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WO2025212647A1 - Antigen-binding protein constructs and uses thereof - Google Patents

Antigen-binding protein constructs and uses thereof

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Publication number
WO2025212647A1
WO2025212647A1 PCT/US2025/022538 US2025022538W WO2025212647A1 WO 2025212647 A1 WO2025212647 A1 WO 2025212647A1 US 2025022538 W US2025022538 W US 2025022538W WO 2025212647 A1 WO2025212647 A1 WO 2025212647A1
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seq
sequence
amino acid
hcvd
cdrs
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French (fr)
Inventor
Brian P. FISKE
Nimish GERA
David NIQUILLE
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Mythic Therapeutics Inc
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Mythic Therapeutics Inc
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/68031—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being an auristatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/68035—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a pyrrolobenzodiazepine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6849—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/77—Internalization into the cell
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance

Definitions

  • the present disclosure relates to the field of antigen-binding molecules.
  • the present disclosure provides novel Delta-like protein 3 (DLL3)-binding proteins, compositions comprising such proteins, and methods of using such proteins for the treatment of DLL3-positive cancers. More specifically, the disclosure relates to DLL3-binding proteins having enhanced physicochemical properties.
  • DLL3 is a member of the Delta/Serrate/Lag-2 (DSL) family of Notch ligands.
  • DLL3 is primarily localized intracellularly rather than at the cell surface, and has been shown to inhibit Notch signaling through cis-inhibition rather than activating Notch through trans-activation. DLL3 plays an important role during embryonic development, particularly in somitogenesis and neurogenesis, but has limited expression in normal adult tissues. [0006] Significantly, DLL3 has been identified as a promising therapeutic target due to its aberrant expression in certain high-grade neuroendocrine tumors, while maintaining minimal expression in normal adult tissues.
  • the present disclosure provides an antibody, antigen-binding protein construct (ABPC), or antigen-binding domain (ABD) thereof, comprising a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein (a) the HCVD comprises an H-CDR1 sequence, an H-CDR2 sequence, and an H-CDR3 sequence selected from the group consisting of the sequences of one of (i) to (xii): (i) to (xii): (i) the sequences of SEQ ID NO: 5, SEQ ID NO: 6, and SEQ ID NO: 7, respectively; (ii) the sequences of SEQ ID NO: 13, SEQ ID NO: 14, and SEQ ID NO: 15, respectively; (iii) the sequences of SEQ ID NO: 21, SEQ ID NO: 22, and SEQ ID NO: 23, respectively; (iv) the sequences of SEQ ID NO: 29, SEQ ID NO: 30, and SEQ ID NO: 31, respectively; (v) the sequences of SEQ ID NO:
  • the antibody or antigen-binding protein construct comprises a heavy and light chain as set forth in one of the following pairs: the sequence of SEQ ID NO: 99 and the sequence of SEQ ID NO: 100, the sequence of SEQ ID NO: 101 and the sequence of SEQ ID NO: 102, the sequence of SEQ ID NO: 103 and the sequence of SEQ ID NO: 104, the sequence of SEQ ID NO: 105 and the sequence of SEQ ID NO: 106, the sequence of SEQ ID NO: 107 and the sequence of SEQ ID NO: 108, the sequence of SEQ ID NO: 109 and the sequence of SEQ ID NO: 110, the sequence of SEQ ID NO: 111 and the sequence of SEQ ID NO: 112, the sequence of SEQ ID NO: 113 and the sequence of SEQ ID NO: 114, the sequence of SEQ ID NO: 115 and the sequence of SEQ ID NO: 116, the sequence of SEQ ID NO: 117 and the sequence of SEQ ID NO: 118, the sequence of SEQ
  • the antibody, antigen-binding protein construct, or ABD includes one or more of the following characteristics: (a) a heavy chain variable domain (HCVD) sequence that is at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identical to any one of SEQ ID NO: 3, SEQ ID NO: 11, SEQ ID NO: 19, SEQ ID NO: 27, SEQ ID NO: 35, SEQ ID NO: 43, Attorney Docket No.: 45395-0068WO1 SEQ ID NO: 51, SEQ ID NO: 59, SEQ ID NO: 67, SEQ ID NO: 75, SEQ ID NO: 83, and SEQ ID NO: 91; and/or (b) a light chain variable domain (LCVD) sequence that is at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identical to any one of SEQ ID NO: SEQ ID NO: 4, SEQ ID NO: 12, SEQ ID NO: 20, SEQ ID NO: 28, S
  • the present disclosure provides an antibody, antigen-binding protein fragment, or ABD comprising an HCVD and an LCVD, wherein: (a) the HCVD comprises an amino acid sequence of any one of SEQ ID NO: 3, SEQ ID NO: 11, SEQ ID NO: 19, SEQ ID NO: 27, SEQ ID NO: 35, SEQ ID NO: 43, SEQ ID NO: 51, SEQ ID NO: 59, SEQ ID NO: 67, SEQ ID NO: 75, SEQ ID NO: 83, and SEQ ID NO: 91; and/or (b) the LCVD comprises an amino acid sequence one any one of SEQ ID NO: 4, SEQ ID NO: 12, SEQ ID NO: 20, SEQ ID NO: 28, SEQ ID NO: 36, SEQ ID NO: 44, SEQ ID NO: 52, SEQ ID NO: 60, SEQ ID NO: 68, SEQ ID NO: 76, SEQ ID NO: 84, and SEQ ID NO: 92.
  • the HCVD comprises an amino acid sequence of any one of S
  • the HCVD amino acid sequence and the LCVD amino acid sequence is selected from the group consisting of: the sequences of SEQ ID NO: 3 and SEQ ID NO: 4, respectively; the sequences of SEQ ID NO: 11 and SEQ ID NO: 12, respectively; the sequences of SEQ ID NO: 19 and SEQ ID NO: 20; the sequences of SEQ ID NO: 27 and SEQ ID NO: 28, respectively; the sequences of SEQ ID NO: 35 and SEQ ID NO: 36, respectively; the sequences of SEQ ID NO: 43 and SEQ ID NO: 44, respectively; the sequences of SEQ ID NO: 51 and SEQ ID NO: 52, respectively; the sequences of SEQ ID NO: 59 and SEQ ID NO: 59, respectively; the sequences of SEQ ID NO: 67 and SEQ ID NO: 67, respectively; the sequences of SEQ ID NO: 75 and SEQ ID NO: 76, respectively; the sequences of SEQ ID NO:
  • the antibody or antigen-binding protein construct comprises a heavy and light chain as set forth in one of the following pairs of sequences: SEQ ID NO: 219 and SEQ ID NO: 220, respectively; SEQ ID NO: 221 and SEQ ID NO: 222, respectively; SEQ ID NO: 223 and SEQ ID NO: 224, respectively; SEQ ID NO: 225 and SEQ ID NO: 226, respectively; SEQ ID NO: 227 and SEQ ID NO: 228, respectively; SEQ ID NO: 229 and SEQ ID NO: 230, respectively; SEQ ID NO: 231 and SEQ ID NO: 232, respectively; SEQ ID NO: 233 and SEQ ID NO: 234, respectively; SEQ ID NO: 235 and SEQ ID NO: 236, respectively; SEQ ID NO: 237 and SEQ ID Attorney Docket No.: 45395-0068WO1 NO: 238, respectively; SEQ ID NO: 239 and SEQ ID NO: 240, respectively; and SEQ ID NO: 241 and S
  • the present disclosure provides isolated nucleic acids encoding the HCVD and/or LCVD of the antibody, ABPC, or ABD as disclosed herein, wherein the nucleic acids comprise: [0025] (a) a polynucleotide encoding the HCVD comprising an H-CDR1 sequence, an H-CDR2 sequence, and an H-CDR3 sequence selected from: [0026] (i) polynucleotides encoding the sequences of SEQ ID NO: 5, SEQ ID NO: 6, and SEQ ID NO: 7, respectively; [0027] (ii) polynucleotides encoding the sequences of SEQ ID NO: 13, SEQ ID NO: 14, and SEQ ID NO: 15, respectively; [0028] (iii) polynucleotides encoding the sequences of SEQ ID NO: 21, SEQ ID NO: 22, and SEQ ID NO: 23, respectively; [0029] (iv) polynucleotides encoding
  • the present disclosure provides isolated nucleic acids encoding the antibody, ABPC, or ABD of any of the preceding claims, wherein the nucleic acids comprise: [0076] (a) a polynucleotide encoding a HCVD comprising an amino acid sequence selected from SEQ ID NO: 3, SEQ ID NO: 11, SEQ ID NO: 19, SEQ ID NO: 27, SEQ ID NO: 35, SEQ ID NO: 43, SEQ ID NO: 51, SEQ ID NO: 59, SEQ ID NO: 67, SEQ ID NO: 75, SEQ ID NO: 83, and SEQ ID NO: 91; and/or [0077] (b) a polynucleotide encoding a LCVD comprising an amino acid sequence selected from SEQ ID NO: 4, SEQ ID NO: 12, SEQ ID NO: 20, SEQ ID NO: 28, SEQ ID NO: 36, SEQ ID NO: 44, SEQ ID NO: 52, SEQ ID NO: 60, SEQ ID
  • the present disclosure provides isolated nucleic acids encoding the antibody or ABPC of any of the preceding claims, wherein the nucleic acids comprise polynucleotides encoding the heavy chain and light chain pairs selected from: [0079] (i) polynucleotides encoding the sequences of SEQ ID NO: 99 and SEQ ID NO: 100, respectively; [0080] (ii) polynucleotides encoding the sequences of SEQ ID NO: 101 and SEQ ID NO: 102, respectively; Attorney Docket No.: 45395-0068WO1 [0081] (iii) polynucleotides encoding the sequences of SEQ ID NO: 103 and SEQ ID NO: 104, respectively; [0082] (iv) polynucleotides encoding the sequences of SEQ ID NO: 105 and SEQ ID NO: 106, respectively; [0083] (v) polynucleotides encoding the sequences of
  • the present disclosure provides isolated nucleic acids that have at least 80% sequence identity to a polynucleotide encoding the HCVD and/or LCVD of the antibody, ABPC, or ABD of any of the preceding claims.
  • the nucleic acids have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to a polynucleotide encoding the HCVD and/or LCVD.
  • the present disclosure encompasses all nucleotide sequences encoding the amino acid sequences of the antibodies, ABPCs, or ABDs described herein due to the degeneracy of the genetic code.
  • the genetic code is redundant, with multiple codons often encoding the same amino acid.
  • different nucleotide sequences can encode identical amino acid sequences of the antibodies, ABPCs, or ABDs.
  • the present disclosure encompasses all such degenerate nucleotide sequences that encode the amino acid sequences described herein.
  • the present disclosure further provides expression vectors comprising the nucleic acids described herein, as well as host cells comprising such expression vectors.
  • the host cell is selected from the group consisting of E. coli, yeast, insect cells, and mammalian cells.
  • the mammalian cell is a CHO cell, HEK293 cell, or NS0 cell.
  • the present disclosure provides methods of producing an antibody, ABPC, or ABD comprising culturing the host cell under conditions suitable for expression of the nucleic acids and recovering the antibody, ABPC, or ABD from the culture.
  • the antibody, antigen-binding antibody construct, or ABD includes one or more of the following characteristics: (a) a heavy chain variable domain (HCVD) sequence that is at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identical to the HCVD sequence of any one of SEQ ID NO: 123, SEQ ID NO: 131, SEQ ID NO: 139, SEQ ID NO: 147, SEQ ID NO: 155, SEQ ID NO: 163, SEQ ID NO: 171, SEQ ID NO: 179, SEQ ID NO: 187, SEQ ID NO: 195, SEQ ID NO: 203, and SEQ ID NO: 211; and/or (b) a light chain variable domain (LCVD) sequence that is at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identical to the LCVD sequence of any one of SEQ ID NO: 124, SEQ ID NO: 132, SEQ ID NO: 140
  • the present disclosure provides an antibody, antigen-binding protein construct, or ABD comprising an HCVD and an LCVD, wherein: (a) the HCVD comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 123, SEQ ID NO: 131, SEQ ID NO: 139, SEQ ID NO: 147, SEQ ID NO: 155, SEQ ID NO: 163, SEQ ID NO: 171, SEQ ID NO: 179, SEQ ID NO: 187, SEQ ID NO: 195, SEQ ID NO: 203, and SEQ ID NO: 211; and/or (b) the LCVD comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 124, SEQ ID NO: 132, SEQ ID NO: 140, SEQ ID NO: 148, SEQ ID NO: 156, SEQ ID NO: 164, SEQ ID NO: 172, SEQ ID NO: 180, SEQ ID NO: 188, SEQ ID NO: 196,
  • the HCVD amino acid sequence and the LCVD amino acid sequence is selected from the group consisting of: SEQ ID NO: 123 and SEQ ID NO: 124, respectively; SEQ ID NO: 131 and SEQ ID NO: 132, respectively; SEQ ID NO: 139 and SEQ ID NO: 140; SEQ ID NO: 147 and SEQ ID NO: 148, respectively; SEQ ID NO: 155 and SEQ ID NO: 156, respectively; SEQ ID NO: 163 and SEQ ID NO: 164, respectively; SEQ ID NO: 171 and SEQ ID NO: 172, respectively; SEQ ID NO: 179 and SEQ ID NO: 179, respectively; SEQ ID NO: 187 and SEQ ID NO: 187, respectively; SEQ ID NO: 195 and SEQ ID NO: 196, respectively; SEQ ID NO: 203 and SEQ ID NO: 204, respectively; and SEQ ID NO: 211 and SEQ ID NO:
  • the DLL3 polypeptide comprises an amino acid sequence selected from the group consisting of the sequences of SEQ ID NO: 1 (mature human DLL3) or SEQ ID NO: 2 (human DLL3 extracellular domain).
  • the antibody, ABPC, or ABD undergoes intracellular internalization when the antibody, ABPC, or ABD binds to a DLL3 polypeptide expressed on a cell surface (e.g., a tumor cell surface).
  • the antibody, antigen binding protein construct (ABPC), or antigen binding domain (ABD) is cytotoxic or cytostatic to the target mammalian cell.
  • the antibody, ABPC, or ABD is cross-reactive with a non-human primate DLL3 and human DLL3. In some aspects, the antibody, ABPC, or ABD is cross-reactive with a non-human primate DLL3, a human DLL3, and one or both of rat DLL3 and a mouse DLL3. In some aspects, the antibody, ABPC, or ABD is cross-reactive with a non-human primate DLL3, a human DLL3, a rat DLL3, and a mouse DLL3. In some aspects, the antibody, the ABPC, or ABD binds to an epitope of DLL3 that is present on the surface of cells from an Old World Monkey.
  • the present disclosure provides a method for treating a DLL3-positive cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of any of the ABPCs, antibodies, or ABDs described herein , wherein the ABPC, antibody, or ABD is conjugated to at least one additional therapeutic agent.
  • additional therapeutic agents include, but are not limited to, isotopes, drugs, toxins, cytokines, enzymes, enzyme inhibitors, hormones, hormone antagonists, growth factors, radionuclides, metals, liposomes, nanoparticles, RNA, DNA or any combination thereof.
  • Humanized DLL3-binding protein light chain CDR sequences MYT# L-CDR1 Seq ID L-CDR2 Seq ID L-CDR3 Seq ID 8 812 QASQSVYSNNYLA 128 RASKLAS 129 QGYFGGGING 130 [0139]
  • Exemplary heavy chains and light chains that can be present in any of the ABPCs and antibodies described herein are shown in Table 8 below.
  • CDR sequences are shown in bold (as defined by Kabat-IMGT) and variable domain framework regions and constant domain sequences are not shown in bold. Table 8.
  • HCVDs and LCVDs include four framework regions, and can be referred to as: “FR1,” “FR2,” “FR3,” and “FR4.”
  • An HCVD has the following format: FR1- H-CDR1-FR2-H-CDR2-FR3-H-CDR3-FR4.
  • An LCVD has the following format: FR1-L-CDR1- FR2-L-CDR2-FR3-L-CDR3-FR4.
  • references to percent or percentage identity when referring to a variable domain refers to the percent sequence identity that is maintained over the length of the reference variable domain without substitutions in the CDR regions (i.e., CDR1, CDR2, and CDR3).
  • a recitation of a variable domain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 99% identical to a reference sequence refers to the percent sequence identity across the length of the reference sequence without substitutions to the CDR sequences (i.e., substitutions are only present in one or more framework regions of the variable domain).
  • the substitution(s) in one or more framework regions are conservative amino acid substitutions.
  • the variable domains (HCVD or LCVD) described herein can have an amino acid sequence at least about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, Attorney Docket No.: 45395-0068WO1 98%, or 99% identity to a reference sequence when the CDR sequences do not include any substitutions.
  • variable domains (HCVD or LCVD) of the present disclosure can include 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more amino acid substitutions compared to a reference variable domain sequence so long as the CDR sequences of the variable domains do not include any amino acid substitutions (i.e., substitutions are only present in the framework regions of the variable domain).
  • the variable domains (HCVD or LCVD) can include 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more amino acid substitutions so long as the CDR sequences of the variable domain does not include any amino acid substitutions.
  • the substitution(s) in one or more framework regions are conservative amino acid substitutions.
  • the present disclosure provides antigen-binding protein (ABP) constructs (ABPCs) that display or may be modified to display enhanced efficacy in toxin liberation in a target mammalian cell, an increase in cell killing, and an increase in endolysosomal delivery.
  • ABSP antigen-binding protein
  • compositions including an effective amount of an ABPC including: a first antigen-binding domain (ABD) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell, where: (a) the dissociation rate of the first ABD 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 ABD 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.
  • ABS first antigen-binding domain
  • the first ABD includes a heavy chain variable domain (HCVD) of an HCVD having the amino acid sequence of one of SEQ ID NO: 3, SEQ ID NO: 11, SEQ ID NO: 19, SEQ ID NO: 27, SEQ ID NO: 35, SEQ ID NO: 43, SEQ ID NO: 51, SEQ ID NO: 59, SEQ ID NO: 67, SEQ ID NO: 75, SEQ ID NO: 83, and SEQ ID NO: 91, each HCVD optionally with at least 1 histidine substitution (e.g., one, two, three, four, or five total histidine substitutions across the set of three H-CDRs).
  • HCVD heavy chain variable domain
  • the first ABD includes a light chain variable domain (LCVD) of an LCVD having the amino acid sequence of one of SEQ ID NO: 4, SEQ ID NO: 12, SEQ ID NO: 20, SEQ ID NO: 28, SEQ ID NO: 36, SEQ ID NO: 44, SEQ ID NO: 52, SEQ ID NO: 60, SEQ ID Attorney Docket No.: 45395-0068WO1 NO: 68, SEQ ID NO: 76, SEQ ID NO: 84, and SEQ ID NO: 92, each LCVD optionally with at least 1 histidine substitution (e.g., one, two, three, four, or five total histidine substitutions across the set of three L-CDRs).
  • each LCVD optionally with at least 1 histidine substitution (e.g., one, two, three, four, or five total histidine substitutions across the set of three L-CDRs).
  • the first ABD includes one of (a) to (l): (a) an HCVD of SEQ ID NO: 3 and/or an LCVD of SEQ ID NO: 4; (b) an HCVD of SEQ ID NO: 11 and/or an LCVD of SEQ ID NO: 12; (c) an HCVD of SEQ ID NO: 19 and/or an LCVD of SEQ ID NO: 20; (d) an HCVD of SEQ ID NO: 27 and/or an LCVD of SEQ ID NO: 28; (e) an HCVD of SEQ ID NO: 35 and/or an LCVD of SEQ ID NO: 36; (f) an HCVD of 43 and/or an LCVD of SEQ ID NO: 44; (g) an HCVD of 51 and/or an LCVD of SEQ ID NO: 52; (h) an HCVD of 59 and/or an LCVD of SEQ ID NO: 60; (i) an HCVD of r SEQ ID NO
  • the first ABD includes one of (a) to (l): (a) an HCVD including the amino acid sequence of SEQ ID NO: 123 and/or an LCVD including the amino acid sequence of SEQ ID NO: 124; (b) an HCVD including the amino acid sequence of SEQ ID NO: 131 and/or an LCVD including the amino acid sequence of SEQ ID NO: 132; (c) an HCVD including the amino acid sequence of SEQ ID NO: 139 and/or an LCVD including the amino acid sequence of SEQ ID NO: 140; (d) an HCVD including the amino acid sequence of SEQ ID NO: 147 and/or an LCVD including the amino acid sequence of SEQ ID NO: 148; (e) an HCVD including the amino acid sequence of SEQ ID NO: 155 and/or an LCVD including the amino acid sequence of SEQ ID NO: 156; (f) an HCVD including the amino acid sequence of SEQ ID NO: 163 and/or an LCVD including the amino acid sequence of SEQ
  • the first ABD includes one of (a) to (l): (a) an HCVD including the sequence of SEQ ID NO: 3 and/or an LCVD including the sequence of SEQ ID NO: 4; (b) an HCVD including the sequence of SEQ ID NO: 11 and/or an LCVD including the sequence of SEQ ID NO: 12; (c) an HCVD including the sequence of SEQ ID NO: 19 and/or an LCVD including the sequence of SEQ ID NO: 20; (d) an HCVD including the sequence of SEQ ID NO: 27 and/or an LCVD including the sequence of SEQ ID NO: 28; (e) an HCVD including the sequence of SEQ ID NO: 35 and/or an LCVD including the sequence of SEQ ID NO: 36; (f) an HCVD including the sequence of SEQ ID NO: 43 and/or an LCVD including the sequence of SEQ ID NO: 44; (g) an HCVD including the sequence of SEQ ID NO: 51 and/or an L
  • the first ABD includes one of (a) to (l): (a) an HCVD including the sequence of SEQ ID NO: 123 and/or an LCVD including the sequence of SEQ ID NO: 124; (b) an HCVD including the sequence of SEQ ID NO: 131 and/or an LCVD including the sequence of SEQ ID NO: 132; (c) an HCVD including the sequence of SEQ ID NO: 139 and/or an LCVD including the sequence of SEQ ID NO: 140; (d) an HCVD including the sequence of SEQ ID NO: 147 and/or an LCVD including the sequence of SEQ ID NO: 148; (e) an HCVD including the Attorney Docket No.: 45395-0068WO1 sequence of SEQ ID NO: 155 and/or an LCVD including the sequence of SEQ ID NO: 156; (f) an HCVD including the sequence of SEQ ID NO: 163 and/or an LCVD including the sequence of SEQ ID NO:
  • the first ABD includes a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein (a) the HCVD comprises an H-CDR1 sequence, an H-CDR2 sequence, and an H-CDR3 sequence selected from the group consisting of one of (i) to (xii): (i) the sequences of SEQ ID NO: 5, SEQ ID NO: 6, and SEQ ID NO: 7, respectively; (ii) the sequences of SEQ ID NO: 13, SEQ ID NO: 14, and SEQ ID NO: 15, respectively; (iii) the sequences of SEQ ID NO: 21, SEQ ID NO: 22, and SEQ ID NO: 23, respectively; (iv) the sequences of SEQ ID NO: 29, SEQ ID NO: 30, and SEQ ID NO: 31, respectively; (v) the sequences of SEQ ID NO: 37, SEQ ID NO: 38, and SEQ ID NO: 39, respectively; (vi) the sequences of SEQ ID NO: 45, SEQ ID NO:
  • the first ABD includes a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein (a) the HCVD comprises an H-CDR1 sequence, an H-CDR2 sequence, and an H-CDR3 sequence selected from the group consisting of one of (i) to (xii): (i) the sequences of SEQ ID NO: 125, SEQ ID NO: 126, and SEQ ID NO: 127, respectively; (ii) the sequences of SEQ ID NO: 133, SEQ ID NO: 134, and SEQ ID NO: 135, respectively; (iii) the sequences of SEQ ID NO: 141, SEQ ID NO: 142, and SEQ ID NO: 143, respectively; (iv) the sequences of SEQ ID NO: 149, SEQ ID NO: 150, and SEQ ID NO: 151, respectively; (v) the sequences of SEQ ID NO: 157, SEQ ID NO: 158, and SEQ ID NO
  • At least one of the H-CDR1, H-CDR2, and H-CDR3 sequences and/or at least one of the L-CDR1, L-CDR2, and L-CDR3 sequences has one or more amino acid position substituted with a histidine (e.g., one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or one, two, three, four, or five total histidine substitutions across the set of three L-CDRs).
  • the ABPC is degraded in the target mammalian cell following internalization of the ABPC by the target mammalian cell.
  • the ABPC includes a conjugated toxin, radioisotope, drug, or small molecule (also called herein “a conjugated composition”).
  • the conjugated composition provides for an increase in toxin liberation in the target mammalian cell as compared to a composition including the same amount of a control ABPC. In some aspects, the conjugated composition provides for at least a 20% increase in toxin liberation in the target mammalian cell as compared to a composition including the same amount of a control ABPC. In some aspects, the conjugated composition provides for at least a 50% increase in toxin liberation in the target mammalian cell as compared to a composition including the same amount of a control ABPC.
  • the conjugated composition provides for at least a 2-fold increase in toxin liberation in the target mammalian cell as compared to a composition including the same amount of a control ABPC.
  • the conjugated Attorney Docket No.: 45395-0068WO1 composition provides for at least a 5-fold increase in toxin liberation in the target mammalian cell as compared to a composition including the same amount of a control ABPC.
  • the conjugated composition provides for an increase in target mammalian cell killing as compared to a composition including the same amount of a control ABPC.
  • the conjugated composition provides for at least a 20% or 50% increase in target mammalian cell killing as compared to a composition including the same amount of a control ABPC. In some aspects, the conjugated composition provides for at least a 2- or 5-fold increase in target mammalian cell killing as compared to a composition including the same amount of a control ABPC. [0157] In some aspects, a composition comprising any of the ABPCs described herein provides for an increase in endolysosomal delivery in the target mammalian cell as compared to a composition including the same amount of a control ABPC.
  • a composition comprising any of the ABPCs described herein provides for at least a 20% or 50% increase in endolysosomal delivery in the target mammalian cell as compared to a composition including the same amount of a control ABPC. In some aspects, a composition comprising any of the ABPCs described herein provides for at least a 2- or 5-fold increase in endolysosomal delivery in the target mammalian cell as compared to a composition including the same amount of a control ABPC.
  • a composition comprising any of the ABPCs described herein results in a less of a reduction in the level of DLL3 presented on the surface of the target mammalian cell as compared to a composition including the same amount of a control ABPC. In some aspects, a composition comprising any of the ABPCs described herein does not result in a detectable reduction in the level of the DLL3 presented on the surface of the target mammalian cell.
  • compositions including an effective amount of an antigen-binding protein construct (ABPC) including: a first ABD that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell; and a conjugated toxin, radioisotope, drug, or small molecule, where: (a) the dissociation rate of the first ABD 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 ABD at a pH of about 4.0 to about 6.5 is greater than the K D at a pH of about 7.0 to about 8.0; and (b) the composition provides for one or more of: an increase in toxin liberation in the target mammalian cell as compared to a composition including the same amount of a control ABPC; an increase in target mammalian cell killing as Attorney Docket No.: 45395-0068
  • the pharmaceutical composition provides for an increase in target mammalian cell killing as compared to a pharmaceutical composition including the same amount of a control ABPC. In some aspects, the pharmaceutical composition provides for at least a 20% or 50% increase in target mammalian cell killing as compared to a pharmaceutical composition including the same amount of a control ABPC. In some aspects, the pharmaceutical composition provides for at least a 2- or 5-fold increase in target mammalian cell killing as compared to a pharmaceutical composition including the same amount of a control ABPC.
  • the pharmaceutical composition provides for an increase in endolysosomal delivery, including at least a 20% or 50% increase in endolysosomal delivery as compared to a pharmaceutical composition including the same amount of a control ABPC. In some aspects, the pharmaceutical composition provides for at least a 2- or 5-fold increase in endolysosomal delivery in the target mammalian cell as compared to a pharmaceutical composition including the same amount of a control ABPC. [0162] In some aspects, the pharmaceutical composition results in a less of a reduction in the level of DLL3 presented on the surface of the target mammalian cell as compared to a pharmaceutical composition including the same amount of a control ABPC.
  • the pharmaceutical composition does not result in a detectable reduction in the level of the DLL3 presented on the surface of the target mammalian cell.
  • the target mammalian cell is a DLL3-positive cancer cell.
  • the dissociation rate of the first ABD at a pH of ⁇ 4.0 to ⁇ 6.5 is at least 10% faster than the dissociation rate of the first ABD at a pH of ⁇ 7.0 to ⁇ 8.0. In some aspects, the dissociation rate of the first ABD at a pH of ⁇ 4.0 to ⁇ 6.5 is at least 3-fold faster than the dissociation rate of the first ABD at a pH of ⁇ 7.0 to ⁇ 8.0.
  • the dissociation rate of the first ABD at a pH of ⁇ 4.0 to ⁇ 6.5 is at least 10-fold faster than the dissociation rate of the first ABD at a pH of ⁇ 7.0 to ⁇ 8.0.
  • the K D of the first ABD at a pH of ⁇ 4.0 to ⁇ 6.5 is at least 10% greater than the first K D of the ABD at a pH of ⁇ 7.0 to ⁇ 8.0.
  • the first K D of the first ABD at a pH of ⁇ 4.0 to ⁇ 6.5 is at least 3-fold greater than the KD of the first ABD at a pH of Attorney Docket No.: 45395-0068WO1 ⁇ 7.0 to ⁇ 8.0.
  • the KD of the first ABD at a pH of ⁇ 4.0 to ⁇ 6.5 is at least 10-fold greater than the KD of the first ABD at a pH of ⁇ 7.0 to ⁇ 8.0.
  • the ABPC is cytotoxic or cytostatic to the target mammalian cell.
  • the first ABD is cross-reactive with a non-human primate DLL3 and human DLL3.
  • the first ABD is cross-reactive with a non-human primate DLL3, a human DLL3, and one or both of rat DLL3 and a mouse DLL3.
  • the first ABD is cross-reactive with a non-human primate DLL3, a human DLL3, a rat DLL3, and a mouse DLL3. In some aspects, the first ABD binds to an epitope of DLL3 that is present on the surface of cells from an Old World Monkey. [0166] In some aspects, the ABPC includes a single polypeptide. In some aspects, the first ABD is selected from a VH domain, a VHH domain, a VNAR domain, and a scFv.
  • the ABPC is a BiTe, a (scFv)2, a nanobody, a nanobody-HSA, a DART, a TandAb, a scDiabody, a scDiabody-CH3, scFv-CH-CL-scFv, a HSAbody, scDiabody-HSA, or a tandem-scFv.
  • the ABPC includes two or more polypeptides.
  • At least one polypeptide of the ABPC is conjugated to the toxin, the radioisotope, the drug, or the small molecule via a cleavable linker. In some aspects, at least one polypeptide of the ABPC is conjugated to the toxin, the radioisotope, the drug, or the small molecule via a non-cleavable linker. [0169] In some aspects, the half-life of the ABPC in vivo is increased as compared to the half- life of a control ABPC in vivo.
  • the half-life of the ABPC in vivo is increased about 50% to about 95% as compared to the half-life of a control ABPC in vivo. In some aspects, the half-life of the ABPC in vivo is increased about 70% to about 95% as compared to the half-life of a control ABPC in vivo. In other aspects, the in vivo half-life may be decreased.
  • control ABPC is capable of specifically binding to DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell, where: (a) the control ABPC includes a first ABD; (b) the dissociation rate of the first ABD of the control ABPC at a pH of ⁇ 4.0 to ⁇ 6.5 is no more than 2-fold faster than the dissociation rate at a pH of ⁇ 7.0 to ⁇ 8.0; and (c) the dissociation constant (K D ) of the first ABD of the control ABPC at a pH of ⁇ 4.0 to ⁇ 6.5 is no more than 2-fold greater than the K D at a pH of ⁇ 7.0 to ⁇ 8.0.
  • control ABPC is capable of specifically binding to DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell, where: (a) the control ABPC includes a first ABD; (b) the dissociation rate of the first ABD of the control ABPC at a pH of ⁇ 4.0 to ⁇ 6.5 is no more than 1-fold faster than the dissociation rate at a pH of ⁇ 7.0 to ⁇ 8.0; and (c) the dissociation constant (KD) of the first ABD of the control ABPC at a pH of ⁇ 4.0 to ⁇ 6.5 is no more than 1-fold greater than the K D at a pH of ⁇ 7.0 to ⁇ 8.0.
  • the control ABPC is selected from one of those disclosed herein.
  • the ABPC includes a second ABD .
  • the second ABD specifically binds to DLL3 (e.g., the same or a different epitope on DLL3 as compared to the first ABD) .
  • the second ABD is the same as the first ABD .
  • the second ABD binds to an epitope on the surface of an immune cell (e.g., a T cell or a NK cell) (e.g., CD3).
  • kits including at least one dose of any of the pharmaceutical compositions described herein.
  • antigen-binding protein constructs including: a first ABD that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell, where: (a) the dissociation rate of the first ABD at a pH of about 4.0 to about 6.5 is faster than the dissociation rate at a pH of about 7.0 to about 8.0; or (b) the dissociation constant (K D ) of the first ABD 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.
  • ABPCs antigen-binding protein constructs
  • the first ABD includes one of: (a) an HCVD including the sequence of SEQ ID NO: 3 and/or an LCVD including the sequence of SEQ ID NO: 4; (b) an HCVD including the sequence of SEQ ID NO: 11 and/or an LCVD including the sequence of SEQ ID NO: 12; (c) an HCVD including the sequence of SEQ ID NO: 19 and/or an LCVD including the sequence of SEQ ID NO: 20; (d) an HCVD including the sequence of SEQ ID NO: 27 and/or an LCVD including the sequence of SEQ ID NO: 28; (e) an HCVD including the sequence of SEQ ID NO: 35 and/or an LCVD including the sequence of SEQ ID NO: 36; (f) an HCVD including the sequence of SEQ ID NO: 43 and/or an LCVD including the sequence of SEQ ID NO: 44; (g) an HCVD including the sequence of SEQ ID NO: 51 and/or an LCVD including the sequence of SEQ ID NO: 12; (
  • the first ABD includes a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein (a) the HCVD comprises an H-CDR1 sequence, an Attorney Docket No.: 45395-0068WO1 H-CDR2 sequence, and an H-CDR3 sequence selected from the group consisting of the sequences of one of (i) to (xii): (i) SEQ ID NO: 5, SEQ ID NO: 6, and SEQ ID NO: 7, respectively; (ii) SEQ ID NO: 13, SEQ ID NO: 14, and SEQ ID NO: 15, respectively; (iii) SEQ ID NO: 21, SEQ ID NO: 22, and SEQ ID NO: 23, respectively; (iv) SEQ ID NO: 29, SEQ ID NO: 30, and SEQ ID NO: 31, respectively; (v) SEQ ID NO: 37, SEQ ID NO: 38, and SEQ ID NO: 39, respectively; (vi) SEQ ID NO: 45, SEQ ID NO: 46, and SEQ ID NO: 45, SEQ ID
  • At least one of the H-CDR1, H-CDR2, and H-CDR3 sequences and/or at least one of the L-CDR1, L-CDR2, and L-CDR3 sequences has one or more amino acid position substituted with a histidine (e.g., one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or one, two, three, four, or five total histidine substitutions across the set of three L-CDRs).
  • a histidine e.g., one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or one, two, three, four, or five total histidine substitutions across the set of three L-CDRs.
  • the first ABD includes one of: (a) an HCVD including the sequence of SEQ ID NO: 123 and/or an LCVD including the sequence of SEQ ID NO: 124; (b) an HCVD including the sequence of SEQ ID NO: 131 and/or an LCVD including the sequence of SEQ ID NO: 132; (c) an HCVD including the sequence of SEQ ID NO: 139 and/or an LCVD including the sequence of SEQ ID NO: 140; (d) an HCVD including the sequence of SEQ ID NO: 147 and/or Attorney Docket No.: 45395-0068WO1 an LCVD including the sequence of SEQ ID NO: 148; (e) an HCVD including the sequence of SEQ ID NO: 155 and/or an LCVD including the sequence of SEQ ID NO: 156; (f) an HCVD including the sequence of SEQ ID NO: 163 and/or an LCVD including the sequence of SEQ ID NO: 164; (g) an HCVD including the sequence of
  • the first ABD includes a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein (a) the HCVD comprises an H-CDR1 sequence, an H-CDR2 sequence, and an H-CDR3 sequence selected from the group consisting of the sequences of one of (i) to (xii): (i) SEQ ID NO: 125, SEQ ID NO: 126, and SEQ ID NO: 127, respectively; (ii) SEQ ID NO: 133, SEQ ID NO: 134, and SEQ ID NO: 135, respectively; (iii) SEQ ID NO: 141, SEQ ID NO: 142, and SEQ ID NO: 143, respectively; (iv) SEQ ID NO: 149, SEQ ID NO: 150, and SEQ ID NO: 151, respectively; (v) SEQ ID NO: 157, SEQ ID NO: 158, and SEQ ID NO: 159, respectively; (vi) SEQ ID NO: 165
  • the ABPC includes a conjugated toxin, radioisotope, drug, or small molecule (also called herein “a conjugated composition”).
  • a conjugated composition including the ABPC provides for an increase in toxin liberation in the target mammalian cell as compared to a conjugated composition including the same amount of a control ABPC.
  • a conjugated composition including the ABPC provides for at least a 20% or 50% increase in toxin liberation in the target mammalian cell as compared to a conjugated composition including the same amount of a control ABPC.
  • a conjugated composition including the ABPC provides for at least a 2- or 5-fold increase in toxin liberation in the target mammalian cell as compared to a conjugated composition including the same amount of a control ABPC.
  • a conjugated composition including the ABPC provides for an increase in target mammalian cell killing as compared to a conjugated composition including the same amount of a control ABPC.
  • a conjugated composition including the ABPC provides for at least a 20% or 50% increase in target mammalian cell killing as compared to a conjugated composition including the same amount of a control ABPC.
  • a conjugated composition including the ABPC provides for at least a 2- or 5-fold increase in target Attorney Docket No.: 45395-0068WO1 mammalian cell killing as compared to a conjugated composition including the same amount of a control ABPC.
  • a composition including the ABPC provides for an increase in endolysosomal delivery in the target mammalian cell as compared to a composition including the same amount of a control ABPC.
  • the ABPC provides for at least a 20% increase in endolysosomal delivery in the target mammalian cell as compared to a composition including the same amount of a control ABPC.
  • a composition including the ABPC provides for at least a 50% increase in endolysosomal delivery in the target mammalian cell as compared to a composition including the same amount of a control ABPC. In some aspects, a composition including the ABPC provides for at least a 2-fold increase in endolysosomal delivery in the target mammalian cell as compared to a composition including the same amount of a control ABPC. In some aspects, a composition including the ABPC provides for at least a 5-fold increase in endolysosomal delivery in the target mammalian cell as compared to a composition including the same amount of a control ABPC.
  • kits including at least one dose of any ABPC described herein.
  • methods of treating a cancer characterized by having a population of DLL3-positive cancer cells including: administering a therapeutically effective amount of any of the pharmaceutical compositions described herein or any of the ABPCs described herein to a subject identified as having a cancer characterized by having the population of cancer cells.
  • the DLL3- positive cancer is a metastasis.
  • the DLL3-positive cancer is a non-T-cell-infiltrating tumor.
  • the DLL-positive cancer is a T-cell infiltrating tumor.
  • Also provided herein are methods of decreasing the risk of developing a metastasis or decreasing the risk of developing an additional metastasis in a subject having a DLL3-positive cancer, the method including: administering a therapeutically effective amount of any one of the pharmaceutical compositions described herein or any of the ABPCs described herein to the subject.
  • the DLL3-positive cancer is a non-T-cell-infiltrating tumor.
  • the DLL3-positive cancer is a T-cell infiltrating tumor.
  • the term “antigen-binding protein construct” is (i) a single polypeptide that includes at least one ABD or (ii) a complex of two or more polypeptides (e.g., the same or different polypeptides) that together form at least one ABD.
  • Non-limiting examples and aspects of antigen-binding protein constructs are described herein. Additional examples and aspects of antigen-binding protein constructs are known in the art.
  • a “multi-specific ABPC” is an ABPC that includes two or more different ABDs that collectively specifically bind two or more different epitopes.
  • the two or more different epitopes may be epitopes on the same antigen (e.g., a single polypeptide present on the surface of a cell) or on different antigens (e.g., different proteins present on the surface of the same cell or present on the surface of different cells).
  • the antigen is present on the surface of the cell.
  • a multi-specific ABPC binds two different epitopes (i.e., a “bispecific ABPC”).
  • a multi-specific ABPC binds three different epitopes (i.e., a “trispecific ABPC”).
  • a multi-specific ABPC binds four different epitopes (i.e., a “quadspecific ABPC”). In some aspects, a multi-specific ABPC binds five different epitopes (i.e., a “quintspecific Attorney Docket No.: 45395-0068WO1 ABPC”). Each binding specificity may be present in any suitable valency. Non-limiting examples of multi-specific ABPC s are described herein.
  • an “Antigen-Binding Protein” or “ABD” is one or more protein domain(s) (e.g., formed from amino acids from a single polypeptide or formed from amino acids from two or more polypeptides (e.g., the same or different polypeptides) that is capable of specifically binding to one or more different antigen(s).
  • an ABD can bind to an antigen or epitope with specificity and affinity similar to that of naturally occurring antibodies.
  • the ABD can be an antibody or a fragment thereof.
  • an ABD can include an alternative scaffold. Non-limiting examples of ABDs are described herein. Additional examples of ABDs are known in the art.
  • an ABD can bind to a single antigen.
  • the term “antibody” is used herein in its broadest sense and includes certain types of immunoglobulin molecules that include one or more ABDs that specifically bind to an antigen or epitope.
  • An antibody specifically includes, e.g., intact antibodies (e.g., intact immunoglobulins, e.g., human IgG (e.g., human IgG1, human IgG2, human IgG3, human IgG4)), antibody fragments (e.g., Fab fragment), and multi-specific antibodies.
  • an ABD is an ABD formed by a VH -VL dimer. Additional examples of an antibody are described herein.
  • an antibody is an example of a type of antigen-binding protein construct.
  • an antibody can be a fully human antibody, a humanized antibody, a chimeric antibody, a veneered antibody, or a rabbit antibody.
  • the CDRs of means the amino acid residues of a given antigen binding domain (e.g., a heavy chain variable domain (HCVD) or a light chain variable domain (LCVD)).
  • CDRs are determined by including the amino acid residues falling under either or both the Kabat and IMGT CDR definitions (i.e., as used herein, residues determined by the “Kabat-IMGT” method).
  • endosomal/lysosomal pathway refers to a network of endosomes (early endosomes, multi-vesicular bodies, late endosomes, and lysosomes) in the cytoplasm of a mammalian cell, wherein molecules are internalized through cell-mediated internalization processes, e.g., pinocytosis, micropinocytosis, receptor-mediated endocytosis, and/or phagocytosis, are sorted.
  • assays for a target protein can be performed Attorney Docket No.: 45395-0068WO1 using methods known in the art (ELISA, Western blot, immunofluorescence, and immunoprecipitation followed by an assay for protein concentration), and can be used to determine the concentration or relative level of the target protein in the endosomes.
  • endosomes in the endosomal/lysosomal pathway can be imaged using immunofluorescence microscopy using an detectably-labelled antibody (e.g., a fluorophore-labelled, a dye-labelled, or a GFP-labelled antibody, e.g., CellLight TM Early Endosome-GFP) that specifically binds to a characteristic protein present in the endosomes (e.g., EEA1 for early endosomes) and a fluorophore-labelled antibody that specifically binds to the protein of interest (e.g., an ABPC), and the level of the target protein in the endosomes can be determined by quantitation of the overlap in the fluorescence emissions of the two different antibodies.
  • an detectably-labelled antibody e.g., a fluorophore-labelled, a dye-labelled, or a GFP-labelled antibody, e.g., CellLight TM Early Endosome-GFP
  • endolysosomal delivery refers to rate of accumulation over time or the total accumulation at a specific timepoint of an ABPC (e.g., any of the ABPCs described herein) in the endosomal/lysosomal pathway in a mammalian cell (e.g., any of the exemplary target mammalian cells described herein).
  • An exemplary method to calculate the increase in endolysosomal delivery of a pH engineered ABPC variant as compared to its corresponding starting ABPC from cellular fluorescence data is to measure the ratio of the variant’s mean fluorescence intensity minus the mean fluorescence intensity of a non-binding IgG control, then all divided by the variant’s corresponding starting ABPC’s mean fluorescence intensity minus the mean fluorescence intensity of the IgG control.
  • An exemplary assay for measuring endolysosomal delivery of any of the ABPCs described herein include those which involve labeling of an ABPC with a fluorescent dye, followed by incubation of the labeled ABPC with cells and measurement of cellular fluorescence as an indicator of endolysosomal delivery of the ABPC (e.g., as described generally in Wustner, Traffic 7(6):699-715, 2006).
  • pH-sensitive dyes which preferentially fluoresce at acidic pH but not neutral pH can be used to label any of the ABPCs described herein, which can then be incubated with cells and the cellular fluorescence measured as an indicator of delivery of the ABPC into acidic endolysosomal compartments.
  • cytostatic to a cell refers to a direct or indirect decrease in the proliferation (cell division) of the cell (e.g., a cancer cell) in vivo or in vitro.
  • the agent can, e.g., directly or indirectly result in cell cycle arrest of the cell (e.g., a cancer cell).
  • an agent that is cytostatic to a cell can reduce the number of cells in a population of the cells that are in S phase (as compared to the number of cells in a population of the cells that are in S phase prior to contact with the agent). In some examples, an agent that is cytostatic to a cell can reduce the percentage of the cells in S phase by at least 20%, at least 40%, at least 60%, or at least 80% (e.g., as compared to the percentage of cells in a population of the cells that are in S phase prior to contact with the agent).
  • cytotoxic to a cell refers to the inducement, directly or indirectly, in the death (e.g., necrosis or apoptosis) of the cell (e.g., a mammalian cell, e.g., a cancer cell).
  • Affinity refers to the strength of the sum total of non-covalent interactions between an antigen-binding site and its binding partner (e.g., an antigen or epitope).
  • affinity refers to intrinsic binding affinity, which reflects a 1:1 interaction between members of an ABD and an antigen or epitope.
  • the affinity of a molecule X for its partner Y can be represented by the dissociation equilibrium constant (K D ).
  • Affinity can be measured by common methods known in the art, including those described herein. Affinity can be determined, e.g., using surface plasmon resonance (SPR) technology (e.g., BIACORE®) or biolayer interferometry (e.g., FORTEBIO ® ). Additional methods for determining the affinity for an ABD and its corresponding antigen or epitope are known in the art.
  • SPR surface plasmon resonance
  • FORTEBIO ® biolayer interferometry
  • Epitopes can, e.g., consist of surface-accessible amino acid residues, sugar side chains, phosphorylated amino acid residues, methylated amino acid residues, and/or acetylated amino acid residues and may have specific three-dimensional structural characteristics, as well as specific charge characteristics.
  • an epitope is defined by a linear amino Attorney Docket No.: 45395-0068WO1 acid sequence of at least about 3 to 6 amino acids, or about 10 to 15 amino acids.
  • an epitope refers to a portion of a full-length protein or a portion thereof that is defined by a three- dimensional structure (e.g., protein folding).
  • an epitope is defined by a discontinuous amino acid sequence that is brought together via protein folding.
  • an epitope is defined by a discontinuous amino acid sequence that is brought together by quaternary structure (e.g., a cleft formed by the interaction of two different polypeptide chains).
  • the amino acid sequences between the residues that define the epitope may not be critical to three- dimensional structure of the epitope.
  • a conformational epitope may be determined and screened using assays that compare binding of antigen-binding protein construct to a denatured version of the antigen, such that a linear epitope is generated.
  • An epitope may include amino acid residues that are directly involved in the binding, and others, which are not directly involved in the binding.
  • Methods for identifying an epitope to which an ABD specifically binds are known in the art, e.g., structure-based analysis (e.g. X-ray crystallography, NMR, and/or electron microscopy) (e.g. on the antigen and/or the antigen-ABD complex) and/or mutagenesis-based analysis (e.g. alanine scanning mutagenesis, glycine scanning mutagenesis, and homology scanning mutagenesis) wherein mutants are measured in a binding assay with a binding partner, many of which are known in the art.
  • structure-based analysis e.g. X-ray crystallography, NMR, and/or electron microscopy
  • mutagenesis-based analysis e.g. alanine scanning mutagenesis, glycine scanning mutagenesis, and homology scanning mutagenesis
  • paratope means a portion of an ABD 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, posttranslationally modified amino acid residues) on the portion of the ABD that specifically binds the antigen and (ii) all monomers (e.g. individual amino acid residues, sugar side chains, posttranslationally modified amino acid residues) on the portion of the antigen that is specifically bound by the ABD.
  • Paratopes can, e.g., consist of surface-accessible amino acid residues and may have specific three-dimensional structural characteristics, as well as specific charge characteristics.
  • a paratope refers to a portion of a full-length ABD or a portion thereof that is defined by a three-dimensional structure (e.g., protein folding).
  • a paratope is defined by a discontinuous amino acid sequence that is brought together via protein folding.
  • an epitope is defined by a discontinuous amino acid sequence that is brought together by quaternary structure (e.g., a cleft formed by the interaction of two different polypeptide chains). The amino acid sequences between the residues that define the paratope may not be critical to three-dimensional structure of the paratope.
  • a paratope may Attorney Docket No.: 45395-0068WO1 comprise amino acid residues that are directly involved in the binding, and others, which are not directly involved in the binding.
  • Methods for identifying a paratope to which an ABD specifically binds are known in the art, e.g., structure-based analysis (e.g., X-ray crystallography, NMR, and/or electron microscopy) (e.g.
  • mutants are measured in a binding assay with a binding partner, many of which are known in the art.
  • mutagenesis-based analysis e.g., alanine scanning mutagenesis, glycine scanning mutagenesis, and homology scanning mutagenesis
  • control ABPC or “control antigen-binding protein construct” means an ABPC that is capable of specifically binding to DLL3 or an epitope of DLL3 presented on the surface of a mammalian cell (e.g., a target mammalian cell), where one or both of the following is true: (a) the dissociation rate of the first ABD at a pH of ⁇ 4.0 to ⁇ 6.5 (e.g., any of the subranges of this range described herein) is no more than 3-fold (e.g., no more than 2.8-fold, no more than 2.6-fold, no more than 2.5-fold, no more than 2.4-fold, no more than 2.2-fold, no more than 2.0-fold, no more than 1.8-fold, no more than 1.6-fold, no more than
  • extracellular space means the liquid exterior to the plasma membrane of a mammalian cell.
  • the extracellular space can be a liquid culture medium.
  • the extracellular space can be, e.g., plasma, serum, blood, interstitial fluid, or lymph.
  • endolysosomal space means the fluid encapsulated by the vesicles and organelles that make-up the endosomal/lysosomal pathway in a mammalian cell.
  • a reduced level or “a decreased level” can be a reduction or decrease of at least a 1% (e.g., ⁇ 2%, ⁇ 4%, ⁇ 6%, ⁇ 8%, ⁇ 10%, ⁇ 12%, ⁇ 14%, ⁇ 16%, ⁇ 18%, ⁇ 20%, ⁇ 22%, ⁇ 24%, ⁇ 26%, ⁇ 30%, ⁇ 35%, ⁇ 40%, ⁇ 45%, ⁇ 50%, ⁇ 55%, ⁇ 60%, ⁇ 65%, ⁇ 70%, ⁇ 75%, ⁇ 80%, ⁇ 85%, ⁇ 90%, ⁇ 95%, or ⁇ 99%) reduction as compared to a reference level or value.
  • a 1% e.g., ⁇ 2%, ⁇ 4%, ⁇ 6%, ⁇ 8%, ⁇ 10%, ⁇ 12%, ⁇ 14%, ⁇ 16%, ⁇ 18%, ⁇ 20%, ⁇ 22%, ⁇ 24%, ⁇ 26%, ⁇ 30%, ⁇ 35%
  • cell killing potency refers to the ability of an agent (e.g., any of the ABPCs described herein) to induce, directly or indirectly, the apoptosis and/or necrosis of a mammalian cell (e.g., a cancer cell), measured as a rate over time or at a relevant timepoint.
  • agent e.g., any of the ABPCs described herein
  • Methods for determining the cell killing potency of a cell are known in the art (e.g., trypan blue staining, Attorney Docket No.: 45395-0068WO1 microscopy, fluorescence-assisted cell sorting, and assays to detect markers of apoptosis (e.g., Annexin V)).
  • cell killing potency can be measured, e.g., by cell killing at a single concentration of an agent, by the IC50 of the agent (i.e. the concentration of the agent whereby half the maximal cell killing potency is achieved), or by the ratio of an agent’s dissociation constant KD on mammalian cells divided by its IC50.
  • the IC50s and/or the KD ratios described herein are compared to those of a control ABPC (as defined herein), and, optionally, demonstrate that the ABPCs described herein have a higher cell killing potency as compared to the control ABPC.
  • toxin liberation refers to the ability of a mammalian cell (e.g., a non-cancerous mammalian cell or a cancer cell) to internalize (e.g., via pinocytosis and/or receptor-mediated endocytosis) any of the ABPCs described herein (e.g., any of ABPCs or control ABPCs described herein) that are conjugated to a toxin, and subsequently release the toxin conjugated to the ABPC, measured as a rate over time or at a specific timepoint.
  • a mammalian cell e.g., a non-cancerous mammalian cell or a cancer cell
  • any of the ABPCs described herein e.g., any of ABPCs or control ABPCs described herein
  • Toxin liberation can be assessed using a variety of different exemplary assays, e.g., ELISA, immunofluorescence, cell killing assays, cell cycle arrest assays, DNA damage assays, mass spectrometry, HPLC, and/or an isotope-labeled toxin.
  • ELISA ELISA
  • immunofluorescence cell killing assays
  • cell cycle arrest assays DNA damage assays
  • HPLC mass spectrometry
  • HPLC mass spectrometry
  • an isotope-labeled toxin e.g., HPLC, HPLC, and/or an isotope-labeled toxin.
  • target cell or “target mammalian cell” or “mammalian target cell” means a mammalian cell that has at least one DLL3 present on its surface.
  • a mammalian target cell can be a cancer cell.
  • a target mammalian cell can have a total of about the following (each ⁇ about 10%): 1-10E6, 1-9E6, 1-8E6, 1-7E6, 1-6E6, 1-5E6, 1-4E6, 1- 3E6, 1-2E6, 1-1E6, 1-800,000, 1-600,000, 1-400,000, 1-200,000, 1-100,000, 1-80,000, 1-80,000, 1-75,000, 1-70,000, 1-65,000, 1-60,000, 1-55,000, 1-50,000, 1-45,000, 1-40,000, 1-35,000, 1- 30,000, 1-25,000, 1-20,000, 1-15,000, 1-10,000, 1-7,500, 1-5,000, 1-4,000, 1-3,000, 1-2,000, 1- 1,000, 1-500, 1-100, 1-50, or 1-10, or any of the ranges of numbers recited in paragraph [0065] of US 2022/0281984, of the DLL3 present on the plasma membrane of the target mammalian cell.
  • the phrase “antigen density” means the number of DLL3 present on the surface of a target mammalian cell or the average number of DLL3 on the surface of a population of particular type of target mammalian cells. It can be measured, e.g., using the Quantibright bead kit or radiolabel (e.g., BD Biosciences PE Phycoerythrin Fluorescence Quantitation Kit, catalog #340495).
  • the phrase “amino acid substituted with a histidine” means the substitution of an amino acid residue that is not histidine in a reference polypeptide sequence with a histidine.
  • DLL3-positive cancer means a cancer cell that has a predetermined level of DLL3 or an epitope of DLL3 presented on its surface.
  • DLL3-positive cancers include: small-cell lung cancer, large cell neuroendocrine carcinoma, pulmonary neuroendocrine cancer, extrapulmonary neuroendocrine cancers, or melanoma.
  • a DLL3-positive cancer can be a metastatic cancer or metastasis.
  • a DLL3-positive cancer can be a primary cancer.
  • the disclosure provides novel DLL3-binding antigen-binding protein constructs (ABPCs) having improved properties over existing DLL3-binding ABPCs.
  • ABPCs novel DLL3-binding antigen-binding protein constructs
  • the disclosure provided DLL3-binding ABPCs wherein (a) the dissociation rate of the first ABD 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 ABD 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.
  • the set of H-CDR1, H-CDR2, and H-CDR3 sequences contains at least one amino acid substituted with a histidine (e.g., one, two, three, four, or five total histidine substitutions across the set of three H- CDRs)).
  • the set of L-CDR1, L-CDR2, and L-CDR3 sequences contains at least one amino acid substituted with a histidine (e.g., one, two, three, four, or five total histidine substitutions across the set of three L-CDRs).
  • the antibody, ABPC, or ABD includes one or more of the following characteristics: (a) a heavy chain variable domain (HCVD) sequence that is at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identical to the HCVD sequence of any one of SEQ ID NOs: 3, 11, 19, 27, 35, 43, 51, 59, 67, 75, 83, and 91; and/or (b) a light chain variable domain (LCVD) sequence that is at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identical to the LCVD sequence of any one of SEQ ID NOs: 4, 12, 20, 28, 36, 44, 52, 60, 68, Attorney Docket No.: 45395-0068WO1 76, 84, and 92.
  • HCVD heavy chain variable domain
  • LCVD light chain variable domain
  • the set of three H-CDRs comprises one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or the set of three L-CDRs comprises one, two, three, four, or five total histidine substitutions across the set of three L-CDRs.
  • the HCVD and LCVD do not include any substitutions in their variable domain framework regions or their constant domain regions.
  • the HCVD amino acid sequence and the LCVD amino acid sequence is selected from the group consisting of: SEQ ID NO: 3 and SEQ ID NO: 4, respectively; SEQ ID NO: 11 and SEQ ID NO: 12, respectively; SEQ ID NO: 19 and SEQ ID NO: 20; SEQ ID NO: 27 and SEQ ID NO: 28, respectively; SEQ ID NO: 35 and SEQ ID NO: 36, respectively; SEQ ID NO: 43 and SEQ ID NO: 44, respectively; SEQ ID NO: 51 and SEQ ID NO: 52, respectively; SEQ ID NO: 59 and SEQ ID NO: 59, respectively; SEQ ID NO: 67 and SEQ ID NO: 67, respectively; SEQ ID NO: 75 and SEQ ID NO: 76, respectively; SEQ ID NO: 83 and SEQ ID NO: 84, respectively; and SEQ ID NO: 91 and SEQ ID NO: 92, respectively.
  • the set of three H-CDRs comprises one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or the set of three L-CDRs comprises one, two, three, four, or five total histidine substitutions across the set of three L-CDRs.
  • the HCVD and LCVD do not include any substitutions in their variable domain framework regions or their constant domain regions.
  • the present disclosure provides an antibody, antigen binding protein construct (ABPC), or antigen binding domain (ABD) thereof, comprising a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein (a) the HCVD comprises an H-CDR1 sequence, an H-CDR2 sequence, and an H-CDR3 sequence selected from the group consisting of the sequences of one of (i) to (xii): (i) SEQ ID NO: 125, SEQ ID NO: 126, and SEQ ID NO: 127, respectively; (ii) SEQ ID NO: 133, SEQ ID NO: 134, and SEQ ID NO: 135, respectively; (iii) SEQ ID NO: 141, SEQ ID NO: 142, and SEQ ID NO: 143, respectively; (iv) SEQ ID NO: 149, SEQ ID NO: 150, and SEQ ID NO: 151, respectively; (v) SEQ ID NO: 149, SEQ ID NO: 150, and SEQ ID NO
  • the set of three H- CDRs comprises one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or the set of three L-CDRs comprises one, two, three, four, or five total histidine substitutions across the set of three L-CDRs.
  • the antibody, ABPC, or ABD includes one or more of the following characteristics: (a) a heavy chain variable domain (HCVD) sequence that is at least 80%, at least Attorney Docket No.: 45395-0068WO1 85%, at least 90%, at least 95%, or at least 99% identical to the HCVD sequence of any one of SEQ ID NOs: 123, 131, 139, 147, 155, 163, 171, 179, 187, 195, 203, and 211; and/or (b) a light chain variable domain (LCVD) sequence that is at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identical to the LCVD sequence of any one of SEQ ID NOs: 124, 132, 140, 148, 156, 164, 172, 180, 188, 196, 204, and 212.
  • HCVD heavy chain variable domain
  • the set of three H-CDRs comprises one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or the set of three L-CDRs comprises one, two, three, four, or five total histidine substitutions across the set of three L-CDRs.
  • the HCVD and LCVD do not include any substitutions in their variable domain framework regions or their constant domain regions.
  • the present disclosure provides an antibody, ABPC, or ABD thereof comprising an HCVD and an LCVD, wherein: (a) the HCVD comprises an amino acid sequence of any one of SEQ ID NO: 123, SEQ ID NO: 131, SEQ ID NO: 139, SEQ ID NO: 147, SEQ ID NO: 155, SEQ ID NO: 163, SEQ ID NO: 171, SEQ ID NO: 179, SEQ ID NO: 187, SEQ ID NO: 195, SEQ ID NO: 203, and SEQ ID NO: 211; and/or (b) the LCVD comprises an amino acid sequence of any one of SEQ ID NO: 124, SEQ ID NO: 132, SEQ ID NO: 140, SEQ ID NO: 148, SEQ ID NO: 156, SEQ ID NO: 164, SEQ ID NO: 172, SEQ ID NO: 180, SEQ ID NO: 188, SEQ ID NO: 196, SEQ ID NO: 204, and
  • the set of three H-CDRs comprises one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or the set of three L-CDRs comprises one, two, three, four, or five total histidine substitutions across the set of three L-CDRs.
  • the HCVD and LCVD do not include any substitutions in their variable domain framework regions or their constant domain regions.
  • the HCVD amino acid sequence and the LCVD amino acid sequence is selected from the group consisting of: SEQ ID NO: 123 and SEQ ID NO: 124, respectively; SEQ ID NO: 131 and SEQ ID NO: 132, respectively; SEQ ID NO: 139 and SEQ ID NO: 140; SEQ ID NO: 147 and SEQ ID NO: 148, respectively; SEQ ID NO: 155 and SEQ ID NO: 156, respectively; SEQ ID NO: 163 and SEQ ID NO: 164, respectively; SEQ ID NO: 171 and SEQ ID NO: 172, respectively; SEQ ID NO: 179 and SEQ ID NO: 179, respectively; SEQ ID NO: 187 and SEQ ID NO: 187, respectively; SEQ ID NO: 195 and SEQ ID NO: 196, respectively; SEQ ID NO: 203 and SEQ ID NO: 204, respectively; and SEQ ID NO: 211 and SEQ ID NO: 212,
  • the set of three H-CDRs comprises one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or the set of three L- Attorney Docket No.: 45395-0068WO1 CDRs comprises one, two, three, four, or five total histidine substitutions across the set of three L- CDRs.
  • the HCVD and LCVD do not include any substitutions in their variable domain framework regions or their constant domain regions.
  • a conjugated composition including the ABPC can provide for an increase (e.g., a detectable increase) (e.g., any of the percents increase or ranges of percents increase recited in US 2022/0281984, which is incorporated by reference herein in its entirety) in toxin liberation in the target mammalian cell (e.g., any of the target mammalian cells described herein) as compared to a conjugated composition including the same amount of a control ABPC (e.g., any of the exemplary control ABPCs described herein).
  • an increase e.g., a detectable increase
  • toxin liberation in the target mammalian cell e.g., any of the target mammalian cells described herein
  • a conjugated composition including the same amount of a control ABPC e.g., any of the exemplary control ABPCs described herein.
  • a conjugated composition including the ABPC can provide for an increase (e.g., a detectable increase) (e.g., any of the folds increase or ranges of folds increase recited in US 2022/0281984) in toxin liberation in the target mammalian cell (e.g., any of the target mammalian cells described herein) as compared to a composition including the same amount of a control ABPC (e.g., any of the exemplary control ABPCs described herein).
  • an increase e.g., a detectable increase
  • a control ABPC e.g., any of the exemplary control ABPCs described herein
  • a conjugated composition including the ABPC can provide for an increase (e.g., a detectable increase) (e.g., at least a 1%, 2%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 120%, 140%, 160%, 180%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 1,000%, 2,000%, 3,000%, 4,000%, 5,000%, 6,000%, 7,000%, 8,000%, 9,000%, or a 10,000% increase, or about a 1% to 10,000% increase (e.g., or any of the subranges)) in target mammalian cell killing as compared to a conjugated composition including the same amount of a control ABPC.
  • an increase e.g., a detectable increase
  • an increase e.g., at least a 1%,
  • a conjugated composition including the ABPC can provide for an increase (e.g., a detectable increase) (e.g., at least a 0.1-, 0.2- , 0.3-, 0.4-, 0.5-, 0.6-, 0.7-, 0.8-, 0.9-, 1.0-, 1.2-, 1.4-, 1.5-, 1.6-, 1.8-, 2.0-, 2.2-, 2.4-, 2.5-, 2.6-, 2.8- , 3.0-, 3.5-, 4.0-, 4.5-, 5.0-, 5.5-, 6.0-, 6.5-, 7.0-, 7.5-, 8.0-, 8.5-, 9.0-, 9.5-, 10-, 15-, 20-, 25-, 30-, Attorney Docket No.: 45395-0068WO1 35-, 40-, 40-, 45-, 50-, 55-, 60-, 65-, 70-, 80-
  • a conjugated composition including any of the ABPCs described herein results in decreased (e.g., ⁇ a 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% decrease, or at least a 99% decrease, about a 1%-99% decrease, or any of the subranges of this range described herein) IC50 (for target mammalian cell killing) as compared to the IC 50 for a conjugated composition including the same amount of a control ABPC.
  • decreased e.g., ⁇ a 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% decrease, or at least a 99% decrease, about a 1%-99% decrease, or any of the subranges of this range described herein
  • IC50 for target ma
  • a composition including any of the ABPCs described herein can provide for an increase (e.g., at least a 0.1-, 0.2-, 0.4-, 0.6-, 0.8-, 1-, 2-, 5-, 10-, 15-, 20-, 25-, 30-, 35-, 40-, 45-, 50-, 55-, 60-, 65-, 70-, 75-, 80-, 85-, 90-, 95-fold increase, or at least a 100-fold increase, or about a 0.1- 500-fold increase (or any of the subranges of this range described herein) in the ratio of KD on target mammalian cells presenting DLL3 on their surface at a neutral pH to IC50 at the neutral pH on the same target cells, e.g., as compared to a control ABPC.
  • an increase e.g., at least a 0.1-, 0.2-, 0.4-, 0.6-, 0.8-, 1-, 2-, 5-, 10-, 15-, 20-, 25-, 30-
  • the target mammalian cell does not express an FcRn receptor, or expresses a lower (e.g., a detectably lower) level (e.g., at least a 1% decreased, at least a 2%, 5%, 10% decrease, at least a 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% decreased, or at least a 99% decreased level) of FcRn receptor as compared to a FcRn expressing control cell (e.g., HUVEC – ThermoFisher #C0035C).
  • a lower e.g., a detectably lower
  • a detectably lower level e.g., at least a 1% decreased, at least a 2%, 5%, 10% decrease, at least a 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%,
  • the target mammalian cell is a DLL3-positive cancer cell.
  • the ABPC is cytotoxic or cytostatic to the target mammalian cell.
  • a composition including any of the ABPCs described herein results in less (e.g., a 1% decrease to about a 99% decrease, or any of the subranges of this range described herein) of a reduction in the level of DLL3 presented on the surface of the target mammalian cell as compared to a composition including the same amount of a control ABPC (e.g., any of the control ABPCs described herein).
  • the composition does not result in a detectable reduction in the level of the DLL3 presented on the surface of the target mammalian cell.
  • the ABPC is cross-reactive with a non-human primate DLL3 and a human DLL3. In some examples, the ABPC is cross-reactive with a non-human primate DLL3, a human DLL3, and one or both of rat DLL3 and a mouse DLL3. In some examples, the ABPC is cross-reactive with a non-human primate DLL3, a human DLL3, a rat DLL3, and a mouse DLL3. In some examples, the ABPC is cross-reactive with mouse DLL3 and rat DLL3.
  • the first ABD binds to an epitope of DLL3 that is present on the surface of cells from an Old World Monkey.
  • a second ABD e.g., any of the exemplary ABDs described herein.
  • the second ABD specifically binds to DLL3 (e.g., the same or a different epitope on DLL3 as compared to the first ABD).
  • the second ABD is the same as the first ABD.
  • the second ABD binds to an epitope on the surface of an immune cell (e.g., a T cell or a NK cell) (e.g., CD3).
  • an immune cell e.g., a T cell or a NK cell
  • any of the antigen-binding protein constructs disclosed herein can also be used as a template for engineering pH-dependent binding (e.g., by introduction of one or more histidines into one or more of its six CDRs).
  • Antigen-Binding Protein Constructs [0258] Any of the antigen-binding protein constructs (ABPCs) described herein can be a single polypeptide, or can include 2, 3, 4, 5, 6, 7, 8, 9, or 10 (the same or different) polypeptides. In some aspects where the ABPC is a single polypeptide, the ABPC can include a single ABD or two ABDs.
  • the first and second ABDs can be identical or different from each other (and can specifically bind to the same or different antigens or epitopes).
  • the first ABD and the second ABD (if present) can each be independently selected from the group of: a VH domain, a VHH domain, a VNAR domain, and a scFv.
  • the antigen-binding protein construct can be a BiTe, a (scFv)2, a nanobody, a nanobody-HSA, a DART, a TandAb, a scDiabody, a scDiabody-CH3, scFv-CH-CL-scFv, a HSAbody, scDiabody- HAS, a tandem-scFv, an Adnectin, a DARPin, a fibronectin, a DEP conjugate, a PROTAB, and a PROTAC.
  • ABDs that can be used when the ABPC is a single polypeptide are known in the art.
  • a VHH domain is a single monomeric variable antibody domain that can be found in camelids.
  • a VNAR domain is a single monomeric variable antibody domain that can be found in cartilaginous fish.
  • V H H domains and V NAR domains are described in, e.g., Cromie et al., Curr. Top. Med. Chem.15:2543-2557, 2016; De Genst et al., Dev. Comp. Immunol. 30:187-198, 2006; De Meyer et al., Trends Biotechnol. 32:263-270, 2014; Kijanka et al., Nanomedicine 10:161-174, 2015; Kovaleva et al., Expert. Opin. Biol.
  • the ABPC is a single polypeptide and includes two ABDs
  • the first ABD and the second ABD can both be VHH domains, or at least one ABD can be a VHH domain.
  • the ABPC includes two or more polypeptides
  • two, three, four, five or six of the polypeptides of the two or more polypeptides can be identical.
  • two or more of the polypeptides of the ABPC can assemble (e.g., non- covalently assemble) to form one or more ABDs, e.g., an antigen-binding fragment of an antibody (e.g., any of the antigen-binding fragments of an antibody described herein), a VHH-scAb, a VHH- Fab, a Dual scFab, a F(ab’)2, a diabody, a crossMab, a DAF (two-in-one), a DAF (four-in-one), a DutaMab, a DT-IgG, a knob
  • Non-limiting examples of an antigen-binding fragment of an Attorney Docket No.: 45395-0068WO1 antibody include an Fv fragment, a Fab fragment, a F(ab')2 fragment, and a Fab' fragment.
  • an antigen-binding fragment of an antibody is an antigen-binding fragment of an IgG (e.g., an antigen-binding fragment of IgG1, IgG2, IgG3, or IgG4) (e.g., an antigen- binding fragment of a human or humanized IgG, e.g., human or humanized IgG1, IgG2, IgG3, or IgG4); an antigen-binding fragment of an IgA (e.g., an antigen-binding fragment of IgA1 or IgA2) (e.g., an antigen-binding fragment of a human or humanized IgA, e.g., a human or humanized IgA1 or IgA2); an antigen-binding fragment of an IgD (e.g., an antigen-binding fragment of a human or humanized IgD); an antigen-binding fragment of an IgE (e.g., an antigen-binding fragment of a human or
  • a “Fv” fragment includes a non-covalently-linked dimer of one HCVD and one LCVD.
  • a “Fab” fragment includes, the constant domain of the light chain and the first constant domain (C H1 ) of the heavy chain, in addition to the heavy and LCVDs of the Fv fragment.
  • a “F(ab')2” fragment includes two Fab fragments joined, near the hinge region, by disulfide bonds.
  • a “dual variable domain immunoglobulin” or “DVD-Ig” refers to multivalent and multispecific binding proteins as described, e.g., in DiGiammarino et al., Methods Mol. Biol.
  • the dissociation constant (KD) of the first ABD (and optionally the second ABD, if present) at a pH of about 4.0 to about 6.5 is greater (e.g., detectably greater) (e.g., at least 0.2-fold greater, or any of the fold greater or ranges of fold greater recited in US 2022/0281984), than the KD at a pH of about 7.0 to about 8.0 (e.g., any of the subranges of this range described herein).
  • the first and second ABDs are identical or are at least 80% identical (e.g., ⁇ 82%, ⁇ 84%, ⁇ 86%, ⁇ 88%, ⁇ 90%, ⁇ 91%, ⁇ 92%, ⁇ 93%, ⁇ 94%, ⁇ 95%, ⁇ 96%, ⁇ 97%, ⁇ 98%, or ⁇ 99% identical) in amino acid sequence to each other.
  • the ABPCs that include a first ABD and a second ABD, the first ABD and the second ABD have a sequence that is less than 80% identical (e.g., ⁇ 75% , ⁇ 70% , ⁇ 65% , ⁇ 60% , ⁇ 55% , ⁇ 50% , ⁇ 45% , ⁇ 40% , ⁇ 35% , ⁇ 30% , ⁇ 25% , ⁇ 20% , ⁇ 15% , ⁇ 10% , or ⁇ 5% identical) to each other.
  • 80% identical e.g., ⁇ 75% , ⁇ 70% , ⁇ 65% , ⁇ 60% , ⁇ 55% , ⁇ 50% , ⁇ 45% , ⁇ 40% , ⁇ 35% , ⁇ 30% , ⁇ 25% , ⁇ 20% , ⁇ 15% , ⁇ 10% , or ⁇ 5% identical
  • the first and second ABD binds two different epitopes (e.g., two different epitopes on DLL3 Attorney Docket No.: 45395-0068WO1 or the first ABD binding specifically to DLL3 and the second ABD binding to an antigen other than DLL3).
  • the K D of the first ABD (and optionally, the second ABD if present) at a pH of about 7.0-8.0 is between about 1 pM-5 ⁇ M (e.g., 1 pM-2 ⁇ M, or any of the ranges of KD recited in WO 2021/022039 at pages 471-492 (or recited in published application US 2022/0281984), which are herein incorporated by reference in their entirety).
  • the half-life of the ABPC in vivo is increased (e.g., a detectable increase) as compared to the half-life of a control ABPC (e.g., any of the exemplary control ABPCs described herein).
  • the half-life of the ABPC in vivo may be decreased as compared to the half-life of a control ABPC.
  • Conjugation [0279]
  • the ABPCs provided herein can be conjugated to a drug (e.g., a chemotherapeutic drug, a small molecule), a toxin, or a radioisotope.
  • a drug e.g., a chemotherapeutic drug, a small molecule
  • a toxin e.g., a toxin
  • a radioisotope e.g., a radioisotope.
  • a conjugated composition An ABPC conjugated to a drug (e.g., a chemotherapeutic drug, a small molecule), a toxin, or a radioisotope is referred to as “a conjugated composition” herein.
  • a drug e.g., a chemotherapeutic drug, a small molecule
  • a toxin e.g., a toxin
  • a radioisotope e.g., a drug conjugated to as “a conjugated composition” herein.
  • at least one polypeptide of any of the ABPCs described herein is conjugated to the toxin, the radioisotope, or the drug via a cleavable linker.
  • the cleavable linker includes a protease cleavage site.
  • the cleavable linker is cleaved on the ABPC once it is transported to the lysosome or late endosome by the target mammalian
  • cleavage of the linker functionally activates the drug or toxin.
  • Attorney Docket No.: 45395-0068WO1 at least one polypeptide of any of the ABPCs described herein is conjugated to the toxin, the radioisotope, or the drug via a non-cleavable linker.
  • the conjugated toxin, radioisotope, or drug is released during lysosomal and/or late endosomal degradation of the ABPC.
  • Non-limiting examples of cleavable linkers include: hydrazone linkers, peptide linkers, disulfide linkers, and thioether linkers.
  • Non-limiting examples of non-cleavable linkers include: maleimide alkane-linkers and maleimide cyclohexane linker (MMC) (see, e.g., McCombs et al., AAPS J.17(2):339-351, 2015).
  • MMC maleimide cyclohexane linker
  • any of the ABPCs described herein is cytotoxic or cytostatic to the target mammalian cell.
  • the ABPCs(e.g., antibodies) provided herein can comprise one or more amino acid substitutions to provide a conjugation site (e.g., conjugated to a drug, a toxin, a radioisotope).
  • the ABPCs (e.g., antibodies) provided herein can have one conjugation site. In some aspects, the ABPCs (e.g., antibodies) described herein can have two conjugation sites. In some aspects, the ABPCs (e.g., antibodies) provided herein can have three or more conjugation sites. [0286] Naturally-occurring cysteine amino acids can also provide conjugation. In some aspects, the ABPCs (e.g., antibodies) provided herein can have a drug, a toxin, or a radioisotope conjugated at one or more naturally-occurring conjugation sites.
  • the ABPCs (e.g., antibodies) provided herein can have a drug, a toxin, or a radioisotope conjugated at one or more naturally- occurring conjugation sites.
  • the ABPCs (e.g., antibodies) provided herein can have a drug, a toxin, or a radioisotope conjugated at one or more naturally occurring conjugation sites and one or more engineered conjugation sites.
  • Conjugation through engineered cysteines is achieved by methods known in the art.
  • engineered cysteine-containing ABPC e.g., antibody
  • a reducing agent for example, tris (2-carboxyethyl) phosphine (TCEP), Dithiothreitol (DTT), or 2-Mercaptoethanol (BME).
  • TCEP 2,2-carboxyethyl) phosphine
  • DTT Dithiothreitol
  • BME 2-Mercaptoethanol
  • the crude conjugated ABPC solution may be further purified by methods known in the art, including hydrophobic interaction chromatography, ion-exchange chromatography, or mixed-mode chromatography such as ceramic hydroxyapatite chromatography. Isolation of chromatography fractions allows selection of the desired ABPC to payload ratio (e.g., desired antibody to payload ratio) and removal of unreacted ABPC (e.g., unreacted antibody), protein aggregates and fragments, and payload- related reaction side products.
  • the purified ABPC drug conjugate e.g., purified antibody drug conjugate
  • an ABPC conjugate e.g., antibody conjugate (ADC)
  • ADC antibody conjugate
  • DLL3-binding IgG herein linked to monomethyl auristatin E (MMAE) via a valine-citrulline (vc) linker
  • MMAE monomethyl auristatin E
  • vc valine-citrulline linker
  • vcMMAE is added to a final vcMMAE:mAb molar ratio of 4:1.
  • the conjugation reaction is carried out in the presence of 10% v/v of DMA and allowed to proceed at 25° C for 3 hours.
  • Expression of an Antigen-Binding Protein Construct in a Cell also provided herein are methods of generating a recombinant cell that expresses an ABPC (e.g., any of the ABPCs described herein) that include: introducing into a cell a nucleic acid encoding the ABPC to produce a recombinant cell; and culturing the recombinant cell under conditions sufficient for the expression of the ABPC.
  • the introducing step includes introducing into a cell an expression vector including a nucleic acid encoding the ABPC to produce a recombinant cell.
  • any of the ABPCs described herein can be produced by any cell, e.g., a eukaryotic cell or a prokaryotic cell.
  • the term “eukaryotic cell” refers to a cell having a distinct, membrane-bound nucleus. Such cells may include, for example, mammalian (e.g., rodent, non- human primate, or human), insect, fungal, or plant cells.
  • the eukaryotic cell is a Attorney Docket No.: 45395-0068WO1 yeast cell, such as Saccharomyces cerevisiae.
  • the eukaryotic cell is a higher eukaryote, such as mammalian, avian, plant, or insect cells.
  • the term “prokaryotic cell” refers to a cell that does not have a distinct, membrane-bound nucleus.
  • the prokaryotic cell is a bacterial cell.
  • cells can be cultured by contacting a cell (e.g., any cell) with a cell culture medium that includes the necessary growth factors and supplements to support cell viability and growth.
  • a cell e.g., any cell
  • a cell culture medium that includes the necessary growth factors and supplements to support cell viability and growth.
  • ABPCs ABPCs from a cell (e.g., a eukaryotic cell) using techniques well-known in the art (e.g., ammonium sulfate precipitation, polyethylene glycol precipitation, ion-exchange chromatography (anion or cation), chromatography based on hydrophobic interaction, metal-affinity chromatography, ligand-affinity chromatography, and size exclusion chromatography).
  • a cell e.g., a eukaryotic cell
  • techniques well-known in the art e.g., ammonium sulfate precipitation, polyethylene glycol precipitation, ion-exchange chromatography (anion or cation), chromatography based on hydrophobic interaction, metal-affinity chromatography, ligand-affinity chromatography, and size exclusion chromatography.
  • Methods of Treatment Provided herein are methods of treating a DLL3-positive cancer characterized by having a population of DLL-3 positive cancer cells, which include: administering a therapeutically effective amount of any of the pharmaceutical compositions described herein or any of the ABPCs described herein to a subject identified as having a cancer characterized by having the population of cancer cells.
  • methods of reducing the volume of a tumor in a subject, wherein the tumor is characterized by having a population of DLL3-positive cancer cells that include: administering a therapeutically effective amount of any of the pharmaceutical compositions described herein or any of the ABPCs described herein to the subject.
  • the volume of at least one tumor (e.g., solid tumor) or tumor location Attorney Docket No.: 45395-0068WO1 (e.g., a site of metastasis) is reduced (e.g., a detectable reduction) by ⁇ 1%, ⁇ 2%, ⁇ 3%, ⁇ 4%, ⁇ 5%, ⁇ 6%, ⁇ 8%, ⁇ 10%, ⁇ 12%, ⁇ 14%, ⁇ 16%, ⁇ 18%, ⁇ 20%, ⁇ 22%, ⁇ 24%, ⁇ 26%, ⁇ 28%, ⁇ 30%, ⁇ 35%, ⁇ 40%, ⁇ 45%, ⁇ 50%, ⁇ 55%, ⁇ 60%, ⁇ 65%, ⁇ 70%, ⁇ 75%, ⁇ 80%, ⁇ 85%, ⁇ 90%, ⁇ 95%, or ⁇ 99%) reduced as compared to the size of the at least one tumor (e.g., solid tumor) before administration of the ABPC.
  • the at least one tumor e.g.,
  • Also provided herein are methods of inducing cell death in a DLL3-positive cancer cell in a subject that include: administering a therapeutically effective amount of any of the pharmaceutical compositions of described herein or any of the ABPCs described herein to the subject.
  • the cell death that is induced is necrosis.
  • the induced cell death is apoptosis.
  • the subject has been previously identified or diagnosed as having a DLL3-positive cancer or as having a DLL3-positive cancer cell.
  • the DLL3-positive cancer is a primary tumor or a metastasis.
  • the DLL3-positive cancer is a non-T-cell-infiltrating tumor. In some aspects of any of the methods described herein, the DLL3- positive cancer is a T-cell-infiltrating tumor.
  • methods of decreasing the risk of developing a metastasis or decreasing the risk of developing an additional metastasis in a subject having a DLL3-positive cancer that include: administering a therapeutically effective amount of any of the pharmaceutical compositions of described herein or any of the ABPCs described herein to the subject (e.g., a subject previously identified or diagnosed as having a DLL3-positive cancer).
  • the risk of developing a metastasis or the risk of developing an additional metastasis is decreased by ⁇ 1%, by ⁇ 2%, ⁇ 3%, ⁇ 4%, ⁇ 5%, ⁇ 6%, ⁇ 8%, ⁇ 10%, ⁇ 12%, ⁇ 14%, ⁇ 16%, ⁇ 18%, ⁇ 20%, ⁇ 25%, ⁇ 30%, ⁇ 35%, ⁇ 40%, ⁇ 45%, ⁇ 50%, ⁇ 55%, ⁇ 60%, ⁇ 65%, ⁇ 70%, ⁇ 75%, ⁇ 80%, ⁇ 85%, ⁇ 90%, ⁇ 95%, or ⁇ 99% in the subject as compared to the risk of a subject having a similar cancer, but administered no treatment or a treatment that does not include the administration of any of the ABPCs described herein.
  • the DLL3-positive cancer is a non-T-cell-infiltrating tumor.
  • the DLL3- Attorney Docket No.: 45395-0068WO1 positive cancer is a T-cell-infiltrating tumor.
  • the cellular compartment is part of the endosomal/lysosomal pathway. In some aspects of any of the methods described herein, the cellular compartment is an endosome.
  • the subject or “subject suitable for treatment” may be a canine (e.g., a dog), feline (e.g., a cat), equine (e.g., a horse), ovine, bovine, porcine, caprine, primate, e.g., a simian (e.g., a monkey (e.g., marmoset, baboon), or an ape (e.g., a gorilla, chimpanzee, orangutan, or gibbon) or a human; or rodent (e.g., a mouse, a guinea pig, a hamster, or a rat).
  • a canine e.g., a dog
  • feline e.g., a cat
  • equine e.g., a horse
  • ovine, bovine, porcine caprine
  • primate e.g., a simian (e.g.,
  • the growth of a solid tumor is primary growth of a solid tumor.
  • the growth of a solid tumor e.g., a solid DLL3-positive tumor
  • the growth of a solid tumor is recurrent growth of a solid tumor.
  • the growth of a solid tumor is metastatic growth of a solid tumor.
  • treatment results in about a 1% decrease to about 99% decrease (or any of the subranges of this range described herein) in the growth of a solid tumor (e.g., a solid DLL3-positive tumor) in the subject (e.g., as compared to the growth of the solid tumor (e.g., solid DLL3-positive Attorney Docket No.: 45395-0068WO1 tumor) in the subject prior to treatment or the growth of a similar solid tumor (e.g., a similar solid DLL3-positive tumor) in a different subject receiving a different treatment or receiving no treatment).
  • a solid tumor e.g., a solid DLL3-positive tumor
  • a similar solid tumor e.g., a similar solid DLL3-positive tumor
  • a solid tumor e.g., a solid DLL3-positive tumor
  • imaging methods e.g., positron emission tomography, X-ray computed tomography, computed axial tomography, and magnetic resonance imaging.
  • Also provided herein are methods of decreasing the risk of developing a metastasis or an additional metastasis over a period of time in a subject identified as having a DLL3- cancer e.g., any of the exemplary DLL3-positive cancers described herein
  • methods of decreasing the risk of developing a metastasis or an additional metastasis over a period of time in a subject identified as having a DLL3- cancer that include administering to the subject a therapeutically effective amount of any of the proteins described herein or any of the pharmaceutical compositions described herein (e.g., as compared to a subject having a similar DLL3-positive cancer and receiving a different treatment or receiving no treatment).
  • the metastasis or additional metastasis is one or more to a bone, lymph nodes, brain, lung, liver, skin, chest wall including bone, cartilage and soft tissue, abdominal cavity, contralateral breast, soft tissue, muscle, bone marrow, ovaries, adrenal glands, and pancreas.
  • the period of time is ⁇ 1 month to ⁇ 3 years (e.g., ⁇ 1-30, 1-24, 2-18, 1-12, 1-10, 1-8, 1-6, 1-5, 1-4, 1-3, 1-2, 2-36, 2-30, 2-24, 2-18, 2- 12, 2-10, 2-8, 2-6, 2-5, 2-4, 2-3, 3-36, 3-30, 3-24, 3-18, 3-12, 3-10, 3-8, 3-6, 3-5, 3-4, 4-36, 4-30, 4-24, 4-18, 4-12, 4-10, 4-8, 4-6, 4-5, 5-36, 5-30, 5-24, 5-18, 5-12, 5-10, 5-8, 5-6, 6-36, 6-30, 6-24, 6-18, 6-12, 6-10, 6-8, 8-36, 8-30, 8-24, 8-18, 8-12, 8-10, 10-36, 10-30, 10-24, 10-18, 10-12, 12- 36, 12-30, 12-24, 12-18, 18-36, 18-30
  • the risk of developing a metastasis or developing an additional metastasis over a period of time in a subject identified as having a DLL3-positive cancer is decreased by ⁇ 1% to ⁇ 99% (e.g., or any of the subranges of this range described herein), e.g., as compared to the risk in a subject having a similar cancer receiving a different treatment or receiving no treatment.
  • DLL3-positive cancer include: lung cancer, prostate cancer, neuroendocrine cancer, melanoma, glioma, glioblastoma, thyroid cancer, bladder cancer, testicular cancer, carcinoma, and medulloblastoma.
  • the DLL3-positive cancer is a small cell lung cancer (SCLC).
  • SCLC small cell lung cancer
  • the DLL3-positive cancer is a prostate cancer. Attorney Docket No.: 45395-0068WO1
  • the DLL3-positive cancer is a neuroendocrine cancer, for example but not solely, a neuroendocrine prostate cancer (NEPC).
  • NEPC neuroendocrine prostate cancer
  • the DLL3-positive cancer is a lung adenocarcinoma with neuroendocrine features.
  • the DLL3-positive cancer is a melanoma including a metastatic melanoma.
  • the patient is further administered one or more additional therapeutic agents (e.g., one or more of a chemotherapeutic agent, a recombinant cytokine or interleukin protein, a kinase inhibitor, and a checkpoint inhibitor).
  • the one or more additional therapeutic agents is administered to the patient at approximately the same time as any of the ABPCs described herein are administered to the patient.
  • the one or more additional therapeutic agents are administered to the patient after the administration of any of the ABPCs described herein to the patient.
  • the one or more additional therapeutic agents are administered to the patient before the administration of any of the ABPCs described herein to the patient.
  • the DLL3-positive cancer is a solid cancer (e.g., a lung cancer, a prostate cancer, a neuroendocrine cancer, a melanoma, a glioma, a glioblastoma, a thyroid cancer, a bladder cancer, a testicular cancer, a carcinoma, or a medulloblastoma).
  • a solid cancer e.g., a lung cancer, a prostate cancer, a neuroendocrine cancer, a melanoma, a glioma, a glioblastoma, a thyroid cancer, a bladder cancer, a testicular cancer, a carcinoma, or a medulloblastoma.
  • compositions can include a pharmaceutically acceptable carrier (e.g., phosphate buffered saline).
  • a pharmaceutically acceptable carrier e.g., phosphate buffered saline.
  • Single or multiple administrations of any of the pharmaceutical compositions described herein can be given to a subject depending on, for example: the dosage and frequency as required and tolerated by the patient.
  • a dosage of the pharmaceutical composition should provide a sufficient quantity of the ABPC to effectively treat or ameliorate conditions, diseases, or symptoms.
  • methods of treating a subject having a DLL3-positive cancer e.g., any of the DLL3-positive cancers described herein
  • administering a therapeutically effective amount of at least one of any of the compositions or pharmaceutical compositions provided herein include administering a therapeutically effective amount of at least one of any of the compositions or pharmaceutical compositions provided herein.
  • kits that include any of the ABPCs described herein, any of the compositions described herein, or any of the pharmaceutical compositions described herein.
  • the kits can include instructions for performing any of the methods described herein.
  • the kits can include at least one dose of any of the compositions (e.g., pharmaceutical compositions) described herein.
  • the kits can provide a syringe for administering any of the pharmaceutical compositions described herein.
  • Antigen-Binding Protein Constructs that include: a first ABD that is capable of specifically binding DLL3, where: (a) the dissociation rate of the first ABD at a pH of about 7.0 to about 8.0 (or any of the subranges of this range described herein) is faster than the dissociation rate at a pH of about 4.0 to about 6.5 (or any of the subranges of this range described herein); and/or (b) the dissociation constant (KD) of the first ABD at a pH of about 7.0 Attorney Docket No.: 45395-0068WO1 to about 8.0 (or any of the subranges of this range) is greater than the KD at a pH of about 4.0 to about 6.5.
  • ABPCs antigen-binding protein constructs
  • the first approach published monoclonal antibodies against DLL3 are used as a Attorney Docket No.: 45395-0068WO1 starting template for introduction of additional mutations that allow engineering of pH-dependent binding to DLL3 and i) enhanced endolysosomal accumulation of a conjugated toxin, as well as ii) enhanced DLL3 recycling to the cell surface.
  • the second approach involves discovery of de novo ABPCs specific for DLL3 via antibody display methods from naive libraries or libraries with defined CDR compositions and screening under conditions designed for selection of pH- engineered ABPCs specific for DLL3. In either case, histidine residues play an important role in engineering pH-dependent binding proteins.
  • Histidine residues are at least partially protonated at a pH below 6.5 owing to its pKa of 6.0. Therefore, if a histidine side chain in an ABD participates in an electrostatic binding interaction with its antigen it will start to turn positively charged at a pH at or below 6.5. This could either weaken or enhance the binding affinity of the interaction at a pH below 6.5, based on the corresponding charge of and interactions with the antigen epitope.
  • CDRs antibody complementarity determining regions
  • the first approach therefore involves histidine-scanning of variable region sequences of published monoclonal antibodies to identify pH-dependent variants.
  • Multiple DLL3-binding monoclonal antibodies have been described in the literature and can be used as a template for engineering pH-dependent binding. Briefly, for a subset of the antibody sequences, CDRs in each chain are identified using the methods described by Kabat et al (Kabat et al.
  • Antibody variants with only one histidine or alanine mutation in a heavy/light chain CDR are generated by co-transfection of Expi293 cells with a) one heavy chain or light chain sequence variant, and b) the corresponding starting ABPC (e.g., the starting DLL3-binding monoclonal antibody) light chain or heavy chain, respectively, using methods known to the art.
  • ABPC e.g., the starting DLL3-binding monoclonal antibody
  • cell culture supernatants are normalized to an antibody expression level of 50 ⁇ g/mL, and captured on an anti-human Fc sensor (Forte Bio).
  • a baseline is established using 1X kinetics buffer (Forte Bio), and the sensor is associated with 100 nM of DLL3 in 1X PBS at pH 7.4 for 300 sec to generate an association curve.
  • the antibody-antigen complex on the sensor is exposed to 1X PBS at either pH 5.5 or pH 7.4 for 300-500 sec.
  • Association and dissociation phase curves are examined for the starting ABPC antibody and each corresponding antibody variant at pH 5.5 and pH 7.4 to inform on two criteria: a) enhanced dissociation (i.e., higher koff values) at pH 5.5 due to histidine or alanine substitution compared to the starting ABPC, and b) reduced dissociation at pH 7.4 (i.e., lower koff values) compared to pH 5.5 in the antibody variant itself and with the starting ABPC.
  • Variants that show either enhanced dissociation at pH 5.5 or reduced dissociation at pH 7.4 or both are selected for further analysis.
  • histidine and alanine mutations obliterate DLL3 binding, others are tolerated with little (e.g., less than 1-fold change in KD or dissociation rate) or no change in DLL3 binding kinetics.
  • histidine is a large, positively charged amino acid
  • these histidine variants and alanine variants with no change are noted as positions that may tolerate a wide range of mutations and lead to antibodies with different sequence but similar binding properties, a designation that is not otherwise apparent.
  • the variants selected for further analysis are expressed at a larger scale and purified using protein A affinity chromatography.
  • Antibodies with a rate of dissociation ratio less than that of the starting ABPC and/or a dissociation constant ratio less than that of the starting ABPC are selected for further assessment of combinatorial substitutions.
  • Favorable histidine and/or alanine amino acid positions can also be combined to enhance pH dependence; this can be done by, e.g., combinatorially or rationally combining histidine and/or alanine substitutions on a given heavy or light chain that individually improve pH dependence, by, e.g., Attorney Docket No.: 45395-0068WO1 combinatorially or rationally combining modified heavy and light chains such that histidine and/or alanine substitutions are present on both chains, or combinations thereof.
  • pH-engineered ABPCs specific for DLL3 Such combinatorial variants are generated and tested/analyzed for differential pH dependence using the methods and protocols described herein, or others known to the art. Antibody variants that have the lowest rate of dissociation ratios and/or dissociation constant ratios are selected as candidates for further analysis (hereafter referred to as “pH-engineered ABPCs specific for DLL3”).
  • the second method for selection of pH-engineered ABPCs specific for DLL3 involves either screening libraries to identify de novo pH-dependent ABPCs specific for DLL3 or ABPCs that could serve as templates for engineering pH-dependent binding as described herein.
  • naive phage/yeast display antibody libraries e.g., Fab, scFv, VHH, VL, or others known to the art
  • phage/yeast display libraries where CDRs have been mutated to express a subset of amino acid residues.
  • Libraries are screened against soluble recombinant DLL3 extracellular domains using methods known to the art with positive selection for variants that bind weakly (e.g., are eluted from beads) at pH 5.0 and bind strongly (e.g., are bound to beads) at pH 7.4. Three rounds of selections are performed.
  • the final round of binders are screened using ELISA for binding to human DLL3 and cyno DLL3 and mouse DLL3 or via mean fluorescence intensity (MFI) in flow cytometric analysis. If more binders with cyno or murine cross-reactivity are desired, the final selection round can instead be performed on cyno DLL3 or murine DLL3.
  • Selected binding proteins are subcloned into mammalian expression vectors and expressed as either full IgG proteins or Fc fusions in Expi293 cells. BLI analysis is performed as described herein for selection of pH-dependent binder variants and confirmed using Biacore. Example 2.
  • pH-engineered ABPCs specific for DLL3 exhibit the desirable property of decreased DLL3 binding at acidic pH (e.g., pH 5.0, pH 5.5), but enhanced binding at higher pH (e.g., pH 7.4), which enhances their accumulation in endolysosomes under physiological conditions.
  • Cells are seeded at approximately 5-10,000 per well in 150 ⁇ L of pH 7.4 culture medium and incubated at 37 °C for 5 minutes at several doses (e.g., a two-fold dilution series) from 1 pM to 1 ⁇ M with one of the following antibodies: a known, control ABPC specific for DLL3, the pH- engineered ABPC specific for DLL3, and an appropriate negative isotype control mAb (e.g., Biolegend Purified Human IgG1 Isotype Control Recombinant Antibody, Cat#403501). Prior to the onset of the experiment, the binding properties of all antibodies are validated using methods known to the art.
  • cells are fixed with 4% formaldehyde (20 min at room temperature) and incubated with an appropriate fluorophore-labeled secondary antibody (e.g., ThermoFisher Mouse anti-Human IgG1 Fc Secondary Antibody, Alexa Fluor 488, Cat#A-10631) for 60 minutes. Unbound reagents are washed with a series of PBS washes, and the cell panels are imaged using confocal microscopy. Upon analysis of the images, significant fluorescence can be observed on the surface of cells bound with the known, control ABPC specific for DLL3 as well as the pH-engineered ABPC specific for DLL3, but little surface binding can be observed for the isotype negative control.
  • an appropriate fluorophore-labeled secondary antibody e.g., ThermoFisher Mouse anti-Human IgG1 Fc Secondary Antibody, Alexa Fluor 488, Cat#A-10631
  • Both pH-engineered ABPCs specific for DLL3 as well as a control ABPC specific for DLL3 are tested.
  • the cells are washed two times with 200 ⁇ L of FACS buffer (1x PBS containing 3% Fetal Bovine Serum) at either pH 7.4 or 5.0 depending on the condition being tested.
  • the purified protein samples are diluted into FACS buffer of the appropriate pH and added to the cells and allowed to bind for one hour on ice.
  • the plates are washed twice as before and resuspended in 1% paraformaldehyde in the appropriate FACS buffer to fix them for flow cytometry analysis. All conditions are read on a flow cytometer (Accuri C6, BD Biosciences). Binding is observed as a shift in the FLI signal (as a MFI) versus secondary alone.
  • An identical but separate plate is also incubated on ice that is Attorney Docket No.: 45395-0068WO1 meant as a no-internalization negative control. Following this incubation, the experimental plate is moved to a 37 °C incubator, the negative control plate is kept on ice to slow or block internalization, and samples are taken at designated time points to create an internalization time course. Samples are placed into a U-bottom 96-well plate, and internalization is quenched via addition of 200 ⁇ L/well of ice-cold FACS buffer. The plates are spun down at 2000xg for 2 minutes, resuspended in 200 ⁇ L ice-cold FACS buffer, spun down again, and resuspended in FACS buffer a second time.
  • the novel ADCs and/or pH-engineered ADCs specific for DLL3 can also demonstrate increased toxin liberation in DLL3+ cells as compared to a control ABPC ADC specific for DLL3 (e.g., a control ABPC DLL3-IgG-DC).
  • an LC-MS/MS method is used to quantify unconjugated (i.e., liberated) MMAE in treated DLL3+ cells (Singh, A.P. and Shah, D.K. Drug Metabolism and Disposition 45.11 (2017): 1120-1132.)
  • An LC-MS/MS system with electrospray interphase and triple quadrupole mass spectrometer is used.
  • an equation for quantifying unconjugated MMAE in a biological sample is derived by dividing the peak area for each drug standard by the peak area obtained for the internal standard. The resultant peak area ratios are then plotted as a function of the standard concentrations, and data points are fitted to the curve using linear regression. Three QC samples are included in the low, middle, and upper ranges of the standard curve to assess the predictive capability of the developed standard curve. The standard curves obtained are then used to deduce the observed concentrations of MMAE in a biologic sample. For measurement of MMAE concentration, treated cell samples are pelleted and reconstituted in fresh media to a final concentration of 0.25 million cells/100 ⁇ L.
  • Decanted cells are stained with Live/Dead eFluor 660.
  • Cells are then centrifuged and washed with FACS buffer (PBS with 2% FBS), after which cell cycle distribution is analyzed with a BD CycletestTM Plus DNA Kit (cat # 340242). Briefly, cells are re- suspended in 76 ⁇ l Solution A and incubated for 10 min at room temperature.61 ⁇ L Solution B is then added, and cells are incubated for another 10 min at room temperature. Finally, 61 ⁇ L of cold Solution C is added, and cells are again incubated for 10 min at room temp.
  • FACS buffer PBS with 2% FBS
  • Cells are resuspended in 70% ethanol for at least 2 h at -20°C. Cells are then washed twice in PBS and suspended in 0.2% Triton X-100 (Sigma) in a 1% (w/v) solution of BSA (Sigma) in PBS for 30 min to suppress nonspecific Ab binding. Cells are centrifuged again (200 g, 5 min) and the cell pellet is suspended in 100 ⁇ L of 1% BSA containing 1:800 diluted anti-histone ⁇ H2AX polyclonal Ab (Trevigen, Gaithersburg, MD).
  • mice and/or monkeys are performed using pH-engineered ABPC specific for DLL3 and control ABPC specific for DLL3 using methods known to the art (e.g., Gupta, P., et al. (2016), mAbs, 8:5, 991-997).
  • a single intravenous bolus e.g., 5 mg/kg
  • a single intravenous bolus e.g., 5 mg/kg
  • bispecific DLL3 bispecific ABPC and demonstration of exemplary properties as compared to a control bispecific ABPC
  • a bispecific antibody that binds two different epitopes on DLL3 is constructed. It is known in the art that biparatopic antibodies can show increased antigen-dependent internalization, and are therefore useful for applications such as antibody-drug conjugates (e.g., see Li et al (2016) A Biparatopic HER2-Targeting Antibody-Drug Conjugate Induces Tumor Regression in Primary Models Refractory to or Ineligible for HER2-Targeted Therapy, Cancer Cell 29:117-29).
  • a pH-engineered DLL3 x DLL3 bispecific, biparatopic ABPC specific for DLL3 is assembled using light chain/heavy chain pairs from two different pH- or non-pH-engineered ABPCs specific for DLL3, each of which binds a distinct epitope on DLL3 that does not overlap with the other epitope.
  • a set of pH-engineered ABPCs specific for DLL3 that bind non-overlapping epitopes are discovered, e.g., using the methods described herein, or others known to one of ordinary skill in the art.
  • a baseline is established using 1X kinetics buffer (Forte Bio), and the sensor is associated with 50 nM of DLL3 in 1X PBS (that has been mixed and pre-incubated for 30 min at 37 °C with a second ABPC specific for DLL3 transfection supernatant or the first ABPC specific for DLL3 transfection supernatant, both normalized to 50ug/mL) at pH 7.4 for 300 sec to generate an association curve.
  • Example 10 Anti-DLL3 antibody discovery in rabbit and characterization of novel anti- DLL3 antibodies
  • Two New Zealand white rabbits were immunized with the recombinant His6-tagged extracellular domain (ECD) of DLL3 (SEQ ID NO: 2) and boosted four times with the same immunogen (200 ⁇ g for initial and final immunizations, 100 ug for interim boosts).
  • Test bleeds were collected after the second and third boost, respectively, and serum titer was determined by anti-DLL3 ELISA in a 384-well plate.
  • the humanized anti-DLL antibodies exhibited properties associated with highly developable biotherapeutic agents. Moreover, the humanized antibodies exhibited distinct binding profiles, with some recognizing certain DLL3 epitopes (e.g., DLL3 Attorney Docket No.: 45395-0068WO1 epitope 1, 3, 5, 6, and 7) and certain truncated DLL3 constructs (e.g., DLL3 EGF1 domain, DSL domain, N-terminus, and the proximal domain of DLL3, EGF6). Further, many of the humanized rabmAb demonstrated single digit nM affinity or below determined by BLI and cell-based binding assays.
  • DLL3 epitopes e.g., DLL3 Attorney Docket No.: 45395-0068WO1 epitope 1, 3, 5, 6, and 7
  • certain truncated DLL3 constructs e.g., DLL3 EGF1 domain, DSL domain, N-terminus, and the proximal domain of DLL3, EGF6
  • HIC hydrophobic interaction chromatography, which was performed on an Agilent 1260 Infinity II HPLC with a Sepax HIC Butyl-NP54.6x100mm column and a 35min method at 1mL/min flow rate with a gradient from 150mM sodium phosphate pH7, 1M NaCl to 150mM sodium phosphate buffer pH7, retention times (RTs) are given in minutes.
  • RTs retention times
  • Polyspecificity is a measure of a given anti-DLL3 antibody’s capacity to bind specifically to proteins other than DLL3. Polyspecificity was determined in ELISA assays against baculovirus particle, DNA, lipopolysaccharide and insulin.
  • Yield means the protein yield after ProA purification of 50mL transfections of expression plasmids encoding the heavy and light chains corresponding to the indicated MYT # antibody in HEK293.
  • Internalization means fold over reference antibody MYT0638.
  • Epipe refers to the region on DLL3 specifically recognized by each indicated anti- DLL3 antibody.
  • Epipe binning is known in the art and may be carried out generally as follows: antibodies against a target antigen are tested against other antibodies in a pairwise fashion to determine whether antibodies specifically block one another's binding to the epitope of an antigen.
  • an antibody is deemed to be a member of the same bin (or epitope bin) when it can substantially, including completely, prevent the binding of a reference member of the same bin.
  • bin member means one of the binders that recognizes a given “epitope bin” (or simply “bin”) of a given antigen (e.g., DLL3).
  • DLL3 a given antigen
  • Epitope Binning Methods As disclosed herein, epitope binning was performed on an octet RH16 instrument using a sandwich assay. As indicated by the data disclosed herein, the novel anti- DLL3 antibodies recognize at least four (4) new epitopes.
  • MYT0638 (the VH and VL set forth in SEQ ID NOs: 241 and 242, respectively), MYT3181 (the VH and VL set forth in SEQ ID NOs: 243 and 244, respectively), and MYT3892 ((the VH and VL set forth in SEQ ID NOs: 247 and 248, respectively), each fully described in US20220313845A1, to Mythic Therapeutics, Inc., which is incorporated herein by reference in its entirety).
  • the twelve (12) humanized antibodies were produced using substantially the same methods from small scale production, and both groups of antibodies were purified over ProA, dialyzed to PBS and diluted to 10ug/mL.
  • FIG.1A provides a schematic of an exemplary sandwich assay binning method. Generally, in a sandwich binning assay the first ABPC is covalently attached to the surface of a biosensor. The antigen is then injected and binds to the first ABPC, followed by injection of the second ABPC.
  • the second Attorney Docket No.: 45395-0068WO1 ABPC binds to the antigen, it creates a ‘sandwich’, indicating that they have different epitopes and belong to separate bins.
  • the second ABPC is blocked from binding to the antigen by the first ABPC, it suggests that they have overlapping epitopes and should be binned together.
  • the first ABPC is covalently attached to the biosensor.
  • the antigen and the second ABPC are combined outside the instrument at saturating conditions and then tested as a complex.
  • the antigen is covalently attached to the biosensor surface.
  • FIG. 1B shows a tumor cell displaying an antigen (i.e., DLL3). Specifically, FIG.
  • FIG. 1B shows the extracellular domains of DLL3 which includes six epidermal growth factor (“EGF”)- like domains, a Delta/Serrate/Lag-2 (“DSL”) domain, and an N-terminal domain.
  • FIG. 1B also shows exemplary ABPCs of the present disclosure binding to specific epitopes of the DLL3 antigen.
  • the Octet RH16 cycle consisted of the following steps: baseline 1 (PBST pH7.4) 60 seconds; loading (Ab1) 180 seconds; baseline 2 (PBST pH7.4) 60 seconds; association (hDLL3) 120 seconds; blocking (trastuzumab) 120 seconds; baseline 3 (PBST pH7.4) 60 seconds; challenge (Ab2) 120s.
  • An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 205, 206, and 207, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 208, 209, and 210, respectively. [0401] Embodiment 2.
  • Embodiment 3 The antigen-binding protein construct of embodiment 1 or 2, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 239 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 240.
  • Embodiment 6 The antigen-binding protein construct of embodiment 4 or 5, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 101 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 102.
  • Embodiment 7 An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 21, 22, and 23, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 24, 25, and 26, respectively.
  • Embodiment 8 Embodiment 8.
  • Embodiment 9 The antigen-binding protein construct of embodiment 7, wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 19 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 20.
  • Embodiment 9 The antigen-binding protein construct of embodiment 7 or 8, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 103 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 104.
  • Embodiment 12 The antigen-binding protein construct of embodiment 10 or 11, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 105 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 106.
  • An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 45, 46, and 47, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 48, 49, and 50, respectively.
  • HCVD heavy chain variable domain
  • LCDVD light chain variable domain
  • Embodiment 18 The antigen-binding protein construct of embodiment 16 or 17, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 109 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 110.
  • Embodiment 21 The antigen-binding protein construct of embodiment 19 or 20, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 111 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 112.
  • Embodiment 22 comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 111 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 112.
  • An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 61, 62, and 63, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 64, 65, and 66, respectively.
  • HCVD heavy chain variable domain
  • LCDVD light chain variable domain
  • Embodiment 24 The antigen-binding protein construct of embodiment 19 or 20, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 113 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 114.
  • Embodiment 25 An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 69, 70, and 71, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 72, 73, and 74, respectively.
  • HCVD heavy chain variable domain
  • LCDVD light chain variable domain
  • Embodiment 26 The antigen-binding protein construct of embodiment 25, wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 67 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 68.
  • Embodiment 27 The antigen-binding protein construct of embodiment 25 or 26, comprising a heavy chain comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 115 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 116.
  • Embodiment 29 The antigen-binding protein construct of embodiment 28, wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical Attorney Docket No.: 45395-0068WO1 to SEQ ID NO: 75 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 76.
  • Embodiment 30 The antigen-binding protein construct of embodiment 28, wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical Attorney Docket No.: 45395-0068WO1 to SEQ ID NO: 75 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 76.
  • the antigen-binding protein construct of embodiment 28 or 29, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 117 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 118.
  • Embodiment 31 comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 117 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 118.
  • An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 85, 86, and 87, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 88, 89, and 90, respectively.
  • HCVD heavy chain variable domain
  • LCDVD light chain variable domain
  • Embodiment 33 The antigen-binding protein construct of embodiment 31 or 32, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 119 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 120.
  • Embodiment 34 Embodiment 34.
  • An antigen-binding protein construct comprising an antigen binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 93, 94, and 95, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 96, 97, and 98, respectively.
  • Embodiment 35 Embodiment 35.
  • Embodiment 38 The antigen-binding protein construct of embodiment 37, wherein the antigen-binding protein construct is a monoclonal antibody comprising an IgG heavy chain constant region.
  • Embodiment 39 The antigen-binding protein construct of embodiment 37 or 38, comprising an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 99 and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 100.
  • Embodiment 40 Embodiment 40.
  • the antigen-binding protein construct of embodiment 37 or 38 comprising an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 101 and an LCVD that comprises a Attorney Docket No.: 45395-0068WO1 sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 102.
  • Embodiment 41 Embodiment 41.
  • the antigen-binding protein construct of embodiment 37 or 38 comprising an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 103 and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 104.
  • HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 103
  • an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 104.
  • the antigen-binding protein construct of embodiment 37 or 38 comprising an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 105 and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 106.
  • HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 105
  • an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 106.
  • the antigen-binding protein construct of embodiment 37 or 38 comprising an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 107 and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 108.
  • HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 107
  • an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 108.
  • the antigen-binding protein construct of embodiment 37 or 38 comprising an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 109 and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 110.
  • an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 109
  • an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 110.
  • the antigen-binding protein construct of embodiment 37 or 38 comprising an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 113 and an LCVD that comprises a Attorney Docket No.: 45395-0068WO1 sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 114.
  • Embodiment 47 Embodiment 47.
  • the antigen-binding protein construct of embodiment 37 or 38 comprising an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 115 and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 116.
  • HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 115
  • an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 116.
  • the antigen-binding protein construct of embodiment 37 or 38 comprising an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 117 and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 118.
  • HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 117
  • an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 118.
  • the antigen-binding protein construct of embodiment 37 or 38 comprising an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 119 and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 120.
  • HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 119
  • an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 120.
  • the antigen-binding protein construct of embodiment 37 or 38 comprising an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 121 and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 122.
  • Embodiment 51 A pharmaceutical composition comprising the antigen-binding protein construct of any one of embodiments 1-50 and a pharmaceutically acceptable excipient.
  • Embodiment 52 Embodiment 52.
  • a method of treating a cancer in a subject in need thereof comprising administering to the subject the DLL3-binding protein construct of any one of embodiments 1-50 or the pharmaceutical composition of embodiment 51.
  • Embodiment 53 A pharmaceutical composition comprising an effective amount of an antigen-binding protein construct (ABPC) comprising: a first antigen-binding domain (ABD) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell, wherein: the dissociation rate of the first ABD at a pH of ⁇ 4.0-6.5 is faster than Attorney Docket No.: 45395-0068WO1 the dissociation rate at a pH of ⁇ 7.0-8.0; and/or the KD of the first ABD at a pH of ⁇ 4.0-6.5 is greater than the KD at a pH of ⁇ 7.0-8.0.
  • ABPC antigen-binding protein construct
  • ABSD antigen-binding domain
  • Embodiment 54 The pharmaceutical composition of embodiment 53, wherein the first ABD comprises a heavy chain variable domain (HCVD) amino acid sequence selected from one of SEQ ID NO: 3, SEQ ID NO: 11, SEQ ID NO: 19, SEQ ID NO: 27, SEQ ID NO: 35, SEQ ID NO: 43, SEQ ID NO: 51, SEQ ID NO: 59, SEQ ID NO: 67, SEQ ID NO: 75, SEQ ID NO: 83, and SEQ ID NO: 91, optionally wherein the HCVD has at least one amino acid substituted with a histidine.
  • HCVD heavy chain variable domain
  • composition of embodiment 54 or 55 wherein the HCVD comprises an amino acid sequence as set forth in one of SEQ ID NOs: 3, 11, 19, 27, 35, 43, 51, 59, 67, 75, 83, and 91 or comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to an amino acid sequence as set forth in one of SEQ ID NOs: 3, 11, 19, 27, 35, 43, 51, 59, 67, 75, 83, and 91, optionally wherein the HCVD has at least one amino acid substituted with a histidine.
  • Embodiment 57 Embodiment 57.
  • invention 55 or 56 wherein the LCVD comprises an amino acid sequence as set forth in one of SEQ ID NOs: 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, and 92 or comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to an amino acid sequence as set forth in one of SEQ ID NOs: 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, and 92, optionally wherein the LCVD has at least one amino acid substituted with a histidine.
  • Embodiment 58 Embodiment 58.
  • HCVD comprises a set of three H-CDRs selected from the group consisting of: SEQ ID NOs: 5, 6, and 7; SEQ ID NOs: 13, 14, and 15; SEQ ID NOs: 21, 22, and 23; SEQ ID NOs: 29, 30, and 31; SEQ ID NOs: 37, 38, and 39; SEQ ID NOs: 45, 46, and 47; SEQ ID NOs: 53, 54, and 55; SEQ ID NOs: 61, 62, and 63; SEQ ID NOs: 69, 70, and 71; SEQ ID NOs: 77, 78, and 79; SEQ ID NOs: Attorney Docket No.: 45395-0068WO1 85, 86, and 87; SEQ ID NOs: 93, 94, and 95, optionally wherein the set of three H-CDRs has collectively one or more position substituted with a histidine.
  • Embodiment 59 The pharmaceutical composition of embodiment 57 or 58, wherein the LCVD comprises a set of three L-CDRs selected from the group consisting of: SEQ ID NOs: 8, 9, and 10; SEQ ID NOs: 16, 17, and 18; SEQ ID NOs: 24, 25, and 26; SEQ ID NOs: 32, 33, and 34; SEQ ID NOs: 40, 41, and 42; SEQ ID NOs: 48, 49, and 50; SEQ ID NOs: 56, 57, and 58; SEQ ID NOs: 64, 65, and 66; SEQ ID NOs: 72, 73, and 74; SEQ ID NOs: 80, 81, and 82; SEQ ID NOs: 88, 89, and 90; SEQ ID NOs: 96, 97, and 98, optionally wherein the set of three L-CDRs has collectively one or more position substituted with a histidine.
  • the set of three L-CDRs has collectively one or more position substituted with
  • Embodiment 60 The pharmaceutical composition of any one of embodiments 53-59, wherein the ABPC is degraded in the target mammalian cell following internalization of the ABPC by the target mammalian cell.
  • Embodiment 61 The pharmaceutical composition of any one of embodiments 53-60, wherein the ABPC further comprises a conjugated toxin, radioisotope, drug, or small molecule.
  • Embodiment 62 The pharmaceutical composition of embodiment 61, wherein the pharmaceutical composition provides for an increase in toxin liberation in the target mammalian cell as compared to a pharmaceutical composition comprising the same amount of a control ABPC.
  • Embodiment 63 Embodiment 63.
  • Embodiment 64 The pharmaceutical composition of any one of embodiments 61-63, wherein the pharmaceutical composition provides for an increase in target mammalian cell killing as compared to a pharmaceutical composition comprising the same amount of a control ABPC.
  • Embodiment 65 Embodiment 65.
  • Embodiment 64 wherein the pharmaceutical composition provides for at least a 20%, 50%, 2-fold, or 5-fold increase in target mammalian cell killing as compared to a pharmaceutical composition comprising the same amount of a control ABPC.
  • Embodiment 66 The pharmaceutical composition of any one of embodiments 53-62, wherein the pharmaceutical composition provides for an increase in endolysosomal delivery in the Attorney Docket No.: 45395-0068WO1 target mammalian cell as compared to a pharmaceutical composition comprising the same amount of a control ABPC.
  • Embodiment 67 Embodiment 67.
  • Embodiment 76 The composition of any one of embodiments 69 to 75, wherein the composition provides for at least a 20%, 50%, 2-fold, or 5-fold increase in toxin liberation in the target mammalian cell, and/or cell killing, and/or at least a 20%, 50%, 2-fold, or 5-fold increase in endolysosomal delivery as compared to a composition comprising the same amount of a control ABPC.
  • Attorney Docket No.: 45395-0068WO1 [0478] Embodiment 77.
  • the ABPC of embodiment 85 wherein the first ABD comprises a heavy chain variable domain (HCVD) amino acid sequence selected from one of SEQ ID NO: 3, SEQ ID NO: 11, SEQ ID NO: 19, SEQ ID NO: 27, SEQ ID NO: 35, SEQ ID NO: 43, SEQ ID NO: 51, SEQ ID NO: 59, SEQ ID NO: 67, SEQ ID NO: 75, SEQ ID NO: 83, and SEQ ID NO: 91, optionally wherein the HCVD has at least one amino acid substituted with a histidine.
  • HCVD heavy chain variable domain
  • the first ABD comprises a light chain variable domain (LCVD) amino acid sequence selected from one of SEQ ID NO: 4, SEQ ID NO: 12, SEQ ID NO: 20, SEQ ID NO: 28, SEQ ID NO: 36, SEQ ID NO: 44, SEQ ID NO: 52, SEQ ID NO: 60, SEQ ID NO: 68, SEQ ID NO: 76, SEQ ID NO: 84, and SEQ ID NO: 92, optionally wherein the HCVD has at least one amino acid substituted with a histidine.
  • Embodiment 88 Embodiment 88.
  • Embodiment 89 Embodiment 89.
  • the LCVD comprises an amino acid sequences of any one of SEQ ID NOs: 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, and 92 or comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to any one of SEQ ID NOs: 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, and 92, optionally wherein the LCVD has at least one amino acid substituted with a histidine.
  • Embodiment 90 Embodiment 90.
  • HCVD comprises a set of three H-CDRs selected from the group consisting of: SEQ ID NOs: 5, 6, and 7; SEQ ID NOs: 13, 14, and 15; SEQ ID NOs: 21, 22, and 23; SEQ ID NOs: 29, 30, and 31; SEQ ID NOs: 37, 38, and 39; SEQ ID NOs: 45, 46, and 47; SEQ ID NOs: 53, 54, and 55; SEQ ID NOs: 61, 62, and 63; SEQ ID NOs: 69, 70, and 71; SEQ ID NOs: 77, 78, and 79; SEQ ID NOs: 85, 86, and 87; SEQ ID Attorney Docket No.: 45395-0068WO1 NOs: 93, 94, and 95, optionally wherein the set of three H-CDRs has collectively one or more amino acid position substituted with a histidine.
  • Embodiment 91 The ABPC of embodiment 89 or 90, wherein the LCVD comprises a set of three L-CDRs selected from the group consisting of: SEQ ID NOs: 8, 9, and 10; SEQ ID NOs: 16, 17, and 18; SEQ ID NOs: 24, 25, and 26; SEQ ID NOs: 32, 33, and 34; SEQ ID NOs: 40, 41, and 42; SEQ ID NOs: 48, 49, and 50; SEQ ID NOs: 56, 57, and 58; SEQ ID NOs: 64, 65, and 66; SEQ ID NOs: 72, 73, and 74; SEQ ID NOs: 80, 81, and 82; SEQ ID NOs: 88, 89, and 90; SEQ ID NOs: 96, 97, and 98, optionally wherein the set of three L-CDRs has collectively one or more amino acid position substituted with a histidine.
  • the set of three L-CDRs has collectively one or more amino acid
  • Embodiment 92 The ABPC of any one of embodiments 85-91, wherein the ABPC is degraded in the target mammalian cell following internalization of the ABPC by the cell; and/or wherein the ABPC further comprises a conjugated toxin, radioisotope, drug, or small molecule; and/or wherein the ABPC provides for an increase in toxin liberation in the cell as compared to the same amount of a control ABPC.
  • Embodiment 93 Embodiment 93.
  • Embodiment 95 The ABPC of embodiment 92, wherein the ABPC provides for at least a 20%, 50%, 2-fold, or 5-fold increase in toxin liberation; and/or wherein the ABPC provides for an increase in target mammalian cell killing as compared to the same amount of a control ABPC.
  • Embodiment 94 The ABPC of embodiment 93, wherein the composition provides for at least a 20%, 50%, 2-fold, or 5-fold increase in target mammalian cell killing as compared to the same amount of a control ABPC.
  • Embodiment 95 Embodiment 95.
  • Embodiment 96 The ABPC of any one of embodiments 85-95, wherein the ABPC results in a less or no detectable reduction in the level of DLL3 presented on the surface of the target mammalian cell as compared to the same amount of a control ABPC.
  • Embodiment 97 Embodiment 97.
  • Embodiment 99 A kit comprising at least one dose of the ABPC of any one of embodiments 85-98. [0504] Embodiment 100.
  • a method of treating a cancer characterized by having a population of DLL3-positive cancer cells comprising administering a therapeutically effective amount of the ABPC of any one of embodiments 1-51, the composition of any one of embodiments 51-85, or the ABPC of any one of embodiments 85-98 to a subject identified as having a cancer characterized by having the population of cancer cells.
  • Embodiment 101 A method of reducing the volume of a tumor in a subject, wherein the tumor is characterized by having DLL3-positive cancer cells, comprising administering a therapeutically effective amount of the ABPC of any one of embodiments 1-51, the composition of any one of embodiments 51-85, or the ABPC of any one of embodiments 85-98 to the subject.
  • Embodiment 102 A method of inducing cell death in a DLL3-positive cancer cell in a subject, comprising administering a therapeutically effective amount of the ABPC of any one of embodiments 1-51, the composition of any one of embodiments 51-85, or the ABPC of any one of embodiments 85-98 to the subject.
  • Embodiment 103 A method of inducing cell death in a DLL3-positive cancer cell in a subject, comprising administering a therapeutically effective amount of the ABPC of any one of embodiments 1-51, the composition of any one of embodiments 51-85, or the ABPC of any one of embodiments 85-98 to the subject.
  • An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 125, 126, and 127, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 128, 129, and 130, respectively.
  • HCVD heavy chain variable domain
  • LCDVD light chain variable domain
  • the antigen-binding protein construct of embodiment 104 wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 123 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 124.
  • the antigen-binding protein construct of embodiment 104 or 105 comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 219 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 220.
  • Embodiment 107 comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 219 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 220.
  • An antigen -binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 133, 134, and 135, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 136, 137, and 138, respectively.
  • HCVD heavy chain variable domain
  • LCDVD light chain variable domain
  • Embodiment 109 The antigen-binding protein construct of embodiment 107 or 108, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 221 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 222.
  • Embodiment 110 Embodiment 110.
  • An anti-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 141, 142, and 143, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 144, 145, and 146, respectively.
  • Embodiment 111 Embodiment 111.
  • the antigen-binding protein construct of embodiment 110 wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 139 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 140.
  • Attorney Docket No.: 45395-0068WO1 [0516]
  • the antigen-binding protein construct of embodiment 110 or 111 comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 223 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 224.
  • Embodiment 113 A antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 149, 150, and 151, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 152, 153, and 154, respectively.
  • HCVD heavy chain variable domain
  • LCDVD light chain variable domain
  • Embodiment 114 The antigen-binding protein construct of embodiment 113, wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 147 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 148.
  • Embodiment 115 Embodiment 115.
  • the antigen-binding protein construct of embodiment 113 or 114 comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 225 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 226.
  • Embodiment 116 comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 225 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 226.
  • An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 157, 158, and 159, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 160, 161, and 162, respectively.
  • HCVD heavy chain variable domain
  • LCDVD light chain variable domain
  • the antigen-binding protein construct of embodiment 116 wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 155 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 156.
  • the antigen-binding protein construct of embodiment 116 or 117 comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 227 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 228.
  • Embodiment 119 Embodiment 119.
  • An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 165, 166, and 167, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 168, 169, and 160, respectively.
  • Embodiment 120 Embodiment 120.
  • Embodiment 121 The antigen-binding protein construct of embodiment 119, wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 163 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 164.
  • Embodiment 121 The antigen-binding protein construct of embodiment 119 or 120, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 229 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 230.
  • Embodiment 122 Embodiment 122.
  • An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 173, 174, and 175, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 176, 177, and 178, respectively.
  • HCVD heavy chain variable domain
  • LCDVD light chain variable domain
  • the antigen-binding protein construct of embodiment 122 wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 171 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 172.
  • the antigen-binding protein construct of embodiment 122 or 123 comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 231 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 232.
  • Embodiment 125 comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 231 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 232.
  • An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 181, 182, and 183, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 184, 185, and 186, respectively.
  • HCVD heavy chain variable domain
  • LCDVD light chain variable domain
  • Embodiment 127 The antigen-binding protein construct of embodiment 122 or 123, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 233 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 234.
  • Embodiment 128 Embodiment 128.
  • An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 189, 190, and 191, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 192, 193, and 194, respectively.
  • HCVD heavy chain variable domain
  • LCDVD light chain variable domain
  • the antigen-binding protein construct of embodiment 128 or 129 comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 235 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 236.
  • Embodiment 131 Embodiment 131.
  • An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 197, 198, and 199, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 200, 201, and 202, respectively.
  • Embodiment 132 Embodiment 132.
  • the antigen-binding protein construct of embodiment 131 wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 195 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 196.
  • Embodiment 133 The antigen-binding protein construct of embodiment 131 or 132, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 237 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 238.
  • Embodiment 133a An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 205, 206, and 207, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 208, 209, and 210, respectively; or wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 203 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO:
  • Embodiment 133b An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 213, 214, and 215, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 216, 217, and 218, respectively; or wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 211 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 212;
  • Embodiment 134 An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 5, 6, and 7, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 8, 9, and 10, respectively.
  • the antigen-binding protein construct of embodiment 134 wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 3 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 4.
  • Embodiment 136 The antigen-binding protein construct of embodiment 134 or 135, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 99 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 100.
  • Embodiment 137 An antigen-binding protein construct comprising an antigen-binding domain of an antibody that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H- CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 181, 182, and 183, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 184, 185, and 186, respectively.
  • HCVD heavy chain variable domain
  • LCDVD light chain variable domain
  • Embodiment 138 The antigen-binding protein construct of embodiment 137, wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 187 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 188.
  • Embodiment 139 Embodiment 139.
  • the antigen-binding protein construct of embodiment 137 or 138 comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 235 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 236.
  • Embodiment 140 comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 235 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 236.
  • Embodiment 141 The antigen-binding protein construct of embodiment 140, wherein the antigen-binding protein construct is a monoclonal antibody comprising an IgG heavy chain constant region.
  • Embodiment 142 The antigen-binding protein construct of embodiment 140 or 141, comprising an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 123 or 219 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 124 or 220.
  • Embodiment 143 Embodiment 143.
  • the antigen-binding protein construct of embodiment 140 or 141 comprising an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 131 or 221 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 132 or 222.
  • Embodiment 144 comprising an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 131 or 221 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 132 or 222.
  • invention 140 or 141 comprising an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 139 or 223 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 140 or 224.
  • Embodiment 145 comprising an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 139 or 223 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 140 or 224.
  • the antigen-binding protein construct of embodiment 140 or 141 comprising an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 147 or 225 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 148 or 226.
  • Embodiment 146 comprising an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 147 or 225 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 148 or 226.
  • the antigen-binding protein construct of embodiment 140 or 141 comprising an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 155 or 227 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 156 or 228.
  • Embodiment 147 Embodiment 147.
  • the antigen-binding protein construct of embodiment 140 or 141 comprising an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 163 or 229 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 164 or 230.
  • Embodiment 148 Embodiment 148.
  • the antigen-binding protein construct of embodiment 140 or 141 comprising an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 171 or 231 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 172 or 232.
  • the antigen-binding protein construct of embodiment 140 or 141 comprising an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 179 or 233 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 180 or 234.
  • Embodiment 150 comprising an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 179 or 233 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 180 or 234.
  • the antigen-binding protein construct of embodiment 140 or 141 comprising an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 187 or 235 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 188 or 236.
  • Embodiment 151 Embodiment 151.
  • the antigen-binding protein construct of embodiment 140 or 141 comprising an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 195 or 237 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 196 or 238.
  • Embodiment 152 Embodiment 152.
  • the antigen-binding protein construct of embodiment 140 or 141 comprising an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 203 or 239 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 204 or 240.
  • Embodiment 153 Embodiment 153.
  • the antigen-binding protein construct of embodiment 140 or 141 comprising an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 211 or 241 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 212 or 242.
  • Embodiment 154 A pharmaceutical composition comprising the antigen-binding protein construct of any one of embodiments 104-153 and a pharmaceutically acceptable excipient.
  • Embodiment 155 Embodiment 155.
  • a method of treating a DLL-positive cancer in a subject in need thereof comprising administering to the subject the antigen-binding protein construct of any one of embodiments 104-153.
  • Embodiment 156 A pharmaceutical composition comprising an effective amount of an antigen-binding protein construct (ABPC) comprising: a first antigen-binding domain (ABD) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell, wherein: the dissociation rate of the first ABD at a pH of ⁇ 4.0-6.5 is faster than the dissociation rate at a pH of ⁇ 7.0-8.0; and/or the KD of the first ABD at a pH of ⁇ 4.0-6.5 is greater than the KD at a pH of ⁇ 7.0-8.0.
  • ABPC antigen-binding protein construct
  • ABSD antigen-binding domain
  • Embodiment 157 The pharmaceutical composition of embodiment 156, wherein the first ABD comprises a heavy chain variable domain (HCVD) amino acid sequence selected from one of SEQ ID NO: 3, SEQ ID NO: 11, SEQ ID NO: 19, SEQ ID NO: 27, SEQ ID NO: 35, SEQ ID NO: 43, SEQ ID NO: 51, SEQ ID NO: 59, SEQ ID NO: 67, SEQ ID NO: 75, SEQ ID NO: 83, and SEQ ID NO: 91, optionally wherein the HCVD has at least one amino acid substituted with a histidine.
  • HCVD heavy chain variable domain
  • LCVD light chain variable domain
  • composition of embodiment 157 or 158 wherein the HCVD comprises an amino acid sequence of any one of SEQ ID NOs: 123, 131, 139, 147, 155, 163, 171, 179, 187, 195, 203, and 211 or comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to any one of SEQ ID NOs: 123, 131, 139, 147, 155, 163, 171, 179, 187, 195, 203, and 211, optionally wherein the HCVD has at least one amino acid substituted with a histidine.
  • Embodiment 160 comprises an amino acid sequence of any one of SEQ ID NOs: 123, 131, 139, 147, 155, 163, 171, 179, 187, 195, 203, and 211 or comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to any one of SEQ ID NOs: 123, 131, 139, 147,
  • embodiment 158 or 159 wherein the LCVD comprises an amino acid sequence of any one of SEQ ID NOs: 124, 132, 140, 148, 156, 164, 172, 180, 188, 196, 204, and 212 or comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to any one of SEQ ID NOs: 124, 132, 140, 148, 156, 164, 172, 180, 188, 196, 204, and 212, optionally wherein the LCVD has at least one amino acid substituted with a histidine.
  • HCVD comprises a set of three H-CDRs selected from the group consisting of: SEQ ID NOs: 125, 126, and 127; SEQ ID NOs: 133, 134, and 135; SEQ ID NOs: 141, 142, and 143; SEQ ID NOs: 149, 150, and 151; SEQ ID NOs: 157, 158, and 159; SEQ ID NOs: 165, 166, and 167; SEQ ID NOs: 173, 174, and 175; SEQ ID NOs: 181, 182, and 183; SEQ ID NOs: 189, 190, and 191; SEQ ID NOs: 197, 198, and 199; SEQ ID NOs: 205, 206, and 207; SEQ ID NOs: 213, 214, and Attorney Docket No.: 45395-0068WO1 215, optionally wherein the set of three H-CDRs has collectively one or more position
  • Embodiment 162 The pharmaceutical composition of embodiment 160 or 161, wherein the LCVD comprises a set of three L-CDRs selected from the group consisting of: SEQ ID NOs: 128, 129, and 130; SEQ ID NOs: 136, 137, and 138; SEQ ID NOs: 144, 145, and 146; SEQ ID NOs: 152, 153, and 154; SEQ ID NOs: 160, 161, and 162; SEQ ID NOs: 168, 169, and 170; SEQ ID NOs: 176, 177, and 178; SEQ ID NOs: 184, 185, and 186; SEQ ID NOs: 192, 193, and 194; SEQ ID NOs: 200, 201, and 202; SEQ ID NOs: 208, 209, and 210; SEQ ID NOs: 216, 217, and 218, optionally wherein the set of three L-CDRs has collectively one or more position substituted with a his
  • Embodiment 163 The pharmaceutical composition of any one of embodiments 156-162, wherein the ABPC is degraded in the target mammalian cell following internalization of the ABPC by the target mammalian cell.
  • Embodiment 164 The pharmaceutical composition of any one of embodiments 156-163, wherein the ABPC further comprises a conjugated toxin, radioisotope, drug, or small molecule.
  • Embodiment 165 The pharmaceutical composition of embodiment 164, wherein the pharmaceutical composition provides for an increase in toxin liberation in the target mammalian cell as compared to a pharmaceutical composition comprising the same amount of a control ABPC.
  • Embodiment 166 Embodiment 166.
  • Embodiment 165 The pharmaceutical composition of embodiment 165, wherein the pharmaceutical composition provides for at least a 20%, 50%, 2-fold, or 5-fold increase in toxin liberation in the target mammalian cell as compared to a pharmaceutical composition comprising the same amount of a control ABPC.
  • Embodiment 167 The pharmaceutical composition of any one of embodiments 164-166, wherein the pharmaceutical composition provides for an increase in target mammalian cell killing as compared to a pharmaceutical composition comprising the same amount of a control ABPC.
  • Embodiment 168 Embodiment 168.
  • Embodiment 169 The pharmaceutical composition of any one of embodiments 156-165, wherein the pharmaceutical composition provides for an increase in endolysosomal delivery in the Attorney Docket No.: 45395-0068WO1 target mammalian cell as compared to a pharmaceutical composition comprising the same amount of a control ABPC.
  • Embodiment 170 Embodiment 170.
  • Embodiment 171 The pharmaceutical composition of any one of embodiments 156-170, wherein the pharmaceutical composition results in a less or no detectable reduction in the level of DLL3 presented on the surface of the target mammalian cell as compared to a pharmaceutical composition comprising the same amount of a control ABPC.
  • Embodiment 172 Embodiment 172.
  • a composition comprising an effective amount of an antigen-binding protein construct (ABPC) comprising: a first ABD that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell; and a conjugated toxin, radioisotope, drug, or small molecule, wherein: [0579] (a) the dissociation rate of the first ABD at a pH of ⁇ 4.0-6.5 is faster than the dissociation rate at a pH of ⁇ 7.0-8.0; or the dissociation constant (KD) of the first ABD at a pH of ⁇ 4.0-6.5 is greater than the KD at a pH of ⁇ 7.0-8.0; and [0580] (b) the composition provides for one or more of: (i) an increase in toxin liberation in the target mammalian cell as compared to a composition comprising the same amount of a control ABPC; (ii) an increase in target mammalian cell killing as compared to a composition comprising the same
  • Embodiment 173 The composition of embodiment 172, wherein the first ABD comprises a heavy chain variable domain (HCVD) amino acid sequence selected from one of SEQ ID NO: 3, SEQ ID NO: 11, SEQ ID NO: 19, SEQ ID NO: 27, SEQ ID NO: 35, SEQ ID NO: 43, SEQ ID NO: 51, SEQ ID NO: 59, SEQ ID NO: 67, SEQ ID NO: 75, SEQ ID NO: 83, and SEQ ID NO: 91, optionally wherein the HCVD has at least one amino acid substituted with a histidine.
  • HCVD heavy chain variable domain
  • Embodiment 175. Embodiment 175.
  • Embodiment 176 comprises an amino acid sequence of any one of SEQ ID NOs: 123, 131, 139, 147, 155, 163, 171, 179, 187, 195, 203, and 211 or comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to any one of SEQ ID NOs: 123, 131, 139, 147,
  • Embodiment 177 comprises an amino acid sequence of any one of SEQ ID NOs: 124, 132, 140, 148, 156, 164, 172, 180, 188, 196, 204, and 212 or comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to any one of SEQ ID NOs: 124, 132, 140, 148, 156
  • composition of embodiment 175 or 176 wherein the HCVD a set of three H-CDRs selected from the group consisting of: SEQ ID NOs: 125, 126, and 127; SEQ ID NOs: 133, 134, and 135; SEQ ID NOs: 141, 142, and 143; SEQ ID NOs: 149, 150, and 151; SEQ ID NOs: 157, 158, and 159; SEQ ID NOs: 165, 166, and 167; SEQ ID NOs: 173, 174, and 175; SEQ ID NOs: 181, 182, and 183; SEQ ID NOs: 189, 190, and 191; SEQ ID NOs: 197, 198, and 199; SEQ ID NOs: 205, 206, and 207; SEQ ID NOs: 213, 214, and 215, optionally wherein the set of three H-CDRs has collectively one or more amino acid position substituted with a histidine.
  • Embodiment 178 The composition of embodiment 176 or 177, wherein the LCVD comprises a set of three L-CDRs selected from the group consisting of: SEQ ID NOs: 128, 129, and 130; SEQ ID NOs: 136, 137, and 138; SEQ ID NOs: 144, 145, and 146; SEQ ID NOs: 152, 153, and 154; SEQ ID NOs: 160, 161, and 162; SEQ ID NOs: 168, 169, and 170; SEQ ID NOs: 176, 177, and 178; SEQ ID NOs: 184, 185, and 186; SEQ ID NOs: 192, 193, and 194; SEQ ID NOs: 200, 201, and 202; SEQ ID NOs: 208, 209, and 210; SEQ ID NOs: 216, 217, and 218, optionally wherein the set of three L-CDRs has collectively one or more amino acid position substituted
  • Embodiment 179 The composition of any one of embodiments 172 to 178, wherein the composition provides for at least a 20%, 50%, 2-fold, or 5-fold increase in toxin liberation in the Attorney Docket No.: 45395-0068WO1 target mammalian cell, and/or cell killing, and/or at least a 20%, 50%, 2-fold, or 5-fold increase in endolysosomal delivery as compared to a composition comprising the same amount of a control ABPC.
  • Embodiment 180 Embodiment 180.
  • Embodiment 182 Embodiment 182.
  • composition of any one of embodiments 156-181, wherein the ABPC comprises two or more polypeptides.
  • Embodiment 183 The composition of any one of embodiments 156-182, wherein at least one polypeptide of the ABPC is conjugated to the toxin, the radioisotope, the drug, or the small molecule via a cleavable or non-cleavable linker.
  • Embodiment 184 Embodiment 184.
  • Embodiment 185 Embodiment 185.
  • composition of any one of embodiments 156-151, wherein the control ABPC is capable of specifically binding to DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell wherein: [0594] (a) the control ABPC comprises a first ABD; [0595] (b) the dissociation rate of the first ABD of the control ABPC at a pH of ⁇ 4.0-6.5 is no more than 2-fold or 3-fold faster than the dissociation rate at a pH of ⁇ 7.0-8.0; and [0596] (c) the dissociation constant (KD) of the first ABD of the control ABPC at a pH of ⁇ 4.0- 6.5 is no more than 2-fold or 3-fold greater than the KD at a pH of ⁇ 7.0-8.0.
  • KD dissociation constant
  • Embodiment 186 The composition of any one of embodiments 156-185, wherein the ABPC further comprises a second ABD. [0598] Embodiment 187. A kit comprising at least one dose of the composition of any one of embodiments 156-186. [0599] Embodiment 188.
  • An antigen-binding protein construct comprising: a first antigen-binding domain (ABD) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell, wherein: the dissociation rate of the first ABD at a pH of ⁇ 4.0-6.5 is faster than the dissociation rate at a pH of ⁇ 7.0-8.0; or the KD of the first ABD at a pH of ⁇ 4.0-6.5 is greater than the KD at a pH of ⁇ 7.0-8.0.
  • ABSPC antigen-binding protein construct
  • the ABPC of embodiment 188 wherein the first ABD comprises a heavy chain variable domain (HCVD) amino acid sequence selected from one of SEQ ID NO: 3, SEQ ID NO: 11, SEQ ID NO: 19, SEQ ID NO: 27, SEQ ID NO: 35, SEQ ID NO: 43, SEQ ID NO: 51, SEQ ID NO: 59, SEQ ID NO: 67, SEQ ID NO: 75, SEQ ID NO: 83, and SEQ ID NO: 91, optionally wherein the HCVD has at least one amino acid substituted with a histidine.
  • HCVD heavy chain variable domain
  • LCVD light chain variable domain
  • the ABPC of embodiment 189 or 190 wherein the HCVD comprises an amino acid sequence of any one of SEQ ID NOs: 123, 131, 139, 147, 155, 163, 171, 179, 187, 195, 203, and 211 or comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to any one of SEQ ID NOs: 123, 131, 139, 147, 155, 163, 171, 179, 187, 195, 203, and 211, optionally wherein the HCVD has at least one amino acid substituted with a histidine.
  • Embodiment 192 Embodiment 192.
  • HCVD comprises a set of three H-CDRs selected from the group consisting of: SEQ ID NOs: 125, 126, and 127; Attorney Docket No.: 45395-0068WO1 SEQ ID NOs: 133, 134, and 135; SEQ ID NOs: 141, 142, and 143; SEQ ID NOs: 149, 150, and 151; SEQ ID NOs: 157, 158, and 159; SEQ ID NOs: 165, 166, and 167; SEQ ID NOs: 173, 174, and 175; SEQ ID NOs: 181, 182, and 183; SEQ ID NOs: 189, 190, and 191; SEQ ID NOs: 197, 198, and 199; SEQ ID NOs: 205, 206, and 207; SEQ ID NOs: 213, 214, and 215, optionally wherein the set of three H-CDRs has collectively one or
  • Embodiment 194 The ABPC of embodiment 192 or 193, wherein the LCVD comprises a set of three L-CDRs selected from the group consisting of: SEQ ID NOs: 128, 129, and 130; SEQ ID NOs: 136, 137, and 138; SEQ ID NOs: 144, 145, and 146; SEQ ID NOs: 152, 153, and 154; SEQ ID NOs: 160, 161, and 162; SEQ ID NOs: 168, 169, and 170; SEQ ID NOs: 176, 177, and 178; SEQ ID NOs: 184, 185, and 186; SEQ ID NOs: 192, 193, and 194; SEQ ID NOs: 200, 201, and 202; SEQ ID NOs: 208, 209, and 210; SEQ ID NOs: 216, 217, and 218, optionally wherein the set of three L-CDRs has collectively one or more amino acid position substituted
  • Embodiment 195 The ABPC of any one of embodiments 188-194, wherein the ABPC is degraded in the target mammalian cell following internalization of the ABPC by the cell; and/or wherein the ABPC further comprises a conjugated toxin, radioisotope, drug, or small molecule; and/or wherein the ABPC provides for an increase in toxin liberation in the cell as compared to the same amount of a control ABPC.
  • Embodiment 196 Embodiment 196.
  • Embodiment 195 wherein the ABPC provides for at least a 20%, 50%, 2-fold, or 5-fold increase in toxin liberation; and/or wherein the ABPC provides for an increase in target mammalian cell killing as compared to the same amount of a control ABPC.
  • Embodiment 197 The ABPC of embodiment 196, wherein the composition provides for at least a 20%, 50%, 2-fold, or 5-fold increase in target mammalian cell killing as compared to the same amount of a control ABPC.
  • Embodiment 198 Embodiment 198.
  • Attorney Docket No.: 45395-0068WO1 [0610]
  • Embodiment 199. The ABPC of any one of embodiments 188-198, wherein the ABPC results in a less or no detectable reduction in the level of DLL3 presented on the surface of the target mammalian cell as compared to the same amount of a control ABPC. [0611] Embodiment 200.
  • Embodiment 203 The ABPC of any one of embodiments 188-199, wherein the ABPC further comprises a second ABD.
  • Embodiment 201 The ABPC of any one of embodiments 188-200, wherein the ABPC further comprises a conjugated toxin, radioisotope, drug, or small molecule.
  • Embodiment 202 A kit comprising at least one dose of the ABPC of any one of embodiments 188-201.
  • Embodiment 203 Embodiment 203.
  • a method of treating a cancer characterized by having a population of DLL3-positive cancer cells comprising administering a therapeutically effective amount of the ABPC of any one of embodiments 104-154, the composition of any one of embodiments 154-188, or the ABPC of any one of embodiments 188-201 to a subject identified as having a cancer characterized by having the population of cancer cells.
  • a method of reducing the volume of a tumor in a subject, wherein the tumor is characterized by having DLL3-positive cancer cells comprising administering a therapeutically effective amount of the ABPC of any one of embodiments 104-154, the composition of any one of embodiments 154-188, or the ABPC of any one of embodiments 188- 201 to the subject.
  • Embodiment 205 A method of inducing cell death in a DLL3-positive cancer cell in a subject, comprising administering a therapeutically effective amount of the antigen-binding protein construct of any one of embodiments 104-154, the composition of any one of embodiments 154-188, or the ABPC of any one of embodiments 188-201 to the subject.
  • Embodiment 206 A method of decreasing the risk of developing a metastasis or an additional metastasis in a subject having a DLL3-positive cancer, comprising administering a therapeutically effective amount of the ABPC of any one of embodiments 104-154, the composition of any one of embodiments 154-188, or the ABPC of any one of embodiments 188- 201 to the subject identified as having the DLL3-positive cancer.
  • Embodiment 207 Embodiment 207.
  • Embodiment 208 Use of the ABPC of any one of embodiments 108-158, the composition of any one of embodiments 158-192, or the ABPC of any one of embodiments 192-205 for treating Attorney Docket No.: 45395-0068WO1 a cancer characterized by having a population of DLL3-positive cancer cells in a subject identified as having said cancer.
  • Embodiment 208 Use of the ABPC of any one of embodiments 108-158, the composition of any one of embodiments 158-192, or the ABPC of any one of embodiments 192-205 for reducing the volume of a tumor in a subject, wherein the tumor is characterized by having DLL3- positive cancer cells.
  • Embodiment 209 Use of the ABPC of any one of embodiments 108-158, the composition of any one of embodiments 158-192, or the ABPC of any one of embodiments 192-205 for reducing the volume of a tumor in a subject, wherein the tumor is characterized by
  • Embodiment 210 Use of the ABPC of any one of embodiments 108-158, the composition of any one of embodiments 158-192, or the ABPC of any one of embodiments 192-205 for inducing cell death in a DLL3-positive cancer cell in a subject.
  • Embodiment 210 Use of the ABPC of any one of embodiments 108-158, the composition of any one of embodiments 158-192, or the ABPC of any one of embodiments 192-205 for decreasing the risk of developing a metastasis or an additional metastasis in a subject having a DLL3-positive cancer .
  • Embodiment 211 Use of the ABPC of any one of embodiments 108-158, the composition of any one of embodiments 158-192, or the ABPC of any one of embodiments 192-205 for decreasing the risk of developing a metastasis or an additional metastasis in a subject having a DLL3-positive cancer .
  • An isolated nucleic acid encoding an antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen- binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 205, 206, and 207, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L- CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 208, 209, and 210, respectively.
  • HCVD heavy chain variable domain
  • LCDVD light chain variable domain
  • Embodiment 212 The isolated nucleic acid of embodiment 211, wherein the nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 203, and the nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 204.
  • the isolated nucleic acid of embodiment 211 or 212 comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 239, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or Attorney Docket No.: 45395-0068WO1 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 240.
  • Embodiment 214 comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 239, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%
  • an isolated nucleic acid encoding an antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen- binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 13, 14, and 15, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L- CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 16, 17, and 18, respectively.
  • HCVD heavy chain variable domain
  • LCVD light chain variable domain
  • the isolated nucleic acid of embodiment 214 or 215, comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 101, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 102.
  • Embodiment 217 comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 101, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding
  • an isolated nucleic acid encoding an antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen- binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 21, 22, and 23, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L- CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 24, 25, and 26, respectively.
  • HCVD heavy chain variable domain
  • LCDVD light chain variable domain
  • Embodiment 218 The isolated nucleic acid of embodiment 217, wherein the nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 19, and the nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 20. [0630] Embodiment 219.
  • the isolated nucleic acid of embodiment 217 or 218, comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 103, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 104.
  • Embodiment 220 comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 103, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence
  • an isolated nucleic acid encoding an antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen- binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 29, 30, and 31, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L- CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 32, 33, and 34, respectively.
  • HCVD heavy chain variable domain
  • LCVD comprises light chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 29, 30, and 31, respectively
  • the LCVD comprises light chain CDRs L-CDR1, L- C
  • nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 27, and the nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 28.
  • Embodiment 222 Embodiment 222.
  • the isolated nucleic acid of embodiment 220 or 221, comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 105, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or Attorney Docket No.: 45395-0068WO1 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 106.
  • an isolated nucleic acid encoding an antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen- binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 37, 38, and 39, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L- CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 40, 41, and 42, respectively.
  • Embodiment 224 Embodiment 224.
  • nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 35
  • nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 36.
  • the isolated nucleic acid of embodiment 223 or 224 comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 107, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 108.
  • Embodiment 226 comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 107, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence
  • An isolated nucleic acid encoding an antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen- binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 45, 46, and 47, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L- CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 48, 49, and 50, respectively.
  • HCVD heavy chain variable domain
  • LCDVD light chain variable domain
  • Embodiment 227 The isolated nucleic acid of embodiment 226, wherein the nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 43, and the nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 44. [0639] Embodiment 228.
  • the isolated nucleic acid of embodiment 226 or 227 comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 109, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 110.
  • an isolated nucleic acid encoding an antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen- binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 53, 54, and 55, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L- CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 56, 57, and 58, respectively.
  • Embodiment 230 Embodiment 230.
  • nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 51
  • nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 52.
  • the isolated nucleic acid of embodiment 229 or 230 comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 111, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or Attorney Docket No.: 45395-0068WO1 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 112. [0643] Embodiment 232.
  • an isolated nucleic acid encoding an antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen- binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 61, 62, and 63, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L- CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 64, 65, and 66, respectively.
  • Embodiment 233 Embodiment 233.
  • nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 59
  • nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 60.
  • the isolated nucleic acid of embodiment 232 or 233 comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 113, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 114.
  • Embodiment 235 comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 113, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence
  • An isolated nucleic acid encoding an antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen- binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 69, 70, and 71, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L- CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 72, 73, and 74, respectively.
  • HCVD heavy chain variable domain
  • LCDVD light chain variable domain
  • Embodiment 236 The isolated nucleic acid of embodiment 235, wherein the nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 67, and the nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 68. [0648] Embodiment 237.
  • the isolated nucleic acid of embodiment 235 or 236, comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 115, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 116.
  • Embodiment 238 comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 115, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence
  • an isolated nucleic acid encoding an antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen- binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 77, 78, and 79, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L- CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 80, 81, and 82, respectively.
  • nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 75
  • nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 76.
  • the isolated nucleic acid of embodiment 248 or 249 comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 117, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or Attorney Docket No.: 45395-0068WO1 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 118.
  • an isolated nucleic acid encoding an antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen- binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 85, 86, and 87, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L- CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 88, 89, and 90, respectively.
  • Embodiment 242 Embodiment 242.
  • nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 83
  • nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 84.
  • the isolated nucleic acid of embodiment 241 or 242, comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 119, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 120.
  • An isolated nucleic acid encoding an antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen- binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 93, 94, and 95, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L- CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 96, 97, and 98, respectively.
  • HCVD heavy chain variable domain
  • LCDVD light chain variable domain
  • Embodiment 245. The isolated nucleic acid of embodiment 244, wherein the nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 91, and the nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 92. [0657] Embodiment 246.
  • the isolated nucleic acid of embodiment 244 or 245, comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 121, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 122.
  • Embodiment 247 comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 121, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence
  • nucleic acid encodes an antigen-binding protein construct selected from the group of an antibody, a VHH-scAb, a VHH-Fab, a Dual scFab, a F(ab')2, a diabody, a crossMab, a DAF (two-in-one), a DAF (four-in-one), a DutaMab, a DT-IgG, a knobs-in-holes common light chain, a knobs-in-holes assembly, a charge pair, a Fab-arm exchange, a SEEDbody, a LUZ-Y, a Fcab, a ⁇ -body, an orthogonal Fab, a DVD-IgG, a IgG(H)-scFv, a scFv-(H)IgG, IgG(L)-scFv, scFv- (L
  • Embodiment 248 The isolated nucleic acid of embodiment 247, wherein the nucleic acid encodes a monoclonal antibody comprising an IgG heavy chain constant region.
  • Embodiment 249. The isolated nucleic acid of embodiment 247 or 248, comprising a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 99, and a Attorney Docket No.: 45395-0068WO1 nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 100.
  • Embodiment 250 The isolated nucleic acid of embodiment 247 or 248, comprising a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 101, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 102.
  • the isolated nucleic acid of embodiment 247 or 248, comprising a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 103, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 104.
  • the isolated nucleic acid of embodiment 247 or 248, comprising a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 105, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 106.
  • the isolated nucleic acid of embodiment 247 or 248, comprising a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 107, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 108.
  • Embodiment 254 comprising a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 107, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino
  • the isolated nucleic acid of embodiment 247 or 248, comprising a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 109, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 110.
  • Embodiment 255 Embodiment 255.
  • the isolated nucleic acid of embodiment 247 or 248, comprising a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 111, and a Attorney Docket No.: 45395-0068WO1 nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 112. [0667] Embodiment 256.
  • the isolated nucleic acid of embodiment 247 or 248, comprising a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 113, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 114.
  • Embodiment 257 comprising a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 113, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino
  • the isolated nucleic acid of embodiment 247 or 248, comprising a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 115, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 116.
  • Embodiment 258 comprising a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 115, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino
  • the isolated nucleic acid of embodiment 247 or 248, comprising a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 117, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 118.
  • the isolated nucleic acid of embodiment 247 or 248, comprising a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 119, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 120.
  • Embodiment 260 comprising a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 119, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid
  • the isolated nucleic acid of embodiment 247 or 248, comprising a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 121, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 122.
  • Embodiment 261. An expression vector comprising the isolated nucleic acid of any one of embodiments 211-260.
  • Embodiment 262. A host cell comprising the expression vector of embodiment 261.
  • Embodiment 263 A method of producing an antigen-binding protein construct, the method comprising: (a) culturing the host cell of embodiment 262 under conditions suitable for expression of the antigen-binding protein construct; and (b) recovering the antigen-binding protein construct from the host cell or culture medium. [0675] Embodiment 264.
  • an antigen-binding protein construct that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell comprising at least one (1) antigen-binding domain (ABD), wherein: the first ABD includes a heavy chain variable domain (HCVD) of an HCVD having the amino acid sequence of one of SEQ ID NO: 3, SEQ ID NO: 11, SEQ ID NO: 19, SEQ ID NO: 27, SEQ ID NO: 35, SEQ ID NO: 43, SEQ ID NO: 51, SEQ ID NO: 59, SEQ ID NO: 67, SEQ ID NO: 75, SEQ ID NO: 83, and SEQ ID NO: 91, each HCVD optionally with at least 1 histidine substitution (e.g., one, two, three, four, or five total histidine substitutions across the set of three H-CDRs) and a light chain variable domain (LCVD) of an LCVD having the amino acid sequence of one of SEQ ID NO: 4, SEQ ID NO
  • Embodiment 265. An antigen-binding protein construct (ABPC) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell comprising at least one (1) antigen-binding domain (ABD), wherein: the first ABD includes one of (a) to (l): (a) an HCVD of SEQ ID NO: 3 and/or an LCVD of SEQ ID NO: 4; (b) an HCVD of SEQ ID NO: 11 and/or an LCVD of SEQ ID NO: 12; (c) an HCVD of SEQ ID NO: 19 and/or an LCVD of SEQ ID NO: 20; (d) an HCVD of SEQ ID NO: 27 and/or an LCVD of SEQ ID NO: 28; (e) an HCVD of SEQ ID NO: 35 and/or an LCVD of SEQ ID NO: 36; (f) an HCVD of 43 and/or an LCVD of SEQ ID NO: 44
  • Embodiment 266 An antigen-binding protein construct (ABPC) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell comprising at least one (1) antigen-binding domain (ABD), wherein: the first ABD includes one of (a) to (l): (a) an HCVD including the amino acid sequence of SEQ ID NO: 123 and/or an LCVD including the amino acid sequence of SEQ ID NO: 124; (b) an HCVD including the amino acid sequence of SEQ ID NO: 131 and/or an LCVD including the amino acid sequence of SEQ ID NO: 132; (c) an HCVD including the amino acid sequence of SEQ ID NO: 139 and/or an LCVD including the amino acid sequence of SEQ ID NO: 140; (d) an HCVD including the amino acid sequence of SEQ ID NO: 147 and/or an LCVD including the amino acid sequence of SEQ ID NO: 148; (e) an ABD including the
  • Embodiment 267 An antigen-binding protein construct (ABPC) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell comprising at least one (1) antigen-binding domain (ABD), wherein: the first ABD includes one of (a) to (l): (a) an HCVD including the sequence of SEQ ID NO: 3 and/or an LCVD including Attorney Docket No.: 45395-0068WO1 the sequence of SEQ ID NO: 4; (b) an HCVD including the sequence of SEQ ID NO: 11 and/or an LCVD including the sequence of SEQ ID NO: 12; (c) an HCVD including the sequence of SEQ ID NO: 19 and/or an LCVD including the sequence of SEQ ID NO: 20; (d) an HCVD including the sequence of SEQ ID NO: 27 and/or an LCVD including the sequence of SEQ ID NO: 28; (e) an HCVD including the sequence of SEQ
  • an antigen-binding protein construct that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell comprising at least one (1) antigen-binding domain (ABD), wherein: the first ABD includes one of (a) to (l): (a) an HCVD including the sequence of SEQ ID NO: 123 and/or an LCVD including the sequence of SEQ ID NO: 124; (b) an HCVD including the sequence of SEQ ID NO: 131 and/or an LCVD including the sequence of SEQ ID NO: 132; (c) an HCVD including the sequence of SEQ ID NO: 139 and/or an LCVD including the sequence of SEQ ID NO: 140; (d) an HCVD including the sequence of SEQ ID NO: 147 and/or an LCVD including the sequence of SEQ ID NO: 148; (e) an HCVD including the sequence of SEQ ID NO: 155 and/or an LCVD including the sequence of SEQ
  • Embodiment 269. An antigen-binding protein construct (ABPC) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell comprising at least one (1) antigen-binding domain (ABD), wherein: the first ABD includes a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein (a) the HCVD comprises an H-CDR1 sequence, an H-CDR2 sequence, and an H-CDR3 sequence selected from the group consisting of one of (i) to (xii): (i) the sequences of SEQ ID NO: 5, SEQ ID NO: 6, and SEQ ID NO: 7, respectively; (ii) the sequences of SEQ ID NO: 13, SEQ ID NO: 14, and SEQ ID NO: 15, respectively; (iii) the sequences of SEQ ID NO: 21, SEQ ID NO: 22, and SEQ ID NO: 23, respectively; (iv) the sequences of SEQ ID NO: 29, S
  • At least one of the H-CDR1, H-CDR2, and H-CDR3 sequences and/or at least one of the L-CDR1, L-CDR2, and L-CDR3 sequences has one or more amino acid position substituted with a histidine (e.g., one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or one, two, three, four, or five total histidine substitutions across the set of three L-CDRs).
  • a histidine e.g., one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or one, two, three, four, or five total histidine substitutions across the set of three L-CDRs.
  • an antigen-binding protein construct that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell comprising at least one (1) antigen-binding domain (ABD), wherein: the first ABD includes a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein (a) the HCVD comprises an H-CDR1 sequence, an H-CDR2 sequence, and an H-CDR3 sequence selected from the group consisting of one of (i) to (xii): (i) the sequences of SEQ ID NO: 125, SEQ ID NO: 126, and SEQ ID NO: 127, respectively; (ii) the sequences of SEQ ID NO: 133, SEQ ID NO: 134, and SEQ ID NO: 135, respectively; (iii) the sequences of SEQ ID NO: 141, SEQ ID NO: 142, and SEQ ID NO: 143, respectively; (iv) the sequences of
  • At least one of the H-CDR1, H- CDR2, and H-CDR3 sequences and/or at least one of the L-CDR1, L-CDR2, and L-CDR3 sequences has one or more amino acid position substituted with a histidine (e.g., one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or one, two, three, four, or five total histidine substitutions across the set of three L-CDRs).
  • a histidine e.g., one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or one, two, three, four, or five total histidine substitutions across the set of three L-CDRs.
  • an antigen-binding protein construct that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell comprising at least one (1) antigen-binding domain (ABD), wherein the first ABD includes a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD) according to one of the following pairs of HCVD and LCVD ((a1/a2) to (l1/l2)): [0683]
  • the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 203, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 203, and/or (3) the sequence of SEQ ID NO: 203 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 203, and (a2) the LCVD comprises (1) the C
  • Embodiment 272 An antigen-binding protein construct (ABPC) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell comprising at least one (1) antigen-binding domain (ABD), wherein the first ABD includes a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD) according to one of the following pairs of HCVD and LCVD ((a1/a2) to (l1/l2)): [0696] (a1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 83, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 83, and/or (3) the sequence of SEQ ID NO: 83 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 83, and (ABPC)
  • Embodiment 273 An isolated nucleic acid comprising a nucleotide sequence encoding a heavy chain variable domain (HCVD) and a nucleotide sequence encoding a light chain variable domain (LCVD) according to one of the following pairs of HCVD and LCVD ((a1/a2) to (l1/l2)): [0709] (a1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 203, and (a2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 204; [0710] (b1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO:
  • Embodiment 27 An isolated nucleic acid comprising a nucleotide sequence encoding a heavy chain variable domain (HCVD) and a nucleotide sequence encoding a light chain variable domain (LCVD) according to one of the following pairs of HCVD and LCVD ((a1/a2) to (l1/l2)): [0722] (a1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 83, and (a2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 84; [0723] (b1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 84
  • Embodiment 275 An expression vector comprising the isolated nucleic acid of any one of embodiments 273 (a1/a2), 273 (b1/b2), 273 (c1/c2), 273 (d1/d2), 273 (e1/e2), 273 (f1/f2), 273 (g1/g2), 273 (h1/h2), 273 (i1/i2), 273 (j1/j2), 273 (k1/k2), 273 (l1/l2), 274 (a1/a2), 274 (b1/b2), Attorney Docket No.: 45395-0068WO1 274 (c1/c2), 274 (d1/d2), 274 (e1/e2), 274 (f1/f2), 274 (g1/g2), 274 (h1/h2), 274 (i1/i2), 274 (j1/j2), 274 (k1/k2), and 274 (l1/l2).
  • Embodiment 276 A host cell comprising the expression vector of embodiment 275.
  • Embodiment 277 A method of producing an antigen-binding protein construct, the method comprising: (a) culturing the host cell of embodiment 276 under conditions suitable for expression of the antigen-binding protein construct; and (b) recovering the antigen-binding protein construct from the host cell or culture medium.
  • Embodiment 278 A pharmaceutical composition comprising an effective amount of the ABPC, antibody, or composition of any one of the preceding embodiments.

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Abstract

Provided herein are antigen-binding protein constructs (ABPCs) that bind DLL3 and uses of the same.

Description

Attorney Docket No.: 45395-0068WO1 ANTIGEN-BINDING PROTEIN CONSTRUCTS AND USES THEREOF CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims priority to U.S. Provisional Patent Application No.63/572,855, filed on April 1, 2024, the content of which is incorporated herein by reference in its entirety. SEQUENCE LISTING [0002] This application contains a Sequence Listing that has been submitted electronically as an XML file named “45395-0068WO1_SL_ST26.XML”. The XML file, created on March 30, 2025, is 338,537 bytes in size, and the material contained within it is hereby incorporated by reference in its entirety. TECHNICAL FIELD [0003] The present disclosure relates to the field of antigen-binding molecules. SUMMARY [0004] The present disclosure provides novel Delta-like protein 3 (DLL3)-binding proteins, compositions comprising such proteins, and methods of using such proteins for the treatment of DLL3-positive cancers. More specifically, the disclosure relates to DLL3-binding proteins having enhanced physicochemical properties. [0005] DLL3 is a member of the Delta/Serrate/Lag-2 (DSL) family of Notch ligands. Unlike other DSL family members, DLL3 is primarily localized intracellularly rather than at the cell surface, and has been shown to inhibit Notch signaling through cis-inhibition rather than activating Notch through trans-activation. DLL3 plays an important role during embryonic development, particularly in somitogenesis and neurogenesis, but has limited expression in normal adult tissues. [0006] Significantly, DLL3 has been identified as a promising therapeutic target due to its aberrant expression in certain high-grade neuroendocrine tumors, while maintaining minimal expression in normal adult tissues. Notably, DLL3 is highly expressed in small-cell lung cancer (SCLC), large cell neuroendocrine carcinoma (LCNEC), pulmonary neuroendocrine cancer, Attorney Docket No.: 45395-0068WO1 various extrapulmonary neuroendocrine cancers, and certain melanomas. These DLL3-positive cancers are often aggressive, with limited treatment options and poor prognosis for patients. [0007] Small-cell lung cancer, which accounts for approximately 15% of all lung cancers, is particularly aggressive with rapid doubling time, early metastatic spread, and development of treatment resistance. Despite initial responses to first-line chemotherapy regimens, most SCLC patients experience disease recurrence, with a 5-year survival rate of less than 7%. Similar challenges exist for patients with other DLL3-positive neuroendocrine cancers. [0008] Several DLL3-binding proteins have been previously described, including antibodies and antibody-drug conjugates (ADCs). Rovalpituzumab tesirine (Rova-T), an anti-DLL3 antibody conjugated to a pyrrolobenzodiazepine dimer toxin, showed initial promise but demonstrated limited efficacy and significant toxicity in clinical trials, leading to discontinuation of its development. Rovalpituzumab (SC16, the antibody component of Rova-T) binds to the extracellular domain of DLL3 (targeting an epitope within the DSL (Delta/Serrate/LAG-2) domain of human DLL3). Other DLL3-targeting approaches including bispecific T-cell engagers (BiTEs) and chimeric antigen receptor (CAR) T cell therapies have shown variable efficacy and safety profiles in preclinical and early clinical studies. [0009] The limited success of previous DLL3-binding proteins can be attributed to various factors, including suboptimal binding affinity, insufficient tumor penetration, inadequate pharmacokinetic properties, and off-target toxicities. Additionally, the heterogeneous expression of DLL3 within tumors and across patient populations presents challenges for developing effective therapeutics. [0010] Therefore, there remains a significant unmet medical need for new and improved DLL3- binding proteins with enhanced therapeutic properties, including higher binding affinity, improved tumor penetration, extended half-life, reduced immunogenicity, and superior safety profiles. Such improved DLL3-binding proteins could provide more effective treatment options for patients with DLL3-positive cancers, including SCLC, LCNEC, pulmonary neuroendocrine cancer, extrapulmonary neuroendocrine cancers, and melanoma, potentially offering improved response rates, longer duration of response, and better overall survival compared to currently available therapies. Attorney Docket No.: 45395-0068WO1 References [0011] Saunders LR, et al. A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo. Sci Transl Med.2015;7(302):302ra136. [0012] Spino M, et al. Cell surface Notch ligand DLL3 is a therapeutic target in isocitrate dehydrogenase-mutant glioma. Clin Cancer Res.2019;25(4):1261-1271. [0013] Giffin MJ, et al. AMG 757, a half-life extended, DLL3-targeted bispecific T-cell engager, shows high potency and sensitivity in preclinical models of small-cell lung cancer. Clin Cancer Res.2021;27(5):1526-1537 [0014] Sharma SK, et al. Preclinical efficacy of anti-DLL3 antibody-drug conjugate rovalpituzumab tesirine against high DLL3-expressing neuroendocrine carcinomas. Clin Cancer Res.2019;25(23):7127-7137 [0015] Rudin CM, et al. Rovalpituzumab tesirine, a DLL3-targeted antibody-drug conjugate, in recurrent small-cell lung cancer: a first-in-human, first-in-class, open-label, phase 1 study. Lancet Oncol.2017;18(1):42-51. [0016] The present disclosure addresses these needs by providing novel human DLL3-binding proteins with significantly improved properties compared to previously known DLL3-binding proteins, offering potential advantages for the treatment of DLL3-positive cancers. [0017] In one aspect, the present disclosure provides an antibody, antigen-binding protein construct (ABPC), or antigen-binding domain (ABD) thereof, comprising a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein (a) the HCVD comprises an H-CDR1 sequence, an H-CDR2 sequence, and an H-CDR3 sequence selected from the group consisting of the sequences of one of (i) to (xii): (i) to (xii): (i) the sequences of SEQ ID NO: 5, SEQ ID NO: 6, and SEQ ID NO: 7, respectively; (ii) the sequences of SEQ ID NO: 13, SEQ ID NO: 14, and SEQ ID NO: 15, respectively; (iii) the sequences of SEQ ID NO: 21, SEQ ID NO: 22, and SEQ ID NO: 23, respectively; (iv) the sequences of SEQ ID NO: 29, SEQ ID NO: 30, and SEQ ID NO: 31, respectively; (v) the sequences of SEQ ID NO: 37, SEQ ID NO: 38, and SEQ ID NO: 39, respectively; (vi) the sequences of SEQ ID NO: 45, SEQ ID NO: 46, and SEQ ID NO: 47, respectively; (vii) the sequences of SEQ ID NO: 53, SEQ ID NO: 54, and SEQ ID NO: 55, respectively; (viii) the sequences of SEQ ID NO: 61, SEQ ID NO: 62, and SEQ ID NO: 63, respectively; (ix) the sequences of SEQ ID NO: 69, SEQ ID NO: 70, and SEQ ID NO: 71, respectively; (x) the sequences of SEQ ID NO: 77, SEQ ID NO: 78, and SEQ ID NO: 79, Attorney Docket No.: 45395-0068WO1 respectively; (xi) the sequences of SEQ ID NO: 85, SEQ ID NO: 86, and SEQ ID NO: 87, respectively; (xii) the sequences of SEQ ID NO: 93, SEQ ID NO: 94, and SEQ ID NO: 95, respectively; and/or (b) the LCVD comprises an L-CDR1 sequence, an L-CDR2 sequence, and an L-CDR3 sequence selected from the group consisting of the sequences of one of (i) to (xii): (i) to (xii): (i) the sequences of SEQ ID NO: 8, SEQ ID NO: 9, and SEQ ID NO: 10, respectively; (ii) the sequences of SEQ ID NO: 16, SEQ ID NO: 17, and SEQ ID NO: 18, respectively; (iii) the sequences of SEQ ID NO: 24, SEQ ID NO: 25, and SEQ ID NO: 26, respectively; (iv) the sequences of SEQ ID NO: 32, SEQ ID NO: 33, and SEQ ID NO: 34, respectively; (v) the sequences of SEQ ID NO: 40, SEQ ID NO: 41, and SEQ ID NO: 42, respectively; (vi) the sequences of SEQ ID NO: 48, SEQ ID NO: 49, and SEQ ID NO: 50, respectively; (vii) the sequences of SEQ ID NO: 56, SEQ ID NO: 57, and SEQ ID NO: 58, respectively; (viii) the sequences of SEQ ID NO: 64, SEQ ID NO: 65, and SEQ ID NO: 66, respectively; (ix) the sequences of SEQ ID NO: 72, SEQ ID NO: 73, and SEQ ID NO: 74, respectively; (x) the sequences of SEQ ID NO: 80, SEQ ID NO: 81, and SEQ ID NO: 82, respectively; (xi) the sequences of SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 90, respectively; and (xii) the sequences of SEQ ID NO: 96, SEQ ID NO: 97, and SEQ ID NO: 98, respectively. [0018] In some aspects, the antibody or antigen-binding protein construct comprises a heavy and light chain as set forth in one of the following pairs: the sequence of SEQ ID NO: 99 and the sequence of SEQ ID NO: 100, the sequence of SEQ ID NO: 101 and the sequence of SEQ ID NO: 102, the sequence of SEQ ID NO: 103 and the sequence of SEQ ID NO: 104, the sequence of SEQ ID NO: 105 and the sequence of SEQ ID NO: 106, the sequence of SEQ ID NO: 107 and the sequence of SEQ ID NO: 108, the sequence of SEQ ID NO: 109 and the sequence of SEQ ID NO: 110, the sequence of SEQ ID NO: 111 and the sequence of SEQ ID NO: 112, the sequence of SEQ ID NO: 113 and the sequence of SEQ ID NO: 114, the sequence of SEQ ID NO: 115 and the sequence of SEQ ID NO: 116, the sequence of SEQ ID NO: 117 and the sequence of SEQ ID NO: 118, the sequence of SEQ ID NO: 119 and the sequence of SEQ ID NO: 120, and the sequence of SEQ ID NO: 121 and the sequence of SEQ ID NO: 122. [0019] In some aspects, the antibody, antigen-binding protein construct, or ABD includes one or more of the following characteristics: (a) a heavy chain variable domain (HCVD) sequence that is at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identical to any one of SEQ ID NO: 3, SEQ ID NO: 11, SEQ ID NO: 19, SEQ ID NO: 27, SEQ ID NO: 35, SEQ ID NO: 43, Attorney Docket No.: 45395-0068WO1 SEQ ID NO: 51, SEQ ID NO: 59, SEQ ID NO: 67, SEQ ID NO: 75, SEQ ID NO: 83, and SEQ ID NO: 91; and/or (b) a light chain variable domain (LCVD) sequence that is at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identical to any one of SEQ ID NO: SEQ ID NO: 4, SEQ ID NO: 12, SEQ ID NO: 20, SEQ ID NO: 28, SEQ ID NO: 36, SEQ ID NO: 44, SEQ ID NO: 52, SEQ ID NO: 60, SEQ ID NO: 68, SEQ ID NO: 76, SEQ ID NO: 84, and SEQ ID NO: 92. [0020] In another aspect, the present disclosure provides an antibody, antigen-binding protein fragment, or ABD comprising an HCVD and an LCVD, wherein: (a) the HCVD comprises an amino acid sequence of any one of SEQ ID NO: 3, SEQ ID NO: 11, SEQ ID NO: 19, SEQ ID NO: 27, SEQ ID NO: 35, SEQ ID NO: 43, SEQ ID NO: 51, SEQ ID NO: 59, SEQ ID NO: 67, SEQ ID NO: 75, SEQ ID NO: 83, and SEQ ID NO: 91; and/or (b) the LCVD comprises an amino acid sequence one any one of SEQ ID NO: 4, SEQ ID NO: 12, SEQ ID NO: 20, SEQ ID NO: 28, SEQ ID NO: 36, SEQ ID NO: 44, SEQ ID NO: 52, SEQ ID NO: 60, SEQ ID NO: 68, SEQ ID NO: 76, SEQ ID NO: 84, and SEQ ID NO: 92. [0021] In some aspects of the antibody, antigen-binding protein construct, or ABD, the HCVD amino acid sequence and the LCVD amino acid sequence is selected from the group consisting of: the sequences of SEQ ID NO: 3 and SEQ ID NO: 4, respectively; the sequences of SEQ ID NO: 11 and SEQ ID NO: 12, respectively; the sequences of SEQ ID NO: 19 and SEQ ID NO: 20; the sequences of SEQ ID NO: 27 and SEQ ID NO: 28, respectively; the sequences of SEQ ID NO: 35 and SEQ ID NO: 36, respectively; the sequences of SEQ ID NO: 43 and SEQ ID NO: 44, respectively; the sequences of SEQ ID NO: 51 and SEQ ID NO: 52, respectively; the sequences of SEQ ID NO: 59 and SEQ ID NO: 59, respectively; the sequences of SEQ ID NO: 67 and SEQ ID NO: 67, respectively; the sequences of SEQ ID NO: 75 and SEQ ID NO: 76, respectively; the sequences of SEQ ID NO: 83 and SEQ ID NO: 84, respectively; and the sequences of SEQ ID NO: 91 and SEQ ID NO: 92, respectively. [0022] In another aspect, the present disclosure provides an antibody, antigen-binding protein construct (ABPC), or antigen binding domain (ABD), comprising a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein (a) the HCVD comprises an H-CDR1 sequence, an H-CDR2 sequence, and an H-CDR3 sequence selected from the group consisting of the sequences of one of (i) to (xii): (i) to (xii): (i) the sequences of SEQ ID NO: 125, SEQ ID NO: 126, and SEQ ID NO: 127, respectively; (ii) the sequences of SEQ ID NO: 133, SEQ ID NO: 134, and SEQ ID NO: 135, respectively; (iii) the sequences of SEQ ID NO: 141, SEQ ID NO: 142, and Attorney Docket No.: 45395-0068WO1 SEQ ID NO: 143, respectively; (iv) the sequences of SEQ ID NO: 149, SEQ ID NO: 150, and SEQ ID NO: 151, respectively; (v) the sequences of SEQ ID NO: 157, SEQ ID NO: 158, and SEQ ID NO: 159, respectively; (vi) the sequences of SEQ ID NO: 165, SEQ ID NO: 166, and SEQ ID NO: 167, respectively; (vii) the sequences of SEQ ID NO: 173, SEQ ID NO: 174, and SEQ ID NO: 175, respectively; (viii) the sequences of SEQ ID NO: 181, SEQ ID NO: 182, and SEQ ID NO: 183, respectively; (ix) the sequences of SEQ ID NO: 189, SEQ ID NO: 190, and SEQ ID NO: 191, respectively; (x) the sequences of SEQ ID NO: 197, SEQ ID NO: 198, and SEQ ID NO: 199, respectively; (xi) the sequences of SEQ ID NO: 205, SEQ ID NO: 206, and SEQ ID NO: 207, respectively; (xii) the sequences of SEQ ID NO: 213, SEQ ID NO: 214, and SEQ ID NO: 215, respectively; and/or (b) the LCVD comprises an L-CDR1 sequence, an L-CDR2 sequence, and an L-CDR3 sequence selected from the group consisting of the sequences of one of (i) to (xii): (i) to (xii): (i) the sequences of SEQ ID NO: 128, SEQ ID NO: 129, and SEQ ID NO: 130, respectively; (ii) the sequences of SEQ ID NO: 136, SEQ ID NO: 137, and SEQ ID NO: 138, respectively; (iii) the sequences of SEQ ID NO: 144, SEQ ID NO: 145, and SEQ ID NO: 146, respectively; (iv) the sequences of SEQ ID NO: 152, SEQ ID NO: 153, and SEQ ID NO: 154, respectively; (v) the sequences of SEQ ID NO: 160, SEQ ID NO: 161, and SEQ ID NO: 162, respectively; (vi) the sequences of SEQ ID NO: 168, SEQ ID NO: 169, and SEQ ID NO: 170, respectively; (vii) the sequences of SEQ ID NO: 176, SEQ ID NO: 177, and SEQ ID NO: 178, respectively; (viii) the sequences of SEQ ID NO: 184, SEQ ID NO: 185, and SEQ ID NO: 186, respectively; (ix) the sequences of SEQ ID NO: 192, SEQ ID NO: 193, and SEQ ID NO: 194, respectively; (x) the sequences of SEQ ID NO: 200, SEQ ID NO: 201, and SEQ ID NO: 202, respectively; (xi) the sequences of SEQ ID NO: 208, SEQ ID NO: 209, and SEQ ID NO: 210, respectively; and (xii) the sequences of SEQ ID NO: 216, SEQ ID NO: 217, and SEQ ID NO: 218, respectively. [0023] In some aspects, the antibody or antigen-binding protein construct comprises a heavy and light chain as set forth in one of the following pairs of sequences: SEQ ID NO: 219 and SEQ ID NO: 220, respectively; SEQ ID NO: 221 and SEQ ID NO: 222, respectively; SEQ ID NO: 223 and SEQ ID NO: 224, respectively; SEQ ID NO: 225 and SEQ ID NO: 226, respectively; SEQ ID NO: 227 and SEQ ID NO: 228, respectively; SEQ ID NO: 229 and SEQ ID NO: 230, respectively; SEQ ID NO: 231 and SEQ ID NO: 232, respectively; SEQ ID NO: 233 and SEQ ID NO: 234, respectively; SEQ ID NO: 235 and SEQ ID NO: 236, respectively; SEQ ID NO: 237 and SEQ ID Attorney Docket No.: 45395-0068WO1 NO: 238, respectively; SEQ ID NO: 239 and SEQ ID NO: 240, respectively; and SEQ ID NO: 241 and SEQ ID NO: 242, respectively. [0024] In certain embodiments, the present disclosure provides isolated nucleic acids encoding the HCVD and/or LCVD of the antibody, ABPC, or ABD as disclosed herein, wherein the nucleic acids comprise: [0025] (a) a polynucleotide encoding the HCVD comprising an H-CDR1 sequence, an H-CDR2 sequence, and an H-CDR3 sequence selected from: [0026] (i) polynucleotides encoding the sequences of SEQ ID NO: 5, SEQ ID NO: 6, and SEQ ID NO: 7, respectively; [0027] (ii) polynucleotides encoding the sequences of SEQ ID NO: 13, SEQ ID NO: 14, and SEQ ID NO: 15, respectively; [0028] (iii) polynucleotides encoding the sequences of SEQ ID NO: 21, SEQ ID NO: 22, and SEQ ID NO: 23, respectively; [0029] (iv) polynucleotides encoding the sequences of SEQ ID NO: 29, SEQ ID NO: 30, and SEQ ID NO: 31, respectively; [0030] (v) polynucleotides encoding the sequences of SEQ ID NO: 37, SEQ ID NO: 38, and SEQ ID NO: 39, respectively; [0031] (vi) polynucleotides encoding the sequences of SEQ ID NO: 45, SEQ ID NO: 46, and SEQ ID NO: 47, respectively; [0032] (vii) polynucleotides encoding the sequences of SEQ ID NO: 53, SEQ ID NO: 54, and SEQ ID NO: 55, respectively; [0033] (viii) polynucleotides encoding the sequences of SEQ ID NO: 61, SEQ ID NO: 62, and SEQ ID NO: 63, respectively; [0034] (ix) polynucleotides encoding the sequences of SEQ ID NO: 69, SEQ ID NO: 70, and SEQ ID NO: 71, respectively; [0035] (x) polynucleotides encoding the sequences of SEQ ID NO: 77, SEQ ID NO: 78, and SEQ ID NO: 79, respectively; [0036] (xi) polynucleotides encoding the sequences of SEQ ID NO: 85, SEQ ID NO: 86, and SEQ ID NO: 87, respectively; [0037] (xii) polynucleotides encoding the sequences of SEQ ID NO: 93, SEQ ID NO: 94, and SEQ ID NO: 95, respectively; Attorney Docket No.: 45395-0068WO1 [0038] (xiii) polynucleotides encoding the sequences of SEQ ID NO: 125, SEQ ID NO: 126, and SEQ ID NO: 127, respectively; [0039] (xiv) polynucleotides encoding the sequences of SEQ ID NO: 133, SEQ ID NO: 134, and SEQ ID NO: 135, respectively; [0040] (xv) polynucleotides encoding the sequences of SEQ ID NO: 141, SEQ ID NO: 142, and SEQ ID NO: 143, respectively; [0041] (xvi) polynucleotides encoding the sequences of SEQ ID NO: 149, SEQ ID NO: 150, and SEQ ID NO: 151, respectively; [0042] (xvii) polynucleotides encoding the sequences of SEQ ID NO: 157, SEQ ID NO: 158, and SEQ ID NO: 159, respectively; [0043] (xviii) polynucleotides encoding the sequences of SEQ ID NO: 165, SEQ ID NO: 166, and SEQ ID NO: 167, respectively; [0044] (xix) polynucleotides encoding the sequences of SEQ ID NO: 173, SEQ ID NO: 174, and SEQ ID NO: 175, respectively; [0045] (xx) polynucleotides encoding the sequences of SEQ ID NO: 181, SEQ ID NO: 182, and SEQ ID NO: 183, respectively; [0046] (xxi) polynucleotides encoding the sequences of SEQ ID NO: 189, SEQ ID NO: 190, and SEQ ID NO: 191, respectively; [0047] (xxii) polynucleotides encoding the sequences of SEQ ID NO: 197, SEQ ID NO: 198, and SEQ ID NO: 199, respectively; [0048] (xxiii) polynucleotides encoding the sequences of SEQ ID NO: 205, SEQ ID NO: 206, and SEQ ID NO: 207, respectively; and [0049] (xxiv) polynucleotides encoding the sequences of SEQ ID NO: 213, SEQ ID NO: 214, and SEQ ID NO: 215, respectively; and/or [0050] (b) a polynucleotide encoding the LCVD comprising an L-CDR1 sequence, an L-CDR2 sequence, and an L-CDR3 sequence selected from: [0051] (i) polynucleotides encoding the sequences of SEQ ID NO: 8, SEQ ID NO: 9, and SEQ ID NO: 10, respectively; [0052] (ii) polynucleotides encoding the sequences of SEQ ID NO: 16, SEQ ID NO: 17, and SEQ ID NO: 18, respectively; Attorney Docket No.: 45395-0068WO1 [0053] (iii) polynucleotides encoding the sequences of SEQ ID NO: 24, SEQ ID NO: 25, and SEQ ID NO: 26, respectively; [0054] (iv) polynucleotides encoding the sequences of SEQ ID NO: 32, SEQ ID NO: 33, and SEQ ID NO: 34, respectively; [0055] (v) polynucleotides encoding the sequences of SEQ ID NO: 40, SEQ ID NO: 41, and SEQ ID NO: 42, respectively; [0056] (vi) polynucleotides encoding the sequences of SEQ ID NO: 48, SEQ ID NO: 49, and SEQ ID NO: 50, respectively; [0057] (vii) polynucleotides encoding the sequences of SEQ ID NO: 56, SEQ ID NO: 57, and SEQ ID NO: 58, respectively; [0058] (viii) polynucleotides encoding the sequences of SEQ ID NO: 64, SEQ ID NO: 65, and SEQ ID NO: 66, respectively; [0059] (ix) polynucleotides encoding the sequences of SEQ ID NO: 72, SEQ ID NO: 73, and SEQ ID NO: 74, respectively; [0060] (x) polynucleotides encoding the sequences of SEQ ID NO: 80, SEQ ID NO: 81, and SEQ ID NO: 82, respectively; [0061] (xi) polynucleotides encoding the sequences of SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 90, respectively; [0062] (xii) polynucleotides encoding the sequences of SEQ ID NO: 96, SEQ ID NO: 97, and SEQ ID NO: 98, respectively; [0063] (xiii) polynucleotides encoding the sequences of SEQ ID NO: 128, SEQ ID NO: 129, and SEQ ID NO: 130, respectively; [0064] (xiv) polynucleotides encoding the sequences of SEQ ID NO: 136, SEQ ID NO: 137, and SEQ ID NO: 138, respectively; [0065] (xv) polynucleotides encoding the sequences of SEQ ID NO: 144, SEQ ID NO: 145, and SEQ ID NO: 146, respectively; [0066] (xvi) polynucleotides encoding the sequences of SEQ ID NO: 152, SEQ ID NO: 153, and SEQ ID NO: 154, respectively; [0067] (xvii) polynucleotides encoding the sequences of SEQ ID NO: 160, SEQ ID NO: 161, and SEQ ID NO: 162, respectively; Attorney Docket No.: 45395-0068WO1 [0068] (xviii) polynucleotides encoding the sequences of SEQ ID NO: 168, SEQ ID NO: 169, and SEQ ID NO: 170, respectively; [0069] (xix) polynucleotides encoding the sequences of SEQ ID NO: 176, SEQ ID NO: 177, and SEQ ID NO: 178, respectively; [0070] (xx) polynucleotides encoding the sequences of SEQ ID NO: 184, SEQ ID NO: 185, and SEQ ID NO: 186, respectively; [0071] (xxi) polynucleotides encoding the sequences of SEQ ID NO: 192, SEQ ID NO: 193, and SEQ ID NO: 194, respectively; [0072] (xxii) polynucleotides encoding the sequences of SEQ ID NO: 200, SEQ ID NO: 201, and SEQ ID NO: 202, respectively; [0073] (xxiii) polynucleotides encoding the sequences of SEQ ID NO: 208, SEQ ID NO: 209, and SEQ ID NO: 210, respectively; and [0074] (xxiv) polynucleotides encoding the sequences of SEQ ID NO: 216, SEQ ID NO: 217, and SEQ ID NO: 218, respectively. [0075] In certain embodiments, the present disclosure provides isolated nucleic acids encoding the antibody, ABPC, or ABD of any of the preceding claims, wherein the nucleic acids comprise: [0076] (a) a polynucleotide encoding a HCVD comprising an amino acid sequence selected from SEQ ID NO: 3, SEQ ID NO: 11, SEQ ID NO: 19, SEQ ID NO: 27, SEQ ID NO: 35, SEQ ID NO: 43, SEQ ID NO: 51, SEQ ID NO: 59, SEQ ID NO: 67, SEQ ID NO: 75, SEQ ID NO: 83, and SEQ ID NO: 91; and/or [0077] (b) a polynucleotide encoding a LCVD comprising an amino acid sequence selected from SEQ ID NO: 4, SEQ ID NO: 12, SEQ ID NO: 20, SEQ ID NO: 28, SEQ ID NO: 36, SEQ ID NO: 44, SEQ ID NO: 52, SEQ ID NO: 60, SEQ ID NO: 68, SEQ ID NO: 76, SEQ ID NO: 84, and SEQ ID NO: 92. [0078] In certain embodiments, the present disclosure provides isolated nucleic acids encoding the antibody or ABPC of any of the preceding claims, wherein the nucleic acids comprise polynucleotides encoding the heavy chain and light chain pairs selected from: [0079] (i) polynucleotides encoding the sequences of SEQ ID NO: 99 and SEQ ID NO: 100, respectively; [0080] (ii) polynucleotides encoding the sequences of SEQ ID NO: 101 and SEQ ID NO: 102, respectively; Attorney Docket No.: 45395-0068WO1 [0081] (iii) polynucleotides encoding the sequences of SEQ ID NO: 103 and SEQ ID NO: 104, respectively; [0082] (iv) polynucleotides encoding the sequences of SEQ ID NO: 105 and SEQ ID NO: 106, respectively; [0083] (v) polynucleotides encoding the sequences of SEQ ID NO: 107 and SEQ ID NO: 108, respectively; [0084] (vi) polynucleotides encoding the sequences of SEQ ID NO: 109 and SEQ ID NO: 110, respectively; [0085] (vii) polynucleotides encoding the sequences of SEQ ID NO: 111 and SEQ ID NO: 112, respectively; [0086] (viii) polynucleotides encoding the sequences of SEQ ID NO: 113 and SEQ ID NO: 114, respectively; [0087] (ix) polynucleotides encoding the sequences of SEQ ID NO: 115 and SEQ ID NO: 116, respectively; [0088] (x) polynucleotides encoding the sequences of SEQ ID NO: 117 and SEQ ID NO: 118, respectively; [0089] (xi) polynucleotides encoding the sequences of SEQ ID NO: 119 and SEQ ID NO: 120, respectively; [0090] (xii) polynucleotides encoding the sequences of SEQ ID NO: 121 and SEQ ID NO: 122, respectively; [0091] (xiii) polynucleotides encoding the sequences of SEQ ID NO: 219 and SEQ ID NO: 220, respectively; [0092] (xiv) polynucleotides encoding the sequences of SEQ ID NO: 221 and SEQ ID NO: 222, respectively; [0093] (xv) polynucleotides encoding the sequences of SEQ ID NO: 223 and SEQ ID NO: 224, respectively; [0094] (xvi) polynucleotides encoding the sequences of SEQ ID NO: 225 and SEQ ID NO: 226, respectively; [0095] (xvii) polynucleotides encoding the sequences of SEQ ID NO: 227 and SEQ ID NO: 228, respectively; Attorney Docket No.: 45395-0068WO1 [0096] (xviii) polynucleotides encoding the sequences of SEQ ID NO: 229 and SEQ ID NO: 230, respectively; [0097] (xix) polynucleotides encoding the sequences of SEQ ID NO: 231 and SEQ ID NO: 232, respectively; [0098] (xx) polynucleotides encoding the sequences of SEQ ID NO: 233 and SEQ ID NO: 234, respectively; [0099] (xxi) polynucleotides encoding the sequences of SEQ ID NO: 235 and SEQ ID NO: 236, respectively; [0100] (xxii) polynucleotides encoding the sequences of SEQ ID NO: 237 and SEQ ID NO: 238, respectively; [0101] (xxiii) polynucleotides encoding the sequences of SEQ ID NO: 239 and SEQ ID NO: 240, respectively; and [0102] (xxiv) polynucleotides encoding the sequences of SEQ ID NO: 241 and SEQ ID NO: 242, respectively. [0103] In certain embodiments, the present disclosure provides isolated nucleic acids that have at least 80% sequence identity to a polynucleotide encoding the HCVD and/or LCVD of the antibody, ABPC, or ABD of any of the preceding claims. In specific embodiments, the nucleic acids have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to a polynucleotide encoding the HCVD and/or LCVD. [0104] In various embodiments, the present disclosure encompasses all nucleotide sequences encoding the amino acid sequences of the antibodies, ABPCs, or ABDs described herein due to the degeneracy of the genetic code. The genetic code is redundant, with multiple codons often encoding the same amino acid. Thus, different nucleotide sequences can encode identical amino acid sequences of the antibodies, ABPCs, or ABDs. The present disclosure encompasses all such degenerate nucleotide sequences that encode the amino acid sequences described herein. [0105] The present disclosure further provides expression vectors comprising the nucleic acids described herein, as well as host cells comprising such expression vectors. In certain embodiments, the host cell is selected from the group consisting of E. coli, yeast, insect cells, and mammalian cells. In specific embodiments, the mammalian cell is a CHO cell, HEK293 cell, or NS0 cell. Attorney Docket No.: 45395-0068WO1 [0106] In further embodiments, the present disclosure provides methods of producing an antibody, ABPC, or ABD comprising culturing the host cell under conditions suitable for expression of the nucleic acids and recovering the antibody, ABPC, or ABD from the culture. [0107] In some aspects, the antibody, antigen-binding antibody construct, or ABD includes one or more of the following characteristics: (a) a heavy chain variable domain (HCVD) sequence that is at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identical to the HCVD sequence of any one of SEQ ID NO: 123, SEQ ID NO: 131, SEQ ID NO: 139, SEQ ID NO: 147, SEQ ID NO: 155, SEQ ID NO: 163, SEQ ID NO: 171, SEQ ID NO: 179, SEQ ID NO: 187, SEQ ID NO: 195, SEQ ID NO: 203, and SEQ ID NO: 211; and/or (b) a light chain variable domain (LCVD) sequence that is at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identical to the LCVD sequence of any one of SEQ ID NO: 124, SEQ ID NO: 132, SEQ ID NO: 140, SEQ ID NO: 148, SEQ ID NO: 156, SEQ ID NO: 164, SEQ ID NO: 172, SEQ ID NO: 180, SEQ ID NO: 188, SEQ ID NO: 196, SEQ ID NO: 204, and SEQ ID NO: 212. [0108] In another aspect, the present disclosure provides an antibody, antigen-binding protein construct, or ABD comprising an HCVD and an LCVD, wherein: (a) the HCVD comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 123, SEQ ID NO: 131, SEQ ID NO: 139, SEQ ID NO: 147, SEQ ID NO: 155, SEQ ID NO: 163, SEQ ID NO: 171, SEQ ID NO: 179, SEQ ID NO: 187, SEQ ID NO: 195, SEQ ID NO: 203, and SEQ ID NO: 211; and/or (b) the LCVD comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 124, SEQ ID NO: 132, SEQ ID NO: 140, SEQ ID NO: 148, SEQ ID NO: 156, SEQ ID NO: 164, SEQ ID NO: 172, SEQ ID NO: 180, SEQ ID NO: 188, SEQ ID NO: 196, SEQ ID NO: 204, and SEQ ID NO: 212. [0109] In some aspects of the antibody, the antigen-binding protein construct, or ABD, the HCVD amino acid sequence and the LCVD amino acid sequence is selected from the group consisting of: SEQ ID NO: 123 and SEQ ID NO: 124, respectively; SEQ ID NO: 131 and SEQ ID NO: 132, respectively; SEQ ID NO: 139 and SEQ ID NO: 140; SEQ ID NO: 147 and SEQ ID NO: 148, respectively; SEQ ID NO: 155 and SEQ ID NO: 156, respectively; SEQ ID NO: 163 and SEQ ID NO: 164, respectively; SEQ ID NO: 171 and SEQ ID NO: 172, respectively; SEQ ID NO: 179 and SEQ ID NO: 179, respectively; SEQ ID NO: 187 and SEQ ID NO: 187, respectively; SEQ ID NO: 195 and SEQ ID NO: 196, respectively; SEQ ID NO: 203 and SEQ ID NO: 204, respectively; and SEQ ID NO: 211 and SEQ ID NO: 212, respectively. Attorney Docket No.: 45395-0068WO1 [0110] In some aspects, the DLL3 polypeptide comprises an amino acid sequence selected from the group consisting of the sequences of SEQ ID NO: 1 (mature human DLL3) or SEQ ID NO: 2 (human DLL3 extracellular domain). In some aspects, the antibody, ABPC, or ABD undergoes intracellular internalization when the antibody, ABPC, or ABD binds to a DLL3 polypeptide expressed on a cell surface (e.g., a tumor cell surface). [0111] In some aspects, the antibody, antigen binding protein construct (ABPC), or antigen binding domain (ABD) is cytotoxic or cytostatic to the target mammalian cell. [0112] In some aspects, the antibody, ABPC, or ABD is cross-reactive with a non-human primate DLL3 and human DLL3. In some aspects, the antibody, ABPC, or ABD is cross-reactive with a non-human primate DLL3, a human DLL3, and one or both of rat DLL3 and a mouse DLL3. In some aspects, the antibody, ABPC, or ABD is cross-reactive with a non-human primate DLL3, a human DLL3, a rat DLL3, and a mouse DLL3. In some aspects, the antibody, the ABPC, or ABD binds to an epitope of DLL3 that is present on the surface of cells from an Old World Monkey. [0113] In some aspects, the ABPC includes a single polypeptide. In some aspects, the ABD is selected from a VH domain, a VHH domain, a VNAR domain, and a scFv. In some aspects, the ABPC is a BiTe, a (scFv)2, a nanobody, a nanobody-HSA, a DART, a TandAb, a scDiabody, a scDiabody-CH3, scFv-CH-CL-scFv, a HSAbody, scDiabody-HSA, or a tandem-scFv. In still other embodiments, the ABPC or ABD is a heavy chain-only antibody. [0114] In some aspects, the ABPC or ABD includes two or more polypeptides. In some aspects, the ABPC is selected from the group of an antibody, a VHH-scAb, a VHH-Fab, a Dual scFab, a F(ab’)2, a diabody, a crossMab, a DAF (two-in-one), a DAF (four-in-one), a DutaMab, a DT-IgG, a knobs-in-holes common light chain, a knobs-in-holes assembly, a charge pair, a Fab-arm exchange, a SEEDbody, a LUZ-Y, a Fcab, a κλ-body, an orthogonal Fab, a DVD-IgG, a IgG(H)- scFv, a scFv-(H)IgG, IgG(L)-scFv, scFv-(L)IgG, IgG(L,H)-Fv, IgG(H)-V, V(H)-IgG, IgG(L)-V, V(L)-IgG, KIH IgG-scFab, 2scFv-IgG, IgG-2scFv, scFv4-Ig, Zybody, DVI-IgG, Diabody-CH3, a triple body, a miniantibody, a minibody, a TriBi minibody, scFv-CH3 KIH, Fab-scFv, a F(ab’)2- scFv2, a scFv-KIH, a Fab-scFv-Fc, a tetravalent HCAb, a scDiabody-Fc, a Diabody-Fc, a tandem scFv-Fc, a VHH-Fc, a tandem VHH-Fc, a VHH-Fc KiH, a Fab-VHH-Fc, an Intrabody, a dock and lock, an ImmTAC, an IgG-IgG conjugate, a Cov-X-Body, a scFv1-PEG-scFv2, an Adnectin, a DARPin, a fibronectin, a DEP conjugate, a PROTAB, and a PROTAC. Attorney Docket No.: 45395-0068WO1 [0115] In other aspects, any of the ABPCs described herein is a monoclonal antibody, a chimeric antibody, a humanized antibody, a multi-specific (e.g., bispecific, trispecific, tetra-specific, etc.) antibody, a multi-paratopic (e.g. biparatopic, tri-paratopic, etc.) antibody. [0116] In some aspects, the ABPC includes a proteolysis-targeting antibody (PROTAB) (as described, e.g., in Marei et al, “Antibody targeting of E3 ubiquitin ligases for receptor degradation. Nature, 6 October 2022). In some aspects, the PROTAB may tether cell-surface E3 ubiquitin ligases to transmembrane proteins, resulting in target degradation both in vitro and in vivo. [0117] In some aspects, at least one polypeptide of the ABPC or ABD is conjugated to the toxin, the radioisotope, the drug, or the small molecule via a cleavable linker. In some aspects, at least one polypeptide of the ABPC is conjugated to the toxin, the radioisotope, the drug, or the small molecule via a non-cleavable linker. [0118] In some aspects, the properties of an ABPC, antibody, or ABD according to this disclosure may be modified to alter its physicochemical properties. In some aspects, the modification may comprise amino acid scanning mutagenesis, e.g., as disclosed in published application US 2022/0281984, which is incorporated by reference herein in its entirety. [0119] In some aspects, the ABPC, antibody, or ABD is degraded in the target mammalian cell following internalization of the ABPC by the target mammalian cell. [0120] In some aspects, the ABPC, antibody, or ABD includes a conjugated toxin, radioisotope, drug, or small molecule (each “a conjugate composition”). [0121] In some aspects, the conjugated composition provides for an increase in toxin liberation in the target mammalian cell as compared to a composition including the same amount of a control ABPC, antibody, or ABD. In some aspects, the conjugated composition provides for at least a 20% increase in toxin liberation in the target mammalian cell as compared to a composition including the same amount of a control ABPC, antibody, or ABD. In some aspects, the conjugated composition provides for at least a 50% increase in toxin liberation in the target mammalian cell as compared to a composition including the same amount of a control ABPC, antibody, or ABD. In some aspects, the conjugated composition provides for at least a 2-fold increase in toxin liberation in the target mammalian cell as compared to a composition including the same amount of a control ABPC, antibody, or ABD. In some aspects, the conjugated composition provides for at least a 5-fold increase in toxin liberation in the target mammalian cell as compared to a composition including the same amount of a control ABPC, antibody, or ABD. Attorney Docket No.: 45395-0068WO1 [0122] In some aspects, the conjugated composition provides for an increase in target mammalian cell killing as compared to a composition including the same amount of a control ABPC, antibody, or ABD. In some aspects, the conjugated composition provides for at least a 20% or 50% increase in target mammalian cell killing as compared to a composition including the same amount of a control ABPC, antibody, or ABD. In some aspects, the conjugated composition provides for at least a 2- or 5-fold increase in target mammalian cell killing as compared to a composition including the same amount of a control ABPC, antibody, or ABD. [0123] In some aspects, the composition provides for an increase in endolysosomal delivery in the target mammalian cell as compared to a composition including the same amount of a control ABPC, antibody, or ABD. In some aspects, the composition provides for at least a 20% or 50% increase in endolysosomal delivery in the target mammalian cell as compared to a composition including the same amount of a control ABPC, antibody, or ABD. In some aspects, the composition provides for at least a 2- or 5-fold increase in endolysosomal delivery in the target mammalian cell as compared to a composition including the same amount of a control ABPC, antibody, or ABD. [0124] In some aspects, the composition results in a less of a reduction in the level of DLL3 presented on the surface of the target mammalian cell as compared to a composition including the same amount of a control ABPC, antibody, or ABD. In some aspects, the composition does not result in a detectable reduction in the level of the DLL3 presented on the surface of the target mammalian cell. [0125] Also provided herein are pharmaceutical compositions including an effective amount of an antigen-binding protein construct (ABPC) including: a first ABD that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell; and a conjugated toxin, radioisotope, drug, or small molecule, where: (a) the dissociation rate of the first ABD 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 ABD 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 for one or more of: an increase in toxin liberation in the target mammalian cell as compared to a composition including the same amount of a control ABPC; an increase in target mammalian cell killing as compared to a composition including the same amount of a control ABPC; and an increase in Attorney Docket No.: 45395-0068WO1 endolysosomal delivery in the target mammalian cell as compared to a composition including the same amount of a control ABPC. [0126] In one aspect, the present disclosure provides a recombinant nucleic acid sequence encoding any of the ABPCs, antibodies, or ABDs described herein. In another aspect, the present disclosure provides a host cell or vector comprising any of the recombinant nucleic acid sequences disclosed herein. [0127] In one aspect, the present disclosure provides a composition comprising any of the ABPCs, antibodies, or antigen-binding domains described herein and a pharmaceutically- acceptable carrier, wherein the ABPC, antibody, or ABDis optionally conjugated to an agent selected from the group consisting of isotopes, dyes, chromogens, contrast agents, drugs, toxins, cytokines, enzymes, proteolysis-targeting antibodies (PROTABs), enzyme inhibitors, hormones, hormone antagonists, growth factors, radionuclides, metals, liposomes, nanoparticles, RNA, DNA or any combination thereof. [0128] In one aspect, the present disclosure provides a method for treating a DLL3-positive cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of any of the ABPCs, antibodies, or ABDs described herein , wherein the ABPC, antibody, or ABD is conjugated to at least one additional therapeutic agent. Examples of such additional therapeutic agents include, but are not limited to, isotopes, drugs, toxins, cytokines, enzymes, enzyme inhibitors, hormones, hormone antagonists, growth factors, radionuclides, metals, liposomes, nanoparticles, RNA, DNA or any combination thereof. The DLL3-positive cancer may be small-cell lung cancer, large cell neuroendocrine carcinoma, pulmonary neuroendocrine cancer, extrapulmonary neuroendocrine cancers, or melanoma. [0129] In another aspect, the present disclosure provides a method for detecting DLL3 protein expression levels in a biological sample comprising contacting the biological sample with an ABPC, antibody, or ABD described herein, and detecting the binding of the ABPC, antibody, or ABD to DLL3 protein in the biological sample. In some embodiments, the ABPC, antibody, or ABD is conjugated to a detectable label; and the binding of the ABPC, antibody, or ABD is detected using the signal generated by the detectable label. [0130] Also disclosed herein are kits for the detection and/or treatment of DLL3-positive cancers comprising at least one of any of the ABPCs, antibodies, or ABDs described herein , or a functional variant (e.g., substitutional variant) thereof and instructions for use. In certain embodiments, the Attorney Docket No.: 45395-0068WO1 ABPD, antibody, or ABD is coupled to one or more detectable labels. In one embodiment, the one or more detectable labels comprise a radioactive label, a fluorescent label, or a chromogenic label. [0131] Additionally, or alternatively, in some embodiments, the kit further comprises a secondary antibody or antigen-binding domain that specifically binds to any of the ABPCs, antibodies, or ABDs that binds specifically to DLL3 described herein. In some aspects, the secondary antibody or antigen-binding domain is coupled to at least one detectable label. In some embodiments, the at least one detectable label is selected from the group of a radioactive label, a fluorescent label, or a chromogenic label. [0132] Exemplary HCVD and LCVD sequences that can be present in any of the ABPCs, antibodies, or antigen-binding domains described herein are shown in Table 1. In Table 1 below (and similar tables herein), the CDRs in the HCVD and LCVD were identified using the methods described by Kabat (Kabat et al. (1992) Sequences of Proteins of Immunological Interest (DIANE publishing) and IMGT (Lefranc MP (1999) “The IMGT unique numbering for Immunoglobulins, T cell receptors and Ig-like domains” The Immunologist 7, 132-136), and for each CDR, residues falling under either or both Kabat and IMGT CDR definitions were called as CDR residues (“Kabat-IMGT” CDRs). The CDR sequences (determined by Kabat-IMGT) in the HCVD and LCVD are shown in bold (identified by Kabat-IMGT) and the framework sequences in the HCVD and LCVD are not shown in bold. Table 1. Rabbit monoclonal DLL3-binding protein heavy chain variable domain (HCVD) and light chain variable domain (LCVD) sequences Clone Heavy Chain Variable Domain (HCVD) Light Chain Variable Domain (LCVD) sequences sequences S S Y Q K N G N S G Attorney Docket No.: 45395-0068WO1 10F6 QSVEESGGRLVTPGTPLTLTCTVSGFSLSSRV AQVLTQTPSSVSAAVGGTVSISCQSSQSVAG MNWVRQAPGKGLEWIGFIDSDGTTYYASWVKG NNWLSWFQQKPGQPPKLLIYAASYLASGVPS RFTISKISTTVDLKVTSLTTEDTATYFCASDW RFKGSGSGTQFTLTISDLESDDAATYYCAGA G S A R F L D L S D Q S F G N R Y S F S Q S F S Q N R Y [0133] Exemplary sets of three H-CDRs (determined by Kabat-IMGT) that can present in an HCVD in any of the ABPCs, antibodies, or ABDs described herein are shown in Table 2 below. Table 2. Rabbit DLL3-binding heavy chain CDR sequences Clone H-CDR1 Seq ID H-CDR2 Seq ID H-CDR3 Seq ID Attorney Docket No.: 45395-0068WO1 10D1 GFSFSDKYYMC 13 CIYAGSSGRTWYANWAKG 14 GRGGWTDYVF 15 5D12 GIDLSDYAMS 21 TVSSGGHKYYASWAKG 22 ARVPHGGSIGYPIPI 23 10F6 GFSLSSRVMN 29 FIDSDGTTYYASWVKG 30 ASDWGTAINI 31 [ an HCVD in any of the ABPCs, antibodies, or ABDs described herein are shown in Table 3 below. Table 3. Rabbit monoclonal DLL3-binding protein light chain CDR sequences Clone L-CDR1 Seq ID L-CDR2 Seq ID L-CDR3 Seq ID 3H11 QASQSVYSNNYLA 8 RASKLAS 9 QGYFGGGING 10 [0135] Exemplary heavy chain and light chain sequences that may be present in any of the ABPCs or antibodies described herein are shown in Table 4 below. In Table 4, the CDR sequences (determined by Kabat-IMGT) are shown in bold and the variable domain framework and the constant domain sequences are not shown in bold. Table 4. Full-length, rabbit anti-DLL3 antibody heavy and light chain sequences Clone Heavy Chain (HC) Light Chain (LC) C P S G A K K T E Attorney Docket No.: 45395-0068WO1 KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHN VTHQGLSSPVTKSFNRGEC HYTQKSLSLSPGK (SEQ ID NO: 99) (SEQ ID NO: 100) C P S G P S V Y V Q C P S G P S V Y V Q C P S G P S V Y V Q C P S G P S V Y V Q C L T G V T N Attorney Docket No.: 45395-0068WO1 NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA ALQSGNSQESVTEQDSKDSTYSL KGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWE SSTLTLSKADYEKHKVYACEVTH SNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC QGLSSPVTKSFNRGEC (SEQ C P S G A K K T E C L T Y T G D S T N K G T P S V Y V Q C L T Y A K K T E C L T Y A K K Attorney Docket No.: 45395-0068WO1 RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQP VDNALQSGNSQESVTEQDSKDST REPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQ YSLSSTLTLSKADYEKHKVYACE PENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMH VTHQGLSSPVTKSFNRGEC C K G S P Q Q D A [ p y q y p y Cs, antibodies, or ABDs described herein are shown in Table 5 below. In Table 5, the CDRs (determined by Kabat-IMGT) are shown in bold and the framework regions are not shown in bold. Table 5. Humanized DLL3-binding protein heavy chain variable domain (HCVD) and light chain variable domain (LCVD) sequences MYT# Heavy Chain Variable Domain Light Chain Variable Domain (LCVD) (HCVD) S S Y K S G N S G G S A G S A Attorney Docket No.: 45395-0068WO1 LRAEDTAVYYCASDWGTAINIWGQGTLV WSGIRAFGQGTKLTVL (SEQ ID NO: TVSS (SEQ ID NO: 155) 156) 8829 EVQLVESGGGLVQPGGSLRLSCTASGFS EIVMTQSPSTLSASVGDRVIITCQASHSIAR F L ) L S D S F G N F D S F S S F S N R Y : [0137] Exemplary sets of three H-CDRs (determined by Kabat-IMGT) that can be present in an HCVD in any of the ABPCs, antibodies, or ABDs described herein are shown in Table 6 below. Table 6. Humanized DLL3-binding heavy chain CDR sequences MYT# CDR-H1 Seq H-CDR2 Seq H-CDR3 Seq ID ID ID 7 5 3 Attorney Docket No.: 45395-0068WO1 8820 GFSLSSRVMN 149 FIDSDGTTYYASWAKG 150 ASDWGTAINI 151 8821 GFSLNNNIMS 157 FIDSDGTTYYASWVNG 158 ASDWGTAINI 159 8829 GFSFSSSHFIC 165 CIFAGSGDTTYYTSWAKG 166 ARVNISMDDYGAFDP 167 5 3 1 9 7 5 [ an LCVD in any of the ABPCs, antibodies, or ABDs described herein are shown in Table 7 below. Table 7. Humanized DLL3-binding protein light chain CDR sequences MYT# L-CDR1 Seq ID L-CDR2 Seq ID L-CDR3 Seq ID 8812 QASQSVYSNNYLA 128 RASKLAS 129 QGYFGGGING 130 [0139] Exemplary heavy chains and light chains that can be present in any of the ABPCs and antibodies described herein are shown in Table 8 below. In Table 8, CDR sequences are shown in bold (as defined by Kabat-IMGT) and variable domain framework regions and constant domain sequences are not shown in bold. Table 8. Full-length, humanized anti-DLL3 antibody heavy and light chain sequences MYT# Heavy Chain (HC) Light Chain (LC) 8812 EVQLVESGGGLVQPGGSLRLSCTASGIDLSSNDMAWVRQA EIVMTQSPSTLSASVGDRVIITC Attorney Docket No.: 45395-0068WO1 SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK (SEQ ID NO: 219) 8815 EVQLVESGGGLVQPGGSLRLSCTASGFSFSDKYYMCWVRQ EIVMTQSPSTLSASVGDRVIITC Attorney Docket No.: 45395-0068WO1 LLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV FYPREAKVQWKVDNALQSGNSQE KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDW SVTEQDSKDSTYSLSSTLTLSKA LNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP DYEKHKVYACEVTHQGLSSPVTK Attorney Docket No.: 45395-0068WO1 YLQMNSLRAEDTAVYYCARYESSSGYMDLWGQGTLVTVSS LIYETSKLASGVPSRFSGSGSGA ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS EFTLTISSLQPDDFATYYCHQAY WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT SYANIDNVFGQGTKLTVLRTVAA [0 s no e a ove, o sequences s own n a es , , , an correspon o CDR sequences. The amino acid sequences outside of the CDRs in an HCVD or LCVD are referred to as “framework region(s)” or “FR(s)”. HCVDs and LCVDs include four framework regions, and can be referred to as: “FR1,” “FR2,” “FR3,” and “FR4.” An HCVD has the following format: FR1- H-CDR1-FR2-H-CDR2-FR3-H-CDR3-FR4. An LCVD has the following format: FR1-L-CDR1- FR2-L-CDR2-FR3-L-CDR3-FR4. [0141] In some embodiments, references to percent or percentage identity when referring to a variable domain (e.g., a HCVD or a LCVD) refers to the percent sequence identity that is maintained over the length of the reference variable domain without substitutions in the CDR regions (i.e., CDR1, CDR2, and CDR3). For example, a recitation of a variable domain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 99% identical to a reference sequence, refers to the percent sequence identity across the length of the reference sequence without substitutions to the CDR sequences (i.e., substitutions are only present in one or more framework regions of the variable domain). In some embodiments, the substitution(s) in one or more framework regions are conservative amino acid substitutions. [0142] In some embodiments, the variable domains (HCVD or LCVD) described herein can have an amino acid sequence at least about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, Attorney Docket No.: 45395-0068WO1 98%, or 99% identity to a reference sequence when the CDR sequences do not include any substitutions. [0143] In some embodiments, the variable domains (HCVD or LCVD) of the present disclosure can include 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more amino acid substitutions compared to a reference variable domain sequence so long as the CDR sequences of the variable domains do not include any amino acid substitutions (i.e., substitutions are only present in the framework regions of the variable domain). In some embodiment, the variable domains (HCVD or LCVD) can include 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more amino acid substitutions so long as the CDR sequences of the variable domain does not include any amino acid substitutions. In some examples, the substitution(s) in one or more framework regions are conservative amino acid substitutions. [0144] In another aspect, the present disclosure provides antigen-binding protein (ABP) constructs (ABPCs) that display or may be modified to display enhanced efficacy in toxin liberation in a target mammalian cell, an increase in cell killing, and an increase in endolysosomal delivery. [0145] In some aspects, the disclosure provides pharmaceutical compositions including an effective amount of an ABPC including: a first antigen-binding domain (ABD) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell, where: (a) the dissociation rate of the first ABD 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 (KD) of the first ABD 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. [0146] In some aspects, the first ABD includes a heavy chain variable domain (HCVD) of an HCVD having the amino acid sequence of one of SEQ ID NO: 3, SEQ ID NO: 11, SEQ ID NO: 19, SEQ ID NO: 27, SEQ ID NO: 35, SEQ ID NO: 43, SEQ ID NO: 51, SEQ ID NO: 59, SEQ ID NO: 67, SEQ ID NO: 75, SEQ ID NO: 83, and SEQ ID NO: 91, each HCVD optionally with at least 1 histidine substitution (e.g., one, two, three, four, or five total histidine substitutions across the set of three H-CDRs). [0147] In some aspects, the first ABD includes a light chain variable domain (LCVD) of an LCVD having the amino acid sequence of one of SEQ ID NO: 4, SEQ ID NO: 12, SEQ ID NO: 20, SEQ ID NO: 28, SEQ ID NO: 36, SEQ ID NO: 44, SEQ ID NO: 52, SEQ ID NO: 60, SEQ ID Attorney Docket No.: 45395-0068WO1 NO: 68, SEQ ID NO: 76, SEQ ID NO: 84, and SEQ ID NO: 92, each LCVD optionally with at least 1 histidine substitution (e.g., one, two, three, four, or five total histidine substitutions across the set of three L-CDRs). [0148] In some aspects, the first ABD includes one of (a) to (l): (a) an HCVD of SEQ ID NO: 3 and/or an LCVD of SEQ ID NO: 4; (b) an HCVD of SEQ ID NO: 11 and/or an LCVD of SEQ ID NO: 12; (c) an HCVD of SEQ ID NO: 19 and/or an LCVD of SEQ ID NO: 20; (d) an HCVD of SEQ ID NO: 27 and/or an LCVD of SEQ ID NO: 28; (e) an HCVD of SEQ ID NO: 35 and/or an LCVD of SEQ ID NO: 36; (f) an HCVD of 43 and/or an LCVD of SEQ ID NO: 44; (g) an HCVD of 51 and/or an LCVD of SEQ ID NO: 52; (h) an HCVD of 59 and/or an LCVD of SEQ ID NO: 60; (i) an HCVD of r SEQ ID NO: 67 and/or an LCVD of SEQ ID NO: 68; (j) an HCVD of SEQ ID NO: 75 and/or an LCVD of SEQ ID NO: 76; (k) an HCVD of SEQ ID NO: 83 and/or an LCVD of SEQ ID NO: 84; and (l) an HCVD of SEQ ID NO: 91 and/or an LCVD of SEQ ID NO: 92, each, HCVD and/or LCVD optionally with one or more amino acids substituted with a histidine (e.g., one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or one, two, three, four, or five total histidine substitutions across the set of three L-CDRs). [0149] In some aspects, the first ABD includes one of (a) to (l): (a) an HCVD including the amino acid sequence of SEQ ID NO: 123 and/or an LCVD including the amino acid sequence of SEQ ID NO: 124; (b) an HCVD including the amino acid sequence of SEQ ID NO: 131 and/or an LCVD including the amino acid sequence of SEQ ID NO: 132; (c) an HCVD including the amino acid sequence of SEQ ID NO: 139 and/or an LCVD including the amino acid sequence of SEQ ID NO: 140; (d) an HCVD including the amino acid sequence of SEQ ID NO: 147 and/or an LCVD including the amino acid sequence of SEQ ID NO: 148; (e) an HCVD including the amino acid sequence of SEQ ID NO: 155 and/or an LCVD including the amino acid sequence of SEQ ID NO: 156; (f) an HCVD including the amino acid sequence of SEQ ID NO: 163 and/or an LCVD including the amino acid sequence of SEQ ID NO: 164; (g) an HCVD including the amino acid sequence of SEQ ID NO: 171 and/or an LCVD including the amino acid sequence of SEQ ID NO: 172; (h) an HCVD including the amino acid sequence of SEQ ID NO: 179 and/or an LCVD including the amino acid sequence of SEQ ID NO: 180; (i) an HCVD including the amino acid sequence of SEQ ID NO: 187 and/or an LCVD including the amino acid sequence of SEQ ID NO: 188; (j) an HCVD including the amino acid sequence of SEQ ID NO: 195 and/or an LCVD including the amino acid sequence of SEQ ID NO: 196; (k) an HCVD including the amino acid Attorney Docket No.: 45395-0068WO1 sequence of SEQ ID NO: 203 and/or an LCVD including the amino acid sequence of SEQ ID NO: 204; and (l) an HCVD including the amino acid sequence of SEQ ID NO: 211 and/or an LCVD including the amino acid sequence of SEQ ID NO: 212, each HCVD and/or LCVD optionally with one or more amino acids substituted with a histidine (e.g., one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or one, two, three, four, or five total histidine substitutions across the set of three L-CDRs). [0150] In some aspects, the first ABD includes one of (a) to (l): (a) an HCVD including the sequence of SEQ ID NO: 3 and/or an LCVD including the sequence of SEQ ID NO: 4; (b) an HCVD including the sequence of SEQ ID NO: 11 and/or an LCVD including the sequence of SEQ ID NO: 12; (c) an HCVD including the sequence of SEQ ID NO: 19 and/or an LCVD including the sequence of SEQ ID NO: 20; (d) an HCVD including the sequence of SEQ ID NO: 27 and/or an LCVD including the sequence of SEQ ID NO: 28; (e) an HCVD including the sequence of SEQ ID NO: 35 and/or an LCVD including the sequence of SEQ ID NO: 36; (f) an HCVD including the sequence of SEQ ID NO: 43 and/or an LCVD including the sequence of SEQ ID NO: 44; (g) an HCVD including the sequence of SEQ ID NO: 51 and/or an LCVD including the sequence of SEQ ID NO: 52; (h) an HCVD including the sequence of SEQ ID NO: 59 and/or an LCVD including the sequence of SEQ ID NO: 60; (i) an HCVD including the sequence of SEQ ID NO: 67 and/or an LCVD including the sequence of SEQ ID NO: 68; (j) an HCVD including the sequence of SEQ ID NO: 75 and/or an LCVD including the sequence of SEQ ID NO: 76; (k) an HCVD including the sequence of SEQ ID NO: 83 and/or an LCVD including the sequence of SEQ ID NO: 84; and (l) an HCVD including the sequence of SEQ ID NO: 91 and/or an LCVD including the sequence of SEQ ID NO: 92, each HCVD and/or LCVD optionally with one or more amino acids substituted with a histidine (e.g., one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or one, two, three, four, or five total histidine substitutions across the set of three L-CDRs). [0151] In some aspects, the first ABD includes one of (a) to (l): (a) an HCVD including the sequence of SEQ ID NO: 123 and/or an LCVD including the sequence of SEQ ID NO: 124; (b) an HCVD including the sequence of SEQ ID NO: 131 and/or an LCVD including the sequence of SEQ ID NO: 132; (c) an HCVD including the sequence of SEQ ID NO: 139 and/or an LCVD including the sequence of SEQ ID NO: 140; (d) an HCVD including the sequence of SEQ ID NO: 147 and/or an LCVD including the sequence of SEQ ID NO: 148; (e) an HCVD including the Attorney Docket No.: 45395-0068WO1 sequence of SEQ ID NO: 155 and/or an LCVD including the sequence of SEQ ID NO: 156; (f) an HCVD including the sequence of SEQ ID NO: 163 and/or an LCVD including the sequence of SEQ ID NO: 164; (g) an HCVD including the sequence of SEQ ID NO: 171 and/or an LCVD including the sequence of SEQ ID NO: 172; (h) an HCVD including the sequence of SEQ ID NO: 179 and/or an LCVD including the sequence of SEQ ID NO: 180; (i) an HCVD including the sequence of SEQ ID NO: 187 and/or an LCVD including the sequence of SEQ ID NO: 188; (j) an HCVD including the sequence of SEQ ID NO: 195 and/or an LCVD including the sequence of SEQ ID NO: 196; (k) an HCVD including the sequence of SEQ ID NO: 203 and/or an LCVD including the sequence of SEQ ID NO: 204; and (l) an HCVD including the sequence of SEQ ID NO: 211 and/or an LCVD including the sequence of SEQ ID NO: 212, each HCVD and/or LCVD optionally with one or more amino acids substituted with a histidine (e.g., one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or one, two, three, four, or five total histidine substitutions across the set of three L-CDRs). [0152] In some aspects, the first ABD includes a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein (a) the HCVD comprises an H-CDR1 sequence, an H-CDR2 sequence, and an H-CDR3 sequence selected from the group consisting of one of (i) to (xii): (i) the sequences of SEQ ID NO: 5, SEQ ID NO: 6, and SEQ ID NO: 7, respectively; (ii) the sequences of SEQ ID NO: 13, SEQ ID NO: 14, and SEQ ID NO: 15, respectively; (iii) the sequences of SEQ ID NO: 21, SEQ ID NO: 22, and SEQ ID NO: 23, respectively; (iv) the sequences of SEQ ID NO: 29, SEQ ID NO: 30, and SEQ ID NO: 31, respectively; (v) the sequences of SEQ ID NO: 37, SEQ ID NO: 38, and SEQ ID NO: 39, respectively; (vi) the sequences of SEQ ID NO: 45, SEQ ID NO: 46, and SEQ ID NO: 47, respectively; (vii) the sequences of SEQ ID NO: 53, SEQ ID NO: 54, and SEQ ID NO: 55, respectively; (viii) the sequences of SEQ ID NO: 61, SEQ ID NO: 62, and SEQ ID NO: 63, respectively; (ix) the sequences of SEQ ID NO: 69, SEQ ID NO: 70, and SEQ ID NO: 71, respectively; (x) the sequences of SEQ ID NO: 77, SEQ ID NO: 78, and SEQ ID NO: 79, respectively; (xi) the sequences of SEQ ID NO: 85, SEQ ID NO: 86, and SEQ ID NO: 87, respectively; and (xii) the sequences of SEQ ID NO: 93, SEQ ID NO: 94, and SEQ ID NO: 95, respectively; and/or (b) the LCVD comprises an L-CDR1 sequence, an L-CDR2 sequence, and an L-CDR3 sequence selected from the group consisting of one of (i) to (xii): (i) the sequences of SEQ ID NO: 8, SEQ ID NO: 9, and SEQ ID NO: 10, respectively; (ii) the sequences of SEQ ID NO: 16, SEQ ID NO: 17, and Attorney Docket No.: 45395-0068WO1 SEQ ID NO: 18, respectively; (iii) the sequences of SEQ ID NO: 24, SEQ ID NO: 25, and SEQ ID NO: 26, respectively; (iv) the sequences of SEQ ID NO: 32, SEQ ID NO: 33, and SEQ ID NO: 34, respectively; (v) the sequences of SEQ ID NO: 40, SEQ ID NO: 41, and SEQ ID NO: 42, respectively; (vi) the sequences of SEQ ID NO: 48, SEQ ID NO: 49, and SEQ ID NO: 50, respectively; (vii) the sequences of SEQ ID NO: 56, SEQ ID NO: 57, and SEQ ID NO: 58, respectively; (viii) the sequences of SEQ ID NO: 64, SEQ ID NO: 65, and SEQ ID NO: 66, respectively; (ix) the sequences of SEQ ID NO: 72, SEQ ID NO: 73, and SEQ ID NO: 74, respectively; (x) the sequences of SEQ ID NO: 80, SEQ ID NO: 81, and SEQ ID NO: 82, respectively; (xi) the sequences of SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 90, respectively; (xii) the sequences of SEQ ID NO: 96, SEQ ID NO: 97, and SEQ ID NO: 98, respectively. In some aspects, at least one of the H-CDR1, H-CDR2, and H-CDR3 sequences and/or at least one of the L-CDR1, L-CDR2, and L-CDR3 sequences has one or more amino acid position substituted with a histidine (e.g., one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or one, two, three, four, or five total histidine substitutions across the set of three L-CDRs). [0153] In some aspects, the first ABD includes a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein (a) the HCVD comprises an H-CDR1 sequence, an H-CDR2 sequence, and an H-CDR3 sequence selected from the group consisting of one of (i) to (xii): (i) the sequences of SEQ ID NO: 125, SEQ ID NO: 126, and SEQ ID NO: 127, respectively; (ii) the sequences of SEQ ID NO: 133, SEQ ID NO: 134, and SEQ ID NO: 135, respectively; (iii) the sequences of SEQ ID NO: 141, SEQ ID NO: 142, and SEQ ID NO: 143, respectively; (iv) the sequences of SEQ ID NO: 149, SEQ ID NO: 150, and SEQ ID NO: 151, respectively; (v) the sequences of SEQ ID NO: 157, SEQ ID NO: 158, and SEQ ID NO: 159, respectively; (vi) the sequences of SEQ ID NO: 165, SEQ ID NO: 166, and SEQ ID NO: 167, respectively; (vii) the sequences of SEQ ID NO: 173, SEQ ID NO: 174, and SEQ ID NO: 175, respectively; (viii) the sequences of SEQ ID NO: 181, SEQ ID NO: 182, and SEQ ID NO: 183, respectively; (ix) the sequences of SEQ ID NO: 189, SEQ ID NO: 190, and SEQ ID NO: 191, respectively; (x) the sequences of SEQ ID NO: 197, SEQ ID NO: 198, and SEQ ID NO: 199, respectively; (xi) the sequences of SEQ ID NO: 205, SEQ ID NO: 206, and SEQ ID NO: 207, respectively; and (xii) the sequences of SEQ ID NO: 213, SEQ ID NO: 214, and SEQ ID NO: 215, respectively; and/or (b) the LCVD comprises an L-CDR1 sequence, an L-CDR2 sequence, and an L-CDR3 sequence Attorney Docket No.: 45395-0068WO1 selected from the group consisting of one of (i) to (xii): (i) the sequences of SEQ ID NO: 128, SEQ ID NO: 129, and SEQ ID NO: 130, respectively; (ii) the sequences of SEQ ID NO: 136, SEQ ID NO: 137, and SEQ ID NO: 138, respectively; (iii) the sequences of SEQ ID NO: 144, SEQ ID NO: 145, and SEQ ID NO: 146, respectively; (iv) the sequences of SEQ ID NO: 152, SEQ ID NO: 153, and SEQ ID NO: 154, respectively; (v) the sequences of SEQ ID NO: 160, SEQ ID NO: 161, and SEQ ID NO: 162, respectively; (vi) the sequences of SEQ ID NO: 168, SEQ ID NO: 169, and SEQ ID NO: 170, respectively; (vii) the sequences of SEQ ID NO: 176, SEQ ID NO: 177, and SEQ ID NO: 178, respectively; (viii) the sequences of SEQ ID NO: 184, SEQ ID NO: 185, and SEQ ID NO: 186, respectively; (ix) the sequences of SEQ ID NO: 192, SEQ ID NO: 193, and SEQ ID NO: 194, respectively; (x) the sequences of SEQ ID NO: 200, SEQ ID NO: 201, and SEQ ID NO: 202, respectively; (xi) the sequences of SEQ ID NO: 208, SEQ ID NO: 209, and SEQ ID NO: 210, respectively; (xii) the sequences of SEQ ID NO: 216, SEQ ID NO: 217, and SEQ ID NO: 218, respectively. In some aspects, at least one of the H-CDR1, H-CDR2, and H-CDR3 sequences and/or at least one of the L-CDR1, L-CDR2, and L-CDR3 sequences has one or more amino acid position substituted with a histidine (e.g., one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or one, two, three, four, or five total histidine substitutions across the set of three L-CDRs). [0154] In some aspects, the ABPC is degraded in the target mammalian cell following internalization of the ABPC by the target mammalian cell. In some aspects, the ABPC includes a conjugated toxin, radioisotope, drug, or small molecule (also called herein “a conjugated composition”). [0155] In some aspects, the conjugated composition provides for an increase in toxin liberation in the target mammalian cell as compared to a composition including the same amount of a control ABPC. In some aspects, the conjugated composition provides for at least a 20% increase in toxin liberation in the target mammalian cell as compared to a composition including the same amount of a control ABPC. In some aspects, the conjugated composition provides for at least a 50% increase in toxin liberation in the target mammalian cell as compared to a composition including the same amount of a control ABPC. In some aspects, the conjugated composition provides for at least a 2-fold increase in toxin liberation in the target mammalian cell as compared to a composition including the same amount of a control ABPC. In some aspects, the conjugated Attorney Docket No.: 45395-0068WO1 composition provides for at least a 5-fold increase in toxin liberation in the target mammalian cell as compared to a composition including the same amount of a control ABPC. [0156] In some aspects, the conjugated composition provides for an increase in target mammalian cell killing as compared to a composition including the same amount of a control ABPC. In some aspects, the conjugated composition provides for at least a 20% or 50% increase in target mammalian cell killing as compared to a composition including the same amount of a control ABPC. In some aspects, the conjugated composition provides for at least a 2- or 5-fold increase in target mammalian cell killing as compared to a composition including the same amount of a control ABPC. [0157] In some aspects, a composition comprising any of the ABPCs described herein provides for an increase in endolysosomal delivery in the target mammalian cell as compared to a composition including the same amount of a control ABPC. In some aspects, a composition comprising any of the ABPCs described herein provides for at least a 20% or 50% increase in endolysosomal delivery in the target mammalian cell as compared to a composition including the same amount of a control ABPC. In some aspects, a composition comprising any of the ABPCs described herein provides for at least a 2- or 5-fold increase in endolysosomal delivery in the target mammalian cell as compared to a composition including the same amount of a control ABPC. [0158] In some aspects, a composition comprising any of the ABPCs described herein results in a less of a reduction in the level of DLL3 presented on the surface of the target mammalian cell as compared to a composition including the same amount of a control ABPC. In some aspects, a composition comprising any of the ABPCs described herein does not result in a detectable reduction in the level of the DLL3 presented on the surface of the target mammalian cell. [0159] Also provided herein are pharmaceutical compositions including an effective amount of an antigen-binding protein construct (ABPC) including: a first ABD that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell; and a conjugated toxin, radioisotope, drug, or small molecule, where: (a) the dissociation rate of the first ABD 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 ABD 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 for one or more of: an increase in toxin liberation in the target mammalian cell as compared to a composition including the same amount of a control ABPC; an increase in target mammalian cell killing as Attorney Docket No.: 45395-0068WO1 compared to a composition including the same amount of a control ABPC; and an increase in endolysosomal delivery in the target mammalian cell as compared to a composition including the same amount of a control ABPC. These pharmaceutical compositions are an example of a conjugated composition. [0160] In some aspects, the pharmaceutical composition provides for an increase in target mammalian cell killing as compared to a pharmaceutical composition including the same amount of a control ABPC. In some aspects, the pharmaceutical composition provides for at least a 20% or 50% increase in target mammalian cell killing as compared to a pharmaceutical composition including the same amount of a control ABPC. In some aspects, the pharmaceutical composition provides for at least a 2- or 5-fold increase in target mammalian cell killing as compared to a pharmaceutical composition including the same amount of a control ABPC. [0161] In some aspects, the pharmaceutical composition provides for an increase in endolysosomal delivery, including at least a 20% or 50% increase in endolysosomal delivery as compared to a pharmaceutical composition including the same amount of a control ABPC. In some aspects, the pharmaceutical composition provides for at least a 2- or 5-fold increase in endolysosomal delivery in the target mammalian cell as compared to a pharmaceutical composition including the same amount of a control ABPC. [0162] In some aspects, the pharmaceutical composition results in a less of a reduction in the level of DLL3 presented on the surface of the target mammalian cell as compared to a pharmaceutical composition including the same amount of a control ABPC. In some aspects, the pharmaceutical composition does not result in a detectable reduction in the level of the DLL3 presented on the surface of the target mammalian cell. In some aspects, the target mammalian cell is a DLL3-positive cancer cell. [0163] In some aspects, the dissociation rate of the first ABD at a pH of ~4.0 to ~6.5 is at least 10% faster than the dissociation rate of the first ABD at a pH of ~7.0 to ~8.0. In some aspects, the dissociation rate of the first ABD at a pH of ~4.0 to ~6.5 is at least 3-fold faster than the dissociation rate of the first ABD at a pH of ~7.0 to ~8.0. In some aspects, the dissociation rate of the first ABD at a pH of ~4.0 to ~6.5 is at least 10-fold faster than the dissociation rate of the first ABD at a pH of ~7.0 to ~8.0. In some aspects, the KD of the first ABD at a pH of ~4.0 to ~6.5 is at least 10% greater than the first KD of the ABD at a pH of ~7.0 to ~8.0. In some aspects, the first KD of the first ABD at a pH of ~4.0 to ~6.5 is at least 3-fold greater than the KD of the first ABD at a pH of Attorney Docket No.: 45395-0068WO1 ~7.0 to ~8.0. In some aspects, the KD of the first ABD at a pH of ~4.0 to ~6.5 is at least 10-fold greater than the KD of the first ABD at a pH of ~7.0 to ~8.0. [0164] In some aspects, the ABPC is cytotoxic or cytostatic to the target mammalian cell. [0165] In some aspects, the first ABD is cross-reactive with a non-human primate DLL3 and human DLL3. In some aspects, the first ABD is cross-reactive with a non-human primate DLL3, a human DLL3, and one or both of rat DLL3 and a mouse DLL3. In some aspects, the first ABD is cross-reactive with a non-human primate DLL3, a human DLL3, a rat DLL3, and a mouse DLL3. In some aspects, the first ABD binds to an epitope of DLL3 that is present on the surface of cells from an Old World Monkey. [0166] In some aspects, the ABPC includes a single polypeptide. In some aspects, the first ABD is selected from a VH domain, a VHH domain, a VNAR domain, and a scFv. In some aspects, the ABPC is a BiTe, a (scFv)2, a nanobody, a nanobody-HSA, a DART, a TandAb, a scDiabody, a scDiabody-CH3, scFv-CH-CL-scFv, a HSAbody, scDiabody-HSA, or a tandem-scFv. [0167] In some aspects, the ABPC includes two or more polypeptides. In some aspects, the ABPC is selected from the group of an antibody, a VHH-scAb, a VHH-Fab, a Dual scFab, a F(ab’)2, a diabody, a crossMab, a DAF (two-in-one), a DAF (four-in-one), a DutaMab, a DT-IgG, a knobs- in-holes common light chain, a knobs-in-holes assembly, a charge pair, a Fab-arm exchange, a SEEDbody, a LUZ-Y, a Fcab, a κλ-body, an orthogonal Fab, a DVD-IgG, a IgG(H)-scFv, a scFv- (H)IgG, IgG(L)-scFv, scFv-(L)IgG, IgG(L,H)-Fv, IgG(H)-V, V(H)-IgG, IgG(L)-V, V(L)-IgG, KIH IgG-scFab, 2scFv-IgG, IgG-2scFv, scFv4-Ig, Zybody, DVI-IgG, Diabody-CH3, a triple body, a miniantibody, a minibody, a TriBi minibody, scFv-CH3 KIH, Fab-scFv, a F(ab’)2-scFv2, a scFv- KIH, a Fab-scFv-Fc, a tetravalent HCAb, a scDiabody-Fc, a Diabody-Fc, a tandem scFv-Fc, a VHH-Fc, a tandem VHH-Fc, a VHH-Fc KiH, a Fab-VHH-Fc, an Intrabody, a dock and lock, an ImmTAC, an IgG-IgG conjugate, a Cov-X-Body, a scFv1-PEG-scFv2, an Adnectin, a DARPin, a fibronectin, a DEP conjugate, a PROTAB, and a PROTAC. [0168] In some aspects, at least one polypeptide of the ABPC is conjugated to the toxin, the radioisotope, the drug, or the small molecule via a cleavable linker. In some aspects, at least one polypeptide of the ABPC is conjugated to the toxin, the radioisotope, the drug, or the small molecule via a non-cleavable linker. [0169] In some aspects, the half-life of the ABPC in vivo is increased as compared to the half- life of a control ABPC in vivo. In some aspects, the half-life of the ABPC in vivo is increased about Attorney Docket No.: 45395-0068WO1 5% to about 95% as compared to the half-life of a control ABPC in vivo. In some aspects, the half- life of the ABPC in vivo is increased about 10% to about 95% as compared to the half-life of a control ABPC in vivo. In some aspects, the half-life of the ABPC in vivo is increased about 30% to about 95% as compared to the half-life of a control ABPC in vivo. In some aspects, the half-life of the ABPC in vivo is increased about 50% to about 95% as compared to the half-life of a control ABPC in vivo. In some aspects, the half-life of the ABPC in vivo is increased about 70% to about 95% as compared to the half-life of a control ABPC in vivo. In other aspects, the in vivo half-life may be decreased. [0170] In some aspects, the control ABPC is capable of specifically binding to DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell, where: (a) the control ABPC includes a first ABD: (b) the dissociation rate of the first ABD of the control ABPC at a pH of ~4.0 to ~6.5 is no more than 3-fold faster than the dissociation rate at a pH of ~7.0 to ~8.0; and (c) the dissociation constant (KD) of the first ABD of the control ABPC at a pH of ~4.0 to ~6.5 is no more than 3-fold greater than the KD at a pH of ~7.0 to ~8.0. [0171] In some aspects, the control ABPC is capable of specifically binding to DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell, where: (a) the control ABPC includes a first ABD; (b) the dissociation rate of the first ABD of the control ABPC at a pH of ~4.0 to ~6.5 is no more than 2-fold faster than the dissociation rate at a pH of ~7.0 to ~8.0; and (c) the dissociation constant (KD) of the first ABD of the control ABPC at a pH of ~4.0 to ~6.5 is no more than 2-fold greater than the KD at a pH of ~7.0 to ~8.0. [0172] In some aspects, the control ABPC is capable of specifically binding to DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell, where: (a) the control ABPC includes a first ABD; (b) the dissociation rate of the first ABD of the control ABPC at a pH of ~4.0 to ~6.5 is no more than 1-fold faster than the dissociation rate at a pH of ~7.0 to ~8.0; and (c) the dissociation constant (KD) of the first ABD of the control ABPC at a pH of ~4.0 to ~6.5 is no more than 1-fold greater than the KD at a pH of ~7.0 to ~8.0. [0173] In some aspects, the control ABPC is selected from one of those disclosed herein. [0174] In some aspects, the ABPC includes a second ABD . In some embodiments, the second ABD specifically binds to DLL3 (e.g., the same or a different epitope on DLL3 as compared to the first ABD) . In some embodiments, the second ABD is the same as the first ABD . In some Attorney Docket No.: 45395-0068WO1 embodiments, the second ABD binds to an epitope on the surface of an immune cell (e.g., a T cell or a NK cell) (e.g., CD3). [0175] Also provided herein are kits including at least one dose of any of the pharmaceutical compositions described herein. [0176] Also provided herein are antigen-binding protein constructs (ABPCs) including: a first ABD that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell, where: (a) the dissociation rate of the first ABD 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 ABD 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. [0177] In some aspects, the first ABD includes one of: (a) an HCVD including the sequence of SEQ ID NO: 3 and/or an LCVD including the sequence of SEQ ID NO: 4; (b) an HCVD including the sequence of SEQ ID NO: 11 and/or an LCVD including the sequence of SEQ ID NO: 12; (c) an HCVD including the sequence of SEQ ID NO: 19 and/or an LCVD including the sequence of SEQ ID NO: 20; (d) an HCVD including the sequence of SEQ ID NO: 27 and/or an LCVD including the sequence of SEQ ID NO: 28; (e) an HCVD including the sequence of SEQ ID NO: 35 and/or an LCVD including the sequence of SEQ ID NO: 36; (f) an HCVD including the sequence of SEQ ID NO: 43 and/or an LCVD including the sequence of SEQ ID NO: 44; (g) an HCVD including the sequence of SEQ ID NO: 51 and/or an LCVD including the sequence of SEQ ID NO: 52; (h) an HCVD including the sequence of SEQ ID NO: 59 and/or an LCVD including the sequence of SEQ ID NO: 60; (i) an HCVD including the sequence of SEQ ID NO: 67 and/or an LCVD including the sequence of SEQ ID NO: 68; (j) an HCVD including the sequence of SEQ ID NO: 75 and/or an LCVD including the sequence of SEQ ID NO: 76; (k) an HCVD including the sequence of SEQ ID NO: 83 and/or an LCVD including the sequence of SEQ ID NO: 84; and (l) an HCVD including the sequence of SEQ ID NO: 91 and/or an LCVD including the sequence of SEQ ID NO: 92, each HCVD and/or LCVD optionally with one or more amino acids substituted with a histidine (e.g., one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or one, two, three, four, or five total histidine substitutions across the set of three L-CDRs). [0178] In some aspects, the first ABD includes a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein (a) the HCVD comprises an H-CDR1 sequence, an Attorney Docket No.: 45395-0068WO1 H-CDR2 sequence, and an H-CDR3 sequence selected from the group consisting of the sequences of one of (i) to (xii): (i) SEQ ID NO: 5, SEQ ID NO: 6, and SEQ ID NO: 7, respectively; (ii) SEQ ID NO: 13, SEQ ID NO: 14, and SEQ ID NO: 15, respectively; (iii) SEQ ID NO: 21, SEQ ID NO: 22, and SEQ ID NO: 23, respectively; (iv) SEQ ID NO: 29, SEQ ID NO: 30, and SEQ ID NO: 31, respectively; (v) SEQ ID NO: 37, SEQ ID NO: 38, and SEQ ID NO: 39, respectively; (vi) SEQ ID NO: 45, SEQ ID NO: 46, and SEQ ID NO: 47, respectively; (vii) SEQ ID NO: 53, SEQ ID NO: 54, and SEQ ID NO: 55, respectively; (viii) SEQ ID NO: 61, SEQ ID NO: 62, and SEQ ID NO: 63, respectively; (ix) SEQ ID NO: 69, SEQ ID NO: 70, and SEQ ID NO: 71, respectively; (x) SEQ ID NO: 77, SEQ ID NO: 78, and SEQ ID NO: 79, respectively; (xi) SEQ ID NO: 85, SEQ ID NO: 86, and SEQ ID NO: 87, respectively; and (xii) SEQ ID NO: 93, SEQ ID NO: 94, and SEQ ID NO: 95, respectively; and/or (b) the LCVD comprises an L-CDR1 sequence, an L-CDR2 sequence, and an L-CDR3 sequence selected from the group consisting the sequences of one of (i) to (xii): ( (i) SEQ ID NO: 8, SEQ ID NO: 9, and SEQ ID NO: 10, respectively; (ii) SEQ ID NO: 16, SEQ ID NO: 17, and SEQ ID NO: 18, respectively; (iii) SEQ ID NO: 24, SEQ ID NO: 25, and SEQ ID NO: 26, respectively; (iv) SEQ ID NO: 32, SEQ ID NO: 33, and SEQ ID NO: 34, respectively; (v) SEQ ID NO: 40, SEQ ID NO: 41, and SEQ ID NO: 42, respectively; (vi) SEQ ID NO: 48, SEQ ID NO: 49, and SEQ ID NO: 50, respectively; (vii) SEQ ID NO: 56, SEQ ID NO: 57, and SEQ ID NO: 58, respectively; (viii) SEQ ID NO: 64, SEQ ID NO: 65, and SEQ ID NO: 66, respectively; (ix) SEQ ID NO: 72, SEQ ID NO: 73, and SEQ ID NO: 74, respectively; (x) SEQ ID NO: 80, SEQ ID NO: 81, and SEQ ID NO: 82, respectively; (xi) SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 90, respectively; (xii) SEQ ID NO: 96, SEQ ID NO: 97, and SEQ ID NO: 98, respectively. In some aspects, at least one of the H-CDR1, H-CDR2, and H-CDR3 sequences and/or at least one of the L-CDR1, L-CDR2, and L-CDR3 sequences has one or more amino acid position substituted with a histidine (e.g., one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or one, two, three, four, or five total histidine substitutions across the set of three L-CDRs). [0179] In some aspects, the first ABD includes one of: (a) an HCVD including the sequence of SEQ ID NO: 123 and/or an LCVD including the sequence of SEQ ID NO: 124; (b) an HCVD including the sequence of SEQ ID NO: 131 and/or an LCVD including the sequence of SEQ ID NO: 132; (c) an HCVD including the sequence of SEQ ID NO: 139 and/or an LCVD including the sequence of SEQ ID NO: 140; (d) an HCVD including the sequence of SEQ ID NO: 147 and/or Attorney Docket No.: 45395-0068WO1 an LCVD including the sequence of SEQ ID NO: 148; (e) an HCVD including the sequence of SEQ ID NO: 155 and/or an LCVD including the sequence of SEQ ID NO: 156; (f) an HCVD including the sequence of SEQ ID NO: 163 and/or an LCVD including the sequence of SEQ ID NO: 164; (g) an HCVD including the sequence of SEQ ID NO: 171 and/or an LCVD including the sequence of SEQ ID NO: 172; (h) an HCVD including the sequence of SEQ ID NO: 179 and/or an LCVD including the sequence of SEQ ID NO: 180; (i) an HCVD including the sequence of SEQ ID NO: 187 and/or an LCVD including the sequence of SEQ ID NO: 188; (j) an HCVD including the sequence of SEQ ID NO: 195 and/or an LCVD including the sequence of SEQ ID NO: 196; (k) an HCVD including the sequence of SEQ ID NO: 203 and/or an LCVD including the sequence of SEQ ID NO: 204; and (l) an HCVD including the sequence of SEQ ID NO: 211 and/or an LCVD including the sequence of SEQ ID NO: 212, each HCVD and/or LCVD optionally with one or more amino acids substituted with a histidine (e.g., one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or one, two, three, four, or five total histidine substitutions across the set of three L-CDRs). [0180] In some aspects, the first ABD includes a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein (a) the HCVD comprises an H-CDR1 sequence, an H-CDR2 sequence, and an H-CDR3 sequence selected from the group consisting of the sequences of one of (i) to (xii): (i) SEQ ID NO: 125, SEQ ID NO: 126, and SEQ ID NO: 127, respectively; (ii) SEQ ID NO: 133, SEQ ID NO: 134, and SEQ ID NO: 135, respectively; (iii) SEQ ID NO: 141, SEQ ID NO: 142, and SEQ ID NO: 143, respectively; (iv) SEQ ID NO: 149, SEQ ID NO: 150, and SEQ ID NO: 151, respectively; (v) SEQ ID NO: 157, SEQ ID NO: 158, and SEQ ID NO: 159, respectively; (vi) SEQ ID NO: 165, SEQ ID NO: 166, and SEQ ID NO: 167, respectively; (vii) SEQ ID NO: 173, SEQ ID NO: 174, and SEQ ID NO: 175, respectively; (viii) SEQ ID NO: 181, SEQ ID NO: 182, and SEQ ID NO: 183, respectively; (ix) SEQ ID NO: 189, SEQ ID NO: 190, and SEQ ID NO: 191, respectively; (x) SEQ ID NO: 197, SEQ ID NO: 198, and SEQ ID NO: 199, respectively; (xi) SEQ ID NO: 205, SEQ ID NO: 206, and SEQ ID NO: 207, respectively; and (xii) SEQ ID NO: 213, SEQ ID NO: 214, and SEQ ID NO: 215, respectively; and/or (b) the LCVD comprises an L-CDR1 sequence, an L-CDR2 sequence, and an L-CDR3 sequence selected from the group consisting of the sequences of one of (i) to (xii): (i) SEQ ID NO: 128, SEQ ID NO: 129, and SEQ ID NO: 130, respectively; (ii) SEQ ID NO: 136, SEQ ID NO: 137, and SEQ ID NO: 138, respectively; (iii) SEQ ID NO: 144, SEQ ID NO: 145, and SEQ ID NO: 146, respectively; (iv) Attorney Docket No.: 45395-0068WO1 SEQ ID NO: 152, SEQ ID NO: 153, and SEQ ID NO: 154, respectively; (v) SEQ ID NO: 160, SEQ ID NO: 161, and SEQ ID NO: 162, respectively; (vi) SEQ ID NO: 168, SEQ ID NO: 169, and SEQ ID NO: 170, respectively; (vii) SEQ ID NO: 176, SEQ ID NO: 177, and SEQ ID NO: 178, respectively; (viii) SEQ ID NO: 184, SEQ ID NO: 185, and SEQ ID NO: 186, respectively; (ix) SEQ ID NO: 192, SEQ ID NO: 193, and SEQ ID NO: 194, respectively; (x) SEQ ID NO: 200, SEQ ID NO: 201, and SEQ ID NO: 202, respectively; (xi) SEQ ID NO: 208, SEQ ID NO: 209, and SEQ ID NO: 210, respectively; (xii) SEQ ID NO: 216, SEQ ID NO: 217, and SEQ ID NO: 218, respectively. In some aspects, at least one of the H-CDR1, H-CDR2, and H-CDR3 sequences and/or at least one of the L-CDR1, L-CDR2, and L-CDR3 sequences has one or more amino acid position substituted with a histidine (e.g., one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or one, two, three, four, or five total histidine substitutions across the set of three L-CDRs). [0181] In some aspects, the ABPC is degraded in the target mammalian cell following internalization of the ABPC by the target mammalian cell. In some aspects, the ABPC includes a conjugated toxin, radioisotope, drug, or small molecule (also called herein “a conjugated composition”). [0182] In some aspects, a conjugated composition including the ABPC provides for an increase in toxin liberation in the target mammalian cell as compared to a conjugated composition including the same amount of a control ABPC. In some aspects, a conjugated composition including the ABPC provides for at least a 20% or 50% increase in toxin liberation in the target mammalian cell as compared to a conjugated composition including the same amount of a control ABPC. In some aspects, a conjugated composition including the ABPC provides for at least a 2- or 5-fold increase in toxin liberation in the target mammalian cell as compared to a conjugated composition including the same amount of a control ABPC. [0183] In some aspects, a conjugated composition including the ABPC provides for an increase in target mammalian cell killing as compared to a conjugated composition including the same amount of a control ABPC. In some aspects, a conjugated composition including the ABPC provides for at least a 20% or 50% increase in target mammalian cell killing as compared to a conjugated composition including the same amount of a control ABPC. In some aspects, a conjugated composition including the ABPC provides for at least a 2- or 5-fold increase in target Attorney Docket No.: 45395-0068WO1 mammalian cell killing as compared to a conjugated composition including the same amount of a control ABPC. [0184] In some aspects, a composition including the ABPC provides for an increase in endolysosomal delivery in the target mammalian cell as compared to a composition including the same amount of a control ABPC. In some aspects, the ABPC provides for at least a 20% increase in endolysosomal delivery in the target mammalian cell as compared to a composition including the same amount of a control ABPC. In some aspects, a composition including the ABPC provides for at least a 50% increase in endolysosomal delivery in the target mammalian cell as compared to a composition including the same amount of a control ABPC. In some aspects, a composition including the ABPC provides for at least a 2-fold increase in endolysosomal delivery in the target mammalian cell as compared to a composition including the same amount of a control ABPC. In some aspects, a composition including the ABPC provides for at least a 5-fold increase in endolysosomal delivery in the target mammalian cell as compared to a composition including the same amount of a control ABPC. [0185] In some aspects, at least one polypeptide of the ABPC is conjugated to the toxin, the radioisotope, the drug, or the small molecule via a cleavable linker. In some aspects, at least one polypeptide of the ABPC is conjugated to the toxin, the radioisotope, the drug, or the small molecule via a non-cleavable linker. [0186] In some aspects, the ABPC includes a second ABD. In some embodiments, the second ABD specifically binds to DLL3 (e.g., the same or a different epitope on DLL3 as compared to the first ABD). In some embodiments, the second ABD is the same as the first ABD. In some embodiments, the second ABD binds to an epitope on the surface of an immune cell (e.g., a T cell or a NK cell) (e.g., CD3). [0187] Also provided herein are kits including at least one dose of any ABPC described herein. [0188] Also provided herein are methods of treating a cancer characterized by having a population of DLL3-positive cancer cells, the method including: administering a therapeutically effective amount of any of the pharmaceutical compositions described herein or any of the ABPCs described herein to a subject identified as having a cancer characterized by having the population of cancer cells. [0189] Also provided herein are methods of reducing the volume of a tumor in a subject, where the tumor is characterized by having DLL-positive cancer cells, the method including: Attorney Docket No.: 45395-0068WO1 administering a therapeutically effective amount of any of the pharmaceutical compositions described herein or any of the ABPCs described herein to the subject. [0190] Also provided herein are methods of inducing cell death in a DLL-positive cancer cell in a subject, where the method includes: administering a therapeutically effective amount of any of the pharmaceutical compositions described herein or any of the ABPCs described herein to the subject. [0191] In some aspects, the DLL3-positive cancer is a primary tumor. In some aspects, the DLL3- positive cancer is a metastasis. [0192] In some aspects, the DLL3-positive cancer is a non-T-cell-infiltrating tumor. In some aspects, the DLL-positive cancer is a T-cell infiltrating tumor. [0193] Also provided herein are methods of decreasing the risk of developing a metastasis or decreasing the risk of developing an additional metastasis in a subject having a DLL3-positive cancer, the method including: administering a therapeutically effective amount of any one of the pharmaceutical compositions described herein or any of the ABPCs described herein to the subject. [0194] In some aspects, the DLL3-positive cancer is a non-T-cell-infiltrating tumor. In some aspects, the DLL3-positive cancer is a T-cell infiltrating tumor. [0195] As used herein, the term “antigen-binding protein construct” is (i) a single polypeptide that includes at least one ABD or (ii) a complex of two or more polypeptides (e.g., the same or different polypeptides) that together form at least one ABD. Non-limiting examples and aspects of antigen-binding protein constructs are described herein. Additional examples and aspects of antigen-binding protein constructs are known in the art. [0196] A “multi-specific ABPC” is an ABPC that includes two or more different ABDs that collectively specifically bind two or more different epitopes. The two or more different epitopes may be epitopes on the same antigen (e.g., a single polypeptide present on the surface of a cell) or on different antigens (e.g., different proteins present on the surface of the same cell or present on the surface of different cells). In some aspects, the antigen is present on the surface of the cell. In some aspects, a multi-specific ABPC binds two different epitopes (i.e., a “bispecific ABPC”). In some aspects, a multi-specific ABPC binds three different epitopes (i.e., a “trispecific ABPC”). In some aspects, a multi-specific ABPC binds four different epitopes (i.e., a “quadspecific ABPC”). In some aspects, a multi-specific ABPC binds five different epitopes (i.e., a “quintspecific Attorney Docket No.: 45395-0068WO1 ABPC”). Each binding specificity may be present in any suitable valency. Non-limiting examples of multi-specific ABPC s are described herein. [0197] An “Antigen-Binding Protein” or “ABD” is one or more protein domain(s) (e.g., formed from amino acids from a single polypeptide or formed from amino acids from two or more polypeptides (e.g., the same or different polypeptides) that is capable of specifically binding to one or more different antigen(s). In some examples, an ABD can bind to an antigen or epitope with specificity and affinity similar to that of naturally occurring antibodies. In some aspects, the ABD can be an antibody or a fragment thereof. In some aspects, an ABD can include an alternative scaffold. Non-limiting examples of ABDs are described herein. Additional examples of ABDs are known in the art. In some examples, an ABD can bind to a single antigen. [0198] The term “antibody” is used herein in its broadest sense and includes certain types of immunoglobulin molecules that include one or more ABDs that specifically bind to an antigen or epitope. An antibody specifically includes, e.g., intact antibodies (e.g., intact immunoglobulins, e.g., human IgG (e.g., human IgG1, human IgG2, human IgG3, human IgG4)), antibody fragments (e.g., Fab fragment), and multi-specific antibodies. One example of an ABD is an ABD formed by a VH -VL dimer. Additional examples of an antibody are described herein. Additional examples of an antibody are known in the art. An antibody is an example of a type of antigen-binding protein construct. In some embodiments, an antibody can be a fully human antibody, a humanized antibody, a chimeric antibody, a veneered antibody, or a rabbit antibody. [0199] As used herein, unless otherwise indicated by the context, “the CDRs of” means the amino acid residues of a given antigen binding domain (e.g., a heavy chain variable domain (HCVD) or a light chain variable domain (LCVD)). Unless otherwise stated, CDRs are determined by including the amino acid residues falling under either or both the Kabat and IMGT CDR definitions (i.e., as used herein, residues determined by the “Kabat-IMGT” method). [0200] The phrase “endosomal/lysosomal pathway” refers to a network of endosomes (early endosomes, multi-vesicular bodies, late endosomes, and lysosomes) in the cytoplasm of a mammalian cell, wherein molecules are internalized through cell-mediated internalization processes, e.g., pinocytosis, micropinocytosis, receptor-mediated endocytosis, and/or phagocytosis, are sorted. [0201] Once the endosomes in the endosomal/lysosomal pathway are purified or isolated, assays for a target protein (e.g., an antigen-binding protein construct described herein) can be performed Attorney Docket No.: 45395-0068WO1 using methods known in the art (ELISA, Western blot, immunofluorescence, and immunoprecipitation followed by an assay for protein concentration), and can be used to determine the concentration or relative level of the target protein in the endosomes. Alternatively, endosomes in the endosomal/lysosomal pathway can be imaged using immunofluorescence microscopy using an detectably-labelled antibody (e.g., a fluorophore-labelled, a dye-labelled, or a GFP-labelled antibody, e.g., CellLightTM Early Endosome-GFP) that specifically binds to a characteristic protein present in the endosomes (e.g., EEA1 for early endosomes) and a fluorophore-labelled antibody that specifically binds to the protein of interest (e.g., an ABPC), and the level of the target protein in the endosomes can be determined by quantitation of the overlap in the fluorescence emissions of the two different antibodies. [0202] The phrase “endolysosomal delivery” refers to rate of accumulation over time or the total accumulation at a specific timepoint of an ABPC (e.g., any of the ABPCs described herein) in the endosomal/lysosomal pathway in a mammalian cell (e.g., any of the exemplary target mammalian cells described herein). [0203] An exemplary method to calculate the increase in endolysosomal delivery of a pH engineered ABPC variant as compared to its corresponding starting ABPC from cellular fluorescence data is to measure the ratio of the variant’s mean fluorescence intensity minus the mean fluorescence intensity of a non-binding IgG control, then all divided by the variant’s corresponding starting ABPC’s mean fluorescence intensity minus the mean fluorescence intensity of the IgG control. [0204] An exemplary assay for measuring endolysosomal delivery of any of the ABPCs described herein include those which involve labeling of an ABPC with a fluorescent dye, followed by incubation of the labeled ABPC with cells and measurement of cellular fluorescence as an indicator of endolysosomal delivery of the ABPC (e.g., as described generally in Wustner, Traffic 7(6):699-715, 2006). Alternatively, pH-sensitive dyes which preferentially fluoresce at acidic pH but not neutral pH can be used to label any of the ABPCs described herein, which can then be incubated with cells and the cellular fluorescence measured as an indicator of delivery of the ABPC into acidic endolysosomal compartments. [0205] The term “population” when used before a noun means two or more of the specific noun. For example, the phrase “a population of cancer cells” means “two or more cancer cells.” Non- limiting examples of cancer cells are described herein. Attorney Docket No.: 45395-0068WO1 [0206] The phrase “cytostatic to a cell” refers to a direct or indirect decrease in the proliferation (cell division) of the cell (e.g., a cancer cell) in vivo or in vitro. When an agent is cytostatic to a cell, the agent can, e.g., directly or indirectly result in cell cycle arrest of the cell (e.g., a cancer cell). In some examples, an agent that is cytostatic to a cell can reduce the number of cells in a population of the cells that are in S phase (as compared to the number of cells in a population of the cells that are in S phase prior to contact with the agent). In some examples, an agent that is cytostatic to a cell can reduce the percentage of the cells in S phase by at least 20%, at least 40%, at least 60%, or at least 80% (e.g., as compared to the percentage of cells in a population of the cells that are in S phase prior to contact with the agent). [0207] The phrase “cytotoxic to a cell” refers to the inducement, directly or indirectly, in the death (e.g., necrosis or apoptosis) of the cell (e.g., a mammalian cell, e.g., a cancer cell). [0208] “Affinity” refers to the strength of the sum total of non-covalent interactions between an antigen-binding site and its binding partner (e.g., an antigen or epitope). Unless indicated otherwise, as used herein, “affinity” refers to intrinsic binding affinity, which reflects a 1:1 interaction between members of an ABD and an antigen or epitope. The affinity of a molecule X for its partner Y can be represented by the dissociation equilibrium constant (KD). Affinity can be measured by common methods known in the art, including those described herein. Affinity can be determined, e.g., using surface plasmon resonance (SPR) technology (e.g., BIACORE®) or biolayer interferometry (e.g., FORTEBIO®). Additional methods for determining the affinity for an ABD and its corresponding antigen or epitope are known in the art. [0209] The term “epitope” means a portion of an antigen that is specifically bound by an ABD through a set of physical interactions between: (i) all monomers (e.g. individual amino acid residues, sugar side chains, and post-translationally modified amino acid residues) on the portion of the ABD 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 portion of the antigen that is specifically bound by the ABD. Epitopes can, e.g., consist of surface-accessible amino acid residues, sugar side chains, phosphorylated amino acid residues, methylated amino acid residues, and/or acetylated amino acid residues and may have specific three-dimensional structural characteristics, as well as specific charge characteristics. Conformational and non- conformational epitopes are distinguished in that binding to the former, but not the latter, may be lost in the presence of denaturing solvents. In some aspects, an epitope is defined by a linear amino Attorney Docket No.: 45395-0068WO1 acid sequence of at least about 3 to 6 amino acids, or about 10 to 15 amino acids. In some aspects, an epitope refers to a portion of a full-length protein or a portion thereof that is defined by a three- dimensional structure (e.g., protein folding). In some aspects, an epitope is defined by a discontinuous amino acid sequence that is brought together via protein folding. In some aspects, an epitope is defined by a discontinuous amino acid sequence that is brought together by quaternary structure (e.g., a cleft formed by the interaction of two different polypeptide chains). The amino acid sequences between the residues that define the epitope may not be critical to three- dimensional structure of the epitope. A conformational epitope may be determined and screened using assays that compare binding of antigen-binding protein construct to a denatured version of the antigen, such that a linear epitope is generated. An epitope may include amino acid residues that are directly involved in the binding, and others, which are not directly involved in the binding. [0210] Methods for identifying an epitope to which an ABD specifically binds are known in the art, e.g., structure-based analysis (e.g. X-ray crystallography, NMR, and/or electron microscopy) (e.g. on the antigen and/or the antigen-ABD complex) and/or mutagenesis-based analysis (e.g. alanine scanning mutagenesis, glycine scanning mutagenesis, and homology scanning mutagenesis) wherein mutants are measured in a binding assay with a binding partner, many of which are known in the art. [0211] The term “paratope” means a portion of an ABD 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, posttranslationally modified amino acid residues) on the portion of the ABD that specifically binds the antigen and (ii) all monomers (e.g. individual amino acid residues, sugar side chains, posttranslationally modified amino acid residues) on the portion of the antigen that is specifically bound by the ABD. Paratopes can, e.g., consist of surface-accessible amino acid residues and may have specific three-dimensional structural characteristics, as well as specific charge characteristics. In some aspects, a paratope refers to a portion of a full-length ABD or a portion thereof that is defined by a three-dimensional structure (e.g., protein folding). In some aspects, a paratope is defined by a discontinuous amino acid sequence that is brought together via protein folding. In some aspects, an epitope is defined by a discontinuous amino acid sequence that is brought together by quaternary structure (e.g., a cleft formed by the interaction of two different polypeptide chains). The amino acid sequences between the residues that define the paratope may not be critical to three-dimensional structure of the paratope. A paratope may Attorney Docket No.: 45395-0068WO1 comprise amino acid residues that are directly involved in the binding, and others, which are not directly involved in the binding. [0212] Methods for identifying a paratope to which an ABD specifically binds are known in the art, e.g., structure-based analysis (e.g., X-ray crystallography, NMR, and/or electron microscopy) (e.g. on the ABD, and/or the ABD-antigen complex), and/or mutagenesis-based analysis (e.g., alanine scanning mutagenesis, glycine scanning mutagenesis, and homology scanning mutagenesis) wherein mutants are measured in a binding assay with a binding partner, many of which are known in the art. [0213] The phrase “present on the surface of a mammalian cell” means (1) an antigen that physically attached to or at least partially embedded in the plasma membrane of a mammalian cell (e.g., a transmembrane protein, a peripheral membrane protein, a lipid-anchored protein (e.g., a GPI-anchor), an N-myristoylated protein, or a S-palmitoylated protein) 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 cell (e.g., a ligand bound to its cognate receptor, where the cognate receptor is physically attached to the plasma membrane). Non-limiting methods for determining the presence of antigen on the surface of a mammalian cell include fluorescence-activated cell sorting (FACS), immunohistochemistry, cell-fractionation assays and Western blotting. [0214] Controls, generally. The appropriate control ABPC(s) to include in a given experiment depends upon, at least, the insight or parameter sought to be elucidated by the study (e.g., difference in internalization, cytotoxicity, or in vivo half-life, relative to such control(s)). [0215] For example, when used in the context of pH-engineered antigen binding protein constructs (e.g., ABPCs that bind better at physiologic pH versus endolysosomal space pH), the phrase “control ABPC” or “control antigen-binding protein construct” means an ABPC that is capable of specifically binding to DLL3 or an epitope of DLL3 presented on the surface of a mammalian cell (e.g., a target mammalian cell), where one or both of the following is true: (a) the dissociation rate of the first ABD at a pH of ~4.0 to ~6.5 (e.g., any of the subranges of this range described herein) is no more than 3-fold (e.g., no more than 2.8-fold, no more than 2.6-fold, no more than 2.5-fold, no more than 2.4-fold, no more than 2.2-fold, no more than 2.0-fold, no more than 1.8-fold, no more than 1.6-fold, no more than 1.5-fold, no more than 1.4-fold, no more than 1.2-fold, no more than 1.0-fold, no more than 0.8-fold, no more than 0.6-fold, no more than 0.5- fold, no more than 0.4-fold, no more than 0.3-fold no more than 0.2-fold, or no more than 0.1- Attorney Docket No.: 45395-0068WO1 fold) faster than the dissociation rate at a pH of ~7.0 to ~8.0 (e.g., any of the subranges of this range described herein); or (b) the dissociation constant (KD) of the first ABD at a pH of ~4.0 to ~6.5 (e.g., any of the subranges of this range described herein) is no more than 3-fold (e.g., no more than 2.8-fold, no more than 2.6-fold, no more than 2.5-fold, no more than 2.4-fold, no more than 2.2-fold, no more than 2.0-fold, no more than 1.8-fold, no more than 1.6-fold, no more than 1.5-fold, no more than 1.4-fold, no more than 1.2-fold, no more than 1.0-fold, no more than 0.8- fold, no more than 0.6-fold, no more than 0.5-fold, no more than 0.4-fold, no more than 0.3-fold no more than 0.2-fold, or no more than 0.1-fold) greater than the KD at a pH of ~7.0 to ~8.0 (e.g., any of the subranges of this range described herein). [0216] In another example, for anti-DLL3 ABPC that already (e.g., naturally) exhibit pH- dependent binding (e.g., an ABPC that exhibits better binding to DLL3 at physiologic pH conditions than at endolysosomal pH conditions), an appropriate control could be a non-pH- dependent ABPC (e.g., an ABPC that exhibits substantially similar binding to DLL3 pH conditions and endolysosomal space pH conditions) that otherwise exhibits to the pH-dependent anti-DLL3 ABPC to be tested. In some embodiments, the non-pH-dependent control ABPC is capable of substantially or completely competing with the anti-DLL3 ABPC to be tested. [0217] The term “extracellular space” means the liquid exterior to the plasma membrane of a mammalian cell. When a mammalian cell is in vitro, the extracellular space can be a liquid culture medium. When a mammalian cell is in vivo, the extracellular space can be, e.g., plasma, serum, blood, interstitial fluid, or lymph. [0218] The term “endolysosomal space” means the fluid encapsulated by the vesicles and organelles that make-up the endosomal/lysosomal pathway in a mammalian cell. [0219] The phrase “a reduced level” or “a decreased level” can be a reduction or decrease of at least a 1% (e.g., ≥2%, ≥4%, ≥6%, ≥8%, ≥10%, ≥12%, ≥14%, ≥16%, ≥18%, ≥20%, ≥22%, ≥24%, ≥26%, ≥30%, ≥35%, ≥40%, ≥45%, ≥50%, ≥55%, ≥60%, ≥65%, ≥70%, ≥75%, ≥80%, ≥85%, ≥90%, ≥95%, or ≥99%) reduction as compared to a reference level or value. [0220] The term “cell killing potency” refers to the ability of an agent (e.g., any of the ABPCs described herein) to induce, directly or indirectly, the apoptosis and/or necrosis of a mammalian cell (e.g., a cancer cell), measured as a rate over time or at a relevant timepoint. Methods for determining the cell killing potency of a cell are known in the art (e.g., trypan blue staining, Attorney Docket No.: 45395-0068WO1 microscopy, fluorescence-assisted cell sorting, and assays to detect markers of apoptosis (e.g., Annexin V)). In non-limiting examples, cell killing potency can be measured, e.g., by cell killing at a single concentration of an agent, by the IC50 of the agent (i.e. the concentration of the agent whereby half the maximal cell killing potency is achieved), or by the ratio of an agent’s dissociation constant KD on mammalian cells divided by its IC50. In some non-limiting examples, the IC50s and/or the KD ratios described herein are compared to those of a control ABPC (as defined herein), and, optionally, demonstrate that the ABPCs described herein have a higher cell killing potency as compared to the control ABPC. [0221] The term “toxin liberation” refers to the ability of a mammalian cell (e.g., a non-cancerous mammalian cell or a cancer cell) to internalize (e.g., via pinocytosis and/or receptor-mediated endocytosis) any of the ABPCs described herein (e.g., any of ABPCs or control ABPCs described herein) that are conjugated to a toxin, and subsequently release the toxin conjugated to the ABPC, measured as a rate over time or at a specific timepoint. Toxin liberation can be assessed using a variety of different exemplary assays, e.g., ELISA, immunofluorescence, cell killing assays, cell cycle arrest assays, DNA damage assays, mass spectrometry, HPLC, and/or an isotope-labeled toxin. [0222] The phrase “target cell” or “target mammalian cell” or “mammalian target cell” means a mammalian cell that has at least one DLL3 present on its surface. In some examples, a mammalian target cell can be a cancer cell. In some aspects of a target mammalian cell can have a total of about the following (each ± about 10%): 1-10E6, 1-9E6, 1-8E6, 1-7E6, 1-6E6, 1-5E6, 1-4E6, 1- 3E6, 1-2E6, 1-1E6, 1-800,000, 1-600,000, 1-400,000, 1-200,000, 1-100,000, 1-80,000, 1-80,000, 1-75,000, 1-70,000, 1-65,000, 1-60,000, 1-55,000, 1-50,000, 1-45,000, 1-40,000, 1-35,000, 1- 30,000, 1-25,000, 1-20,000, 1-15,000, 1-10,000, 1-7,500, 1-5,000, 1-4,000, 1-3,000, 1-2,000, 1- 1,000, 1-500, 1-100, 1-50, or 1-10, or any of the ranges of numbers recited in paragraph [0065] of US 2022/0281984, of the DLL3 present on the plasma membrane of the target mammalian cell. [0223] The phrase “antigen density” means the number of DLL3 present on the surface of a target mammalian cell or the average number of DLL3 on the surface of a population of particular type of target mammalian cells. It can be measured, e.g., using the Quantibright bead kit or radiolabel (e.g., BD Biosciences PE Phycoerythrin Fluorescence Quantitation Kit, catalog #340495). [0224] The phrase “amino acid substituted with a histidine” means the substitution of an amino acid residue that is not histidine in a reference polypeptide sequence with a histidine. Non-limiting Attorney Docket No.: 45395-0068WO1 methods for substituting an amino acid residue in a reference polypeptide with a histidine are described herein. Additional methods for substituting an amino acid residue in a reference polypeptide with a histidine are known in the art. [0225] The phrase “amino acid substituted with an alanine” means the substitution of an amino acid residue that is a histidine in a reference polypeptide sequence with an alanine. Non-limiting methods for substituting a histidine in a reference polypeptide with an alanine are described herein. Additional methods for substituting a histidine in a reference polypeptide with an alanine are known in the art. [0226] The term “DLL3-positive cancer” means a cancer cell that has a predetermined level of DLL3 or an epitope of DLL3 presented on its surface. Non-limiting examples of DLL3-positive cancers include: small-cell lung cancer, large cell neuroendocrine carcinoma, pulmonary neuroendocrine cancer, extrapulmonary neuroendocrine cancers, or melanoma. In some embodiments, a DLL3-positive cancer can be a metastatic cancer or metastasis. In some embodiments, a DLL3-positive cancer can be a primary cancer. [0227] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Methods and materials are described herein for use in the present invention; other, suitable methods and materials known in the art can 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, will control. [0228] Other features and advantages of the invention will be apparent from the following detailed description and figures, and from the claims. BRIEF DESCRIPTION OF DRAWINGS [0229] FIGs. 1A-1B Present schematics illustrating epitope binning methods including a sandwich assay (FIG.1A) and a tumor cell presenting an antigen (DLL3) with exemplary antigen- binding protein constructs binding portions thereof (FIG.1B). Attorney Docket No.: 45395-0068WO1 DETAILED DESCRIPTION [0230] Provided herein are antigen-binding protein constructs (ABPCs) that include: a first ABD that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell. [0231] In one aspect, the disclosure provides novel DLL3-binding antigen-binding protein constructs (ABPCs) having improved properties over existing DLL3-binding ABPCs. [0232] In another aspect, the disclosure provided DLL3-binding ABPCs wherein (a) the dissociation rate of the first ABD 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 (KD) of the first ABD 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. In some examples of these ABPCs, the ABPC is degraded in the target mammalian cell following internalization of the ABPC by the target mammalian cell. Some examples of any of the ABPCs described herein can further include a conjugated toxin, radioisotope, drug, or small molecule (e.g., a fluorophore or dye). [0233] In another aspect, the ABPCs include: a first ABD that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell; and a conjugated toxin, radioisotope, drug, or small molecule, where: (a) the dissociation rate of the first ABD 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 (KD) of the first ABD 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) a composition including the ABPC provides for one or more (e.g., two or three) of: an increase (e.g., a detectable increase) in toxin liberation 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. [0234] In one aspect, the present disclosure provides an antibody, antigen binding protein construct (ABPC), or antigen binding domain (ABD) thereof, comprising a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein (a) the HCVD comprises an H-CDR1 sequence, an H-CDR2 sequence, and an H-CDR3 sequence selected from the group consisting of the sequences of one of (i) to (xii): (i) SEQ ID NO: 5, SEQ ID NO: 6, and SEQ ID Attorney Docket No.: 45395-0068WO1 NO: 7, respectively; (ii) SEQ ID NO: 13, SEQ ID NO: 14, and SEQ ID NO: 15, respectively; (iii) SEQ ID NO: 21, SEQ ID NO: 22, and SEQ ID NO: 23, respectively; (iv) SEQ ID NO: 29, SEQ ID NO: 30, and SEQ ID NO: 31, respectively; (v) SEQ ID NO: 37, SEQ ID NO: 38, and SEQ ID NO: 39, respectively; (vi) SEQ ID NO: 45, SEQ ID NO: 46, and SEQ ID NO: 47, respectively; (vii) SEQ ID NO: 53, SEQ ID NO: 54, and SEQ ID NO: 55, respectively; (viii) SEQ ID NO: 61, SEQ ID NO: 62, and SEQ ID NO: 63, respectively; (ix) SEQ ID NO: 69, SEQ ID NO: 70, and SEQ ID NO: 71, respectively; (x) SEQ ID NO: 77, SEQ ID NO: 78, and SEQ ID NO: 79, respectively; (xi) SEQ ID NO: 85, SEQ ID NO: 86, and SEQ ID NO: 87, respectively; (xii) SEQ ID NO: 93, SEQ ID NO: 94, and SEQ ID NO: 95, respectively; and/or (b) the LCVD comprises an L-CDR1 sequence, an L-CDR2 sequence, and an L-CDR3 sequence selected from the group consisting of the sequences of one of (i) to (xii): (i) SEQ ID NO: 8, SEQ ID NO: 9, and SEQ ID NO: 10, respectively; (ii) SEQ ID NO: 16, SEQ ID NO: 17, and SEQ ID NO: 18, respectively; (iii) SEQ ID NO: 24, SEQ ID NO: 25, and SEQ ID NO: 26, respectively; (iv) SEQ ID NO: 32, SEQ ID NO: 33, and SEQ ID NO: 34, respectively; (v) SEQ ID NO: 40, SEQ ID NO: 41, and SEQ ID NO: 42, respectively; (vi) SEQ ID NO: 48, SEQ ID NO: 49, and SEQ ID NO: 50, respectively; (vii) SEQ ID NO: 56, SEQ ID NO: 57, and SEQ ID NO: 58, respectively; (viii) SEQ ID NO: 64, SEQ ID NO: 65, and SEQ ID NO: 66, respectively; (ix) SEQ ID NO: 72, SEQ ID NO: 73, and SEQ ID NO: 74, respectively; (x) SEQ ID NO: 80, SEQ ID NO: 81, and SEQ ID NO: 82, respectively; (xi) SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 90, respectively; and (xii) SEQ ID NO: 96, SEQ ID NO: 97, and SEQ ID NO: 98, respectively. In some aspects, the set of H-CDR1, H-CDR2, and H-CDR3 sequences contains at least one amino acid substituted with a histidine (e.g., one, two, three, four, or five total histidine substitutions across the set of three H- CDRs)). In some aspects, the set of L-CDR1, L-CDR2, and L-CDR3 sequences contains at least one amino acid substituted with a histidine (e.g., one, two, three, four, or five total histidine substitutions across the set of three L-CDRs). [0235] In some aspects, the antibody, ABPC, or ABD includes one or more of the following characteristics: (a) a heavy chain variable domain (HCVD) sequence that is at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identical to the HCVD sequence of any one of SEQ ID NOs: 3, 11, 19, 27, 35, 43, 51, 59, 67, 75, 83, and 91; and/or (b) a light chain variable domain (LCVD) sequence that is at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identical to the LCVD sequence of any one of SEQ ID NOs: 4, 12, 20, 28, 36, 44, 52, 60, 68, Attorney Docket No.: 45395-0068WO1 76, 84, and 92. In some aspects, the set of three H-CDRs comprises one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or the set of three L-CDRs comprises one, two, three, four, or five total histidine substitutions across the set of three L-CDRs. In some embodiments, the HCVD and LCVD do not include any substitutions in their variable domain framework regions or their constant domain regions. [0236] In another aspect, the present disclosure provides an antibody, ABPC, or ABD thereof comprising an HCVD and an LCVD, wherein: (a) the HCVD comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 3, SEQ ID NO: 11, SEQ ID NO: 19, SEQ ID NO: 27, SEQ ID NO: 35, SEQ ID NO: 43, SEQ ID NO: 51, SEQ ID NO: 59, SEQ ID NO: 67, SEQ ID NO: 75, SEQ ID NO: 83, and SEQ ID NO: 91; and/or (b) the LCVD comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 4, SEQ ID NO: 12, SEQ ID NO: 20, SEQ ID NO: 28, SEQ ID NO: 36, SEQ ID NO: 44, SEQ ID NO: 52, SEQ ID NO: 60, SEQ ID NO: 68, SEQ ID NO: 76, SEQ ID NO: 84, and SEQ ID NO: 92. In some aspects, the set of three H-CDRs comprises one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or the set of three L-CDRs comprises one, two, three, four, or five total histidine substitutions across the set of three L-CDRs. In some embodiments, the HCVD and LCVD do not include any substitutions in their variable domain framework regions or their constant domain regions. [0237] In some aspects of the antibody, ABPC, or ABD, the HCVD amino acid sequence and the LCVD amino acid sequence is selected from the group consisting of: SEQ ID NO: 3 and SEQ ID NO: 4, respectively; SEQ ID NO: 11 and SEQ ID NO: 12, respectively; SEQ ID NO: 19 and SEQ ID NO: 20; SEQ ID NO: 27 and SEQ ID NO: 28, respectively; SEQ ID NO: 35 and SEQ ID NO: 36, respectively; SEQ ID NO: 43 and SEQ ID NO: 44, respectively; SEQ ID NO: 51 and SEQ ID NO: 52, respectively; SEQ ID NO: 59 and SEQ ID NO: 59, respectively; SEQ ID NO: 67 and SEQ ID NO: 67, respectively; SEQ ID NO: 75 and SEQ ID NO: 76, respectively; SEQ ID NO: 83 and SEQ ID NO: 84, respectively; and SEQ ID NO: 91 and SEQ ID NO: 92, respectively. In some aspects, the set of three H-CDRs comprises one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or the set of three L-CDRs comprises one, two, three, four, or five total histidine substitutions across the set of three L-CDRs. In some embodiments, the HCVD and LCVD do not include any substitutions in their variable domain framework regions or their constant domain regions. Attorney Docket No.: 45395-0068WO1 [0238] In another aspect, the present disclosure provides an antibody, antigen binding protein construct (ABPC), or antigen binding domain (ABD) thereof, comprising a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein (a) the HCVD comprises an H-CDR1 sequence, an H-CDR2 sequence, and an H-CDR3 sequence selected from the group consisting of the sequences of one of (i) to (xii): (i) SEQ ID NO: 125, SEQ ID NO: 126, and SEQ ID NO: 127, respectively; (ii) SEQ ID NO: 133, SEQ ID NO: 134, and SEQ ID NO: 135, respectively; (iii) SEQ ID NO: 141, SEQ ID NO: 142, and SEQ ID NO: 143, respectively; (iv) SEQ ID NO: 149, SEQ ID NO: 150, and SEQ ID NO: 151, respectively; (v) SEQ ID NO: 157, SEQ ID NO: 158, and SEQ ID NO: 159, respectively; (vi) SEQ ID NO: 165, SEQ ID NO: 166, and SEQ ID NO: 167, respectively; (vii) SEQ ID NO: 173, SEQ ID NO: 174, and SEQ ID NO: 175, respectively; (viii) SEQ ID NO: 181, SEQ ID NO: 182, and SEQ ID NO: 183, respectively; (ix) SEQ ID NO: 189, SEQ ID NO: 190, and SEQ ID NO: 191, respectively; (x) SEQ ID NO: 197, SEQ ID NO: 198, and SEQ ID NO: 199, respectively; (xi) SEQ ID NO: 205, SEQ ID NO: 206, and SEQ ID NO: 207, respectively; (xii) SEQ ID NO: 213, SEQ ID NO: 214, and SEQ ID NO: 215, respectively; and/or (b) the LCVD comprises an L-CDR1 sequence, an L-CDR2 sequence, and an L-CDR3 sequence selected from the group consisting of the sequences of one of (i) to (xii): (i) SEQ ID NO: 128, SEQ ID NO: 129, and SEQ ID NO: 130, respectively; (ii) SEQ ID NO: 136, SEQ ID NO: 137, and SEQ ID NO: 138, respectively; (iii) SEQ ID NO: 144, SEQ ID NO: 145, and SEQ ID NO: 146, respectively; (iv) SEQ ID NO: 152, SEQ ID NO: 153, and SEQ ID NO: 154, respectively; (v) SEQ ID NO: 160, SEQ ID NO: 161, and SEQ ID NO: 162, respectively; (vi) SEQ ID NO: 168, SEQ ID NO: 169, and SEQ ID NO: 170, respectively; (vii) SEQ ID NO: 176, SEQ ID NO: 177, and SEQ ID NO: 178, respectively; (viii) SEQ ID NO: 184, SEQ ID NO: 185, and SEQ ID NO: 186, respectively; (ix) SEQ ID NO: 192, SEQ ID NO: 193, and SEQ ID NO: 194, respectively; (x) SEQ ID NO: 200, SEQ ID NO: 201, and SEQ ID NO: 202, respectively; (xi) SEQ ID NO: 208, SEQ ID NO: 209, and SEQ ID NO: 210, respectively; and (xii) SEQ ID NO: 216, SEQ ID NO: 217, and SEQ ID NO: 218, respectively. In some aspects, the set of three H- CDRs comprises one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or the set of three L-CDRs comprises one, two, three, four, or five total histidine substitutions across the set of three L-CDRs. [0239] In some aspects, the antibody, ABPC, or ABD includes one or more of the following characteristics: (a) a heavy chain variable domain (HCVD) sequence that is at least 80%, at least Attorney Docket No.: 45395-0068WO1 85%, at least 90%, at least 95%, or at least 99% identical to the HCVD sequence of any one of SEQ ID NOs: 123, 131, 139, 147, 155, 163, 171, 179, 187, 195, 203, and 211; and/or (b) a light chain variable domain (LCVD) sequence that is at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identical to the LCVD sequence of any one of SEQ ID NOs: 124, 132, 140, 148, 156, 164, 172, 180, 188, 196, 204, and 212. In some aspects, the set of three H-CDRs comprises one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or the set of three L-CDRs comprises one, two, three, four, or five total histidine substitutions across the set of three L-CDRs. In some embodiments, the HCVD and LCVD do not include any substitutions in their variable domain framework regions or their constant domain regions. [0240] In another aspect, the present disclosure provides an antibody, ABPC, or ABD thereof comprising an HCVD and an LCVD, wherein: (a) the HCVD comprises an amino acid sequence of any one of SEQ ID NO: 123, SEQ ID NO: 131, SEQ ID NO: 139, SEQ ID NO: 147, SEQ ID NO: 155, SEQ ID NO: 163, SEQ ID NO: 171, SEQ ID NO: 179, SEQ ID NO: 187, SEQ ID NO: 195, SEQ ID NO: 203, and SEQ ID NO: 211; and/or (b) the LCVD comprises an amino acid sequence of any one of SEQ ID NO: 124, SEQ ID NO: 132, SEQ ID NO: 140, SEQ ID NO: 148, SEQ ID NO: 156, SEQ ID NO: 164, SEQ ID NO: 172, SEQ ID NO: 180, SEQ ID NO: 188, SEQ ID NO: 196, SEQ ID NO: 204, and SEQ ID NO: 212. In some aspects, the set of three H-CDRs comprises one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or the set of three L-CDRs comprises one, two, three, four, or five total histidine substitutions across the set of three L-CDRs. In some embodiments, the HCVD and LCVD do not include any substitutions in their variable domain framework regions or their constant domain regions. [0241] In some aspects of the antibody, ABPC, or ABD, the HCVD amino acid sequence and the LCVD amino acid sequence is selected from the group consisting of: SEQ ID NO: 123 and SEQ ID NO: 124, respectively; SEQ ID NO: 131 and SEQ ID NO: 132, respectively; SEQ ID NO: 139 and SEQ ID NO: 140; SEQ ID NO: 147 and SEQ ID NO: 148, respectively; SEQ ID NO: 155 and SEQ ID NO: 156, respectively; SEQ ID NO: 163 and SEQ ID NO: 164, respectively; SEQ ID NO: 171 and SEQ ID NO: 172, respectively; SEQ ID NO: 179 and SEQ ID NO: 179, respectively; SEQ ID NO: 187 and SEQ ID NO: 187, respectively; SEQ ID NO: 195 and SEQ ID NO: 196, respectively; SEQ ID NO: 203 and SEQ ID NO: 204, respectively; and SEQ ID NO: 211 and SEQ ID NO: 212, respectively. In some aspects, the set of three H-CDRs comprises one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or the set of three L- Attorney Docket No.: 45395-0068WO1 CDRs comprises one, two, three, four, or five total histidine substitutions across the set of three L- CDRs. In some embodiments, the HCVD and LCVD do not include any substitutions in their variable domain framework regions or their constant domain regions. [0242] Also provided herein are pharmaceutical compositions including any of the ABPCs described herein. Also provided herein are methods of treating a subject in need thereof that include administering a therapeutically effective amount of any of the ABPCs described herein to the subject. [0243] In some aspects, a conjugated composition including the ABPC (e.g., any of the ABPCs described herein) can provide for an increase (e.g., a detectable increase) (e.g., any of the percents increase or ranges of percents increase recited in US 2022/0281984, which is incorporated by reference herein in its entirety) in toxin liberation in the target mammalian cell (e.g., any of the target mammalian cells described herein) as compared to a conjugated composition including the same amount of a control ABPC (e.g., any of the exemplary control ABPCs described herein). [0244] In some aspects, a conjugated composition including the ABPC (e.g., any of the ABPCs described herein) can provide for an increase (e.g., a detectable increase) (e.g., any of the folds increase or ranges of folds increase recited in US 2022/0281984) in toxin liberation in the target mammalian cell (e.g., any of the target mammalian cells described herein) as compared to a composition including the same amount of a control ABPC (e.g., any of the exemplary control ABPCs described herein). [0245] In some aspects, a conjugated composition including the ABPC (e.g., any of the ABPCs described herein) can provide for an increase (e.g., a detectable increase) (e.g., at least a 1%, 2%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 120%, 140%, 160%, 180%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 1,000%, 2,000%, 3,000%, 4,000%, 5,000%, 6,000%, 7,000%, 8,000%, 9,000%, or a 10,000% increase, or about a 1% to 10,000% increase (e.g., or any of the subranges)) in target mammalian cell killing as compared to a conjugated composition including the same amount of a control ABPC. [0246] In some aspects, a conjugated composition including the ABPC (e.g., any of the ABPCs described herein) can provide for an increase (e.g., a detectable increase) (e.g., at least a 0.1-, 0.2- , 0.3-, 0.4-, 0.5-, 0.6-, 0.7-, 0.8-, 0.9-, 1.0-, 1.2-, 1.4-, 1.5-, 1.6-, 1.8-, 2.0-, 2.2-, 2.4-, 2.5-, 2.6-, 2.8- , 3.0-, 3.5-, 4.0-, 4.5-, 5.0-, 5.5-, 6.0-, 6.5-, 7.0-, 7.5-, 8.0-, 8.5-, 9.0-, 9.5-, 10-, 15-, 20-, 25-, 30-, Attorney Docket No.: 45395-0068WO1 35-, 40-, 40-, 45-, 50-, 55-, 60-, 65-, 70-, 80-, 85-, 90-, 95-fold increase, or at least a 100-fold increase, or a 0.1-100-fold increase in target mammalian cell killing as compared to a conjugated composition including the same amount of a control ABPC. [0247] In some aspects, a conjugated composition including any of the ABPCs described herein (e.g., upon contacting target mammalian cells presenting DLL3 on their surface) results in decreased (e.g., ≥ a 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% decrease, or at least a 99% decrease, about a 1%-99% decrease, or any of the subranges of this range described herein) IC50 (for target mammalian cell killing) as compared to the IC50 for a conjugated composition including the same amount of a control ABPC. [0248] In some aspects, a composition including any of the ABPCs described herein (e.g., upon contacting target mammalian cells presenting DLL3 on their surface) can provide for an increase (e.g., at least a 0.1-, 0.2-, 0.4-, 0.6-, 0.8-, 1-, 2-, 5-, 10-, 15-, 20-, 25-, 30-, 35-, 40-, 45-, 50-, 55-, 60-, 65-, 70-, 75-, 80-, 85-, 90-, 95-fold increase, or at least a 100-fold increase, or about a 0.1- 500-fold increase (or any of the subranges of this range described herein) in the ratio of KD on target mammalian cells presenting DLL3 on their surface at a neutral pH to IC50 at the neutral pH on the same target cells, e.g., as compared to a control ABPC. [0249] In some aspects, a composition including the ABPC (e.g., any of the ABPCs described herein) can provide for an increase (e.g., a detectable increase) (e.g., at least a 1%, 2%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 120%, 140%, 160%, 180%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 1,000%, 2,000%, 3,000%, 4,000%, 5,000%, 6,000%, 7,000%, 8,000%, 9,000% increase, or at least a 10,000% increase, or about a 1%-10,000% increase (e.g., or any of the subranges of this range described herein)) in endolysosomal delivery in the target mammalian cell as compared to a composition including the same amount of a control ABPC. [0250] In some aspects, a composition including the ABPC can provide for an increase (e.g., ≥ a 0.1-, 0.2-, 0.3-, 0.4-, 0.5-, 0.6-, 0.7-, 0.8-, 0.9-, 1.0-, 1.2-, 1.4-, 1.5-, 1.6-, 1.8-, 2.0-, 2.2-, 2.4-, 2.5- , 2.6-, 2.8-, 3.0-, 3.5-, 4.0-, 4.5-, 5.0-, 5.5-, 6.0-, 6.5-, 7.0-, 7.5-, 8.0-, 8.5-, 9.0-, 9.5-, 10-, 15-, 20-, 25-, 30-, 35-, 40-, 45-, 50-, 55-, 60-, 65-, 70-, 75-, 80-, 85-, 90-, 95-fold increase, or at least a 100- fold increase, or about a 0.1-100-fold increase in endolysosomal delivery in the target mammalian cell as compared to a composition including the same amount of a control ABPC. Attorney Docket No.: 45395-0068WO1 [0251] In some aspects of any of the ABPCs described herein, the target mammalian cell does not express an FcRn receptor, or expresses a lower (e.g., a detectably lower) level (e.g., at least a 1% decreased, at least a 2%, 5%, 10% decrease, at least a 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% decreased, or at least a 99% decreased level) of FcRn receptor as compared to a FcRn expressing control cell (e.g., HUVEC – ThermoFisher #C0035C). In some examples, the target mammalian cell is a DLL3-positive cancer cell. In some examples, the ABPC is cytotoxic or cytostatic to the target mammalian cell. [0252] In some examples, a composition including any of the ABPCs described herein (e.g., upon administration to a subject) results in less (e.g., a 1% decrease to about a 99% decrease, or any of the subranges of this range described herein) of a reduction in the level of DLL3 presented on the surface of the target mammalian cell as compared to a composition including the same amount of a control ABPC (e.g., any of the control ABPCs described herein). In some examples, the composition does not result in a detectable reduction in the level of the DLL3 presented on the surface of the target mammalian cell. [0253] In some examples, the ABPC is cross-reactive with a non-human primate DLL3 and a human DLL3. In some examples, the ABPC is cross-reactive with a non-human primate DLL3, a human DLL3, and one or both of rat DLL3 and a mouse DLL3. In some examples, the ABPC is cross-reactive with a non-human primate DLL3, a human DLL3, a rat DLL3, and a mouse DLL3. In some examples, the ABPC is cross-reactive with mouse DLL3 and rat DLL3. In some examples, the first ABD binds to an epitope of DLL3 that is present on the surface of cells from an Old World Monkey. [0254] Some examples of any of the ABPCs described herein can further include a second ABD (e.g., any of the exemplary ABDs described herein). In some embodiments, the second ABD specifically binds to DLL3 (e.g., the same or a different epitope on DLL3 as compared to the first ABD). In some embodiments, the second ABD is the same as the first ABD. In some embodiments, the second ABD binds to an epitope on the surface of an immune cell (e.g., a T cell or a NK cell) (e.g., CD3). [0255] Non-limiting aspects of these methods are described below, and can be used in any combination without limitation. Additional aspects of these methods are known in the art. Attorney Docket No.: 45395-0068WO1 DLL3 or Epitope of DLL3 [0256] Multiple DLL3-binding monoclonal antibodies have been described in the literature and can be used as a template for engineering pH-dependent binding. The amino acid sequence of human DLL3 can be found in SEQ ID NO: 1 and the amino acid sequence of the extracellular domain of human DLL3 can be found in SEQ ID NO: 2. [0257] Any of the antigen-binding protein constructs disclosed herein can also be used as a template for engineering pH-dependent binding (e.g., by introduction of one or more histidines into one or more of its six CDRs). Antigen-Binding Protein Constructs [0258] Any of the antigen-binding protein constructs (ABPCs) described herein can be a single polypeptide, or can include 2, 3, 4, 5, 6, 7, 8, 9, or 10 (the same or different) polypeptides. In some aspects where the ABPC is a single polypeptide, the ABPC can include a single ABD or two ABDs. In some aspects where the ABPC is a single polypeptide and includes two ABDs, the first and second ABDs can be identical or different from each other (and can specifically bind to the same or different antigens or epitopes). [0259] In some aspects where the ABPC is a single polypeptide, the first ABD and the second ABD (if present) can each be independently selected from the group of: a VH domain, a VHH domain, a VNAR domain, and a scFv. In some aspects where the ABPC is a single polypeptide, the antigen-binding protein construct can be a BiTe, a (scFv)2, a nanobody, a nanobody-HSA, a DART, a TandAb, a scDiabody, a scDiabody-CH3, scFv-CH-CL-scFv, a HSAbody, scDiabody- HAS, a tandem-scFv, an Adnectin, a DARPin, a fibronectin, a DEP conjugate, a PROTAB, and a PROTAC. Additional examples of ABDs that can be used when the ABPC is a single polypeptide are known in the art. [0260] A VHH domain is a single monomeric variable antibody domain that can be found in camelids. A VNAR domain is a single monomeric variable antibody domain that can be found in cartilaginous fish. Non-limiting aspects of VHH domains and VNAR domains are described in, e.g., Cromie et al., Curr. Top. Med. Chem.15:2543-2557, 2016; De Genst et al., Dev. Comp. Immunol. 30:187-198, 2006; De Meyer et al., Trends Biotechnol. 32:263-270, 2014; Kijanka et al., Nanomedicine 10:161-174, 2015; Kovaleva et al., Expert. Opin. Biol. Ther.14:1527-1539, 2014; Krah et al., Immunopharmacol. Immunotoxicol. 38:21-28, 2016; Mujic-Delic et al., Trends Pharmacol. Sci.35:247-255, 2014; Muyldermans, J. Biotechnol.74:277-302, 2001; Muyldermans Attorney Docket No.: 45395-0068WO1 et al., Trends Biochem. Sci. 26:230-235, 2001; Muyldermans, Ann. Rev. Biochem. 82:775-797, 2013; Rahbarizadeh et al., Immunol. Invest. 40:299-338, 2011; Van Audenhove et al., EBioMedicine 8:40-48, 2016; Van Bockstaele et al., Curr. Opin. Investig. Drugs 10:1212-1224, 2009; Vincke et al., Methods Mol. Biol.911:15-26, 2012; and Wesolowski et al., Med. Microbiol. Immunol.198:157-174, 2009. [0261] In some aspects where the ABPC is a single polypeptide and includes two ABDs, the first ABD and the second ABD can both be VHH domains, or at least one ABD can be a VHH domain. In some aspects where the ABPC is a single polypeptide and includes two ABDs, the first ABD and the second ABD are both VNAR domains, or at least one ABD is a VNAR domain. In some aspects where the ABPC is a single polypeptide, the first ABD is a scFv domain. In some aspects where the ABPC is a single polypeptide and includes two ABDs, the first ABD and the second ABD can both be scFv domains, or at least one ABD can be a scFv domain. [0262] In some aspects, the ABPC can include two or more polypeptides (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 polypeptides). In some aspects where the ABPC includes two or more polypeptides, two, three, four, five or six of the polypeptides of the two or more polypeptides can be identical. [0263] In some aspects where the ABPC includes two or more polypeptides (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 polypeptides), two or more of the polypeptides of the ABPC can assemble (e.g., non- covalently assemble) to form one or more ABDs, e.g., an antigen-binding fragment of an antibody (e.g., any of the antigen-binding fragments of an antibody described herein), a VHH-scAb, a VHH- Fab, a Dual scFab, a F(ab’)2, a diabody, a crossMab, a DAF (two-in-one), a DAF (four-in-one), a DutaMab, a DT-IgG, a knobs-in-holes common light chain, a knobs-in-holes assembly, a charge pair, a Fab-arm exchange, a SEEDbody, a LUZ-Y, a Fcab, a κλ-body, an orthogonal Fab, a DVD- IgG, a IgG(H)-scFv, a scFv-(H)IgG, IgG(L)-scFv, scFv-(L)IgG, IgG(L,H)-Fv, IgG(H)-V, V(H)- IgG, IgG(L)-V, V(L)-IgG, KIH IgG-scFab, 2scFv-IgG, IgG-2scFv, scFv4-Ig, Zybody, DVI-IgG, Diabody-CH3, a triple body, a miniantibody, a minibody, a TriBi minibody, scFv-CH3 KIH, Fab- scFv, a F(ab’)2-scFv2, a scFv-KIH, a Fab-scFv-Fc, a tetravalent HCAb, a scDiabody-Fc, a Diabody-Fc, a tandem scFv-Fc, a VHH-Fc, a tandem VHH-Fc, a VHH-Fc KiH, a Fab-VHH-Fc, an Intrabody, a dock and lock, an ImmTAC, an IgG-IgG conjugate, a Cov-X-Body, a scFv1-PEG- scFv2, an Adnectin, a DARPin, a fibronectin, a DEP conjugate, a PROTAB, and a PROTAC. See, e.g., Spiess et al., Mol. Immunol. 67:95-106, 2015, incorporated in its entirety herewith, for a description of these elements. Non-limiting examples of an antigen-binding fragment of an Attorney Docket No.: 45395-0068WO1 antibody include an Fv fragment, a Fab fragment, a F(ab')2 fragment, and a Fab' fragment. Additional examples of an antigen-binding fragment of an antibody is an antigen-binding fragment of an IgG (e.g., an antigen-binding fragment of IgG1, IgG2, IgG3, or IgG4) (e.g., an antigen- binding fragment of a human or humanized IgG, e.g., human or humanized IgG1, IgG2, IgG3, or IgG4); an antigen-binding fragment of an IgA (e.g., an antigen-binding fragment of IgA1 or IgA2) (e.g., an antigen-binding fragment of a human or humanized IgA, e.g., a human or humanized IgA1 or IgA2); an antigen-binding fragment of an IgD (e.g., an antigen-binding fragment of a human or humanized IgD); an antigen-binding fragment of an IgE (e.g., an antigen-binding fragment of a human or humanized IgE); or an antigen-binding fragment of an IgM (e.g., an antigen-binding fragment of a human or humanized IgM). [0264] A “Fv” fragment includes a non-covalently-linked dimer of one HCVD and one LCVD. [0265] A “Fab” fragment includes, the constant domain of the light chain and the first constant domain (CH1) of the heavy chain, in addition to the heavy and LCVDs of the Fv fragment. [0266] A “F(ab')2” fragment includes two Fab fragments joined, near the hinge region, by disulfide bonds. [0267] A “dual variable domain immunoglobulin” or “DVD-Ig” refers to multivalent and multispecific binding proteins as described, e.g., in DiGiammarino et al., Methods Mol. Biol. 899:145-156, 2012; Jakob et al., MABs 5:358-363, 2013; and U.S. Patent Nos. 7,612,181; 8,258,268; 8,586,714; 8,716,450; 8,722,855; 8,735,546; and 8,822,645, each of which is incorporated by reference in its entirety. [0268] DARTs are described in, e.g., Garber, Nature Reviews Drug Discovery 13:799-801, 2014. [0269] Additional aspects of ABPCs are known in the art. Antigen-Binding Domains [0270] In some aspects of any of the antigen-binding protein constructs (ABPCs) described herein, the dissociation rate of the first ABD (and optionally the second ABD, if present) at a pH of about 4.0 to about 6.5 (e.g., about 4.0 to about 6.4, or any of the ranges of pH recited in US 2022/0281984) is faster (e.g., at least 5% faster, or any of the % faster or ranges of % faster recited in US 2022/0281984) than the dissociation rate at a pH of about 7.0 to about 8.0 (e.g., about 7.0- 7.9, 7.0-7.8, 7.0-7.7, 7.0-7.6, 7.0-7.5, 7.0-7.4, 7.0-7.3, 7.0-7.2, 7.0-7.1, 7.1-8.0, 7.1-7.9, 7.1-7.8, 7.1-7.7, 7.1-7.6, 7.1-7.5, 7.1-7.4, 7.1-7.3, 7.1-7.2, 7.2-8.0, 7.2-7.9, 7.2-7.8, 7.2-7.7, 7.2-7.6, 7.2- 7.5, 7.2-7.4, 7.2-7.3, 7.3-8.0, 7.3-7.9, 7.3-7.8, 7.3-7.7, 7.3-7.6, 7.3-7.5, 7.3-7.4, 7.4-8.0, 7.4-7.9, Attorney Docket No.: 45395-0068WO1 7.4-7.8, 7.4-7.7, 7.4-7.6, 7.4-7.5, 7.5-8.0, 7.5-7.9, 7.5-7.8, 7.5-7.7, 7.5-7.6, 7.5-8.0, 7.6-7.9, 7.6- 7.8, 7.6-7.7, 7.7-8.0, 7.7-7.9, 7.7-7.8, 7.8-8.0, 7.8-7.9, or about 7.9-8.0). [0271] In some aspects of any of the ABPCs described herein, the dissociation constant (KD) of the first ABD (and optionally the second ABD, if present) at a pH of about 4.0 to about 6.5 (e.g., any of the subranges of this range described herein) is greater (e.g., detectably greater) (e.g., at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 80, 85, 90, 95, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300, 320, 340, 360, 380, 400, 420, 440, 460, 480, 500, 1,000, 2,000, 3,000, 4,000, 5,000, 6,000, 7,000, 8,000, 9,000, or at least about 10,000% greater, or about 5% to about 10,000% greater, or any of the ranges of percents greater KD recited in US 2022/0281984), than the KD at a pH of about 7.0 to about 8.0 (e.g., any of the subranges of this range described herein). [0272] In some aspects of any of the antigen-binding protein constructs (ABPCs) described herein, the dissociation rate of the first ABD (and optionally the second ABD, if present) at a pH of about 4.0 to about 6.5 (e.g., any of the subranges of this range described herein) is faster (e.g., at least 0.2-fold faster, or any of the folds faster or ranges of folds faster recited in US 2022/0281984), than the dissociation rate at a pH of ~7.0 to ~8.0 (e.g., or any of the subranges). [0273] In some aspects of any of the antigen-binding protein constructs (ABPCs) described herein, the dissociation constant (KD) of the first ABD (and optionally the second ABD, if present) at a pH of about 4.0 to about 6.5 (e.g., any of the subranges of this range described herein) is greater (e.g., detectably greater) (e.g., at least 0.2-fold greater, or any of the fold greater or ranges of fold greater recited in US 2022/0281984), than the KD at a pH of about 7.0 to about 8.0 (e.g., any of the subranges of this range described herein). [0274] In some aspects of the ABPCs that include a first ABD and a second ABD, the first and second ABDs are identical or are at least 80% identical (e.g., ≥82%, ≥84%, ≥86%, ≥88%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, or ≥99% identical) in amino acid sequence to each other. In some aspects, the ABPCs that include a first ABD and a second ABD, the first ABD and the second ABD have a sequence that is less than 80% identical (e.g., <75% , <70% , <65% , <60% , <55% , <50% , <45% , <40% , <35% , <30% , <25% , <20% , <15% , <10% , or <5% identical) to each other. In some aspects of ABPCs that include a first and a second ABD, the first and second ABD binds two different epitopes (e.g., two different epitopes on DLL3 Attorney Docket No.: 45395-0068WO1 or the first ABD binding specifically to DLL3 and the second ABD binding to an antigen other than DLL3). [0275] In some aspects of any of the ABPCs described herein, the KD of the first ABD (and optionally, the second ABD if present) at a pH of about 7.0-8.0 (e.g., any of the subranges of this range described herein) is between about 1 pM-5 µM (e.g., 1 pM-2 µM, or any of the ranges of KD recited in WO 2021/022039 at pages 471-492 (or recited in published application US 2022/0281984), which are herein incorporated by reference in their entirety). [0276] In some aspects of any of the ABPCs described herein, the KD of the first ABD (and optionally, the second ABD, if present) at a pH of about 4.0-6.5 (e.g., any of the subranges of this range described herein) can be greater than 1 nM (e.g., between about 1 nM-1 mM, or any of the ranges of KD recited in US 2022/0281984). [0277] A variety of different methods known in the art can be used to determine the KD values of any of the antigen-binding protein constructs described herein (e.g., an electrophoretic mobility shift assay, a filter binding assay, surface plasmon resonance, a biomolecular binding kinetics assay, in vitro binding assay on antigen-expressing cells, etc.). [0278] In some examples, the half-life of the ABPC in vivo is increased (e.g., a detectable increase) as compared to the half-life of a control ABPC (e.g., any of the exemplary control ABPCs described herein). Conversely, in some examples, the half-life of the ABPC in vivo may be decreased as compared to the half-life of a control ABPC. Conjugation [0279] In some aspects, the ABPCs provided herein can be conjugated to a drug (e.g., a chemotherapeutic drug, a small molecule), a toxin, or a radioisotope. Non-limiting examples of drugs, toxins, and radioisotopes (e.g., useful for the treatment of cancer) are known in the art. An ABPC conjugated to a drug (e.g., a chemotherapeutic drug, a small molecule), a toxin, or a radioisotope is referred to as “a conjugated composition” herein. [0280] In some aspects, at least one polypeptide of any of the ABPCs described herein is conjugated to the toxin, the radioisotope, or the drug via a cleavable linker. In some aspects, the cleavable linker includes a protease cleavage site. In some aspects, the cleavable linker is cleaved on the ABPC once it is transported to the lysosome or late endosome by the target mammalian cell. In some aspects, cleavage of the linker functionally activates the drug or toxin. Attorney Docket No.: 45395-0068WO1 [0281] In some aspects, at least one polypeptide of any of the ABPCs described herein is conjugated to the toxin, the radioisotope, or the drug via a non-cleavable linker. In some aspects, the conjugated toxin, radioisotope, or drug is released during lysosomal and/or late endosomal degradation of the ABPC. [0282] Non-limiting examples of cleavable linkers include: hydrazone linkers, peptide linkers, disulfide linkers, and thioether linkers. See, e.g., Carter et al., Cancer J. 14(3):154-169, 2008; Sanderson et al., Clin. Cancer Res. 11(2 Pt1):843-852, 2005; Chari et al., Acc. Chem. Res. 41(1):98-107, 2008; Oflazoglu et al., Clin. Cancer Res. 14(19): 6171-6180, 2008; and Lu et al., Int. J. Mol. Sci.17(4): 561, 2016. [0283] Non-limiting examples of non-cleavable linkers include: maleimide alkane-linkers and maleimide cyclohexane linker (MMC) (see, e.g., McCombs et al., AAPS J.17(2):339-351, 2015). [0284] In some aspects, any of the ABPCs described herein is cytotoxic or cytostatic to the target mammalian cell. [0285] In some aspects, the ABPCs(e.g., antibodies) provided herein can comprise one or more amino acid substitutions to provide a conjugation site (e.g., conjugated to a drug, a toxin, a radioisotope). In some aspects, the ABPCs (e.g., antibodies) provided herein can have one conjugation site. In some aspects, the ABPCs (e.g., antibodies) described herein can have two conjugation sites. In some aspects, the ABPCs (e.g., antibodies) provided herein can have three or more conjugation sites. [0286] Naturally-occurring cysteine amino acids can also provide conjugation. In some aspects, the ABPCs (e.g., antibodies) provided herein can have a drug, a toxin, or a radioisotope conjugated at one or more naturally-occurring conjugation sites. In some aspects, the ABPCs (e.g., antibodies) provided herein can have a drug, a toxin, or a radioisotope conjugated at one or more naturally- occurring conjugation sites. In some aspects, the ABPCs (e.g., antibodies) provided herein can have a drug, a toxin, or a radioisotope conjugated at one or more naturally occurring conjugation sites and one or more engineered conjugation sites. [0287] Conjugation through engineered cysteines is achieved by methods known in the art. Briefly, engineered cysteine-containing ABPC (e.g., antibody) is prepared for conjugation by treatment with a reducing agent, for example, tris (2-carboxyethyl) phosphine (TCEP), Dithiothreitol (DTT), or 2-Mercaptoethanol (BME). In the reduction reaction the reducing reagent with disulfide bonds in the ABPC (e.g., antibody), breaking interchain disulfides and removing Attorney Docket No.: 45395-0068WO1 disulfide caps from the engineered cysteines. An optional reoxidation step, achieved by exposure of the solution to air, or an oxidizing agent such as dehydroascorbic acid, allows reformation of the interchain disulfide bonds, leaving the engineered cysteines with a thiolate reactive group. Conjugation with a maleimide functionality on the linker-payload, maleimide-vc-MMAE, is achieved by reaction with the payload in buffered solution, containing cosolvent such as ethanol, dimethylacetamide (DMA), or dimethyl sulfoxide (DMSO). The crude conjugated ABPC (e.g., conjugated antibody) solution is purified by size exclusion chromatography, or selective filtration methods, such as tangential flow filtration. In this step, residual unreacted payload, reducing agent and oxidizing agents are removed from the reaction mixture, and the conjugated ABPC product (e.g., conjugated antibody product) may be transferred into a desirable formulation buffer. [0288] Conjugation through hinge cysteines is achieved by similar methods, using ABPCs (e.g., antibodies) with, or without, additional engineered cysteine conjugation sites. Briefly, the ABPC (e.g., antibody) is prepared for conjugation by treatment with a reducing agent, for example, tris (2-carboxyethyl) phosphine (TCEP) or Dithiothreitol (DTT). The reducing strength and concentration of the reducing agent are selected such that some or all of the interchain disulfide bonds are reduced leaving free cysteines for conjugation. The solution may be directly conjugated in the presence of excess reducing agent. Conjugation with a maleimide functionality on the linker- payload, maleimide-vc-MMAE, is achieved by reaction with the payload in buffered solution, containing cosolvent such as ethanol, dimethylacetamide (DMA), or dimethyl sulfoxide (DMSO). Unreacted linker-payload may be rendered non-reactive by addition of a sacrificial thiolate molecule such as acetyl-cysteine. The crude conjugated ABPC solution (e.g., crude conjugated antibody solution) may be further purified by methods known in the art, including hydrophobic interaction chromatography, ion-exchange chromatography, or mixed-mode chromatography such as ceramic hydroxyapatite chromatography. Isolation of chromatography fractions allows selection of the desired ABPC to payload ratio (e.g., desired antibody to payload ratio) and removal of unreacted ABPC (e.g., unreacted antibody), protein aggregates and fragments, and payload- related reaction side products. The purified ABPC drug conjugate (e.g., purified antibody drug conjugate) may be further purified by size exclusion chromatography, or selective filtration methods, such as TFF. In this step the conjugated ABPC product (e.g., conjugated antibody drug conjugate product) may also be transferred into a desirable formulation buffer. Attorney Docket No.: 45395-0068WO1 [0289] In some examples, an ABPC conjugate (e.g., antibody conjugate) can be made comprising an ABPC (e.g., antibody) linked to monomethyl auristatin E (MMAE) via a valine-citrulline (vc) linker (hereafter, DLL3-IgG-DC). Conjugation of the ABPC (e.g., antibody) with vcMMAE begins with a partial reduction of the DLL3-IgG followed by reaction with maleimidocaproyl-Val- Cit-PABC-MMAE (vcMMAE). The DLL3-IgG (10 mg/mL) is partially reduced by addition of TCEP (molar equivalents of TCEP:mAb is 2:1) followed by incubation at 4° C overnight. The reduction reaction is then warmed to 25° C. To conjugate all of the thiols, vcMMAE is added to a final vcMMAE:reduced Cys molar ratio of 1:10. The conjugation reaction is carried out in the presence of 10% v/v of DMA and allowed to proceed at 25° C for 60 minutes. [0290] In some examples, an ABPC conjugate (e.g., antibody conjugate (ADC)) is made comprising the DLL3-binding IgG (hereafter, DLL3-IgG) described herein linked to monomethyl auristatin E (MMAE) via a valine-citrulline (vc) linker (hereafter, DLL3-IgG-DC). Conjugation of the ABPC (e.g., antibody) with vcMMAE begins with a partial reduction of the DLL3-IgG followed by reaction with maleimidocaproyl-Val-Cit-PABC-MMAE (vcMMAE). The DLL3-IgG (10 mg/mL) is reduced by addition of DTT (molar equivalents of DTT:mAb is 100:1) followed by incubation at 25° C overnight. The reduced DLL3-IgG (10 mg/mL) is then re-oxidized by exposure to DHAA (molar equivalents of DHAA:mAb is 10:1) followed by incubation at 25° C for 2 hours. To conjugate all of the thiols, vcMMAE is added to a final vcMMAE:mAb molar ratio of 4:1. The conjugation reaction is carried out in the presence of 10% v/v of DMA and allowed to proceed at 25° C for 3 hours. Expression of an Antigen-Binding Protein Construct in a Cell [0291] Also provided herein are methods of generating a recombinant cell that expresses an ABPC (e.g., any of the ABPCs described herein) that include: introducing into a cell a nucleic acid encoding the ABPC to produce a recombinant cell; and culturing the recombinant cell under conditions sufficient for the expression of the ABPC. In some aspects, the introducing step includes introducing into a cell an expression vector including a nucleic acid encoding the ABPC to produce a recombinant cell. [0292] Any of the ABPCs described herein can be produced by any cell, e.g., a eukaryotic cell or a prokaryotic cell. As used herein, the term “eukaryotic cell” refers to a cell having a distinct, membrane-bound nucleus. Such cells may include, for example, mammalian (e.g., rodent, non- human primate, or human), insect, fungal, or plant cells. In some aspects, the eukaryotic cell is a Attorney Docket No.: 45395-0068WO1 yeast cell, such as Saccharomyces cerevisiae. In some aspects, the eukaryotic cell is a higher eukaryote, such as mammalian, avian, plant, or insect cells. As used herein, the term “prokaryotic cell” refers to a cell that does not have a distinct, membrane-bound nucleus. In some aspects, the prokaryotic cell is a bacterial cell. [0293] Methods of culturing cells are well known in the art. Cells can be maintained in vitro under conditions that favor proliferation, differentiation, and growth. Briefly, cells can be cultured by contacting a cell (e.g., any cell) with a cell culture medium that includes the necessary growth factors and supplements to support cell viability and growth. [0294] Methods of introducing nucleic acids and expression vectors into a cell (e.g., a eukaryotic cell) are known in the art. Non-limiting examples of methods that can be used to introduce a nucleic acid into a cell include lipofection, transfection, electroporation, microinjection, calcium phosphate transfection, dendrimer-based transfection, cationic polymer transfection, cell squeezing, sonoporation, optical transfection, impalection, hydrodynamic delivery, magnetofection, viral transduction (e.g., adenoviral and lentiviral transduction), and nanoparticle transfection. [0295] Provided herein are methods that further include isolation of the ABPCs from a cell (e.g., a eukaryotic cell) using techniques well-known in the art (e.g., ammonium sulfate precipitation, polyethylene glycol precipitation, ion-exchange chromatography (anion or cation), chromatography based on hydrophobic interaction, metal-affinity chromatography, ligand-affinity chromatography, and size exclusion chromatography). Methods of Treatment [0296] Provided herein are methods of treating a DLL3-positive cancer characterized by having a population of DLL-3 positive cancer cells, which include: administering a therapeutically effective amount of any of the pharmaceutical compositions described herein or any of the ABPCs described herein to a subject identified as having a cancer characterized by having the population of cancer cells. [0297] Also provided herein are methods of reducing the volume of a tumor in a subject, wherein the tumor is characterized by having a population of DLL3-positive cancer cells, that include: administering a therapeutically effective amount of any of the pharmaceutical compositions described herein or any of the ABPCs described herein to the subject. In some aspects of any of the methods described herein, the volume of at least one tumor (e.g., solid tumor) or tumor location Attorney Docket No.: 45395-0068WO1 (e.g., a site of metastasis) is reduced (e.g., a detectable reduction) by ≥1%, ≥2%, ≥3%, ≥4%, ≥5%, ≥6%, ≥8%, ≥10%, ≥12%, ≥14%, ≥16%, ≥18%, ≥20%, ≥22%, ≥24%, ≥26%, ≥28%, ≥30%, ≥35%, ≥40%, ≥45%, ≥50%, ≥55%, ≥60%, ≥65%, ≥70%, ≥75%, ≥80%, ≥85%, ≥90%, ≥95%, or ≥99%) reduced as compared to the size of the at least one tumor (e.g., solid tumor) before administration of the ABPC. [0298] Also provided herein are methods of inducing cell death in a DLL3-positive cancer cell in a subject, that include: administering a therapeutically effective amount of any of the pharmaceutical compositions of described herein or any of the ABPCs described herein to the subject. In some aspects, the cell death that is induced is necrosis. In some aspects, the induced cell death is apoptosis. [0299] In some embodiments of any of the methods described herein, the subject has been previously identified or diagnosed as having a DLL3-positive cancer or as having a DLL3-positive cancer cell. [0300] In some aspects of any of the methods described herein, the DLL3-positive cancer is a primary tumor or a metastasis. [0301] In some aspects of any of the methods described herein, the DLL3-positive cancer is a non-T-cell-infiltrating tumor. In some aspects of any of the methods described herein, the DLL3- positive cancer is a T-cell-infiltrating tumor. [0302] Provided herein are methods of decreasing the risk of developing a metastasis or decreasing the risk of developing an additional metastasis in a subject having a DLL3-positive cancer, that include: administering a therapeutically effective amount of any of the pharmaceutical compositions of described herein or any of the ABPCs described herein to the subject (e.g., a subject previously identified or diagnosed as having a DLL3-positive cancer). In some aspects, the risk of developing a metastasis or the risk of developing an additional metastasis is decreased by ≥1%, by ≥2%, ≥3%, ≥4%, ≥5%, ≥6%, ≥8%, ≥10%, ≥12%, ≥14%, ≥16%, ≥18%, ≥20%, ≥25%, ≥30%, ≥35%, ≥40%, ≥45%, ≥50%, ≥55%, ≥60%, ≥65%, ≥70%, ≥75%, ≥80%, ≥85%, ≥90%, ≥95%, or ≥99% in the subject as compared to the risk of a subject having a similar cancer, but administered no treatment or a treatment that does not include the administration of any of the ABPCs described herein. [0303] In some aspects of any of the methods described herein, the DLL3-positive cancer is a non-T-cell-infiltrating tumor. In some aspects of any of the methods described herein, the DLL3- Attorney Docket No.: 45395-0068WO1 positive cancer is a T-cell-infiltrating tumor. In some aspects of any of the methods described herein, the cellular compartment is part of the endosomal/lysosomal pathway. In some aspects of any of the methods described herein, the cellular compartment is an endosome. [0304] The term “subject” refers to any mammal. In some aspects, the subject or “subject suitable for treatment” may be a canine (e.g., a dog), feline (e.g., a cat), equine (e.g., a horse), ovine, bovine, porcine, caprine, primate, e.g., a simian (e.g., a monkey (e.g., marmoset, baboon), or an ape (e.g., a gorilla, chimpanzee, orangutan, or gibbon) or a human; or rodent (e.g., a mouse, a guinea pig, a hamster, or a rat). In some aspects, the subject or “subject suitable for treatment” may be a non- human mammal, especially mammals that are conventionally used as models for demonstrating therapeutic efficacy in humans (e.g., murine, lapine, porcine, canine or primate animals) may be employed. [0305] As used herein, treating includes reducing the number, frequency, or severity of one or more (e.g., two, three, four, or five) signs or symptoms of a cancer (e.g., a DLL3-positive cancer) in a patient having a cancer (e.g., any of the cancers described herein). For example, treatment can reduce cancer progression, reduce the severity of a cancer, or reduce the risk of re-occurrence of a cancer (e.g., a DLL3-positive cancer) in a subject having the cancer. [0306] Provided herein are methods of inhibiting the growth of a solid tumor (e.g., a DLL3- positive solid tumor) in a subject (e.g., any of the subjects described herein) that include administering to the subject a therapeutically effective amount of any of the ABPCs described herein or any of the pharmaceutical compositions described herein (e.g., as compared to the growth of the solid tumor in the subject prior to treatment or the growth of a similar solid tumor (e.g., a similar DLL3-positive solid tumor) in a different subject receiving a different treatment or receiving no treatment). [0307] In some aspects of any of the methods described herein, the growth of a solid tumor (e.g., a solid DLL3-positive tumor) is primary growth of a solid tumor. In some aspects of any of the methods described herein, the growth of a solid tumor (e.g., a solid DLL3-positive tumor) is recurrent growth of a solid tumor. In some aspects of any of the methods described herein, the growth of a solid tumor (e.g., a solid DLL3-positive tumor) is metastatic growth of a solid tumor. In some aspects, treatment results in about a 1% decrease to about 99% decrease (or any of the subranges of this range described herein) in the growth of a solid tumor (e.g., a solid DLL3-positive tumor) in the subject (e.g., as compared to the growth of the solid tumor (e.g., solid DLL3-positive Attorney Docket No.: 45395-0068WO1 tumor) in the subject prior to treatment or the growth of a similar solid tumor (e.g., a similar solid DLL3-positive tumor) in a different subject receiving a different treatment or receiving no treatment). The growth of a solid tumor (e.g., a solid DLL3-positive tumor) in a subject can be assessed by a variety of different imaging methods, e.g., positron emission tomography, X-ray computed tomography, computed axial tomography, and magnetic resonance imaging. [0308] Also provided herein are methods of decreasing the risk of developing a metastasis or an additional metastasis over a period of time in a subject identified as having a DLL3- cancer (e.g., any of the exemplary DLL3-positive cancers described herein) that include administering to the subject a therapeutically effective amount of any of the proteins described herein or any of the pharmaceutical compositions described herein (e.g., as compared to a subject having a similar DLL3-positive cancer and receiving a different treatment or receiving no treatment). In some aspects of any of the methods described herein, the metastasis or additional metastasis is one or more to a bone, lymph nodes, brain, lung, liver, skin, chest wall including bone, cartilage and soft tissue, abdominal cavity, contralateral breast, soft tissue, muscle, bone marrow, ovaries, adrenal glands, and pancreas. [0309] In some aspects of any of the methods described herein, the period of time is ~1 month to ~3 years (e.g., ~1-30, 1-24, 2-18, 1-12, 1-10, 1-8, 1-6, 1-5, 1-4, 1-3, 1-2, 2-36, 2-30, 2-24, 2-18, 2- 12, 2-10, 2-8, 2-6, 2-5, 2-4, 2-3, 3-36, 3-30, 3-24, 3-18, 3-12, 3-10, 3-8, 3-6, 3-5, 3-4, 4-36, 4-30, 4-24, 4-18, 4-12, 4-10, 4-8, 4-6, 4-5, 5-36, 5-30, 5-24, 5-18, 5-12, 5-10, 5-8, 5-6, 6-36, 6-30, 6-24, 6-18, 6-12, 6-10, 6-8, 8-36, 8-30, 8-24, 8-18, 8-12, 8-10, 10-36, 10-30, 10-24, 10-18, 10-12, 12- 36, 12-30, 12-24, 12-18, 18-36, 18-30, 18-24, 24-36, 24-30, or ~30-36 months). [0310] In some aspects, the risk of developing a metastasis or developing an additional metastasis over a period of time in a subject identified as having a DLL3-positive cancer is decreased by ~1% to ~99% (e.g., or any of the subranges of this range described herein), e.g., as compared to the risk in a subject having a similar cancer receiving a different treatment or receiving no treatment. [0311] Non-limiting examples of DLL3-positive cancer include: lung cancer, prostate cancer, neuroendocrine cancer, melanoma, glioma, glioblastoma, thyroid cancer, bladder cancer, testicular cancer, carcinoma, and medulloblastoma. Additional examples of DLL3-positive cancer are known in the art. [0312] In an embodiment, the DLL3-positive cancer is a small cell lung cancer (SCLC). [0313] In an embodiment, the DLL3-positive cancer is a prostate cancer. Attorney Docket No.: 45395-0068WO1 [0314] In an embodiment, the DLL3-positive cancer is a neuroendocrine cancer, for example but not solely, a neuroendocrine prostate cancer (NEPC). [0315] In an embodiment, the DLL3-positive cancer is a lung adenocarcinoma with neuroendocrine features. [0316] In an embodiment, the DLL3-positive cancer is a melanoma including a metastatic melanoma. [0317] In an embodiment, the DLL3-positive cancer is a low-grade glioma or a high-grade glioma. [0318] In an embodiment, the DLL3-positive cancer is a glioblastoma. [0319] In an embodiment, the DLL3-positive cancer is a medullary thyroid cancer. [0320] In an embodiment, the DLL3-positive cancer is a bladder cancer. [0321] In an embodiment, the DLL3-positive cancer is a testicular cancer. [0322] In an embodiment, the DLL3-positive cancer is a Merkel cell carcinoma. [0323] In an embodiment, the DLL3-positive cancer is a medulloblastoma. [0324] In some aspects, the patient is further administered one or more additional therapeutic agents (e.g., one or more of a chemotherapeutic agent, a recombinant cytokine or interleukin protein, a kinase inhibitor, and a checkpoint inhibitor). In some aspects, the one or more additional therapeutic agents is administered to the patient at approximately the same time as any of the ABPCs described herein are administered to the patient. In some aspects, the one or more additional therapeutic agents are administered to the patient after the administration of any of the ABPCs described herein to the patient. In some aspects, the one or more additional therapeutic agents are administered to the patient before the administration of any of the ABPCs described herein to the patient. [0325] In some aspects of any of the methods described herein, the DLL3-positive cancer is a solid cancer (e.g., a lung cancer, a prostate cancer, a neuroendocrine cancer, a melanoma, a glioma, a glioblastoma, a thyroid cancer, a bladder cancer, a testicular cancer, a carcinoma, or a medulloblastoma). [0326] Non-limiting examples of DLL3-positive cancers include: small cell lung cancer (SCLC), prostate cancer, neuroendocrine cancer (e.g., large cell neuroendocrine carcinoma, pulmonary neuroendocrine cancer, or extrapulmonary neuroendocrine cancer), lung adenocarcinoma with neuroendocrine features, metastatic melanoma, low-grade glioma, high-grade glioma, Attorney Docket No.: 45395-0068WO1 glioblastoma, medullary thyroid cancer, bladder cancer, testicular cancer, and Merkel cell carcinoma. In some embodiments, the DLL3-positive cancer can be a metastatic cancer or a metastasis. In some embodiments, the DLL3-positive cancer can be a primary cancer. Compositions [0327] Also provided herein are compositions (e.g., pharmaceutical compositions) that include at least one of any of the ABPCs described herein. In some aspects, the compositions (e.g., pharmaceutical compositions) can be disposed in a sterile vial or a pre-loaded syringe. [0328] In some aspects, the compositions (e.g., pharmaceutical compositions) are formulated for different routes of administration (e.g., intravenous, subcutaneous, intramuscular, or intratumoral). In some aspects, the compositions (e.g., pharmaceutical compositions) can include a pharmaceutically acceptable carrier (e.g., phosphate buffered saline). Single or multiple administrations of any of the pharmaceutical compositions described herein can be given to a subject depending on, for example: the dosage and frequency as required and tolerated by the patient. A dosage of the pharmaceutical composition should provide a sufficient quantity of the ABPC to effectively treat or ameliorate conditions, diseases, or symptoms. Also provided herein are methods of treating a subject having a DLL3-positive cancer (e.g., any of the DLL3-positive cancers described herein) that include administering a therapeutically effective amount of at least one of any of the compositions or pharmaceutical compositions provided herein. Kits [0329] Also provided herein are kits that include any of the ABPCs described herein, any of the compositions described herein, or any of the pharmaceutical compositions described herein. In some aspects, the kits can include instructions for performing any of the methods described herein. In some aspects, the kits can include at least one dose of any of the compositions (e.g., pharmaceutical compositions) described herein. In some aspects, the kits can provide a syringe for administering any of the pharmaceutical compositions described herein. Antigen-Binding Protein Constructs [0330] Also provided are antigen-binding protein constructs (ABPCs) that include: a first ABD that is capable of specifically binding DLL3, where: (a) the dissociation rate of the first ABD at a pH of about 7.0 to about 8.0 (or any of the subranges of this range described herein) is faster than the dissociation rate at a pH of about 4.0 to about 6.5 (or any of the subranges of this range described herein); and/or (b) the dissociation constant (KD) of the first ABD at a pH of about 7.0 Attorney Docket No.: 45395-0068WO1 to about 8.0 (or any of the subranges of this range) is greater than the KD at a pH of about 4.0 to about 6.5. [0331] Also provided herein are pharmaceutical compositions including any of the ABPCs described herein. Also provided herein are methods of treating a subject in need thereof that include administering a therapeutically effective amount of any of the ABPCs described herein to the subject. Methods of Improving pH Dependence of an Antigen-Binding Protein Construct [0332] Also provided herein are methods of improving pH dependence of an antigen-binding protein construct, the method comprises providing a starting antigen-binding protein construct comprising an ABD and introducing one or more histidine amino acid substitutions into one or more CDRs of the ABD (e.g., one, two, three, four, or five total histidine substitutions in the set of three H-CDRs of the ABD and/or one, two, three, four, or five total histidine substitutions in the set of three L-CDRs of the ABD) in the starting antigen-binding protein construct, wherein the method results in the generation of an antigen-binding protein construct having one or both of: (a) an increased (e.g., at least a 0.1-fold increase to about a 100-fold increase, or any of the subranges of this range described herein) ratio of the dissociation rate of the ABD at a pH of about 4.0 to about 6.5 to the dissociation rate at a pH of about 7.0 to about 8.0, as compared to the starting antigen-binding protein construct, and (b) an increased (e.g., at least a 0.1-fold increase to about a 100-fold increase, or any of the subranges of this range described herein) ratio the dissociation constant (KD) of the ABD at a pH of about 4.0 to about 6.5 to the KD at a pH of about 7.0 to about 8.0, as compared to the starting antigen-binding protein construct. [0333] The invention is further described in the following examples, which do not limit the scope of the invention described in the claims. EXAMPLES Example 1. Generation of DLL3 binders and engineering of pH binding dependence [0334] The methods disclosed herein are useful for characterizing antigen binding protein constructs (ABPCs) including determining whether a given ABPC variant exhibits pH-dependent antigen binding relative to a starting (e.g., non-modified) control ABPC. [0335] Briefly here, pH- or non-pH-engineered ABPCs specific for DLL3 are generated using two methods. In the first approach, published monoclonal antibodies against DLL3 are used as a Attorney Docket No.: 45395-0068WO1 starting template for introduction of additional mutations that allow engineering of pH-dependent binding to DLL3 and i) enhanced endolysosomal accumulation of a conjugated toxin, as well as ii) enhanced DLL3 recycling to the cell surface. The second approach involves discovery of de novo ABPCs specific for DLL3 via antibody display methods from naive libraries or libraries with defined CDR compositions and screening under conditions designed for selection of pH- engineered ABPCs specific for DLL3. In either case, histidine residues play an important role in engineering pH-dependent binding proteins. [0336] Histidine residues are at least partially protonated at a pH below 6.5 owing to its pKa of 6.0. Therefore, if a histidine side chain in an ABD participates in an electrostatic binding interaction with its antigen it will start to turn positively charged at a pH at or below 6.5. This could either weaken or enhance the binding affinity of the interaction at a pH below 6.5, based on the corresponding charge of and interactions with the antigen epitope. Thus, systematic introduction of histidines into antibody complementarity determining regions (CDRs) in an antibody or other binder library (e.g., an scFv library) can be used to identify substitutions that will affect an ABD’s interaction with an antigen at lower pH values. The first approach therefore involves histidine-scanning of variable region sequences of published monoclonal antibodies to identify pH-dependent variants. [0337] Multiple DLL3-binding monoclonal antibodies have been described in the literature and can be used as a template for engineering pH-dependent binding. Briefly, for a subset of the antibody sequences, CDRs in each chain are identified using the methods described by Kabat et al (Kabat et al. (1992) Sequences of Proteins of Immunological Interest (DIANE publishing) and IMGT (Lefranc MP (1999) "The IMGT unique numbering for Immunoglobulins, T cell receptors and Ig-like domains" The Immunologist 7, 132-136), and for each CDR, residues falling under either or both Kabat and IMGT CDR definitions were called as CDR residues. To engineer pH- dependent sequence variants, individual amino acid residues within the heavy chain and/or light chain CDRs are systematically substituted with a histidine, one at a time. In cases where the starting CDR residue is a histidine, it is mutated to an alanine. Antibody variants with only one histidine or alanine mutation in a heavy/light chain CDR are generated by co-transfection of Expi293 cells with a) one heavy chain or light chain sequence variant, and b) the corresponding starting ABPC (e.g., the starting DLL3-binding monoclonal antibody) light chain or heavy chain, respectively, using methods known to the art. After allowing for a period of protein expression, Attorney Docket No.: 45395-0068WO1 cell culture supernatants are collected, quantified, and the pH dependence of the variant is evaluated using biolayer interferometry (BLI) or other methods known to the art. Briefly, cell culture supernatants are normalized to an antibody expression level of 50 µg/mL, and captured on an anti-human Fc sensor (Forte Bio). A baseline is established using 1X kinetics buffer (Forte Bio), and the sensor is associated with 100 nM of DLL3 in 1X PBS at pH 7.4 for 300 sec to generate an association curve. In the dissociation phase, the antibody-antigen complex on the sensor is exposed to 1X PBS at either pH 5.5 or pH 7.4 for 300-500 sec. Association and dissociation phase curves are examined for the starting ABPC antibody and each corresponding antibody variant at pH 5.5 and pH 7.4 to inform on two criteria: a) enhanced dissociation (i.e., higher koff values) at pH 5.5 due to histidine or alanine substitution compared to the starting ABPC, and b) reduced dissociation at pH 7.4 (i.e., lower koff values) compared to pH 5.5 in the antibody variant itself and with the starting ABPC. Variants that show either enhanced dissociation at pH 5.5 or reduced dissociation at pH 7.4 or both are selected for further analysis. It is also noted that while some histidine and alanine mutations obliterate DLL3 binding, others are tolerated with little (e.g., less than 1-fold change in KD or dissociation rate) or no change in DLL3 binding kinetics. Especially because histidine is a large, positively charged amino acid, these histidine variants and alanine variants with no change are noted as positions that may tolerate a wide range of mutations and lead to antibodies with different sequence but similar binding properties, a designation that is not otherwise apparent. The variants selected for further analysis are expressed at a larger scale and purified using protein A affinity chromatography. Binding kinetics (kon and koff) of the purified starting ABPC and variant antibodies are measured at pH 5.5 and pH 7.4 using Biacore (GE Healthcare). The ratio of the antibody’s rate of dissociation (koff at pH 7.4 divided by koff at pH 5.5) is also used as a quantitative assessment of pH-dependent binding; similarly, the dissociation constant KD is calculated at both pH 5.5 and pH 7.4 as koff divided by kon and the ratio of the antibody’s dissociation constant (KD at pH 7.4 divided by KD at pH 5.5) is also used as a quantitative assessment of pH-dependent binding. Antibodies with a rate of dissociation ratio less than that of the starting ABPC and/or a dissociation constant ratio less than that of the starting ABPC are selected for further assessment of combinatorial substitutions. Favorable histidine and/or alanine amino acid positions can also be combined to enhance pH dependence; this can be done by, e.g., combinatorially or rationally combining histidine and/or alanine substitutions on a given heavy or light chain that individually improve pH dependence, by, e.g., Attorney Docket No.: 45395-0068WO1 combinatorially or rationally combining modified heavy and light chains such that histidine and/or alanine substitutions are present on both chains, or combinations thereof. Such combinatorial variants are generated and tested/analyzed for differential pH dependence using the methods and protocols described herein, or others known to the art. Antibody variants that have the lowest rate of dissociation ratios and/or dissociation constant ratios are selected as candidates for further analysis (hereafter referred to as “pH-engineered ABPCs specific for DLL3”). [0338] The second method for selection of pH-engineered ABPCs specific for DLL3 involves either screening libraries to identify de novo pH-dependent ABPCs specific for DLL3 or ABPCs that could serve as templates for engineering pH-dependent binding as described herein. Two types of libraries can be used for these selections: naive phage/yeast display antibody libraries (e.g., Fab, scFv, VHH, VL, or others known to the art) or phage/yeast display libraries where CDRs have been mutated to express a subset of amino acid residues. Libraries are screened against soluble recombinant DLL3 extracellular domains using methods known to the art with positive selection for variants that bind weakly (e.g., are eluted from beads) at pH 5.0 and bind strongly (e.g., are bound to beads) at pH 7.4. Three rounds of selections are performed. The final round of binders are screened using ELISA for binding to human DLL3 and cyno DLL3 and mouse DLL3 or via mean fluorescence intensity (MFI) in flow cytometric analysis. If more binders with cyno or murine cross-reactivity are desired, the final selection round can instead be performed on cyno DLL3 or murine DLL3. Selected binding proteins are subcloned into mammalian expression vectors and expressed as either full IgG proteins or Fc fusions in Expi293 cells. BLI analysis is performed as described herein for selection of pH-dependent binder variants and confirmed using Biacore. Example 2. In vitro demonstration of pH-dependent binding to DLL3, pH-dependent release of DLL3, enhanced endolysosomal delivery in DLL3+ cells, and increased DLL3 antigen density in DLL3+ cells after exposure to pH-engineered ABPCs specific for DLL3 as compared to control ABPCs specific for DLL3. [0339] As discussed herein, pH-engineered ABPCs specific for DLL3 exhibit the desirable property of decreased DLL3 binding at acidic pH (e.g., pH 5.0, pH 5.5), but enhanced binding at higher pH (e.g., pH 7.4), which enhances their accumulation in endolysosomes under physiological conditions. Attorney Docket No.: 45395-0068WO1 pH-dependent binding to DLL3 on cells [0340] To demonstrate that pH-engineered ABPCs specific for DLL3 binds cell surface DLL3 at neutral pH, a cell surface binding assay is performed. A panel of human cells that are DLL3+ is assembled. Methods of identifying and quantifying gene expression (e.g., DLL3) for a given cell line are known to the art, and include, e.g., consulting the Cancer Cell Line Encyclopedia to ascertain the expression level and/or mutation status of a given gene in a tumor cell line), rtPCR, microarray, or RNA-Seq analysis, or cell staining with anti-DLL3 antibodies known in the art. Cells are seeded at approximately 5-10,000 per well in 150 µL of pH 7.4 culture medium and incubated at 37 ℃ for 5 minutes at several doses (e.g., a two-fold dilution series) from 1 pM to 1 µM with one of the following antibodies: a known, control ABPC specific for DLL3, the pH- engineered ABPC specific for DLL3, and an appropriate negative isotype control mAb (e.g., Biolegend Purified Human IgG1 Isotype Control Recombinant Antibody, Cat#403501). Prior to the onset of the experiment, the binding properties of all antibodies are validated using methods known to the art. Following the 5 minute incubation, cells are fixed with 4% formaldehyde (20 min at room temperature) and incubated with an appropriate fluorophore-labeled secondary antibody (e.g., ThermoFisher Mouse anti-Human IgG1 Fc Secondary Antibody, Alexa Fluor 488, Cat#A-10631) for 60 minutes. Unbound reagents are washed with a series of PBS washes, and the cell panels are imaged using confocal microscopy. Upon analysis of the images, significant fluorescence can be observed on the surface of cells bound with the known, control ABPC specific for DLL3 as well as the pH-engineered ABPC specific for DLL3, but little surface binding can be observed for the isotype negative control. To isolate the effect of pH on surface binding, the same experiment is repeated twice, with the primary antibody incubation taking place at sequentially lower pH (e.g., pH 6.5 and 5.5 and 5.0). Analysis of the resulting confocal microscopy images can show significant fluorescence on the surface of cells bound with all mAbs tested, excepting the isotype negative control, and that this fluorescence decreases for the pH-engineered ABPC specific for DLL3 as the pH decreases. Alternatively, cells are analyzed for mean fluorescent intensity by flow cytometry using methods known in the art. A dissociation constant KD on cells at neutral pH of the antibodies analyzed is determined by nonlinear regression methods known in the art (e.g., a Scatchard plot). Taken together, the results can show that the pH engineering process results in the creation of a pH-engineered ABPC specific for DLL3 that is pH-dependent in its binding properties and that it more effectively binds at neutral pH as compared to more acidic pH. Other Attorney Docket No.: 45395-0068WO1 methods of assessing the pH dependence of the pH-engineered ABPCs specific for DLL3 are known in the art and include, e.g., using flow cytometry to measure ABPC surface binding. pH-dependent release of DLL3 in cells [0341] To demonstrate that pH-engineered ABPCs specific for DLL3 are capable of releasing DLL3 at low pH after binding at a neutral pH, a variant of the cell surface binding assay described above is performed using methods known to the art (e.g., as generally described in Gera N. (2012) PLoS ONE 7(11): e48928). Briefly, an appropriate DLL3+ cell line is harvested and 50,000 cells per well are plated in a U-Bottomed 96-well microplate. Three conditions are tested; binding and secondary staining at pH 7.4, binding and secondary staining at pH 5.0, and binding at pH 7.4 followed by release at pH 5.0 for 30 minutes and secondary staining at pH 7.4. Both pH-engineered ABPCs specific for DLL3 as well as a control ABPC specific for DLL3 are tested. The cells are washed two times with 200 μL of FACS buffer (1x PBS containing 3% Fetal Bovine Serum) at either pH 7.4 or 5.0 depending on the condition being tested. The purified protein samples are diluted into FACS buffer of the appropriate pH and added to the cells and allowed to bind for one hour on ice. After incubation with the primary antibodies the pH 7.4 and pH 5.0 conditions are washed twice as before, and then 100 µl of secondary rat anti-human Fc AF488 (BioLegend 410706) or other appropriate antibody, diluted 1:50, or anti Myc-Tag mouse mAb-AF488 (Cell Signaling Technologies 2279S) diluted 1:50 is added in FACS buffer of the appropriate pH, and incubated for 30 minutes on ice. The pH 5.0 release condition is washed twice with FACS buffer pH 7.4 and then resuspended in 100 µl of FACS buffer pH 5.0 and incubated on ice for 30 minutes, followed by secondary staining in FACS buffer pH 7.4 as described for the other conditions. The plates are washed twice as before and resuspended in 1% paraformaldehyde in the appropriate FACS buffer to fix them for flow cytometry analysis. All conditions are read on a flow cytometer (Accuri C6, BD Biosciences). Binding is observed as a shift in the FLI signal (as a MFI) versus secondary alone. Upon analysis of the data, it can be determined that both the pH-engineered ABPC specific for DLL3 as well as the control ABPC specific for DLL3 effectively bind the surface of DLL3+ cells at neutral pH, but the pH-engineered ABPC specific for DLL3 binds poorly at pH 5.0; similarly, it can be determined that the pH-engineered ABPC specific for DLL3 binds effectively at pH 7.4, but then releases/unbinds DLL3 at pH 5.0. Attorney Docket No.: 45395-0068WO1 Enhanced endolysosomal delivery in DLL3+ cells of pH-engineered ABPCs specific for DLL3 as compared to control ABPCs specific for DLL3 (pHrodo) [0342] To verify and demonstrate that ABPCs specific for DLL3 achieve endolysosomal localization following cellular uptake, an internalization assay is performed using methods known to the art (e.g., Mahmutefendic et al., Int. J. Biochem. Cell Bio., 2011). Briefly, as described herein, a panel of human cells that express DLL3 highly is assembled using methods known to the art. Cells are plated, washed three times with PBS, and incubated at 37 °C for 60 minutes in media at neutral pH, with added concentrations of 2 micrograms per milliliter of a known, control ABPC specific for DLL3 (e.g., as described herein), the pH-engineered ABPC specific for DLL3, and an appropriate negative isotype control mAb (e.g., as described herein). In a subset of cells, validation of antibody internalization and endosomal localization is performed using methods known to the art; e.g., cells are fixed in 4% formaldehyde as described herein, permeabilized using TWEEN 20 or other methods known to the art (Jamur MC et al (2010) Permeabilization of cell membranes, Methods Mol Biol.588:63-6), additionally stained with an endosomal marker, e.g., a fluorescent RAB11 antibody (RAB11 Antibody, Alexa Fluor 488, 3H18L5, ABfinity™ Rabbit Monoclonal), stained with an appropriate fluorescently labeled anti-human secondary antibody (e.g., as described herein), and imaged using confocal fluorescence microscopy, as described herein. Analysis of the confocal images can be used to show that both the pH-engineered ABPC specific for DLL3 as well as the control ABPC specific for DLL3 are internalized and accumulate in the endolysosomes. [0343] To demonstrate that pH-engineered ABPCs specific for DLL3 achieve enhanced endolysosomal accumulation relative to a control ABPC specific for DLL3, a pHrodo-based internalization assay is performed using both a known, control ABPC specific for DLL3 as well as the pH-engineered ABPC specific for DLL3. The assay makes use of pHrodo™ iFL (P36014, ThermoFisher), a dye whose fluorescence increases with decreasing pH, such that its level of fluorescence outside the cell at neutral pH is lower than its level of fluorescence inside the acidic pH environment of endolysosomes. Briefly, an appropriate DLL3+ cell line is suspended in its recommended media and plated in a 24-well plate at a density of 2,000,000 cells/mL, 1 mL per well. While keeping the cells on ice, 1 mL of 2x pHrodo iFL-labeled antibody is added to each well, the well is pipetted/mixed five times, and the plate is incubated in a light-protected environment for 45 minutes, on ice. An identical but separate plate is also incubated on ice that is Attorney Docket No.: 45395-0068WO1 meant as a no-internalization negative control. Following this incubation, the experimental plate is moved to a 37 °C incubator, the negative control plate is kept on ice to slow or block internalization, and samples are taken at designated time points to create an internalization time course. Samples are placed into a U-bottom 96-well plate, and internalization is quenched via addition of 200 µL/well of ice-cold FACS buffer. The plates are spun down at 2000xg for 2 minutes, resuspended in 200 µL ice-cold FACS buffer, spun down again, and resuspended in FACS buffer a second time. Finally, the samples are loaded into a flow cytometer for read-out of cellular pHrodo fluorescence using excitation and emission wavelengths consistent with the excitation and emission maxima of the pHrodo iFL Red dye (566 nm and 590 nm, respectively). Upon completion of the flow cytometry experiment and analysis of the data, it can be observed that cells treated with the pH-engineered ABPC specific for DLL3 have a higher pHrodo iFL signal relative to a known, control ABPC specific for DLL3, indicating that pH-engineered ABPCs specific for DLL3 achieve enhanced endolysosomal accumulation relative to a control ABPC specific for DLL3. [0344] Alternatively, to demonstrate that pH-engineered ABPCs specific for DLL3 achieve enhanced endolysosomal accumulation relative to a control ABPC specific for DLL3, a variation of the above-described experiment is performed. DLL3+ cells are plated, washed three times with PBS, and incubated at 37 °C for 60 minutes in media at neutral pH with added concentrations of 2 µg/mL of either pH-engineered ABPC specific for DLL3 or control ABPC specific for DLL3. Following incubation, cells are washed three times with PBS, fixed and permeabilized, and stained with a panel of appropriately selected antibodies that bind late endosomal markers as well as lysosomes (e.g., RAB7, and LAMP1; Cell Signaling Technology, Endosomal Marker Antibody Sampler Kit #12666; AbCam, Anti-LAMP2 antibody [GL2A7], ab13524). After primary antibody staining, cells are stained with an appropriate mixture of fluorescently labeled secondary antibodies (e.g., Goat Anti-Human IgG (H&L) Secondary Antibody (Alexa Fluor 647) Cat# A- 21445, and Abcam Goat Anti-Rabbit IgG H&L (Alexa Fluor 488), Cat# ab150077), imaged using confocal fluorescence microscopy, and regions of co-localization of signal from DLL3-specific antibodies and endosomal markers are visualized and quantified. Upon analysis of the data, it can be revealed that there is increased co-localization of endolysosomal and DLL3-specific antibody signal in wells treated with the pH-engineered ABPCs specific for DLL3 as compared to wells treated with control ABPC specific for DLL3, and can thereby demonstrate that pH-engineered Attorney Docket No.: 45395-0068WO1 ABPCs specific for DLL3 achieve enhanced endolysosomal accumulation relative to control ABPC specific for DLL3. Increased DLL3 antigen density in DLL3+ cells after exposure to pH-engineered ABPCs specific for DLL3 as compared to control ABPCs specific for DLL3 [0345] To demonstrate that treatment of cells with the pH-engineered ABPCs specific for DLL3 does not result in a detectable reduction of the level of DLL3 on the surface of cells exposed to the pH-engineered ABPCs specific for DLL3, or that said treatment results in less of a reduction of the level of DLL3 on the surface of cells exposed to the pH-engineered ABPC specific for DLL3 versus a control ABPC specific for DLL3, an antigen density study is performed using flow cytometry. Briefly, 4.0x10^5 cells that express DLL3 are plated per well in a 96-well plate in 100 µL media. Cells are treated with a titration from 1 pM to 1 µM of i) pH-engineered ABPCs specific for DLL3, ii) a first control ABPC specific for DLL3, iii) an appropriate isotype control, and iv) an untreated control. Cells are incubated for 2 hours at 37 °C, at which point all cells are incubated with 200 nM of a fluorophore-labeled second control ABPC specific for DLL3 (e.g., as described herein) which has a different epitope (as determined by, e.g., competitive binding studies on cells) than either the first control ABPC specific for DLL3 or the pH-engineered ABPCs specific for DLL3 for 30 minutes at 4 °C. Following this 30-minute incubation, the MFI (MFI) of all cells is read out using, e.g., flow cytometry, using methods known to one of ordinary skill in the art. In parallel, a quantitative standard curve that can be used to quantify the presence of DLL3 on the surface of treated cells as a function of MFI is generated using a commercially available quantification kit (e.g., BD Biosciences PE Phycoerythrin Fluorescence Quantitation Kit, catalog #340495); the quantitative standard curve is created by following the manufacturer’s instructions. Other methods of determining the absolute number of DLL3 on the cell surface are known in the art and include, e.g., use of radioisotopically labeled reagents. Upon analysis of the data, it can be revealed that at least one antibody concentration, cells treated with a control ABPC specific for DLL3 experience a reduction of the level of DLL3 on their surface, whereas cells treated with pH- engineered ABPCs specific for DLL3 experience a significantly smaller reduction or no reduction at all, both relative to the isotype and untreated controls. Example 3. Conjugation of ABPCs specific for DLL3 to cytotoxic drugs [0346] An antigen-binding protein construct conjugate (ADC) is made comprising the DLL3- binding IgG (hereafter, DLL3-IgG) described herein linked to monomethyl auristatin E (MMAE) Attorney Docket No.: 45395-0068WO1 via a valine-citrulline (vc) linker (hereafter, DLL3-IgG-DC). Conjugation of the antigen-binding protein construct with vcMMAE begins with a partial reduction of the DLL3-IgG followed by reaction with maleimidocaproyl-Val-Cit-PABC-MMAE (vcMMAE). The DLL3-IgG (20 mg/mL) is partially reduced by addition of TCEP (molar equivalents of TCEP:mAb is 2:1) followed by incubation at 0° C overnight. The reduction reaction is then warmed to 20° C. To conjugate all of the thiols, vcMMAE is added to a final vcMMAE:reduced Cys molar ratio of 1:15. The conjugation reaction is carried out in the presence of 10% v/v of DMSO and allowed to proceed at 20° C for 60 minutes. [0347] After the conjugation reaction, excess free N(acetyl)-Cysteine (2 equivalents vs. vcMMAE charge) is added to quench unreacted vcMMAE to produce the Cys-Val-Cit-MMAE adduct. The Cys quenching reaction is allowed to proceed at 20° C for approximately 30 minutes. The Cys-quenched reaction mixture is purified as per below. The above conjugation method can also be used to conjugate maleimidocaproyl monomethylauristatin F (mcMMAF) to an antigen- binding protein construct. [0348] The DLL3-IgG-DC is purified using a batch purification method. The reaction mixture is treated with the appropriate amount of water washed Bu-HIC resin (ToyoPearl; Tosoh Biosciences), i.e., seven weights of resin is added to the mixture. The resin/reaction mixture is stirred for the appropriate time, and monitored by analytical hydrophobic interaction chromatography for removal of drug conjugate products, filtered through a coarse polypropylene filter, and washed by two bed volumes of a buffer (0.28 M sodium chloride, 7 mM potassium phosphate, pH 7). The combined filtrate and rinses are combined and analyzed for product profile by HIC HPLC. The combined filtrate and rinses are buffer exchanged by ultrafiltration/diafiltration (UF/DF) to 15 mM histidine, pH 6 with 10 diavolumes 15 nM histidine buffer. [0349] A similar protocol can be used to conjugate DNA toxins such as SG3249 and SGD-1910 to DLL3-IgG (see Tiberghien AC et al (2016) Design and Synthesis of Tesirine, a Clinical Antibody−Drug Conjugate Pyrrolobenzodiazepine Dimer Payload, ACS Med Chem Lett 7:983−987). Briefly, for SG3249, DLL3-IgG (15 mg, 100 nanomoles) is diluted into 13.5 mL of a reduction buffer containing 10 mM sodium borate pH 8.4, 2.5 mM EDTA and a final antibody concentration of 1.11 mg/mL. A 10 mM solution of TCEP is added (1.5 molar equivalent/antibody, 150 nanomoles, 15 microliters) and the reduction mixture is heated at +37 °C for 1.5 hours in an incubator. After cooling down to room temperature, SG3249 is added as a DMSO solution (5 Attorney Docket No.: 45395-0068WO1 molar equivalent/antibody, 500 nanomoles, in 1.5 mL DMSO). The solution is mixed for 1.25 hours at room temperature, then the conjugation is quenched by addition of N-acetyl cysteine (1 micromole, 100 microliters at 10 mM), and injected into an AKTA™ Pure FPLC using a GE Healthcare HiLoadTM 26/600 column packed with Superdex 200 PG, and eluted with 2.6 mL/min of sterile-filtered phosphate-buffered saline (PBS). Fractions corresponding to the DLL3-IgG-DC monomer peak are pooled, concentrated using a 15mL Amicon Ultracell 50KDa MWCO spin filter, analyzed and sterile-filtered. UHPLC analysis on a Shimadzu Prominence system using a Phenomenex Aeris 3.6u XB-C18 150 x 2.1 mm column eluting with a gradient of water and acetonitrile on a reduced sample of DLL3-IgG-DC at 280 nm and 330 nm (SG3249 specific) can show a mixture of light and heavy chains attached to several molecules of SG3249, consistent with a drug-per-antibody ratio (DAR) of 1 to 4 molecules of SG3249 per antibody. UHPLC analysis on a Shimadzu Prominence system using a Phenomenex Yarra 3u SEC-3000300 mm x 4.60 mm column eluting with sterile-filtered SEC buffer containing 200 mM potassium phosphate pH 6.95, 250 mM potassium chloride and 10% isopropanol (v/v) on a sample of DLL3-IgG-DC at 280 nm can show a monomer purity of over 90% with no impurity detected. UHPLC SEC analysis allows determination of final DLL3-IgG-DC yield of greater than 30%. [0350] Alternatively, methods to conjugate toxins to antibodies via lysine residues are known in the art (e.g., see Catcott KC et al (2016) Microscale screening of antibody libraries as maytansinoid antibody-drug conjugates, MAbs 8:513-23). In addition, similar methods to the above can be used to conjugate drugs and toxins to non-IgG formats with disulfide bonds, such as Vh-Fcs. Example 4. Demonstration of enhanced cytotoxicity of ABPC ADCs specific for DLL3 in DLL3+ cells as compared to a control ABPC ADC specific for DLL3 [0351] The cytotoxic activity of both novel candidate ABPC ADCs specific for DLL3 (e.g., a novel or pH-engineered DLL3-IgG-DC) and control ABPC ADCs specific for DLL3 (e.g., a control ABPC DLL3-IgG-DC) are separately evaluated on a panel of DLL3+ cell lines expressing a variety of antigen densities (e.g., as described herein) and a DLL3-negative cell line, selected using the methods described herein, and, optionally, cells expressing transgenic DLL3, e.g., HEK293 cells transfected with DLL3 using methods known in the art (e.g., Expi293™ Expression System Kit ThermoFisher Catalog number: A14635). For purposes of validation, prior to use, all cell lines are tested for expression of DLL3 using methods known to the art, e.g., qPCR, flow cytometry, mRNA RPKM, and antibody staining using anti-DLL3 antibodies known to the art Attorney Docket No.: 45395-0068WO1 (e.g., as described herein) followed by visualization of the stain using fluorescence microscopy, immunohistochemistry, flow cytometry, ELISA, or other methods known to the art. To evaluate the cytotoxicity of compounds, cells are seeded at approximately 10-40,000 per well in 150 microliters of culture medium, then treated with graded doses of compounds from 1pM to 1 µM in quadruplicates at the initiation of the assay. Cytotoxicity assays are carried out for 96 hours after addition of test compounds. Fifty microliters of resazurin dye are added to each well during the last 4 to 6 hours of the incubation to assess viable cells at the end of culture. Dye reduction is determined by fluorescence spectrometry using the excitation and emission wavelengths of 535 nm and 590 nm, respectively. For analysis, the extent of resazurin reduction by the treated cells is compared to that of untreated control cells, and percent cytotoxicity is determined. Alternatively, a WST-8 kit is used to measure cytotoxicity per the manufacturer’s instructions (e.g., Dojindo Molecular Technologies Catalog# CCK-8). IC50, the concentration at which half-maximal killing is observed, is calculated using curve-fitting methods known in the art. Upon analysis of the data, it can be determined that pH-engineered and control ABPC ADCs specific for DLL3 are substantially cytotoxic to one or more DLL3+ cell line, but less toxic to DLL3-negative cells. It also can be determined that pH-engineered ADCs specific for DLL3 are more cytotoxic to one or more DLL3+ cell lines than control ABPC ADCs specific for DLL3 because: a) they show greater depth of killing at one or more concentrations or, b) they show lower IC50 or, c) they show a greater ratio of their dissociation constant KD on cells at neutral pH (as described herein) divided by their IC50 on those same cells. Each of the foregoing techniques may be used to characterize anti-DLL3 ABPCs irrespective of whether they have been subjected to pH-engineering. [0352] Additionally, the cytotoxic activity of ABPCs specific for DLL3 can be measured in a secondary ADC assay. Secondary ADC assays are known in the art (e.g., Moradec Cat# αHFc- NC-MMAF and Cat# αHFc-CL-MMAE, and associated manufacturer’s instructions). Briefly, the assay is carried out as in the previous paragraph, except the ABPC specific for DLL3 is substituted for the ADC specific for DLL3, and to evaluate the cytotoxicity of compounds, cells are seeded at approximately 10-40,000 per well in 150 microliters of culture medium, then treated with graded doses of ABPC specific for DLL3 from 1pM to 1 µM (final concentration in culture medium, having been pre-mixed with 100nM, final concentration in culture medium, of Moradec Cat# αHFc-NC-MMAF secondary ADC reagent and pre-incubated at 37°C for 30min before addition of the mixture to the culture medium) in quadruplicates at the initiation of the assay. Attorney Docket No.: 45395-0068WO1 [0353] The cytotoxic activity of pH-engineered ADCs specific for DLL3 and control ABPC ADCs specific for DLL3 conjugates, as well as ABPCs specific for DLL3 in a secondary ADC assay, are additionally measured by a cell proliferation assay employing the following protocol (Promega Corp. Technical Bulletin TB288; Mendoza et al., Cancer Res.62:5485-5488, 2002): [0354] 1. An aliquot of 100 microliters of cell culture containing about 104 cells (e.g., DLL3+ cells as described herein) in medium is deposited in each well of a 96-well, opaque-walled plate. [0355] 2. Control wells are prepared containing medium and without cells. [0356] 3. ADC specific for DLL3 is added to the experimental wells at a range of concentrations from 1pM-1uM and incubated for 1-5 days. Alternatively, in a secondary ADC assay, 100nM secondary ADC reagent (final concentration in culture medium, Moradec Cat# αHFc-NC-MMAF) and ABPC specific for DLL3 at a range of concentrations from 1pM-1uM (final concentration in culture medium) are pre-mixed and pre-incubated at 37°C for 30min before addition of the mixture to the culture medium, and incubated for 1-5 days. [0357] 4. The plates are equilibrated to RT for approximately 30 minutes. [0358] 5. A volume of CellTiter-Glo Reagent equal to the volume of cell culture medium present in each well is added. [0359] 6. The contents are mixed for 2 minutes on an orbital shaker to induce cell lysis. [0360] 7. The plate is incubated at RT for 10 minutes to stabilize the luminescence signal. [0361] 8. Luminescence is recorded; reported in graphs as RLU = relative luminescence units. Example 5. Demonstration of enhanced toxin liberation of ABPC ADCs specific for DLL3 in DLL3+ cells as compared to a control ABPC ADC specific for DLL3 [0362] The novel ADCs and/or pH-engineered ADCs specific for DLL3 (e.g., a pH-engineered DLL3-IgG-DC) can also demonstrate increased toxin liberation in DLL3+ cells as compared to a control ABPC ADC specific for DLL3 (e.g., a control ABPC DLL3-IgG-DC). After treatment of DLL3+ cells with pH-engineered and control ABPC ADCs specific for DLL3 as described herein, an LC-MS/MS method is used to quantify unconjugated (i.e., liberated) MMAE in treated DLL3+ cells (Singh, A.P. and Shah, D.K. Drug Metabolism and Disposition 45.11 (2017): 1120-1132.) An LC-MS/MS system with electrospray interphase and triple quadrupole mass spectrometer is used. For the detection of MMAE, a XBridge BEH Amide column (Waters, Milford, MA) is used with mobile phase A as water (with 5 mM ammonium formate and 0.1% formic acid) and mobile phase B as 95:5 acetonitrile/water (with 0.1% formic acid and 1 mM ammonium formate), using Attorney Docket No.: 45395-0068WO1 a gradient at a flow rate of 0.25 mL/min at 40 °C. The total duration of the chromatographic run is 12 minutes, where two MRM scans (718.5/686.5 and 718.5/152.1 amu) are monitored. Deuterated (d8) MMAE (MCE MedChem Express, Monmouth Junction, NJ) is used as an internal standard. First, an equation for quantifying unconjugated MMAE in a biological sample is derived by dividing the peak area for each drug standard by the peak area obtained for the internal standard. The resultant peak area ratios are then plotted as a function of the standard concentrations, and data points are fitted to the curve using linear regression. Three QC samples are included in the low, middle, and upper ranges of the standard curve to assess the predictive capability of the developed standard curve. The standard curves obtained are then used to deduce the observed concentrations of MMAE in a biologic sample. For measurement of MMAE concentration, treated cell samples are pelleted and reconstituted in fresh media to a final concentration of 0.25 million cells/100 μL. Samples are spiked with d8-MMAE (1 ng/mL) before performing cell lysis by the addition of a 2-fold volume of ice-cold methanol followed by freeze-thaw cycle of 45 minutes at -20 °C. The final cell lysate is obtained by centrifuging the samples at 13,000 rpm for 15 minutes at 4 °C followed by collection of supernatant. For the preparation of standards and QC samples, a fresh cell suspension (0.25 million/100 μl) is spiked with known concentrations of MMAE and internal standard (d8-MMAE) before a procedure similar to the cell lysis mentioned above. The resulting cell lysates are then evaporated and reconstituted in mobile phase B before injection into LC-MS/MS. The concentration of unconjugated MMAE in lysates of DLL3+ cells treated with pH-engineered ADCs specific for DLL3 is observed to be greater than that in DLL3+ cells treated with control ABPC ADC specific for DLL3. [0363] For tubulin-inhibiting toxins, toxin liberation is also assessed by monitoring of cell viability and cell cycle phase. ~2.0x10^5 DLL3+ cells are plated in a 96-well flat bottom plate and treated with pH-engineered and control ABPC ADCs specific for DLL3 as described herein. After treatment, cells are transferred to a 96-round bottom plate, and the plate is centrifuged at 400 rcf for 2 min to decant supernatant. Decanted cells are stained with Live/Dead eFluor 660. Cells are then centrifuged and washed with FACS buffer (PBS with 2% FBS), after which cell cycle distribution is analyzed with a BD Cycletest™ Plus DNA Kit (cat # 340242). Briefly, cells are re- suspended in 76 µl Solution A and incubated for 10 min at room temperature.61 µL Solution B is then added, and cells are incubated for another 10 min at room temperature. Finally, 61 µL of cold Solution C is added, and cells are again incubated for 10 min at room temp. Immediately after the Attorney Docket No.: 45395-0068WO1 last incubation step, cells are analyzed by flow cytometry (without washing) at a flow rate of 10 µL/sec. Increased G2/M-phase arrest can be observed with exposure to pH-engineered ADCs specific for DLL3 as compared to control ABPC ADC specific for DLL3. [0364] For DNA-damaging toxins (e.g., pyrrolobenzodiazepine or “PBD”), DNA damage is assessed by measuring the phosphorylated histone H2AX (γH2AX). H2AX is normally phosphorylated in response to double-strand breaks in DNA; however, increased levels γH2AX may also be observed as a result of treatment with DNA-cross-linking toxins such as PBD or cisplatin (Huang, X. et al. 2004, Cytometry Part A 58A, 99–110). DLL3+ cells are treated with pH-engineered and control ABPC ADCs specific for DLL3 as described herein. After treatment, cells are rinsed with PBS, and then fixed in suspension in 1% methanol-free formaldehyde (Polysciences, Warrington, PA) in PBS at 0 °C for 15 min. Cells are resuspended in 70% ethanol for at least 2 h at -20°C. Cells are then washed twice in PBS and suspended in 0.2% Triton X-100 (Sigma) in a 1% (w/v) solution of BSA (Sigma) in PBS for 30 min to suppress nonspecific Ab binding. Cells are centrifuged again (200 g, 5 min) and the cell pellet is suspended in 100 µL of 1% BSA containing 1:800 diluted anti-histone γH2AX polyclonal Ab (Trevigen, Gaithersburg, MD). The cells are then incubated overnight at 4 °C, washed twice with PBS, and resuspended in 100 µL of 1:30 diluted FITC-conjugated F(ab’)2 fragment of swine anti-rabbit immunoglobulin (DAKO, Carpinteria, CA) for 30 min at room temperature in the dark. The cells are then counterstained with 5 µg/mL of PI (Molecular Probes, Eugene, OR) dissolved in PBS containing 100 µg/mL of DNase-free RNase A (Sigma), for 20 min at room temperature. Cellular fluorescence of the FITC γH2AX signal and the PI counterstain are measured using flow cytometry using methods known in the art. When comparing cells within the same stage of the cell cycle (based on total DNA content), treated DLL3+ cells can be observed to have an increased FITC γH2AX signal relative to untreated DLL3+ cells (which serve as a baseline). Furthermore, DLL3+ cells treated with pH-engineered ADCs specific for DLL3 can be observed to have a greater increase in levels of γH2AX over baseline than cells treated with a control ABPC ADC specific for DLL3. In addition to the γH2AX assay, DNA cross-linking can be more directly assessed with a Comet assay (Chandna, S. (2004) Cytometry 61A, 127–133). [0365] In addition, as disclosed herein, pH-engineered and control ABPCs can be assayed using the methods in this example without direct conjugation by performing a secondary ADC assay instead of using primary conjugated ADCs. Attorney Docket No.: 45395-0068WO1 Example 6. Demonstration of increased or decreased half-life of pH-engineered ABPCs specific for DLL3 as compared to a control ABPC specific for DLL3 [0366] One of the surprising aspects of the novel ABPCs specific for DLL3 (and any pH- engineered variants) described by the disclosure can be their ability to facilitate increased dissociation of ABPCs from the DLL3 within the endosome or lysosome resulting in a decreased or increased serum half-life relative to control ABPCs specific for DLL3 or ABPCs that are not specific for DLL3. To demonstrate these properties, a series of animal studies in mice and/or monkeys is performed using pH-engineered ABPC specific for DLL3 and control ABPC specific for DLL3 using methods known to the art (e.g., Gupta, P., et al. (2016), mAbs, 8:5, 991-997). Briefly, to conduct mouse studies, a single intravenous bolus (e.g., 5 mg/kg) of either pH- engineered ABPC specific for DLL3 or control ABPC specific for DLL3 is administered via tail vein to two groups of NOD SCID mice (e.g. Jackson Labs NOD.CB17-Prkdcscid/J Stock No: 001303) xenografted with a DLL3+ cell line (e.g., as described herein). Xenografted mice are prepared by growing 1-5 million DLL3+ cells in vitro and inoculating subcutaneously into the right flank of the mouse. Tumors are size matched at 300 mm3. Measurements of the length (L) and width (W) of the tumors are taken via electronic caliper and the volume is calculated according to the following equation: V=L×W^2/2. Blood samples are collected via retro-orbital bleeds from each group at each of the following time points: 15m, 30m, 1h, 8h, 24h, and 3d, 7d, 10d, 14d, 17d, 21d, and 28d. Samples are processed to collect serum, and antibody concentrations are quantified using ELISA or other methods known to the art (e.g., PAC assay or MAC assay; Fischer, S.K. et al. (2012), mAbs, 4:5, 623-631, utilizing, e.g., anti-human Fc antibody Jackson ImmunoResearch Labs, Cat# 109–006–006). Antibody concentrations of pH-engineered ABPC specific for DLL3 and control ABPC specific for DLL3 are plotted as a function of time. Upon analysis of the data, it can be observed that the pH-engineered ABPC specific for DLL3 has a significantly longer or shorter serum half-life relative to control ABPC specific for DLL3. If the pH-engineered and control ABPCs specific for DLL3 are cross-reactive with the mouse homolog of DLL3, a similar experiment can be repeated with non-xenografted mice. [0367] Optionally, if the pH-engineered and control ABPCs specific for DLL3 are cross-reactive with the cynomolgus monkey homolog of DLL3, a similar experiment can be performed on monkeys (e.g., cynomolgus monkeys). An equal number of male and female monkeys (e.g., n = 1-2 each) are administered a bolus of either pH-engineered ABPC specific for DLL3 or control Attorney Docket No.: 45395-0068WO1 ABPC specific for DLL3 at a dose of, e.g., 1 mg/kg via saphenous vein injection. Alternatively, several different doses of DLL3-binding protein are administered across a group of several monkeys. Blood samples are collected via the peripheral vein or femoral vein at intervals similar to those described above, and analyzed for the presence of either pH-engineered ABPC specific for DLL3 or control ABPC specific for DLL3 using methods known to the art (e.g., ELISA). Upon analysis of the data, it can be observed that pH-engineered ABPC specific for DLL3 has a significantly longer or shorter serum half-life relative to control ABPC specific for DLL3. In some cases, this effect is observed only in certain doses, whereas in others it is observed across doses. In particular cases, increased half-life is desirable, especially where less frequent patient dosing is advantageous. [0368] In addition, the half-life of pH-engineered and control ABPC ADCs specific for DLL3 can be assessed using the above methods by substituting pH-engineered and control ABPC ADCs specific for DLL3 for the pH-engineered and control ABPCs specific for DLL3 (i.e., studying the ABPCs after conjugation to a drug or toxin, as described herein). Example 7. Increased potency of ADCs specific for DLL3 vs. a control ABPC ADC specific for DLL3 in mouse xenograft models [0369] The enhanced anti-tumor activity of the novel ABPCs specific for DLL3 (and any pH- engineered variants) against DLL3+ tumors can be demonstrated in a subcutaneous xenograft model of DLL3+ cells. For the experiments, 1-5 million DLL3+ cells are grown in vitro and inoculated subcutaneously per mouse into the right flank of female immunodeficient (e.g., SCID- Beige or NOD scid) mice. Tumors are size matched at 100-200 mm3, and dosed intraperitoneally (IP) (1 dose given every ~4-7 days for a total of ~2-6 doses). Measurements of the length (L) and width (W) of the tumors are taken via electronic caliper and the volume is calculated according to the following equation: V=L×W^2/2. A bolus (e.g., 5 mg/kg) of either pH-engineered ADC specific for DLL3 or control ABPC ADC specific for DLL3 is administered via tail vein. Tumor growth inhibition (TGI) and tumor growth delay (TGD) and survival are significantly improved with administration of pH-engineered ADC specific for DLL3 compared to administration of control ABPC ADC specific for DLL3 at the same regimen. [0370] Optionally, spread of tumor cells into the various tissues is determined in sacrificed animals. Metastasis is measured according to Schneider, T., et al., Clin. Exp. Metas. 19 (2002) 571-582. Briefly, tissues are harvested and human Alu sequences are quantified by real-time PCR. Attorney Docket No.: 45395-0068WO1 Higher human DNA levels, quantified by real-time PCR, correspond to higher levels of metastasis. Levels of human Alu sequences (correlating to invasion of tumor cells into secondary tissue) are significantly lower in animals treated with pH-engineered ADC specific for DLL3, corresponding to reduced metastasis, compared to mice treated with control ABPC ADC specific for DLL3 at the same regimen. Alternatively, the enhanced anti-tumor activity of the pH-engineered ADC specific for DLL3 can be shown in DLL3+ patient-derived xenograft models. Example 8. Creation of a bispecific DLL3 bispecific ABPC and demonstration of exemplary properties as compared to a control bispecific ABPC [0371] To create an ABPC specific for DLL3 with modified toxicity and internalization properties, a bispecific antibody that binds two different epitopes on DLL3 is constructed. It is known in the art that biparatopic antibodies can show increased antigen-dependent internalization, and are therefore useful for applications such as antibody-drug conjugates (e.g., see Li et al (2016) A Biparatopic HER2-Targeting Antibody-Drug Conjugate Induces Tumor Regression in Primary Models Refractory to or Ineligible for HER2-Targeted Therapy, Cancer Cell 29:117-29). Briefly, a pH-engineered DLL3 x DLL3 bispecific, biparatopic ABPC specific for DLL3 is assembled using light chain/heavy chain pairs from two different pH- or non-pH-engineered ABPCs specific for DLL3, each of which binds a distinct epitope on DLL3 that does not overlap with the other epitope. A set of pH-engineered ABPCs specific for DLL3 that bind non-overlapping epitopes are discovered, e.g., using the methods described herein, or others known to one of ordinary skill in the art. Briefly, two binders are selected on the basis that they bind substantially different epitopes on DLL3, as determined by, e.g., a binding competition assay as in Abdiche YN et al (2009) Exploring blocking assays using Octet, ProteOn, and Biacore biosensors, Anal Biochem 386:172- 80. Alternatively, briefly, as described herein, cell culture supernatants of cells transfected with a first ABPC specific for DLL3 are normalized to an antibody expression level of 50 µg/mL, and captured on an anti-human Fc sensor (Forte Bio). A baseline is established using 1X kinetics buffer (Forte Bio), and the sensor is associated with 50 nM of DLL3 in 1X PBS (that has been mixed and pre-incubated for 30 min at 37 °C with a second ABPC specific for DLL3 transfection supernatant or the first ABPC specific for DLL3 transfection supernatant, both normalized to 50ug/mL) at pH 7.4 for 300 sec to generate an association curve. If the association rate in the presence of the second ABPC specific for DLL3 is significantly faster (as calculated by the instrument software, or as seen by an elevated level of association over time) than the association rate in the presence of the Attorney Docket No.: 45395-0068WO1 first ABPC specific for DLL3, then the second ABPC specific for DLL3 is deemed to bind a non- overlapping epitope of DLL3. Optionally, each antibody is screened for its internalization properties when bound to its epitope on a cell expressing DLL3, and well-internalizing antibodies are selected. Assays for determining the internalization rate of a molecule present on the surface of a cell are known to the art. See, e.g., Wiley et al. (1991) J. Biol. Chem.266: 11083-11094; and Sorkin and Duex (2010) Curr. Protoc. Cell Biol. Chapter, Unit-15.14; Vainshtein et al. (2015) Pharm Res. 32: 286-299. Once selected, heavy and light chain constructs with engineered mutations for heavy and light chain pairing (Spiess et al., “Alternative molecular formats and therapeutic applications of bispecific antibodies,” 2015) are synthesized for both arms. Bispecific ABPCs specific for DLL3 are produced by co-expression of corresponding heavy and light chain plasmids in, e.g., Expi293 cells. Cell culture supernatants are harvested and subjected to Protein A purification. Heterodimeric ABPCs specific for DLL3 are separated from homodimeric species via additional purification steps such as ion exchange chromatography, hydrophobic interaction chromatography, and mixed mode chromatography. The purified pH-engineered DLL3 x DLL3 bispecific, biparatopic ABPCs specific for DLL3 are characterized via mass spectrometry to confirm the purity and absence of homodimeric species and size exclusion chromatography to confirm the presence of monomeric antigen-binding protein construct species. For the product antibody, binding to the DLL3 is confirmed via Biacore analysis. Other methods of bispecific antibody production are known to the art and could also be used to create a bispecific antibody, e.g., the DLL3 x DLL3 bispecific, biparatopic ABPCs specific for DLL3 described herein (e.g., Labrijn et al (2014) “Controlled Fab-arm exchange for the generation of stable bispecific IgG1” Nature Protocols 9:2450–2463, accessed at Nature’s website, as would be apparent to one of ordinary skill in the art. Alternatively, instead of a DLL3 x DLL3 ABPC specific for DLL3, a pH- engineered DLL3 x BINDER ABPC specific for DLL3 can be constructed using similar methods apparent to one skilled in the art, where BINDER is any antibody that has been published in the art or discovered using methods like those herein or those known in the art (e.g., display-based or immunization-based methods). [0372] Next, exemplary properties of pH-engineered DLL3 x DLL3 ABPCs specific for DLL3 can be demonstrated using the methods described herein, with the appropriate control being a control ABPC monospecific or bispecific ABPC specific for DLL3. Briefly, it can be shown that, as compared to a control, the pH-engineered DLL3 x DLL3 ABPCs specific for DLL3: a) bind in Attorney Docket No.: 45395-0068WO1 a pH-dependent manner to cells, e.g., bind at a neutral pH but not an acidic pH and b) release from cells in a pH-dependent manner, e.g. bind at a neutral pH and release at an acidic pH and c) show enhanced endolysosomal accumulation in DLL3+ cells and d) show increased DLL3 antigen density after exposure to DLL3+ cells and e) when conjugated to a toxin, show increased cytotoxicity to DLL3+ cells and f) when conjugated to a toxin, show increased toxin liberation when incubated with DLL3+ cells and g) show decreased half-life when exposed to DLL3 antigen in a relevant animal model and h) when conjugated to a toxin, show increased efficacy in a mouse xenograft model of DLL3+ cells. Similarly, the exemplary properties of pH-engineered DLL3 x BINDER ABPCs specific for DLL3 can be demonstrated using the methods described herein, with the appropriate control being a control ABPC DLL3 x BINDER bispecific ABPC specific for DLL3. [0373] Any of the foregoing techniques may be employed in the characterization of pH- engineered and non-pH-engineered ABPCs. Example 9. Characterization of cellular internalization and endolysosomal delivery of anti- DLL3 ABPCs including pH-engineered variants thereof [0374] Selected anti-DLL3 antibodies or antibody variants are analyzed for internalization and endolysosomal delivery DLL3+ cells (e.g. grown per providers instructions). Cell counts are determined using trypan blue staining and the Countess II FL Automated Cell Counter (ThermoFisher; AMQAF1000). Cells are then diluted to 75,000 cells/mL and 100µl/well are seeded into 96-well flat bottom cell culture plates (Genesee Scientific; 25-109) for overnight incubation at 37 °C and 5% CO2. The following day, anti-DLL3 pH engineered antibody variants, starting ABPC antibodies, control IgG1 isotype control (BP0297, Bioxcell), and vehicle control are diluted in native culture media, and then mixed 1:1 with a 3x molar ratio Zenon pHrodo iFL Human IgG Labeling Reagent (ThermoFisher; Z25611). The mixture is incubated for 30 minutes at room temperature, the existing media is removed from the plated cells and the mixture is added. The mixture of cells, anti-DLL3 antibody variants, and Zenon pHrodo iFL Human IgG Labeling Reagent was incubated at 37 °C, 5% CO2 for 24 hours. Following incubation, the media is removed and cells are washed with 100 µL of room temperature culture medium. Following the wash 50 µL of Trypsin solution (ThermoFisher Scientific; 12605036) is added and the plate incubated at 37 °C until most of the cells are detached, followed by addition of 50 µL of culture medium. Cells are transferred to a 96-well U-bottom plate (Genesee Scientific; 25-221) and spun down at 2000 Attorney Docket No.: 45395-0068WO1 RPM for 2 minutes. Cells are washed 2x with 200 µL of ice-cold FACS buffer (phosphate buffered saline (PBS), pH 7.4+2mM ethylenediaminetetraacetic acid (EDTA)+2% (v/v) HI FBS) before being resuspended in 150 µL of FACS buffer. Cells (Median green fluorescence intensity is detected using an Attune NxT flow cytometer (ThermoFisher Scientific). Data is analyzed using Flowjo analysis software. pHrodo green is a pH sensitive dye that fluoresces in the low pH environment of the endosomes and lysosomes and therefore can be used to quantify antibody internalization and endolysosomal delivery. Internalization and endolysosomal delivery of anti- DLL3 starting ABPC’s and variants at 25nM in DLL3+ cells is measured by pHrodo green median fluorescence intensity. Several pH engineered anti-DLL3 antibody variants show increased median fluorescence intensity relative to their corresponding starting ABPC antibodies demonstrating that increased dissociation at lower pH leads to enhanced internalization and endolysosomal delivery inside cells as shown by increased fluorescence or increased fluorescence as compared to IgG1 isotype control. Increased endolysosomal delivery is quantitated for each pH engineered anti- DLL3 antibody variant on the top of each bar as a ratio of: the variant’s median fluorescence intensity minus the median fluorescence intensity of the IgG control, then all divided by the variant’s corresponding starting ABPC’s median fluorescence intensity minus the median fluorescence intensity of the IgG control. For example, pH-engineered variant antibodies as disclosed herein may show increased internalization and endolysosomal delivery relative to their respective parental antibodies. [0375] Such pH engineered anti-DLL3 antibody variants with increased median fluorescence intensity relative to their starting ABPC antibodies are selected for further analysis. [0376] Any of the foregoing techniques may be employed in the characterization of pH- engineered and non-pH-engineered ABPCs. Example 10. Anti-DLL3 antibody discovery in rabbit and characterization of novel anti- DLL3 antibodies [0377] Two New Zealand white rabbits were immunized with the recombinant His6-tagged extracellular domain (ECD) of DLL3 (SEQ ID NO: 2) and boosted four times with the same immunogen (200µg for initial and final immunizations, 100 ug for interim boosts). Test bleeds were collected after the second and third boost, respectively, and serum titer was determined by anti-DLL3 ELISA in a 384-well plate. Both rabbits showed a strong immune response to DLL3 and splenocytes were collected from one animal. Antibody secreting B cells were labeled with Attorney Docket No.: 45395-0068WO1 DLL3, sorted, and cultured in 96-well plates. Based on an anti-DLL3 ELISA, supernatants of 288 B cells were selected for a cytotoxicity assay (for additional details, see Example 4) on DLL3 positive NCI-H82 cells with an anti-rabbit Fc non-cleavable MMAF secondary ADC. The antibody/ADC mixture and cells were incubated for 3 days and the percentage of viable cells was determined with a plate reader using the CellTiter-Glo assay. One hundred-thirty (130) B cells that produced NCI-H82 cytotoxic supernatants were selected for sequencing of the VH and VL regions resulting in 48 unique pairs. The rabbit sequences were humanized by grafting the complementary determining regions (CDRs) into a generic human framework (Borras et al. Journal of Biological Chemistry 2010, 285, 9054-9066). DNA encoding the heavy and light chain for each humanized candidate was transfected into HEK293 cells and the produced antibodies were purified over ProA agarose. Of the 48 candidates, 14 anti-DLL3 antibodies showed binding to recombinant DLL3 by biolayer interferometry (BLI, Octet RH16) and were further characterized. [0378] Specificity and cross-reactivity were assessed by BLI using recombinant DLL1 or DLL4 and DLL3 from cynomolgus monkey or mouse, respectively. Binding to NCI-H82 cells was tested with a fluorescently labeled anti-human Fc secondary antibody (AF488, Attune Nxt flow cytometer). Developability of the anti-DLL3 antibodies was assessed by HPLC analysis (size exclusion and hydrophobic interaction chromatography) as well as polyspecificity assays using plates coated with baculovirus particles, lipopolysaccharide, DNA or insulin, respectively with an anti-human Fc horseradish peroxidase conjugated secondary antibody. To assess the potential of anti-DLL3 antibodies for use in ADCs, internalization on NCI-H82 cells was tested with an anti- human Fc secondary antibody conjugated to a pH sensitive fluorescent dye (pHrodo Green). Briefly, the antibody mixture was incubated with cells for 24 h, the cells were washed and analyzed on an Attune Nxt flow cytometer (see Example 9 for additional details on this method). [0379] The results of the foregoing analyses are summarized in Table 9. Table 9. Characteristics of the novel, anti-DLL3, humanized rabbit monoclonal antibodies Hum SEC HI BLI Affini Epit DLL3 Cross-reactivity Yield Internali anize C ty on ope domain zation Attorney Docket No.: 45395-0068WO1 N- 8812 98.3 8.96 5 3 3.55 0.8576 6 terminu - - - - 0.5408 1.55 s [0380] Each of the results summarized in this Example were produced using protocols performed substantially as described herein (see, e.g., the Examples). Briefly, the following humanized antibodies, each comprising an IgG heavy chain constant domain and a kappa light chain constant domain, were produced using the ordinary methods detailed in the examples: 8812 (VH of SEQ ID NO: 123 & VL of SEQ ID NO: 124), 8815 (VH of SEQ ID NO: 131 & VL of SEQ ID NO: 132), 8819 (VH of SEQ ID NO: 139 & VL of SEQ ID NO: 140), 8820 (VH of SEQ ID NO: 147 & VL of SEQ ID NO: 148), 8821 (VH of SEQ ID NO: 155 & VL of SEQ ID NO: 156), 8829 (VH of SEQ ID NO: 163 & VL of SEQ ID NO: 164), 8837 (VH of SEQ ID NO: 171 & VL of SEQ ID NO: 172), 8838 (VH of SEQ ID NO: 179 & VL of SEQ ID NO: 180), 8843 (VH of SEQ ID NO: 187 & VL of SEQ ID NO: 188), 8844 (VH of SEQ ID NO: 195 & VL of SEQ ID NO: 196), 8847 (VH of SEQ ID NO: 203 & VL of SEQ ID NO: 204), and 8849 (VH of SEQ ID NO: 211 & VL of SEQ ID NO: 212). [0381] As indicated in Table 9, the humanized anti-DLL antibodies exhibited properties associated with highly developable biotherapeutic agents. Moreover, the humanized antibodies exhibited distinct binding profiles, with some recognizing certain DLL3 epitopes (e.g., DLL3 Attorney Docket No.: 45395-0068WO1 epitope 1, 3, 5, 6, and 7) and certain truncated DLL3 constructs (e.g., DLL3 EGF1 domain, DSL domain, N-terminus, and the proximal domain of DLL3, EGF6). Further, many of the humanized rabmAb demonstrated single digit nM affinity or below determined by BLI and cell-based binding assays. And further distinguishing these novel anti-DLL3-binding constructs, multiple patterns of cross-species-reactivity and cross-DLL3 isoform-reactivity were observed. Finally, the ability of the humanized antibodies to bind cells that express DLL3 (or the indicated truncations thereof) was confirmed by expressing full length DLL3 (or the indicated truncations thereof) in HEK293T cells and staining with the humanized rabmAb (data not shown). [0382] As used in Table 9, the abbreviations have the following meanings: [0383] “SEC” means size exclusion chromatography, which was performed on an Agilent 1260 Infinity II HPLC with a TSKgel SuperSW mAb HTP HPLC column and a 0.35mL mL/min flow rate of 0.2M sodium phosphate pH6.7, retention times (RTs) are given in minutes. “HIC” means hydrophobic interaction chromatography, which was performed on an Agilent 1260 Infinity II HPLC with a Sepax HIC Butyl-NP54.6x100mm column and a 35min method at 1mL/min flow rate with a gradient from 150mM sodium phosphate pH7, 1M NaCl to 150mM sodium phosphate buffer pH7, retention times (RTs) are given in minutes. [0384] “Polyspecificity” is a measure of a given anti-DLL3 antibody’s capacity to bind specifically to proteins other than DLL3. Polyspecificity was determined in ELISA assays against baculovirus particle, DNA, lipopolysaccharide and insulin. Antibodies were flagged if they showed higher signal than control antibodies with known developability liabilities. None of the antibodies recited in Table 5 were flagged for polyspecificity. [0385] “BLI” means biolayer interferometry, which was determined on a RED96e or RH16 instrument with variable concentrations of DLL3 antigen. Equilibrium binding constants (KD) were determined with the Octet Analysis software using a 1:1 binding model for fitting. [0386] “Affinity” has the meaning recited in this disclosure, and was determined by dose titration on NCI-H82 cells using a fluorescently labelled secondary antibody against human Fc. [0387] “DLL3 domain” refers to the DLL3 domain specifically recognized by each indicated anti-DLL3 antibody. Domain mapping was performed by HEK293 display of truncated DLL3 constructs (NB: n/a = not applicable, as MYT8815 bound to all truncation variants, analogous to MYT8847, but likely non-specifically). Attorney Docket No.: 45395-0068WO1 [0388] “Cross-reactivity” refers to the capacity of a given antibody to bind to different DLL proteins from different species, and was determined using recombinant cynomolgus or mouse DLL3, human DLL1 and human DLL4. [0389] “Yield” means the protein yield after ProA purification of 50mL transfections of expression plasmids encoding the heavy and light chains corresponding to the indicated MYT # antibody in HEK293. [0390] Internalization “FOR” means fold over reference antibody MYT0638. [0391] “Epitope” refers to the region on DLL3 specifically recognized by each indicated anti- DLL3 antibody. [0392] “Epitope binning” is known in the art and may be carried out generally as follows: antibodies against a target antigen are tested against other antibodies in a pairwise fashion to determine whether antibodies specifically block one another's binding to the epitope of an antigen. As used herein, an antibody is deemed to be a member of the same bin (or epitope bin) when it can substantially, including completely, prevent the binding of a reference member of the same bin. Accordingly, “bin member” means one of the binders that recognizes a given “epitope bin” (or simply “bin”) of a given antigen (e.g., DLL3). [0393] Epitope Binning Methods. As disclosed herein, epitope binning was performed on an octet RH16 instrument using a sandwich assay. As indicated by the data disclosed herein, the novel anti- DLL3 antibodies recognize at least four (4) new epitopes. The following antibodies were produced in large scale: MYT0638 (the VH and VL set forth in SEQ ID NOs: 241 and 242, respectively), MYT3181 (the VH and VL set forth in SEQ ID NOs: 243 and 244, respectively), and MYT3892 ((the VH and VL set forth in SEQ ID NOs: 247 and 248, respectively), each fully described in US20220313845A1, to Mythic Therapeutics, Inc., which is incorporated herein by reference in its entirety). The twelve (12) humanized antibodies were produced using substantially the same methods from small scale production, and both groups of antibodies were purified over ProA, dialyzed to PBS and diluted to 10ug/mL. Sequences for the VH and VL domains are presented in Table 5 and sequences for the complete heavy and light chains are presented in Table 6. [0394] The antigen was a 100 nM solution of human DLL3 (ECD, His tag: C-terminus). FIG.1A provides a schematic of an exemplary sandwich assay binning method. Generally, in a sandwich binning assay the first ABPC is covalently attached to the surface of a biosensor. The antigen is then injected and binds to the first ABPC, followed by injection of the second ABPC. If the second Attorney Docket No.: 45395-0068WO1 ABPC binds to the antigen, it creates a ‘sandwich’, indicating that they have different epitopes and belong to separate bins. Alternatively, if the second ABPC is blocked from binding to the antigen by the first ABPC, it suggests that they have overlapping epitopes and should be binned together. [0395] Similar to the sandwich assay format, the first ABPC is covalently attached to the biosensor. The antigen and the second ABPC are combined outside the instrument at saturating conditions and then tested as a complex. [0396] In a tandem binning assay, the antigen is covalently attached to the biosensor surface. The first ABPC is injected under saturating conditions, followed by testing of the second ABPC. If both ABPCs bind to the immobilized antigen, the two ABPCs have different epitopes and belong in different bins. Conversely, if the second ABPC does not bind to the antigen, it suggests that the first ABPC sufficiently blocks the epitope resulting in binning two ABPCs together. [0397] FIG. 1B shows a tumor cell displaying an antigen (i.e., DLL3). Specifically, FIG. 1B shows the extracellular domains of DLL3 which includes six epidermal growth factor (“EGF”)- like domains, a Delta/Serrate/Lag-2 (“DSL”) domain, and an N-terminal domain. FIG. 1B also shows exemplary ABPCs of the present disclosure binding to specific epitopes of the DLL3 antigen. [0398] The Octet RH16 cycle consisted of the following steps: baseline 1 (PBST pH7.4) 60 seconds; loading (Ab1) 180 seconds; baseline 2 (PBST pH7.4) 60 seconds; association (hDLL3) 120 seconds; blocking (trastuzumab) 120 seconds; baseline 3 (PBST pH7.4) 60 seconds; challenge (Ab2) 120s. [0399] As summarized in the Table above, the novel anti-DLL3-binding protein constructs exhibit desirable properties and superior technical effect when compared to the reference antibodies. Table 10. An potential alignment of selected H-CDRs and L-CDRs across the various epitope 4 DLL3-binders Heavy Chain CDR Alignments Light Chain CDR Alignments Attorney Docket No.: 45395-0068WO1 H-CDR2 SEQ ID NO: 142 TVSG-GG-HK-YYASWAKG SEQ ID NO: 150 FIDSDGT---TYYASWAKG Embodiments [0400] Embodiment 1. An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 205, 206, and 207, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 208, 209, and 210, respectively. [0401] Embodiment 2. The antigen-binding protein construct of embodiment 1, wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 203 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 204. [0402] Embodiment 3. The antigen-binding protein construct of embodiment 1 or 2, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 239 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 240. [0403] Embodiment 4. An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 13, 14, and 15, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 16, 17, and 18, respectively. [0404] Embodiment 5. The antigen-binding protein construct of embodiment 4, wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical Attorney Docket No.: 45395-0068WO1 to SEQ ID NO: 11 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 12. [0405] Embodiment 6. The antigen-binding protein construct of embodiment 4 or 5, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 101 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 102. [0406] Embodiment 7. An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 21, 22, and 23, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 24, 25, and 26, respectively. [0407] Embodiment 8. The antigen-binding protein construct of embodiment 7, wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 19 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 20. [0408] Embodiment 9. The antigen-binding protein construct of embodiment 7 or 8, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 103 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 104. [0409] Embodiment 10. An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 29, 30, and 31, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 32, 33, and 34, respectively. [0410] Embodiment 11. The antigen-binding protein construct of embodiment 10, wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical Attorney Docket No.: 45395-0068WO1 to SEQ ID NO: 27 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 28. [0411] Embodiment 12. The antigen-binding protein construct of embodiment 10 or 11, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 105 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 106. [0412] Embodiment 13. An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 37, 38, and 39, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 40, 41, and 42, respectively. [0413] Embodiment 14. The antigen-binding protein construct of embodiment 13, wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 35 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 36. [0414] Embodiment 15. The antigen-binding protein construct of embodiment 13 or 14, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 107 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 108. [0415] Embodiment 16. An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 45, 46, and 47, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 48, 49, and 50, respectively. [0416] Embodiment 17. The antigen-binding protein construct of embodiment 16, wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical Attorney Docket No.: 45395-0068WO1 to SEQ ID NO: 43 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 44. [0417] Embodiment 18. The antigen-binding protein construct of embodiment 16 or 17, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 109 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 110. [0418] Embodiment 19. A antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 53, 54, and 55, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 56, 57, and 58, respectively. [0419] Embodiment 20. The antigen-binding protein construct of embodiment 19, wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 51 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 52. [0420] Embodiment 21. The antigen-binding protein construct of embodiment 19 or 20, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 111 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 112. [0421] Embodiment 22. An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 61, 62, and 63, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 64, 65, and 66, respectively. [0422] Embodiment 23. The antigen-binding protein construct of embodiment 22, wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical Attorney Docket No.: 45395-0068WO1 to SEQ ID NO: 59 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 60. [0423] Embodiment 24. The antigen-binding protein construct of embodiment 19 or 20, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 113 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 114. [0424] Embodiment 25. An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 69, 70, and 71, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 72, 73, and 74, respectively. [0425] Embodiment 26. The antigen-binding protein construct of embodiment 25, wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 67 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 68. [0426] Embodiment 27. The antigen-binding protein construct of embodiment 25 or 26, comprising a heavy chain comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 115 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 116. [0427] Embodiment 28. An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 77, 78, and 79, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 80, 81, and 82, respectively. [0428] Embodiment 29. The antigen-binding protein construct of embodiment 28, wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical Attorney Docket No.: 45395-0068WO1 to SEQ ID NO: 75 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 76. [0429] Embodiment 30. The antigen-binding protein construct of embodiment 28 or 29, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 117 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 118. [0430] Embodiment 31. An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 85, 86, and 87, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 88, 89, and 90, respectively. [0431] Embodiment 32. The antigen-binding protein construct of embodiment 31, wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 83 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 84. [0432] Embodiment 33. The antigen-binding protein construct of embodiment 31 or 32, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 119 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 120. [0433] Embodiment 34. An antigen-binding protein construct comprising an antigen binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 93, 94, and 95, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 96, 97, and 98, respectively. [0434] Embodiment 35. The antigen-binding protein construct of embodiment 34, wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical Attorney Docket No.: 45395-0068WO1 to SEQ ID NO: 91 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 92. [0435] Embodiment 36. The antigen-binding protein construct of embodiment 34 or 35, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 121 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 122. [0436] Embodiment 37. The antigen-binding protein construct of any one of embodiments 1 to 36, wherein the antigen-binding protein construct is selected from the group of an antibody, a VHH-scAb, a VHH-Fab, a Dual scFab, a F(ab’)2, a diabody, a crossMab, a DAF (two-in-one), a DAF (four-in-one), a DutaMab, a DT-IgG, a knobs-in-holes common light chain, a knobs-in-holes assembly, a charge pair, a Fab-arm exchange, a SEEDbody, a LUZ-Y, a Fcab, a κλ-body, an orthogonal Fab, a DVD-IgG, a IgG(H)-scFv, a scFv-(H)IgG, IgG(L)-scFv, scFv-(L)IgG, IgG(L,H)-Fv, IgG(H)-V, V(H)-IgG, IgG(L)-V, V(L)-IgG, KIH IgG-scFab, 2scFv-IgG, IgG- 2scFv, scFv4-Ig, Zybody, DVI-IgG, Diabody-CH3, a triple body, a miniantibody, a minibody, a TriBi minibody, scFv-CH3 KIH, Fab-scFv, a F(ab’)2-scFv2, a scFv-KIH, a Fab-scFv-Fc, a tetravalent HCAb, a scDiabody-Fc, a Diabody-Fc, a tandem scFv-Fc, a VHH-Fc, a tandem VHH- Fc, a VHH-Fc KiH, a Fab-VHH-Fc, an Intrabody, a dock and lock, an ImmTAC, an IgG-IgG conjugate, a Cov-X-Body, a scFv1-PEG-scFv2, an Adnectin, a DARPin, a fibronectin, a DEP conjugate, and a PROTAB. [0437] Embodiment 38. The antigen-binding protein construct of embodiment 37, wherein the antigen-binding protein construct is a monoclonal antibody comprising an IgG heavy chain constant region. [0438] Embodiment 39. The antigen-binding protein construct of embodiment 37 or 38, comprising an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 99 and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 100. [0439] Embodiment 40. The antigen-binding protein construct of embodiment 37 or 38, comprising an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 101 and an LCVD that comprises a Attorney Docket No.: 45395-0068WO1 sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 102. [0440] Embodiment 41. The antigen-binding protein construct of embodiment 37 or 38, comprising an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 103 and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 104. [0441] Embodiment 42. The antigen-binding protein construct of embodiment 37 or 38, comprising an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 105 and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 106. [0442] Embodiment 43. The antigen-binding protein construct of embodiment 37 or 38, comprising an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 107 and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 108. [0443] Embodiment 44. The antigen-binding protein construct of embodiment 37 or 38, comprising an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 109 and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 110. [0444] Embodiment 45. The antigen-binding protein construct of embodiment 37 or 38, comprising an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 111 and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 112. [0445] Embodiment 46. The antigen-binding protein construct of embodiment 37 or 38, comprising an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 113 and an LCVD that comprises a Attorney Docket No.: 45395-0068WO1 sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 114. [0446] Embodiment 47. The antigen-binding protein construct of embodiment 37 or 38, comprising an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 115 and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 116. [0447] Embodiment 48. The antigen-binding protein construct of embodiment 37 or 38, comprising an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 117 and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 118. [0448] Embodiment 49. The antigen-binding protein construct of embodiment 37 or 38, comprising an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 119 and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 120. [0449] Embodiment 50. The antigen-binding protein construct of embodiment 37 or 38, comprising an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 121 and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 122. [0450] Embodiment 51. A pharmaceutical composition comprising the antigen-binding protein construct of any one of embodiments 1-50 and a pharmaceutically acceptable excipient. [0451] Embodiment 52. A method of treating a cancer in a subject in need thereof comprising administering to the subject the DLL3-binding protein construct of any one of embodiments 1-50 or the pharmaceutical composition of embodiment 51. [0452] Embodiment 53. A pharmaceutical composition comprising an effective amount of an antigen-binding protein construct (ABPC) comprising: a first antigen-binding domain (ABD) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell, wherein: the dissociation rate of the first ABD at a pH of ~4.0-6.5 is faster than Attorney Docket No.: 45395-0068WO1 the dissociation rate at a pH of ~7.0-8.0; and/or the KD of the first ABD at a pH of ~4.0-6.5 is greater than the KD at a pH of ~7.0-8.0. [0453] Embodiment 54. The pharmaceutical composition of embodiment 53, wherein the first ABD comprises a heavy chain variable domain (HCVD) amino acid sequence selected from one of SEQ ID NO: 3, SEQ ID NO: 11, SEQ ID NO: 19, SEQ ID NO: 27, SEQ ID NO: 35, SEQ ID NO: 43, SEQ ID NO: 51, SEQ ID NO: 59, SEQ ID NO: 67, SEQ ID NO: 75, SEQ ID NO: 83, and SEQ ID NO: 91, optionally wherein the HCVD has at least one amino acid substituted with a histidine. [0454] Embodiment 55. The pharmaceutical composition of embodiment 53 or 54, wherein the first ABD comprises a light chain variable domain (LCVD) amino acid sequence selected from one of SEQ ID NO: 4, SEQ ID NO: 12, SEQ ID NO: 20, SEQ ID NO: 28, SEQ ID NO: 36, SEQ ID NO: 44, SEQ ID NO: 52, SEQ ID NO: 60, SEQ ID NO: 68, SEQ ID NO: 76, SEQ ID NO: 84, and SEQ ID NO: 92, optionally wherein the LCVD has at least one amino acid substituted with a histidine. [0455] Embodiment 56. The pharmaceutical composition of embodiment 54 or 55, wherein the HCVD comprises an amino acid sequence as set forth in one of SEQ ID NOs: 3, 11, 19, 27, 35, 43, 51, 59, 67, 75, 83, and 91 or comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to an amino acid sequence as set forth in one of SEQ ID NOs: 3, 11, 19, 27, 35, 43, 51, 59, 67, 75, 83, and 91, optionally wherein the HCVD has at least one amino acid substituted with a histidine. [0456] Embodiment 57. The pharmaceutical composition of embodiment 55 or 56, wherein the LCVD comprises an amino acid sequence as set forth in one of SEQ ID NOs: 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, and 92 or comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to an amino acid sequence as set forth in one of SEQ ID NOs: 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, and 92, optionally wherein the LCVD has at least one amino acid substituted with a histidine. [0457] Embodiment 58. The pharmaceutical composition of embodiment 56 or 57, wherein the HCVD comprises a set of three H-CDRs selected from the group consisting of: SEQ ID NOs: 5, 6, and 7; SEQ ID NOs: 13, 14, and 15; SEQ ID NOs: 21, 22, and 23; SEQ ID NOs: 29, 30, and 31; SEQ ID NOs: 37, 38, and 39; SEQ ID NOs: 45, 46, and 47; SEQ ID NOs: 53, 54, and 55; SEQ ID NOs: 61, 62, and 63; SEQ ID NOs: 69, 70, and 71; SEQ ID NOs: 77, 78, and 79; SEQ ID NOs: Attorney Docket No.: 45395-0068WO1 85, 86, and 87; SEQ ID NOs: 93, 94, and 95, optionally wherein the set of three H-CDRs has collectively one or more position substituted with a histidine. [0458] Embodiment 59. The pharmaceutical composition of embodiment 57 or 58, wherein the LCVD comprises a set of three L-CDRs selected from the group consisting of: SEQ ID NOs: 8, 9, and 10; SEQ ID NOs: 16, 17, and 18; SEQ ID NOs: 24, 25, and 26; SEQ ID NOs: 32, 33, and 34; SEQ ID NOs: 40, 41, and 42; SEQ ID NOs: 48, 49, and 50; SEQ ID NOs: 56, 57, and 58; SEQ ID NOs: 64, 65, and 66; SEQ ID NOs: 72, 73, and 74; SEQ ID NOs: 80, 81, and 82; SEQ ID NOs: 88, 89, and 90; SEQ ID NOs: 96, 97, and 98, optionally wherein the set of three L-CDRs has collectively one or more position substituted with a histidine. [0459] Embodiment 60. The pharmaceutical composition of any one of embodiments 53-59, wherein the ABPC is degraded in the target mammalian cell following internalization of the ABPC by the target mammalian cell. [0460] Embodiment 61. The pharmaceutical composition of any one of embodiments 53-60, wherein the ABPC further comprises a conjugated toxin, radioisotope, drug, or small molecule. [0461] Embodiment 62. The pharmaceutical composition of embodiment 61, wherein the pharmaceutical composition provides for an increase in toxin liberation in the target mammalian cell as compared to a pharmaceutical composition comprising the same amount of a control ABPC. [0462] Embodiment 63. The pharmaceutical composition of embodiment 62, wherein the pharmaceutical composition provides for at least a 20%, 50%, 2-fold, or 5-fold increase in toxin liberation in the target mammalian cell as compared to a pharmaceutical composition comprising the same amount of a control ABPC. [0463] Embodiment 64. The pharmaceutical composition of any one of embodiments 61-63, wherein the pharmaceutical composition provides for an increase in target mammalian cell killing as compared to a pharmaceutical composition comprising the same amount of a control ABPC. [0464] Embodiment 65. The pharmaceutical composition of embodiment 64, wherein the pharmaceutical composition provides for at least a 20%, 50%, 2-fold, or 5-fold increase in target mammalian cell killing as compared to a pharmaceutical composition comprising the same amount of a control ABPC. [0465] Embodiment 66. The pharmaceutical composition of any one of embodiments 53-62, wherein the pharmaceutical composition provides for an increase in endolysosomal delivery in the Attorney Docket No.: 45395-0068WO1 target mammalian cell as compared to a pharmaceutical composition comprising the same amount of a control ABPC. [0466] Embodiment 67. The pharmaceutical composition of embodiment 66, wherein the pharmaceutical composition provides for at least a 20%, 50%, 2-fold, or 5-fold increase in endolysosomal delivery in the target mammalian cell as compared to a pharmaceutical composition comprising the same amount of a control ABPC. [0467] Embodiment 68. The pharmaceutical composition of any one of embodiments 53-67, wherein the pharmaceutical composition results in a less or no detectable reduction in the level of DLL3 presented on the surface of the target mammalian cell as compared to a pharmaceutical composition comprising the same amount of a control ABPC. [0468] Embodiment 69. A composition comprising an effective amount of an antigen-binding protein construct (ABPC) comprising: a first ABD that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell; and a conjugated toxin, radioisotope, drug, or small molecule, wherein: [0469] (a) the dissociation rate of the first ABD at a pH of ~4.0-6.5 is faster than the dissociation rate at a pH of ~7.0-8.0; or the dissociation constant (KD) of the first ABD at a pH of ~4.0-6.5 is greater than the KD at a pH of ~7.0-8.0; and [0470] (b) the composition provides for one or more of: (i) an increase in toxin liberation in the target mammalian cell as compared to a composition comprising the same amount of a control ABPC; (ii) an increase in target mammalian cell killing as compared to a composition comprising the same amount of a control ABPC; and/or (iii) an increase in endolysosomal delivery in the target mammalian cell as compared to a composition comprising the same amount of a control ABPC. [0471] Embodiment 70. The composition of embodiment 69, wherein the first ABD comprises a heavy chain variable domain (HCVD) amino acid sequence selected from one of SEQ ID NO: 3, SEQ ID NO: 11, SEQ ID NO: 19, SEQ ID NO: 27, SEQ ID NO: 35, SEQ ID NO: 43, SEQ ID NO: 51, SEQ ID NO: 59, SEQ ID NO: 67, SEQ ID NO: 75, SEQ ID NO: 83, and SEQ ID NO: 91, optionally wherein the HCVD has at least one amino acid substituted with a histidine. [0472] Embodiment 71. The composition of embodiment 69 or 70, wherein the first ABD comprises a light chain variable domain (LCVD) amino acid sequence selected from one of SEQ ID NO: 4, SEQ ID NO: 12, SEQ ID NO: 20, SEQ ID NO: 28, SEQ ID NO: 36, SEQ ID NO: 44, Attorney Docket No.: 45395-0068WO1 SEQ ID NO: 52, SEQ ID NO: 60, SEQ ID NO: 68, SEQ ID NO: 76, SEQ ID NO: 84, and SEQ ID NO: 92, optionally wherein the HCVD has at least one amino acid substituted with a histidine. [0473] Embodiment 72. The composition of embodiment 70 or 71, wherein the HCVD comprises an amino acid sequence of any one of SEQ ID NOs: 3, 11, 19, 27, 35, 43, 51, 59, 67, 75, 83, and 91 or comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to an amino acid sequence of any one of SEQ ID NOs: 3, 11, 19, 27, 35, 43, 51, 59, 67, 75, 83, and 91, optionally wherein the HCVD has at least one amino acid substituted with a histidine. [0474] Embodiment 73. The composition of embodiment 71 or 72, wherein the LCVD comprises an amino acid sequence of any one of SEQ ID NOs: 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, and 92 or comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to an amino acid sequence of any one of SEQ ID NOs: 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, and 92, optionally wherein the LCVD has at least one amino acid substituted with a histidine. [0475] Embodiment 74. The composition of embodiment 72 or 73, wherein the HCVD comprises a set of three H-CDRs selected from the group consisting of: SEQ ID NOs: 5, 6, and 7; SEQ ID NOs: 13, 14, and 15; SEQ ID NOs: 21, 22, and 23; SEQ ID NOs: 29, 30, and 31; SEQ ID NOs: 37, 38, and 39; SEQ ID NOs: 45, 46, and 47; SEQ ID NOs: 53, 54, and 55; SEQ ID NOs: 61, 62, and 63; SEQ ID NOs: 69, 70, and 71; SEQ ID NOs: 77, 78, and 79; SEQ ID NOs: 85, 86, and 87; SEQ ID NOs: 93, 94, and 95, optionally wherein the set of three H-CDRs has collectively one or more amino acid position substituted with a histidine. [0476] Embodiment 75. The composition of embodiment 73 or 74, wherein the LCVD comprises a set of three L-CDRs selected from the group consisting of: SEQ ID NOs: 8, 9, and 10; SEQ ID NOs: 16, 17, and 18; SEQ ID NOs: 24, 25, and 26; SEQ ID NOs: 32, 33, and 34; SEQ ID NOs: 40, 41, and 42; SEQ ID NOs: 48, 49, and 50; SEQ ID NOs: 56, 57, and 58; SEQ ID NOs: 64, 65, and 66; SEQ ID NOs: 72, 73, and 74; SEQ ID NOs: 80, 81, and 82; SEQ ID NOs: 88, 89, and 90; SEQ ID NOs: 96, 97, and 98, optionally wherein the set of three L-CDRs has collectively one or more amino acid position substituted with a histidine. [0477] Embodiment 76. The composition of any one of embodiments 69 to 75, wherein the composition provides for at least a 20%, 50%, 2-fold, or 5-fold increase in toxin liberation in the target mammalian cell, and/or cell killing, and/or at least a 20%, 50%, 2-fold, or 5-fold increase in endolysosomal delivery as compared to a composition comprising the same amount of a control ABPC. Attorney Docket No.: 45395-0068WO1 [0478] Embodiment 77. The composition of any one of embodiments 53-76, wherein the dissociation rate of the ABD at a pH of ~4.0-6.5 is at least 10%, 3-fold, or 10-fold faster than the dissociation rate of the ABD at a pH of ~7.0-8.0 and/or the KD of the first ABD at a pH of ~4.0- 6.5 is at least 10%, 3-fold, or 10-fold greater than the KD of the first ABD at a pH of ~7.0-8.0. [0479] Embodiment 78. The composition of any one of embodiments 53-77, wherein the ABPC comprises a single polypeptide, optionally wherein the first ABD is selected from a VH domain, a VHH domain, a VNAR domain, and a scFv; and/or wherein the ABPC is a BiTe, a (scFv)2, a nanobody, a nanobody-HSA, a DART, a TandAb, a scDiabody, a scDiabody-CH3, scFv-CH-CL- scFv, a HSAbody, scDiabody-HSA, a tandem-scFv, and a PROTAB. [0480] Embodiment 79. The composition of any one of embodiments 53-78, wherein the ABPC comprises two or more polypeptides. [0481] Embodiment 80. The composition of any one of embodiments 53-79, wherein at least one polypeptide of the ABPC is conjugated to the toxin, the radioisotope, the drug, or the small molecule via a cleavable or non-cleavable linker. [0482] Embodiment 81. The composition of any of embodiments 53-80, wherein the half-life of the ABPC in vivo is increased as compared to the half-life of a control ABPC in vivo, optionally wherein the increase is ~5%-95%, ~10%-95%, ~30%-95%, ~50%-95%, or ~70%-95% as compared to the half-life of a control ABPC in vivo. [0483] Embodiment 82. The composition of any one of embodiments 53-48, wherein the control ABPC is capable of specifically binding to DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell, wherein: [0484] (a) the control ABPC comprises a first ABD; [0485] (b) the dissociation rate of the first ABD of the control ABPC at a pH of ~4.0-6.5 is no more than 2-fold or 3-fold faster than the dissociation rate at a pH of ~7.0-8.0; and [0486] (c) the dissociation constant (KD) of the first ABD of the control ABPC at a pH of ~4.0- 6.5 is no more than 2-fold or 3-fold greater than the KD at a pH of ~7.0-8.0. [0487] Embodiment 83. The composition of any one of embodiments 53-82, wherein the ABPC further comprises a second ABD. [0488] Embodiment 84. A kit comprising at least one dose of the composition of any one of embodiments 53-83. Attorney Docket No.: 45395-0068WO1 [0489] Embodiment 85. An antigen-binding protein construct (ABPC) comprising: a first antigen-binding domain (ABD) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell, wherein: the dissociation rate of the first ABD at a pH of ~4.0-6.5 is faster than the dissociation rate at a pH of ~7.0-8.0; or the KD of the first ABD at a pH of ~4.0-6.5 is greater than the KD at a pH of ~7.0-8.0. [0490] Embodiment 86. The ABPC of embodiment 85, wherein the first ABD comprises a heavy chain variable domain (HCVD) amino acid sequence selected from one of SEQ ID NO: 3, SEQ ID NO: 11, SEQ ID NO: 19, SEQ ID NO: 27, SEQ ID NO: 35, SEQ ID NO: 43, SEQ ID NO: 51, SEQ ID NO: 59, SEQ ID NO: 67, SEQ ID NO: 75, SEQ ID NO: 83, and SEQ ID NO: 91, optionally wherein the HCVD has at least one amino acid substituted with a histidine. [0491] Embodiment 87. The ABPC of embodiment 85 or 86, wherein the first ABD comprises a light chain variable domain (LCVD) amino acid sequence selected from one of SEQ ID NO: 4, SEQ ID NO: 12, SEQ ID NO: 20, SEQ ID NO: 28, SEQ ID NO: 36, SEQ ID NO: 44, SEQ ID NO: 52, SEQ ID NO: 60, SEQ ID NO: 68, SEQ ID NO: 76, SEQ ID NO: 84, and SEQ ID NO: 92, optionally wherein the HCVD has at least one amino acid substituted with a histidine. [0492] Embodiment 88. The ABPC of embodiment 86 or 87, wherein the HCVD comprises an amino acid sequence of any one of SEQ ID NOs: 3, 11, 19, 27, 35, 43, 51, 59, 67, 75, 83, and 91 or comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to any one of SEQ ID NOs: 3, 11, 19, 27, 35, 43, 51, 59, 67, 75, 83, and 91, optionally wherein the HCVD has at least one amino acid substituted with a histidine. [0493] Embodiment 89. The ABPC of embodiment 87 or 88, wherein the LCVD comprises an amino acid sequences of any one of SEQ ID NOs: 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, and 92 or comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to any one of SEQ ID NOs: 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, and 92, optionally wherein the LCVD has at least one amino acid substituted with a histidine. [0494] Embodiment 90. The ABPC of embodiment 88 or 89, wherein the HCVD comprises a set of three H-CDRs selected from the group consisting of: SEQ ID NOs: 5, 6, and 7; SEQ ID NOs: 13, 14, and 15; SEQ ID NOs: 21, 22, and 23; SEQ ID NOs: 29, 30, and 31; SEQ ID NOs: 37, 38, and 39; SEQ ID NOs: 45, 46, and 47; SEQ ID NOs: 53, 54, and 55; SEQ ID NOs: 61, 62, and 63; SEQ ID NOs: 69, 70, and 71; SEQ ID NOs: 77, 78, and 79; SEQ ID NOs: 85, 86, and 87; SEQ ID Attorney Docket No.: 45395-0068WO1 NOs: 93, 94, and 95, optionally wherein the set of three H-CDRs has collectively one or more amino acid position substituted with a histidine. [0495] Embodiment 91. The ABPC of embodiment 89 or 90, wherein the LCVD comprises a set of three L-CDRs selected from the group consisting of: SEQ ID NOs: 8, 9, and 10; SEQ ID NOs: 16, 17, and 18; SEQ ID NOs: 24, 25, and 26; SEQ ID NOs: 32, 33, and 34; SEQ ID NOs: 40, 41, and 42; SEQ ID NOs: 48, 49, and 50; SEQ ID NOs: 56, 57, and 58; SEQ ID NOs: 64, 65, and 66; SEQ ID NOs: 72, 73, and 74; SEQ ID NOs: 80, 81, and 82; SEQ ID NOs: 88, 89, and 90; SEQ ID NOs: 96, 97, and 98, optionally wherein the set of three L-CDRs has collectively one or more amino acid position substituted with a histidine. [0496] Embodiment 92. The ABPC of any one of embodiments 85-91, wherein the ABPC is degraded in the target mammalian cell following internalization of the ABPC by the cell; and/or wherein the ABPC further comprises a conjugated toxin, radioisotope, drug, or small molecule; and/or wherein the ABPC provides for an increase in toxin liberation in the cell as compared to the same amount of a control ABPC. [0497] Embodiment 93. The ABPC of embodiment 92, wherein the ABPC provides for at least a 20%, 50%, 2-fold, or 5-fold increase in toxin liberation; and/or wherein the ABPC provides for an increase in target mammalian cell killing as compared to the same amount of a control ABPC. [0498] Embodiment 94. The ABPC of embodiment 93, wherein the composition provides for at least a 20%, 50%, 2-fold, or 5-fold increase in target mammalian cell killing as compared to the same amount of a control ABPC. [0499] Embodiment 95. The ABPC of any one of embodiments 85-94, wherein the ABPC provides for an increase in endolysosomal delivery in the target mammalian cell as compared to the same amount of a control ABPC; optionally wherein the increase is at least a 20%, 50%, 2- fold, or 5-fold increase. [0500] Embodiment 96. The ABPC of any one of embodiments 85-95, wherein the ABPC results in a less or no detectable reduction in the level of DLL3 presented on the surface of the target mammalian cell as compared to the same amount of a control ABPC. [0501] Embodiment 97. The ABPC of any one of embodiments 85-96, wherein the ABPC further comprises a second ABD. [0502] Embodiment 98. The ABPC of any one of embodiments 85-97, wherein the ABPC further comprises a conjugated toxin, radioisotope, drug, or small molecule. Attorney Docket No.: 45395-0068WO1 [0503] Embodiment 99. A kit comprising at least one dose of the ABPC of any one of embodiments 85-98. [0504] Embodiment 100. A method of treating a cancer characterized by having a population of DLL3-positive cancer cells, comprising administering a therapeutically effective amount of the ABPC of any one of embodiments 1-51, the composition of any one of embodiments 51-85, or the ABPC of any one of embodiments 85-98 to a subject identified as having a cancer characterized by having the population of cancer cells. [0505] Embodiment 101. A method of reducing the volume of a tumor in a subject, wherein the tumor is characterized by having DLL3-positive cancer cells, comprising administering a therapeutically effective amount of the ABPC of any one of embodiments 1-51, the composition of any one of embodiments 51-85, or the ABPC of any one of embodiments 85-98 to the subject. [0506] Embodiment 102. A method of inducing cell death in a DLL3-positive cancer cell in a subject, comprising administering a therapeutically effective amount of the ABPC of any one of embodiments 1-51, the composition of any one of embodiments 51-85, or the ABPC of any one of embodiments 85-98 to the subject. [0507] Embodiment 103. A method of decreasing the risk of developing a metastasis or an additional metastasis in a subject having a DLL3-positive cancer, comprising administering a therapeutically effective amount of the ABPC of any one of embodiments 1-51, the composition of any one of embodiments 51-85, or the ABPC of any one of embodiments 85-98 to the subject identified as having the DLL3-positive cancer. [0508] Embodiment 104. An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 125, 126, and 127, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 128, 129, and 130, respectively. [0509] Embodiment 105. The antigen-binding protein construct of embodiment 104, wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 123 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 124. Attorney Docket No.: 45395-0068WO1 [0510] Embodiment 106. The antigen-binding protein construct of embodiment 104 or 105, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 219 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 220. [0511] Embodiment 107. An antigen -binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 133, 134, and 135, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 136, 137, and 138, respectively. [0512] Embodiment 108. The antigen-binding protein construct of embodiment 107, wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 131 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 132. [0513] Embodiment 109. The antigen-binding protein construct of embodiment 107 or 108, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 221 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 222. [0514] Embodiment 110. An anti-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 141, 142, and 143, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 144, 145, and 146, respectively. [0515] Embodiment 111. The antigen-binding protein construct of embodiment 110, wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 139 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 140. Attorney Docket No.: 45395-0068WO1 [0516] Embodiment 112. The antigen-binding protein construct of embodiment 110 or 111, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 223 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 224. [0517] Embodiment 113. A antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 149, 150, and 151, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 152, 153, and 154, respectively. [0518] Embodiment 114. The antigen-binding protein construct of embodiment 113, wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 147 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 148. [0519] Embodiment 115. The antigen-binding protein construct of embodiment 113 or 114, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 225 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 226. [0520] Embodiment 116. An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 157, 158, and 159, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 160, 161, and 162, respectively. [0521] Embodiment 117. The antigen-binding protein construct of embodiment 116, wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 155 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 156. Attorney Docket No.: 45395-0068WO1 [0522] Embodiment 118. The antigen-binding protein construct of embodiment 116 or 117, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 227 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 228. [0523] Embodiment 119. An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 165, 166, and 167, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 168, 169, and 160, respectively. [0524] Embodiment 120. The antigen-binding protein construct of embodiment 119, wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 163 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 164. [0525] Embodiment 121. The antigen-binding protein construct of embodiment 119 or 120, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 229 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 230. [0526] Embodiment 122. An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 173, 174, and 175, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 176, 177, and 178, respectively. [0527] Embodiment 123. The antigen-binding protein construct of embodiment 122, wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 171 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 172. Attorney Docket No.: 45395-0068WO1 [0528] Embodiment 124. The antigen-binding protein construct of embodiment 122 or 123, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 231 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 232. [0529] Embodiment 125. An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 181, 182, and 183, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 184, 185, and 186, respectively. [0530] Embodiment 126. The antigen-binding protein construct of embodiment 125, wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 179 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 180. [0531] Embodiment 127. The antigen-binding protein construct of embodiment 122 or 123, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 233 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 234. [0532] Embodiment 128. An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 189, 190, and 191, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 192, 193, and 194, respectively. [0533] Embodiment 129. The antigen-binding protein construct of embodiment 128, wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 187 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 188. Attorney Docket No.: 45395-0068WO1 [0534] Embodiment 130. The antigen-binding protein construct of embodiment 128 or 129, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 235 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 236. [0535] Embodiment 131. An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 197, 198, and 199, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 200, 201, and 202, respectively. [0536] Embodiment 132. The antigen-binding protein construct of embodiment 131, wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 195 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 196. [0537] Embodiment 133. The antigen-binding protein construct of embodiment 131 or 132, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 237 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 238. [0538] Embodiment 133a. An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 205, 206, and 207, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 208, 209, and 210, respectively; or wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 203 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 204; or wherein the antigen-binding protein construct comprises a heavy chain comprising an amino acid sequence that is at least about Attorney Docket No.: 45395-0068WO1 90%, 95%, 98%, or 100% identical to SEQ ID NO: 239 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 240. [0539] Embodiment 133b. An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 213, 214, and 215, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 216, 217, and 218, respectively; or wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 211 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 212; or wherein the antigen-binding protein construct comprises a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 241 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 242. [0540] Embodiment 134. An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 5, 6, and 7, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 8, 9, and 10, respectively. [0541] Embodiment 135. The antigen-binding protein construct of embodiment 134, wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 3 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 4. [0542] Embodiment 136. The antigen-binding protein construct of embodiment 134 or 135, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 99 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 100. Attorney Docket No.: 45395-0068WO1 [0543] Embodiment 137. An antigen-binding protein construct comprising an antigen-binding domain of an antibody that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H- CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 181, 182, and 183, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 184, 185, and 186, respectively. [0544] Embodiment 138. The antigen-binding protein construct of embodiment 137, wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 187 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 188. [0545] Embodiment 139. The antigen-binding protein construct of embodiment 137 or 138, comprising a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 235 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 236. [0546] Embodiment 140. The antigen-binding protein construct of any one of embodiments 104 to 139, wherein the DLL3-binding protein construct is selected from the group of an antibody, a VHH-scAb, a VHH-Fab, a Dual scFab, a F(ab')2, a diabody, a crossMab, a DAF (two-in-one), a DAF (four-in-one), a DutaMab, a DT-IgG, a knobs-in-holes common light chain, a knobs-in-holes assembly, a charge pair, a Fab-arm exchange, a SEEDbody, a LUZ-Y, a Fcab, a κλ-body, an orthogonal Fab, a DVD-IgG, a IgG(H)-scFv, a scFv-(H)IgG, IgG(L)-scFv, scFv-(L)IgG, IgG(L,H)-Fv, IgG(H)-V, V(H)-IgG, IgG(L)-V, V(L)-IgG, KIH IgG-scFab, 2scFv-IgG, IgG- 2scFv, scFv4-Ig, Zybody, DVI-IgG, Diabody-CH3, a triple body, a miniantibody, a minibody, a TriBi minibody, scFv-CH3 KIH, Fab-scFv, a F(ab')2-scFv2, a scFv-KIH, a Fab-scFv-Fc, a tetravalent HCAb, a scDiabody-Fc, a Diabody-Fc, a tandem scFv-Fc, a VHH-Fc, a tandem VHH- Fc, a VHH-Fc KiH, a Fab-VHH-Fc, an Intrabody, a dock and lock, an ImmTAC, an IgG-IgG conjugate, a Cov-X-Body, a scFv1-PEG-scFv2, an Adnectin, a DARPin, a fibronectin, a DEP conjugate, and a PROTAB. Attorney Docket No.: 45395-0068WO1 [0547] Embodiment 141. The antigen-binding protein construct of embodiment 140, wherein the antigen-binding protein construct is a monoclonal antibody comprising an IgG heavy chain constant region. [0548] Embodiment 142. The antigen-binding protein construct of embodiment 140 or 141, comprising an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 123 or 219 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 124 or 220. [0549] Embodiment 143. The antigen-binding protein construct of embodiment 140 or 141, comprising an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 131 or 221 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 132 or 222. [0550] Embodiment 144. The antigen-binding protein construct of embodiment 140 or 141, comprising an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 139 or 223 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 140 or 224. [0551] Embodiment 145. The antigen-binding protein construct of embodiment 140 or 141, comprising an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 147 or 225 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 148 or 226. [0552] Embodiment 146. The antigen-binding protein construct of embodiment 140 or 141, comprising an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 155 or 227 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 156 or 228. [0553] Embodiment 147. The antigen-binding protein construct of embodiment 140 or 141, comprising an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 163 or 229 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 164 or 230. [0554] Embodiment 148. The antigen-binding protein construct of embodiment 140 or 141, comprising an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 171 or 231 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 172 or 232. Attorney Docket No.: 45395-0068WO1 [0555] Embodiment 149. The antigen-binding protein construct of embodiment 140 or 141, comprising an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 179 or 233 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 180 or 234. [0556] Embodiment 150. The antigen-binding protein construct of embodiment 140 or 141, comprising an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 187 or 235 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 188 or 236. [0557] Embodiment 151. The antigen-binding protein construct of embodiment 140 or 141, comprising an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 195 or 237 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 196 or 238. [0558] Embodiment 152. The antigen-binding protein construct of embodiment 140 or 141, comprising an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 203 or 239 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 204 or 240. [0559] Embodiment 153. The antigen-binding protein construct of embodiment 140 or 141, comprising an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 211 or 241 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 212 or 242. [0560] Embodiment 154. A pharmaceutical composition comprising the antigen-binding protein construct of any one of embodiments 104-153 and a pharmaceutically acceptable excipient. [0561] Embodiment 155. A method of treating a DLL-positive cancer in a subject in need thereof comprising administering to the subject the antigen-binding protein construct of any one of embodiments 104-153. [0562] Embodiment 156. A pharmaceutical composition comprising an effective amount of an antigen-binding protein construct (ABPC) comprising: a first antigen-binding domain (ABD) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell, wherein: the dissociation rate of the first ABD at a pH of ~4.0-6.5 is faster than the dissociation rate at a pH of ~7.0-8.0; and/or the KD of the first ABD at a pH of ~4.0-6.5 is greater than the KD at a pH of ~7.0-8.0. Attorney Docket No.: 45395-0068WO1 [0563] Embodiment 157. The pharmaceutical composition of embodiment 156, wherein the first ABD comprises a heavy chain variable domain (HCVD) amino acid sequence selected from one of SEQ ID NO: 3, SEQ ID NO: 11, SEQ ID NO: 19, SEQ ID NO: 27, SEQ ID NO: 35, SEQ ID NO: 43, SEQ ID NO: 51, SEQ ID NO: 59, SEQ ID NO: 67, SEQ ID NO: 75, SEQ ID NO: 83, and SEQ ID NO: 91, optionally wherein the HCVD has at least one amino acid substituted with a histidine. [0564] Embodiment 158. The pharmaceutical composition of embodiment 156 or 157, wherein the first ABD comprises a light chain variable domain (LCVD) amino acid sequence selected from one of SEQ ID NO: 4, SEQ ID NO: 12, SEQ ID NO: 20, SEQ ID NO: 28, SEQ ID NO: 36, SEQ ID NO: 44, SEQ ID NO: 52, SEQ ID NO: 60, SEQ ID NO: 68, SEQ ID NO: 76, SEQ ID NO: 84, and SEQ ID NO: 92, optionally wherein the HCVD has at least one amino acid substituted with a histidine. [0565] Embodiment 159. The pharmaceutical composition of embodiment 157 or 158, wherein the HCVD comprises an amino acid sequence of any one of SEQ ID NOs: 123, 131, 139, 147, 155, 163, 171, 179, 187, 195, 203, and 211 or comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to any one of SEQ ID NOs: 123, 131, 139, 147, 155, 163, 171, 179, 187, 195, 203, and 211, optionally wherein the HCVD has at least one amino acid substituted with a histidine. [0566] Embodiment 160. The pharmaceutical composition of embodiment 158 or 159, wherein the LCVD comprises an amino acid sequence of any one of SEQ ID NOs: 124, 132, 140, 148, 156, 164, 172, 180, 188, 196, 204, and 212 or comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to any one of SEQ ID NOs: 124, 132, 140, 148, 156, 164, 172, 180, 188, 196, 204, and 212, optionally wherein the LCVD has at least one amino acid substituted with a histidine. [0567] Embodiment 161. The pharmaceutical composition of embodiment 159 or 160, wherein the HCVD comprises a set of three H-CDRs selected from the group consisting of: SEQ ID NOs: 125, 126, and 127; SEQ ID NOs: 133, 134, and 135; SEQ ID NOs: 141, 142, and 143; SEQ ID NOs: 149, 150, and 151; SEQ ID NOs: 157, 158, and 159; SEQ ID NOs: 165, 166, and 167; SEQ ID NOs: 173, 174, and 175; SEQ ID NOs: 181, 182, and 183; SEQ ID NOs: 189, 190, and 191; SEQ ID NOs: 197, 198, and 199; SEQ ID NOs: 205, 206, and 207; SEQ ID NOs: 213, 214, and Attorney Docket No.: 45395-0068WO1 215, optionally wherein the set of three H-CDRs has collectively one or more position substituted with a histidine. [0568] Embodiment 162. The pharmaceutical composition of embodiment 160 or 161, wherein the LCVD comprises a set of three L-CDRs selected from the group consisting of: SEQ ID NOs: 128, 129, and 130; SEQ ID NOs: 136, 137, and 138; SEQ ID NOs: 144, 145, and 146; SEQ ID NOs: 152, 153, and 154; SEQ ID NOs: 160, 161, and 162; SEQ ID NOs: 168, 169, and 170; SEQ ID NOs: 176, 177, and 178; SEQ ID NOs: 184, 185, and 186; SEQ ID NOs: 192, 193, and 194; SEQ ID NOs: 200, 201, and 202; SEQ ID NOs: 208, 209, and 210; SEQ ID NOs: 216, 217, and 218, optionally wherein the set of three L-CDRs has collectively one or more position substituted with a histidine. [0569] Embodiment 163. The pharmaceutical composition of any one of embodiments 156-162, wherein the ABPC is degraded in the target mammalian cell following internalization of the ABPC by the target mammalian cell. [0570] Embodiment 164. The pharmaceutical composition of any one of embodiments 156-163, wherein the ABPC further comprises a conjugated toxin, radioisotope, drug, or small molecule. [0571] Embodiment 165. The pharmaceutical composition of embodiment 164, wherein the pharmaceutical composition provides for an increase in toxin liberation in the target mammalian cell as compared to a pharmaceutical composition comprising the same amount of a control ABPC. [0572] Embodiment 166. The pharmaceutical composition of embodiment 165, wherein the pharmaceutical composition provides for at least a 20%, 50%, 2-fold, or 5-fold increase in toxin liberation in the target mammalian cell as compared to a pharmaceutical composition comprising the same amount of a control ABPC. [0573] Embodiment 167. The pharmaceutical composition of any one of embodiments 164-166, wherein the pharmaceutical composition provides for an increase in target mammalian cell killing as compared to a pharmaceutical composition comprising the same amount of a control ABPC. [0574] Embodiment 168. The pharmaceutical composition of embodiment 167, wherein the pharmaceutical composition provides for at least a 20%, 50%, 2-fold, or 5-fold increase in target mammalian cell killing as compared to a pharmaceutical composition comprising the same amount of a control ABPC. [0575] Embodiment 169. The pharmaceutical composition of any one of embodiments 156-165, wherein the pharmaceutical composition provides for an increase in endolysosomal delivery in the Attorney Docket No.: 45395-0068WO1 target mammalian cell as compared to a pharmaceutical composition comprising the same amount of a control ABPC. [0576] Embodiment 170. The pharmaceutical composition of embodiment 169, wherein the pharmaceutical composition provides for at least a 20%, 50%, 2-fold, or 5-fold increase in endolysosomal delivery in the target mammalian cell as compared to a pharmaceutical composition comprising the same amount of a control ABPC. [0577] Embodiment 171. The pharmaceutical composition of any one of embodiments 156-170, wherein the pharmaceutical composition results in a less or no detectable reduction in the level of DLL3 presented on the surface of the target mammalian cell as compared to a pharmaceutical composition comprising the same amount of a control ABPC. [0578] Embodiment 172. A composition comprising an effective amount of an antigen-binding protein construct (ABPC) comprising: a first ABD that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell; and a conjugated toxin, radioisotope, drug, or small molecule, wherein: [0579] (a) the dissociation rate of the first ABD at a pH of ~4.0-6.5 is faster than the dissociation rate at a pH of ~7.0-8.0; or the dissociation constant (KD) of the first ABD at a pH of ~4.0-6.5 is greater than the KD at a pH of ~7.0-8.0; and [0580] (b) the composition provides for one or more of: (i) an increase in toxin liberation in the target mammalian cell as compared to a composition comprising the same amount of a control ABPC; (ii) an increase in target mammalian cell killing as compared to a composition comprising the same amount of a control ABPC; and/or (iii) an increase in endolysosomal delivery in the target mammalian cell as compared to a composition comprising the same amount of a control ABPC. [0581] Embodiment 173. The composition of embodiment 172, wherein the first ABD comprises a heavy chain variable domain (HCVD) amino acid sequence selected from one of SEQ ID NO: 3, SEQ ID NO: 11, SEQ ID NO: 19, SEQ ID NO: 27, SEQ ID NO: 35, SEQ ID NO: 43, SEQ ID NO: 51, SEQ ID NO: 59, SEQ ID NO: 67, SEQ ID NO: 75, SEQ ID NO: 83, and SEQ ID NO: 91, optionally wherein the HCVD has at least one amino acid substituted with a histidine. [0582] Embodiment 174. The composition of embodiment 172 or 173, wherein the first ABD comprises a light chain variable domain (LCVD) amino acid sequence selected from one of SEQ ID NO: 4, SEQ ID NO: 12, SEQ ID NO: 20, SEQ ID NO: 28, SEQ ID NO: 36, SEQ ID NO: 44, Attorney Docket No.: 45395-0068WO1 SEQ ID NO: 52, SEQ ID NO: 60, SEQ ID NO: 68, SEQ ID NO: 76, SEQ ID NO: 84, and SEQ ID NO: 92, optionally wherein the LCVD has at least one amino acid substituted with a histidine. [0583] Embodiment 175. The composition of embodiment 173 or 174, wherein the HCVD comprises an amino acid sequence of any one of SEQ ID NOs: 123, 131, 139, 147, 155, 163, 171, 179, 187, 195, 203, and 211 or comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to any one of SEQ ID NOs: 123, 131, 139, 147, 155, 163, 171, 179, 187, 195, 203, and 211, optionally wherein the HCVD has at least one amino acid substituted with a histidine. [0584] Embodiment 176. The composition of embodiment 174 or 175, wherein the LCVD comprises an amino acid sequence of any one of SEQ ID NOs: 124, 132, 140, 148, 156, 164, 172, 180, 188, 196, 204, and 212 or comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to any one of SEQ ID NOs: 124, 132, 140, 148, 156, 164, 172, 180, 188, 196, 204, and 212, optionally wherein the LCVD has at least one amino acid substituted with a histidine. [0585] Embodiment 177. The composition of embodiment 175 or 176, wherein the HCVD a set of three H-CDRs selected from the group consisting of: SEQ ID NOs: 125, 126, and 127; SEQ ID NOs: 133, 134, and 135; SEQ ID NOs: 141, 142, and 143; SEQ ID NOs: 149, 150, and 151; SEQ ID NOs: 157, 158, and 159; SEQ ID NOs: 165, 166, and 167; SEQ ID NOs: 173, 174, and 175; SEQ ID NOs: 181, 182, and 183; SEQ ID NOs: 189, 190, and 191; SEQ ID NOs: 197, 198, and 199; SEQ ID NOs: 205, 206, and 207; SEQ ID NOs: 213, 214, and 215, optionally wherein the set of three H-CDRs has collectively one or more amino acid position substituted with a histidine. [0586] Embodiment 178. The composition of embodiment 176 or 177, wherein the LCVD comprises a set of three L-CDRs selected from the group consisting of: SEQ ID NOs: 128, 129, and 130; SEQ ID NOs: 136, 137, and 138; SEQ ID NOs: 144, 145, and 146; SEQ ID NOs: 152, 153, and 154; SEQ ID NOs: 160, 161, and 162; SEQ ID NOs: 168, 169, and 170; SEQ ID NOs: 176, 177, and 178; SEQ ID NOs: 184, 185, and 186; SEQ ID NOs: 192, 193, and 194; SEQ ID NOs: 200, 201, and 202; SEQ ID NOs: 208, 209, and 210; SEQ ID NOs: 216, 217, and 218, optionally wherein the set of three L-CDRs has collectively one or more amino acid position substituted with a histidine. [0587] Embodiment 179. The composition of any one of embodiments 172 to 178, wherein the composition provides for at least a 20%, 50%, 2-fold, or 5-fold increase in toxin liberation in the Attorney Docket No.: 45395-0068WO1 target mammalian cell, and/or cell killing, and/or at least a 20%, 50%, 2-fold, or 5-fold increase in endolysosomal delivery as compared to a composition comprising the same amount of a control ABPC. [0588] Embodiment 180. The composition of any one of embodiments 156-179, wherein the dissociation rate of the first ABD at a pH of ~4.0-6.5 is at least 10%, 3-fold, or 10-fold faster than the dissociation rate of the first ABD at a pH of ~7.0-8.0 and/or the KD of the first ABD at a pH of ~4.0-6.5 is at least 10%, 3-fold, or 10-fold greater than the KD of the first ABD at a pH of ~7.0- 8.0. [0589] Embodiment 181. The composition of any one of embodiments 156-179, wherein the ABPC comprises a single polypeptide, optionally wherein the ABD is selected from a VH domain, a VHH domain, a VNAR domain, and a scFv; and/or wherein the ABPC is a BiTe, a (scFv)2, a nanobody, a nanobody-HSA, a DART, a TandAb, a scDiabody, a scDiabody-CH3, scFv-CH-CL- scFv, a HSAbody, scDiabody-HSA, a tandem-scFv, and a PROTAB. [0590] Embodiment 182. The composition of any one of embodiments 156-181, wherein the ABPC comprises two or more polypeptides. [0591] Embodiment 183. The composition of any one of embodiments 156-182, wherein at least one polypeptide of the ABPC is conjugated to the toxin, the radioisotope, the drug, or the small molecule via a cleavable or non-cleavable linker. [0592] Embodiment 184. The composition of any of embodiments 156-183, wherein the half-life of the ABPC in vivo is increased as compared to the half-life of a control ABPC in vivo, optionally wherein the increase is ~5%-95%, ~10%-95%, ~30%-95%, ~50%-95%, or ~70%-95% as compared to the half-life of a control ABPC in vivo. [0593] Embodiment 185. The composition of any one of embodiments 156-151, wherein the control ABPC is capable of specifically binding to DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell, wherein: [0594] (a) the control ABPC comprises a first ABD; [0595] (b) the dissociation rate of the first ABD of the control ABPC at a pH of ~4.0-6.5 is no more than 2-fold or 3-fold faster than the dissociation rate at a pH of ~7.0-8.0; and [0596] (c) the dissociation constant (KD) of the first ABD of the control ABPC at a pH of ~4.0- 6.5 is no more than 2-fold or 3-fold greater than the KD at a pH of ~7.0-8.0. Attorney Docket No.: 45395-0068WO1 [0597] Embodiment 186. The composition of any one of embodiments 156-185, wherein the ABPC further comprises a second ABD. [0598] Embodiment 187. A kit comprising at least one dose of the composition of any one of embodiments 156-186. [0599] Embodiment 188. An antigen-binding protein construct (ABPC) comprising: a first antigen-binding domain (ABD) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell, wherein: the dissociation rate of the first ABD at a pH of ~4.0-6.5 is faster than the dissociation rate at a pH of ~7.0-8.0; or the KD of the first ABD at a pH of ~4.0-6.5 is greater than the KD at a pH of ~7.0-8.0. [0600] Embodiment 189. The ABPC of embodiment 188, wherein the first ABD comprises a heavy chain variable domain (HCVD) amino acid sequence selected from one of SEQ ID NO: 3, SEQ ID NO: 11, SEQ ID NO: 19, SEQ ID NO: 27, SEQ ID NO: 35, SEQ ID NO: 43, SEQ ID NO: 51, SEQ ID NO: 59, SEQ ID NO: 67, SEQ ID NO: 75, SEQ ID NO: 83, and SEQ ID NO: 91, optionally wherein the HCVD has at least one amino acid substituted with a histidine. [0601] Embodiment 190. The ABPC of embodiment 188 or 189, wherein the first ABD comprises a light chain variable domain (LCVD) amino acid sequence selected from one of SEQ ID NO: 4, SEQ ID NO: 12, SEQ ID NO: 20, SEQ ID NO: 28, SEQ ID NO: 36, SEQ ID NO: 44, SEQ ID NO: 52, SEQ ID NO: 60, SEQ ID NO: 68, SEQ ID NO: 76, SEQ ID NO: 84, and SEQ ID NO: 92, optionally wherein the LCVD has at least one amino acid substituted with a histidine. [0602] Embodiment 191. The ABPC of embodiment 189 or 190, wherein the HCVD comprises an amino acid sequence of any one of SEQ ID NOs: 123, 131, 139, 147, 155, 163, 171, 179, 187, 195, 203, and 211 or comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to any one of SEQ ID NOs: 123, 131, 139, 147, 155, 163, 171, 179, 187, 195, 203, and 211, optionally wherein the HCVD has at least one amino acid substituted with a histidine. [0603] Embodiment 192. The ABPC of embodiment 190 or 191, wherein the LCVD comprises an amino acid sequence of any one of SEQ ID NOs: 124, 132, 140, 148, 156, 164, 172, 180, 188, 196, 204, and 212 or comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to any one of SEQ ID NOs: 124, 132, 140, 148, 156, 164, 172, 180, 188, 196, 204, and 212, optionally wherein the LCVD has at least one amino acid substituted with a histidine. [0604] Embodiment 193. The ABPC of embodiment 191 or 192, wherein the HCVD comprises a set of three H-CDRs selected from the group consisting of: SEQ ID NOs: 125, 126, and 127; Attorney Docket No.: 45395-0068WO1 SEQ ID NOs: 133, 134, and 135; SEQ ID NOs: 141, 142, and 143; SEQ ID NOs: 149, 150, and 151; SEQ ID NOs: 157, 158, and 159; SEQ ID NOs: 165, 166, and 167; SEQ ID NOs: 173, 174, and 175; SEQ ID NOs: 181, 182, and 183; SEQ ID NOs: 189, 190, and 191; SEQ ID NOs: 197, 198, and 199; SEQ ID NOs: 205, 206, and 207; SEQ ID NOs: 213, 214, and 215, optionally wherein the set of three H-CDRs has collectively one or more amino acid position substituted with a histidine. [0605] Embodiment 194. The ABPC of embodiment 192 or 193, wherein the LCVD comprises a set of three L-CDRs selected from the group consisting of: SEQ ID NOs: 128, 129, and 130; SEQ ID NOs: 136, 137, and 138; SEQ ID NOs: 144, 145, and 146; SEQ ID NOs: 152, 153, and 154; SEQ ID NOs: 160, 161, and 162; SEQ ID NOs: 168, 169, and 170; SEQ ID NOs: 176, 177, and 178; SEQ ID NOs: 184, 185, and 186; SEQ ID NOs: 192, 193, and 194; SEQ ID NOs: 200, 201, and 202; SEQ ID NOs: 208, 209, and 210; SEQ ID NOs: 216, 217, and 218, optionally wherein the set of three L-CDRs has collectively one or more amino acid position substituted with a histidine. [0606] Embodiment 195. The ABPC of any one of embodiments 188-194, wherein the ABPC is degraded in the target mammalian cell following internalization of the ABPC by the cell; and/or wherein the ABPC further comprises a conjugated toxin, radioisotope, drug, or small molecule; and/or wherein the ABPC provides for an increase in toxin liberation in the cell as compared to the same amount of a control ABPC. [0607] Embodiment 196. The ABPC of embodiment 195, wherein the ABPC provides for at least a 20%, 50%, 2-fold, or 5-fold increase in toxin liberation; and/or wherein the ABPC provides for an increase in target mammalian cell killing as compared to the same amount of a control ABPC. [0608] Embodiment 197. The ABPC of embodiment 196, wherein the composition provides for at least a 20%, 50%, 2-fold, or 5-fold increase in target mammalian cell killing as compared to the same amount of a control ABPC. [0609] Embodiment 198. The ABPC of any one of embodiments 188-197, wherein the ABPC provides for an increase in endolysosomal delivery in the target mammalian cell as compared to the same amount of a control ABPC; optionally wherein the increase is at least a 20%, 50%, 2- fold, or 5-fold increase. Attorney Docket No.: 45395-0068WO1 [0610] Embodiment 199. The ABPC of any one of embodiments 188-198, wherein the ABPC results in a less or no detectable reduction in the level of DLL3 presented on the surface of the target mammalian cell as compared to the same amount of a control ABPC. [0611] Embodiment 200. The ABPC of any one of embodiments 188-199, wherein the ABPC further comprises a second ABD. [0612] Embodiment 201. The ABPC of any one of embodiments 188-200, wherein the ABPC further comprises a conjugated toxin, radioisotope, drug, or small molecule. [0613] Embodiment 202. A kit comprising at least one dose of the ABPC of any one of embodiments 188-201. [0614] Embodiment 203. A method of treating a cancer characterized by having a population of DLL3-positive cancer cells, comprising administering a therapeutically effective amount of the ABPC of any one of embodiments 104-154, the composition of any one of embodiments 154-188, or the ABPC of any one of embodiments 188-201 to a subject identified as having a cancer characterized by having the population of cancer cells. [0615] Embodiment 204. A method of reducing the volume of a tumor in a subject, wherein the tumor is characterized by having DLL3-positive cancer cells, comprising administering a therapeutically effective amount of the ABPC of any one of embodiments 104-154, the composition of any one of embodiments 154-188, or the ABPC of any one of embodiments 188- 201 to the subject. [0616] Embodiment 205. A method of inducing cell death in a DLL3-positive cancer cell in a subject, comprising administering a therapeutically effective amount of the antigen-binding protein construct of any one of embodiments 104-154, the composition of any one of embodiments 154-188, or the ABPC of any one of embodiments 188-201 to the subject. [0617] Embodiment 206. A method of decreasing the risk of developing a metastasis or an additional metastasis in a subject having a DLL3-positive cancer, comprising administering a therapeutically effective amount of the ABPC of any one of embodiments 104-154, the composition of any one of embodiments 154-188, or the ABPC of any one of embodiments 188- 201 to the subject identified as having the DLL3-positive cancer. [0618] Embodiment 207. Use of the ABPC of any one of embodiments 108-158, the composition of any one of embodiments 158-192, or the ABPC of any one of embodiments 192-205 for treating Attorney Docket No.: 45395-0068WO1 a cancer characterized by having a population of DLL3-positive cancer cells in a subject identified as having said cancer. [0619] Embodiment 208. Use of the ABPC of any one of embodiments 108-158, the composition of any one of embodiments 158-192, or the ABPC of any one of embodiments 192-205 for reducing the volume of a tumor in a subject, wherein the tumor is characterized by having DLL3- positive cancer cells. [0620] Embodiment 209. Use of the ABPC of any one of embodiments 108-158, the composition of any one of embodiments 158-192, or the ABPC of any one of embodiments 192-205 for inducing cell death in a DLL3-positive cancer cell in a subject. [0621] Embodiment 210. Use of the ABPC of any one of embodiments 108-158, the composition of any one of embodiments 158-192, or the ABPC of any one of embodiments 192-205 for decreasing the risk of developing a metastasis or an additional metastasis in a subject having a DLL3-positive cancer . [0622] Embodiment 211. An isolated nucleic acid encoding an antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen- binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 205, 206, and 207, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L- CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 208, 209, and 210, respectively. [0623] Embodiment 212. The isolated nucleic acid of embodiment 211, wherein the nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 203, and the nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 204. [0624] Embodiment 213. The isolated nucleic acid of embodiment 211 or 212, comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 239, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or Attorney Docket No.: 45395-0068WO1 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 240. [0625] Embodiment 214. An isolated nucleic acid encoding an antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen- binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 13, 14, and 15, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L- CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 16, 17, and 18, respectively. [0626] Embodiment 215. The isolated nucleic acid of embodiment 214, wherein the nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 11, and the nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 12. [0627] Embodiment 216. The isolated nucleic acid of embodiment 214 or 215, comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 101, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 102. [0628] Embodiment 217. An isolated nucleic acid encoding an antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen- binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 21, 22, and 23, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L- CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 24, 25, and 26, respectively. Attorney Docket No.: 45395-0068WO1 [0629] Embodiment 218. The isolated nucleic acid of embodiment 217, wherein the nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 19, and the nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 20. [0630] Embodiment 219. The isolated nucleic acid of embodiment 217 or 218, comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 103, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 104. [0631] Embodiment 220. An isolated nucleic acid encoding an antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen- binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 29, 30, and 31, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L- CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 32, 33, and 34, respectively. [0632] Embodiment 221. The isolated nucleic acid of embodiment 10, wherein the nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 27, and the nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 28. [0633] Embodiment 222. The isolated nucleic acid of embodiment 220 or 221, comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 105, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or Attorney Docket No.: 45395-0068WO1 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 106. [0634] Embodiment 223. An isolated nucleic acid encoding an antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen- binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 37, 38, and 39, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L- CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 40, 41, and 42, respectively. [0635] Embodiment 224. The isolated nucleic acid of embodiment 13, wherein the nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 35, and the nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 36. [0636] Embodiment 225. The isolated nucleic acid of embodiment 223 or 224, comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 107, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 108. [0637] Embodiment 226. An isolated nucleic acid encoding an antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen- binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 45, 46, and 47, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L- CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 48, 49, and 50, respectively. Attorney Docket No.: 45395-0068WO1 [0638] Embodiment 227. The isolated nucleic acid of embodiment 226, wherein the nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 43, and the nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 44. [0639] Embodiment 228. The isolated nucleic acid of embodiment 226 or 227, comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 109, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 110. [0640] Embodiment 229. An isolated nucleic acid encoding an antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen- binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 53, 54, and 55, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L- CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 56, 57, and 58, respectively. [0641] Embodiment 230. The isolated nucleic acid of embodiment 19, wherein the nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 51, and the nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 52. [0642] Embodiment 231. The isolated nucleic acid of embodiment 229 or 230, comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 111, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or Attorney Docket No.: 45395-0068WO1 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 112. [0643] Embodiment 232. An isolated nucleic acid encoding an antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen- binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 61, 62, and 63, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L- CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 64, 65, and 66, respectively. [0644] Embodiment 233. The isolated nucleic acid of embodiment 232, wherein the nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 59, and the nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 60. [0645] Embodiment 234. The isolated nucleic acid of embodiment 232 or 233, comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 113, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 114. [0646] Embodiment 235. An isolated nucleic acid encoding an antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen- binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 69, 70, and 71, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L- CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 72, 73, and 74, respectively. Attorney Docket No.: 45395-0068WO1 [0647] Embodiment 236. The isolated nucleic acid of embodiment 235, wherein the nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 67, and the nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 68. [0648] Embodiment 237. The isolated nucleic acid of embodiment 235 or 236, comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 115, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 116. [0649] Embodiment 238. An isolated nucleic acid encoding an antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen- binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 77, 78, and 79, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L- CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 80, 81, and 82, respectively. [0650] Embodiment 239. The isolated nucleic acid of embodiment 238, wherein the nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 75, and the nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 76. [0651] Embodiment 240. The isolated nucleic acid of embodiment 248 or 249, comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 117, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or Attorney Docket No.: 45395-0068WO1 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 118. [0652] Embodiment 241. An isolated nucleic acid encoding an antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen- binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 85, 86, and 87, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L- CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 88, 89, and 90, respectively. [0653] Embodiment 242. The isolated nucleic acid of embodiment 241, wherein the nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 83, and the nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 84. [0654] Embodiment 243. The isolated nucleic acid of embodiment 241 or 242, comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 119, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 120. [0655] Embodiment 244. An isolated nucleic acid encoding an antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen- binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 93, 94, and 95, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L- CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 96, 97, and 98, respectively. Attorney Docket No.: 45395-0068WO1 [0656] Embodiment 245. The isolated nucleic acid of embodiment 244, wherein the nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 91, and the nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 92. [0657] Embodiment 246. The isolated nucleic acid of embodiment 244 or 245, comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 121, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 122. [0658] Embodiment 247. The isolated nucleic acid of any one of embodiments 211 to 246, wherein the nucleic acid encodes an antigen-binding protein construct selected from the group of an antibody, a VHH-scAb, a VHH-Fab, a Dual scFab, a F(ab')2, a diabody, a crossMab, a DAF (two-in-one), a DAF (four-in-one), a DutaMab, a DT-IgG, a knobs-in-holes common light chain, a knobs-in-holes assembly, a charge pair, a Fab-arm exchange, a SEEDbody, a LUZ-Y, a Fcab, a κλ-body, an orthogonal Fab, a DVD-IgG, a IgG(H)-scFv, a scFv-(H)IgG, IgG(L)-scFv, scFv- (L)IgG, IgG(L,H)-Fv, IgG(H)-V, V(H)-IgG, IgG(L)-V, V(L)-IgG, KIH IgG-scFab, 2scFv-IgG, IgG-2scFv, scFv4-Ig, Zybody, DVI-IgG, Diabody-CH3, a triple body, a miniantibody, a minibody, a TriBi minibody, scFv-CH3 KIH, Fab-scFv, a F(ab')2-scFv2, a scFv-KIH, a Fab-scFv-Fc, a tetravalent HCAb, a scDiabody-Fc, a Diabody-Fc, a tandem scFv-Fc, a VHH-Fc, a tandem VHH- Fc, a VHH-Fc KiH, a Fab-VHH-Fc, an Intrabody, a dock and lock, an ImmTAC, an IgG-IgG conjugate, a Cov-X-Body, a scFv1-PEG-scFv2, an Adnectin, a DARPin, a fibronectin, a DEP conjugate, and a PROTAB. [0659] Embodiment 248. The isolated nucleic acid of embodiment 247, wherein the nucleic acid encodes a monoclonal antibody comprising an IgG heavy chain constant region. [0660] Embodiment 249. The isolated nucleic acid of embodiment 247 or 248, comprising a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 99, and a Attorney Docket No.: 45395-0068WO1 nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 100. [0661] Embodiment 250. The isolated nucleic acid of embodiment 247 or 248, comprising a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 101, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 102. [0662] Embodiment 251. The isolated nucleic acid of embodiment 247 or 248, comprising a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 103, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 104. [0663] Embodiment 252. The isolated nucleic acid of embodiment 247 or 248, comprising a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 105, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 106. [0664] Embodiment 253. The isolated nucleic acid of embodiment 247 or 248, comprising a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 107, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 108. [0665] Embodiment 254. The isolated nucleic acid of embodiment 247 or 248, comprising a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 109, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 110. [0666] Embodiment 255. The isolated nucleic acid of embodiment 247 or 248, comprising a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 111, and a Attorney Docket No.: 45395-0068WO1 nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 112. [0667] Embodiment 256. The isolated nucleic acid of embodiment 247 or 248, comprising a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 113, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 114. [0668] Embodiment 257. The isolated nucleic acid of embodiment 247 or 248, comprising a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 115, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 116. [0669] Embodiment 258. The isolated nucleic acid of embodiment 247 or 248, comprising a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 117, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 118. [0670] Embodiment 259. The isolated nucleic acid of embodiment 247 or 248, comprising a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 119, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 120. [0671] Embodiment 260. The isolated nucleic acid of embodiment 247 or 248, comprising a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 121, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 122. [0672] Embodiment 261. An expression vector comprising the isolated nucleic acid of any one of embodiments 211-260. [0673] Embodiment 262. A host cell comprising the expression vector of embodiment 261. Attorney Docket No.: 45395-0068WO1 [0674] Embodiment 263. A method of producing an antigen-binding protein construct, the method comprising: (a) culturing the host cell of embodiment 262 under conditions suitable for expression of the antigen-binding protein construct; and (b) recovering the antigen-binding protein construct from the host cell or culture medium. [0675] Embodiment 264. An antigen-binding protein construct (ABPC) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell comprising at least one (1) antigen-binding domain (ABD), wherein: the first ABD includes a heavy chain variable domain (HCVD) of an HCVD having the amino acid sequence of one of SEQ ID NO: 3, SEQ ID NO: 11, SEQ ID NO: 19, SEQ ID NO: 27, SEQ ID NO: 35, SEQ ID NO: 43, SEQ ID NO: 51, SEQ ID NO: 59, SEQ ID NO: 67, SEQ ID NO: 75, SEQ ID NO: 83, and SEQ ID NO: 91, each HCVD optionally with at least 1 histidine substitution (e.g., one, two, three, four, or five total histidine substitutions across the set of three H-CDRs) and a light chain variable domain (LCVD) of an LCVD having the amino acid sequence of one of SEQ ID NO: 4, SEQ ID NO: 12, SEQ ID NO: 20, SEQ ID NO: 28, SEQ ID NO: 36, SEQ ID NO: 44, SEQ ID NO: 52, SEQ ID NO: 60, SEQ ID NO: 68, SEQ ID NO: 76, SEQ ID NO: 84, and SEQ ID NO: 92, each LCVD optionally with at least 1 histidine substitution (e.g., one, two, three, four, or five total histidine substitutions across the set of three L-CDRs). [0676] Embodiment 265. An antigen-binding protein construct (ABPC) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell comprising at least one (1) antigen-binding domain (ABD), wherein: the first ABD includes one of (a) to (l): (a) an HCVD of SEQ ID NO: 3 and/or an LCVD of SEQ ID NO: 4; (b) an HCVD of SEQ ID NO: 11 and/or an LCVD of SEQ ID NO: 12; (c) an HCVD of SEQ ID NO: 19 and/or an LCVD of SEQ ID NO: 20; (d) an HCVD of SEQ ID NO: 27 and/or an LCVD of SEQ ID NO: 28; (e) an HCVD of SEQ ID NO: 35 and/or an LCVD of SEQ ID NO: 36; (f) an HCVD of 43 and/or an LCVD of SEQ ID NO: 44; (g) an HCVD of 51 and/or an LCVD of SEQ ID NO: 52; (h) an HCVD of 59 and/or an LCVD of SEQ ID NO: 60; (i) an HCVD of r SEQ ID NO: 67 and/or an LCVD of SEQ ID NO: 68; (j) an HCVD of SEQ ID NO: 75 and/or an LCVD of SEQ ID NO: 76; (k) an HCVD of SEQ ID NO: 83 and/or an LCVD of SEQ ID NO: 84; and (l) an HCVD of SEQ ID NO: 91 and/or an LCVD of SEQ ID NO: 92, each, HCVD and/or LCVD optionally with one or more amino acids substituted with a histidine (e.g., one, two, three, four, or five total histidine Attorney Docket No.: 45395-0068WO1 substitutions across the set of three H-CDRs and/or one, two, three, four, or five total histidine substitutions across the set of three L-CDRs). [0677] Embodiment 266. An antigen-binding protein construct (ABPC) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell comprising at least one (1) antigen-binding domain (ABD), wherein: the first ABD includes one of (a) to (l): (a) an HCVD including the amino acid sequence of SEQ ID NO: 123 and/or an LCVD including the amino acid sequence of SEQ ID NO: 124; (b) an HCVD including the amino acid sequence of SEQ ID NO: 131 and/or an LCVD including the amino acid sequence of SEQ ID NO: 132; (c) an HCVD including the amino acid sequence of SEQ ID NO: 139 and/or an LCVD including the amino acid sequence of SEQ ID NO: 140; (d) an HCVD including the amino acid sequence of SEQ ID NO: 147 and/or an LCVD including the amino acid sequence of SEQ ID NO: 148; (e) an HCVD including the amino acid sequence of SEQ ID NO: 155 and/or an LCVD including the amino acid sequence of SEQ ID NO: 156; (f) an HCVD including the amino acid sequence of SEQ ID NO: 163 and/or an LCVD including the amino acid sequence of SEQ ID NO: 164; (g) an HCVD including the amino acid sequence of SEQ ID NO: 171 and/or an LCVD including the amino acid sequence of SEQ ID NO: 172; (h) an HCVD including the amino acid sequence of SEQ ID NO: 179 and/or an LCVD including the amino acid sequence of SEQ ID NO: 180; (i) an HCVD including the amino acid sequence of SEQ ID NO: 187 and/or an LCVD including the amino acid sequence of SEQ ID NO: 188; (j) an HCVD including the amino acid sequence of SEQ ID NO: 195 and/or an LCVD including the amino acid sequence of SEQ ID NO: 196; (k) an HCVD including the amino acid sequence of SEQ ID NO: 203 and/or an LCVD including the amino acid sequence of SEQ ID NO: 204; and (l) an HCVD including the amino acid sequence of SEQ ID NO: 211 and/or an LCVD including the amino acid sequence of SEQ ID NO: 212, each HCVD and/or LCVD optionally with one or more amino acids substituted with a histidine (e.g., one, two, three, four, or five total histidine substitutions across the set of three H- CDRs and/or one, two, three, four, or five total histidine substitutions across the set of three L- CDRs). [0678] Embodiment 267. An antigen-binding protein construct (ABPC) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell comprising at least one (1) antigen-binding domain (ABD), wherein: the first ABD includes one of (a) to (l): (a) an HCVD including the sequence of SEQ ID NO: 3 and/or an LCVD including Attorney Docket No.: 45395-0068WO1 the sequence of SEQ ID NO: 4; (b) an HCVD including the sequence of SEQ ID NO: 11 and/or an LCVD including the sequence of SEQ ID NO: 12; (c) an HCVD including the sequence of SEQ ID NO: 19 and/or an LCVD including the sequence of SEQ ID NO: 20; (d) an HCVD including the sequence of SEQ ID NO: 27 and/or an LCVD including the sequence of SEQ ID NO: 28; (e) an HCVD including the sequence of SEQ ID NO: 35 and/or an LCVD including the sequence of SEQ ID NO: 36; (f) an HCVD including the sequence of SEQ ID NO: 43 and/or an LCVD including the sequence of SEQ ID NO: 44; (g) an HCVD including the sequence of SEQ ID NO: 51 and/or an LCVD including the sequence of SEQ ID NO: 52; (h) an HCVD including the sequence of SEQ ID NO: 59 and/or an LCVD including the sequence of SEQ ID NO: 60; (i) an HCVD including the sequence of SEQ ID NO: 67 and/or an LCVD including the sequence of SEQ ID NO: 68; (j) an HCVD including the sequence of SEQ ID NO: 75 and/or an LCVD including the sequence of SEQ ID NO: 76; (k) an HCVD including the sequence of SEQ ID NO: 83 and/or an LCVD including the sequence of SEQ ID NO: 84; and (l) an HCVD including the sequence of SEQ ID NO: 91 and/or an LCVD including the sequence of SEQ ID NO: 92, each HCVD and/or LCVD optionally with one or more amino acids substituted with a histidine (e.g., one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or one, two, three, four, or five total histidine substitutions across the set of three L-CDRs); [0679] Embodiment 268. An antigen-binding protein construct (ABPC) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell comprising at least one (1) antigen-binding domain (ABD), wherein: the first ABD includes one of (a) to (l): (a) an HCVD including the sequence of SEQ ID NO: 123 and/or an LCVD including the sequence of SEQ ID NO: 124; (b) an HCVD including the sequence of SEQ ID NO: 131 and/or an LCVD including the sequence of SEQ ID NO: 132; (c) an HCVD including the sequence of SEQ ID NO: 139 and/or an LCVD including the sequence of SEQ ID NO: 140; (d) an HCVD including the sequence of SEQ ID NO: 147 and/or an LCVD including the sequence of SEQ ID NO: 148; (e) an HCVD including the sequence of SEQ ID NO: 155 and/or an LCVD including the sequence of SEQ ID NO: 156; (f) an HCVD including the sequence of SEQ ID NO: 163 and/or an LCVD including the sequence of SEQ ID NO: 164; (g) an HCVD including the sequence of SEQ ID NO: 171 and/or an LCVD including the sequence of SEQ ID NO: 172; (h) an HCVD including the sequence of SEQ ID NO: 179 and/or an LCVD including the sequence of SEQ ID NO: 180; (i) an HCVD including the sequence of SEQ ID NO: 187 and/or an LCVD Attorney Docket No.: 45395-0068WO1 including the sequence of SEQ ID NO: 188; (j) an HCVD including the sequence of SEQ ID NO: 195 and/or an LCVD including the sequence of SEQ ID NO: 196; (k) an HCVD including the sequence of SEQ ID NO: 203 and/or an LCVD including the sequence of SEQ ID NO: 204; and (l) an HCVD including the sequence of SEQ ID NO: 211 and/or an LCVD including the sequence of SEQ ID NO: 212, each HCVD and/or LCVD optionally with one or more amino acids substituted with a histidine (e.g., one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or one, two, three, four, or five total histidine substitutions across the set of three L-CDRs). [0680] Embodiment 269. An antigen-binding protein construct (ABPC) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell comprising at least one (1) antigen-binding domain (ABD), wherein: the first ABD includes a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein (a) the HCVD comprises an H-CDR1 sequence, an H-CDR2 sequence, and an H-CDR3 sequence selected from the group consisting of one of (i) to (xii): (i) the sequences of SEQ ID NO: 5, SEQ ID NO: 6, and SEQ ID NO: 7, respectively; (ii) the sequences of SEQ ID NO: 13, SEQ ID NO: 14, and SEQ ID NO: 15, respectively; (iii) the sequences of SEQ ID NO: 21, SEQ ID NO: 22, and SEQ ID NO: 23, respectively; (iv) the sequences of SEQ ID NO: 29, SEQ ID NO: 30, and SEQ ID NO: 31, respectively; (v) the sequences of SEQ ID NO: 37, SEQ ID NO: 38, and SEQ ID NO: 39, respectively; (vi) the sequences of SEQ ID NO: 45, SEQ ID NO: 46, and SEQ ID NO: 47, respectively; (vii) the sequences of SEQ ID NO: 53, SEQ ID NO: 54, and SEQ ID NO: 55, respectively; (viii) the sequences of SEQ ID NO: 61, SEQ ID NO: 62, and SEQ ID NO: 63, respectively; (ix) the sequences of SEQ ID NO: 69, SEQ ID NO: 70, and SEQ ID NO: 71, respectively; (x) the sequences of SEQ ID NO: 77, SEQ ID NO: 78, and SEQ ID NO: 79, respectively; (xi) the sequences of SEQ ID NO: 85, SEQ ID NO: 86, and SEQ ID NO: 87, respectively; and (xii) the sequences of SEQ ID NO: 93, SEQ ID NO: 94, and SEQ ID NO: 95, respectively; and/or (b) the LCVD comprises an L-CDR1 sequence, an L-CDR2 sequence, and an L-CDR3 sequence selected from the group consisting of one of (i) to (xii): (i) the sequences of SEQ ID NO: 8, SEQ ID NO: 9, and SEQ ID NO: 10, respectively; (ii) the sequences of SEQ ID NO: 16, SEQ ID NO: 17, and SEQ ID NO: 18, respectively; (iii) the sequences of SEQ ID NO: 24, SEQ ID NO: 25, and SEQ ID NO: 26, respectively; (iv) the sequences of SEQ ID NO: 32, SEQ ID NO: 33, and SEQ ID NO: 34, respectively; (v) the sequences of SEQ ID NO: 40, SEQ ID Attorney Docket No.: 45395-0068WO1 NO: 41, and SEQ ID NO: 42, respectively; (vi) the sequences of SEQ ID NO: 48, SEQ ID NO: 49, and SEQ ID NO: 50, respectively; (vii) the sequences of SEQ ID NO: 56, SEQ ID NO: 57, and SEQ ID NO: 58, respectively; (viii) the sequences of SEQ ID NO: 64, SEQ ID NO: 65, and SEQ ID NO: 66, respectively; (ix) the sequences of SEQ ID NO: 72, SEQ ID NO: 73, and SEQ ID NO: 74, respectively; (x) the sequences of SEQ ID NO: 80, SEQ ID NO: 81, and SEQ ID NO: 82, respectively; (xi) the sequences of SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 90, respectively; (xii) the sequences of SEQ ID NO: 96, SEQ ID NO: 97, and SEQ ID NO: 98, respectively. In some aspects, at least one of the H-CDR1, H-CDR2, and H-CDR3 sequences and/or at least one of the L-CDR1, L-CDR2, and L-CDR3 sequences has one or more amino acid position substituted with a histidine (e.g., one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or one, two, three, four, or five total histidine substitutions across the set of three L-CDRs). [0681] Embodiment 270. An antigen-binding protein construct (ABPC) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell comprising at least one (1) antigen-binding domain (ABD), wherein: the first ABD includes a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein (a) the HCVD comprises an H-CDR1 sequence, an H-CDR2 sequence, and an H-CDR3 sequence selected from the group consisting of one of (i) to (xii): (i) the sequences of SEQ ID NO: 125, SEQ ID NO: 126, and SEQ ID NO: 127, respectively; (ii) the sequences of SEQ ID NO: 133, SEQ ID NO: 134, and SEQ ID NO: 135, respectively; (iii) the sequences of SEQ ID NO: 141, SEQ ID NO: 142, and SEQ ID NO: 143, respectively; (iv) the sequences of SEQ ID NO: 149, SEQ ID NO: 150, and SEQ ID NO: 151, respectively; (v) the sequences of SEQ ID NO: 157, SEQ ID NO: 158, and SEQ ID NO: 159, respectively; (vi) the sequences of SEQ ID NO: 165, SEQ ID NO: 166, and SEQ ID NO: 167, respectively; (vii) the sequences of SEQ ID NO: 173, SEQ ID NO: 174, and SEQ ID NO: 175, respectively; (viii) the sequences of SEQ ID NO: 181, SEQ ID NO: 182, and SEQ ID NO: 183, respectively; (ix) the sequences of SEQ ID NO: 189, SEQ ID NO: 190, and SEQ ID NO: 191, respectively; (x) the sequences of SEQ ID NO: 197, SEQ ID NO: 198, and SEQ ID NO: 199, respectively; (xi) the sequences of SEQ ID NO: 205, SEQ ID NO: 206, and SEQ ID NO: 207, respectively; and (xii) the sequences of SEQ ID NO: 213, SEQ ID NO: 214, and SEQ ID NO: 215, respectively; and/or (b) the LCVD comprises an L-CDR1 sequence, an L-CDR2 sequence, and an L-CDR3 sequence selected from the group consisting of one of (i) to (xii): (i) the sequences of Attorney Docket No.: 45395-0068WO1 SEQ ID NO: 128, SEQ ID NO: 129, and SEQ ID NO: 130, respectively; (ii) the sequences of SEQ ID NO: 136, SEQ ID NO: 137, and SEQ ID NO: 138, respectively; (iii) the sequences of SEQ ID NO: 144, SEQ ID NO: 145, and SEQ ID NO: 146, respectively; (iv) the sequences of SEQ ID NO: 152, SEQ ID NO: 153, and SEQ ID NO: 154, respectively; (v) the sequences of SEQ ID NO: 160, SEQ ID NO: 161, and SEQ ID NO: 162, respectively; (vi) the sequences of SEQ ID NO: 168, SEQ ID NO: 169, and SEQ ID NO: 170, respectively; (vii) the sequences of SEQ ID NO: 176, SEQ ID NO: 177, and SEQ ID NO: 178, respectively; (viii) the sequences of SEQ ID NO: 184, SEQ ID NO: 185, and SEQ ID NO: 186, respectively; (ix) the sequences of SEQ ID NO: 192, SEQ ID NO: 193, and SEQ ID NO: 194, respectively; (x) the sequences of SEQ ID NO: 200, SEQ ID NO: 201, and SEQ ID NO: 202, respectively; (xi) the sequences of SEQ ID NO: 208, SEQ ID NO: 209, and SEQ ID NO: 210, respectively; (xii) the sequences of SEQ ID NO: 216, SEQ ID NO: 217, and SEQ ID NO: 218, respectively. In some aspects, at least one of the H-CDR1, H- CDR2, and H-CDR3 sequences and/or at least one of the L-CDR1, L-CDR2, and L-CDR3 sequences has one or more amino acid position substituted with a histidine (e.g., one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or one, two, three, four, or five total histidine substitutions across the set of three L-CDRs). [0682] Embodiment 271. An antigen-binding protein construct (ABPC) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell comprising at least one (1) antigen-binding domain (ABD), wherein the first ABD includes a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD) according to one of the following pairs of HCVD and LCVD ((a1/a2) to (l1/l2)): [0683] (a1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 203, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 203, and/or (3) the sequence of SEQ ID NO: 203 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 203, and (a2) the LCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 204, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 204, and/or (3) the sequence of SEQ ID NO: 204 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 204; Attorney Docket No.: 45395-0068WO1 [0684] (b1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 211, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 211, and/or (3) the sequence of SEQ ID NO: 211 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 211, and (b2) the LCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 212, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 212, and/or (3) the sequence of SEQ ID NO: 212 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 212; [0685] (c1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 171, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 171, and/or (3) the sequence of SEQ ID NO: 171 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 171, and (c2) the LCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 172, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 172, and/or (3) the sequence of SEQ ID NO: 172 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 172; [0686] (d1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 179, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 179, and/or (3) the sequence of SEQ ID NO: 179 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 179, and (d2) the LCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 180, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 180, and/or (3) the sequence of SEQ ID NO: 180 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 180; [0687] (e1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 187, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 187, and/or (3) the sequence of SEQ ID NO: 187 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: Attorney Docket No.: 45395-0068WO1 187, and (e2) the LCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 188, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 188, and/or (3) the sequence of SEQ ID NO: 188 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 188; [0688] (f1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 195, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 195, and/or (3) the sequence of SEQ ID NO: 195 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 195, and (f2) the LCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 196, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 196, and/or (3) the sequence of SEQ ID NO: 196 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 196; [0689] (g1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 123, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 123, and/or (3) the sequence of SEQ ID NO: 123 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 123, and (g2) the LCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 124, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 124, and/or (3) the sequence of SEQ ID NO: 124 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 124; [0690] (h1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 131, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 131, and/or (3) the sequence of SEQ ID NO: 131 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 131, and (h2) the LCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 132, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 132, and/or (3) the sequence of SEQ ID NO: 132 comprising a Attorney Docket No.: 45395-0068WO1 conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 132; [0691] (i1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 139, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 139, and/or (3) the sequence of SEQ ID NO: 139 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 139, and (i2) the LCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 140, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 140, and/or (3) the sequence of SEQ ID NO: 140 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 140; [0692] (j1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 147, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 147, and/or (3) the sequence of SEQ ID NO: 147 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 147, and (j2) the LCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 148, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 148, and/or (3) the sequence of SEQ ID NO: 148 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 148; [0693] (k1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 155, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 155, and/or (3) the sequence of SEQ ID NO: 155 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 155, and (k2) the LCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 156, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 156, and/or (3) the sequence of SEQ ID NO: 156 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 156; and [0694] (l1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 163, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of Attorney Docket No.: 45395-0068WO1 SEQ ID NO: 163, and/or (3) the sequence of SEQ ID NO: 163 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 163, and (l2) the LCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 164, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 164, and/or (3) the sequence of SEQ ID NO: 164 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 164. [0695] Embodiment 272. An antigen-binding protein construct (ABPC) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell comprising at least one (1) antigen-binding domain (ABD), wherein the first ABD includes a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD) according to one of the following pairs of HCVD and LCVD ((a1/a2) to (l1/l2)): [0696] (a1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 83, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 83, and/or (3) the sequence of SEQ ID NO: 83 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 83, and (a2) the LCVD comprising (1) the CDRs of the sequence of SEQ ID NO: 84, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 84, and/or (3) the sequence of SEQ ID NO: 84 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 84; [0697] (b1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 91, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 91, and/or (3) the sequence of SEQ ID NO: 91 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 91, and (b2) the LCVD comprising (1) the CDRs of the sequence of SEQ ID NO: 92, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 92, and/or (3) the sequence of SEQ ID NO: 92 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 92; [0698] (c1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 51, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 51, and/or (3) the sequence of SEQ ID NO: 51 comprising a conservative amino acid Attorney Docket No.: 45395-0068WO1 substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 51, and (c2) the LCVD comprising (1) the CDRs of the sequence of SEQ ID NO: 52, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 52, and/or (3) the sequence of SEQ ID NO: 52 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 52; [0699] (d1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 59, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 59, and/or (3) the sequence of SEQ ID NO: 59 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 59, and (d2) the LCVD comprising (1) the CDRs of the sequence of SEQ ID NO: 60, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 60, and/or (3) the sequence of SEQ ID NO: 60 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 60; [0700] (e1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 67, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 67, and/or (3) the sequence of SEQ ID NO: 67 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 67, and (e2) the LCVD comprising (1) the CDRs of the sequence of SEQ ID NO: 68, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 68, and/or (3) the sequence of SEQ ID NO: 68 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 68; [0701] (f1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 75, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 75, and/or (3) the sequence of SEQ ID NO: 75 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 75, and (f2) the LCVD comprising (1) the CDRs of the sequence of SEQ ID NO: 76, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 76, and/or (3) the sequence of SEQ ID NO: 76 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 76; [0702] (g1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 3, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of Attorney Docket No.: 45395-0068WO1 SEQ ID NO: 3, and/or (3) the sequence of SEQ ID NO: 3 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 3, and (g2) the LCVD comprising (1) the CDRs of the sequence of SEQ ID NO: 4, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 4, and/or (3) the sequence of SEQ ID NO: 4 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 4; [0703] (h1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 11, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 11, and/or (3) the sequence of SEQ ID NO: 11 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 11, and (h2) the LCVD comprising (1) the CDRs of the sequence of SEQ ID NO: 12, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 12, and/or (3) the sequence of SEQ ID NO: 12 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 12; [0704] (i1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 19, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 19, and/or (3) the sequence of SEQ ID NO: 19 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 19, and (i2) the LCVD comprising (1) the CDRs of the sequence of SEQ ID NO: 20, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 20, and/or (3) the sequence of SEQ ID NO: 20 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 20; [0705] (j1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 27, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 27, and/or (3) the sequence of SEQ ID NO: 27 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 27, and (j2) the LCVD comprising (1) the CDRs of the sequence of SEQ ID NO: 28, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 28, and/or (3) the sequence of SEQ ID NO: 28 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 28; Attorney Docket No.: 45395-0068WO1 [0706] (k1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 35, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 35, and/or (3) the sequence of SEQ ID NO: 35 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 35, and (k2) the LCVD comprising (1) the CDRs of the sequence of SEQ ID NO: 36, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 36, and/or (3) the sequence of SEQ ID NO: 36 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 36; and [0707] (l1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 43, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 43, and/or (3) the sequence of SEQ ID NO: 43 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 43, and (l2) the LCVD comprising (1) the CDRs of the sequence of SEQ ID NO: 44, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 44, and/or (3) the sequence of SEQ ID NO: 44 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 44. [0708] Embodiment 273. An isolated nucleic acid comprising a nucleotide sequence encoding a heavy chain variable domain (HCVD) and a nucleotide sequence encoding a light chain variable domain (LCVD) according to one of the following pairs of HCVD and LCVD ((a1/a2) to (l1/l2)): [0709] (a1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 203, and (a2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 204; [0710] (b1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 211, and (b2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 212; [0711] (c1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 171, and (c2) a nucleotide sequence Attorney Docket No.: 45395-0068WO1 encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 172; [0712] (d1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 179, and (d2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 180; [0713] (e1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 187, and (e2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 188; [0714] (f1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 195, and (f2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 196; [0715] (g1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 123, and (g2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 124; [0716] (h1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 131, and (h2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 132; [0717] (i1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 139, and (i2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 140; [0718] (j1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 147, and (j2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 148; Attorney Docket No.: 45395-0068WO1 [0719] (k1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 155, and (k2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 156; and [0720] (l1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 163, and (l2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 164. [0721] Embodiment 274. An isolated nucleic acid comprising a nucleotide sequence encoding a heavy chain variable domain (HCVD) and a nucleotide sequence encoding a light chain variable domain (LCVD) according to one of the following pairs of HCVD and LCVD ((a1/a2) to (l1/l2)): [0722] (a1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 83, and (a2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 84; [0723] (b1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 91, and (b2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 92; [0724] (c1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 51, and (c2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 52; [0725] (d1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 59, and (d2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 60; [0726] (e1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 67, and (e2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 68; Attorney Docket No.: 45395-0068WO1 [0727] (f1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 75, and (f2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 76; [0728] (g1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 3, and (g2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 4; [0729] (h1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 11, and (h2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 12; [0730] (i1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 19, and (i2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 20; [0731] (j1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 27, and (j2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 28; [0732] (k1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 35, and (k2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 36; and [0733] (l1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 43, and (l2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 44. [0734] Embodiment 275. An expression vector comprising the isolated nucleic acid of any one of embodiments 273 (a1/a2), 273 (b1/b2), 273 (c1/c2), 273 (d1/d2), 273 (e1/e2), 273 (f1/f2), 273 (g1/g2), 273 (h1/h2), 273 (i1/i2), 273 (j1/j2), 273 (k1/k2), 273 (l1/l2), 274 (a1/a2), 274 (b1/b2), Attorney Docket No.: 45395-0068WO1 274 (c1/c2), 274 (d1/d2), 274 (e1/e2), 274 (f1/f2), 274 (g1/g2), 274 (h1/h2), 274 (i1/i2), 274 (j1/j2), 274 (k1/k2), and 274 (l1/l2). [0735] Embodiment 276. A host cell comprising the expression vector of embodiment 275. [0736] Embodiment 277. A method of producing an antigen-binding protein construct, the method comprising: (a) culturing the host cell of embodiment 276 under conditions suitable for expression of the antigen-binding protein construct; and (b) recovering the antigen-binding protein construct from the host cell or culture medium. [0737] Embodiment 278. A pharmaceutical composition comprising an effective amount of the ABPC, antibody, or composition of any one of the preceding embodiments. OTHER EMBODIMENTS [0738] It is to be understood that while the invention has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims.

Claims

Attorney Docket No.: 45395-0068WO1 WHAT IS CLAIMED IS: 1. An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein the HCVD comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 205, 206, and 207, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 208, 209, and 210, respectively; and/or wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 203 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 204; and/or wherein the ABD comprises a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 239 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 240. 2. An antigen-binding protein construct comprising an antigen-binding domain (ABD) that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein: (a) the HCVD comprises heavy chain complementarity determining regions H-CDR1, H- CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 13, 14, and 15, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L- CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 16, 17, and 18, respectively; and/or wherein the ABD comprises an HCVD that comprises amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 11 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 12; or wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 101 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 102; (b) the ABD comprises an HCVD that comprises heavy chain complementarity determining regions H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set Attorney Docket No.: 45395-0068WO1 forth in SEQ ID NOs: 21, 22, and 23, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 24, 25, and 26, respectively; and/or wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 19 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 20; or wherein the ABD comprises a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 103 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 104; (c) the HCVD comprises heavy chain complementarity determining regions H-CDR1, H- CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 29, 30, and 31, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L- CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 32, 33, and 34, respectively; and/or wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 27 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 28; or wherein the ABD comprises a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 105 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 106; (d) the HCVD comprises heavy chain complementarity determining regions H-CDR1, H- CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 37, 38, and 39, respectively; and/or wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 40, 41, and 42, respectively; and/or wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 35 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 36; or wherein the ABD comprises a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 107 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 108; (e) the HCVD comprises heavy chain complementarity determining regions H-CDR1, H- CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 45, 46, and Attorney Docket No.: 45395-0068WO1 47, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L- CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 48, 49, and 50, respectively; and/or wherein the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 43 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 44; and/or the ABD comprises a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 109 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 110; (f) the HCVD comprises heavy chain complementarity determining regions H-CDR1, H- CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 53, 54, and 55, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L- CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 56, 57, and 58, respectively; and/or the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 51 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 52; and/or the ABD comprises a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 111 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 112; (g) the HCVD comprises heavy chain complementarity determining regions H-CDR1, H- CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 61, 62, and 63, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L- CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 64, 65, and 66, respectively; and/or the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 59 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 60; and/or the ABD comprises a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 113 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 114; (h) the HCVD comprises heavy chain complementarity determining regions H-CDR1, H- CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 69, 70, and 71, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L- Attorney Docket No.: 45395-0068WO1 CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 72, 73, and 74, respectively; and/or the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 67 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 68; and/or the ABD comprises a heavy chain comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 115 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 116; (i) the HCVD comprises heavy chain complementarity determining regions H-CDR1, H- CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 77, 78, and 79, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L- CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 80, 81, and 82, respectively; and/or the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 75 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 76; and/or the ABD comprises a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 117 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 118; (j) the HCVD comprises heavy chain complementarity determining regions H-CDR1, H- CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 85, 86, and 87, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L- CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 88, 89, and 90, respectively; and/or the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 83 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 84; and/or the ABD comprises a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 119 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 120; or (k) the HCVD comprises heavy chain complementarity determining regions H-CDR1, H- CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 93, 94, and 95, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L- CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 96, 97, and 98, Attorney Docket No.: 45395-0068WO1 respectively; and/or the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 91 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 92; and/or the ABD comprises a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 121 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to SEQ ID NO: 122; 3. The antigen-binding protein construct (ABPC) of any one of claims 1 or 2, wherein the antigen-binding protein construct is selected from the group of an antibody, a VHH-scAb, a VHH-Fab, a Dual scFab, a F(ab’)2, a diabody, a crossMab, a DAF (two-in-one), a DAF (four-in- one), a DutaMab, a DT-IgG, a knobs-in-holes common light chain, a knobs-in-holes assembly, a charge pair, a Fab-arm exchange, a SEEDbody, a LUZ-Y, a Fcab, a κλ-body, an orthogonal Fab, a DVD-IgG, a IgG(H)-scFv, a scFv-(H)IgG, IgG(L)-scFv, scFv-(L)IgG, IgG(L,H)-Fv, IgG(H)- V, V(H)-IgG, IgG(L)-V, V(L)-IgG, KIH IgG-scFab, 2scFv-IgG, IgG-2scFv, scFv4-Ig, Zybody, DVI-IgG, Diabody-CH3, a triple body, a miniantibody, a minibody, a TriBi minibody, scFv-CH3 KIH, Fab-scFv, a F(ab’)2-scFv2, a scFv-KIH, a Fab-scFv-Fc, a tetravalent HCAb, a scDiabody- Fc, a Diabody-Fc, a tandem scFv-Fc, a VHH-Fc, a tandem VHH-Fc, a VHH-Fc KiH, a Fab- VHH-Fc, an Intrabody, a dock and lock, an ImmTAC, an IgG-IgG conjugate, a Cov-X-Body, a scFv1-PEG-scFv2, an Adnectin, a DARPin, a fibronectin, a DEP conjugate, and a PROTAB. 4. The ABPC of claim 3, wherein the ABPC: (a) is a monoclonal antibody comprising an IgG heavy chain constant region; and comprises an HCVD and an LCVD of one of the following ((b) to (z)): (b) an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO: 99 and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO: 100; (c) an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO: 101 and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO: 102; Attorney Docket No.: 45395-0068WO1 (d) an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO: and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO:; (e) an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO: and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO:; (f) an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO: and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO:; (g) an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO: and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO:; (h) an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO: and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO:; (i) an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO: and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO:; Attorney Docket No.: 45395-0068WO1 (j) an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO: and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO:; (k) an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO: and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO:; (l) an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO: and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO:; (m) an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO: and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO:; (n) an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO: and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO:; (o) an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO: and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO:; Attorney Docket No.: 45395-0068WO1 (p) an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO: and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO:; (q) an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO: and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO:; (r) an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO: and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO:; (s) an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO: and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO:; (t) an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO: and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO:; (u) an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO: and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO:; Attorney Docket No.: 45395-0068WO1 (v) an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO: 187 and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO: 188; (w) an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO: 195 and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO: 196; (x) an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO: 203 and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO: 204; and (y) an HCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO: 211 and an LCVD that comprises a sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to, and optionally comprising the CDRs of, the sequence set forth in SEQ ID NO: 212. 5. A pharmaceutical composition comprising the antigen-binding protein construct of any one of claims 1 to 4 and a pharmaceutically acceptable excipient. 6. A method of treating a cancer in a subject in need thereof comprising administering to the subject the ABPC of any one of claims 1 to 4 or the pharmaceutical composition of claim 5. 7. A pharmaceutical composition comprising an effective amount of an antigen-binding protein construct (ABPC) comprising: a first antigen-binding domain (ABD) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell, optionally wherein: the dissociation rate of the first ABD at a pH of ~4.0-6.5 is faster than the dissociation rate at a pH of ~7.0-8.0; and/or the KD of the first ABD at a pH of ~4.0-6.5 is greater than the KD at a pH of ~7.0-8.0. Attorney Docket No.: 45395-0068WO1 8. The pharmaceutical composition of claim 5 or 7, wherein the HCVD comprises an amino acid sequence as set forth in one of SEQ ID NOs: 3, 11, 19, 27, 35, 43, 51, 59, 67, 75, 83, and 91 or comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally having the same CDRs as, an amino acid sequence as set forth in one of SEQ ID NOs: 3, 11, 19, 27, 35, 43, 51, 59, 67, 75, 83, and 91, optionally wherein the HCVD has at least one amino acid substituted with a histidine; and the LCVD comprises an amino acid sequence as set forth in one of SEQ ID NOs: 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, and 92 or comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally having the same CDRs as, an amino acid sequence as set forth in one of SEQ ID NOs: 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, and 92, optionally wherein the LCVD has at least one amino acid substituted with a histidine. 9. The pharmaceutical composition of claim 8, wherein the first ABD comprises a heavy chain variable domain (HCVD) amino acid sequence selected from one of SEQ ID NO: 3, SEQ ID NO: 11, SEQ ID NO: 19, SEQ ID NO: 27, SEQ ID NO: 35, SEQ ID NO: 43, SEQ ID NO: 51, SEQ ID NO: 59, SEQ ID NO: 67, SEQ ID NO: 75, SEQ ID NO: 83, and SEQ ID NO: 91, optionally wherein the HCVD has at least one amino acid substituted with a histidine; and/or the first ABD comprises a light chain variable domain (LCVD) amino acid sequence selected from one of SEQ ID NO: 4, SEQ ID NO: 12, SEQ ID NO: 20, SEQ ID NO: 28, SEQ ID NO: 36, SEQ ID NO: 44, SEQ ID NO: 52, SEQ ID NO: 60, SEQ ID NO: 68, SEQ ID NO: 76, SEQ ID NO: 84, and SEQ ID NO: 92, optionally wherein the LCVD has at least one amino acid substituted with a histidine. 10. The pharmaceutical composition of claim 8 or 9, wherein the HCVD comprises a set of three H-CDRs selected from the group consisting of: SEQ ID NOs: 5, 6, and 7; SEQ ID NOs: 13, 14, and 15; SEQ ID NOs: 21, 22, and 23; SEQ ID NOs: 29, 30, and 31; SEQ ID NOs: 37, 38, and 39; SEQ ID NOs: 45, 46, and 47; SEQ ID NOs: 53, 54, and 55; SEQ ID NOs: 61, 62, and 63; SEQ ID NOs: 69, 70, and 71; SEQ ID NOs: 77, 78, and 79; SEQ ID NOs: 85, 86, and 87; SEQ ID NOs: 93, 94, and 95, optionally wherein the set of three H-CDRs has collectively one or more position substituted with a histidine; and/or the LCVD comprises a set of three L-CDRs selected from the group consisting of: SEQ ID NOs: 8, 9, and 10; SEQ ID NOs: 16, 17, and 18; SEQ ID NOs: 24, 25, and 26; SEQ ID NOs: 32, 33, and 34; SEQ ID NOs: 40, 41, and 42; SEQ ID NOs: 48, 49, and 50; SEQ ID NOs: 56, 57, and 58; SEQ ID NOs: 64, 65, and 66; SEQ ID Attorney Docket No.: 45395-0068WO1 NOs: 72, 73, and 74; SEQ ID NOs: 80, 81, and 82; SEQ ID NOs: 88, 89, and 90; SEQ ID NOs: 96, 97, and 98, optionally wherein the set of three L-CDRs has collectively one or more position substituted with a histidine. 11. The pharmaceutical composition of any one of the preceding claims, wherein the ABPC is degraded in the target mammalian cell following internalization of the ABPC by the target mammalian cell; and/or wherein the ABPC further comprises a conjugated toxin, radioisotope, drug, or small molecule; and/or wherein the pharmaceutical composition results in a less or no detectable reduction in the level of DLL3 presented on the surface of the target mammalian cell. 12. A conjugated composition comprising an effective amount of an antigen-binding protein construct (ABPC) comprising: a first ABD that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell and wherein the first ABD comprises an HCVD and an LCVD; and a conjugated toxin, radioisotope, drug, or small molecule, wherein: (a) the first ABD comprises an HCVD amino acid sequence selected from one of SEQ ID NO: 3, SEQ ID NO: 11, SEQ ID NO: 19, SEQ ID NO: 27, SEQ ID NO: 35, SEQ ID NO: 43, SEQ ID NO: 51, SEQ ID NO: 59, SEQ ID NO: 67, SEQ ID NO: 75, SEQ ID NO: 83, and SEQ ID NO: 91, optionally wherein the HCVD has at least one amino acid substituted with a histidine; and/or (b) the first ABD comprises a light chain variable domain (LCVD) amino acid sequence selected from one of SEQ ID NO: 4, SEQ ID NO: 12, SEQ ID NO: 20, SEQ ID NO: 28, SEQ ID NO: 36, SEQ ID NO: 44, SEQ ID NO: 52, SEQ ID NO: 60, SEQ ID NO: 68, SEQ ID NO: 76, SEQ ID NO: 84, and SEQ ID NO: 92, optionally wherein the HCVD has at least one amino acid substituted with a histidine; and/or (c) the HCVD comprises an amino acid sequence of any one of SEQ ID NOs: 3, 11, 19, 27, 35, 43, 51, 59, 67, 75, 83, and 91 or comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to an amino acid sequence of any one of SEQ ID NOs: 3, 11, 19, 27, 35, 43, 51, 59, 67, 75, 83, and 91, optionally wherein the HCVD has at least one amino acid substituted with a histidine; and/or (d) the LCVD comprises an amino acid sequence of any one of SEQ ID NOs: 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, and 92 or comprises an amino acid sequence that is at least about Attorney Docket No.: 45395-0068WO1 90%, 95%, 98%, or 100% identical to an amino acid sequence of any one of SEQ ID NOs: 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, and 92, optionally wherein the LCVD has at least one amino acid substituted with a histidine; and/or (e) the HCVD comprises a set of three H-CDRs selected from the group consisting of: SEQ ID NOs: 5, 6, and 7; SEQ ID NOs: 13, 14, and 15; SEQ ID NOs: 21, 22, and 23; SEQ ID NOs: 29, 30, and 31; SEQ ID NOs: 37, 38, and 39; SEQ ID NOs: 45, 46, and 47; SEQ ID NOs: 53, 54, and 55; SEQ ID NOs: 61, 62, and 63; SEQ ID NOs: 69, 70, and 71; SEQ ID NOs: 77, 78, and 79; SEQ ID NOs: 85, 86, and 87; SEQ ID NOs: 93, 94, and 95, optionally wherein the set of three H-CDRs has collectively one or more amino acid position substituted with a histidine; and/or (f) the LCVD comprises a set of three L-CDRs selected from the group consisting of: SEQ ID NOs: 8, 9, and 10; SEQ ID NOs: 16, 17, and 18; SEQ ID NOs: 24, 25, and 26; SEQ ID NOs: 32, 33, and 34; SEQ ID NOs: 40, 41, and 42; SEQ ID NOs: 48, 49, and 50; SEQ ID NOs: 56, 57, and 58; SEQ ID NOs: 64, 65, and 66; SEQ ID NOs: 72, 73, and 74; SEQ ID NOs: 80, 81, and 82; SEQ ID NOs: 88, 89, and 90; SEQ ID NOs: 96, 97, and 98, optionally wherein the set of three L-CDRs has collectively one or more amino acid position substituted with a histidine; and/or wherein the ABPC comprises a single polypeptide, optionally wherein the first ABD is selected from a VH domain, a VHH domain, a VNAR domain, and a scFv; and/or wherein the ABPC is a BiTe, a (scFv)2, a nanobody, a nanobody-HSA, a DART, a TandAb, a scDiabody, a scDiabody- CH3, scFv-CH-CL-scFv, a HSAbody, scDiabody-HSA, a tandem-scFv, and a PROTAB. 13. The ABPC or composition of any one of the preceding claims, wherein the ABPC comprises two or more polypeptides; and/or wherein at least one polypeptide of the ABPC is conjugated to a payload via a cleavable or non-cleavable linker, optionally wherein the payload is selected from a nucleic acid, a steroid, a toxin, a radioisotope, a drug, and a small molecule. 14. The ABPC or composition of any one of the preceding claims, wherein the ABPC further comprises a second ABD. 15. A kit comprising at least one dose of the ABPC or composition of any one of the preceding claims. Attorney Docket No.: 45395-0068WO1 16. An antigen-binding protein construct (ABPC) comprising a first ABD comprising a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein: (a) the HCVD comprises an amino acid sequence selected from one of SEQ ID NO: 3, SEQ ID NO: 11, SEQ ID NO: 19, SEQ ID NO: 27, SEQ ID NO: 35, SEQ ID NO: 43, SEQ ID NO: 51, SEQ ID NO: 59, SEQ ID NO: 67, SEQ ID NO: 75, SEQ ID NO: 83, and SEQ ID NO: 91, optionally wherein the HCVD has at least one amino acid substituted with a histidine; and/or (b) the LCVD comprises an amino acid sequence selected from one of SEQ ID NO: 4, SEQ ID NO: 12, SEQ ID NO: 20, SEQ ID NO: 28, SEQ ID NO: 36, SEQ ID NO: 44, SEQ ID NO: 52, SEQ ID NO: 60, SEQ ID NO: 68, SEQ ID NO: 76, SEQ ID NO: 84, and SEQ ID NO: 92, optionally wherein the HCVD has at least one amino acid substituted with a histidine; and/or (c) the HCVD comprises an amino acid sequence of any one of SEQ ID NOs: 3, 11, 19, 27, 35, 43, 51, 59, 67, 75, 83, and 91 or comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally having the same CDRs as, any one of SEQ ID NOs: 3, 11, 19, 27, 35, 43, 51, 59, 67, 75, 83, and 91, optionally wherein the HCVD has at least one amino acid substituted with a histidine; and/or wherein the LCVD comprises an amino acid sequences of any one of SEQ ID NOs: 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, and 92 or comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally having the same CDRs as, any one of SEQ ID NOs: 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, and 92, optionally wherein the LCVD has at least one amino acid substituted with a histidine; (d) the HCVD comprises a set of three H-CDRs selected from the group consisting of: SEQ ID NOs: 5, 6, and 7; SEQ ID NOs: 13, 14, and 15; SEQ ID NOs: 21, 22, and 23; SEQ ID NOs: 29, 30, and 31; SEQ ID NOs: 37, 38, and 39; SEQ ID NOs: 45, 46, and 47; SEQ ID NOs: 53, 54, and 55; SEQ ID NOs: 61, 62, and 63; SEQ ID NOs: 69, 70, and 71; SEQ ID NOs: 77, 78, and 79; SEQ ID NOs: 85, 86, and 87; SEQ ID NOs: 93, 94, and 95, optionally wherein the set of three H-CDRs has collectively one or more amino acid position substituted with a histidine; and/or (e) the LCVD comprises a set of three L-CDRs selected from the group consisting of: SEQ ID NOs: 8, 9, and 10; SEQ ID NOs: 16, 17, and 18; SEQ ID NOs: 24, 25, and 26; SEQ ID NOs: 32, 33, and 34; SEQ ID NOs: 40, 41, and 42; SEQ ID NOs: 48, 49, and 50; SEQ ID NOs: 56, 57, and 58; SEQ ID NOs: 64, 65, and 66; SEQ ID NOs: 72, 73, and 74; SEQ ID NOs: 80, 81, Attorney Docket No.: 45395-0068WO1 and 82; SEQ ID NOs: 88, 89, and 90; SEQ ID NOs: 96, 97, and 98, optionally wherein the set of three L-CDRs has collectively one or more amino acid position substituted with a histidine. 17. A method of treating a cancer characterized by having a population of DLL3-positive cancer cells, comprising administering a therapeutically effective amount of the ABPC or composition of any one of the preceding claims to a subject identified as having a cancer characterized by having the population of cancer cells. 18. A method of reducing the volume of a tumor in a subject, wherein the tumor is characterized by having DLL3-positive cancer cells, comprising administering a therapeutically effective amount of the ABPC or composition of any one of the preceding claims to the subject. 19. A method of inducing cell death in a DLL3-positive cancer cell in a subject, comprising administering a therapeutically effective amount of the ABPC or composition of any one of the preceding claims to the subject. 20. A method of decreasing the risk of developing a metastasis or an additional metastasis in a subject having a DLL3-positive cancer, comprising administering a therapeutically effective amount of the ABPC or composition of any one of the preceding claims to the subject identified as having the DLL3-positive cancer. 21. An antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein: (a) the HCVD comprises heavy chain complementarity determining regions H-CDR1, H- CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 125, 126, and 127, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 128, 129, and 130, respectively; and/or the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 123 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 124; and/or comprises a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 219 and a light chain comprising Attorney Docket No.: 45395-0068WO1 an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 220; (b) the HCVD comprises heavy chain complementarity determining regions H-CDR1, H- CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 133, 134, and 135, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 136, 137, and 138, respectively; and/or the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 131 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 132; and/or comprises a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 221 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 222; (c) the HCVD comprises heavy chain complementarity determining regions H-CDR1, H- CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 141, 142, and 143, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 144, 145, and 146, respectively; and/or the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 139 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 140; and/or comprises a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 223 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 224; (d) the HCVD comprises heavy chain complementarity determining regions H-CDR1, H- CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 149, 150, and 151, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 152, 153, and 154, respectively; and/or the HCVD comprises an amino acid sequence that is at least about 90%, Attorney Docket No.: 45395-0068WO1 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 147 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 148; and/or comprises a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 225 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 226; (e) the HCVD comprises heavy chain complementarity determining regions H-CDR1, H- CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 157, 158, and 159, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 160, 161, and 162, respectively; and/or the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 155 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 156; and/or comprises a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 227 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 228; (f) the HCVD comprises heavy chain complementarity determining regions H-CDR1, H- CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 165, 166, and 167, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 168, 169, and 160, respectively; and/or the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 163 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 164; and/or comprises a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 229 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 230; Attorney Docket No.: 45395-0068WO1 (g) the HCVD comprises heavy chain complementarity determining regions H-CDR1, H- CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 173, 174, and 175, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 176, 177, and 178, respectively; and/or the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 171 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 172; and/or comprises a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 231 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 232; (h) the HCVD comprises heavy chain complementarity determining regions H-CDR1, H- CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 181, 182, and 183, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 184, 185, and 186, respectively; and/or the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 179 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 180; and/or comprises a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 233 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 234; (i) the HCVD comprises heavy chain complementarity determining regions H-CDR1, H- CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 189, 190, and 191, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 192, 193, and 194, respectively; and/or the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 187 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% Attorney Docket No.: 45395-0068WO1 identical to, and optionally has the same CDRs of, SEQ ID NO: 188; and/or comprises a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 235 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 236; (j) the HCVD comprises heavy chain complementarity determining regions H-CDR1, H- CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 197, 198, and 199, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 200, 201, and 202, respectively; and/or the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 195 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 196; and/or comprises a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 237 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 238; (k) the HCVD comprises heavy chain complementarity determining regions H-CDR1, H- CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 205, 206, and 207, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 208, 209, and 210, respectively; and/or the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 203 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 204; and/or comprises a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 239 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 240; or (l) the HCVD comprises heavy chain complementarity determining regions H-CDR1, H- CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 213, 214, Attorney Docket No.: 45395-0068WO1 and 215, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 216, 217, and 218, respectively; and/or the HCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 211 and the LCVD comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 212; and/or comprises a heavy chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 241 and a light chain comprising an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs of, SEQ ID NO: 242. 22. The antigen-binding protein construct of claim 21, wherein the DLL3-binding protein construct is selected from the group of an antibody, a VHH-scAb, a VHH-Fab, a Dual scFab, a F(ab')2, a diabody, a crossMab, a DAF (two-in-one), a DAF (four-in-one), a DutaMab, a DT- IgG, a knobs-in-holes common light chain, a knobs-in-holes assembly, a charge pair, a Fab-arm exchange, a SEEDbody, a LUZ-Y, a Fcab, a κλ-body, an orthogonal Fab, a DVD-IgG, a IgG(H)- scFv, a scFv-(H)IgG, IgG(L)-scFv, scFv-(L)IgG, IgG(L,H)-Fv, IgG(H)-V, V(H)-IgG, IgG(L)-V, V(L)-IgG, KIH IgG-scFab, 2scFv-IgG, IgG-2scFv, scFv4-Ig, Zybody, DVI-IgG, Diabody-CH3, a triple body, a miniantibody, a minibody, a TriBi minibody, scFv-CH3 KIH, Fab-scFv, a F(ab')2-scFv2, a scFv-KIH, a Fab-scFv-Fc, a tetravalent HCAb, a scDiabody-Fc, a Diabody-Fc, a tandem scFv-Fc, a VHH-Fc, a tandem VHH-Fc, a VHH-Fc KiH, a Fab-VHH-Fc, an Intrabody, a dock and lock, an ImmTAC, an IgG-IgG conjugate, a Cov-X-Body, a scFv1-PEG-scFv2, an Adnectin, a DARPin, a fibronectin, a DEP conjugate, and a PROTAB. 23. The antigen-binding protein construct of claim 22, wherein the antigen-binding protein construct is a monoclonal antibody comprising an IgG heavy chain constant region; and/or comprising an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 123 or 219 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 124 or 220. 24. The antigen-binding protein construct of claim 22 or 23, comprising: Attorney Docket No.: 45395-0068WO1 (a) an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 131 or 221 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 132 or 222; (b) an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 139 or 223 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 140 or 224; (c) an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 147 or 225 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 148 or 226; (d) an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 155 or 227 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 156 or 228; (e) an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 163 or 229 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 230; (f) an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 231 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 164 or 232; (g) an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 179 or 233 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 180 or 234; (h) an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 187 or 235 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 188 or 236; (i) an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 195 or 237 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 196 or 238; (j) an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 203 or 239 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 204 or 240; or Attorney Docket No.: 45395-0068WO1 (k) an HCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 211 or 241 and an LCVD sequence that is at least 96%, 97%, 98%, at least 99%, or 100% identical to the sequence set forth in SEQ ID NO: 212 or 242. 25. A pharmaceutical composition comprising the antigen-binding protein construct of any one of claims 21 to 24 and a pharmaceutically acceptable excipient. 26. A method of treating a DLL-positive cancer in a subject in need thereof comprising administering to the subject the antigen-binding protein construct of any one of claims 21 to 24 or the pharmaceutical composition of claim 25. 27. The ABPC of any one of claims 21 to 24 or the pharmaceutical composition of claim 25, wherein: (a) the HCVD comprises an amino acid sequence of any one of SEQ ID NOs: 123, 131, 139, 147, 155, 163, 171, 179, 187, 195, 203, and 211 or comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs as, any one of SEQ ID NOs: 123, 131, 139, 147, 155, 163, 171, 179, 187, 195, 203, and 211, optionally wherein the HCVD has at least one amino acid substituted with a histidine; and the LCVD comprises an amino acid sequence of any one of SEQ ID NOs: 124, 132, 140, 148, 156, 164, 172, 180, 188, 196, 204, and 212 or comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs as, any one of SEQ ID NOs: 124, 132, 140, 148, 156, 164, 172, 180, 188, 196, 204, and 212, optionally wherein the LCVD has at least one amino acid substituted with a histidine; or (b) the HCVD comprises a set of three H-CDRs selected from the group consisting of: SEQ ID NOs: 125, 126, and 127; SEQ ID NOs: 133, 134, and 135; SEQ ID NOs: 141, 142, and 143; SEQ ID NOs: 149, 150, and 151; SEQ ID NOs: 157, 158, and 159; SEQ ID NOs: 165, 166, and 167; SEQ ID NOs: 173, 174, and 175; SEQ ID NOs: 181, 182, and 183; SEQ ID NOs: 189, 190, and 191; SEQ ID NOs: 197, 198, and 199; SEQ ID NOs: 205, 206, and 207; SEQ ID NOs: 213, 214, and 215, optionally wherein the set of three H-CDRs has collectively one or more position substituted with a histidine; and the LCVD comprises a set of three L-CDRs selected from the group consisting of: SEQ ID NOs: 128, 129, and 130; SEQ ID NOs: 136, 137, and 138; SEQ ID NOs: 144, 145, and 146; SEQ ID NOs: 152, 153, and 154; SEQ ID NOs: 160, 161, and 162; SEQ ID NOs: 168, 169, and 170; SEQ ID NOs: 176, 177, and 178; SEQ ID NOs: 184, 185, Attorney Docket No.: 45395-0068WO1 and 186; SEQ ID NOs: 192, 193, and 194; SEQ ID NOs: 200, 201, and 202; SEQ ID NOs: 208, 209, and 210; SEQ ID NOs: 216, 217, and 218, optionally wherein the set of three L-CDRs has collectively one or more position substituted with a histidine. 28. ABPC of any one of claims 21 to 24 or the pharmaceutical composition of claim 25, wherein: (a) the HCVD comprises an amino acid sequence of any one of SEQ ID NOs: 123, 131, 139, 147, 155, 163, 171, 179, 187, 195, 203, and 211 or comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs as, any one of SEQ ID NOs: 123, 131, 139, 147, 155, 163, 171, 179, 187, 195, 203, and 211; and the LCVD comprises an amino acid sequence of any one of SEQ ID NOs: 124, 132, 140, 148, 156, 164, 172, 180, 188, 196, 204, and 212 or comprises an amino acid sequence that is at least about 90%, 95%, 98%, or 100% identical to, and optionally has the same CDRs as, any one of SEQ ID NOs: 124, 132, 140, 148, 156, 164, 172, 180, 188, 196, 204, and 212; or (b) the HCVD a set of three H-CDRs selected from the group consisting of: SEQ ID NOs: 125, 126, and 127; SEQ ID NOs: 133, 134, and 135; SEQ ID NOs: 141, 142, and 143; SEQ ID NOs: 149, 150, and 151; SEQ ID NOs: 157, 158, and 159; SEQ ID NOs: 165, 166, and 167; SEQ ID NOs: 173, 174, and 175; SEQ ID NOs: 181, 182, and 183; SEQ ID NOs: 189, 190, and 191; SEQ ID NOs: 197, 198, and 199; SEQ ID NOs: 205, 206, and 207; SEQ ID NOs: 213, 214, and 215; and the LCVD comprises a set of three L-CDRs selected from the group consisting of: SEQ ID NOs: 128, 129, and 130; SEQ ID NOs: 136, 137, and 138; SEQ ID NOs: 144, 145, and 146; SEQ ID NOs: 152, 153, and 154; SEQ ID NOs: 160, 161, and 162; SEQ ID NOs: 168, 169, and 170; SEQ ID NOs: 176, 177, and 178; SEQ ID NOs: 184, 185, and 186; SEQ ID NOs: 192, 193, and 194; SEQ ID NOs: 200, 201, and 202; SEQ ID NOs: 208, 209, and 210; SEQ ID NOs: 216, 217, and 218. 29. The ABPC or composition of any one of the preceding claims, wherein at least one polypeptide of the ABPC is conjugated to the toxin, the radioisotope, the drug, or the small molecule via a cleavable or non-cleavable linker; and/or wherein the half-life of the ABPC in vivo is increased as compared to the half-life of a control ABPC in vivo, optionally wherein the increase is ~5%-95%, ~10%-95%, ~30%-95%, ~50%-95%, or ~70%-95% as compared to the half-life of a control ABPC in vivo. Attorney Docket No.: 45395-0068WO1 30. The composition of any one of the preceding claims, wherein the ABPC further comprises a second ABD. 31. A kit comprising at least one dose of the composition of any one of the preceding claims. 32. The ABPC of any one of the preceding claims, wherein the ABPC is degraded in the target mammalian cell following internalization of the ABPC by the cell; and/or wherein the ABPC further comprises a conjugated toxin, radioisotope, drug, or small molecule; and/or wherein the ABPC provides for an increase in toxin liberation in the cell as compared to the same amount of a control ABPC. 33. Use of the ABPC, composition, or pharmaceutical composition of any one of the preceding claims for treating a cancer characterized by having a population of DLL3-positive cancer cells in a subject identified as having said cancer; and/or use of the ABPC, composition, or pharmaceutical composition of any one of the preceding claims for reducing the volume of a tumor in a subject, wherein the tumor is characterized by having DLL3-positive cancer cells; and/or use of the ABPC, composition, or pharmaceutical composition of any one of the preceding claims for inducing cell death in a DLL3-positive cancer cell in a subject; and/or use of the ABPC, composition, or pharmaceutical composition of any one of the preceding claims for decreasing the risk of developing a metastasis or an additional metastasis in a subject having a DLL3-positive cancer. 34. An isolated nucleic acid encoding an antigen-binding protein construct comprising an antigen-binding domain that specifically binds to DLL3, wherein the antigen-binding domain comprises a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein: (a) the HCVD comprises heavy chain CDRs H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 205, 206, and 207, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 208, 209, and 210, respectively; and/or wherein the nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 203, and the nucleic acid encoding the LCVD Attorney Docket No.: 45395-0068WO1 comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 204; and/or comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 239, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 240; (b) the HCVD comprises heavy chain CDRs H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 13, 14, and 15, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 16, 17, and 18, respectively; and/or wherein the nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 11, and the nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 12; and/or comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 101, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 102; (c) the HCVD comprises heavy chain CDRs H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 21, 22, and 23, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 24, 25, and 26, respectively; and/or wherein the nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 19, and the nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 20; and/or comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical Attorney Docket No.: 45395-0068WO1 to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 103, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 104; (d) the HCVD comprises heavy chain CDRs H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 29, 30, and 31, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 32, 33, and 34, respectively; and/or wherein the nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 27, and the nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 28; and/or comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 105, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 106; (e) the HCVD comprises heavy chain CDRs H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 37, 38, and 39, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 40, 41, and 42, respectively; and/or wherein the nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 35, and the nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 36; and/or comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 107, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% Attorney Docket No.: 45395-0068WO1 identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 108; (f) the HCVD comprises heavy chain CDRs H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 45, 46, and 47, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 48, 49, and 50, respectively; and/or wherein the nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 43, and the nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 44; and/or comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 109, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 110; (g) the HCVD comprises heavy chain CDRs H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 53, 54, and 55, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 56, 57, and 58, respectively; and/or wherein the nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 51, and the nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 52; and/or comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 111, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 112; Attorney Docket No.: 45395-0068WO1 (h) the HCVD comprises heavy chain CDRs H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 61, 62, and 63, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 64, 65, and 66, respectively; and/or wherein the nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 59, and the nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 60; and/or comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 113, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 114; (i) the HCVD comprises heavy chain CDRs H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 69, 70, and 71, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 72, 73, and 74, respectively; and/or wherein the nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 67, and the nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 68; and/or comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 115, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 116; (j) the HCVD comprises heavy chain CDRs H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 77, 78, and 79, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising Attorney Docket No.: 45395-0068WO1 the amino acid sequences set forth in SEQ ID NOs: 80, 81, and 82, respectively; and/or wherein the nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 75, and the nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 76; and/or comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 117, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 118; (k) the HCVD comprises heavy chain CDRs H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 85, 86, and 87, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 88, 89, and 90, respectively; and/or wherein the nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 83, and the nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 84; and/or comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 119, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 120; or, (l) the HCVD comprises heavy chain CDRs H-CDR1, H-CDR2, and H-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 93, 94, and 95, respectively; and wherein the LCVD comprises light chain CDRs L-CDR1, L-CDR2, and L-CDR3, comprising the amino acid sequences set forth in SEQ ID NOs: 96, 97, and 98, respectively; and/or wherein the nucleic acid encoding the HCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence Attorney Docket No.: 45395-0068WO1 set forth in SEQ ID NO: 91, and the nucleic acid encoding the LCVD comprises a nucleotide sequence that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 92; and/or comprising a nucleotide sequence encoding a heavy chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 121, and a nucleotide sequence encoding a light chain that is at least about 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 122. 35. The isolated nucleic acid of any one of the preceding claims, wherein the nucleic acid encodes an antigen-binding protein construct selected from the group of an antibody, a VHH- scAb, a VHH-Fab, a Dual scFab, a F(ab')2, a diabody, a crossMab, a DAF (two-in-one), a DAF (four-in-one), a DutaMab, a DT-IgG, a knobs-in-holes common light chain, a knobs-in-holes assembly, a charge pair, a Fab-arm exchange, a SEEDbody, a LUZ-Y, a Fcab, a κλ-body, an orthogonal Fab, a DVD-IgG, a IgG(H)-scFv, a scFv-(H)IgG, IgG(L)-scFv, scFv-(L)IgG, IgG(L,H)-Fv, IgG(H)-V, V(H)-IgG, IgG(L)-V, V(L)-IgG, KIH IgG-scFab, 2scFv-IgG, IgG- 2scFv, scFv4-Ig, Zybody, DVI-IgG, Diabody-CH3, a triple body, a miniantibody, a minibody, a TriBi minibody, scFv-CH3 KIH, Fab-scFv, a F(ab')2-scFv2, a scFv-KIH, a Fab-scFv-Fc, a tetravalent HCAb, a scDiabody-Fc, a Diabody-Fc, a tandem scFv-Fc, a VHH-Fc, a tandem VHH-Fc, a VHH-Fc KiH, a Fab-VHH-Fc, an Intrabody, a dock and lock, an ImmTAC, an IgG- IgG conjugate, a Cov-X-Body, a scFv1-PEG-scFv2, an Adnectin, a DARPin, a fibronectin, a DEP conjugate, and a PROTAB. 36. The isolated nucleic acid of claim 35, wherein the nucleic acid encodes a monoclonal antibody comprising an IgG heavy chain constant region. 37. The isolated nucleic acid of claim 35 or 36, comprising: (a) a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 99, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 100; Attorney Docket No.: 45395-0068WO1 (b) a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 101, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 102; (c) a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 103, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 104; (d) a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 105, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 106; (e) a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 107, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 108; (f) a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 109, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 110; (g) a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 111, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 112; Attorney Docket No.: 45395-0068WO1 (h) a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 113, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 114; (i) a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 115, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 116; (j) a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 117, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 118; (k) a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 119, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 120; or (l) a nucleotide sequence encoding an HCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 121, and a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 122. 38. An antigen-binding protein construct (ABPC) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell comprising at least one (1) antigen-binding domain (ABD), wherein: the first ABD includes a heavy chain variable domain (HCVD) of an HCVD having the amino acid sequence of one of SEQ ID NO: 3, SEQ ID NO: 11, SEQ ID NO: 19, SEQ ID NO: 27, SEQ ID NO: 35, SEQ ID NO: 43, SEQ ID NO: 51, SEQ ID NO: 59, SEQ ID NO: 67, SEQ ID NO: 75, SEQ ID NO: 83, and SEQ ID NO: Attorney Docket No.: 45395-0068WO1 91, each HCVD optionally with at least 1 histidine substitution (e.g., one, two, three, four, or five total histidine substitutions across the set of three H-CDRs) and a light chain variable domain (LCVD) of an LCVD having the amino acid sequence of one of SEQ ID NO: 4, SEQ ID NO: 12, SEQ ID NO: 20, SEQ ID NO: 28, SEQ ID NO: 36, SEQ ID NO: 44, SEQ ID NO: 52, SEQ ID NO: 60, SEQ ID NO: 68, SEQ ID NO: 76, SEQ ID NO: 84, and SEQ ID NO: 92, each LCVD optionally with at least 1 histidine substitution (e.g., one, two, three, four, or five total histidine substitutions across the set of three L-CDRs). 39. An antigen-binding protein construct (ABPC) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell comprising at least one (1) antigen-binding domain (ABD), wherein: the first ABD includes one of (a) to (l): (a) an HCVD of SEQ ID NO: 3 and/or an LCVD of SEQ ID NO: 4; (b) an HCVD of SEQ ID NO: 11 and/or an LCVD of SEQ ID NO: 12; (c) an HCVD of SEQ ID NO: 19 and/or an LCVD of SEQ ID NO: 20; (d) an HCVD of SEQ ID NO: 27 and/or an LCVD of SEQ ID NO: 28; (e) an HCVD of SEQ ID NO: 35 and/or an LCVD of SEQ ID NO: 36; (f) an HCVD of 43 and/or an LCVD of SEQ ID NO: 44; (g) an HCVD of 51 and/or an LCVD of SEQ ID NO: 52; (h) an HCVD of 59 and/or an LCVD of SEQ ID NO: 60; (i) an HCVD of r SEQ ID NO: 67 and/or an LCVD of SEQ ID NO: 68; (j) an HCVD of SEQ ID NO: 75 and/or an LCVD of SEQ ID NO: 76; (k) an HCVD of SEQ ID NO: 83 and/or an LCVD of SEQ ID NO: 84; and (l) an HCVD of SEQ ID NO: 91 and/or an LCVD of SEQ ID NO: 92, each, HCVD and/or LCVD optionally with one or more amino acids substituted with a histidine (e.g., one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or one, two, three, four, or five total histidine substitutions across the set of three L-CDRs). 40. An antigen-binding protein construct (ABPC) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell comprising at least one (1) antigen-binding domain (ABD), wherein: the first ABD includes one of (a) to (l): (a) an HCVD including the amino acid sequence of, and/or the same CDRs as, the sequence of SEQ ID NO: 123 and/or an LCVD including the amino acid sequence of, and/or the same CDRs as, the sequence of SEQ ID NO: 124; Attorney Docket No.: 45395-0068WO1 (b) an HCVD including the amino acid sequence of, and/or the same CDRs as, the sequence of SEQ ID NO: 131 and/or an LCVD including the amino acid sequence of, and/or the same CDRs as, the sequence of SEQ ID NO: 132; (c) an HCVD including the amino acid sequence of, and/or the same CDRs as, the sequence of SEQ ID NO: 139 and/or an LCVD including the amino acid sequence of, and/or the same CDRs as, the sequence of SEQ ID NO: 140; (d) an HCVD including the amino acid sequence of, and/or the same CDRs as, the sequence of SEQ ID NO: 147 and/or an LCVD including the amino acid sequence of, and/or the same CDRs as, the sequence of SEQ ID NO: 148; (e) an HCVD including the amino acid sequence of, and/or the same CDRs as, the sequence of SEQ ID NO: 155 and/or an LCVD including the amino acid sequence of, and/or the same CDRs as, the sequence of SEQ ID NO: 156; (f) an HCVD including the amino acid sequence of, and/or the same CDRs as, the sequence of SEQ ID NO: 163 and/or an LCVD including the amino acid sequence of, and/or the same CDRs as, the sequence of SEQ ID NO: 164; (g) an HCVD including the amino acid sequence of, and/or the same CDRs as, the sequence of SEQ ID NO: 171 and/or an LCVD including the amino acid sequence of, and/or the same CDRs as, the sequence of SEQ ID NO: 172; (h) an HCVD including the amino acid sequence of, and/or the same CDRs as, the sequence of SEQ ID NO: 179 and/or an LCVD including the amino acid sequence of, and/or the same CDRs as, the sequence of SEQ ID NO: 180; (i) an HCVD including the amino acid sequence of, and/or the same CDRs as, the sequence of SEQ ID NO: 187 and/or an LCVD including the amino acid sequence of, and/or the same CDRs as, the sequence of SEQ ID NO: 188; (j) an HCVD including the amino acid sequence of, and/or the same CDRs as, the sequence of SEQ ID NO: 195 and/or an LCVD including the amino acid sequence of, and/or the same CDRs as, the sequence of SEQ ID NO: 196; Attorney Docket No.: 45395-0068WO1 (k) an HCVD including the amino acid sequence of, and/or the same CDRs as, the sequence of SEQ ID NO: 203 and/or an LCVD including the amino acid sequence of, and/or the same CDRs as, the sequence of SEQ ID NO: 204; and (l) an HCVD including the amino acid sequence of, and/or the same CDRs as, the sequence of SEQ ID NO: 211 and/or an LCVD including the amino acid sequence of, and/or the same CDRs as, the sequence of SEQ ID NO: 212, each HCVD and/or LCVD optionally with one or more amino acids substituted with a histidine (e.g., one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or one, two, three, four, or five total histidine substitutions across the set of three L-CDRs). 41. An antigen-binding protein construct (ABPC) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell comprising at least one (1) antigen-binding domain (ABD), wherein: the first ABD includes one of (a) to (l): (a) an HCVD including the sequence of SEQ ID NO: 3 and/or an LCVD including the sequence of SEQ ID NO: 4; (b) an HCVD including the sequence of SEQ ID NO: 11 and/or an LCVD including the sequence of SEQ ID NO: 12; (c) an HCVD including the sequence of SEQ ID NO: 19 and/or an LCVD including the sequence of SEQ ID NO: 20; (d) an HCVD including the sequence of SEQ ID NO: 27 and/or an LCVD including the sequence of SEQ ID NO: 28; (e) an HCVD including the sequence of SEQ ID NO: 35 and/or an LCVD including the sequence of SEQ ID NO: 36; (f) an HCVD including the sequence of SEQ ID NO: 43 and/or an LCVD including the sequence of SEQ ID NO: 44; (g) an HCVD including the sequence of SEQ ID NO: 51 and/or an LCVD including the sequence of SEQ ID NO: 52; (h) an HCVD including the sequence of SEQ ID NO: 59 and/or an LCVD including the sequence of SEQ ID NO: 60; (i) an HCVD including the sequence of SEQ ID NO: 67 and/or an LCVD including the sequence of SEQ ID NO: 68; (j) an HCVD including the sequence of SEQ ID NO: 75 and/or an LCVD including the sequence of SEQ ID NO: 76; (k) an HCVD including the sequence of SEQ ID NO: 83 and/or an LCVD including the sequence of SEQ ID NO: 84; and (l) an HCVD including the sequence of SEQ ID NO: 91 and/or an LCVD including the sequence of SEQ ID NO: 92, each HCVD and/or LCVD optionally with one or more amino acids substituted with a histidine (e.g., one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or one, two, three, four, or five total histidine substitutions across the set of three L-CDRs); Attorney Docket No.: 45395-0068WO1 42. An antigen-binding protein construct (ABPC) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell comprising at least one (1) antigen-binding domain (ABD), wherein: the first ABD includes one of (a) to (l): (a) an HCVD including the sequence of SEQ ID NO: 123 and/or an LCVD including the sequence of SEQ ID NO: 124; (b) an HCVD including the sequence of SEQ ID NO: 131 and/or an LCVD including the sequence of SEQ ID NO: 132; (c) an HCVD including the sequence of SEQ ID NO: 139 and/or an LCVD including the sequence of SEQ ID NO: 140; (d) an HCVD including the sequence of SEQ ID NO: 147 and/or an LCVD including the sequence of SEQ ID NO: 148; (e) an HCVD including the sequence of SEQ ID NO: 155 and/or an LCVD including the sequence of SEQ ID NO: 156; (f) an HCVD including the sequence of SEQ ID NO: 163 and/or an LCVD including the sequence of SEQ ID NO: 164; (g) an HCVD including the sequence of SEQ ID NO: 171 and/or an LCVD including the sequence of SEQ ID NO: 172; (h) an HCVD including the sequence of SEQ ID NO: 179 and/or an LCVD including the sequence of SEQ ID NO: 180; (i) an HCVD including the sequence of SEQ ID NO: 187 and/or an LCVD including the sequence of SEQ ID NO: 188; (j) an HCVD including the sequence of SEQ ID NO: 195 and/or an LCVD including the sequence of SEQ ID NO: 196; (k) an HCVD including the sequence of SEQ ID NO: 203 and/or an LCVD including the sequence of SEQ ID NO: 204; and (l) an HCVD including the sequence of SEQ ID NO: 211 and/or an LCVD including the sequence of SEQ ID NO: 212, each HCVD and/or LCVD optionally with one or more amino acids substituted with a histidine (e.g., one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or one, two, three, four, or five total histidine substitutions across the set of three L-CDRs). 43. An antigen-binding protein construct (ABPC) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell comprising at least one (1) antigen-binding domain (ABD), wherein: the first ABD includes a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein (a) the HCVD comprises an H-CDR1 sequence, an H-CDR2 sequence, and an H-CDR3 sequence selected from the group consisting of one of (i) to (xii): (i) the sequences of SEQ ID NO: 5, SEQ ID NO: 6, and SEQ ID NO: 7, respectively; (ii) the sequences of SEQ ID NO: 13, SEQ ID NO: 14, and SEQ ID NO: 15, respectively; (iii) the sequences of SEQ ID NO: 21, SEQ ID NO: 22, and SEQ ID NO: 23, respectively; (iv) the sequences of SEQ ID NO: 29, SEQ ID NO: 30, and SEQ ID Attorney Docket No.: 45395-0068WO1 NO: 31, respectively; (v) the sequences of SEQ ID NO: 37, SEQ ID NO: 38, and SEQ ID NO: 39, respectively; (vi) the sequences of SEQ ID NO: 45, SEQ ID NO: 46, and SEQ ID NO: 47, respectively; (vii) the sequences of SEQ ID NO: 53, SEQ ID NO: 54, and SEQ ID NO: 55, respectively; (viii) the sequences of SEQ ID NO: 61, SEQ ID NO: 62, and SEQ ID NO: 63, respectively; (ix) the sequences of SEQ ID NO: 69, SEQ ID NO: 70, and SEQ ID NO: 71, respectively; (x) the sequences of SEQ ID NO: 77, SEQ ID NO: 78, and SEQ ID NO: 79, respectively; (xi) the sequences of SEQ ID NO: 85, SEQ ID NO: 86, and SEQ ID NO: 87, respectively; and (xii) the sequences of SEQ ID NO: 93, SEQ ID NO: 94, and SEQ ID NO: 95, respectively; and/or (b) the LCVD comprises an L-CDR1 sequence, an L-CDR2 sequence, and an L-CDR3 sequence selected from the group consisting of one of (i) to (xii): (i) the sequences of SEQ ID NO: 8, SEQ ID NO: 9, and SEQ ID NO: 10, respectively; (ii) the sequences of SEQ ID NO: 16, SEQ ID NO: 17, and SEQ ID NO: 18, respectively; (iii) the sequences of SEQ ID NO: 24, SEQ ID NO: 25, and SEQ ID NO: 26, respectively; (iv) the sequences of SEQ ID NO: 32, SEQ ID NO: 33, and SEQ ID NO: 34, respectively; (v) the sequences of SEQ ID NO: 40, SEQ ID NO: 41, and SEQ ID NO: 42, respectively; (vi) the sequences of SEQ ID NO: 48, SEQ ID NO: 49, and SEQ ID NO: 50, respectively; (vii) the sequences of SEQ ID NO: 56, SEQ ID NO: 57, and SEQ ID NO: 58, respectively; (viii) the sequences of SEQ ID NO: 64, SEQ ID NO: 65, and SEQ ID NO: 66, respectively; (ix) the sequences of SEQ ID NO: 72, SEQ ID NO: 73, and SEQ ID NO: 74, respectively; (x) the sequences of SEQ ID NO: 80, SEQ ID NO: 81, and SEQ ID NO: 82, respectively; (xi) the sequences of SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 90, respectively; (xii) the sequences of SEQ ID NO: 96, SEQ ID NO: 97, and SEQ ID NO: 98, respectively, optionally wherein at least one of the H-CDR1, H-CDR2, and H-CDR3 sequences and/or at least one of the L-CDR1, L-CDR2, and L-CDR3 sequences has one or more amino acid position substituted with a histidine (e.g., one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or one, two, three, four, or five total histidine substitutions across the set of three L-CDRs). 44. An antigen-binding protein construct (ABPC) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell comprising at least one (1) antigen-binding domain (ABD), wherein: the first ABD includes a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD), wherein (a) the HCVD comprises an H-CDR1 sequence, an H-CDR2 sequence, and an H-CDR3 sequence selected from Attorney Docket No.: 45395-0068WO1 the group consisting of one of (i) to (xii): (i) the sequences of SEQ ID NO: 125, SEQ ID NO: 126, and SEQ ID NO: 127, respectively; (ii) the sequences of SEQ ID NO: 133, SEQ ID NO: 134, and SEQ ID NO: 135, respectively; (iii) the sequences of SEQ ID NO: 141, SEQ ID NO: 142, and SEQ ID NO: 143, respectively; (iv) the sequences of SEQ ID NO: 149, SEQ ID NO: 150, and SEQ ID NO: 151, respectively; (v) the sequences of SEQ ID NO: 157, SEQ ID NO: 158, and SEQ ID NO: 159, respectively; (vi) the sequences of SEQ ID NO: 165, SEQ ID NO: 166, and SEQ ID NO: 167, respectively; (vii) the sequences of SEQ ID NO: 173, SEQ ID NO: 174, and SEQ ID NO: 175, respectively; (viii) the sequences of SEQ ID NO: 181, SEQ ID NO: 182, and SEQ ID NO: 183, respectively; (ix) the sequences of SEQ ID NO: 189, SEQ ID NO: 190, and SEQ ID NO: 191, respectively; (x) the sequences of SEQ ID NO: 197, SEQ ID NO: 198, and SEQ ID NO: 199, respectively; (xi) the sequences of SEQ ID NO: 205, SEQ ID NO: 206, and SEQ ID NO: 207, respectively; and (xii) the sequences of SEQ ID NO: 213, SEQ ID NO: 214, and SEQ ID NO: 215, respectively; and/or (b) the LCVD comprises an L-CDR1 sequence, an L-CDR2 sequence, and an L-CDR3 sequence selected from the group consisting of one of (i) to (xii): (i) the sequences of SEQ ID NO: 128, SEQ ID NO: 129, and SEQ ID NO: 130, respectively; (ii) the sequences of SEQ ID NO: 136, SEQ ID NO: 137, and SEQ ID NO: 138, respectively; (iii) the sequences of SEQ ID NO: 144, SEQ ID NO: 145, and SEQ ID NO: 146, respectively; (iv) the sequences of SEQ ID NO: 152, SEQ ID NO: 153, and SEQ ID NO: 154, respectively; (v) the sequences of SEQ ID NO: 160, SEQ ID NO: 161, and SEQ ID NO: 162, respectively; (vi) the sequences of SEQ ID NO: 168, SEQ ID NO: 169, and SEQ ID NO: 170, respectively; (vii) the sequences of SEQ ID NO: 176, SEQ ID NO: 177, and SEQ ID NO: 178, respectively; (viii) the sequences of SEQ ID NO: 184, SEQ ID NO: 185, and SEQ ID NO: 186, respectively; (ix) the sequences of SEQ ID NO: 192, SEQ ID NO: 193, and SEQ ID NO: 194, respectively; (x) the sequences of SEQ ID NO: 200, SEQ ID NO: 201, and SEQ ID NO: 202, respectively; (xi) the sequences of SEQ ID NO: 208, SEQ ID NO: 209, and SEQ ID NO: 210, respectively; (xii) the sequences of SEQ ID NO: 216, SEQ ID NO: 217, and SEQ ID NO: 218, respectively, optionally wherein at least one of the H-CDR1, H-CDR2, and H-CDR3 sequences and/or at least one of the L-CDR1, L-CDR2, and L-CDR3 sequences has one or more amino acid position substituted with a histidine (e.g., one, two, three, four, or five total histidine substitutions across the set of three H-CDRs and/or one, two, three, four, or five total histidine substitutions across the set of three L-CDRs). Attorney Docket No.: 45395-0068WO1 45. An antigen-binding protein construct (ABPC) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell comprising at least one (1) antigen-binding domain (ABD), wherein the first ABD includes a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD) according to one of the following pairs of HCVD and LCVD ((a1/a2) to (l1/l2)): (a1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 203, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 203, and/or (3) the sequence of SEQ ID NO: 203 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 203, and (a2) the LCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 204, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 204, and/or (3) the sequence of SEQ ID NO: 204 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 204; (b1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 211, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 211, and/or (3) the sequence of SEQ ID NO: 211 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 211, and (b2) the LCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 212, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 212, and/or (3) the sequence of SEQ ID NO: 212 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 212; (c1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 171, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 171, and/or (3) the sequence of SEQ ID NO: 171 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 171, and (c2) the LCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 172, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 172, and/or (3) the sequence of SEQ ID NO: 172 Attorney Docket No.: 45395-0068WO1 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 172; (d1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 179, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 179, and/or (3) the sequence of SEQ ID NO: 179 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 179, and (d2) the LCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 180, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 180, and/or (3) the sequence of SEQ ID NO: 180 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 180; (e1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 187, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 187, and/or (3) the sequence of SEQ ID NO: 187 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 187, and (e2) the LCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 188, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 188, and/or (3) the sequence of SEQ ID NO: 188 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 188; (f1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 195, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 195, and/or (3) the sequence of SEQ ID NO: 195 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 195, and (f2) the LCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 196, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 196, and/or (3) the sequence of SEQ ID NO: 196 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 196; (g1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 123, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the Attorney Docket No.: 45395-0068WO1 sequence of SEQ ID NO: 123, and/or (3) the sequence of SEQ ID NO: 123 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 123, and (g2) the LCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 124, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 124, and/or (3) the sequence of SEQ ID NO: 124 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 124; (h1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 131, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 131, and/or (3) the sequence of SEQ ID NO: 131 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 131, and (h2) the LCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 132, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 132, and/or (3) the sequence of SEQ ID NO: 132 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 132; (i1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 139, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 139, and/or (3) the sequence of SEQ ID NO: 139 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 139, and (i2) the LCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 140, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 140, and/or (3) the sequence of SEQ ID NO: 140 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 140; (j1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 147, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 147, and/or (3) the sequence of SEQ ID NO: 147 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 147, and (j2) the LCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 148, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or Attorney Docket No.: 45395-0068WO1 99% identical to the sequence of SEQ ID NO: 148, and/or (3) the sequence of SEQ ID NO: 148 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 148; (k1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 155, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 155, and/or (3) the sequence of SEQ ID NO: 155 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 155, and (k2) the LCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 156, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 156, and/or (3) the sequence of SEQ ID NO: 156 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 156; and (l1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 163, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 163, and/or (3) the sequence of SEQ ID NO: 163 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 163, and (l2) the LCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 164, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 164, and/or (3) the sequence of SEQ ID NO: 164 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 164. 46. An antigen-binding protein construct (ABPC) that is capable of specifically binding DLL3 or an epitope of DLL3 presented on the surface of a target mammalian cell comprising at least one (1) antigen-binding domain (ABD), wherein the first ABD includes a heavy chain variable domain (HCVD) and a light chain variable domain (LCVD) according to one of the following pairs of HCVD and LCVD ((a1/a2) to (l1/l2)): (a1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 83, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 83, and/or (3) the sequence of SEQ ID NO: 83 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 83, and (a2) the LCVD comprising (1) the CDRs of the sequence of SEQ ID NO: 84, (2) an Attorney Docket No.: 45395-0068WO1 amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 84, and/or (3) the sequence of SEQ ID NO: 84 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 84; (b1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 91, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 91, and/or (3) the sequence of SEQ ID NO: 91 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 91, and (b2) the LCVD comprising (1) the CDRs of the sequence of SEQ ID NO: 92, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 92, and/or (3) the sequence of SEQ ID NO: 92 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 92; (c1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 51, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 51, and/or (3) the sequence of SEQ ID NO: 51 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 51, and (c2) the LCVD comprising (1) the CDRs of the sequence of SEQ ID NO: 52, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 52, and/or (3) the sequence of SEQ ID NO: 52 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 52; (d1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 59, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 59, and/or (3) the sequence of SEQ ID NO: 59 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 59, and (d2) the LCVD comprising (1) the CDRs of the sequence of SEQ ID NO: 60, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 60, and/or (3) the sequence of SEQ ID NO: 60 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 60; Attorney Docket No.: 45395-0068WO1 (e1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 67, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 67, and/or (3) the sequence of SEQ ID NO: 67 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 67, and (e2) the LCVD comprising (1) the CDRs of the sequence of SEQ ID NO: 68, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 68, and/or (3) the sequence of SEQ ID NO: 68 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 68; (f1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 75, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 75, and/or (3) the sequence of SEQ ID NO: 75 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 75, and (f2) the LCVD comprising (1) the CDRs of the sequence of SEQ ID NO: 76, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 76, and/or (3) the sequence of SEQ ID NO: 76 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 76; (g1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 3, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 3, and/or (3) the sequence of SEQ ID NO: 3 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 3, and (g2) the LCVD comprising (1) the CDRs of the sequence of SEQ ID NO: 4, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 4, and/or (3) the sequence of SEQ ID NO: 4 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 4; (h1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 11, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 11, and/or (3) the sequence of SEQ ID NO: 11 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID Attorney Docket No.: 45395-0068WO1 NO: 11, and (h2) the LCVD comprising (1) the CDRs of the sequence of SEQ ID NO: 12, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 12, and/or (3) the sequence of SEQ ID NO: 12 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 12; (i1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 19, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 19, and/or (3) the sequence of SEQ ID NO: 19 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 19, and (i2) the LCVD comprising (1) the CDRs of the sequence of SEQ ID NO: 20, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 20, and/or (3) the sequence of SEQ ID NO: 20 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 20; (j1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 27, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 27, and/or (3) the sequence of SEQ ID NO: 27 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 27, and (j2) the LCVD comprising (1) the CDRs of the sequence of SEQ ID NO: 28, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 28, and/or (3) the sequence of SEQ ID NO: 28 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 28; (k1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 35, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 35, and/or (3) the sequence of SEQ ID NO: 35 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 35, and (k2) the LCVD comprising (1) the CDRs of the sequence of SEQ ID NO: 36, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 36, and/or (3) the sequence of SEQ ID NO: 36 comprising a Attorney Docket No.: 45395-0068WO1 conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 36; (l1) the HCVD comprises (1) the CDRs of the sequence of SEQ ID NO: 43, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 43, and/or (3) the sequence of SEQ ID NO: 43 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 43, and (l2) the LCVD comprising (1) the CDRs of the sequence of SEQ ID NO: 44, (2) an amino acid sequence that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the sequence of SEQ ID NO: 44, and/or (3) the sequence of SEQ ID NO: 44 comprising a conservative amino acid substitution at an amino acid position other than in the CDRs of the sequence of SEQ ID NO: 44. 47. An isolated nucleic acid comprising a nucleotide sequence encoding a heavy chain variable domain (HCVD) and a nucleotide sequence encoding a light chain variable domain (LCVD) according to one of the following pairs of HCVD and LCVD ((a1/a2) to (l1/l2)): (a1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 203, and (a2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 204; (b1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 211, and (b2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 212; (c1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 171, and (c2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 172; (d1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 179, and (d2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 180; Attorney Docket No.: 45395-0068WO1 (e1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 187, and (e2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 188; (f1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 195, and (f2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 196; (g1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 123, and (g2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 124; (h1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 131, and (h2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 132; (i1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 139, and (i2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 140; (j1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 147, and (j2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 148; (k1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 155, and (k2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 156; and (l1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 163, and (l2) a nucleotide sequence Attorney Docket No.: 45395-0068WO1 encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 164. 48. An isolated nucleic acid comprising a nucleotide sequence encoding a heavy chain variable domain (HCVD) and a nucleotide sequence encoding a light chain variable domain (LCVD) according to one of the following pairs of HCVD and LCVD ((a1/a2) to (l1/l2)): (a1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 83, and (a2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 84; (b1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 91, and (b2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 92; (c1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 51, and (c2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 52; (d1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 59, and (d2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 60; (e1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 67, and (e2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 68; (f1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 75, and (f2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 76; (g1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 3, and (g2) a nucleotide sequence Attorney Docket No.: 45395-0068WO1 encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 4; (h1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 11, and (h2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 12; (i1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 19, and (i2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 20; (j1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 27, and (j2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 28; (k1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 35, and (k2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 36; and (l1) the HCVD is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 43, and (l2) a nucleotide sequence encoding an LCVD that is at least 85%, 90%, 95%, 98%, or 100% identical to a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 44. 49. An expression vector comprising the isolated nucleic acid of any one of claims 47 (a1/a2), 47 (b1/b2), 47 (c1/c2), 47 (d1/d2), 47 (e1/e2), 47 (f1/f2), 47 (g1/g2), 47 (h1/h2), 47 (i1/i2), 47 (j1/j2), 47 (k1/k2), 47 (l1/l2), 48 (a1/a2), 48 (b1/b2), 48 (c1/c2), 48 (d1/d2), 48 (e1/e2), 48 (f1/f2), 48 (g1/g2), 48 (h1/h2), 48 (i1/i2), 48 (j1/j2), 48 (k1/k2), and 48 (l1/l2). 50. An expression vector comprising an isolated nucleic acid comprising a nucleotide sequence encoding an ABPC as set forth in any one of claims 38, 37, 38, 39, 40, 41, 42, 43, 44, 45, and 46. Attorney Docket No.: 45395-0068WO1 51. An expression vector comprising an isolated nucleic acid comprising a nucleotide sequence encoding an ABPC or antibody as set forth in any one of the preceding claims. 52. A host cell comprising the expression vector of one of claims 49, 50, and 51. 53. A method of producing an antigen-binding protein construct, the method comprising: (a) culturing the host cell of claim 52 under conditions suitable for expression of the antigen- binding protein construct; and (b) recovering the antigen-binding protein construct from the host cell or culture medium. 54. A pharmaceutical composition comprising an effective amount of the ABPC of any one of claims 38, 37, 38, 39, 40, 41, 42, 43, 44, 45, and 46, or the ABPC, antibody, or conjugated composition of any one of the preceding claims.
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