84, and wherein the heavy chain variable domain comprises alanine at position 35 or 98 of SEQ ID NO: 84; 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 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 selected from the group consisting of: 29, 31, 32, 34, 36, 37, 38, 40, 56, 60, 61, 95, 96, 97 or 100 of SEQ ID NO: 85.

[0183] In some instances of any 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 histidine at any combination of one or more of the amino acid positions listed in Table 1 of SEQ ID NO:84, and wherein the heavy chain variable domain comprises alanine at position 35 and / or 98 of SEQ ID NO:84.

[0184] Table 3. Exemplary combinations of amino acid positions in SEQ ID NO:84 that can be replaced with histidine

[0185]

[0186]

[0187] In some instances of any 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, wherein the light chain variable domain comprises histidine at any combination of one or more of the amino acid positions listed in Table 4 of SEQ ID NO:85.

[0188] Table 4. Exemplary combinations of amino acid positions in SEQ ID NO:85 that can be replaced with histidine

[0189]

[0190]

[0191]

[0192] In some instances of any 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 histidine at any combination of one or more amino acid positions listed in Table 3 of SEQ ID NO:84; 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 histidine at any combination of one or more amino acid positions listed in Table 4 of SEQ ID NO:85.

[0193] In some instances of any 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 histidine at any combination of one or more amino acid positions listed in Table 3 of SEQ ID NO:84, and wherein the heavy chain variable domain comprises alanine at position 35 of SEQ ID NO:84; 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 histidine at any combination of one or more amino acid positions listed in Table 4 of SEQ ID NO:84.

[0194] In some instances of any 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 histidine at any combination of one or more amino acid positions listed in Table 3 of SEQ ID NO:84, and wherein the heavy chain variable domain comprises alanine at position 98 of SEQ ID NO:84; 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 histidine at any combination of one or more amino acid positions listed in Table 4 of SEQ ID NO:84.

[0195] In some instances of any 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 histidine at any combination of one or more (e.g., two, three, four, five, six, seven, eight, nine or ten) amino acid positions listed in Table 3 of SEQ ID NO:84.

[0196] In some instances of any 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 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 histidine at any combination of one or more amino acid positions listed in Table 3 of SEQ ID NO:84.

[0197] In some instances of any 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 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 histidine at any combination of one or more amino acid positions listed in Table 3 of SEQ ID NO:84.

[0198] In some instances of any 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 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 histidine at any combination of one or more amino acid positions listed in Table 3 of SEQ ID NO:84.

[0199] In some instances of any 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 in 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 combination of one or more of the specific combinations of amino acid positions listed in Table 3 of SEQ ID NO: 84.

[0200] In some instances of any 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 in 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 combination of one or more of the specific combinations of amino acid positions listed in Table 3 of SEQ ID NO: 84.

[0201] In some instances of any 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 in 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 combination of one or more of the specific combinations of amino acid positions listed in Table 3 of SEQ ID NO: 84.

[0202] In some instances of any 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 in 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 combination of one or more of the amino acid positions listed in Table 3 of SEQ ID NO:84.

[0203] In some instances of any 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 in 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 combination of one or more of the amino acid positions listed in Table 3 of SEQ ID NO:84.

[0204] In some instances of any 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 in 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 combination of one or more of the amino acid positions listed in Table 3 of SEQ ID NO:84.

[0205] In some instances of any 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 in 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 combination of one or more of the amino acid positions listed in Table 3 of SEQ ID NO:84.

[0206] In some instances of any 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 in 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 combination of one or more of the amino acid positions listed in Table 3 of SEQ ID NO: 84.

[0207] In some instances of any 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 in 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 combination of one or more of the amino acid positions listed in Table 3 of SEQ ID NO: 84.

[0208] In some instances of any 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 in 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 combination of one or more of the amino acid positions listed in Table 3 of SEQ ID NO: 84.

[0209] In some instances of any 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 in 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 combination of one or more of the amino acid positions listed in Table 3 of SEQ ID NO: 84.

[0210] In some instances of any 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 histidine at position 100 in 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 histidine at any combination of one or more amino acid positions listed in Table 3 in SEQ ID NO:84.

[0211] In some instances of any ABPCs described herein, the first antigen-binding domain comprises the 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 are replaced with alanine. In some instances of any ABPCs described herein, the first antigen-binding domain comprises the 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 are replaced with alanine. In some instances of any ABPCs described herein, the first antigen-binding domain comprises: the 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 are replaced with alanine; and the 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 are replaced with alanine. In some instances of any ABPCs described herein, the heavy chain variable domain of hu139.10 comprises SEQ ID NO:84. In some instances of any ABPCs described herein, the light chain variable domain of hu139.10 comprises SEQ ID NO:85.

[0212] In some instances of any ABPC described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising CDR1, CDR2, and CDR3 that respectively comprise SEQ ID NO:86, SEQ ID NO:87, and SEQ ID NO:88, 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:86 - 88 are collectively replaced with alanine. In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising CDR1, CDR2, and CDR3 that respectively comprise SEQ ID NO:89, SEQ ID NO:90, and SEQ ID NO:91, 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:89 - 91 are collectively replaced with alanine. In some instances of any ABPC described herein, the first antigen-binding domain comprises: a heavy chain variable domain comprising CDR1, CDR2, and CDR3 that respectively comprise SEQ ID NO:86, SEQ ID NO:87, and SEQ ID NO:88, 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:86 - 88 are collectively replaced with alanine; and a light chain variable domain comprising CDR1, CDR2, and CDR3 that respectively comprise SEQ ID NO:89, SEQ ID NO:90, and SEQ ID NO:91, 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:89 - 91 are collectively replaced with alanine.

[0213] In some instances of any ABPC described herein, the first antigen-binding domain comprises a heavy-chain variable domain of any 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.

[0214] In some instances of any ABPC 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.

[0215] In some instances of any 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.

[0216] In some instances of any ABPC 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.

[0217] In some instances of any 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.

[0218] In some instances of any ABPC 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.

[0219] In some instances of any 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.

[0220] In some instances of any ABPC 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.

[0221] In some instances of any ABPC 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.

[0222] In some instances of any ABPC 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.

[0223] In some instances of any ABPC 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.

[0224] In some instances of any 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.

[0225] In some instances of any ABPC 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.

[0226] In some instances of any 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.

[0227] In some instances of any 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.

[0228] In some instances of any ABPC 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.

[0229] In some instances of any ABPC 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.

[0230] In some instances of any 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.

[0231] In some instances of any 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.

[0232] In some instances of any 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.

[0233] In some instances of any ABPC 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.

[0234] In some instances of any 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.

[0235] In some instances of any ABPC 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.

[0236] In some instances of any ABPC 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.

[0237] In some instances of any ABPC 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.

[0238] In some instances of any 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.

[0239] In some instances of any ABPC 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.

[0240] In some instances of any 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.

[0241] In some instances of any ABPC 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.

[0242] In some instances of any 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.

[0243] In some instances of any ABPC 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.

[0244] In some instances of any 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.

[0245] In some instances of any 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.

[0246] In some instances of any 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.

[0247] In some instances of any ABPC 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.

[0248] In some instances of any ABPC described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising: SEQ ID NO: 164, SEQ ID NO: 165, SEQ ID NO: 166 or SEQ ID NO: 167.

[0249] In some instances of any ABPC 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.

[0250] In some instances of any 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.

[0251] In some instances of any ABPC 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.

[0252] In some instances of any 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.

[0253] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising: SEQ ID NO: 168, SEQ ID NO: 169, SEQ ID NO: 170, SEQ ID NO: 171, SEQ ID NO: 172, SEQ ID NO: 173, SEQ ID NO: 174, SEQ ID NO: 175, SEQ ID NO: 176 or SEQ ID NO: 177.

[0254] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 168 and a heavy chain variable domain comprising: SEQ ID NO: 84, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 164, SEQ ID NO: 165, SEQ ID NO: 166 or SEQ ID NO: 167.

[0255] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 169 and a heavy chain variable domain comprising: SEQ ID NO: 84, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 164, SEQ ID NO: 165, SEQ ID NO: 166 or SEQ ID NO: 167.

[0256] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 170 and a heavy chain variable domain comprising: SEQ ID NO: 84, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 164, SEQ ID NO: 165, SEQ ID NO: 166 or SEQ ID NO: 167.

[0257] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 171 and a heavy chain variable domain comprising: SEQ ID NO: 84, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 164, SEQ ID NO: 165, SEQ ID NO: 166 or SEQ ID NO: 167.

[0258] In some examples of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 172 and a heavy chain variable domain comprising: SEQ ID NO: 84, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 164, SEQ ID NO: 165, SEQ ID NO: 166 or SEQ ID NO: 167.

[0259] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 173 and a heavy chain variable domain comprising: SEQ ID NO: 84, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 164, SEQ ID NO: 165, SEQ ID NO: 166 or SEQ ID NO: 167.

[0260] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 174 and a heavy chain variable domain comprising: SEQ ID NO: 84, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 164, SEQ ID NO: 165, SEQ ID NO: 166 or SEQ ID NO: 167.

[0261] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 175 and a heavy chain variable domain comprising: SEQ ID NO: 84, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 164, SEQ ID NO: 165, SEQ ID NO: 166 or SEQ ID NO: 167.

[0262] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 176 and a heavy chain variable domain comprising: SEQ ID NO: 84, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 164, SEQ ID NO: 165, SEQ ID NO: 166 or SEQ ID NO: 167.

[0263] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 177 and a heavy chain variable domain comprising: SEQ ID NO: 84, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 164, SEQ ID NO: 165, SEQ ID NO: 166 or SEQ ID NO: 167.

[0264] In some instances of any ABPCs described herein, the first antigen-binding domain comprises the 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 are replaced with histidine. In some instances of any ABPCs described herein, the first antigen-binding domain comprises the 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 are replaced with histidine. In some instances of any ABPCs described herein, the first antigen-binding domain comprises: the 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 are replaced with histidine; and the 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 are replaced with histidine. In some instances of any ABPCs described herein, the heavy chain variable domain of huAD208.4.1 comprises SEQ ID NO:178. In some instances of any ABPCs described herein, the light chain variable domain of huAD208.4.1 comprises SEQ ID NO:179.

[0265] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy-chain variable domain comprising CDR1, CDR2, and CDR3 that respectively comprise SEQ ID NO: 180, SEQ ID NO: 181, and SEQ ID NO: 182, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs: 180 - 182 are jointly substituted with histidine. In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light-chain variable domain comprising CDR1, CDR2, and CDR3 that respectively comprise SEQ ID NO: 183, SEQ ID NO: 184, and SEQ ID NO: 185, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs: 183 - 185 are jointly substituted with histidine. In some instances of any ABPCs described herein, the first antigen-binding domain comprises: a heavy-chain variable domain comprising CDR1, CDR2, and CDR3 that respectively comprise SEQ ID NO: 180, SEQ ID NO: 181, and SEQ ID NO: 182, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs: 180 - 182 are jointly substituted with histidine; and a light-chain variable domain comprising CDR1, CDR2, and CDR3 that respectively comprise SEQ ID NO: 183, SEQ ID NO: 184, and SEQ ID NO: 185, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs: 183 - 185 are jointly substituted with histidine.

[0266] In some instances of any 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, wherein the heavy-chain variable domain comprises 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 selected from the group consisting of: 33, 52, 56, 57 or 106 in SEQ ID NO: 178. In some instances of any 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, wherein the light-chain variable domain comprises 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 selected from the group consisting of: 25, 26, 28, 29, 31, 36, 37, 57, 59, 94, 95, 96 or 100 in SEQ ID NO: 179. In some instances of any 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, wherein the heavy-chain variable domain comprises 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 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, wherein the light-chain variable domain comprises 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 selected from the group consisting of: 25, 26, 28, 29, 31, 36, 37, 57, 59, 94, 95, 96 or 100.

[0267] In some instances of any 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, wherein the heavy chain variable domain comprises histidine at any combination of one or more amino acid positions listed in Table 5 of SEQ ID NO: 178.

[0268] Table 5. Exemplary combinations of amino acid positions in SEQ ID NO: 178 that can be substituted with histidine

[0269]

[0270] In some instances of any 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, wherein the light chain variable domain comprises histidine at any combination of one or more amino acid positions listed in Table 6 of SEQ ID NO: 179.

[0271] Table 6. Exemplary combinations of amino acid positions in SEQ ID NO: 179 that can be substituted with histidine

[0272]

[0273]

[0274] In some instances of any 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, wherein the heavy chain variable domain comprises histidine at any combination of one or more amino acid positions listed in Table 5 of SEQ ID NO: 178; 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, wherein the light chain variable domain comprises histidine at any combination of one or more amino acid positions listed in Table 6 of SEQ ID NO: 179.

[0275] In some instances of any 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, wherein the heavy chain variable domain comprises histidine at any combination of one or more (e.g., two, three, four, five, six, seven, eight, nine or ten) amino acid positions listed in Table 5 of SEQ ID NO:178.

[0276] In some instances of any 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 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 histidine at any combination of one or more amino acid positions listed in Table 5 of SEQ ID NO:178.

[0277] In some instances of any 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 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 histidine at any combination of one or more amino acid positions listed in Table 5 of SEQ ID NO:178.

[0278] In some instances of any 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 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 histidine at any combination of one or more amino acid positions listed in Table 5 of SEQ ID NO:178.

[0279] In some instances of any 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 combination of one or more of the specific combinations of amino acid positions listed in Table 5 of SEQ ID NO: 178.

[0280] In some instances of any 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 combination of one or more of the specific combinations of amino acid positions listed in Table 5 of SEQ ID NO: 178.

[0281] In some instances of any 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 combination of one or more of the specific combinations of amino acid positions listed in Table 5 of SEQ ID NO: 178.

[0282] In some instances of any 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 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 histidine at any combination of one or more of the amino acid positions listed in Table 5 of SEQ ID NO: 178.

[0283] In some instances of any 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 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 histidine at any combination of one or more of the amino acid positions listed in Table 5 of SEQ ID NO: 178.

[0284] In some instances of any 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 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 histidine at any combination of one or more of the amino acid positions listed in Table 5 of SEQ ID NO: 178.

[0285] In some instances of any 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 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 histidine at any combination of one or more of the amino acid positions listed in Table 5 of SEQ ID NO: 178.

[0286] In some instances of any 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 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 histidine at any combination of one or more of the specific combinations of amino acid positions listed in Table 5 of SEQ ID NO: 178.

[0287] In some instances of any 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 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 histidine at any combination of one or more of the specific combinations of amino acid positions listed in Table 5 of SEQ ID NO: 178.

[0288] In some instances of any 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 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 histidine at any combination of one or more of the specific combinations of amino acid positions listed in Table 5 of SEQ ID NO: 178.

[0289] In some instances of any ABPCs described herein, the first antigen-binding domain comprises the 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 are replaced with alanine. In some instances of any ABPCs described herein, the first antigen-binding domain comprises the 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 are replaced with alanine. In some instances of any ABPCs described herein, the first antigen-binding domain comprises: the 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 are replaced with alanine; and the 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 are replaced with alanine. In some instances of any ABPCs described herein, the heavy-chain variable domain of huAD208.4.1 comprises SEQ ID NO:178. In some instances of any ABPCs described herein, the light-chain variable domain of huAD208.4.1 comprises SEQ ID NO:179.

[0290] In some instances of any ABPC described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising CDR1, CDR2, and CDR3 that respectively comprise SEQ ID NO: 180, SEQ ID NO: 181, and SEQ ID NO: 182, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NOs: 180 - 182 are collectively replaced with alanine. In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising CDR1, CDR2, and CDR3 that respectively comprise SEQ ID NO: 183, SEQ ID NO: 184, and SEQ ID NO: 185, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NOs: 183 - 185 are collectively replaced with alanine. In some instances of any ABPC described herein, the first antigen-binding domain comprises: a heavy chain variable domain comprising CDR1, CDR2, and CDR3 that respectively comprise SEQ ID NO: 180, SEQ ID NO: 181, and SEQ ID NO: 182, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NOs: 180 - 182 are collectively replaced with alanine; and a light chain variable domain comprising CDR1, CDR2, and CDR3 that respectively comprise SEQ ID NO: 183, SEQ ID NO: 184, and SEQ ID NO: 185, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NOs: 183 - 185 are collectively replaced with alanine.

[0291] In some instances of any ABPC described herein, the first antigen-binding domain comprises a heavy chain variable domain of any 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.

[0292] In some instances of any 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.

[0293] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 179 and a heavy chain variable domain comprising: SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226 or SEQ ID NO: 227.

[0294] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 228 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226 or SEQ ID NO: 227.

[0295] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 229 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226 or SEQ ID NO: 227.

[0296] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 230 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226 or SEQ ID NO: 227.

[0297] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 231 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226 or SEQ ID NO: 227.

[0298] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 232 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226 or SEQ ID NO: 227.

[0299] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 233 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226 or SEQ ID NO: 227.

[0300] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 234 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226 or SEQ ID NO: 227.

[0301] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 235 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226 or SEQ ID NO: 227.

[0302] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 236 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226 or SEQ ID NO: 227.

[0303] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 237 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226 or SEQ ID NO: 227.

[0304] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 238 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226 or SEQ ID NO: 227.

[0305] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 239 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226 or SEQ ID NO: 227.

[0306] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 240 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226 or SEQ ID NO: 227.

[0307] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 241 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226 or SEQ ID NO: 227.

[0308] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 242 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226 or SEQ ID NO: 227.

[0309] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 243 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226 or SEQ ID NO: 227.

[0310] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 244 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226 or SEQ ID NO: 227.

[0311] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 245 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226 or SEQ ID NO: 227.

[0312] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 246 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226 or SEQ ID NO: 227.

[0313] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 247 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226 or SEQ ID NO: 227.

[0314] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 248 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226 or SEQ ID NO: 227.

[0315] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 249 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226 or SEQ ID NO: 227.

[0316] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 250 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226 or SEQ ID NO: 227.

[0317] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 251 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226 or SEQ ID NO: 227.

[0318] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 252 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226 or SEQ ID NO: 227.

[0319] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 253 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226 or SEQ ID NO: 227.

[0320] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 254 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, or SEQ ID NO: 227.

[0321] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 255 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226 or SEQ ID NO: 227.

[0322] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 256 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226 or SEQ ID NO: 227.

[0323] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 257 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226 or SEQ ID NO: 227.

[0324] In some instances of any ABPC described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising: SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260 or SEQ ID NO: 261.

[0325] In some instances of any ABPC described herein, the first antigen-binding domain comprises a heavy-chain variable domain comprising SEQ ID NO: 258 and a light-chain variable domain comprising: SEQ ID NO: 179, SEQ ID NO: 228, SEQ ID NO: 229, SEQ ID NO: 230, SEQ ID NO: 231, SEQ ID NO: 232, SEQ ID NO: 233, SEQ ID NO: 234, SEQ ID NO: 235, SEQ ID NO: 236, SEQ ID NO: 237, SEQ ID NO: 238, SEQ ID NO: 239, SEQ ID NO: 240, SEQ ID NO: 241, SEQ ID NO: 242, SEQ ID NO: 243, SEQ ID NO: 244, SEQ ID NO: 245, SEQ ID NO: 246, SEQ ID NO: 247, SEQ ID NO: 248, SEQ ID NO: 249, SEQ ID NO: 250, SEQ ID NO: 251, SEQ ID NO: 252, SEQ ID NO: 253, SEQ ID NO: 254, SEQ ID NO: 255, SEQ ID NO: 256, or SEQ ID NO: 257.

[0326] In some instances of any ABPC described herein, the first antigen-binding domain comprises a heavy-chain variable domain comprising SEQ ID NO: 259 and a light-chain variable domain selected from the group consisting 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, and SEQ ID NO: 257.

[0327] In some instances of any ABPC described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO: 260 and a light chain variable domain comprising: SEQ ID NO: 179, SEQ ID NO: 228, SEQ ID NO: 229, SEQ ID NO: 230, SEQ ID NO: 231, SEQ ID NO: 232, SEQ ID NO: 233, SEQ ID NO: 234, SEQ ID NO: 235, SEQ ID NO: 236, SEQ ID NO: 237, SEQ ID NO: 238, SEQ ID NO: 239, SEQ ID NO: 240, SEQ ID NO: 241, SEQ ID NO: 242, SEQ ID NO: 243, SEQ ID NO: 244, SEQ ID NO: 245, SEQ ID NO: 246, SEQ ID NO: 247, SEQ ID NO: 248, SEQ ID NO: 249, SEQ ID NO: 250, SEQ ID NO: 251, SEQ ID NO: 252, SEQ ID NO: 253, SEQ ID NO: 254, SEQ ID NO: 255, SEQ ID NO: 256 or SEQ ID NO: 257.

[0328] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy-chain variable domain comprising SEQ ID NO: 261 and a light-chain variable domain comprising: SEQ ID NO: 179, SEQ ID NO: 228, SEQ ID NO: 229, SEQ ID NO: 230, SEQ ID NO: 231, SEQ ID NO: 232, SEQ ID NO: 233, SEQ ID NO: 234, SEQ ID NO: 235, SEQ ID NO: 236, SEQ ID NO: 237, SEQ ID NO: 238, SEQ ID NO: 239, SEQ ID NO: 240, SEQ ID NO: 241, SEQ ID NO: 242, SEQ ID NO: 243, SEQ ID NO: 244, SEQ ID NO: 245, SEQ ID NO: 246, SEQ ID NO: 247, SEQ ID NO: 248, SEQ ID NO: 249, SEQ ID NO: 250, SEQ ID NO: 251, SEQ ID NO: 252, SEQ ID NO: 253, SEQ ID NO: 254, SEQ ID NO: 255, SEQ ID NO: 256 or SEQ ID NO: 257.

[0329] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light-chain variable domain comprising: SEQ ID NO: 262, SEQ ID NO: 263, SEQ ID NO: 264, SEQ ID NO: 265, SEQ ID NO: 266, SEQ ID NO: 267, SEQ ID NO: 268, SEQ ID NO: 269, SEQ ID NO: 270 or SEQ ID NO: 271.

[0330] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 262 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260 or SEQ ID NO: 261.

[0331] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 263 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260 or SEQ ID NO: 261.

[0332] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 264 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260 or SEQ ID NO: 261.

[0333] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 265 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260 or SEQ ID NO: 261.

[0334] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 266 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260 or SEQ ID NO: 261.

[0335] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 267 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260 or SEQ ID NO: 261.

[0336] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 268 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260 or SEQ ID NO: 261.

[0337] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 269 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260 or SEQ ID NO: 261.

[0338] In some examples of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 270 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260 or SEQ ID NO: 261.

[0339] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 271 and a heavy chain variable domain comprising: SEQ ID NO: 178, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260 or SEQ ID NO: 261.

[0340] In some instances of any ABPCs described herein, the first antigen-binding domain comprises the heavy-chain variable domain of huAD208.12.1 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 are replaced with histidine. In some instances of any ABPCs described herein, the first antigen-binding domain comprises the light-chain variable domain of huAD208.12.1 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 are replaced with histidine. In some instances of any ABPCs described herein, the first antigen-binding domain comprises: the heavy-chain variable domain of huAD208.12.1 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 are replaced with histidine; and the light-chain variable domain of huAD208.12.1 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 are replaced with histidine. In some instances of any ABPCs described herein, the heavy-chain variable domain of huAD208.12.1 comprises SEQ ID NO:272. In some instances of any ABPCs described herein, the light-chain variable domain of huAD208.12.1 comprises SEQ ID NO:273.

[0341] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy-chain variable domain comprising CDR1, CDR2, and CDR3 that respectively comprise SEQ ID NO: 274, SEQ ID NO: 275, and SEQ ID NO: 276, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs: 274-276 are jointly substituted with histidine. In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light-chain variable domain comprising CDR1, CDR2, and CDR3 that respectively comprise SEQ ID NO: 277, SEQ ID NO: 278, and SEQ ID NO: 279, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs: 277-279 are jointly substituted with histidine. In some instances of any ABPCs described herein, the first antigen-binding domain comprises: a heavy-chain variable domain comprising CDR1, CDR2, and CDR3 that respectively comprise SEQ ID NO: 274, SEQ ID NO: 275, and SEQ ID NO: 276, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs: 274-276 are jointly substituted with histidine; and a light-chain variable domain comprising CDR1, CDR2, and CDR3 that respectively comprise SEQ ID NO: 277, SEQ ID NO: 278, and SEQ ID NO: 279, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs: 277-279 are jointly substituted with histidine.

[0342] In some instances of any 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: 272, wherein the heavy-chain variable domain comprises 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 selected from the group consisting of: 24, 27, 29, 62, 63, 98 or 108 of SEQ ID NO: 272. In some instances of any 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: 273, wherein the light-chain variable domain comprises 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 selected from the group consisting of: 27, 28, 29, 31, 32, 89, 92 or 93 of SEQ ID NO: 273. In some instances of any 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: 272, wherein the heavy-chain variable domain comprises 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 selected from the group consisting of: 24, 27, 29, 62, 63, 98 or 108; and a light-chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identical to SEQ ID NO: 273, wherein the light-chain variable domain comprises 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 selected from the group consisting of: 27, 28, 29, 31, 32, 89, 92 or 93.

[0343] In some instances of any ABPC described herein, the heavy chain variable domain comprises a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identical to SEQ ID NO:272, wherein the heavy chain variable domain comprises histidine at any combination of one or more of the amino acid positions listed in Table 7 of SEQ ID NO:272.

[0344] Table 7. Exemplary combinations of amino acid positions in SEQ ID NO:272 that can be substituted with histidine

[0345]

[0346] In some instances of any ABPC described herein, the light chain variable domain comprises a light chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identical to SEQ ID NO:273, wherein the light chain variable domain comprises histidine at any combination of one or more of the amino acid positions listed in Table 8 of SEQ ID NO:273.

[0347] Table 8. Exemplary combinations of amino acid positions in SEQ ID NO:273 that can be substituted with histidine

[0348]

[0349]

[0350] In some instances of any ABPC described herein, the first antigen-binding domain comprises: a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identical to SEQ ID NO:272, wherein the heavy chain variable domain comprises histidine at any combination of one or more of the amino acid positions listed in Table 7 of SEQ ID NO:272; and a light chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identical to SEQ ID NO:273, wherein the light chain variable domain comprises histidine at any combination of one or more of the amino acid positions listed in Table 8 of SEQ ID NO:273.

[0351] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 273 and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identical to SEQ ID NO: 272, wherein the heavy chain variable domain comprises histidine at any combination of one or more (e.g., two, three, four, five, six, seven, eight, nine or ten) amino acid positions listed in Table 7 of SEQ ID NO: 272.

[0352] In some instances of any ABPCs described herein, the first antigen-binding domain comprises: a light chain variable domain that is at least 90% identical to SEQ ID NO: 273, wherein the light chain variable domain comprises histidine at position 27 of SEQ ID NO: 273; and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identical to SEQ ID NO: 272, wherein the heavy chain variable domain comprises histidine at any combination of one or more amino acid positions listed in Table 7 of SEQ ID NO: 272.

[0353] In some instances of any ABPCs described herein, the first antigen-binding domain comprises: a light chain variable domain that is at least 90% identical to SEQ ID NO: 273, wherein the light chain variable domain comprises histidine at position 28 of SEQ ID NO: 273; and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identical to SEQ ID NO: 272, wherein the heavy chain variable domain comprises histidine at any combination of one or more amino acid positions listed in Table 7 of SEQ ID NO: 272.

[0354] In some instances of any ABPCs described herein, the first antigen-binding domain comprises: a light chain variable domain that is at least 90% identical to SEQ ID NO: 273, wherein the light chain variable domain comprises histidine at position 29 of SEQ ID NO: 273; and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identical to SEQ ID NO: 272, wherein the heavy chain variable domain comprises histidine at any combination of one or more amino acid positions listed in Table 7 of SEQ ID NO: 272.

[0355] In some instances of any ABPCs described herein, the first antigen-binding domain comprises: a light chain variable domain that is at least 90% identical to SEQ ID NO: 273, wherein the light chain variable domain comprises histidine at position 31 in SEQ ID NO: 273; and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identical to SEQ ID NO: 272, wherein the heavy chain variable domain comprises histidine at any combination of one or more of the specific combinations of amino acid positions listed in Table 7 of SEQ ID NO: 272.

[0356] In some instances of any ABPCs described herein, the first antigen-binding domain comprises: a light chain variable domain that is at least 90% identical to SEQ ID NO: 273, wherein the light chain variable domain comprises histidine at position 32 in SEQ ID NO: 273; and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identical to SEQ ID NO: 272, wherein the heavy chain variable domain comprises histidine at any combination of one or more of the specific combinations of amino acid positions listed in Table 7 of SEQ ID NO: 272.

[0357] In some instances of any ABPCs described herein, the first antigen-binding domain comprises: a light chain variable domain that is at least 90% identical to SEQ ID NO: 273, wherein the light chain variable domain comprises histidine at position 89 in SEQ ID NO: 273; and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identical to SEQ ID NO: 272, wherein the heavy chain variable domain comprises histidine at any combination of one or more of the specific combinations of amino acid positions listed in Table 7 of SEQ ID NO: 272.

[0358] In some instances of any ABPCs described herein, the first antigen-binding domain comprises: a light chain variable domain that is at least 90% identical to SEQ ID NO: 273, wherein the light chain variable domain comprises a histidine at position 92 in SEQ ID NO: 273; and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identical to SEQ ID NO: 272, wherein the heavy chain variable domain comprises a histidine at any combination of one or more of the specific combinations of amino acid positions listed in Table 7 of SEQ ID NO: 272.

[0359] In some instances of any ABPCs described herein, the first antigen-binding domain comprises: a light chain variable domain that is at least 90% identical to SEQ ID NO: 273, wherein the light chain variable domain comprises a histidine at position 93 in SEQ ID NO: 273; and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identical to SEQ ID NO: 272, wherein the heavy chain variable domain comprises a histidine at any combination of one or more of the specific combinations of amino acid positions listed in Table 7 of SEQ ID NO: 272.

[0360] In some instances of any ABPCs described herein, the first antigen-binding domain comprises the heavy-chain variable domain of huAD208.12.1 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 are replaced with alanines. In some instances of any ABPCs described herein, the first antigen-binding domain comprises the light-chain variable domain of huAD208.12.1 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 are replaced with alanines. In some instances of any ABPCs described herein, the first antigen-binding domain comprises: the heavy-chain variable domain of huAD208.12.1 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 are replaced with alanines; and the light-chain variable domain of huAD208.12.1 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 are replaced with alanines. In some instances of any ABPCs described herein, the heavy-chain variable domain of huAD208.12.1 comprises SEQ ID NO:272. In some instances of any ABPCs described herein, the light-chain variable domain of huAD208.12.1 comprises SEQ ID NO:273.

[0361] In some instances of any ABPC described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising CDR1, CDR2, and CDR3 that respectively comprise SEQ ID NO: 274, SEQ ID NO: 275, and SEQ ID NO: 276, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NOs: 274-276 are collectively replaced with alanine. In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising CDR1, CDR2, and CDR3 that respectively comprise SEQ ID NO: 277, SEQ ID NO: 278, and SEQ ID NO: 279, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NOs: 277-279 are collectively replaced with alanine. In some instances of any ABPC described herein, the first antigen-binding domain comprises: a heavy chain variable domain comprising CDR1, CDR2, and CDR3 that respectively comprise SEQ ID NO: 274, SEQ ID NO: 275, and SEQ ID NO: 276, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NOs: 274-276 are collectively replaced with alanine; and a light chain variable domain comprising CDR1, CDR2, and CDR3 that respectively comprise SEQ ID NO: 277, SEQ ID NO: 278, and SEQ ID NO: 279, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NOs: 277-279 are collectively replaced with alanine.

[0362] In some instances of any ABPC described herein, the first antigen-binding domain comprises a heavy chain variable domain of any of the following: SEQ ID NO:272, SEQ ID NO:280, SEQ ID NO:281, SEQ ID NO:282, SEQ ID NO:283, SEQ ID NO:284, SEQ ID NO:285, SEQ ID NO:286, SEQ ID NO:287, SEQ ID NO:288, SEQID NO:289, SEQ ID NO:290, SEQ ID NO:291, SEQ ID NO:292, SEQ ID NO:293, SEQ ID NO:294, SEQ ID NO:295, SEQ ID NO:296, SEQ ID NO:297, SEQ ID NO:298, SEQ ID NO:299, SEQID NO:300, SEQ ID NO:301, SEQ ID NO:302, SEQ ID NO:303, SEQ ID NO:304, SEQ ID NO:305, SEQ ID NO:306, SEQ ID NO:307, SEQ ID NO:308, SEQ ID NO:309, SEQ ID NO:310, SEQID NO:311, SEQ ID NO:312, SEQ ID NO:313, SEQ ID NO:314, SEQ ID NO:315, SEQ ID NO:316, SEQ ID NO:317, SEQ ID NO:318, SEQ ID NO:319, SEQ ID NO:320, SEQ ID NO:321, SEQID NO:322 or SEQ ID NO:323.

[0363] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain of any of SEQ ID NO:273, SEQ ID NO:324, SEQ ID NO:325, SEQ ID NO:326, SEQ ID NO:327, SEQ ID NO:328, SEQ ID NO:329, SEQ ID NO:330, SEQ ID NO:331, SEQ ID NO:332, SEQ ID NO:333, SEQ ID NO:334, SEQ ID NO:335, SEQ ID NO:336, SEQ ID NO:337, SEQ ID NO:338, SEQ ID NO:339, SEQ ID NO:340, SEQ ID NO:341, SEQ ID NO:342, SEQ ID NO:343, SEQ ID NO:344, SEQ ID NO:345, SEQ ID NO:346, SEQ ID NO:347, SEQ ID NO:348, SEQ ID NO:349 or SEQ ID NO:350.

[0364] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 273 and a heavy chain variable domain comprising: SEQ ID NO: 280, SEQ ID NO: 281, SEQ ID NO: 282, SEQ ID NO: 283, SEQ ID NO: 284, SEQ ID NO: 285, SEQ ID NO: 286, SEQ ID NO: 287, SEQ ID NO: 288, SEQ ID NO: 289, SEQ ID NO: 290, SEQ ID NO: 291, SEQ ID NO: 292, SEQ ID NO: 293, SEQ ID NO: 294, SEQ ID NO: 295, SEQ ID NO: 296, SEQ ID NO: 297, SEQ ID NO: 298, SEQ ID NO: 299, SEQ ID NO: 300, SEQ ID NO: 301, SEQ ID NO: 302, SEQ ID NO: 303, SEQ ID NO: 304, SEQ ID NO: 305, SEQ ID NO: 306, SEQ ID NO: 307, SEQ ID NO: 308, SEQ ID NO: 309, SEQ ID NO: 310, SEQ ID NO: 311, SEQ ID NO: 312, SEQ ID NO: 313, SEQ ID NO: 314, SEQ ID NO: 315, SEQ ID NO: 316, SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 320, SEQ ID NO: 321, SEQ ID NO: 322, or SEQ ID NO: 323.

[0365] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 324 and a heavy chain variable domain comprising: SEQ ID NO: 272, SEQ ID NO: 280, SEQ ID NO: 281, SEQ ID NO: 282, SEQ ID NO: 283, SEQ ID NO: 284, SEQ ID NO: 285, SEQ ID NO: 286, SEQ ID NO: 287, SEQ ID NO: 288, SEQ ID NO: 289, SEQ ID NO: 290, SEQ ID NO: 291, SEQ ID NO: 292, SEQ ID NO: 293, SEQ ID NO: 294, SEQ ID NO: 295, SEQ ID NO: 296, SEQ ID NO: 297, SEQ ID NO: 298, SEQ ID NO: 299, SEQ ID NO: 300, SEQ ID NO: 301, SEQ ID NO: 302, SEQ ID NO: 303, SEQ ID NO: 304, SEQ ID NO: 305, SEQ ID NO: 306, SEQ ID NO: 307, SEQ ID NO: 308, SEQ ID NO: 309, SEQ ID NO: 310, SEQ ID NO: 311, SEQ ID NO: 312, SEQ ID NO: 313, SEQ ID NO: 314, SEQ ID NO: 315, SEQ ID NO: 316, SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 320, SEQ ID NO: 321, SEQ ID NO: 322 or SEQ ID NO: 323.

[0366] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 325 and a heavy chain variable domain comprising: SEQ ID NO: 272, SEQ ID NO: 280, SEQ ID NO: 281, SEQ ID NO: 282, SEQ ID NO: 283, SEQ ID NO: 284, SEQ ID NO: 285, SEQ ID NO: 286, SEQ ID NO: 287, SEQ ID NO: 288, SEQ ID NO: 289, SEQ ID NO: 290, SEQ ID NO: 291, SEQ ID NO: 292, SEQ ID NO: 293, SEQ ID NO: 294, SEQ ID NO: 295, SEQ ID NO: 296, SEQ ID NO: 297, SEQ ID NO: 298, SEQ ID NO: 299, SEQ ID NO: 300, SEQ ID NO: 301, SEQ ID NO: 302, SEQ ID NO: 303, SEQ ID NO: 304, SEQ ID NO: 305, SEQ ID NO: 306, SEQ ID NO: 307, SEQ ID NO: 308, SEQ ID NO: 309, SEQ ID NO: 310, SEQ ID NO: 311, SEQ ID NO: 312, SEQ ID NO: 313, SEQ ID NO: 314, SEQ ID NO: 315, SEQ ID NO: 316, SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 320, SEQ ID NO: 321, SEQ ID NO: 322 or SEQ ID NO: 323.

[0367] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 326 and a heavy chain variable domain comprising: SEQ ID NO: 272, SEQ ID NO: 280, SEQ ID NO: 281, SEQ ID NO: 282, SEQ ID NO: 283, SEQ ID NO: 284, SEQ ID NO: 285, SEQ ID NO: 286, SEQ ID NO: 287, SEQ ID NO: 288, SEQ ID NO: 289, SEQ ID NO: 290, SEQ ID NO: 291, SEQ ID NO: 292, SEQ ID NO: 293, SEQ ID NO: 294, SEQ ID NO: 295, SEQ ID NO: 296, SEQ ID NO: 297, SEQ ID NO: 298, SEQ ID NO: 299, SEQ ID NO: 300, SEQ ID NO: 301, SEQ ID NO: 302, SEQ ID NO: 303, SEQ ID NO: 304, SEQ ID NO: 305, SEQ ID NO: 306, SEQ ID NO: 307, SEQ ID NO: 308, SEQ ID NO: 309, SEQ ID NO: 310, SEQ ID NO: 311, SEQ ID NO: 312, SEQ ID NO: 313, SEQ ID NO: 314, SEQ ID NO: 315, SEQ ID NO: 316, SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 320, SEQ ID NO: 321, SEQ ID NO: 322 or SEQ ID NO: 323.

[0368] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 327 and a heavy chain variable domain comprising: SEQ ID NO: 272, SEQ ID NO: 280, SEQ ID NO: 281, SEQ ID NO: 282, SEQ ID NO: 283, SEQ ID NO: 284, SEQ ID NO: 285, SEQ ID NO: 286, SEQ ID NO: 287, SEQ ID NO: 288, SEQ ID NO: 289, SEQ ID NO: 290, SEQ ID NO: 291, SEQ ID NO: 292, SEQ ID NO: 293, SEQ ID NO: 294, SEQ ID NO: 295, SEQ ID NO: 296, SEQ ID NO: 297, SEQ ID NO: 298, SEQ ID NO: 299, SEQ ID NO: 300, SEQ ID NO: 301, SEQ ID NO: 302, SEQ ID NO: 303, SEQ ID NO: 304, SEQ ID NO: 305, SEQ ID NO: 306, SEQ ID NO: 307, SEQ ID NO: 308, SEQ ID NO: 309, SEQ ID NO: 310, SEQ ID NO: 311, SEQ ID NO: 312, SEQ ID NO: 313, SEQ ID NO: 314, SEQ ID NO: 315, SEQ ID NO: 316, SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 320, SEQ ID NO: 321, SEQ ID NO: 322 or SEQ ID NO: 323.

[0369] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 328 and a heavy chain variable domain comprising: SEQ ID NO: 272, SEQ ID NO: 280, SEQ ID NO: 281, SEQ ID NO: 282, SEQ ID NO: 283, SEQ ID NO: 284, SEQ ID NO: 285, SEQ ID NO: 286, SEQ ID NO: 287, SEQ ID NO: 288, SEQ ID NO: 289, SEQ ID NO: 290, SEQ ID NO: 291, SEQ ID NO: 292, SEQ ID NO: 293, SEQ ID NO: 294, SEQ ID NO: 295, SEQ ID NO: 296, SEQ ID NO: 297, SEQ ID NO: 298, SEQ ID NO: 299, SEQ ID NO: 300, SEQ ID NO: 301, SEQ ID NO: 302, SEQ ID NO: 303, SEQ ID NO: 304, SEQ ID NO: 305, SEQ ID NO: 306, SEQ ID NO: 307, SEQ ID NO: 308, SEQ ID NO: 309, SEQ ID NO: 310, SEQ ID NO: 311, SEQ ID NO: 312, SEQ ID NO: 313, SEQ ID NO: 314, SEQ ID NO: 315, SEQ ID NO: 316, SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 320, SEQ ID NO: 321, SEQ ID NO: 322 or SEQ ID NO: 323.

[0370] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 329 and a heavy chain variable domain comprising: SEQ ID NO: 272, SEQ ID NO: 280, SEQ ID NO: 281, SEQ ID NO: 282, SEQ ID NO: 283, SEQ ID NO: 284, SEQ ID NO: 285, SEQ ID NO: 286, SEQ ID NO: 287, SEQ ID NO: 288, SEQ ID NO: 289, SEQ ID NO: 290, SEQ ID NO: 291, SEQ ID NO: 292, SEQ ID NO: 293, SEQ ID NO: 294, SEQ ID NO: 295, SEQ ID NO: 296, SEQ ID NO: 297, SEQ ID NO: 298, SEQ ID NO: 299, SEQ ID NO: 300, SEQ ID NO: 301, SEQ ID NO: 302, SEQ ID NO: 303, SEQ ID NO: 304, SEQ ID NO: 305, SEQ ID NO: 306, SEQ ID NO: 307, SEQ ID NO: 308, SEQ ID NO: 309, SEQ ID NO: 310, SEQ ID NO: 311, SEQ ID NO: 312, SEQ ID NO: 313, SEQ ID NO: 314, SEQ ID NO: 315, SEQ ID NO: 316, SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 320, SEQ ID NO: 321, SEQ ID NO: 322 or SEQ ID NO: 323.

[0371] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 330 and a heavy chain variable domain comprising: SEQ ID NO: 272, SEQ ID NO: 280, SEQ ID NO: 281, SEQ ID NO: 282, SEQ ID NO: 283, SEQ ID NO: 284, SEQ ID NO: 285, SEQ ID NO: 286, SEQ ID NO: 287, SEQ ID NO: 288, SEQ ID NO: 289, SEQ ID NO: 290, SEQ ID NO: 291, SEQ ID NO: 292, SEQ ID NO: 293, SEQ ID NO: 294, SEQ ID NO: 295, SEQ ID NO: 296, SEQ ID NO: 297, SEQ ID NO: 298, SEQ ID NO: 299, SEQ ID NO: 300, SEQ ID NO: 301, SEQ ID NO: 302, SEQ ID NO: 303, SEQ ID NO: 304, SEQ ID NO: 305, SEQ ID NO: 306, SEQ ID NO: 307, SEQ ID NO: 308, SEQ ID NO: 309, SEQ ID NO: 310, SEQ ID NO: 311, SEQ ID NO: 312, SEQ ID NO: 313, SEQ ID NO: 314, SEQ ID NO: 315, SEQ ID NO: 316, SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 320, SEQ ID NO: 321, SEQ ID NO: 322 or SEQ ID NO: 323.

[0372] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 331 and a heavy chain variable domain comprising: SEQ ID NO: 272, SEQ ID NO: 280, SEQ ID NO: 281, SEQ ID NO: 282, SEQ ID NO: 283, SEQ ID NO: 284, SEQ ID NO: 285, SEQ ID NO: 286, SEQ ID NO: 287, SEQ ID NO: 288, SEQ ID NO: 289, SEQ ID NO: 290, SEQ ID NO: 291, SEQ ID NO: 292, SEQ ID NO: 293, SEQ ID NO: 294, SEQ ID NO: 295, SEQ ID NO: 296, SEQ ID NO: 297, SEQ ID NO: 298, SEQ ID NO: 299, SEQ ID NO: 300, SEQ ID NO: 301, SEQ ID NO: 302, SEQ ID NO: 303, SEQ ID NO: 304, SEQ ID NO: 305, SEQ ID NO: 306, SEQ ID NO: 307, SEQ ID NO: 308, SEQ ID NO: 309, SEQ ID NO: 310, SEQ ID NO: 311, SEQ ID NO: 312, SEQ ID NO: 313, SEQ ID NO: 314, SEQ ID NO: 315, SEQ ID NO: 316, SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 320, SEQ ID NO: 321, SEQ ID NO: 322 or SEQ ID NO: 323.

[0373] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 332 and a heavy chain variable domain comprising: SEQ ID NO: 272, SEQ ID NO: 280, SEQ ID NO: 281, SEQ ID NO: 282, SEQ ID NO: 283, SEQ ID NO: 284, SEQ ID NO: 285, SEQ ID NO: 286, SEQ ID NO: 287, SEQ ID NO: 288, SEQ ID NO: 289, SEQ ID NO: 290, SEQ ID NO: 291, SEQ ID NO: 292, SEQ ID NO: 293, SEQ ID NO: 294, SEQ ID NO: 295, SEQ ID NO: 296, SEQ ID NO: 297, SEQ ID NO: 298, SEQ ID NO: 299, SEQ ID NO: 300, SEQ ID NO: 301, SEQ ID NO: 302, SEQ ID NO: 303, SEQ ID NO: 304, SEQ ID NO: 305, SEQ ID NO: 306, SEQ ID NO: 307, SEQ ID NO: 308, SEQ ID NO: 309, SEQ ID NO: 310, SEQ ID NO: 311, SEQ ID NO: 312, SEQ ID NO: 313, SEQ ID NO: 314, SEQ ID NO: 315, SEQ ID NO: 316, SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 320, SEQ ID NO: 321, SEQ ID NO: 322 or SEQ ID NO: 323.

[0374] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 333 and a heavy chain variable domain comprising: SEQ ID NO: 272, SEQ ID NO: 280, SEQ ID NO: 281, SEQ ID NO: 282, SEQ ID NO: 283, SEQ ID NO: 284, SEQ ID NO: 285, SEQ ID NO: 286, SEQ ID NO: 287,...

Claims

1. A pharmaceutical composition comprising an effective amount of an antigen-binding protein construct (ABPC), the antigen-binding protein construct comprising: A first antigen-binding domain capable of specifically binding to LRRC15 or an epitope of LRRC15 presented on the surface of a target mammalian cell, wherein the first antigen-binding domain comprises: (a) A heavy-chain variable domain that is at least 90% identical to SEQ ID NO:1 and comprises three complementarity-determining regions (CDRs) in SEQ ID NO:1, except that the heavy-chain variable domain comprises histidine at one or more positions selected from the group consisting of: 33, 34, 50, 52, 57, 59, 100, 102, 103, 107, 108, and 109, and a light-chain variable domain that comprises the light-chain CDRs in SEQ ID NO:2, wherein the light-chain variable domain is at least 90% identical to SEQ ID NO:2 and comprises the three CDRs present in SEQ ID NO:2, except that the light-chain variable domain comprises histidine at one or more positions selected from the group consisting of: 32, 34, 50, 51, 89, 90, 92, 93, 94, and 96; A heavy-chain variable domain that is at least 90% identical to SEQ ID NO:1 and comprises the three CDRs present in SEQ ID NO:1, except that the heavy-chain variable domain comprises histidine at one or more positions selected from the group consisting of: 33, 34, 50, 52, 57, 59, 100, 102, 103, 107, 108, and 109, and a light-chain variable domain that is at least 90% identical to SEQ ID NO:2 and comprises the three CDRs present in SEQ ID NO:2; or A heavy-chain variable domain that is at least 90% identical to SEQ ID NO:1 and comprises the three CDRs present in SEQ ID NO:1, and a light-chain variable domain that is at least 90% identical to SEQ ID NO:2 and comprises the three CDRs present in SEQ ID NO:2, except that the light-chain variable domain comprises histidine at one or more positions 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 and contains three CDRs in SEQ ID NO:84, except that the heavy chain variable domain contains histidine at one or more positions selected from the group consisting of: 27, 29, 32, 50, 54, 58, 99, 100, 102, 104, and 105 in SEQ ID NO:84, and a light chain variable domain that is at least 90% identical to SEQ ID NO:85 and contains three CDRs present in SEQ ID NO:85, except that the light chain variable domain contains histidine at one or more positions selected from the group consisting of: 29, 31, 32, 34, 36, 37, 38, 40, 56, 60, 61, 95, 96, 97, and 100 in SEQ ID NO:85; A heavy chain variable domain that is at least 90% identical to SEQ ID NO:84 and contains three CDRs present in SEQ ID NO:84, except that the heavy chain variable domain contains histidine at one or more positions selected from the group consisting of: 27, 29, 32, 50, 54, 58, 99, 100, 102, 104, and 105 in SEQ ID NO:84, and a light chain variable domain that is at least 90% identical to SEQ ID NO:85 and contains three CDRs present in SEQ ID NO:85; or A heavy chain variable domain that is at least 90% identical to SEQ ID NO:84 and contains three CDRs present in SEQ ID NO:84, and a light chain variable domain that is at least 90% identical to SEQ ID NO:85 and contains three CDRs present in SEQ ID NO:85, except that the light chain variable domain contains histidine at one or more positions selected from the group consisting of: 29, 31, 32, 34, 36, 37, 38, 40, 56, 60, 61, 95, 96, 97, and 100 in SEQ ID NO:85; (c) A heavy chain variable domain that is at least 90% identical to SEQ ID NO:178 and contains three CDRs in SEQ ID NO:178, except that the heavy chain variable domain contains histidine at one or more positions selected from the group consisting of: 33, 52, 56, 57, or 106 in SEQ ID NO:178, and a light chain variable domain that is at least 90% identical to SEQ ID NO:179 and contains three CDRs present in SEQ ID NO:179, except that the light chain variable domain contains histidine at one or more positions selected from the group consisting of: 25, 26, 28, 29, 31, 36, 37, 57, 59, 94, 95, 96, and 100 in SEQ ID NO:179; A heavy chain variable domain that is at least 90% identical to SEQ ID NO:178 and contains the three CDRs present in SEQ ID NO:178, except that the heavy chain variable domain contains histidine at one or more positions selected from the group consisting of: 33, 52, 56, 57, or 106 of SEQ ID NO:178, and a light chain variable domain that is at least 90% identical to SEQ ID NO:179 and contains the three CDRs present in SEQ ID NO:179; or A heavy chain variable domain that is at least 90% identical to SEQ ID NO:178 and contains the three CDRs present in SEQ ID NO:178, and a light chain variable domain that is at least 90% identical to SEQ ID NO:179 and contains the three CDRs present in SEQ ID NO:179, except that the light chain variable domain contains histidine at one or more positions selected from the group consisting of: 25, 26, 28, 29, 31, 36, 37, 57, 59, 94, 95, 96, and 100 of SEQ ID NO:179; or (d) A heavy chain variable domain that is at least 90% identical to SEQ ID NO:272 and contains the three CDRs present in SEQ ID NO:272, except that the heavy chain variable domain contains histidine at one or more positions selected from the group consisting of: 24, 27, 29, 62, 63, 98, and 108 of SEQ ID NO:272, and a light chain variable domain that is at least 90% identical to SEQ ID NO:273 and contains the three CDRs present in SEQ ID NO:273, except that the light chain variable domain contains histidine at one or more positions selected from the group consisting of: 27, 28, 29, 31, 32, 89, 92, and 93 of SEQ ID NO:273; A heavy chain variable domain that is at least 90% identical to SEQ ID NO:272 and contains the three CDRs present in SEQ ID NO:272, except that the heavy chain variable domain contains histidine at one or more positions selected from the group consisting of: 24, 27, 29, 62, 63, 98, and 108 of SEQ ID NO:272, and a light chain variable domain that is at least 90% identical to SEQ ID NO:273 and contains the three light chain CDRs present in SEQ ID NO:273; or A heavy chain variable domain that is at least 90% identical to SEQ ID NO:272 and contains the three CDRs present in SEQ ID NO:272, and a light chain variable domain that is at least 90% identical to SEQ ID NO:273 and contains the three CDRs present in SEQ ID NO:273, wherein the light chain variable domain contains histidine at one or more positions selected from the group consisting of: 27, 28, 29, 31, 32, 89, 92, and 93 in SEQ ID NO:273; Wherein: (i) 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 (ii) The dissociation constant (K D ) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is greater than the K D at a pH of about 7.0 to about 8.

0.

3. The pharmaceutical composition according to claim 1, wherein after the ABPC is internalized by the target mammalian cell, the ABPC is degraded in the target mammalian cell.

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

5. A pharmaceutical composition comprising an effective amount of an antigen-binding protein construct (ABPC), the antigen-binding protein construct comprising: A first antigen-binding domain capable of specifically binding to LRRC15 or an epitope of LRRC15 presented on the surface of a target mammalian cell; and A conjugated toxin, radioisotope, drug, or small molecule, Wherein the first antigen-binding domain comprises: (a) A heavy chain variable domain that is at least 90% identical to SEQ ID NO:1 and contains the three complementarity-determining regions (CDRs) in SEQ ID NO:1, wherein the heavy chain variable domain contains histidine at one or more positions selected from the group consisting of: 33, 34, 50, 52, 57, 59, 100, 102, 103, 107, 108, and 109 in SEQ ID NO:1, and a light chain variable domain containing the light chain CDRs of SEQ ID NO:2, wherein the light chain variable domain is at least 90% identical to SEQ ID NO:2 and contains the three CDRs present in SEQ ID NO:2, wherein the light chain variable domain contains histidine at one or more positions selected from the group consisting of: 32, 34, 50, 51, 89, 90, 92, 93, 94, and 96 in SEQ ID NO:2; A heavy chain variable domain that is at least 90% identical to SEQ ID NO:1 and contains the three CDRs present in SEQ ID NO:1, except that the heavy chain variable domain contains histidine at one or more positions selected from the group consisting of: 33, 34, 50, 52, 57, 59, 100, 102, 103, 107, 108, and 109, and a light chain variable domain that is at least 90% identical to SEQ ID NO:2 and contains the three CDRs present in SEQ ID NO:2; or A heavy chain variable domain that is at least 90% identical to SEQ ID NO:1 and contains the three CDRs present in SEQ ID NO:1, and a light chain variable domain that is at least 90% identical to SEQ ID NO:2 and contains the three CDRs present in SEQ ID NO:2, except that the light chain variable domain contains histidine at one or more positions 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 and contains the three CDRs present in SEQ ID NO:84, except that the heavy chain variable domain contains histidine at one or more positions 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% identical to SEQ ID NO:85 and contains the three CDRs present in SEQ ID NO:85, except that the light chain variable domain contains histidine at one or more positions selected from the group consisting of: 29, 31, 32, 34, 36, 37, 38, 40, 56, 60, 61, 95, 96, 97, and 100; A heavy chain variable domain that is at least 90% identical to SEQ ID NO:84 and contains the three CDRs present in SEQ ID NO:84, except that the heavy chain variable domain contains histidine at one or more positions 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% identical to SEQ ID NO:85 and contains the three CDRs present in SEQ ID NO:85; or A heavy chain variable domain that is at least 90% identical to SEQ ID NO:84 and contains the three CDRs present in SEQ ID NO:84, and a light chain variable domain that is at least 90% identical to SEQ ID NO:85 and contains the three CDRs present in SEQ ID NO:85, wherein the light chain variable domain contains histidine at one or more positions selected from the group consisting of: 29, 31, 32, 34, 36, 37, 38, 40, 56, 60, 61, 95, 96, 97, and 100 of SEQ ID NO:85; (c) A heavy chain variable domain that is at least 90% identical to SEQ ID NO:178 and contains the three CDRs present in SEQ ID NO:178, wherein the heavy chain variable domain contains histidine at one or more positions selected from the group consisting of: 33, 52, 56, 57, or 106 of SEQ ID NO:178, and a light chain variable domain that is at least 90% identical to SEQ ID NO:179 and contains the three CDRs present in SEQ ID NO:179, wherein the light chain variable domain contains histidine at one or more positions selected from the group consisting of: 25, 26, 28, 29, 31, 36, 37, 57, 59, 94, 95, 96, and 100 of SEQ ID NO:179; A heavy chain variable domain that is at least 90% identical to SEQ ID NO:178 and contains the three CDRs present in SEQ ID NO:178, wherein the heavy chain variable domain contains histidine at one or more positions selected from the group consisting of: 33, 52, 56, 57, or 106 of SEQ ID NO:178, and a light chain variable domain that is at least 90% identical to SEQ ID NO:179 and contains the three CDRs present in SEQ ID NO:179; or A heavy chain variable domain that is at least 90% identical to SEQ ID NO:178 and contains the three CDRs present in SEQ ID NO:178, and a light chain variable domain that is at least 90% identical to SEQ ID NO:179 and contains the three CDRs present in SEQ ID NO:179, wherein the light chain variable domain contains histidine at one or more positions selected from the group consisting of: 25, 26, 28, 29, 31, 36, 37, 57, 59, 94, 95, 96, and 100 of SEQ ID NO:179; or (d) a heavy chain variable domain that is at least 90% identical to SEQ ID NO: 272 and contains three CDRs in SEQ ID NO: 272, wherein the heavy chain variable domain differs in that it contains histidine at one or more positions selected from the group consisting of 24, 27, 29, 62, 63, 98, and 108 in SEQ ID NO: 272, and a light chain variable domain that is at least 90% identical to SEQ ID NO: 273 and contains three CDRs present in SEQ ID NO: 273, wherein the light chain variable domain differs in that it contains histidine at one or more positions selected from the group consisting of 27, 28, 29, 31, 32, 89, 92, and 93 in SEQ ID NO: 273; a heavy chain variable domain that is at least 90% identical to SEQ ID NO: 272 and contains three CDRs present in SEQ ID NO: 272, wherein the heavy chain variable domain differs in that it contains histidine at one or more positions selected from the group consisting of 24, 27, 29, 62, 63, 98, and 108 in SEQ ID NO: 272, and a light chain variable domain that is at least 90% identical to SEQ ID NO: 273 and contains three light chain CDRs present in SEQ ID NO: 273; or a heavy chain variable domain that is at least 90% identical to SEQ ID NO: 272 and contains three CDRs present in SEQ ID NO: 272, and a light chain variable domain that is at least 90% identical to SEQ ID NO: 273 and contains three CDRs present in SEQ ID NO: 273, wherein the light chain variable domain differs in that it contains histidine at one or more positions selected from the group consisting of 27, 28, 29, 31, 32, 89, 92, and 93 in SEQ ID NO: 273; wherein: (i) 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 ) of the first antigen-binding domain at a pH of from about 4.0 to about 6.5 is greater than the K D at a pH of from about 7.0 to about 8.0; and (ii) the composition provides one or more of the following: an increase in toxin release in the target mammalian cells as compared to a composition containing the same amount of a control ABPC; an increase in target mammalian cell killing as compared to a composition containing the same amount of a control ABPC; and an increase in endolysosomal delivery in the target mammalian cells as compared to a composition containing the same amount of a control ABPC.

5. The pharmaceutical composition according to any one of claims 1-4, wherein the first antigen-binding domain comprises: (a) The following light chain variable domains: 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 The following heavy chain variable domains: SEQ ID NO:1, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82 or SEQ ID NO:83, wherein the first antigen-binding domain does not comprise: (i) the light chain variable domain of SEQ ID NO:2 and the heavy chain variable domain of SEQ ID NO:1; (ii) the light chain variable domain of SEQ ID NO:2 and a heavy chain variable domain that is not one of the following: SEQ ID NO:20, 21, 23, 25, 30, 32, 43, 45, 46, 50 - 52 or 80 - 83; or (iii) the heavy chain variable domain of SEQ ID NO:1 and a light chain variable domain that is not one of the following: SEQ ID NO:61, 63 - 65, 71, 72, 74 - 76 or 78; (b) The following light chain variable domains: SEQ ID NO:85, SEQ ID NO:137, SEQ ID NO:139, SEQ ID NO:140, SEQ ID NO:142, SEQ ID NO:144, SEQ ID NO:145, SEQ ID NO:146, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:153, SEQ ID NO:154, SEQ ID NO:156, SEQ ID NO:157, SEQ ID NO:158, SEQ ID NO:161, SEQ ID NO:169, SEQ ID NO:170, SEQ ID NO:171, SEQ ID NO:172, SEQ ID NO:173, SEQ ID NO:174, SEQ ID NO:175, SEQ ID NO:176 or SEQ ID NO:177, and / or The following heavy chain variable domains: SEQ ID NO:84, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:98, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:126, SEQ ID NO:127 or SEQ ID NO:166, wherein the first antigen-binding domain does not include: (i) The light chain variable domain of SEQ ID NO:85 and the heavy chain variable domain of SEQ ID NO:84; (ii) The light chain variable domain of SEQ ID NO:85 and a heavy chain variable domain that is not one of the following: SEQ ID NO:93, 95, 98, 101, 102, 106, 110, 120 - 122, 124, 126, 127 or 166; or (iii) The heavy chain variable domain of SEQ ID NO:84 and a light chain variable domain that is not one of the following: SEQ ID NO:137, 139, 140, 142, 144 - 146, 148, 149, 153, 154, 156 - 158, 161 or 169 - 177; (c) The following light chain variable domains: 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 The following heavy chain variable domains: 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 does not include: (i) the light chain variable domain of SEQ ID NO: 179 and the heavy chain variable domain of SEQ ID NO: 178; (ii) the light chain variable domain of SEQ ID NO: 179 and a heavy chain variable domain that is not one of the following: SEQ ID NOs: 196, 201, 205, 206, 225, or 258 - 261; or (iii) the heavy chain variable domain of SEQ ID NO: 178 and a light chain variable domain that is not one of the following: SEQ ID NOs: 229, 230, 232, 233, 235, 240, 241, 246, 248, 251 - 253, 257, 263, 264, or 268 - 271; or (d) the light chain variable domains of the following: 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 the heavy chain variable domains of the following: 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 does not contain: (i) the light chain variable domain of SEQ ID NO: 273 and the heavy chain variable domain of SEQ ID NO: 272; (ii) the light chain variable domain of SEQ ID NO: 273 and a heavy chain variable domain that is not one of the following: SEQ ID NOs: 281, 284, 286, 305, 306, 311, or 321; or (iii) the heavy chain variable domain of SEQ ID NO: 272 and a light chain variable domain that is not one of the following: SEQ ID NOs: 327 - 329, 331, 332, 342, 345, or 346.

6. The pharmaceutical composition according to any one of claims 1 - 5, wherein the composition provides the following: an increase in the release of the toxin in the target mammalian cells as compared to a composition comprising the same amount of control ABPC; and / or an increase in the killing of target mammalian cells as compared to a composition comprising the same amount of control ABPC.

7. The pharmaceutical composition according to any one of claims 1 - 6, wherein the composition provides an increase in the endolysosomal delivery in the target mammalian cells as compared to a composition comprising the same amount of control ABPC.

8. The pharmaceutical composition according to any one of claims 1 - 7, wherein the composition: results in less reduction in the level of LRRC15 presented on the surface of the target mammalian cells as compared to a composition comprising the same amount of control ABPC; or does not cause a detectable reduction in the level of LRRC15 presented on the surface of the target mammalian cells.

9. The pharmaceutical composition according to any one of claims 1 - 8, wherein the target mammalian cells are cancer cells.

10. The pharmaceutical composition according to any one of claims 1 - 9, wherein the ABPC is cytotoxic or cytostatic to the target mammalian cells.

11. The pharmaceutical composition according to any one of claims 1 - 10, wherein the ABPC: has cross - reactivity with non - human primate LRRC15 and human LRRC15; or has cross - reactivity with non - human primate LRRC15, human LRRC15, and one or both of rat LRRC15 and mouse LRRC15.

12. The pharmaceutical composition according to any one of claims 1 - 11, wherein the ABPC comprises a single polypeptide.

13. The pharmaceutical composition according to claim 12, wherein the antigen - binding domain is selected from the group consisting of: VH domain, VHH domain, VNAR domain, and scFv.

14. The pharmaceutical composition according to any one of claims 1 - 11, wherein the ABPC comprises two or more polypeptides.

15. The pharmaceutical composition according to claim 14, wherein the ABPC is an antibody.

16. The pharmaceutical composition according to any one of claims 1 - 15, wherein the half - life of the ABPC in vivo is decreased as compared to the half - life of the control ABPC in vivo.

17. The pharmaceutical composition according to any one of claims 1 - 16, wherein the ABPC further comprises a second antigen - binding domain.

18. An antigen - binding protein construct (ABPC) comprising: a first antigen - binding domain that is capable of specifically binding to LRRC15 or an epitope of LRRC15 presented on the surface of target mammalian cells, wherein the first antigen - binding domain comprises: (a) A heavy chain variable domain that is at least 90% identical to SEQ ID NO:1 and contains three complementarity-determining regions (CDRs) in SEQ ID NO:1, except that the heavy chain variable domain contains histidine at one or more positions selected from the group consisting of: 33, 34, 50, 52, 57, 59, 100, 102, 103, 107, 108, and 109 in SEQ ID NO:1, and a light chain variable domain that contains the light chain CDRs in SEQ ID NO:2, wherein the light chain variable domain is at least 90% identical to SEQ ID NO:2 and contains the three CDRs present in SEQ ID NO:2, except that the light chain variable domain contains histidine at one or more positions selected from the group consisting of: 32, 34, 50, 51, 89, 90, 92, 93, 94, and 96 in SEQ ID NO:2; A heavy chain variable domain that is at least 90% identical to SEQ ID NO:1 and contains the three CDRs present in SEQ ID NO:1, except that the heavy chain variable domain contains histidine at one or more positions selected from the group consisting of: 33, 34, 50, 52, 57, 59, 100, 102, 103, 107, 108, and 109 in SEQ ID NO:1, and a light chain variable domain that is at least 90% identical to SEQ ID NO:2 and contains the three CDRs present in SEQ ID NO:2; or A heavy chain variable domain that is at least 90% identical to SEQ ID NO:1 and contains the three CDRs present in SEQ ID NO:1, and a light chain variable domain that is at least 90% identical to SEQ ID NO:2 and contains the three CDRs present in SEQ ID NO:2, except that the light chain variable domain contains histidine at one or more positions selected from the group consisting of: 32, 34, 50, 51, 89, 90, 92, 93, 94, and 96 in SEQ ID NO:2; (b) A heavy chain variable domain that is at least 90% identical to SEQ ID NO:84 and contains the three CDRs in SEQ ID NO:84, except that the heavy chain variable domain contains histidine at one or more positions selected from the group consisting of: 27, 29, 32, 50, 54, 58, 99, 100, 102, 104, and 105 in SEQ ID NO:84, and a light chain variable domain that is at least 90% identical to SEQ ID NO:85 and contains the three CDRs present in SEQ ID NO:85, except that the light chain variable domain contains histidine at one or more positions selected from the group consisting of: 29, 31, 32, 34, 36, 37, 38, 40, 56, 60, 61, 95, 96, 97, and 100 in SEQ ID NO:85; A heavy chain variable domain that is at least 90% identical to SEQ ID NO:84 and contains the three CDRs present in SEQ ID NO:84, except that the heavy chain variable domain contains histidine at one or more positions selected from the group consisting of: 27, 29, 32, 50, 54, 58, 99, 100, 102, 104, and 105 in SEQ ID NO:84, and a light chain variable domain that is at least 90% identical to SEQ ID NO:85 and contains the three CDRs present in SEQ ID NO:85; or A heavy chain variable domain that is at least 90% identical to SEQ ID NO:84 and contains the three CDRs present in SEQ ID NO:84, and a light chain variable domain that is at least 90% identical to SEQ ID NO:85 and contains the three CDRs present in SEQ ID NO:85, except that the light chain variable domain contains histidine at one or more positions selected from the group consisting of: 29, 31, 32, 34, 36, 37, 38, 40, 56, 60, 61, 95, 96, 97, and 100 in SEQ ID NO:85; (c) A heavy chain variable domain that is at least 90% identical to SEQ ID NO:178 and contains the three CDRs in SEQ ID NO:178, except that the heavy chain variable domain contains histidine at one or more positions selected from the group consisting of: 33, 52, 56, 57, or 106 in SEQ ID NO:178, and a light chain variable domain that is at least 90% identical to SEQ ID NO:179 and contains the three CDRs present in SEQ ID NO:179, except that the light chain variable domain contains histidine at one or more positions selected from the group consisting of: 25, 26, 28, 29, 31, 36, 37, 57, 59, 94, 95, 96, and 100 in SEQ ID NO:179; A heavy chain variable domain that is at least 90% identical to SEQ ID NO:178 and contains the three CDRs present in SEQ ID NO:178, except that the heavy chain variable domain contains histidine at one or more positions selected from the group consisting of: 33, 52, 56, 57 or 106 of SEQ ID NO:178, and a light chain variable domain that is at least 90% identical to SEQ ID NO:179 and contains the three CDRs present in SEQ ID NO:179; or A heavy chain variable domain that is at least 90% identical to SEQ ID NO:178 and contains the three CDRs present in SEQ ID NO:178, and a light chain variable domain that is at least 90% identical to SEQ ID NO:179 and contains the three CDRs present in SEQ ID NO:179, except that the light chain variable domain contains histidine at one or more positions selected from the group consisting of: 25, 26, 28, 29, 31, 36, 37, 57, 59, 94, 95, 96 and 100 of SEQ ID NO:179; or (d) A heavy chain variable domain that is at least 90% identical to SEQ ID NO:272 and contains the three CDRs present in SEQ ID NO:272, except that the heavy chain variable domain contains histidine at one or more positions selected from the group consisting of: 24, 27, 29, 62, 63, 98 and 108 of SEQ ID NO:272, and a light chain variable domain that is at least 90% identical to SEQ ID NO:273 and contains the three CDRs present in SEQ ID NO:273, except that the light chain variable domain contains histidine at one or more positions selected from the group consisting of: 27, 28, 29, 31, 32, 89, 92 and 93 of SEQ ID NO:273; A heavy chain variable domain that is at least 90% identical to SEQ ID NO:272 and contains the three CDRs present in SEQ ID NO:272, except that the heavy chain variable domain contains histidine at one or more positions selected from the group consisting of: 24, 27, 29, 62, 63, 98 and 108 of SEQ ID NO:272, and a light chain variable domain that is at least 90% identical to SEQ ID NO:273 and contains the three light chain CDRs present in SEQ ID NO:273; or A heavy chain variable domain that is at least 90% identical to SEQ ID NO: 272 and contains the three CDRs present in SEQ ID NO: 272, and a light chain variable domain that is at least 90% identical to SEQ ID NO: 273 and contains the three CDRs present in SEQ ID NO: 273, wherein the light chain variable domain contains histidine at one or more positions selected from the group consisting of 27, 28, 29, 31, 32, 89, 92, and 93 in SEQ ID NO: 273; Wherein: (i) 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 (ii) The dissociation constant (K D ) of the first antigen-binding domain at a pH of from about 4.0 to about 6.5 is greater than the K D at a pH of from about 7.0 to about 8.

0.

19. The ABPC according to claim 18, wherein after the ABPC is internalized by the target mammalian cell, the ABPC is degraded in the target mammalian cell.

20. The ABPC according to claim 18 or 19, wherein the ABPC further comprises a conjugated toxin, radioisotope, drug, or small molecule.

21. An antigen-binding protein construct (ABPC) comprising: A first antigen-binding domain that is capable of specifically binding to LRRC15 or an epitope of LRRC15 presented on the surface of a target mammalian cell; and A conjugated toxin, radioisotope, drug, or small molecule, Wherein the first antigen-binding domain comprises: (a) a heavy chain variable domain that is at least 90% identical to SEQ ID NO: 1 and contains the three complementarity-determining regions (CDRs) in SEQ ID NO: 1, wherein the heavy chain variable domain contains histidine at one or more positions selected from the group consisting of 33, 34, 50, 52, 57, 59, 100, 102, 103, 107, 108, and 109 in SEQ ID NO: 1, and a light chain variable domain containing the light chain CDRs of SEQ ID NO: 2, wherein the light chain variable domain is at least 90% identical to SEQ ID NO: 2 and contains the three CDRs present in SEQ ID NO: 2, wherein the light chain variable domain contains histidine at one or more positions selected from the group consisting of 32, 34, 50, 51, 89, 90, 92, 93, 94, and 96 in SEQ ID NO: 2; A heavy chain variable domain that is at least 90% identical to SEQ ID NO:1 and contains the three CDRs present in SEQ ID NO:1, except that the heavy chain variable domain contains histidine at one or more positions selected from the group consisting of: 33, 34, 50, 52, 57, 59, 100, 102, 103, 107, 108, and 109 of SEQ ID NO:1, and a light chain variable domain that is at least 90% identical to SEQ ID NO:2 and contains the three CDRs present in SEQ ID NO:2; or A heavy chain variable domain that is at least 90% identical to SEQ ID NO:1 and contains the three CDRs present in SEQ ID NO:1, and a light chain variable domain that is at least 90% identical to SEQ ID NO:2 and contains the three CDRs present in SEQ ID NO:2, except that the light chain variable domain contains histidine at one or more positions selected from the group consisting of: 32, 34, 50, 51, 89, 90, 92, 93, 94, and 96 of SEQ ID NO:2; (b) A heavy chain variable domain that is at least 90% identical to SEQ ID NO:84 and contains the three CDRs present in SEQ ID NO:84, except that the heavy chain variable domain contains histidine at one or more positions selected from the group consisting of: 27, 29, 32, 50, 54, 58, 99, 100, 102, 104, and 105 of SEQ ID NO:84, and a light chain variable domain that is at least 90% identical to SEQ ID NO:85 and contains the three CDRs present in SEQ ID NO:85, except that the light chain variable domain contains histidine at one or more positions selected from the group consisting of: 29, 31, 32, 34, 36, 37, 38, 40, 56, 60, 61, 95, 96, 97, and 100 of SEQ ID NO:85; A heavy chain variable domain that is at least 90% identical to SEQ ID NO:84 and contains the three CDRs present in SEQ ID NO:84, except that the heavy chain variable domain contains histidine at one or more positions selected from the group consisting of: 27, 29, 32, 50, 54, 58, 99, 100, 102, 104, and 105 of SEQ ID NO:84, and a light chain variable domain that is at least 90% identical to SEQ ID NO:85 and contains the three CDRs present in SEQ ID NO:85; or A heavy chain variable domain that is at least 90% identical to SEQ ID NO:84 and contains the three CDRs present in SEQ ID NO:84, and a light chain variable domain that is at least 90% identical to SEQ ID NO:85 and contains the three CDRs present in SEQ ID NO:85, wherein the light chain variable domain contains histidine at one or more positions selected from the group consisting of: 29, 31, 32, 34, 36, 37, 38, 40, 56, 60, 61, 95, 96, 97, and 100 of SEQ ID NO:85; (c) A heavy chain variable domain that is at least 90% identical to SEQ ID NO:178 and contains the three CDRs present in SEQ ID NO:178, wherein the heavy chain variable domain contains histidine at one or more positions selected from the group consisting of: 33, 52, 56, 57, or 106 of SEQ ID NO:178, and a light chain variable domain that is at least 90% identical to SEQ ID NO:179 and contains the three CDRs present in SEQ ID NO:179, wherein the light chain variable domain contains histidine at one or more positions selected from the group consisting of: 25, 26, 28, 29, 31, 36, 37, 57, 59, 94, 95, 96, and 100 of SEQ ID NO:179; A heavy chain variable domain that is at least 90% identical to SEQ ID NO:178 and contains the three CDRs present in SEQ ID NO:178, wherein the heavy chain variable domain contains histidine at one or more positions selected from the group consisting of: 33, 52, 56, 57, or 106 of SEQ ID NO:178, and a light chain variable domain that is at least 90% identical to SEQ ID NO:179 and contains the three CDRs present in SEQ ID NO:179; or A heavy chain variable domain that is at least 90% identical to SEQ ID NO:178 and contains the three CDRs present in SEQ ID NO:178, and a light chain variable domain that is at least 90% identical to SEQ ID NO:179 and contains the three CDRs present in SEQ ID NO:179, wherein the light chain variable domain contains histidine at one or more positions selected from the group consisting of: 25, 26, 28, 29, 31, 36, 37, 57, 59, 94, 95, 96, and 100 of SEQ ID NO:179; or (d) A heavy chain variable domain that is at least 90% identical to SEQ ID NO: 272 and contains the three CDRs in SEQ ID NO: 272, except that the heavy chain variable domain contains histidine at one or more positions selected from the group consisting of: 24, 27, 29, 62, 63, 98, and 108 of SEQ ID NO: 272, and a light chain variable domain that is at least 90% identical to SEQ ID NO: 273 and contains the three CDRs present in SEQ ID NO: 273, except that the light chain variable domain contains histidine at one or more positions selected from the group consisting of: 27, 28, 29, 31, 32, 89, 92, and 93 of SEQ ID NO: 273; A heavy chain variable domain that is at least 90% identical to SEQ ID NO: 272 and contains the three CDRs present in SEQ ID NO: 272, except that the heavy chain variable domain contains histidine at one or more positions selected from the group consisting of: 24, 27, 29, 62, 63, 98, and 108 of SEQ ID NO: 272, and a light chain variable domain that is at least 90% identical to SEQ ID NO: 273 and contains the three light chain CDRs present in SEQ ID NO: 273; or A heavy chain variable domain that is at least 90% identical to SEQ ID NO: 272 and contains the three CDRs present in SEQ ID NO: 272, and a light chain variable domain that is at least 90% identical to SEQ ID NO: 273 and contains the three CDRs present in SEQ ID NO: 273, except that the light chain variable domain contains histidine at one or more positions selected from the group consisting of: 27, 28, 29, 31, 32, 89, 92, and 93 of SEQ ID NO: 273; Wherein: (i) 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 ) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is greater than the K D at a pH of about 7.0 to about 8.0; and (ii) The composition comprising the ABPC provides one or more of the following: An increase in the release of toxin in the target mammalian cells compared to a composition comprising the same amount of a control ABPC; An increase in the killing of target mammalian cells compared to a composition comprising the same amount of a control ABPC; and An increase in the endolysosomal delivery in the target mammalian cells compared to a composition comprising the same amount of a control ABPC.

22. The ABPC according to any one of claims 18 - 21, wherein the first antigen-binding domain comprises: (a) The following light chain variable domains: 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 The following heavy chain variable domains: SEQ ID NO:1, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82 or SEQ ID NO:83, wherein the first antigen-binding domain does not comprise: (i) the light chain variable domain of SEQ ID NO:2 and the heavy chain variable domain of SEQ ID NO:1; (ii) the light chain variable domain of SEQ ID NO:2 and a heavy chain variable domain that is not one of the following: SEQ ID NO:20, 21, 23, 25, 30, 32, 43, 45, 46, 50 - 52 or 80 - 83; or (iii) the heavy chain variable domain of SEQ ID NO:1 and a light chain variable domain that is not one of the following: SEQ ID NO:61, 63 - 65, 71, 72, 74 - 76 or 78; (b) The following light chain variable domains: SEQ ID NO:85, SEQ ID NO:137, SEQ ID NO:139, SEQ ID NO:140, SEQ ID NO:142, SEQ ID NO:144, SEQ ID NO:145, SEQ ID NO:146, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:153, SEQ ID NO:154, SEQ ID NO:156, SEQ ID NO:157, SEQ ID NO:158, SEQ ID NO:161, SEQ ID NO:169, SEQ ID NO:170, SEQ ID NO:171, SEQ ID NO:172, SEQ ID NO:173, SEQ ID NO:174, SEQ ID NO:175, SEQ ID NO:176 or SEQ ID NO:177, and / or The following heavy chain variable domains: SEQ ID NO:84, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:98, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:126, SEQ ID NO:127 or SEQ ID NO:166, Wherein the first antigen-binding domain does not include: (i) The light chain variable domain of SEQ ID NO:85 and the heavy chain variable domain of SEQ ID NO:84; (ii) The light chain variable domain of SEQ ID NO:85 and a heavy chain variable domain that is not one of the following: SEQ ID NO:93, 95, 98, 101, 102, 106, 110, 120 - 122, 124, 126, 127 or 166; or (iii) The heavy chain variable domain of SEQ ID NO:84 and a light chain variable domain that is not one of the following: SEQ ID NO:137, 139, 140, 142, 144 - 146, 148, 149, 153, 154, 156 - 158, 161 or 169 - 177; (c) The following light chain variable domains: 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 The following heavy chain variable domains: 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 does not include: (i) the light chain variable domain of SEQ ID NO: 179 and the heavy chain variable domain of SEQ ID NO: 178; (ii) the light chain variable domain and the heavy chain variable domain of SEQ ID NO: 179, wherein the heavy chain variable domain is not one of the following: SEQ ID NOs: 196, 201, 205, 206, 225, or 258 - 261; or (iii) the heavy chain variable domain and the light chain variable domain of SEQ ID NO: 178, wherein the light chain variable domain is not one of the following: SEQ ID NOs: 229, 230, 232, 233, 235, 240, 241, 246, 248, 251 - 253, 257, 263, 264, or 268 - 271; or (d) the light chain variable domains of the following: 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 the heavy chain variable domains of the following: 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 does not contain: (i) the light chain variable domain of SEQ ID NO: 273 and the heavy chain variable domain of SEQ ID NO: 272; (ii) the light chain variable domain and the heavy chain variable domain of SEQ ID NO: 273, wherein the heavy chain variable domain is not one of the following: SEQ ID NOs: 281, 284, 286, 305, 306, 311, or 321; or (iii) the heavy chain variable domain and the light chain variable domain of SEQ ID NO: 272, wherein the light chain variable domain is not one of the following: SEQ ID NOs: 327 - 329, 331, 332, 342, 345, or 346.

23. The ABPC according to any one of claims 18 - 22, wherein the composition comprising the ABPC provides the following: an increase in the release of toxin in the target mammalian cells as compared to a composition comprising the same amount of a control ABPC; and / or an increase in the killing of target mammalian cells as compared to a composition comprising the same amount of a control ABPC.

24. The ABPC according to any one of claims 18 - 23, wherein the composition comprising the ABPC provides an increase in endolysosomal delivery in the target mammalian cells as compared to a composition comprising the same amount of a control ABPC.

25. The ABPC according to any one of claims 18-24, wherein the composition comprising the ABPC: results in less reduction in the level of LRRC15 presented on the surface of the target mammalian cells as compared to a composition comprising the same amount of a control ABPC; or does not cause a detectable reduction in the level of LRRC15 presented on the surface of the target mammalian cells.

26. The ABPC according to any one of claims 18-25, wherein the target mammalian cells are cancer cells.

27. The ABPC according to any one of claims 18-26, wherein the ABPC is cytotoxic or cytostatic to the target mammalian cells.

28. The ABPC according to any one of claims 18-27, wherein the ABPC: has cross-reactivity with non-human primate LRRC15 and human LRRC15; or has cross-reactivity with non-human primate LRRC15, human LRRC15, and one or both of rat LRRC15 and mouse LRRC15.

29. The ABPC according to any one of claims 18-28, wherein the ABPC comprises a single polypeptide.

30. The ABPC according to claim 29, wherein the antigen-binding domain is selected from the group consisting of a VH domain, a VHH domain, a VNAR domain, and a scFv.

31. The ABPC according to any one of claims 18-28, wherein the ABPC comprises two or more polypeptides.

32. The ABPC according to claim 31, wherein the ABPC is an antibody.

33. The ABPC according to any one of claims 18-32, wherein the half-life of the ABPC in vivo is decreased as compared to the half-life of a control ABPC in vivo.

34. The ABPC according to any one of claims 18-33, wherein the ABPC further comprises a second antigen-binding domain.

35. A kit comprising at least one dose of the pharmaceutical composition according to any one of claims 1-17 or the ABPC according to any one of claims 18-34.

36. Use of the pharmaceutical composition according to any one of claims 1-17 or the ABPC according to any one of claims 18-34 in the manufacture of a medicament for a method of treating cancer, the cancer being characterized by having a population of cancer cells that have LRRC15 or an epitope of LRRC15 presented on the surface of the cancer cells, the method comprising: administering to a subject identified as having cancer characterized by having the population of cancer cells a therapeutically effective amount of the pharmaceutical composition according to any one of claims 1-17 or the ABPC according to any one of claims 18-34.

37. Use of the pharmaceutical composition according to any one of claims 1-17 or ABPC according to any one of claims 18-34 in the manufacture of a medicament for a method of reducing the volume of a tumor in a subject, wherein the tumor is characterized by having a population of cancer cells, the cancer cells having LRRC15 or an epitope of LRRC15 presented on the surface of the cancer cells, the method comprising: Administering a therapeutically effective amount of the pharmaceutical composition according to any one of claims 1-17 or ABPC according to any one of claims 18-34 to a subject identified as having a cancer characterized by having the population of cancer cells.

38. Use of the pharmaceutical composition according to any one of claims 1-17 or ABPC according to any one of claims 18-34 in the manufacture of a medicament for a method of inducing cell death in cancer cells of a subject, wherein the cancer cells have LRRC15 or an epitope of LRRC15 presented on their surface, wherein the method comprises: Administering a therapeutically effective amount of the pharmaceutical composition according to any one of claims 1-17 or ABPC according to any one of claims 18-34 to a subject identified as having a cancer characterized by having the population of cancer cells.

39. Use of the pharmaceutical composition according to any one of claims 1-17 or ABPC according to any one of claims 18-34 in the manufacture of a medicament for a method of reducing the risk of metastasis or reducing the risk of additional metastasis in a subject having cancer, wherein the tumor is characterized by having a population of cancer cells, the cancer cells having LRRC15 or an epitope of LRRC15 presented on the surface of the cancer cells, the method comprising: Administering a therapeutically effective amount of the pharmaceutical composition according to any one of claims 1-17 or ABPC according to any one of claims 18-34 to a subject identified as having a cancer characterized by having the population of cancer cells.

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