Antigen binding protein constructs and uses thereof

Abstract

Provided herein are antigen binding protein constructs capable of specifically binding to FOLR1 or an epitope of FOLR1 presented on the surface of a target mammalian cell, wherein the antigen binding is pH dependent. Uses of the antigen binding protein constructs are also provided.

Description

[0001] This application is a divisional application of a Chinese patent application with an application date of June 5, 2020, an application number of 202080056438.5, and an invention title of "Antigen-Binding Protein Constructs and Their Uses".

[0002] Cross-reference to related applications

[0003] This application claims priority to U.S. Provisional Patent Application 62 / 858,310, filed June 6, 2019, and U.S. Provisional Patent Application 62 / 897,965, filed September 9, 2019. The content of each of these applications is hereby incorporated by reference in its entirety. Technical field

[0004] The present disclosure relates to the field of biotechnology and, more particularly, to antigen-binding molecules. Background art

[0005] Antibody-drug conjugates have been designed to combat a variety of diseases. A particular advantage of this approach is that antibody-drug conjugates can have cytostatic or cytotoxic effects. Despite years of development, there is a need for improved antibody-drug conjugates. Summary of the invention

[0006] 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 (e.g., a detectable increase) from target mammalian cells, increased killing of target mammalian cells (e.g., a detectable increase), and increased endolysosomal delivery (e.g., a detectable increase)).

[0007] Provided herein are pharmaceutical compositions comprising an effective amount of an antigen-binding protein construct (ABPC) comprising: a first antigen-binding domain capable of specifically binding to FOLR1 or an epitope of FOLR1 presented on the surface of a target mammalian cell, wherein: (a) the dissociation rate of the first antigen-binding domain is faster at a pH of about 4.0 to about 6.5 than at a pH of about 7.0 to about 8.0; or (b) the dissociation constant (KD) of the first antigen-binding domain is greater at a pH of about 4.0 to about 6.5 than at a pH of about 7.0 to about 8.0.

[0008] In some embodiments of any of the pharmaceutical compositions described herein, the ABPC degrades in the target mammalian cell after the ABPC has been internalized by the target mammalian cell.

[0009] In some embodiments of any of the pharmaceutical compositions described herein, the ABPC comprises a conjugated toxin, radioisotope, drug, or small molecule.

[0010] The present disclosure also provides a pharmaceutical composition comprising an effective amount of an antigen-binding protein construct (ABPC) comprising: a first antigen-binding domain capable of specifically binding to an epitope of FOLR1 or FOLR1 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 (KD) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is greater than the KD 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.

[0011] In some embodiments of any of the pharmaceutical compositions described herein, the first antigen-binding domain comprises one of (a) to (c): (a) the heavy chain variable domain of mirvetuximab with one or more amino acids substituted with histidine, wherein the heavy chain variable domain of mirvetuximab comprises SEQ ID NO:1; and / or the light chain variable domain of mirvetuximab with one or more amino acids substituted with histidine, wherein the light chain variable domain of mirvetuximab comprises SEQ ID NO:2; (b) the heavy chain variable domain of STRO-002 with one or more amino acids substituted with histidine, wherein the heavy chain variable domain of STRO-002 comprises SEQ ID NO:105; and / or the light chain variable domain of STRO-002 with one or more amino acids substituted with histidine, wherein the light chain variable domain of STRO-002 comprises SEQ ID NO:106; (c) the heavy chain variable domain of farletuzumab with one or more amino acids substituted with histidine, wherein the heavy chain variable domain of farletuzumab comprises SEQ ID NO:184; and / or the light chain variable domain of farletuzumab with one or more amino acids substituted with histidine, wherein the light chain variable domain of farletuzumab comprises SEQ ID NO:185.

[0012] In some embodiments of any of the pharmaceutical compositions described herein, the first FOLR1-binding domain comprises one of (a) to (c): (a) a heavy-chain variable domain comprising CDR1, CDR2, and CDR3 that are SEQ ID NO: 3-5, respectively, wherein one or more amino acid positions in total among SEQ ID NO: 3-5 are substituted with histidine; and / or a light-chain variable domain comprising CDR1, CDR2, and CDR3 that are SEQ ID NO: 6-8, respectively, wherein one or more amino acid positions in total among SEQ ID NO: 6-8 are substituted with histidine; (b) a heavy-chain variable domain comprising CDR1, CDR2, and CDR3 that are SEQ ID NO: 107-109, respectively, wherein one or more amino acid positions in total among SEQ ID NO: 107-109 are substituted with histidine; and / or a light-chain variable domain comprising CDR1, CDR2, and CDR3 that are SEQ ID NO: 110-112, respectively, wherein one or more amino acid positions in total among SEQ ID NO: 110-112 are substituted with histidine; (c) a heavy-chain variable domain comprising CDR1, CDR2, and CDR3 that are SEQ ID NO: 186-188, respectively, wherein one or more amino acid positions in total among SEQ ID NO: 186-188 are substituted with histidine; and a light-chain variable domain comprising CDR1, CDR2, and CDR3 that are SEQ ID NO: 189-191, respectively, wherein one or more amino acid positions in total among SEQ ID NO: 189-191 are substituted with histidine.

[0013] In some embodiments of any of the pharmaceutical compositions described herein, the first antigen-binding domain comprises one of (a) to (c): (a) a heavy-chain variable domain having at least 90% identity to SEQ ID NO:1, wherein the heavy-chain variable domain comprises histidine at one or more positions selected from the group consisting of: 24, 27, 29, 31, 32, 33, 34, 50, 54, 55, 57, 58, 59, 60, 97, 98, 99, 100, 102, 103, 105 and 107 in SEQ ID NO:1; and / or a light-chain variable domain having at least 90% identity to SEQ ID NO:2, wherein the light-chain variable domain comprises histidine at one or more positions selected from the group consisting of: 28, 30, 31, 32, 34, 35, 36, 55, 59, 93, 94, 95, 96, 97, 98 and 100 in SEQ ID NO:2; (b) a heavy-chain variable domain having at least 90% identity to SEQ ID NO:105, wherein the heavy-chain variable domain comprises histidine at one or more positions selected from the group consisting of: 29, 33, 34, 50, 51, 52, 53, 55, 56, 57, 101, 102, 103, 108, 109, 110, 111, 112 and 113 in SEQ ID NO:105; and a light-chain variable domain having at least 90% identity to SEQ ID NO:106, wherein the light-chain variable domain comprises histidine at one or more positions selected from the group consisting of: 28, 29, 30, 31, 50, 92, 93, 94, 95 and 96 in SEQ ID NO:106; (c) a heavy-chain variable domain having at least 90% identity to SEQ ID NO:184, wherein the heavy-chain variable domain comprises histidine at one or more positions selected from the group consisting of: 26, 27, 28, 29, 30, 32, 33, 34, 53, 56, 57, 59, 62, 63, 103 and 105 in SEQ ID NO:184; and / or a light-chain variable domain having at least 90% identity to SEQ ID NO:185, wherein the light-chain variable domain comprises histidine at one or more positions selected from the group consisting of: 29, 33, 34, 51, 52, 53, 54, 55, 90, 92, 94, 96, 97, 98, 99 and 100 in SEQ ID NO:185.

[0014] In some embodiments of any of the pharmaceutical compositions described herein, the first antigen-binding domain comprises one of (a) to (c): (a) a light chain variable domain of: SEQ ID NO:2, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81 or SEQ ID NO:83; and / or a heavy chain variable domain of: SEQ ID NO:1, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, 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 or SEQ ID NO:103, 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 SEQ ID NO:14, 17, 19, 21-24, 26, 28, 30, 31, 33-36, 43-46, 48, 49, 51, 53, and 85-103; (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:58, 60-62, 64-66, 68, 70, 74, 76-81, and 83; and / or (b) the following light chain variable domains: SEQ ID NO:106, SEQ ID NO:161, SEQ ID NO:162, SEQ ID NO:163, SEQ ID NO:164, SEQ ID NO:168, SEQ ID NO:177, SEQ ID NO:178, SEQ ID NO:179, SEQ ID NO:180, SEQ ID NO:181, or SEQ ID NO:182; and / or the following heavy chain variable domains: SEQ ID NO:105, SEQ ID NO:116, 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:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:144, SEQ ID NO:145, SEQ ID NO:146, SEQ ID NO:151, SEQ ID NO:152, SEQ ID NO:153, SEQ ID NO:154, SEQ ID NO:155, or SEQ ID NO:156, wherein the first antigen-binding domain does not comprise (i) the light chain variable domain of SEQ ID NO:106 and the heavy chain variable domain of SEQ ID NO:105; (ii) the light chain variable domain of SEQ ID NO:106 and a heavy chain variable domain that is not one of SEQ ID NO:116, 120-126, 128-130, 144-146, and 151-156; (iii) the heavy chain variable domain of SEQ ID NO:105 and a light chain variable domain that is not one of SEQ ID NO:161-164, 168, and 177-182;(c) The following light chain variable domains: SEQ ID NO:185, SEQ ID NO:233, 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:247, SEQ ID NO:249, SEQ ID NO:251, SEQ ID NO:253, SEQ ID NO:254, SEQ ID NO:255, SEQ ID NO:256 or SEQ ID NO:257; and / or the following heavy chain variable domains: SEQ ID NO:184, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:205, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:211, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:221, SEQ ID NO:225 or SEQ ID NO:227, wherein the first antigen-binding domain does not comprise (i) the light chain variable domain of SEQ ID NO:185 and the heavy chain variable domain of SEQ ID NO:184; (ii) the light chain variable domain of SEQ ID NO:185 and a heavy chain variable domain that is not one of SEQ ID NO:192-196, 198-200, 205, 208, 209, 211, 214, 215, 221, 225 and 227; (iii) the heavy chain variable domain of SEQ ID NO:184 and a light chain variable domain that is not one of SEQ ID NO:233, 237-244, 247, 249, 251 and 253-257).;

[0015] In some embodiments of any of the pharmaceutical compositions described herein, the composition provides: an increase in toxin release in the target mammalian cells compared to a composition comprising the same amount of control ABPC; and / or an increase in target mammalian cell killing compared to a composition comprising the same amount of control ABPC.

[0016] In some embodiments of any of the pharmaceutical compositions described herein, the composition provides an increase in endolysosomal delivery in the target mammalian cells compared to a composition comprising the same amount of control ABPC.

[0017] In some embodiments of any of the pharmaceutical compositions described herein, the composition causes less reduction in the level of FOLR1 presented on the surface of 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 FOLR1 presented on the surface of target mammalian cells.

[0018] In some embodiments of any of the pharmaceutical compositions described herein, the target mammalian cells are cancer cells. In some embodiments of any of the pharmaceutical compositions described herein, the ABPC is cytotoxic or cytostatic to the target mammalian cells.

[0019] In some embodiments of any of the pharmaceutical compositions described herein, the ABPC is cross-reactive with non-human primate FOLR1 and human FOLR1, or is cross-reactive with one or both of non-human primate FOLR1, human FOLR1, and rat FOLR1 and mouse FOLR1.

[0020] In some embodiments of any of the pharmaceutical compositions described herein, the ABPC comprises a single polypeptide. In some embodiments of any 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 any of the pharmaceutical compositions described herein, the ABPC comprises two or more polypeptides. In some embodiments of any of the pharmaceutical compositions described herein, the ABPC is an antibody.

[0021] In some embodiments of any of the pharmaceutical compositions described herein, the half-life of the ABPC in vivo is reduced as compared to the half-life of control ABPC in vivo.

[0022] In some embodiments of any of the pharmaceutical compositions described herein, the ABPC comprises a second antigen-binding domain.

[0023] The present invention also provides an antigen-binding protein construct (ABPC) comprising: a first antigen-binding domain capable of specifically binding to FOLR1 or an epitope of FOLR1 presented on the surface of target mammalian cells, 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 (KD) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is greater than the KD at a pH of about 7.0 to about 8.0.

[0024] In some embodiments of any of the ABCPs described herein, the ABPC degrades in the target mammalian cell after the ABPC has been internalized by the target mammalian cell. In some embodiments of any of the ABCPs described herein, the ABPC comprises a conjugated toxin, radioisotope, drug, or small molecule.

[0025] The present disclosure also provides an antigen-binding protein construct (ABPC) comprising:

[0026] a first antigen-binding domain capable of specifically binding FOLR1 or an epitope of FOLR1 presented on the surface of a target mammalian cell; and a conjugated toxin, radioisotope, drug, or small molecule, wherein (a) the first antigen-binding domain has a faster dissociation rate at a pH of about 4.0 to about 6.5 than at a pH of about 7.0 to about 8.0 or the first antigen-binding domain has a larger dissociation constant (KD) at a pH of about 4.0 to about 6.5 than 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 cell 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 cell as compared to a composition comprising the same amount of a control ABPC.

[0027] In some embodiments of any of the ABCPs described herein, the first antigen-binding domain comprises one of (a) to (c): (a) a heavy chain variable domain of mirvetuximab in which one or more amino acids are replaced with histidine, wherein the heavy chain variable domain of mirvetuximab comprises SEQ ID NO:1; and / or a light chain variable domain of mirvetuximab in which one or more amino acids are replaced with histidine, wherein the light chain variable domain of mirvetuximab comprises SEQ ID NO:2; (b) a heavy chain variable domain of STRO-002 in which one or more amino acids are replaced with histidine, wherein the heavy chain variable domain of STRO-002 comprises SEQ ID NO:105; and / or a light chain variable domain of STRO-002 in which one or more amino acids are replaced with histidine, wherein the light chain variable domain of STRO-002 comprises SEQ ID NO:106; (c) a heavy chain variable domain of farletuzumab in which one or more amino acids are replaced with histidine, wherein the heavy chain variable domain of farletuzumab comprises SEQ ID NO:184; and / or a light chain variable domain of farletuzumab in which one or more amino acids are replaced with histidine, wherein the light chain variable domain of farletuzumab comprises SEQ ID NO:185.

[0028] In some embodiments of any ABCP described herein, the first FOLR1-binding domain comprises one of (a) to (c): (a) a heavy-chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 3-5, respectively, wherein one or more amino acid positions in SEQ ID NOs: 3-5 are replaced with histidine; and / or a light-chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 6-8, respectively, wherein one or more amino acid positions in SEQ ID NOs: 6-8 are replaced with histidine; (b) a heavy-chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 107-109, respectively, wherein one or more amino acid positions in SEQ ID NOs: 107-109 are replaced with histidine; and / or a light-chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 110-112, respectively, wherein one or more amino acid positions in SEQ ID NOs: 110-112 are replaced with histidine; (c) a heavy-chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 186-188, respectively, wherein one or more amino acid positions in SEQ ID NOs: 186-188 are replaced with histidine; and / or a light-chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 189-191, respectively, wherein one or more amino acid positions in SEQ ID NOs: 189-191 are replaced with histidine.

[0029] In some embodiments of any ABCP described herein, the first antigen-binding domain comprises one of (a) to (c): (a) a heavy-chain variable domain having at least 90% identity to SEQ ID NO:1, wherein the heavy-chain variable domain comprises histidine at one or more positions selected from the group consisting of: 24, 27, 29, 31, 32, 33, 34, 50, 54, 55, 57, 58, 59, 60, 97, 98, 99, 100, 102, 103, 105 and 107 in SEQ ID NO:1; and / or a light-chain variable domain having at least 90% identity to SEQ ID NO:2, wherein the light-chain variable domain comprises histidine at one or more positions selected from the group consisting of: 28, 30, 31, 32, 34, 35, 36, 55, 59, 93, 94, 95, 96, 97, 98 and 100 in SEQ ID NO:2; (b) a heavy-chain variable domain having at least 90% identity to SEQ ID NO:105, wherein the heavy-chain variable domain comprises histidine at one or more positions selected from the group consisting of: 29, 33, 34, 50, 51, 52, 53, 55, 56, 57, 101, 102, 103, 108, 109, 110, 111, 112 and 113 in SEQ ID NO:105; and / or

[0030] a light-chain variable domain having at least 90% identity to SEQ ID NO:106, wherein the light-chain variable domain comprises histidine at one or more positions selected from the group consisting of: 28, 29, 30, 31, 50, 92, 93, 94, 95 and 96 in SEQ ID NO:106; (c) a heavy-chain variable domain having at least 90% identity to SEQ ID NO:184, wherein the heavy-chain variable domain comprises histidine at one or more positions selected from the group consisting of: 26, 27, 28, 29, 30, 32, 33, 34, 53, 56, 57, 59, 62, 63, 103 and 105 in SEQ ID NO:184; and / or a light-chain variable domain having at least 90% identity to SEQ ID NO:185, wherein the light-chain variable domain comprises histidine at one or more positions selected from the group consisting of: 29, 33, 34, 51, 52, 53, 54, 55, 90, 92, 94, 96, 97, 98, 99 and 100 in SEQ ID NO:185.

[0031] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises one of (a) to (c): (a) a light chain variable domain of: SEQ ID NO:2, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81 or SEQ ID NO:83, and / or

[0032] The following heavy chain variable domains: SEQ ID NO:1, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, 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 or SEQ ID NO:103, 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 SEQ ID NO:14, 17, 19, 21-24, 26, 28, 30, 31, 33-36, 43-46, 48, 49, 51, 53 and 85-103; (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:58, 60-62, 64-66, 68, 70, 74, 76-81 and 83; and / or (b) the following light chain variable domains: SEQ ID NO:106, SEQ ID NO:161, SEQ ID NO:162, SEQ ID NO:163, SEQ ID NO:164, SEQ ID NO:168, SEQ ID NO:177, SEQ ID NO:178, SEQ ID NO:179, SEQ ID NO:180, SEQ ID NO:181 or SEQ ID NO:182, and / or

[0033] The following heavy chain variable domains: SEQ ID NO:105, SEQ ID NO:116, 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:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:144, SEQ ID NO:145, SEQ ID NO:146, SEQ ID NO:151, SEQ ID NO:152, SEQ ID NO:153, SEQ ID NO:154, SEQ ID NO:155 or SEQ ID NO:156, wherein the first antigen-binding domain does not comprise (i) the light chain variable domain of SEQ ID NO:106 and the heavy chain variable domain of SEQ ID NO:105; (ii) the light chain variable domain of SEQ ID NO:106 and a heavy chain variable domain other than one of SEQ ID NO:116, 120-126, 128-130, 144-146 and 151-156; (iii) the heavy chain variable domain of SEQ ID NO:105 and a light chain variable domain other than one of SEQ ID NO:161-164, 168 and 177-182; (c) the following light chain variable domains: SEQ ID NO:185, SEQ ID NO:233, 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:247, SEQ ID NO:249, SEQ ID NO:251, SEQ ID NO:253, SEQ ID NO:254, SEQ ID NO:255, SEQ ID NO:256 or SEQ ID NO:257;and / or the following heavy chain variable domains: SEQ ID NO:184, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:205, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:211, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:221, SEQ ID NO:225 or SEQ ID NO:227, wherein the first antigen-binding domain does not comprise (i) the light chain variable domain of SEQ ID NO:185 and the heavy chain variable domain of SEQ ID NO:184; (ii) the light chain variable domain of SEQ ID NO:185 and a heavy chain variable domain that is not one of SEQ ID NO:192-196, 198-200, 205, 208, 209, 211, 214, 215, 221, 225 and 227; (iii) the heavy chain variable domain of SEQ ID NO:184 and a light chain variable domain that is not one of SEQ ID NO:233, 237-244, 247, 249, 251 and 253-257.;

[0034] In some embodiments of any of the ABCPs described herein, the composition comprising the ABPC provides: an increase in toxin release in the target mammalian cells as compared to a composition comprising the same amount of a control ABPC; and / or an increase in target mammalian cell killing as compared to a composition comprising the same amount of a control ABPC.

[0035] In some embodiments of any of the ABCPs described herein, 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.

[0036] In some embodiments of any of the ABCPs described herein, the composition comprising the ABPC causes less reduction in the level of FOLR1 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 FOLR1 presented on the surface of the target mammalian cells.

[0037] In some embodiments of any of the ABCPs described herein, the target mammalian cells are cancer cells. In some embodiments of any of the ABCPs described herein, the ABPC is cytotoxic or cytostatic to the target mammalian cells.

[0038] In some embodiments of any of the ABCPs described herein, the ABPC is cross-reactive with non-human primate FOLR1 and human FOLR1, or is cross-reactive with one or both of non-human primate FOLR1, human FOLR1, and rat FOLR1 and mouse FOLR1.

[0039] In some embodiments of any of the ABCPs described herein, the ABPC comprises a single polypeptide.

[0040] In some embodiments of any of the ABCPs 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 any of the ABCPs described herein, the ABPC comprises two or more polypeptides. In some embodiments of any of the ABCPs described herein, the ABPC is an antibody.

[0041] In some embodiments of any of the ABCPs described herein, the half-life of the ABPC in vivo is reduced compared to the half-life of a control ABPC in vivo.

[0042] In some embodiments of any of the ABCPs described herein, the ABPC comprises a second antigen-binding domain.

[0043] Also provided herein are kits comprising at least one dose of any of the pharmaceutical compositions described herein or any of the ABCPs described herein.

[0044] Also provided herein is a method of treating cancer characterized by a population of cancer cells having FOLR1 or an epitope of FOLR1 presented on the surface, the method comprising administering a therapeutically effective amount of the pharmaceutical composition of any one of claims 1-20 or the ABPC of any one of claims 21-40 to a subject identified as having cancer characterized by having the population of cancer cells.

[0045] Also provided herein is a method of reducing the tumor volume in a subject, wherein the tumor is characterized by a population of cancer cells having FOLR1 or an epitope of FOLR1 presented on the surface, the method comprising administering a therapeutically effective amount of the pharmaceutical composition of any one of claims 1-20 or the ABPC of any one of claims 21-40 to a subject identified as having cancer characterized by having the population of cancer cells.

[0046] The present invention also provides a method for inducing cell death in cancer cells in a subject, wherein FOLR1 or an epitope of FOLR1 is presented on the surface of the cancer cells, and the method comprises administering a therapeutically effective amount of the pharmaceutical composition according to any one of claims 1-20 or the ABPC according to any one of claims 21-40 to a subject identified as having cancer, the cancer being characterized by having the population of cancer cells.

[0047] The present invention also provides a method for reducing the risk of developing metastases or reducing the risk of developing additional metastases in a subject having cancer, wherein the cancer is characterized by having a population of cancer cells on the surface of which FOLR1 or an epitope of FOLR1 is presented, and the method comprises administering a therapeutically effective amount of the pharmaceutical composition according to any one of claims 1-20 or the ABPC according to any one of claims 21-40 to a subject identified as having cancer, the cancer being characterized by having the population of cancer cells.

[0048] The present invention provides 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 FOLR1 or an epitope of FOLR1 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 (KD) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is greater than the KD at a pH of about 7.0 to about 8.0.

[0049] In some embodiments of any 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.

[0050] In some embodiments of any of the pharmaceutical compositions described herein, the ABPC comprises a conjugated toxin, radioisotope, drug, or small molecule.

[0051] The present invention also provides 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 FOLR1 or an epitope of FOLR1 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 (KD) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is greater than the KD 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 cell 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 cell as compared to a composition comprising the same amount of a control ABPC.

[0052] In some embodiments of any of the pharmaceutical compositions described herein, the first antigen-binding domain comprises one of (a) to (c): (a) the heavy chain variable domain of mirvetuximab in which one or more amino acids are replaced by histidine, wherein the heavy chain variable domain of mirvetuximab comprises SEQ ID NO:1; and / or the light chain variable domain of mirvetuximab in which one or more amino acids are replaced by histidine, wherein the light chain variable domain of mirvetuximab comprises SEQ ID NO:2; (b) the heavy chain variable domain of STRO-002 in which one or more amino acids are replaced by histidine, wherein the heavy chain variable domain of STRO-002 comprises SEQ ID NO:105; and / or the light chain variable domain of STRO-002 in which one or more amino acids are replaced by histidine, wherein the light chain variable domain of STRO-002 comprises SEQ ID NO:106; (c) the heavy chain variable domain of farletuzumab in which one or more amino acids are replaced by histidine, wherein the heavy chain variable domain of farletuzumab comprises SEQ ID NO:184; and / or the light chain variable domain of farletuzumab in which one or more amino acids are replaced by histidine, wherein the light chain variable domain of farletuzumab comprises SEQ ID NO:185.

[0053] In some embodiments of any of the pharmaceutical compositions described herein, the first FOLR1 binding domain comprises one of (a) to (c): (a) a heavy chain variable domain comprising CDR1, CDR2, and CDR3 that are SEQ ID NO: 3-5, respectively, wherein one or more amino acid positions in SEQ ID NO: 3-5 are replaced with histidine; and / or a light chain variable domain comprising CDR1, CDR2, and CDR3 that are SEQ ID NO: 6-8, respectively, wherein one or more amino acid positions in SEQ ID NO: 6-8 are replaced with histidine; (b) a heavy chain variable domain comprising CDR1, CDR2, and CDR3 that are SEQ ID NO: 107-109, respectively, wherein one or more amino acid positions in SEQ ID NO: 107-109 are replaced with histidine; and / or a light chain variable domain comprising CDR1, CDR2, and CDR3 that are SEQ ID NO: 110-112, respectively, wherein one or more amino acid positions in SEQ ID NO: 110-112 are replaced with histidine; (c) a heavy chain variable domain comprising CDR1, CDR2, and CDR3 that are SEQ ID NO: 186-188, respectively, wherein one or more amino acid positions in SEQ ID NO: 186-188 are replaced with histidine; and a light chain variable domain comprising CDR1, CDR2, and CDR3 that are SEQ ID NO: 189-191, respectively, wherein one or more amino acid positions in SEQ ID NO: 189-191 are replaced with histidine.

[0054] In some embodiments of any of the pharmaceutical compositions described herein, the first antigen-binding domain comprises one of (a) to (c): (a) a heavy chain variable domain having at least 90% identity to SEQ ID NO:1, wherein the heavy chain variable domain comprises histidine at one or more positions selected from the group consisting of: 24, 27, 29, 31, 32, 33, 34, 50, 54, 55, 57, 58, 59, 60, 97, 98, 99, 100, 102, 103, 105 and 107 in SEQ ID NO:1; and / or a light chain variable domain having at least 90% identity to SEQ ID NO:2, wherein the light chain variable domain comprises histidine at one or more positions selected from the group consisting of: 28, 30, 31, 32, 34, 35, 36, 55, 59, 93, 94, 95, 96, 97, 98 and 100 in SEQ ID NO:2; (b) a heavy chain variable domain having at least 90% identity to SEQ ID NO:105, wherein the heavy chain variable domain comprises histidine at one or more positions selected from the group consisting of: 29, 33, 34, 50, 51, 52, 53, 55, 56, 57, 101, 102, 103, 108, 109, 110, 111, 112 and 113 in SEQ ID NO:105; and a light chain variable domain having at least 90% identity to SEQ ID NO:106, wherein the light chain variable domain comprises histidine at one or more positions selected from the group consisting of: 28, 29, 30, 31, 50, 92, 93, 94, 95 and 96 in SEQ ID NO:106; (c) a heavy chain variable domain having at least 90% identity to SEQ ID NO:184, wherein the heavy chain variable domain comprises histidine at one or more positions selected from the group consisting of: 26, 27, 28, 29, 30, 32, 33, 34, 53, 56, 57, 59, 62, 63, 103 and 105 in SEQ ID NO:184; and / or a light chain variable domain having at least 90% identity to SEQ ID NO:185, wherein the light chain variable domain comprises histidine at one or more positions selected from the group consisting of: 29, 33, 34, 51, 52, 53, 54, 55, 90, 92, 94, 96, 97, 98, 99 and 100 in SEQ ID NO:185.

[0055] In some embodiments of any of the pharmaceutical compositions described herein, the first antigen-binding domain comprises one of (a) to (c): (a) a light chain variable domain of: SEQ ID NO:2, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81 or SEQ ID NO:83; and / or a heavy chain variable domain of: SEQ ID NO:1, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, 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 or SEQ ID NO:103, 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 SEQ ID NO:14, 17, 19, 21-24, 26, 28, 30, 31, 33-36, 43-46, 48, 49, 51, 53, and 85-103; (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:58, 60-62, 64-66, 68, 70, 74, 76-81, and 83; and / or (b) the following light chain variable domains: SEQ ID NO:106, SEQ ID NO:161, SEQ ID NO:162, SEQ ID NO:163, SEQ ID NO:164, SEQ ID NO:168, SEQ ID NO:177, SEQ ID NO:178, SEQ ID NO:179, SEQ ID NO:180, SEQ ID NO:181, or SEQ ID NO:182; and / or the following heavy chain variable domains: SEQ ID NO:105, SEQ ID NO:116, 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:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:144, SEQ ID NO:145, SEQ ID NO:146, SEQ ID NO:151, SEQ ID NO:152, SEQ ID NO:153, SEQ ID NO:154, SEQ ID NO:155, or SEQ ID NO:156, wherein the first antigen-binding domain does not comprise (i) the light chain variable domain of SEQ ID NO:106 and the heavy chain variable domain of SEQ ID NO:105; (ii) the light chain variable domain of SEQ ID NO:106 and a heavy chain variable domain that is not one of SEQ ID NO:105, 116, 120-126, 128-130, 144-146, and 151-156; (iii) the heavy chain variable domain of SEQ ID NO:105 and a light chain variable domain that is not one of SEQ ID NO:161-164, 168, and 177-182;(c) The following light chain variable domains: SEQ ID NO:185, SEQ ID NO:233, 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:247, SEQ ID NO:249, SEQ ID NO:251, SEQ ID NO:253, SEQ ID NO:254, SEQ ID NO:255, SEQ ID NO:256 or SEQ ID NO:257; and / or the following heavy chain variable domains: SEQ ID NO:184, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:205, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:211, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:221, SEQ ID NO:225 or SEQ ID NO:227, wherein the first antigen-binding domain does not comprise (i) the light chain variable domain of SEQ ID NO:185 and the heavy chain variable domain of SEQ ID NO:184; (ii) the light chain variable domain of SEQ ID NO:185 and a heavy chain variable domain that is not one of SEQ ID NO:184, 192-196, 198-200, 205, 208, 209, 211, 214, 215, 221, 225 and 227; (iii) the heavy chain variable domain of SEQ ID NO:184 and a light chain variable domain that is not one of SEQ ID NO:233, 237-244, 247, 249, 251 and 253-257).;

[0056] In some embodiments of any of the pharmaceutical compositions described herein, the composition provides: an increase in toxin release in the target mammalian cells compared to a composition comprising the same amount of control ABPC; and / or an increase in target mammalian cell killing compared to a composition comprising the same amount of control ABPC.

[0057] In some embodiments of any of the pharmaceutical compositions described herein, the composition provides an increase in endolysosomal delivery in the target mammalian cells compared to a composition comprising the same amount of control ABPC.

[0058] In some embodiments of any of the pharmaceutical compositions described herein, the composition causes less of a decrease in the level of FOLR1 presented on the surface of the target mammalian cells compared to a composition comprising the same amount of control ABPC; or does not cause a detectable decrease in the level of FOLR1 presented on the surface of the target mammalian cells.

[0059] In some embodiments of any of the pharmaceutical compositions described herein, the target mammalian cells are cancer cells. In some embodiments of any of the pharmaceutical compositions described herein, the ABPC is cytotoxic or cytostatic to the target mammalian cells.

[0060] In some embodiments of any of the pharmaceutical compositions described herein, the ABPC is cross-reactive with non-human primate FOLR1 and human FOLR1, or is cross-reactive with one or both of non-human primate FOLR1, human FOLR1, and rat FOLR1 and mouse FOLR1.

[0061] In some embodiments of any of the pharmaceutical compositions described herein, the ABPC comprises a single polypeptide. In some embodiments of any 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 any of the pharmaceutical compositions described herein, the ABPC comprises two or more polypeptides. In some embodiments of any of the pharmaceutical compositions described herein, the ABPC is an antibody.

[0062] In some embodiments of any of the pharmaceutical compositions described herein, the half-life of the ABPC in vivo is reduced compared to the half-life of control ABPC in vivo.

[0063] In some embodiments of any of the pharmaceutical compositions described herein, the ABPC comprises a second antigen-binding domain.

[0064] The present invention also provides an antigen-binding protein construct (ABPC), the antigen-binding protein construct comprising: a first antigen-binding domain capable of specifically binding to FOLR1 or an epitope of FOLR1 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 (KD) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is greater than the KD at a pH of about 7.0 to about 8.0.

[0065] In some embodiments of any ABPC described herein, the ABPC is degraded in the target mammalian cell after being internalized by the target mammalian cell.

[0066] In some embodiments of any ABPC described herein, the ABPC comprises a conjugated toxin, radioisotope, drug, or small molecule.

[0067] The present invention also provides an antigen-binding protein construct (ABPC), the antigen-binding protein construct comprising: a first antigen-binding domain capable of specifically binding to FOLR1 or an epitope of FOLR1 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 (KD) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is greater than the KD 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 cell 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 cell as compared to a composition comprising the same amount of a control ABPC.

[0068] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises one of (a) to (c): (a) the heavy chain variable domain of mirvetuximab with one or more amino acids replaced by histidine, wherein the heavy chain variable domain of mirvetuximab comprises SEQ ID NO:1; and / or the light chain variable domain of mirvetuximab with one or more amino acids replaced by histidine, wherein the light chain variable domain of mirvetuximab comprises SEQ ID NO:2; (b) the heavy chain variable domain of STRO-002 with one or more amino acids replaced by histidine, wherein the heavy chain variable domain of STRO-002 comprises SEQ ID NO:105; and / or the light chain variable domain of STRO-002 with one or more amino acids replaced by histidine, wherein the light chain variable domain of STRO-002 comprises SEQ ID NO:106; (c) the heavy chain variable domain of farletuzumab with one or more amino acids replaced by histidine, wherein the heavy chain variable domain of farletuzumab comprises SEQ ID NO:184; and / or the light chain variable domain of farletuzumab with one or more amino acids replaced by histidine, wherein the light chain variable domain of farletuzumab comprises SEQ ID NO:185.

[0069] In some embodiments of any ABPC described herein, the first FOLR1-binding domain comprises one of (a) to (c): (a) a heavy-chain variable domain comprising CDR1, CDR2, and CDR3 that are SEQ ID NO: 3-5, respectively, with a total of one or more amino acid positions in SEQ ID NO: 3-5 substituted with histidine; and / or a light-chain variable domain comprising CDR1, CDR2, and CDR3 that are SEQ ID NO: 6-8, respectively, with a total of one or more amino acid positions in SEQ ID NO: 6-8 substituted with histidine; (b) a heavy-chain variable domain comprising CDR1, CDR2, and CDR3 that are SEQ ID NO: 107-109, respectively, with a total of one or more amino acid positions in SEQ ID NO: 107-109 substituted with histidine; and / or a light-chain variable domain comprising CDR1, CDR2, and CDR3 that are SEQ ID NO: 110-112, respectively, with a total of one or more amino acid positions in SEQ ID NO: 110-112 substituted with histidine; (c) a heavy-chain variable domain comprising CDR1, CDR2, and CDR3 that are SEQ ID NO: 186-188, respectively, with a total of one or more amino acid positions in SEQ ID NO: 186-188 substituted with histidine; and / or a light-chain variable domain comprising CDR1, CDR2, and CDR3 that are SEQ ID NO: 189-191, respectively, with a total of one or more amino acid positions in SEQ ID NO: 189-191 substituted with histidine.

[0070] In some embodiments of any ABPC described herein, the first antigen-binding domain comprises one of (a) to (c): (a) a heavy-chain variable domain having at least 90% identity with SEQ ID NO:1, wherein the heavy-chain variable domain comprises histidine at one or more positions selected from the group consisting of: 24, 27, 29, 31, 32, 33, 34, 50, 54, 55, 57, 58, 59, 60, 97, 98, 99, 100, 102, 103, 105 and 107 in SEQ ID NO:1; and / or a light-chain variable domain having at least 90% identity with SEQ ID NO:2, wherein the light-chain variable domain comprises histidine at one or more positions selected from the group consisting of: 28, 30, 31, 32, 34, 35, 36, 55, 59, 93, 94, 95, 96, 97, 98 and 100 in SEQ ID NO:2; (b) a heavy-chain variable domain having at least 90% identity with SEQ ID NO:105, wherein the heavy-chain variable domain comprises histidine at one or more positions selected from the group consisting of: 29, 33, 34, 50, 51, 52, 53, 55, 56, 57, 101, 102, 103, 108, 109, 110, 111, 112 and 113 in SEQ ID NO:105; and / or a light-chain variable domain having at least 90% identity with SEQ ID NO:106, wherein the light-chain variable domain comprises histidine at one or more positions selected from the group consisting of: 28, 29, 30, 31, 50, 92, 93, 94, 95 and 96 in SEQ ID NO:106; (c) a heavy-chain variable domain having at least 90% identity with SEQ ID NO:184, wherein the heavy-chain variable domain comprises histidine at one or more positions selected from the group consisting of: 26, 27, 28, 29, 30, 32, 33, 34, 53, 56, 57, 59, 62, 63, 103 and 105 in SEQ ID NO:184; and / or a light-chain variable domain having at least 90% identity with SEQ ID NO:185, wherein the light-chain variable domain comprises histidine at one or more positions selected from the group consisting of: 29, 33, 34, 51, 52, 53, 54, 55, 90, 92, 94, 96, 97, 98, 99 and 100 in SEQ ID NO:185.

[0071] In some embodiments of any ABPC described herein, the first antigen-binding domain comprises one of (a) to (c): (a) a light chain variable domain of: SEQ ID NO:2, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81 or SEQ ID NO:83; and / or a heavy chain variable domain of: SEQ ID NO:1, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, 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 or SEQ ID NO:103, 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 SEQ ID NO:14, 17, 19, 21 - 24, 26, 28, 30, 31, 33 - 36, 43 - 46, 48, 49, 51, 53, and 85 - 103; (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:58, 60 - 62, 64 - 66, 68, 70, 74, 76 - 81, and 83; and / or (b) the following light chain variable domains: SEQ ID NO:106, SEQ ID NO:161, SEQ ID NO:162, SEQ ID NO:163, SEQ ID NO:164, SEQ ID NO:168, SEQ ID NO:177, SEQ ID NO:178, SEQ ID NO:179, SEQ ID NO:180, SEQ ID NO:181, or SEQ ID NO:182; and / or the following heavy chain variable domains: SEQ ID NO:105, SEQ ID NO:116, 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:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:144, SEQ ID NO:145, SEQ ID NO:146, SEQ ID NO:151, SEQ ID NO:152, SEQ ID NO:153, SEQ ID NO:154, SEQ ID NO:155, or SEQ ID NO:156, wherein the first antigen-binding domain does not comprise (i) the light chain variable domain of SEQ ID NO:106 and the heavy chain variable domain of SEQ ID NO:105; (ii) the light chain variable domain of SEQ ID NO:106 and a heavy chain variable domain that is not one of SEQ ID NO:116, 120 - 126, 128 - 130, 144 - 146, and 151 - 156; (iii) the heavy chain variable domain of SEQ ID NO:105 and a light chain variable domain that is not one of SEQ ID NO:161 - 164, 168, and 177 - 182;(c) The following light chain variable domains: SEQ ID NO:185, SEQ ID NO:233, 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:247, SEQ ID NO:249, SEQ ID NO:251, SEQ ID NO:253, SEQ ID NO:254, SEQ ID NO:255, SEQ ID NO:256 or SEQ ID NO:257; and / or the following heavy chain variable domains: SEQ ID NO:184, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:205, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:211, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:221, SEQ ID NO:225 or SEQ ID NO:227, wherein the first antigen-binding domain does not comprise (i) the light chain variable domain of SEQ ID NO:185 and the heavy chain variable domain of SEQ ID NO:184; (ii) the light chain variable domain of SEQ ID NO:185 and a heavy chain variable domain that is not one of SEQ ID NO:192-196, 198-200, 205, 208, 209, 211, 214, 215, 221, 225 and 227; (iii) the heavy chain variable domain of SEQ ID NO:184 and a light chain variable domain that is not one of SEQ ID NO:233, 237-244, 247, 249, 251 and 253-257).;

[0072] In some embodiments of any ABPC described herein, the composition comprising the ABPC provides: an increase in toxin release in the target mammalian cells as compared to a composition comprising the same amount of a control ABPC; and / or an increase in target mammalian cell killing as compared to a composition comprising the same amount of a control ABPC.

[0073] In some embodiments of any of the ABPCs described herein, 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.

[0074] In some embodiments of any of the ABPCs described herein, the composition comprising the ABPC causes less of a decrease in the level of FOLR1 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 FOLR1 presented on the surface of the target mammalian cells.

[0075] In some embodiments of any of the ABPCs described herein, the target mammalian cells are cancer cells. In some embodiments of any of the ABPCs described herein, the ABPC is cytotoxic or cytostatic to the target mammalian cells.

[0076] In some embodiments of any of the ABPCs described herein, the ABPC has cross-reactivity with non-human primate FOLR1 and human FOLR1, or with one or both of non-human primate FOLR1, human FOLR1, and rat FOLR1 and mouse FOLR1.

[0077] In some embodiments of any of the ABPCs described herein, the ABPC comprises a single polypeptide.

[0078] In some embodiments of any of the ABPCs described herein, the antigen-binding domain is selected from the group consisting of a VH domain, a VHH domain, a VNAR domain, and a scFv. In some embodiments of any of the ABPCs described herein, the ABPC comprises two or more polypeptides. In some embodiments of any of the ABPCs described herein, the ABPC is an antibody.

[0079] In some embodiments of any of the ABPCs described herein, the ABPC has a reduced half-life in vivo as compared to the half-life in vivo of a control ABPC.

[0080] In some embodiments of any of the ABPCs described herein, the ABPC comprises a second antigen-binding domain.

[0081] The present disclosure also provides a kit comprising at least one dose of any of the pharmaceutical compositions described herein or any of the ABPCs described herein.

[0082] The present invention also provides methods of treating cancer characterized by a population of cancer cells presenting FOLR1 or an epitope of FOLR1 on their surface, the method comprising administering a therapeutically effective amount of any one of the pharmaceutical compositions described herein or any one of the ABPCs described herein to a subject identified as having cancer characterized by having such a population of cancer cells.

[0083] The present invention also provides methods of reducing the tumor volume in a subject, wherein the tumor is characterized by a population of cancer cells presenting FOLR1 or an epitope of FOLR1 on their surface, the method comprising administering a therapeutically effective amount of any pharmaceutical composition described herein or any one of the ABPCs described herein to a subject identified as having cancer characterized by having such a population of cancer cells.

[0084] The present invention also provides methods of inducing cell death in cancer cells in a subject, wherein the cancer cells present FOLR1 or an epitope of FOLR1 on their surface, the method comprising administering a therapeutically effective amount of any one of the pharmaceutical compositions described herein or any one of the ABPCs described herein to a subject identified as having cancer characterized by having such a population of cancer cells.

[0085] The present invention also provides methods of reducing the risk of developing metastases or reducing the risk of developing additional metastases in a subject having cancer, wherein the cancer is characterized by a population of cancer cells presenting FOLR1 or an epitope of FOLR1 on their surface, the method comprising administering a therapeutically effective amount of any one of the pharmaceutical compositions described herein or any one of the ABPCs described herein to a subject identified as having cancer characterized by having such a population of cancer cells.

[0086] 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.

[0087] Additional examples and aspects of antigen-binding protein constructs are known in the art.

[0088] A "multispecific antigen-binding protein construct" is an antigen-binding protein construct that includes two or more different antigen-binding domains that commonly and specifically bind two or more different epitopes. The two or more different epitopes can be epitopes on the same antigen (e.g., a single polypeptide present on a 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 a 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.

[0089] An "antigen-binding domain" is one or more protein domains (e.g., formed from amino acids from a single polypeptide or from amino acids from two or more polypeptides (e.g., the same polypeptide or different polypeptides)) that are capable of specifically binding to one or more different antigens. In some instances, the antigen-binding domain can 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 include 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, the antigen-binding domain can bind to a single antigen.

[0090] The term "antibody" is used herein in its broadest sense and includes certain types of immunoglobulin molecules that include 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.

[0091] 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 endocytosis processes (e.g., pinocytosis, micropinocytosis, receptor-mediated endocytosis, and / or phagocytosis) are sorted.

[0092] Once the 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.

[0093] Alternatively, immunofluorescence microscopy can be used to image endosomes in the endosomal / lysosomal pathway using a detectable-labeled antibody (e.g., a fluorophore-labeled antibody, a dye-labeled antibody, or a GFP-labeled antibody, such as CellLightTM Early Endosome-GFP) that specifically binds to a characteristic protein present in the endosomes (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), 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.

[0094] The phrase "endolysosomal delivery" refers to the rate of accumulation over time or the total accumulation rate at a specific time point of an antigen-binding protein construct (e.g., any antigen-binding protein construct as described herein) in the endosomal / lysosomal pathway of a mammalian cell (e.g., any exemplary target mammalian cell as described herein).

[0095] An exemplary method for calculating the increased endosomal delivery of a pH-engineered ABPC variant compared to its corresponding starting ABPC from cellular 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.

[0096] Exemplary assays for measuring endosomal delivery of any of the ABPCs described herein include those involving: labeling the ABPC with a fluorescent dye, followed by incubating the labeled ABPC with cells and measuring the cellular 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 of the ABPCs described herein, and then the ABPC can be incubated with cells and the cellular fluorescence measured as an indicator of ABPC delivery to acidic endolysosomal compartments.

[0097] When the term "population" is used before a noun, it means two or more specific nouns. For example, the phrase "population of cancer cells" means "two or more cancer cells". Non - limiting examples of cancer cells are described herein.

[0098] The phrase "cytostatic to a cell" refers to a direct or indirect decrease in the proliferation (cell division) of cells (e.g., cancer cells) 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., 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).

[0099] 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, such as a cancer cell).

[0100] "Affinity" refers to the total strength of non - covalent interactions between an antigen - binding site and its binding partner (e.g., an antigen or epitope). Unless otherwise specified, as used herein, "affinity" refers to the intrinsic binding affinity, which reflects the 1:1 interaction between an antigen - binding domain and an antigen or 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 common methods known in the art, including those described herein. Affinity can be measured, for example, using surface plasmon resonance (SPR) technology (e.g., ) or biolayer interferometry technology (e.g., ).

[0101] Additional methods for determining the affinity of an antigen-binding domain for its corresponding antigen or epitope are known in the art.

[0102] The term "epitope" means a portion of an antigen that is specifically bound by an antigen-binding domain through a set of physical interactions between: (i) all monomers (such as individual amino acid residues, sugar side chains, and post-translationally modified amino acid residues) on the portion of the antigen-binding domain that specifically binds the antigen, and (ii) all monomers (such as individual amino acid residues, sugar side chains, post-translationally modified amino acid residues) on the portion of the antigen that is specifically bound by the antigen-binding domain. An epitope can consist, for example, 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 conformational and non-

[0103] conformational epitopes 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.

[0104] In some embodiments, an epitope refers to a portion of a full-length protein or a portion 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 a protein fold. 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 the 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 the antigen can be used to identify and screen conformational epitopes in order to generate linear epitopes.

[0105] An epitope can include amino acid residues directly involved in binding and other amino acid residues not directly involved in binding.

[0106] Methods for identifying the epitopes specifically bound by an antigen-binding domain 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 the antigen-antigen-binding domain complex) and / or mutagenesis-based analysis (e.g., alanine-scanning mutagenesis, glycine-scanning mutagenesis, and homologous-scanning mutagenesis), wherein mutants are measured in a binding assay with a binding partner, and many mutants are known in the art.

[0107] 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 (e.g., individual amino acid residues, sugar side chains, post-translationally modified amino acid residues) on the part of the antigen-binding domain that specifically binds the antigen, and (ii) all monomers (e.g., individual amino acid residues, sugar side chains, post-translationally modified amino acid residues) on the part of the antigen that is specifically bound by the antigen-binding domain.

[0108] A 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, a 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, a complementary site is defined by discontinuous amino acid sequences that are brought together via protein folding. In some embodiments, an 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).

[0109] The amino acid sequence between the residues that define a complementary site may not be critical for the three-dimensional structure of the complementary site. A complementary site can contain amino acid residues directly involved in binding and other amino acid residues not directly involved in binding.

[0110] 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 the 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 assayed for binding in a binding assay with a binding partner, and many mutants are known in the art.

[0111] The phrase "present on the surface of a mammalian cell" means (1) an antigen (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) that is physically attached to or at least partially embedded in the plasma membrane of a mammalian cell or (2) an antigen that is stably bound 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 a mammalian cell include fluorescence-activated cell sorting (FACS), immunohistochemistry, cell fractionation assays, and Western blotting.

[0112] The phrase "control ABPC" or "control antigen-binding protein construct" means (i) an ABPC that is capable of specifically binding to FOLR1 or an epitope of FOLR1 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 about 4.0 to about 6.5 (e.g., any sub-range within this range described herein) is faster than the dissociation rate at a pH of about 7.0 to about 8.0 (e.g., any sub-range within this range described herein), by 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);

[0113] or (b) the dissociation constant (K D ) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 (e.g., any sub-range within this range described herein) is greater than the K D at a pH of about 7.0 to about 8.0 (e.g., any sub-range within this range described herein), by 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); and / or (ii) mirvetuximab; and / or (iii) STRO-002; and / or (iv) farletuzumab.

[0114] 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.

[0115] The term "endolysosomal space" means the fluid enclosed by the vesicles and organelles that make up the endosome / lysosome pathway in mammalian cells. The phrases "reduced level" or "decreased level" can be at least 1% lower or decreased (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.

[0116] 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), measured as a 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 such as 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 higher cytotoxic efficacy compared to the control ABPC.

[0117] 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 ABPC described herein conjugated to a toxin (e.g., any ABPC described herein or a control ABPC) and subsequently release the toxin conjugated to the ABPC, measured as a 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, cytotoxicity assays, cell cycle arrest assays, DNA damage assays, mass spectrometry, HPLC, and / or isotopically labeled toxins.

[0118] The phrase "target cell" or "target mammalian cell" or "mammalian target cell" means a mammalian cell that has at least one FOLR1 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 50,000, about 10 to about 45,000, about 10 to about 40,000, about 10 to about 35,000, about 10 to about 30,000, about 10 to about 25,000, about 10 to about 20,000, about 10 to about 15,000, about 10 to about 10,000, about 10 to about 7,500, from about 10 to about 5,000, from about 10 to about 4,000, from about 10 to about 3,000, from about 10 to about 2,000, from about 10 to about 1,000, from about 10 to about 500, from about 10 to about 100, from about 10 to about 50, from about 50 to about 10,000,000, from about 50 to about 9,000,000, from about 50 to about 8,000,000, from about 50 to about 7,000,000, from about 50 to about 6,000,000, from about 50 to about 5,000,000, from about 50 to about 4,000,000, from about 50 to about 3,000,000, from about 50 to about 2,000,000, from about 50 to about 1,000,000, from about 50 to about 800,000, from about 50 to about 600,000, from about 50 to about 400,000, from about 50 to about 200,000, from about 50 to about 100,000, from about 50 to about 80,000, from about 50 to about 80,000, from about 50 to about 75,000, from about 50 to about 70,000, from about 50 to about 65,000, from about 50 to about 60,000, from about 50 to about 55,000, from about 50 to about 50,000, from about 50 to about 45,000, from about 50 to about 40,000, from about 50 to about 35,000, from about 50 to about 30,000, from about 50 to about 25,000, from about 50 to about 20,000, from about 50 to about 15,000, from about 50 to about 10,000, from about 50 to about 7,500, from about 50 to about 5,000, from about 50 to about 4,000, from about 50 to about 3,000, from about 50 to about 2,000, from about 50 to about 1,000, from about 50 to about 500, from about 50 to about 100, from about 100 to about 10,000,000, from about 100 to about 9,000,000, from about 100 to about 8,000,000, from about 100 to about 7,000,000, from about 100 to about 6,000,000, from about 100 to about 5,000,000, from about 100 to about 4,000,000, from about 100 to about 3,000,000, from about 100 to about 2,000,000, from about 100 to about 1,000,000, from about 100 to about 800,000, from about 100 to about 600,000, from about 100 to about 400,000, from about 100 to about 200,000, from about 100 to about 100,000, from about 100 to about 80,000, from about 100 to about 75,000, from about 100 to about 70,000, from about 100 to about 65,000, from about 100 to about 60,000, from about 100 to about 55,000, from about 100 to about 50,000, from about 100 to about 45,000, from about 100 to about 40,000, from about 100 to about 35,000, from about 100 to about 30,000, from about 100 to about 25,000, from about 100 to about 20,000, from about 100 to about 15,000, from about 100 to about 10,000, from about 100 to about 7,500, from about 100 to about 5,000, from about 100 to about 4,000, from about 100 to about 3,000, from about 100 to about 2,000, from about 100 to about 1,000, from about 100 to about 500, from about 500 to about 10,000,000, from about 500 to about 9,000,000, from about 500 to about 8,000,000, from about 500 to about 7,000,000, from about 500 to about 6,000,000, from about 500 to about 5,000,000, from about 500 to about 4,000,000, from about 500 to about 3,000,000, from about 500 to about 2,000,000, from about 500 to about 1,000,000, from about 500 to about 800,000, from about 500 to about 600,000, from about 500 to about 400,000, from about 500 to about 200,000, from about 500 to about 100,000, from about 500 to about 80,000, from about 500 to about 75,000, from about 500 to about 70,000, from about 500 to about 65,000, from about 500 to about 60,000, from about 500 to about 55,000, from about 500 to about 50,000, from about 500 to about 45,000, from about 500 to about 40,000, from about 500 to about 35,000, from about 500 to about 30,000, from about 500 to about 25,000, from about 500 to about 20,000, from about 500 to about 15,000, from about 500 to about 10,000, from about 500 to about 7,500, from about 500 to about 5,000, from about 500 to about 4,000, from about 500 to about 3,000, from about 500 to about 2,000, from about 500 to about 1,000, from about 1,000 to about 10,000,000, from about 1,000 to about 9,000,000, from about 1,000 to about 8,000,000, from about 1,000 to about 7,000,000, from about 1,000 to about 6,000,000, from about 1,000 to about 5,000,000, from about 1,000 to about 4,000,000, from about 1,000 to about 3,000,000, from about 1,000 to about 2,000,000, from about 1,000 to about 1,000,000, from about 1,000 to about 800,000, from about 1,000 to about 600,000, from about 1,000 to about 400,000, from about 1,000 to about 200,000, from about 1,000 to about 100,000, from about 1,000 to about 80,000, from about 1,000 to about 75,000, from about 1,000 to about 70,000, from about 1,000 to about 65,000, from about 1,000 to about 60,000, from about 1,000 to about 55,000, from about 1,000 to about 50,000, from about 1,000 to about 45,000, from about 1,000 to about 40,000, from about 1,000 to about 35,000, from about 1,0 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 50,000, about 2,000 to about 45,000, about 2,000 to about 40,000, about 2,000 to about 35,000, about 2,000 to about 30,000, about 2,000 to about 25,000, about 2,000 to about 20,000, about 2,000 to about 15,000, about 2,000 to about 10,000, about 2,000 to about 7,500, about 2,000 to about 5,000, about 2,000 to about 4,000, about 2,000 to about 3,000, about 3,000 to about 10,000,000, about 3,000 to about 9,000,000, about 3,000 to about 8,000,000, about 3,000 to about 7,000,000, about 3,000 to about 6,000,000, about 3,000 to about 5,000,000, about 3,000 to about 4,000,000, 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, from about 3,000 to about 60,000, from about 3,000 to about 55,000, from about 3,000 to about 50,000, from about 3,000 to about 45,000, from about 3,000 to about 40,000, from about 3,000 to about 35,000, from about 3,000 to about 30,000, from about 3,000 to about 25,000, from about 3,000 to about 20,000, from about 3,000 to about 15,000, from about 3,000 to about 10,000, from about 3,000 to about 7,500, from about 3,000 to about 5,000, from about 3,000 to about 4,000, from about 4,000 to about 10,000,000, from about 4,000 to about 9,000,000, from about 4,000 to about 8,000,000, from about 4,000 to about 7,000,000, from about 4,000 to about 6,000,000, from about 4,000 to about 5,000,000, from about 4,000 to about 4,000,000, from about 4,000 to about 3,000,000, from about 4,000 to about 2,000,000, from about 4,000 to about 1,000,000, from about 4,000 to about 800,000, from about 4,000 to about 600,000, from about 4,000 to about 400,000, from about 4,000 to about 200,000, from about 4,000 to about 100,000, from about 4,000 to about 80,000, from about 4,000 to about 75,000, from about 4,000 to about 70,000, from about 4,000 to about 65,000, from about 4,000 to about 60,000, from about 4,000 to about 55,000, from about 4,000 to about 50,000, from about 4,000 to about 45,000, from about 4,000 to about 40,000, from about 4,000 to about 35,000, from about 4,000 to about 30,000, from about 4,000 to about 25,000, from about 4,000 to about 20,000, from about 4,000 to about 15,000, from about 4,000 to about 10,000, from about 4,000 to about 7,500, from about 4,000 to about 5,000, from about 5,000 to about 10,000,000, from about 5,000 to about 9,000,000, from about 5,000 to about 8,000,000, from about 5,000 to about 7,000,000, from about 5,000 to about 6,000,000, from about 5,000 to about 5,000,000, from about 5,000 to about 4,000,000, from about 5,000 to about 3,000,000, from about 5,000 to about 2,000,000, from about 5,000 to about 1,000,000, from about 5,000 to about 800,000, from about 5,000 to about 600,000, from about 5,000 to about 400,000, from about 5,000 to about 200,000, from about 5,000 to about 100,000, from about 5,000 to about 80,000, from about 5,000 to about 75,000, from about 5,000 to about 70,000, from about 5,000 to about 65,000, from about 5,000 to about 60,000, from about 5,000 to about 55,000, from about 5,000 to about 50,000, from about 5,000 to about 45,000, from about 5,000 to about 40,000, from about 5,000 to about 35,000, from about 5,000 to about 30,000, from about 5,000 to about 25,000, from about 5,000 to about 20,000, from about 5,000 to about 15,000, from about 5,000 to about 10,000, from about 5,000 to about 7,500, from about 7,500 to about 10,000,000, from about 7,500 to about 9,000,000, from about 7,500 to about 8,000,000, from about 7,500 to about 7,000,000, from about 7,500 to about 6,000,000, from about 7,500 to about 5,000,000, from about 7,500 to about 4,000,000, from about 7,500 to about 3,000,000, from about 7,500 to about 2,000,000, from about 7,500 to about 1,000,000, from about 7,500 to about 800,000, from about 7,500 to about 600,000, from about 7,500 to about 400,000, from about 7,500 to about 200,000, from about 7,500 to about 100,000, from about 7,500 to about 80,000, from about 7,500 to about 75,000, from about 7,500 to about 70,000, from about 7,500 to about 65,000, from about 7,500 to about 60,000, from about 7,500 to about 55,000, from about 7,500 to about 50,000, from about 7,500 to about 45,000, from about 7,500 to about 40,000, from about 7,500 to about 35,000, from about 7,500 to about 30,000, from about 7,500 to about 25,000, from about 7,500 to about 20,000, from about 7,500 to about 15,000, from about 7,500 to about 10,000, from about 10,000 to about 10,000,000, from about 10,000 to about 9,000,000, from about 10,000 to about 8,000,000, from about 10,000 to about 7,000,000, from about 10,000 to about 6,000,000, from about 10,000 to about 5,000,000, from about 10,000 to about 4,000,000, from about 10,000 to about 3,000,000, from about 10,000 to about 2,000,000, from about 10,000 to about 1,000,000, from about 10,000 to about 800,000, from about 10,000 to about 600,000, from about 10,000 to about 400,000, from about 10,000 to about 200,000, from about 10,000 to about 100,000, from about 10,0 to approximately 80,000, approximately 10,000 to approximately 75,000, approximately 10,000 to approximately 70,000, approximately 10,000 to approximately 65,000, approximately 10,000 to approximately 60,000, approximately 10,000 to approximately 55,000, approximately 10,000 to approximately 50,000, approximately 10,000 to approximately 45,000, approximately 10,000 to approximately 40,000, approximately 10,000 to approximately 35,000, approximately 10,000 to approximately 30,000, approximately 10,000 to approximately 25,000, approximately 10,000 to approximately 20,000, approximately 10,000 to approximately 15,000, approximately 15,000 to approximately 10,000,000, approximately 15,000 to approximately 9,000,000, approximately 15,000 to approximately 8,000,000, approximately 15,000 to approximately 7,000,000, approximately 15,000 to approximately 6,000,000, approximately 15,000 to approximately 5,000,000, approximately 15,000 to approximately 4,000,000, approximately 15,000 to approximately 3,000,000, approximately 15,000 to approximately 2,000,000, approximately 15,000 to approximately 1,000,000, approximately 15,000 to approximately 800,000, approximately 15,000 to approximately 600,000, approximately 15,000 to approximately 400,000, approximately 15,000 to approximately 200,000, approximately 15,000 to approximately 100,000, approximately 15,000 to approximately 80,000, approximately 15,000 to approximately 75,000, approximately 15,000 to approximately 70,000, approximately 15,000 to approximately 65,000, approximately 15,000 to approximately 60,000, approximately 15,000 to approximately 55,000, approximately 15,000 to approximately 50,000, approximately 15,000 to approximately 45,000, approximately 15,000 to approximately 40,000, approximately 15,000 to approximately 35,000, approximately 15,000 to approximately 30,000, approximately 15,000 to approximately 25,000, approximately 15,000 to approximately 20,000, approximately 20,000 to approximately 10,000,000, approximately 20,000 to approximately 9,000,000, approximately 20,000 to approximately 8,000,000, approximately 20,000 to approximately 7,000,000, approximately 20,000 to approximately 6,000,000, approximately 20,000 to approximately 5,000,000, approximately 20,000 to approximately 4,000,000, approximately 20,000 to approximately 3,000,000, approximately 20,000 to approximately 2,000,000, approximately 20,000 to approximately 1,000,000, approximately 20,000 to approximately 800,000, approximately 20,000 to approximately 600,000, approximately 20,000 to approximately 400,000, approximately 20,000 to approximately 200,000, approximately 20,000 to approximately 100,000, approximately 20,000 to approximately 80,000, approximately 20,0 to about 75,000, about 20,000 to about 70,000, about 20,000 to about 65,000, about 20,000 to about 60,000, about 20,000 to about 55,000, about 20,000 to about 50,000, about 20,000 to about 45,000, about 20,000 to about 40,000, about 20,000 to about 35,000, about 20,000 to about 30,000, about 20,000 to about 25,000, about 25,000 to about 10,000,000, about 25,000 to about 9,000,000, about 25,000 to about 8,000,000, about 25,000 to about 7,000,000, about 25,000 to about 6,000,000, about 25,000 to about 5,000,000, about 25,000 to about 4,000,000, about 25,000 to about 3,000,000, about 25,000 to about 2,000,000, about 25,000 to about 1,000,000, about 25,000 to about 800,000, about 25,000 to about 600,000, about 25,000 to about 400,000, about 25,000 to about 200,000, about 25,000 to about 100,000, about 25,000 to about 80,000, about 25,000 to about 75,000, about 25,000 to about 70,000, about 25,000 to about 65,000, about 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 30,000 to about 60,000, about 30,000 to about 55,000, about 30,0 to about 50,000, about 30,000 to about 45,000, about 30,000 to about 40,000, about 30,000 to about 35,000, about 35,000 to about 10,000,000, about 35,000 to about 9,000,000, about 35,000 to about 8,000,000, about 35,000 to about 7,000,000, about 35,000 to about 6,000,000, about 35,000 to about 5,000,000, about 35,000 to about 4,000,000, about 35,000 to about 3,000,000, about 35,000 to about 2,000,000, about 35,000 to about 1,000,000, about 35,000 to about 800,000, about 35,000 to about 600,000, about 35,000 to about 400,000, about 35,000 to about 200,000, about 35,000 to about 100,000, about 35,000 to about 80,000, about 35,000 to about 75,000, about 35,000 to about 70,000, about 35,000 to about 65,000, about 35,000 to about 60,000, about 35,000 to about 55,000, about 35,000 to about 50,000, about 35,000 to about 45,000, about 35,000 to about 40,000, about 40,000 to about 10,000,000, about 40,000 to about 9,000,000, about 40,000 to about 8,000,000, about 40,000 to about 7,000,000, about 40,000 to about 6,000,000, about 40,000 to about 5,000,000, about 40,000 to about 4,000,000, about 40,000 to about 3,000,000, about 40,000 to about 2,000,000, about 40,000 to about 1,000,000, about 40,000 to about 800,000, about 40,000 to about 600,000, about 40,000 to about 400,000, about 40,000 to about 200,000, about 40,000 to about 100,000, about 40,000 to about 80,000, about 40,000 to about 75,000, about 40,000 to about 70,000, about 40,000 to about 65,000, about 40,000 to about 60,000, about 40,000 to about 55,000, about 40,000 to about 50,000, about 40,000 to about 45,000, about 45,000 to about 10,000,000, about 45,000 to about 9,000,000, about 45,000 to about 8,000,000, about 45,000 to about 7,000,000, about 45,000 to about 6,000,000, about 45,000 to about 5,000,000, from about 45,000 to about 4,000,000, from about 45,000 to about 3,000,000, from about 45,000 to about 2,000,000, from about 45,000 to about 1,000,000, from about 45,000 to about 800,000, from about 45,000 to about 600,000, from about 45,000 to about 400,000, from about 45,000 to about 200,000, from about 45,000 to about 100,000, from about 45,000 to about 80,000, from about 45,000 to about 75,000, from about 45,000 to about 70,000, from about 45,000 to about 65,000, from about 45,000 to about 60,000, from about 45,000 to about 55,000, from about 45,000 to about 50,000, from about 50,000 to about 10,000,000, from about 50,000 to about 9,000,000, from about 50,000 to about 8,000,000, from about 50,000 to about 7,000,000, from about 50,000 to about 6,000,000, from about 50,000 to about 5,000,000, from about 50,000 to about 4,000,000, from about 50,000 to about 3,000,000, from about 50,000 to about 2,000,000, from about 50,000 to about 1,000,000, from about 50,000 to about 800,000, from about 50,000 to about 600,000, from about 50,000 to about 400,000, from about 50,000 to about 200,000, from about 50,000 to about 100,000, from about 50,000 to about 80,000, from about 50,000 to about 75,000, from about 50,000 to about 70,000, from about 50,000 to about 65,000, from about 50,000 to about 60,000, from about 50,000 to about 55,000, from about 55,000 to about 10,000,000, from about 55,000 to about 9,000,000, from about 55,000 to about 8,000,000, from about 55,000 to about 7,000,000, from about 55,000 to about 6,000,000, from about 55,000 to about 5,000,000, from about 55,000 to about 4,000,000, from about 55,000 to about 3,000,000, from about 55,000 to about 2,000,000, from about 55,000 to about 1,000,000, from about 55,000 to about 800,000, from about 55,000 to about 600,000, from about 55,000 to about 400,000, from about 55,000 to about 200,000, from about 55,000 to about 100,000, from about 55,000 to about 80,000, from about 55,000 to about 75,000, from about 55,000 to about 70,000, from about 55,000 to about 65,000, from about 55,000 to about 60,000, from about 60,000 to about 10,000,000, from about 60,000 to about 9,000,000, from about 60,000 to about 8,000,000, from about 60,000 to about 7,000,000, from about 60,000 to about 6,000,000, from about 60,000 to about 5,000,000, from about 60,000 to about 4,000,000, from about 60,000 to about 3,000,000, from about 60,000 to about 2,000,000, from about 60,000 to about 1,000,000, from about 60,000 to about 800,000, from about 60,000 to about 600,000, from about 60,000 to about 400,000, from about 60,000 to about 200,000, from about 60,000 to about 100,000, from about 60,000 to about 80,000, from about 60,000 to about 75,000, from about 60,000 to about 70,000, from about 60,000 to about 65,000, from about 65,000 to about 10,000,000, from about 65,000 to about 9,000,000, from about 65,000 to about 8,000,000, from about 65,000 to about 7,000,000, from about 65,000 to about 6,000,000, from about 65,000 to about 5,000,000, from about 65,000 to about 4,000,000, from about 65,000 to about 3,000,000, from about 65,000 to about 2,000,000, from about 65,000 to about 1,000,000, from about 65,000 to about 800,000, from about 65,000 to about 600,000, from about 65,000 to about 400,000, from about 65,000 to about 200,000, from about 65,000 to about 100,000, from about 65,000 to about 80,000, from about 65,000 to about 75,000, from about 65,000 to about 70,000, from about 70,000 to about 10,000,000, from about 70,000 to about 9,000,000, from about 70,000 to about 8,000,000, from about 70,000 to about 7,000,000, from about 70,000 to about 6,000,000, from about 70,000 to about 5,000,000, from about 70,000 to about 4,000,000, from about 70,000 to about 3,000,000, from about 70,000 to about 2,000,000, from about 70,000 to about 1,000,000, from about 70,000 to about 800,000, from about 70,000 to about 600,000, from about 70,000 to about 400,000, from about 70,000 to about 200,000, from about 70,000 to about 100,000, from about 70,000 to about 90,000, from about 70,000 to about 80,000, from about 80,000 to about 10,000,000, from about 80,0 to approximately 9,000,000, approximately 80,000 to approximately 8,000,000, approximately 80,000 to approximately 7,000,000, approximately 80,000 to approximately 6,000,000, approximately 80,000 to approximately 5,000,000, approximately 80,000 to approximately 4,000,000, approximately 80,000 to approximately 3,000,000, approximately 80,000 to approximately 2,000,000, approximately 80,000 to approximately 1,000,000, approximately 80,000 to approximately 800,000, approximately 80,000 to approximately 600,000, approximately 80,000 to approximately 400,000, approximately 80,000 to approximately 200,000, approximately 80,000 to approximately 100,000, approximately 80,000 to approximately 90,000, approximately 90,000 to approximately 10,000,000, approximately 90,000 to approximately 9,000,000, approximately 90,000 to approximately 8,000,000, approximately 90,000 to approximately 7,000,000, approximately 90,000 to approximately 6,000,000, approximately 90,000 to approximately 5,000,000, approximately 90,000 to approximately 4,000,000, approximately 90,000 to approximately 3,000,000, approximately 90,000 to approximately 2,000,000, approximately 90,000 to approximately 1,000,000, approximately 90,000 to approximately 800,000, approximately 90,000 to approximately 600,000, approximately 90,000 to approximately 400,000, approximately 90,000 to approximately 200,000, approximately 90,000 to approximately 100,000, approximately 100,000 to approximately 10,000,000, approximately 100,000 to approximately 9,000,000, approximately 100,000 to approximately 8,000,000, approximately 100,000 to approximately 7,000,000, approximately 100,000 to approximately 6,000,000, approximately 100,000 to approximately 5,000,000, approximately 100,000 to approximately 4,000,000, approximately 100,000 to approximately 3,000,000, approximately 100,000 to approximately 2,000,000, approximately 100,000 to approximately 1,000,000, approximately 100,000 to approximately 800,000, approximately 100,000 to approximately 600,000, approximately 100,000 to approximately 400,000, approximately 100,000 to approximately 200,000, approximately 200,000 to approximately 10,000,000, approximately 200,000 to approximately 9,000,000, approximately 200,000 to approximately 8,000,000, approximately 200,000 to approximately 7,000,000, approximately 200,000 to approximately 6,000,000, approximately 200,000 to approximately 5,000,000, approximately 200,000 to approximately 4,000,000, approximately 200,000 to approximately 3,000,000, approximately 200,000 to approximately 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 3,000,000, about 600,000 to about 2,000,000, about 600,000 to about 1,000,000, about 600,000 to about 800,000, about 800,000 to about 10,000,000, about 800,000 to about 9,000,000, about 800,000 to about 8,000,000, about 800,000 to about 7,000,000, about 800,000 to about 6,000,000, about 800,000 to about 5,000,000, about 800,000 to about 4,000,000, about 800,000 to about 3,000,000, about 800,000 to about 2,000,000, about 800,000 to about 1,000,000, about 1,000,000 to about 10,000,000, about 1,000,000 to about 9,000,000, about 1,000,000 to about 8,000,000, about 1,000,000 to about 7,000,000, about 1,000,000 to about 6,000,000, about 1,000,000 to about 5,000,000, about 1,000,000 to about 4,000,000, about 1,000,000 to about 3,000,000, about 1,000,000 to about 2,000,000, about 2,000,000 to about 10,000,000, about 2,000,000 to about 9,000,000, about 2,000,000 to about 8,000,000, about 2,000,000 to about 7,000,000, about 2,000,000 to about 6,000,000, about 2,000,000 to about 5,000,000, 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 4,000,000 to about 5,000,000, about 5,000,000 to about 10,000,000, about 5,000,000 to about 9,000,000, about 5,000,000 to about 8,000,000, about 5,000,000 to about 7,000,000, about 5,000,000 to about 6,000,000, about 6,000,000 to about 10,000,000, about 6,000,000 to about 9,000,000, about 6,000,000 to about 8,000,000, about 6,000,000 to about 7,000,000, about 7,000,000 to about 10,000,000, about 7,000,000 to about 9,000,000, about 7,000,000 to about 8,000,000, about 8,000,000 to about 10,000,000, about 8,000,000 to about 9,000,000, or about 9,000,000 to about 10,000,000 of FOLR1.,

[0119] The phrase "antigen density" means the number of FOLR1 present on the surface of target mammalian cells or the average number of FOLR1 present on the surface of a population of a particular type of target mammalian cells. "Antigen density" can be measured using, for example, the Quantibright bead kit or a radiolabel (e.g., the BD Biosciences PE Phycoerythrin Quantitation Kit, catalog number

[0120] 340495).

[0121] The phrase "an amino acid is replaced by histidine" means that an amino acid residue that is not histidine in the reference polypeptide sequence is replaced by histidine. Non-limiting methods for replacing amino acid residues in a reference polypeptide with histidine are described herein. Additional methods for replacing amino acid residues in a reference polypeptide with histidine are known in the art.

[0122] The phrase "an amino acid is replaced by alanine" means that an amino acid residue that is histidine in the 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.

[0123] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Methods and materials for use in the present invention are described herein, and 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 incorporated by reference in their entirety. In case of conflict, the present specification (including definitions) shall prevail.

[0124] Other features and advantages of the present invention will be apparent from the following detailed description and figures, and from the claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0125] Figure 1 : SDS PAGE of mirvetuximab histidine scans and alanine scans. The harvested Expi293 cell culture supernatants were loaded onto a non-reducing SDS PAGE gel to confirm the expression of mirvetuximab and histidine scan and alanine scan variants. Arrows indicate the corresponding sizes of IgG on the non-reducing SDS PAGE gel. MYT0596 is mirvetuximab, and the remaining lanes (MYT0597-MYT0637) are mirvetuximab heavy chain histidine scans and alanine scan variants.

[0126] Figures 2a to 2ap : Binding of starting ABPC of mirvetuximab and histidine scan and alanine scan variants to FOLR1 determined by biolayer interferometry. As illustrated in the figure, MYT0596 (mirvetuximab) and MYT0597-MYT0637 (heavy chain histidine scans and alanine scan variants) were captured on an anti-human Fc biosensor and associated with FOLR1 at low pH or high pH.

[0127] Figure 3: Construct identifiers for the SEQ ID NO correspondence table. Constructs, heavy chain histidine scans, and alanine scan variants are listed in the first column of the table, listing the SEQ ID NO corresponding to the construct on the left and the appropriate heavy chain, light chain, and CDR categories along the top.

[0128] Figure 4 : SDS PAGE of mirvetuximab 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 mirvetuximab histidine scan and alanine scan variants. The arrows indicate the corresponding sizes of IgG on the non-reducing SDS PAGE gel. MYT1559-MYT1589 are mirvetuximab light chain histidine scan and alanine scan variants.

[0129] Figures 5a to 5ae : Binding of mirvetuximab histidine scan and alanine scan variants to FOLR1 determined by biolayer interferometry. As illustrated in the figure, MYT1559–MYT1589 (light chain histidine scan and alanine scan variants) were captured on an anti-human Fc biosensor and associated with FOLR1 at low or high pH.

[0130] Figure 6 : Construct identifiers for the SEQ ID NO correspondence table. Constructs, light chain histidine scans, and alanine scan variants are listed in the first column of the table, listing the SEQ ID NO corresponding to the construct on the left and the appropriate heavy chain, light chain, and CDR categories along the top.

[0131] Figure 7 : SDS PAGE of mirvetuximab 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 mirvetuximab histidine scan and alanine scan variants. The arrows indicate the corresponding sizes of IgG on the non-reducing SDS PAGE gel. MYT1142-MYT1161 are mirvetuximab heavy chain combination histidine scan and alanine scan variants.

[0132] Figures 8a to 8t : Binding of mirvetuximab histidine scan and alanine scan variants to FOLR1 determined by biolayer interferometry. As illustrated in the figure, MYT1142-MYT1161 (heavy chain combination histidine scan and alanine scan variants) were captured on an anti-human Fc biosensor and associated with FOLR1 at low or high pH.

[0133] Figure 9: Construct identifiers for the SEQ ID NO correspondence table. Constructs, heavy chain combinatorial histidine scans, and alanine scan variants are listed in the first column of the table, listing the SEQ ID NO corresponding to the construct on the left and the appropriate heavy chain, light chain, and CDR classes along the top.

[0134] Figure 10 : SDS PAGE of STRO-002 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 STRO-002 and histidine scan and alanine scan variants. Arrows indicate the corresponding sizes of IgG on the non-reducing SDS PAGE gel. MYT2224 is STRO-002, and the remaining lanes (MYT2225–MYT2268) are STRO-002 heavy chain histidine scan and alanine scan variants.

[0135] Figures 11a to 11as : Binding of STRO-002 starting ABPC and histidine scan and alanine scan variants to FOLR1 measured by biolayer interferometry. As illustrated in the figure, MYT2224 (STRO-002) and MYT2225–MYT2268 (heavy chain histidine scan and alanine scan variants) were captured on an anti-human Fc biosensor and associated with FOLR1 at low or high pH.

[0136] Figure 12 : Construct identifiers for the SEQ ID NO correspondence table. Constructs, heavy chain histidine scans, and alanine scan variants are listed in the first column of the table, listing the SEQ ID NO corresponding to the construct on the left and the appropriate heavy chain, light chain, and CDR classes along the top.

[0137] Figure 13 : SDS PAGE of STRO-002 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 STRO-002 histidine scan and alanine scan variants. Arrows indicate the corresponding sizes of IgG on the non-reducing SDS PAGE gel. MYT4493–MYT4519 are STRO-002 light chain histidine scan and alanine scan variants.

[0138] Figures 14a to 14aa : Binding of STRO-002 histidine scan and alanine scan variants to FOLR1 measured by biolayer interferometry. As illustrated in the figure, MYT4493–MYT4519 (light chain histidine scan and alanine scan variants) were captured on an anti-human Fc biosensor and associated with FOLR1 at low or high pH.

[0139] Figure 15 : Construct identifiers for the SEQ ID NO correspondence table. Constructs, light chain histidine scans, and alanine scan variants are listed in the first column of the table, listing the SEQ ID NO corresponding to the construct on the left and the appropriate heavy chain, light chain, and CDR classes along the top.

[0140] Figure 16 : SDS PAGE of farletuzumab histidine scans and alanine scans. The harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS PAGE gel to confirm the expression of farletuzumab and histidine scan and alanine scan variants. Arrows indicate the corresponding sizes of IgG on the non-reducing SDS PAGE gel. MYT2184 is farletuzumab, and the remaining lanes (MYT2185–MYT2223) are farletuzumab heavy chain histidine scans and alanine scan variants.

[0141] Figures 17a to 17an : Binding of farletuzumab starting ABPC and histidine scan and alanine scan variants to FOLR1 measured by biolayer interferometry. As illustrated in the figure, MYT2184 (farletuzumab) and MYT2185–MYT2223 (heavy chain histidine scans and alanine scan variants) were captured on an anti-human Fc biosensor and associated with FOLR1 at low or high pH.

[0142] Figure 18 : Construct identifiers for the SEQ ID NO correspondence table. Constructs, heavy chain histidine scans, and alanine scan variants are listed in the first column of the table, listing the SEQ ID NO corresponding to the construct on the left and the appropriate heavy chain, light chain, and CDR classes along the top.

[0143] Figure 19 : SDS PAGE of farletuzumab histidine scans and alanine scans. The harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS PAGE gel to confirm the expression of farletuzumab histidine scan and alanine scan variants. Arrows indicate the corresponding sizes of IgG on the non-reducing SDS PAGE gel. MYT4520–MYT4546 are farletuzumab light chain histidine scans and alanine scan variants.

[0144] Figures 20a to 20aa : Binding of farletuzumab histidine scan and alanine scan variants to FOLR1 measured by biolayer interferometry. As illustrated in the figure, MYT4520–MYT4546 (light chain histidine scans and alanine scan variants) were captured on an anti-human Fc biosensor and associated with FOLR1 at low or high pH.

[0145] Figure 21 : Construct identifiers for the SEQ ID NO correspondence table. Constructs, light chain histidine scans, and alanine scan variants are listed in the first column of the table, listing the SEQ ID NOs corresponding to the constructs on the left and the appropriate heavy chain, light chain, and CDR classes along the top.

[0146] Figure 22 : Internalization of anti-FOLR1 mAb in NIH:OVCAR-3 cells. Internalization and endolysosomal delivery of anti-FOLR1 pH-engineered antibody variants, the corresponding starting ABPC antibody, control IgG1 isotype control (BP0297, Bioxcell), and vehicle control were determined as described in Figure 22 and measured by mean fluorescence intensity on NIH:OVCAR-3 cells over 24 hours. Error bars represent standard deviation. Numbers above the bars represent fold change compared to wild type.

[0147] Figures 23a - 23c : Characterization of the binding affinity of anti-FOLR1 mAb. Binding of anti-FOLR1 mAb to NIH:OVCAR-3 cells was determined. Figure 23a Mirvetuximab with an IC50 of 0.250 nM is shown, Figure 23b MYT0603 with an IC50 of 0.650 nM is shown, Figure 23c MYT1154 with an IC50 of 0.396 nM is shown.

[0148] Figure 24 : Melting temperature of selected anti-FOLR1 mAbs. The melting temperatures of mirvetuximab (MYT0596) and histidine and alanine scan variants were 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 listed in the shown table. Constructs are listed in the first column Tm 1 of the table, and if applicable (e.g., if the plot has two local maxima), Tm 2 is listed in the second and third columns, respectively. Detailed Description

[0149] The present disclosure provides an antigen-binding protein construct (ABPC) that comprises a first antigen-binding domain capable of specifically binding to FOLR1 or an epitope of FOLR1 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; and / 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. In some instances of these ABPCs, the ABPC degrades in the target mammalian cell after being internalized by the target mammalian cell. Some instances of any ABPC described herein may further comprise a conjugated toxin, radioisotope, drug, or small molecule (e.g., a fluorophore or dye).

[0150] Also provided is an antigen-binding protein construct (ABPC) that comprises a first antigen-binding domain capable of specifically binding to FOLR1 or an epitope of FOLR1 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 cell 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 cell as compared to a composition comprising the same amount of a control ABPC.

[0151] In some instances of any ABPCs described herein, the first antigen-binding domain comprises the heavy-chain variable domain of mavrilimumab 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 mavrilimumab 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 mavrilimumab 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 mavrilimumab 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 mavrilimumab comprises SEQ ID NO:1. In some instances of any ABPCs described herein, the light-chain variable domain of mavrilimumab comprises SEQ ID NO:2.

[0152] 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 are SEQ ID NO:3, SEQ ID NO:4, and SEQ ID NO:5, respectively, wherein 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 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 are SEQ ID NO:6, SEQ ID NO:7, and SEQ ID NO:8, respectively, wherein 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 substituted with histidine. In some instances of any ABPC described herein, the first antigen-binding domain includes: a heavy-chain variable domain comprising CDR1, CDR2, and CDR3 that are SEQ ID NO:3, SEQ ID NO:4, and SEQ ID NO:5, respectively, wherein 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 substituted with histidine; and a light-chain variable domain comprising CDR1, CDR2, and CDR3 that are SEQ ID NO:6, SEQ ID NO:7, and SEQ ID NO:8, respectively, wherein 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 substituted with histidine.

[0153] In some instances of any ABPC described herein, the first antigen-binding domain comprises a heavy-chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity 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: 24, 27, 29, 31, 32, 33, 34, 50, 54, 55, 57, 58, 59, 60, 97, 98, 99, 100, 102, 103, 105 and 107 in SEQ ID NO:1. In some instances of any ABPC described herein, the first antigen-binding domain comprises a light-chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity 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: 28, 30, 31, 32, 34, 35, 36, 55, 59, 93, 94, 95, 96, 97, 98 and 100 in SEQ ID NO:2.In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity 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: 24, 27, 29, 31, 32, 33, 34, 50, 54, 55, 57, 58, 59, 60, 97, 98, 99, 100, 102, 103, 105 and 107 in SEQ ID NO:1, and a light chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity 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: 28, 30, 31, 32, 34, 35, 36, 55, 59, 93, 94, 95, 96, 97, 98 and 100 in SEQ ID NO:2.

[0154] In some instances of any ABPCs described herein, the heavy chain variable domain comprises a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO:1, wherein the heavy chain variable domain comprises histidine at any particular combination of one or more amino acid positions in SEQ ID NO:1 listed in Table 1.

[0155] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO:1, wherein the heavy chain variable domain comprises alanine at position 52 in SEQ ID NO:1.

[0156] In some instances of any ABPCs described herein, the first antigen-binding domain comprises: a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO:1, wherein the heavy chain variable domain comprises alanine at position 52 of SEQ ID NO:1; and a light chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity 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: 28, 30, 31, 32, 34, 35, 36, 38, 55, 59, 93, 94, 95, 96, 97, 98 and 100 of SEQ ID NO:2.

[0157] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity 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: 24, 27, 29, 31, 32, 33, 34, 50, 54, 55, 57, 58, 59, 60, 97, 98, 99, 100, 102, 103, 105 and 107 in SEQ ID NO:1, and wherein the heavy chain variable domain comprises alanine at position 52 in SEQ ID NO:1. In some instances of any ABPCs described herein, the first antigen-binding domain comprises: a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity 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: 24, 27, 29, 31, 32, 33, 34, 50, 54, 55, 57, 58, 59, 60, 97, 98, 99, 100, 102, 103, 105 and 107 in SEQ ID NO:1, and wherein the heavy chain variable domain comprises alanine at position 52 in SEQ ID NO:100; and a light chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity 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: 28, 30, 31, 32, 34, 35, 36, 55, 59, 93, 94, 95, 96, 97, 98 and 100 in SEQ ID NO:2.

[0158] In some instances of any ABPCs described herein, the heavy chain variable domain comprises a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO:1, wherein the heavy chain variable domain comprises histidine at any specific combination of one or more amino acid positions in SEQ ID NO:1 listed in Table 1 and wherein the heavy chain variable domain comprises alanine at position 52 in SEQ ID NO:1.

[0159] Table 1. Exemplary combinations of amino acid positions in SEQ ID NO:1 that can be substituted with histidine

[0160]

[0161]

[0162]

[0163]

[0164]

[0165]

[0166]

[0167]

[0168] In some instances of any ABPCs described herein, the light chain variable domain comprises a light chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO:2, wherein the light chain variable domain comprises histidine at any specific combination of one or more amino acid positions in SEQ ID NO:2 listed in Table 2.

[0169] In some instances of any ABPCs described herein, the first antigen binding domain comprises a light chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO:2, wherein the light chain variable domain comprises alanine at position 38 in SEQ ID NO:2.

[0170] In some instances of any ABPCs described herein, the first antigen-binding domain comprises: a light chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO:2, wherein the light chain variable domain comprises alanine at position 38 of SEQ ID NO:2; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity 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: 24, 27, 29, 31, 32, 33, 34, 50, 54, 55, 57, 58, 59, 60, 97, 98, 99, 100, 102, 103, 105 and 107 of SEQ ID NO:1.

[0171] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity 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: 28, 30, 31, 32, 34, 35, 36, 55, 59, 93, 94, 95, 96, 97, 98 and 100 in SEQ ID NO:2, and wherein the light chain variable domain comprises alanine at position 38 in SEQ ID NO:2. In some instances of any ABPCs described herein, the first antigen-binding domain comprises: a light chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity 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: 28, 30, 31, 32, 34, 35, 36, 55, 59, 93, 94, 95, 96, 97, 98 and 100 in SEQ ID NO:2, and wherein the light chain variable domain comprises alanine at position 38 in SEQ ID NO:2; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity 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: 24, 27, 29, 31, 32, 33, 34, 50, 54, 55, 57, 58, 59, 60, 97, 98, 99, 100, 102, 103, 105 and 107 in SEQ ID NO:1.

[0172] In some instances of any ABPCs described herein, the light chain variable domain comprises a light chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO:2, wherein the light chain variable domain comprises histidine at any particular combination of one or more amino acid positions in SEQ ID NO:2 listed in Table 2 and wherein the light chain variable domain comprises alanine at position 38 in SEQ ID NO:2.

[0173] Table 2. Exemplary combinations of amino acid positions in SEQ ID NO:2 that can be replaced with histidine

[0174]

[0175]

[0176]

[0177]

[0178] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO:1, wherein the heavy chain variable domain comprises histidine at any particular combination of one or more amino acid positions in SEQ ID NO:1 listed in Table 1; and a light chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO:2, wherein the light chain variable domain comprises histidine at any particular combination of one or more amino acid positions in SEQ ID NO:2 listed in Table 2.

[0179] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy-chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identity to SEQ ID NO:1, wherein the heavy-chain variable domain comprises histidine at any specific combination of one or more amino acid positions in SEQ ID NO:1 listed in Table 1, and wherein the heavy-chain variable domain comprises alanine at position 52 in SEQ ID NO:1; and a light-chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identity to SEQ ID NO:2, wherein the light-chain variable domain comprises histidine at any specific combination of one or more amino acid positions in SEQ ID NO:2 listed in Table 2.

[0180] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light-chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identity to SEQ ID NO:2, wherein the light-chain variable domain comprises histidine at any specific combination of one or more amino acid positions in SEQ ID NO:2 listed in Table 2, and wherein the light-chain variable domain comprises alanine at position 38 in SEQ ID NO:2; and a heavy-chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identity to SEQ ID NO:1, wherein the heavy-chain variable domain comprises histidine at any specific combination of one or more amino acid positions in SEQ ID NO:1 listed in Table 1.

[0181] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light-chain variable domain having at least 90% identity to SEQ ID NO:2, wherein the light-chain variable domain comprises histidine at position 28 in SEQ ID NO:2; and a heavy-chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identity to SEQ ID NO:1, wherein the heavy-chain variable domain comprises histidine at any specific combination of one or more amino acid positions in SEQ ID NO:1 listed in Table 1.

[0182] 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 having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO:1, wherein the heavy chain variable domain comprises histidine at any specific combination of one or more (e.g., two, three, four, five, six, seven, eight, nine or ten) amino acid positions in SEQ ID NO:1 listed in Table 1.

[0183] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO:2, wherein the light chain variable domain comprises histidine at position 30 in SEQ ID NO:2; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO:1, wherein the heavy chain variable domain comprises histidine at any specific combination of one or more amino acid positions in SEQ ID NO:1 listed in Table 1.

[0184] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO:2, wherein the light chain variable domain comprises histidine at position 31 in SEQ ID NO:2; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO:1, wherein the heavy chain variable domain comprises histidine at any specific combination of one or more amino acid positions in SEQ ID NO:1 listed in Table 1.

[0185] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO:2, wherein the light chain variable domain comprises histidine at position 32 in SEQ ID NO:2; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO:1, wherein the heavy chain variable domain comprises histidine at any specific combination of one or more amino acid positions in SEQ ID NO:1 listed in Table 1.

[0186] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 34 in SEQ ID NO:2; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any specific combination of one or more amino acid positions in SEQ ID NO:1 listed in Table 1.

[0187] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 35 in SEQ ID NO:2; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any specific combination of one or more amino acid positions in SEQ ID NO:1 listed in Table 1.

[0188] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 36 in SEQ ID NO:2; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any specific combination of one or more amino acid positions in SEQ ID NO:1 listed in Table 1.

[0189] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 55 in SEQ ID NO:2; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any specific combination of one or more amino acid positions in SEQ ID NO:1 listed in Table 1.

[0190] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 59 in SEQ ID NO:2; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any specific combination of one or more amino acid positions in SEQ ID NO:1 listed in Table 1.

[0191] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 93 in SEQ ID NO:2; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any specific combination of one or more amino acid positions in SEQ ID NO:1 listed in Table 1.

[0192] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 94 in SEQ ID NO:2; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any specific combination of one or more amino acid positions in SEQ ID NO:1 listed in Table 1.

[0193] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 95 in SEQ ID NO:2; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any specific combination of one or more amino acid positions in SEQ ID NO:1 listed in Table 1.

[0194] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 96 in SEQ ID NO:2; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any particular combination of one or more amino acid positions in SEQ ID NO:1 listed in Table 1.

[0195] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 97 in SEQ ID NO:2; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any particular combination of one or more amino acid positions in SEQ ID NO:1 listed in Table 1.

[0196] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 98 in SEQ ID NO:2; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any particular combination of one or more amino acid positions in SEQ ID NO:1 listed in Table 1.

[0197] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 100 in SEQ ID NO:2; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any particular combination of one or more amino acid positions in SEQ ID NO:1 listed in Table 1.

[0198] In some instances of any ABPCs described herein, the first antigen-binding domain comprises the heavy chain variable domain of mavrilimumab 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 mavrilimumab 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 mavrilimumab 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 mavrilimumab 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 mavrilimumab comprises SEQ ID NO:1. In some instances of any ABPCs described herein, the light chain variable domain of mavrilimumab comprises SEQ ID NO:2.

[0199] 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 are SEQ ID NO:3, SEQ ID NO:4, and SEQ ID NO:5, respectively, and one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NOs: 3-5 are replaced with alanine. 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 are SEQ ID NO:6, SEQ ID NO:7, and SEQ ID NO:8, respectively, and one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NOs: 6-8 are replaced with alanine. In some instances of any ABPCs described herein, the first antigen-binding domain includes: a heavy-chain variable domain comprising CDR1, CDR2, and CDR3 that are SEQ ID NO:3, SEQ ID NO:4, and SEQ ID NO:5, respectively, and one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NOs: 3-5 are replaced with alanine; and a light-chain variable domain comprising CDR1, CDR2, and CDR3 that are SEQ ID NO:6, SEQ ID NO:7, and SEQ ID NO:8, respectively, and one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NOs: 6-8 are replaced with alanine.

[0200] 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, SEQ ID NO:52 or SEQ ID NO:53.

[0201] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain of: SEQ ID NO:2, 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, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83 or SEQ ID NO:84.

[0202] In some instances of any ABPC 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: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, SEQ ID NO:52 or SEQ ID NO:53.

[0203] In some instances of any ABPC 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, SEQ ID NO:52 or SEQ ID NO:53.

[0204] In some instances of any ABPC 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, SEQ ID NO:52 or SEQ ID NO:53.

[0205] In some instances of any ABPC 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, SEQ ID NO:52 or SEQ ID NO:53.

[0206] 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, SEQ ID NO:52 or SEQ ID NO:53.

[0207] 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, SEQ ID NO:52 or SEQ ID NO:53.

[0208] 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, SEQ ID NO:52 or SEQ ID NO:53.

[0209] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:60 and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52 or SEQ ID NO:53.

[0210] In some instances of any ABPC 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, SEQ ID NO:52 or SEQ ID NO:53.

[0211] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 62 and a heavy chain variable domain comprising: SEQ ID NO: 1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52 or SEQ ID NO: 53.

[0212] 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, SEQ ID NO:52 or SEQ ID NO:53.

[0213] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:64 and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52 or SEQ ID NO:53.

[0214] 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, SEQ ID NO:52 or SEQ ID NO:53.

[0215] 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, SEQ ID NO:52 or SEQ ID NO:53.

[0216] 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, SEQ ID NO:52 or SEQ ID NO:53.

[0217] 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, SEQ ID NO:52 or SEQ ID NO:53.

[0218] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:69 and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52 or SEQ ID NO:53.

[0219] 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, SEQ ID NO:52 or SEQ ID NO:53.

[0220] 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, SEQ ID NO:52 or SEQ ID NO:53.

[0221] 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, SEQ ID NO:52 or SEQ ID NO:53.

[0222] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:73 and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52 or SEQ ID NO:53.

[0223] 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, SEQ ID NO:52 or SEQ ID NO:53.

[0224] 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, SEQ ID NO:52 or SEQ ID NO:53.

[0225] 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, SEQ ID NO:52 or SEQ ID NO:53.

[0226] 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, SEQ ID NO:52 or SEQ ID NO:53.

[0227] 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, SEQ ID NO:52 or SEQ ID NO:53.

[0228] 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, SEQ ID NO:52 or SEQ ID NO:53.

[0229] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:80 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, SEQ ID NO:52 or SEQ ID NO:53.

[0230] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:81 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, SEQ ID NO:52 or SEQ ID NO:53.

[0231] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:82 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, SEQ ID NO:52 or SEQ ID NO:53.

[0232] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:83 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, SEQ ID NO:52 or SEQ ID NO:53.

[0233] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:84 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, SEQ ID NO:52 or SEQ ID NO:53.

[0234] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising: SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, 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 or SEQ ID NO:104..

[0235] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81 or SEQ ID NO:83.

[0236] In some instances of any ABPCs described herein, the first antigen-binding domain comprises: a heavy chain variable domain comprising SEQ ID NO:85 and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81 or SEQ ID NO:83.

[0237] In some instances of any ABPCs described herein, the first antigen-binding domain comprises: a heavy chain variable domain comprising SEQ ID NO:86 and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81 or SEQ ID NO:83.

[0238] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:87 and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81 or SEQ ID NO:83.

[0239] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:88 and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81 or SEQ ID NO:83.

[0240] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:89 and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81 or SEQ ID NO:83.

[0241] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:90: and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81 or SEQ ID NO:83.

[0242] In some instances of any ABPCs described herein, the first antigen-binding domain comprises: a heavy chain variable domain comprising SEQ ID NO:91 and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81 or SEQ ID NO:83.

[0243] In some instances of any ABPCs described herein, the first antigen-binding domain comprises: a heavy chain variable domain comprising SEQ ID NO:92 and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81 or SEQ ID NO:83.

[0244] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:93 and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81 or SEQ ID NO:83.

[0245] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:94 and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81 or SEQ ID NO:83.

[0246] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:95 and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81 or SEQ ID NO:83.

[0247] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy-chain variable domain comprising SEQ ID NO:96 and a light-chain variable domain comprising: SEQ ID NO:2, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81 or SEQ ID NO:83.

[0248] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy-chain variable domain comprising SEQ ID NO:97 and a light-chain variable domain comprising: SEQ ID NO:2, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81 or SEQ ID NO:83.

[0249] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy-chain variable domain comprising SEQ ID NO:98 and a light-chain variable domain comprising SEQ ID NO:2, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81 or SEQ ID NO:83.

[0250] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:99 and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, or SEQ ID NO:83.

[0251] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising: SEQ ID NO:100 and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, or SEQ ID NO:83.

[0252] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:101 and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, or SEQ ID NO:83.

[0253] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO: 102 and a light chain variable domain comprising: SEQ ID NO: 2, SEQ ID NO: 58, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 68, SEQ ID NO: 70, SEQ ID NO: 74, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81 or SEQ ID NO: 83.

[0254] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO: 103 and a light chain variable domain comprising: SEQ ID NO: 2, SEQ ID NO: 58, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 68, SEQ ID NO: 70, SEQ ID NO: 74, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81 or SEQ ID NO: 83.

[0255] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO: 104 and a light chain variable domain comprising: SEQ ID NO: 2, SEQ ID NO: 58, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 68, SEQ ID NO: 70, SEQ ID NO: 74, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81 or SEQ ID NO: 83.

[0256] In some instances of any ABPCs described herein, the first antigen-binding domain comprises the heavy chain variable domain of STRO-002 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 STRO-002 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 STRO-002 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 STRO-002 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 STRO-002 comprises SEQ ID NO:105. In some instances of any ABPCs described herein, the light chain variable domain of STRO-002 comprises SEQ ID NO:106.

[0257] 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 are SEQ ID NO:107, SEQ ID NO:108, and SEQ ID NO:109, respectively, and 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 NO:107-109 are 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 are SEQ ID NO:110, SEQ ID NO:111, and SEQ ID NO:112, respectively, and 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 NO:110-112 are substituted with histidine. In some instances of any ABPCs described herein, the first antigen-binding domain includes: a heavy-chain variable domain comprising CDR1, CDR2, and CDR3 that are SEQ ID NO:107, SEQ ID NO:108, and SEQ ID NO:109, respectively, and 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 NO:107-109 are substituted with histidine; and a light-chain variable domain comprising CDR1, CDR2, and CDR3 that are SEQ ID NO:110, SEQ ID NO:111, and SEQ ID NO:112, respectively, and 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 NO:110-112 are substituted with histidine.

[0258] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 105, 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: 29, 33, 34, 50, 51, 52, 53, 55, 56, 57, 101, 102, 103, 108, 109, 110, 111, 112 and 113 in SEQ ID NO: 105. In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 106, 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: 28, 29, 30, 31, 50, 92, 93, 94, 95 and 96 in SEQ ID NO: 106.In some instances of any ABPCs described herein, the first antigen-binding domain comprises: a heavy-chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 105, 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: 29, 33, 34, 50, 51, 52, 53, 55, 56, 57, 101, 102, 103, 108, 109, 110, 111, 112 and 113 in SEQ ID NO: 105; and a light-chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 106, 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: 28, 29, 30, 31, 50, 92, 93, 94, 95 and 96 in SEQ ID NO: 106.

[0259] In some instances of any ABPCs described herein, the heavy-chain variable domain comprises a heavy-chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 105, wherein the heavy-chain variable domain comprises histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 105 listed in Table 3.

[0260] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy-chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 105, wherein the heavy-chain variable domain comprises alanine at position 35 in SEQ ID NO: 105.

[0261] In some instances of any ABPCs described herein, the first antigen-binding domain comprises: a heavy-chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 105, wherein the heavy-chain variable domain comprises alanine at position 35 of SEQ ID NO: 105; and a light-chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 106, 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: 28, 29, 30, 31, 50, 92, 93, 94, 95 and 96 of SEQ ID NO: 106.

[0262] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy-chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 105, 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: 29, 33, 34, 50, 51, 52, 53, 55, 56, 57, 101, 102, 103, 108, 109, 110, 111, 112 and 113 in SEQ ID NO: 105, and wherein the heavy-chain variable domain comprises alanine at position 35 in SEQ ID NO: 105. In some instances of any ABPCs described herein, the first antigen-binding domain comprises: a heavy-chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 105, 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: 29, 33, 34, 50, 51, 52, 53, 55, 56, 57, 101, 102, 103, 108, 109, 110, 111, 112 and 113 in SEQ ID NO: 105, and wherein the heavy-chain variable domain comprises alanine at position 35 in SEQ ID NO: 105; and a light-chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 106, 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: 28, 29, 30, 31, 50, 92, 93, 94, 95 and 96 in SEQ ID NO: 106.

[0263] In some instances of any ABPC described herein, the heavy chain variable domain comprises a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 105, wherein the heavy chain variable domain comprises histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 105 listed in Table 3 and wherein the heavy chain variable domain comprises alanine at position 35 in SEQ ID NO: 105.

[0264] Table 3. Exemplary combinations of amino acid positions in SEQ ID NO: 105 that can be substituted with histidine

[0265]

[0266]

[0267]

[0268]

[0269]

[0270]

[0271] In some instances of any ABPC described herein, the light chain variable domain comprises a light chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 106, wherein the light chain variable domain comprises histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 106 listed in Table 4.

[0272] In some instances of any ABPC described herein, the first antigen-binding domain comprises a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 106, wherein the heavy chain variable domain comprises alanine at position 91 in SEQ ID NO: 106.

[0273] In some instances of any ABPC described herein, the first antigen-binding domain comprises: a light chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 106, wherein the light chain variable domain comprises alanine at position 91 of SEQ ID NO: 2; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 105, 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: 29, 33, 34, 50, 51, 52, 53, 55, 56, 57, 101, 102, 103, 108, 109, 110, 111, 112 and 113 of SEQ ID NO: 105.

[0274] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 106, 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: 28, 29, 30, 31, 50, 92, 93, 94, 95 and 96 in SEQ ID NO: 106, and wherein the light chain variable domain comprises alanine at position 91 in SEQ ID NO: 106. In some instances of any ABPCs described herein, the first antigen-binding domain comprises: a light chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 106, 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: 28, 29, 30, 31, 50, 92, 93, 94, 95 and 96 in SEQ ID NO: 106, and wherein the light chain variable domain comprises alanine at position 91 in SEQ ID NO: 106; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 105, 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: 29, 33, 34, 50, 51, 52, 53, 55, 56, 57, 101, 102, 103, 108, 109, 110, 111, 112 and 113 in SEQ ID NO: 105.

[0275] In some instances of any ABPCs described herein, the light chain variable domain comprises a light chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO:106, wherein the light chain variable domain comprises histidine at any specific combination of one or more amino acid positions in SEQ ID NO:106 listed in Table 4 and wherein the light chain variable domain comprises alanine at position 91 in SEQ ID NO:106.

[0276] Table 4. Exemplary combinations of amino acid positions in SEQ ID NO:106 that may be replaced with histidine

[0277]

[0278]

[0279] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO:105, wherein the heavy chain variable domain comprises histidine at any specific combination of one or more amino acid positions in SEQ ID NO:105 listed in Table 3; and a light chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO:106, wherein the light chain variable domain comprises histidine at any specific combination of one or more amino acid positions in SEQ ID NO:106 listed in Table 4.

[0280] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 105, wherein the heavy chain variable domain comprises histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 105 listed in Table 3, and wherein the heavy chain variable domain comprises alanine at position 35 in SEQ ID NO: 105; and a light chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 106, wherein the light chain variable domain comprises histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 106 listed in Table 4.

[0281] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 106, wherein the light chain variable domain comprises histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 106 listed in Table 4, and wherein the light chain variable domain comprises alanine at position 91 in SEQ ID NO: 106; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 105, wherein the heavy chain variable domain comprises histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 105 listed in Table 3.

[0282] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO: 106, wherein the light chain variable domain comprises histidine at position 28 in SEQ ID NO: 106; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 105, wherein the heavy chain variable domain comprises histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 105 listed in Table 3.

[0283] In some instances of any ABPC described herein, the first antigen-binding domain comprises: a light chain variable domain comprising SEQ ID NO: 106, and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 105, wherein the heavy chain variable domain comprises histidine at any particular combination of one or more (e.g., two, three, four, five, six, seven, eight, nine or ten) amino acid positions in SEQ ID NO: 105 listed in Table 3.

[0284] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO: 106, wherein the light chain variable domain comprises histidine at position 29 in SEQ ID NO: 106; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 105, wherein the heavy chain variable domain comprises histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 105 listed in Table 3.

[0285] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO: 106, wherein the light chain variable domain comprises histidine at position 30 in SEQ ID NO: 106; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 105, wherein the heavy chain variable domain comprises histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 105 listed in Table 3.

[0286] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO: 106, wherein the light chain variable domain comprises histidine at position 31 in SEQ ID NO: 106; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 105, wherein the heavy chain variable domain comprises histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 105 listed in Table 3.

[0287] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO: 106, wherein the light chain variable domain comprises histidine at position 50 in SEQ ID NO: 106; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 105, wherein the heavy chain variable domain comprises histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 105 listed in Table 3.

[0288] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO: 106, wherein the light chain variable domain comprises alanine at position 91 in SEQ ID NO: 106; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 105, wherein the heavy chain variable domain comprises histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 105 listed in Table 3.

[0289] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO: 106, wherein the light chain variable domain comprises histidine at position 92 in SEQ ID NO: 106; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 105, wherein the heavy chain variable domain comprises histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 105 listed in Table 3.

[0290] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO: 106, wherein the light chain variable domain comprises a histidine at position 93 in SEQ ID NO: 106; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 105, wherein the heavy chain variable domain comprises a histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 105 listed in Table 3.

[0291] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO: 106, wherein the light chain variable domain comprises a histidine at position 94 in SEQ ID NO: 106; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 105, wherein the heavy chain variable domain comprises a histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 105 listed in Table 3.

[0292] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO: 106, wherein the light chain variable domain comprises a histidine at position 95 in SEQ ID NO: 106; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 105, wherein the heavy chain variable domain comprises a histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 105 listed in Table 3.

[0293] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO: 106, wherein the light chain variable domain comprises a histidine at position 96 in SEQ ID NO: 106; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 105, wherein the heavy chain variable domain comprises a histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 105 listed in Table 3.

[0294] In some instances of any ABPCs described herein, the first antigen-binding domain comprises the heavy chain variable domain of STRO-002 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 STRO-002 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 STRO-002 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 STRO-002 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 STRO-002 comprises SEQ ID NO: 105. In some instances of any ABPCs described herein, the light chain variable domain of STRO-002 comprises SEQ ID NO: 106.

[0295] 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 are SEQ ID NO:107, SEQ ID NO:108, and SEQ ID NO:109, respectively, wherein one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) of the histidines in SEQ ID NO:107-109 are 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 are SEQ ID NO:110, SEQ ID NO:111, and SEQ ID NO:112, respectively, wherein one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) of the histidines in SEQ ID NO:110-112 are replaced with alanine. In some instances of any ABPC described herein, the first antigen-binding domain includes: a heavy chain variable domain comprising CDR1, CDR2, and CDR3 that are SEQ ID NO:107, SEQ ID NO:108, and SEQ ID NO:109, respectively, wherein one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) of the histidines in SEQ ID NO:107-109 are replaced with alanine; and a light chain variable domain comprising CDR1, CDR2, and CDR3 that are SEQ ID NO:110, SEQ ID NO:111, and SEQ ID NO:112, respectively, wherein one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) of the histidines in SEQ ID NO:110-112 are replaced with alanine.

[0296] 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:105, 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: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, or SEQ ID NO:156.

[0297] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain of: SEQ ID NO:106, SEQ ID NO:157, SEQ ID NO:158, SEQ ID NO:159, SEQ ID NO:160, SEQ ID NO:161, SEQ ID NO:162, SEQ ID NO:163, SEQ ID NO:164, SEQ ID NO:165, SEQ ID NO:166, SEQ ID NO:167, 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, SEQ ID NO:177, SEQ ID NO:178, SEQ ID NO:179, SEQ ID NO:180, SEQ ID NO:181, SEQ ID NO:182 or SEQ ID NO:183.

[0298] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 106 and a heavy chain variable domain comprising: SEQ ID NO: 105, 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: 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 or SEQ ID NO: 156.

[0299] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 157 and a heavy chain variable domain comprising: SEQ ID NO: 105, 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: 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 or SEQ ID NO: 156.

[0300] 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: 105, 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: 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 or SEQ ID NO: 156.

[0301] 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: 105, 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: 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 or SEQ ID NO: 156.

[0302] 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: 105, 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: 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 or SEQ ID NO: 156.

[0303] 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: 105, 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: 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 or SEQ ID NO: 156.

[0304] 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: 105, 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: 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 or SEQ ID NO: 156.

[0305] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 163 and a heavy chain variable domain comprising: SEQ ID NO: 105, 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: 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 or SEQ ID NO: 156.

[0306] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 164 and a heavy chain variable domain comprising: SEQ ID NO: 105, 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: 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 or SEQ ID NO: 156.

[0307] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 165 and a heavy chain variable domain comprising: SEQ ID NO: 105, 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: 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 or SEQ ID NO: 156.

[0308] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 166 and a heavy chain variable domain comprising: SEQ ID NO: 105, 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: 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 or SEQ ID NO: 156.

[0309] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 167 and a heavy chain variable domain comprising: SEQ ID NO: 105, 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: 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 or SEQ ID NO: 156.

[0310] In some instances of any ABPC 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: 105, 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: 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 or SEQ ID NO: 156.

[0311] In some instances of any ABPCs 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: 105, 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: 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 or SEQ ID NO: 156.

[0312] In some instances of any ABPCs 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: 105, 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: 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 or SEQ ID NO: 156.

[0313] 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: 105, 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: 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 or SEQ ID NO: 156.

[0314] In some instances 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: 105, 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: 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 or SEQ ID NO: 156.

[0315] In some instances of any ABPCs 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: 105, 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: 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 or SEQ ID NO: 156.

[0316] 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: 105, 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: 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 or SEQ ID NO: 156.

[0317] In some instances of any ABPC 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: 105, 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: 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 or SEQ ID NO: 156.

[0318] In some instances of any ABPCs 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: 105, 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: 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 or SEQ ID NO: 156.

[0319] In some instances of any ABPCs 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: 105, 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: 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 or SEQ ID NO: 156.

[0320] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 178 and a heavy chain variable domain comprising: SEQ ID NO: 105, 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: 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 or SEQ ID NO: 156.

[0321] 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: 105, 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: 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 or SEQ ID NO: 156.

[0322] In some instances of any ABPC described herein, the first antigen-binding domain comprises: a light chain variable domain comprising SEQ ID NO: 180 and a heavy chain variable domain comprising: SEQ ID NO: 105, 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: 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 or SEQ ID NO: 156.

[0323] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 181 and a heavy chain variable domain comprising: SEQ ID NO: 105, 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: 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 or SEQ ID NO: 156.

[0324] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 182 and a heavy chain variable domain comprising: SEQ ID NO: 105, 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: 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 or SEQ ID NO: 156.

[0325] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO: 183 and a heavy chain variable domain comprising: SEQ ID NO: 105, 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: 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 or SEQ ID NO: 156.

[0326] In some instances of any ABPCs described herein, the first antigen-binding domain comprises the heavy chain variable domain of farletuzumab 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 farletuzumab 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 farletuzumab 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 farletuzumab 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 farletuzumab comprises SEQ ID NO:184. In some instances of any ABPCs described herein, the light chain variable domain of farletuzumab comprises SEQ ID NO:185.

[0327] In some instances of any ABPC described herein, the first antigen-binding domain comprises: a heavy variable domain comprising CDR1, CDR2, and CDR3 that are SEQ ID NO:186, SEQ ID NO:187, and SEQ ID NO:188, respectively, with one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NO:186 - 188 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 are SEQ ID NO:189, SEQ ID NO:190, and SEQ ID NO:191, respectively, with one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NO:189 - 191 substituted with histidine. In some instances of any ABPC described herein, the first antigen-binding domain includes: a heavy chain variable domain comprising CDR1, CDR2, and CDR3 that are SEQ ID NO:186, SEQ ID NO:187, and SEQ ID NO:188, respectively, with one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NO:186 - 188 substituted with histidine; and a light chain variable domain comprising CDR1, CDR2, and CDR3 that are SEQ ID NO:189, SEQ ID NO:190, and SEQ ID NO:191, respectively, with one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NO:189 - 191 substituted with histidine.

[0328] In some instances of any ABPC described herein, the first antigen-binding domain comprises a heavy-chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 184, 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: 26, 27, 28, 29, 30, 32, 33, 34, 53, 56, 57, 59, 62, 63, 103 and 105 in SEQ ID NO: 184. In some instances of any ABPC described herein, the first antigen-binding domain comprises a light-chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 185, 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, 33, 34, 51, 52, 53, 54, 55, 90, 92, 94, 96, 97, 98, 99 and 100 in SEQ ID NO: 185.In some instances of any ABPCs described herein, the first antigen-binding domain comprises: a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 184, 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: 26, 27, 28, 29, 30, 32, 33, 34, 53, 56, 57, 59, 62, 63, 103 and 105 in SEQ ID NO: 184; and a light chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 185, 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, 33, 34, 51, 52, 53, 54, 55, 90, 92, 94, 96, 97, 98, 99 and 100 in SEQ ID NO: 185.

[0329] In some instances of any ABPCs described herein, the heavy chain variable domain comprises a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 184, wherein the heavy chain variable domain comprises histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 184 listed in Table 5.

[0330] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 184, wherein the heavy chain variable domain comprises alanine at position 99 in SEQ ID NO: 184.

[0331] In some instances of any ABPCs described herein, the first antigen-binding domain comprises: a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 184, wherein the heavy chain variable domain comprises alanine at position 99 of SEQ ID NO: 184; and a light chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 185, 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, 33, 34, 51, 52, 53, 54, 55, 90, 92, 94, 96, 97, 98, 99 and 100 of SEQ ID NO: 185.

[0332] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 184, 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: 26, 27, 28, 29, 30, 32, 33, 34, 53, 56, 57, 59, 62, 63, 103 and 105 in SEQ ID NO: 184, and wherein the heavy chain variable domain comprises alanine at position 99 in SEQ ID NO: 184. In some instances of any ABPCs described herein, the first antigen-binding domain comprises: a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 184, 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: 26, 27, 28, 29, 30, 32, 33, 34, 53, 56, 57, 59, 62, 63, 103 and 105 in SEQ ID NO: 184, and wherein the heavy chain variable domain comprises alanine at position 99 in SEQ ID NO: 184; and a light chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 185, 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, 33, 34, 51, 52, 53, 54, 55, 90, 92, 94, 96, 97, 98, 99 and 100 in SEQ ID NO: 185.

[0333] In some instances of any ABPCs described herein, the heavy chain variable domain comprises a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 184, wherein the heavy chain variable domain comprises histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 184 listed in Table 5 and wherein the heavy chain variable domain comprises alanine at position 99 in SEQ ID NO: 184.

[0334] Table 5. Exemplary combinations of amino acid positions in SEQ ID NO: 184 that may be substituted with histidine

[0335]

[0336]

[0337]

[0338]

[0339] In some instances of any ABPCs described herein, the light chain variable domain comprises a light chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 185, wherein the light chain variable domain comprises histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 185 listed in Table 6.

[0340] In some instances of any ABPCs described herein, the first antigen binding domain comprises a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 185, wherein the heavy chain variable domain comprises alanine at position 35 in SEQ ID NO: 185.

[0341] In some instances of any ABPCs described herein, the first antigen-binding domain comprises: a light chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 185, wherein the light chain variable domain comprises alanine at position 35 of SEQ ID NO: 185; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 184, 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: 26, 27, 28, 29, 30, 32, 33, 34, 53, 56, 57, 59, 62, 63, 103 and 105 of SEQ ID NO: 184.

[0342] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 185, 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, 33, 34, 51, 52, 53, 54, 55, 90, 92, 94, 96, 97, 98, 99 and 100 in SEQ ID NO: 185, and wherein the light chain variable domain comprises alanine at position 35 in SEQ ID NO: 185. In some instances of any ABPCs described herein, the first antigen-binding domain comprises: a light chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 185, 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, 33, 34, 51, 52, 53, 54, 55, 90, 92, 94, 96, 97, 98, 99 and 100 in SEQ ID NO: 185, and wherein the light chain variable domain comprises alanine at position 35 in SEQ ID NO: 185; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 184, 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: 26, 27, 28, 29, 30, 32, 33, 34, 53, 56, 57, 59, 62, 63, 103 and 105 in SEQ ID NO: 184.

[0343] In some instances of any ABPCs described herein, the light chain variable domain comprises a light chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 185, wherein the light chain variable domain comprises histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 185 listed in Table 6 and wherein the light chain variable domain comprises alanine at position 35 in SEQ ID NO: 185.

[0344] Table 6. Exemplary combinations of amino acid positions in SEQ ID NO: 185 that may be replaced with histidine

[0345]

[0346]

[0347]

[0348]

[0349] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 184, wherein the heavy chain variable domain comprises histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 184 listed in Table 5; and a light chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 186, wherein the light chain variable domain comprises histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 185 listed in Table 6.

[0350] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy-chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 184, wherein the heavy-chain variable domain comprises histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 184 listed in Table 5, and wherein the heavy-chain variable domain comprises alanine at position 99 in SEQ ID NO: 184; and a light-chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 185, wherein the light-chain variable domain comprises histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 185 listed in Table 6.

[0351] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy-chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 184, wherein the heavy-chain variable domain comprises histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 184 listed in Table 5, and wherein the heavy-chain variable domain comprises alanine at position 99 in SEQ ID NO: 184; and a light-chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 185, wherein the light-chain variable domain comprises histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 185 listed in Table 6.

[0352] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 185, wherein the light chain variable domain comprises histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 185 listed in Table 6, and wherein the light chain variable domain comprises alanine at position 35 in SEQ ID NO: 185; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 184, wherein the heavy chain variable domain comprises histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 184 listed in Table 5.

[0353] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO: 185, wherein the light chain variable domain comprises histidine at position 29 in SEQ ID NO: 185; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 184, wherein the heavy chain variable domain comprises histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 184 listed in Table 5.

[0354] In some instances of any ABPCs described herein, the first antigen-binding domain comprises: a light chain variable domain comprising SEQ ID NO: 185, and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 184, wherein the heavy chain variable domain comprises histidine at any particular combination of one or more (e.g., two, three, four, five, six, seven, eight, nine or ten) amino acid positions in SEQ ID NO: 184 listed in Table 5.

[0355] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO: 185, wherein the light chain variable domain comprises a histidine at position 33 in SEQ ID NO: 185; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 184, wherein the heavy chain variable domain comprises a histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 184 listed in Table 5.

[0356] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO: 185, wherein the light chain variable domain comprises a histidine at position 34 in SEQ ID NO: 185; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 184, wherein the heavy chain variable domain comprises a histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 184 listed in Table 5.

[0357] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO: 185, wherein the light chain variable domain comprises an alanine at position 35 in SEQ ID NO: 185; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 184, wherein the heavy chain variable domain comprises a histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 184 listed in Table 5.

[0358] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO: 185, wherein the light chain variable domain comprises a histidine at position 51 in SEQ ID NO: 185; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 184, wherein the heavy chain variable domain comprises a histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 184 listed in Table 5.

[0359] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO: 185, wherein the light chain variable domain comprises a histidine at position 52 in SEQ ID NO: 185; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 184, wherein the heavy chain variable domain comprises a histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 184 listed in Table 5.

[0360] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO: 185, wherein the light chain variable domain comprises a histidine at position 53 in SEQ ID NO: 185; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 184, wherein the heavy chain variable domain comprises a histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 184 listed in Table 5.

[0361] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO: 185, wherein the light chain variable domain comprises a histidine at position 54 in SEQ ID NO: 185; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 184, wherein the heavy chain variable domain comprises a histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 184 listed in Table 5.

[0362] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO: 185, wherein the light chain variable domain comprises a histidine at position 55 in SEQ ID NO: 185; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 184, wherein the heavy chain variable domain comprises a histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 184 listed in Table 5.

[0363] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO: 185, wherein the light chain variable domain comprises a histidine at position 90 in SEQ ID NO: 185; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 184, wherein the heavy chain variable domain comprises a histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 184 listed in Table 5.

[0364] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO: 185, wherein the light chain variable domain comprises a histidine at position 92 in SEQ ID NO: 185; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 184, wherein the heavy chain variable domain comprises a histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 184 listed in Table 5.

[0365] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO: 185, wherein the light chain variable domain comprises a histidine at position 94 in SEQ ID NO: 185; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 184, wherein the heavy chain variable domain comprises a histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 184 listed in Table 5.

[0366] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO: 185, wherein the light chain variable domain comprises a histidine at position 96 in SEQ ID NO: 185; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 184, wherein the heavy chain variable domain comprises a histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 184 listed in Table 5.

[0367] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO: 185, wherein the light chain variable domain comprises a histidine at position 97 in SEQ ID NO: 185; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 184, wherein the heavy chain variable domain comprises a histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 184 listed in Table 5.

[0368] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO: 185, wherein the light chain variable domain comprises a histidine at position 98 in SEQ ID NO: 185; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 184, wherein the heavy chain variable domain comprises a histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 184 listed in Table 5.

[0369] In some instances of any ABPC described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO: 185, wherein the light chain variable domain comprises a histidine at position 99 in SEQ ID NO: 185; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 184, wherein the heavy chain variable domain comprises a histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 184 listed in Table 5.

[0370] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain having at least 90% identity to SEQ ID NO: 185, wherein the light chain variable domain comprises a histidine at position 100 in SEQ ID NO: 185; and a heavy chain variable domain having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99% or 100%) identity to SEQ ID NO: 184, wherein the heavy chain variable domain comprises a histidine at any particular combination of one or more amino acid positions in SEQ ID NO: 184 listed in Table 5.

[0371] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain of farletuzumab 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 by alanines. In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain of farletuzumab 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 by alanines. In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain of farletuzumab 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 by alanines; and a light chain variable domain of farletuzumab 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 by alanines. In some instances of any ABPCs described herein, the heavy chain variable domain of farletuzumab comprises SEQ ID NO: 184. In some instances of any ABPCs described herein, the light chain variable domain of farletuzumab comprises SEQ ID NO: 185.

[0372] 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 are SEQ ID NO:186, SEQ ID NO:187, and SEQ ID NO:188, respectively, wherein one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) of the histidines in SEQ ID NO:186 - 188 are replaced with alanine. 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 are SEQ ID NO:189, SEQ ID NO:190, and SEQ ID NO:191, respectively, wherein one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) of the histidines in SEQ ID NO:189 - 191 are replaced with alanine. In some instances of any ABPCs described herein, the first antigen-binding domain includes: a heavy chain variable domain comprising CDR1, CDR2, and CDR3 that are SEQ ID NO:186, SEQ ID NO:187, and SEQ ID NO:188, respectively, wherein one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) of the histidines in SEQ ID NO:186 - 188 are replaced with alanine; and a light chain variable domain comprising CDR1, CDR2, and CDR3 that are SEQ ID NO:189, SEQ ID NO:190, and SEQ ID NO:191, respectively, wherein one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) of the histidines in SEQ ID NO:189 - 191 are replaced with alanine.

[0373] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain of any of: SEQ ID NO:184, 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:228, SEQ ID NO:229 or SEQ ID NO:230.

[0374] In some instances of any ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain of: SEQ ID NO:185, 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.

[0375] In some instances of any ABPC described herein, the first antigen-binding domain comprises: a light chain variable domain comprising SEQ ID NO: 185 and a heavy chain variable domain comprising: SEQ ID NO: 184, 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: 228, SEQ ID NO: 229 or SEQ ID NO: 230.

[0376] 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: 184, 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: 228, SEQ ID NO: 229 or SEQ ID NO: 230.

[0377] In some instances of any ABPCs 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: 184, 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: 228, SEQ ID NO: 229 or SEQ ID NO: 230.

[0378] 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: 184, 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: 228, SEQ ID NO: 229 or SEQ ID NO: 230.

[0379] 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: 184, 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: 228, SEQ ID NO: 229 or SEQ ID NO: 230.

[0380] 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: 184, 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: 228, SEQ ID NO: 229 or SEQ ID NO: 230.

[0381] In some instances of any ABPCs 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: 184, 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: 228, SEQ ID NO: 229 or SEQ ID NO: 230.

[0382] 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: 184, 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: 228, SEQ ID NO: 229 or SEQ ID NO: 230.

[0383] 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: 184, 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: 228, SEQ ID NO: 229 or SEQ ID NO: 230.

[0384] 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: 184, 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: 228, SEQ ID NO: 229 or SEQ ID NO: 230.

[0385] 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: 184, 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: 228, SEQ ID NO: 229 or SEQ ID NO: 230.

[0386] In some instances of any ABPC 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: 184, 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: 228, SEQ ID NO: 229 or SEQ ID NO: 230.

[0387] In some instances of any ABPCs 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: 184, 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: 228, SEQ ID NO: 229 or SEQ ID NO: 230.

[0388] 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: 184, 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: 228, SEQ ID NO: 229 or SEQ ID NO: 230.

[0389] In some instances of any ABPCs 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: 184, 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: 228, SEQ ID NO: 229 or SEQ ID NO: 230.

[0390] In some instances of any ABPCs 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: 184, 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: 228, SEQ ID NO: 229 or SEQ ID NO: 230.

[0391] In some instances of any ABPCs 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: 184, 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: 228, SEQ ID NO: 229 or SEQ ID NO: 230.

[0392] 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: 184, 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: 228, SEQ ID NO: 229 or SEQ ID NO: 230.

[0393] In some instances of any ABPCs 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: 184, 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: 228, SEQ ID NO: 229 or SEQ ID NO: 230.

[0394] 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: 184, 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: 228, SEQ ID NO: 229 or SEQ ID NO: 230.

[0395] 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: 184, 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: 228, SEQ ID NO: 229 or SEQ ID NO: 230.

[0396] In some instances of any ABPC 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: 184, 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: 228, SEQ ID NO: 229 or SEQ ID NO: 230.

[0397] In some instances of any ABPCs 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: 184, 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: 228, SEQ ID NO: 229 or SEQ ID NO: 230.

[0398] In some instances of any ABPCs 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: 184, 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: 228, SEQ ID NO: 229 or SEQ ID NO: 230.

[0399] In some instances of any ABPCs 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: 184, 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: 228, SEQ ID NO: 229 or SEQ ID NO: 230.

[0400] In some instances of any ABPCs 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: 184, 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: 228, SEQ ID NO: 229 or SEQ ID NO: 230.

[0401] In some instances of any ABPC 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: 184, 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: 228, SEQ ID NO: 229 or SEQ ID NO: 230.

[0402] 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: 184, 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: 228, SEQ ID NO: 229 or SEQ ID NO: 230.

[0403] The present invention also provides a pharmaceutical composition comprising any ABPC described herein. The present invention also provides a method of treating a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of any ABPC described herein.

[0404] In some instances of any of the ABPCs described herein, a composition comprising the ABPC (e.g., any of the ABPCs described herein) provides an increase (e.g., a detectable increase) in the release of toxin from target mammalian cells (e.g., any of the target mammalian cells described herein) compared to a composition comprising the same amount of a control ABPC (e.g., any of the exemplary control ABPCs described herein) (e.g., an increase of at least 1%, at least 2%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, 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%, at least 100%, at least 120%, at least 140%, at least 160%, at least 180%, at least 200%, at least 250%, at least 300%, at least 350%, at least 400%, at least 450%, at least 500%, at least 1,000%, at least 2,000%, at least 3,000%, at least 4,000%, at least 5,000%, at least 6,000%, at least 7,000%, at least 8,000%, at least 9,000% or at least 10,000%, or an increase of about 1% to about 10,000%, about 1% to about 9,000%, about 1% to about 8,000%, about 1% to about 7,000%, about 1% to about 6,000%, 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,An increase of 000%, an increase of about 1% to about 500%, an increase of about 1% to about 450%, an increase of about 1% to about 400%, an increase of about 1% to about 350%, an increase of about 1% to about 300%, an increase of about 1% to about 250%, an increase of about 1% to about 200%, an increase of about 1% to about 180%, an increase of about 1% to about 160%, an increase of about 1% to about 140%, an increase of about 1% to about 120%, an increase of about 1% to about 100%, an increase of about 1% to about 95%, an increase of about 1% to about 90%, an increase of about 1% to about 85%, an increase of about 1% to about 80%, an increase of about 1% to about 75%, an increase of about 1% to about 70%, an increase of about 1% to about 65%, an increase of about 1% to about 60%, an increase of about 1% to about 55%, an increase of about 1% to about 50%, an increase of about 1% to about 45%, an increase of about 1% to about 40%, an increase of about 1% to about 35%, an increase of about 1% to about 25%, an increase of about 1% to about 20%, an increase of about 1% to about 15%, an increase of about 1% to about 10%, an increase of about 1% to about 5%, an increase of about 2% to about 10,000%, an increase of about 2% to about 9,000%, an increase of about 2% to about 8,000%, an increase of about 2% to about 7,000%, an increase of about 2% to about 6,000%, an increase of about 2% to about 5,000%, an increase of about 2% to about 4,000%, an increase of about 2% to about 3,000%, an increase of about 2% to about 2,000%, an increase of about 2% to about 1,An increase of 000%, an increase of about 2% to about 500%, an increase of about 2% to about 450%, an increase of about 2% to about 400%, an increase of about 2% to about 350%, an increase of about 2% to about 300%, an increase of about 2% to about 250%, an increase of about 2% to about 200%, an in...

Claims

1. A pharmaceutical composition, the pharmaceutical composition comprising an effective amount of an antigen-binding protein construct (ABPC), the antigen-binding protein construct comprising: A first antigen-binding domain that is capable of specifically binding to FOLR1 or an epitope of FOLR1 presented on the surface of a target mammalian cell, wherein the first antigen-binding domain comprises: (a)(i) A heavy-chain variable domain having at least 90% identity with SEQ ID NO:1 and comprising three complementarity-determining regions (CDRs) present in SEQ ID NO: 1, except that the heavy-chain variable domain includes histidine at one or more positions selected from the group consisting of: 24, 27, 29, 31, 32, 33, 34, 50, 54, 55, 57, 58, 59, 60, 97, 98, 99, 100, 102, 103, 105, and 107 in SEQ ID NO:1; and a light-chain variable domain having at least 90% identity with SEQ ID NO:2 and comprising three CDRs present in SEQ ID NO:2, except that the light-chain variable domain includes histidine at one or more positions selected from the group consisting of: 28, 30, 31, 32, 34, 35, 36, 55, 59, 93, 94, 95, 96, 97, 98, and 100 in SEQ ID NO:2; (ii) A heavy-chain variable domain having at least 90% identity with SEQ ID NO:1 and comprising three CDRs present in SEQ ID NO:1, except that the heavy-chain variable domain includes histidine at one or more positions selected from the group consisting of: 24, 27, 29, 31, 32, 33, 34, 50, 54, 55, 57, 58, 59, 60, 97, 98, 99, 100, 102, 103, 105, and 107 in SEQ ID NO:1; and a light-chain variable domain having at least 90% identity with SEQ ID NO:2 and comprising three CDRs present in SEQ ID NO:2; or (iii) A heavy-chain variable domain having at least 90% identity with SEQ ID NO:1 and comprising three CDRs present in SEQ ID NO:1, and a light-chain variable domain having at least 90% identity with SEQ ID NO:2 and comprising three CDRs present in SEQ ID NO:2, except that the light-chain variable domain includes histidine at one or more positions selected from the group consisting of: 28, 30, 31, 32, 34, 35, 36, 55, 59, 93, 94, 95, 96, 97, 98, and 100 in SEQ ID NO:2; (b)(i) A heavy chain variable domain having at least 90% identity with SEQ ID NO: 105 and comprising three complementarity-determining regions (CDRs) present in SEQ ID NO: 105, except that the heavy chain variable domain includes histidine at one or more positions selected from the group consisting of: 29, 33, 34, 50, 51, 52, 53, 55, 56, 57, 101, 102, 103, 108, 109, 110, 111, 112, and 113 in SEQ ID NO: 105; and a light chain variable domain having at least 90% identity with SEQ ID NO: 106 and comprising three CDRs present in SEQ ID NO: 106, except that the light chain variable domain includes histidine at one or more positions selected from the group consisting of: 28, 29, 30, 31, 50, 92, 93, 94, 95, and 96 in SEQ ID NO: 106; (ii) A heavy chain variable domain having at least 90% identity with SEQ ID NO: 105 and comprising three CDRs present in SEQ ID NO: 105, except that the heavy chain variable domain includes histidine at one or more positions selected from the group consisting of: 29, 33, 34, 50, 51, 52, 53, 55, 56, 57, 101, 102, 103, 108, 109, 110, 111, 112, and 113 in SEQ ID NO: 105; and a light chain variable domain having at least 90% identity with SEQ ID NO: 106 and comprising three CDRs present in SEQ ID NO: 106; or (iii) A heavy chain variable domain having at least 90% identity with SEQ ID NO: 105 and comprising three CDRs present in SEQ ID NO: 105, and a light chain variable domain having at least 90% identity with SEQ ID NO: 106 and comprising three CDRs present in SEQ ID NO: 106, except that the light chain variable domain includes histidine at one or more positions selected from the group consisting of: 28, 29, 30, 31, 50, 92, 93, 94, 95, and 96 in SEQ ID NO: 106; or (c)(i) A heavy chain variable domain having at least 90% identity with SEQ ID NO: 184 and comprising three complementarity-determining regions (CDRs) present in SEQ ID NO: 184, except that the heavy chain variable domain includes histidine at one or more positions selected from the group consisting of: 26, 27, 28, 29, 30, 32, 33, 34, 53, 56, 57, 59, 62, 63, 103, and 105 in SEQ ID NO: 184; and a light chain variable having at least 90% identity with SEQ ID NO: 185 and comprising three CDRs present in SEQ ID NO: 185 A domain, except that one or more positions of the light chain variable domain selected from the group consisting of the following in SEQ ID NO: 185 include histidine: 29, 33, 34, 51, 52, 53, 54, 55, 90, 92, 94, 96, 97, 98, 99, and 100; (ii) a heavy chain variable domain having at least 90% identity to SEQ ID NO: 184 and comprising three CDRs present in SEQ ID NO: 184, except that one or more positions of the heavy chain variable domain selected from the group consisting of the following in SEQ ID NO: 184 include histidine: 26, 27, 28, 29, 30, 32, 33, 34, 53, 56, 57, 59, 62, 63, 103, and 105; and a light chain variable domain having at least 90% identity to SEQ ID NO: 185 and comprising three CDRs present in SEQ ID NO: 185; or (iii) a heavy chain variable domain having at least 90% identity to SEQ ID NO: 184 and comprising three CDRs present in SEQ ID NO: 184, and a light chain variable domain having at least 90% identity to SEQ ID NO: 185 and comprising three CDRs present in SEQ ID NO: 185, except that one or more positions of the light chain variable domain selected from the group consisting of the following in SEQ ID NO: 185 include histidine: 29, 33, 34, 51, 52, 53, 54, 55, 90, 92, 94, 96, 97, 98, 99, and 100, wherein: 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 (KD) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is greater than the KD at a pH of about 7.0 to about 8.

0.

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

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

4. 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 FOLR1 or an epitope of FOLR1 presented on the surface of a target mammalian cell; and a conjugated toxin, radioisotope, drug, or small molecule, wherein: (a) the first antigen-binding domain comprises: ​ ​ (A) (i) A heavy chain variable domain having at least 90% identity with SEQ ID NO:1 and comprising three complementarity-determining regions (CDRs) present in SEQ ID NO:1, except that the heavy chain variable domain includes histidine at one or more positions selected from the group consisting of: 24, 27, 29, 31, 32, 33, 34, 50, 54, 55, 57, 58, 59, 60, 97, 98, 99, 100, 102, 103, 105, and 107; and a light chain variable domain having at least 90% identity with SEQ ID NO:2 and comprising three CDRs present in SEQ ID NO:2, except that the light chain variable domain includes histidine at one or more positions selected from the group consisting of: 28, 30, 31, 32, 34, 35, 36, 55, 59, 93, 94, 95, 96, 97, 98, and 100; (ii) A heavy chain variable domain having at least 90% identity with SEQ ID NO:1 and comprising three CDRs present in SEQ ID NO:1, except that the heavy chain variable domain includes histidine at one or more positions selected from the group consisting of: 24, 27, 29, 31, 32, 33, 34, 50, 54, 55, 57, 58, 59, 60, 97, 98, 99, 100, 102, 103, 105, and 107; and a light chain variable domain having at least 90% identity with SEQ ID NO:2 and comprising three CDRs present in SEQ ID NO:2; or (iii) A heavy chain variable domain having at least 90% identity with SEQ ID NO:1 and comprising three CDRs present in SEQ ID NO:1, and a light chain variable domain having at least 90% identity with SEQ ID NO:2 and comprising three CDRs present in SEQ ID NO:2, except that the light chain variable domain includes histidine at one or more positions selected from the group consisting of: 28, 30, 31, 32, 34, 35, 36, 55, 59, 93, 94, 95, 96, 97, 98, and 100; (B)(i) A heavy chain variable domain having at least 90% identity with SEQ ID NO: 105 and comprising three complementarity-determining regions (CDRs) present in SEQ ID NO: 105, except that the heavy chain variable domain includes histidine at one or more positions selected from the group consisting of: 29, 33, 34, 50, 51, 52, 53, 55, 56, 57, 101, 102, 103, 108, 109, 110, 111, 112, and 113 in SEQ ID NO: 105; and a light chain variable domain having at least 90% identity with SEQ ID NO: 106 and comprising three CDRs present in SEQ ID NO: 106, except that the light chain variable domain includes histidine at one or more positions selected from the group consisting of: 28, 29, 30, 31, 50, 92, 93, 94, 95, and 96; (ii) A heavy chain variable domain having at least 90% identity with SEQ ID NO: 105 and comprising three CDRs present in SEQ ID NO: 105, except that the heavy chain variable domain includes histidine at one or more positions selected from the group consisting of: 29, 33, 34, 50, 51, 52, 53, 55, 56, 57, 101, 102, 103, 108, 109, 110, 111, 112, and 113 in SEQ ID NO: 105; and a light chain variable domain having at least 90% identity with SEQ ID NO: 106 and comprising three CDRs present in SEQ ID NO: 106; or (iii) A heavy chain variable domain having at least 90% identity with SEQ ID NO: 105 and comprising three CDRs present in SEQ ID NO: 105, and a light chain variable domain having at least 90% identity with SEQ ID NO: 106 and comprising three CDRs present in SEQ ID NO: 106, except that the light chain variable domain includes histidine at one or more positions selected from the group consisting of: 28, 29, 30, 31, 50, 92, 93, 94, 95, and 96; or (C)(i) A heavy chain variable domain having at least 90% identity with SEQ ID NO: 184 and comprising three complementarity-determining regions (CDRs) present in SEQ ID NO: 184, except that the heavy chain variable domain includes histidine at one or more positions selected from the group consisting of: 26, 27, 28, 29, 30, 32, 33, 34, 53, 56, 57, 59, 62, 63, 103, and 105 in SEQ ID NO: 184; and a light chain variable a domain, except that the light chain variable domain has histidine at one or more positions selected from the group consisting of the following in SEQ ID NO: 185: 29, 33, 34, 51, 52, 53, 54, 55, 90, 92, 94, 96, 97, 98, 99, and 100; (ii) a heavy chain variable domain having at least 90% identity with SEQ ID NO: 184 and comprising three CDRs present in SEQ ID NO: 184, except that the heavy chain variable domain has histidine at one or more positions selected from the group consisting of the following in SEQ ID NO: 184: 26, 27, 28, 29, 30, 32, 33, 34, 53, 56, 57, 59, 62, 63, 103, and 105; and a light chain variable domain having at least 90% identity with SEQ ID NO: 185 and comprising three CDRs present in SEQ ID NO: 185; or (iii) a heavy chain variable domain having at least 90% identity with SEQ ID NO: 184 and comprising three CDRs present in SEQ ID NO: 184, and a light chain variable domain having at least 90% identity with SEQ ID NO: 185 and comprising three CDRs present in SEQ ID NO: 185, except that the light chain variable domain has histidine at one or more positions selected from the group consisting of the following in SEQ ID NO: 185: 29, 33, 34, 51, 52, 53, 54, 55, 90, 92, 94, 96, 97, 98, 99, and 100; (b) the first antigen-binding domain has a dissociation rate at a pH of about 4.0 to about 6.5 that 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 that is greater than the KD at a pH of about 7.0 to about 8.0; and (c) the composition provides one or more of the following: an increase in toxin release in the target mammalian cells compared to a composition comprising the same amount of a control ABPC; an increase in target mammalian cell killing compared to a composition comprising the same amount of a control ABPC; and an increase in endolysosomal delivery in the target mammalian cells compared to a composition comprising 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:58, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, or SEQ ID NO:83, and / or The following heavy chain variable domains: SEQ ID NO:1, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, 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, or SEQ ID NO:103, 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 any one of SEQ ID NOs: 14, 17, 19, 21-24, 26, 28, 30, 31, 33-36, 43-46, 48, 49, 51, 53, and 85-103; (iii) the heavy chain variable domain of SEQ ID NO: 1 and a light chain variable domain that is not any one of SEQ ID NOs: 58, 60-62, 64-66, 68, 70, 74, 76-81, and 83; (b) the following light chain variable domains: SEQ ID NO: 106, SEQ ID NO: 161, SEQ ID NO: 162, SEQ ID NO: 163, SEQ ID NO: 164, SEQ ID NO: 168, SEQ ID NO: 177, SEQ ID NO: 178, SEQ ID NO: 179, SEQ ID NO: 180, SEQ ID NO: 181, or SEQ ID NO: 182, and / or the following heavy chain variable domains: SEQ ID NO: 105, SEQ ID NO: 116, 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: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 151, SEQ ID NO: 152, SEQ ID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156, wherein the first antigen-binding domain does not comprise (i) the light chain variable domain of SEQ ID NO: 106 and the heavy chain variable domain of SEQ ID NO: 105; (ii) the light chain variable domain of SEQ ID NO: 106 and a heavy chain variable domain that is not any one of SEQ ID NOs: 116, 120-126, 128-130, 144-146, and 151-156; (iii) the heavy chain variable domain of SEQ ID NO: 105 and a light chain variable domain that is not any one of SEQ ID NOs: 161-164, 168, and 177-182; or (c) The following light chain variable domains: SEQ ID NO:185, SEQ ID NO:233, 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:247, SEQ ID NO:249, SEQ ID NO:251, SEQ ID NO:253, SEQ ID NO:254, SEQ ID NO:255, SEQ ID NO:256, or SEQ ID NO:257, and / or The following heavy chain variable domains: SEQ ID NO:184, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:205, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:211, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:221, SEQ ID NO:225, or SEQ ID NO:227, wherein the first antigen-binding domain does not comprise (i) the light chain variable domain of SEQ ID NO:185 and the heavy chain variable domain of SEQ ID NO:184; (ii) the light chain variable domain of SEQ ID NO:185 and a heavy chain variable domain other than any one of SEQ ID NO:192 - 196, 198 - 200, 205, 208, 209, 211, 214, 215, 221, 225, and 227; (iii) the heavy chain variable domain of SEQ ID NO:184 and a light chain variable domain other than any one of SEQ ID NO:233, 237 - 244, 247, 249, 251, and 253 - 257.

6. The pharmaceutical composition according to any one of claims 1 - 5, wherein the composition provides: an increase in the release of 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: causes less reduction in the level of FOLR1 presented on the surface of the target mammalian cells as compared to a composition containing the same amount of control ABPC; or does not cause a detectable reduction in the level of FOLR1 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 FOLR1 and human FOLR1; or has cross-reactivity with non-human primate FOLR1, human FOLR1, and one or both of rat FOLR1 and mouse FOLR1.

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 in vivo half-life of the ABPC is reduced as compared to the in vivo half-life of control ABPC.

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 capable of specifically binding to FOLR1 or an epitope of FOLR1 presented on the surface of target mammalian cells, wherein the first antigen-binding domain comprises: (a)(i) a heavy chain variable domain having at least 90% identity with SEQ ID NO:1 and comprising three complementarity-determining regions (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: 24, 27, 29, 31, 32, 33, 34, 50, 54, 55, 57, 58, 59, 60, 97, 98, 99, 100, 102, 103, 105, and 107 in SEQ ID NO:1; and a light chain variable domain having at least 90% identity with SEQ ID NO:2 and comprising 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: 28, 30, 31, 32, 34, 35, 36, 55, 59, 93, 94, 95, 96, 97, 98 and 100; (ii) a heavy chain variable domain having at least 90% identity with SEQ ID NO:1 and comprising three CDRs present in SEQ ID NO:1, except that the heavy chain variable domain includes histidine at one or more positions selected from the group consisting of: 24, 27, 29, 31, 32, 33, 34, 50, 54, 55, 57, 58, 59, 60, 97, 98, 99, 100, 102, 103, 105 and 107; and a light chain variable domain having at least 90% identity with SEQ ID NO:2 and comprising three CDRs present in SEQ ID NO:2; or (iii) a heavy chain variable domain having at least 90% identity with SEQ ID NO:1 and comprising three CDRs present in SEQ ID NO:1, and a light chain variable domain having at least 90% identity with SEQ ID NO:2 and comprising three CDRs present in SEQ ID NO:2, except that the light chain variable domain includes histidine at one or more positions selected from the group consisting of: 28, 30, 31, 32, 34, 35, 36, 55, 59, 93, 94, 95, 96, 97, 98 and 100; (b) (i) a heavy chain variable domain having at least 90% identity with SEQ ID NO:105 and comprising three complementarity determining regions (CDRs) present in SEQ ID NO:105, except that the heavy chain variable domain includes histidine at one or more positions selected from the group consisting of: 29, 33, 34, 50, 51, 52, 53, 55, 56, 57, 101, 102, 103, 108, 109, 110, 111, 112 and 113; and a light chain variable domain having at least 90% identity with SEQ ID NO:106 and comprising three CDRs present in SEQ ID NO:106, except that the light chain variable domain includes histidine at one or more positions selected from the group consisting of: 28, 29, 30, 31, 50, 92, 93, 94, 95 and 96; (ii) a heavy chain variable domain having at least 90% identity with SEQ ID NO:105 and comprising three CDRs present in SEQ ID NO:105, except that the heavy chain variable domain includes histidine at one or more positions selected from the group consisting of Histidine: 29, 33, 34, 50, 51, 52, 53, 55, 56, 57, 101, 102, 103, 108, 109, 110, 111, 112, and 113; and a light chain variable domain having at least 90% identity to SEQ ID NO:106 and comprising three CDRs present in SEQ ID NO:106; or (iii) a heavy chain variable domain having at least 90% identity to SEQ ID NO:105 and comprising three CDRs present in SEQ ID NO:105, and a light chain variable domain having at least 90% identity to SEQ ID NO:106 and comprising three CDRs present in SEQ ID NO:106, except that the light chain variable domain includes histidine at one or more positions selected from the group consisting of: 28, 29, 30, 31, 50, 92, 93, 94, 95, and 96 in SEQ ID NO:106; or (c)(i) a heavy chain variable domain having at least 90% identity to SEQ ID NO:184 and comprising three complementarity-determining regions (CDRs) present in SEQ ID NO:184, except that the heavy chain variable domain includes histidine at one or more positions selected from the group consisting of: 26, 27, 28, 29, 30, 32, 33, 34, 53, 56, 57, 59, 62, 63, 103, and 105 in SEQ ID NO:184; and a light chain variable domain having at least 90% identity to SEQ ID NO:185 and comprising three CDRs present in SEQ ID NO:185, except that the light chain variable domain includes histidine at one or more positions selected from the group consisting of: 29, 33, 34, 51, 52, 53, 54, 55, 90, 92, 94, 96, 97, 98, 99, and 100 in SEQ ID NO:185; (ii) a heavy chain variable domain having at least 90% identity to SEQ ID NO:184 and comprising three CDRs present in SEQ ID NO:184, except that the heavy chain variable domain includes histidine at one or more positions selected from the group consisting of: 26, 27, 28, 29, 30, 32, 33, 34, 53, 56, 57, 59, 62, 63, 103, and 105; and a light chain variable domain having at least 90% identity to SEQ ID NO:185 and comprising three CDRs present in SEQ ID NO:185; or ​ ​ ​ ​ ​ ​ ​ ​ (iii) a heavy chain variable domain having at least 90% identity to SEQ ID NO: 184 and comprising three CDRs present in SEQ ID NO: 184, and a light chain variable domain having at least 90% identity to SEQ ID NO: 185 and comprising three CDRs present in SEQ ID NO: 185, except that the light chain variable domain comprises histidine at one or more positions selected from the group consisting of: 29, 33, 34, 51, 52, 53, 54, 55, 90, 92, 94, 96, 97, 98, 99 and 100 in SEQ ID NO: 185; and wherein: 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 (KD) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is greater than the KD at a pH of about 7.0 to about 8.

0.

19. The ABPC according to claim 18, wherein the ABPC is degraded in the target mammalian cell after the ABPC is internalized by 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 capable of specifically binding FOLR1 or an epitope of FOLR1 presented on the surface of a target mammalian cell; and a conjugated toxin, radioisotope, drug or small molecule, wherein: (a) the first antigen-binding domain comprises: (A) (i) a heavy chain variable domain having at least 90% identity to SEQ ID NO: 1 and comprising three complementarity-determining regions (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: 24, 27, 29, 31, 32, 33, 34, 50, 54, 55, 57, 58, 59, 60, 97, 98, 99, 100, 102, 103, 105 and 107 in SEQ ID NO: 1; and a light chain variable domain having at least 90% identity to SEQ ID NO: 2 and comprising 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: 28, 30, 31, 32, 34, 35, 36, 55, 59, 93, 94, 95, 96, 97, 98 and 100 in SEQ ID NO: 2; (ii) a heavy chain variable domain having at least 90% identity to SEQ ID NO:1 and comprising 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: 24, 27, 29, 31, 32, 33, 34, 50, 54, 55, 57, 58, 59, 60, 97, 98, 99, 100, 102, 103, 105 and 107; and a light chain variable domain having at least 90% identity to SEQ ID NO:2 and comprising the three CDRs present in SEQ ID NO:2; or (iii) a heavy chain variable domain having at least 90% identity to SEQ ID NO:1 and comprising the three CDRs present in SEQ ID NO:1, and a light chain variable domain having at least 90% identity to SEQ ID NO:2 and comprising 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: 28, 30, 31, 32, 34, 35, 36, 55, 59, 93, 94, 95, 96, 97, 98 and 100; (B) (i) a heavy chain variable domain having at least 90% identity to SEQ ID NO:105 and comprising the three complementarity determining regions (CDRs) present in SEQ ID NO:105, except that the heavy chain variable domain comprises histidine at one or more positions selected from the group consisting of: 29, 33, 34, 50, 51, 52, 53, 55, 56, 57, 101, 102, 103, 108, 109, 110, 111, 112 and 113; and a light chain variable domain having at least 90% identity to SEQ ID NO:106 and comprising the three CDRs present in SEQ ID NO:106, except that the light chain variable domain comprises histidine at one or more positions selected from the group consisting of: 28, 29, 30, 31, 50, 92, 93, 94, 95 and 96; (ii) a heavy chain variable domain having at least 90% identity to SEQ ID NO:105 and comprising the three CDRs present in SEQ ID NO:105, except that the heavy chain variable domain comprises histidine at one or more positions selected from the group consisting of: 29, 33, 34, 50, 51, 52, 53, 55, 56, 57, 101, 102, 103, 108, 109, 110, 111, 112 and 113; and having at least 90% identity to SEQ ID NO:106 A light chain variable domain having at least 90% identity and comprising three CDRs present in SEQ ID NO: 106; or (iii) A heavy chain variable domain having at least 90% identity with SEQ ID NO: 105 and comprising three CDRs present in SEQ ID NO: 105, and a light chain variable domain having at least 90% identity with SEQ ID NO: 106 and comprising three CDRs present in SEQ ID NO: 106, except that the light chain variable domain includes histidine at one or more positions selected from the group consisting of: 28, 29, 30, 31, 50, 92, 93, 94, 95 and 96 in SEQ ID NO: 106; or (C)(i) A heavy chain variable domain having at least 90% identity with SEQ ID NO: 184 and comprising three complementarity determining regions (CDRs) present in SEQ ID NO: 184, except that the heavy chain variable domain includes histidine at one or more positions selected from the group consisting of: 26, 27, 28, 29, 30, 32, 33, 34, 53, 56, 57, 59, 62, 63, 103 and 105 in SEQ ID NO: 184; and a light chain variable domain having at least 90% identity with SEQ ID NO: 185 and comprising three CDRs present in SEQ ID NO: 185, except that the light chain variable domain includes histidine at one or more positions selected from the group consisting of: 29, 33, 34, 51, 52, 53, 54, 55, 90, 92, 94, 96, 97, 98, 99 and 100 in SEQ ID NO: 185; (ii) A heavy chain variable domain having at least 90% identity with SEQ ID NO: 184 and comprising three CDRs present in SEQ ID NO: 184, except that the heavy chain variable domain includes histidine at one or more positions selected from the group consisting of: 26, 27, 28, 29, 30, 32, 33, 34, 53, 56, 57, 59, 62, 63, 103 and 105 in SEQ ID NO: 184; and a light chain variable domain having at least 90% identity with SEQ ID NO: 185 and comprising three CDRs present in SEQ ID NO: 185; or (iii) A heavy chain variable domain having at least 90% identity with SEQ ID NO: 184 and comprising three CDRs present in SEQ ID NO: 184, and a light chain variable domain having at least 90% identity with SEQ ID NO: 185 and comprising three CDRs present in SEQ ID NO: 185, except that the light chain variable domain in SEQ ID NO: 185 ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ One or more positions selected from the group consisting of 185 include histidine: 29, 33, 34, 51, 52, 53, 54, 55, 90, 92, 94, 96, 97, 98, 99, and 100; (b) 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 (KD) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is greater than the KD at a pH of about 7.0 to about 8.0; and (c) The composition provides one or more of the following: An increase in toxin release in the target mammalian cells compared to a composition comprising the same amount of control ABPC; An increase in target mammalian cell killing compared to a composition comprising the same amount of control ABPC; and An increase in endolysosomal delivery in the target mammalian cells compared to a composition comprising the same amount of 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:58, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:68, SEQ IDNO:70, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ IDNO:80, SEQ ID NO:81, or SEQ ID NO:83, and / or The following heavy chain variable domains: SEQ ID NO:1, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, 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, or SEQ ID NO:103, 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 any one of SEQ ID NO:14, 17, 19, 21-24, 26, 28, 30, 31, 33-36, 43-46, 48, 49, 51, 53, and 85-103; (iii) the heavy chain variable domain of SEQ ID NO:1 and a light chain variable domain that is not any one of SEQ ID NO:58, 60-62, 64-66, 68, 70, 74, 76-81, and 83; (b) The following light chain variable domains: SEQ ID NO:106, SEQ ID NO:161, SEQ ID NO:162, SEQ ID NO:163, SEQ ID NO:164, SEQ ID NO:168, SEQ ID NO:177, SEQ ID NO:178, SEQ ID NO:179, SEQ ID NO:180, SEQ ID NO:181, or SEQ ID NO:182, and / or The following heavy chain variable domains: SEQ ID NO:105, SEQ ID NO:116, 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:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:144, SEQ ID NO:145, SEQ ID NO:146, SEQ ID NO:151, SEQ ID NO:152, SEQ ID NO:153, SEQ ID NO:154, SEQ ID NO:155, or SEQ ID NO:156, wherein the first antigen-binding domain does not comprise (i) the light chain variable domain of SEQ ID NO:106 and the heavy chain variable domain of SEQ ID NO:105; (ii) the light chain variable domain of SEQ ID NO:106 and a heavy chain variable domain other than any one of SEQ ID NO:116, 120-126, 128-130, 144-146, and 151-156; (iii) the heavy chain variable domain of SEQ ID NO:105 and a light chain variable domain other than any one of SEQ ID NO:161-164, 168, and 177-182; or (c) The following light chain variable domains: SEQ ID NO:185, SEQ ID NO:233, 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:247, SEQ ID NO:249, SEQ ID NO:251, SEQ ID NO:253, SEQ ID NO:254, SEQ ID NO:255, SEQ ID NO:256, or SEQ ID NO:257, and / or The following heavy chain variable domains: SEQ ID NO:184, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:205, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:211, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:221, SEQ ID NO:225, or SEQ ID NO:227, wherein the first antigen-binding domain does not comprise (i) the light chain variable domain of SEQ ID NO:185 and the heavy chain variable domain of SEQ ID NO:184; (ii) the light chain variable domain of SEQ ID NO:185 and a heavy chain variable domain that is not any one of SEQ ID NO:192 - 196, 198 - 200, 205, 208, 209, 211, 214, 215, 221, 225, and 227; (iii) the heavy chain variable domain of SEQ ID NO:184 and a light chain variable domain that is not any one of SEQ ID NO:233, 237 - 244, 247, 249, 251, and 253 - 257.

23. The ABPC according to any one of claims 18 - 22, wherein the composition comprising the ABPC provides: 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 of a decrease in the level of FOLR1 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 result in a detectable decrease in the level of FOLR1 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 FOLR1 and human FOLR1; or Is cross-reactive with one or both of non-human primate FOLR1, human FOLR1, and rat FOLR1 and mouse FOLR1.

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: VH domain, VHH domain, VNAR domain, and 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 reduced 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 a population of cancer cells having FOLR1 or an epitope of FOLR1 presented on the surface, the method comprising: Administering 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 to a subject identified as having cancer, the cancer being characterized by having the population of cancer cells.

37. 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 reducing the tumor volume in a subject, wherein the tumor is characterized by a population of cancer cells having FOLR1 or an epitope of FOLR1 presented on the surface, the method comprising: Administering 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 to a subject identified as having cancer, the cancer being characterized by having the population of cancer cells.

38. 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 inducing cell death in cancer cells in a subject, wherein the cancer cells have FOLR1 or an epitope of FOLR1 presented on the surface, wherein the method comprising: Administering a therapeutically effective amount of a pharmaceutical composition as described in any one of claims 1-17 or an ABPC as described in any one of claims 18-34 to a subject identified as having cancer, said cancer being characterized by having said population of cancer cells.

39. Use of a pharmaceutical composition as described in any one of claims 1-17 or an ABPC as described in any one of claims 18-34 in the manufacture of a medicament for reducing the risk of developing metastases or reducing the risk of developing additional metastases in a subject having cancer, wherein said cancer is characterized by having a population of cancer cells with FOLR1 or an epitope of FOLR1 presented on the surface, said method comprising: Administering a therapeutically effective amount of a pharmaceutical composition as described in any one of claims 1-17 or an ABPC as described in any one of claims 18-34 to a subject identified as having cancer, said cancer being characterized by having said population of cancer cells.

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