WO2022204249A1 - Variants of humanized anti-muc16 ectodomain antibodies for treatment of muc16 overexpressing tumors - Google Patents

Abstract

The present disclosure provides variants of humanized anti-MUC16 immunoglobulin-related compositions that specifically bind to the C -terminal 114 amino acid residues of mature MUC16 (e.g., 4H11) and uses thereof.

Description

VARIANTS OF HUMANIZED ANTI-MUC16 ECTODOMAIN ANTIBODIES FOR TREATMENT OF MUC16 OVEREXPRESSING TUMORS CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of and priority to U.S. Provisional Patent Application No.63/165,402, filed March 24, 2021, the entire contents of which are incorporated herein by reference. TECHNICAL FIELD [0002] The present technology relates generally to variants of humanized anti-MUC16 immunoglobulin-related compositions that specifically bind to the C-terminal 114 amino acid residues of mature MUC16 (e.g., 4H11) and uses thereof. STATEMENT OF GOVERNMENT SUPPORT [0003] This invention was made with government support under grant number CA190174- 01A1 awarded by the National Cancer Institute (NCI). The government has certain rights in the invention. BACKGROUND [0004] The following description of the background of the present technology is provided simply as an aid in understanding the present technology and is not admitted to describe or constitute prior art to the present technology. [0005] Overexpressed Mucin 16 (MUC16) is highly related with cancer progression, metastasis, and therapy resistance in multiple malignancies. The proteolytic cleavage of MUC16 form independent bimodular fragments, a circulating shed form (CA 125) known as ovarian cancer biomarker and a membrane-bound unshed form which is critical in determining unique mechanistic roles of MUC16 and therapeutic interventions. The limited tissue expression of MUC16 has made it an attractive focus for antibody based, targeted therapy development in high grade serous ovarian cancer (HGSOC). However, much of this activity has utilized antibodies targeting tandem repeat region. This strategy has two significant shortcomings: tandem repeat protein is present in the circulation and limiting off target effects particularly on mesothelial surfaces. The OC125/M11 epitopes, present in the tandem repeat region are nonlinear complex sequences dependent on folding and enhanced by glycosylation processes. These characteristics have limited detailed analysis of the tandem repeat epitope structure. [0006] Antibodies that effectively target MUC16 ectodomain are urgently needed for immunotherapeutic approaches. SUMMARY OF THE PRESENT TECHNOLOGY [0007] In one aspect, the present disclosure provides an anti-mucin 16 (MUC16) construct comprising an antibody moiety that immunospecifically recognizes a mucin 16 (MUC16) polypeptide, wherein the antibody moiety comprises a heavy chain immunoglobulin variable domain (VH) and a light chain immunoglobulin variable domain (VL), wherein: (a) the VH comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, and (b) a VL domain including an amino acid sequence of SEQ ID NO: 3 or SEQ ID NO: 4, wherein the V_H domain further comprises at least one amino acid substitution corresponding to at least one amino acid residue selected from among S30, A54, G55, G56, F101, and/or Y108 of SEQ ID NO: 1 or SEQ ID NO: 2, and/or wherein the V_L domain further comprises at least one amino acid substitution corresponding to at least one amino acid residue selected from among N31, R33, Q38, and/or S97 of SEQ ID NO: 3 or SEQ ID NO: 4. In any and all embodiments of the anti-MUC16 construct disclosed herein, the VH domain further comprises 1, 2, 3, 4, 5 or 6 amino acid substitutions corresponding to any one or more amino acid residues selected from among S30, A54, G55, G56, F101, and/or Y108 of SEQ ID NO: 1 or SEQ ID NO: 2. Additionally or alternatively, in some embodiments of the anti-MUC16 construct disclosed herein, the V_L domain further comprises 1, 2, 3, or 4 amino acid substitutions corresponding to any one or more amino acid residues selected from among N31, R33, Q38, and/or S97 of SEQ ID NO: 3 or SEQ ID NO: 4. In some embodiments of the anti-MUC16 construct disclosed herein, the at least one amino acid substitution corresponding to S30, G55, G56, F101, and/or Y108 of SEQ ID NO: 1 or SEQ ID NO: 2 is one or more of S30Y, S30H, S30F, S30W, G55L, G55P, G55V, G55E, G56T, G56V, G56P, F101N, F101T, F101W, F101Q, or Y108R. Additionally or alternatively, in any and all embodiments of the anti-MUC16 construct disclosed herein, the at least one amino acid substitution corresponding to N31, R33, Q38, and/or S97 of SEQ ID NO: 3 or SEQ ID NO: 4 is one or more of N31Q, N31V, N31S, N31K, N31T, N31P, R33N, R33V, R33S, R33T, R33E, Q38T, Q38D, Q38L, Q38P, Q38H, Q38R, Q38V, S97R, S97Q, S97E, S97H, S97L, S97P, S97V, S97N, or S97D. [0008] In one aspect, the present disclosure provides an anti-mucin 16 (MUC16) construct comprising an antibody moiety that immunospecifically recognizes a mucin 16 (MUC16) polypeptide, wherein the antibody moiety comprises a sequence selected from among SEQ ID NOs: 5-8, wherein the anti-MUC16 antibody moiety further comprises at least one amino acid substitution corresponding to at least one amino acid residue selected from among S30, A54, G55, G56, F101, Y108, N179, R181, Q186, and/or S245 of any of SEQ ID NOs: 5-8. Additionally or alternatively, in some embodiments, the anti-MUC16 antibody moiety further comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions corresponding to any one or more amino acid residues selected from among S30, A54, G55, G56, F101, Y108, N179, R181, Q186, and/or S245 of any of SEQ ID NOs: 5-8. Additionally or alternatively, in some embodiments, the at least one amino acid substitution corresponding to S30, G55, G56, F101, Y108, N179, R181, Q186, and/or S245 of any of SEQ ID NOs: 5-8 is one or more of S30Y, S30H, S30F, S30W, G55L, G55P, G55V, G55E, G56T, G56V, G56P, F101N, F101T, F101W, F101Q, Y108R, N179Q, N179V, N179S, N179K, N179T, N179P, R181N, R181V, R181S, R181T, R181E, Q186T, Q186D, Q186L, Q186P, Q186H, Q186R, Q186V, S245R, S245Q, S245E, S245H, S245L, S245P, S245V, S245N, or S245D. [0009] In some embodiments of the anti-MUC16 construct disclosed herein, the antibody moiety immunospecifically binds to the ectodomain of MUC16, or to a MUC16 c114 polypeptide comprising the amino acid sequence of SEQ ID NO: 11. Additionally or alternatively, in some embodiments of the anti-MUC16 construct disclosed herein, the antibody moiety is a full-length antibody, a monoclonal antibody, a Fab, a Fabʹ, a F(abʹ)2, an Fv, or a single chain Fv (scFv). [0010] Additionally or alternatively, in some embodiments, the anti-MUC16 construct inhibits in vitro invasion of a MUC16-expressing tumor cell in a Matrigel invasion assay, optionally wherein the MUC16-expressing tumor cell is an ovarian tumor cell. In certain embodiments, MUC16 is glycosylated, preferably at N24 or N30 relative to SEQ ID NO: 11. [0011] In any of the preceding embodiments of the anti-MUC16 construct disclosed herein, the antibody moiety comprises human-derived heavy and light chain constant regions, optionally wherein the heavy chain constant region has an isotype selected from the group consisting of gamma l, gamma 2, gamma 3, and gamma 4, and optionally wherein the light chain constant region has an isotype selected from the group consisting of kappa and lambda. In other embodiments, the antibody moiety is an immunoglobulin comprising two identical heavy chains and two identical light chains, optionally wherein the immunoglobulin is an IgG. [0012] Additionally or alternatively, in some embodiments, the anti-MUC16 construct is monospecific, multispecific, or bispecific, optionally wherein the multispecific or bispecific anti-MUC16 construct comprises an anti-CD3 antibody moiety. [0013] In any and all embodiments of the anti-MUC16 construct disclosed herein, the anti- MUC16 construct is (i) a tandem scFv, optionally wherein the tandem scFv comprises two scFvs linked by a peptide linker; (ii) a diabody (Db); (iii) a single chain diabody (scDb); (iv) a dual-affinity retargeting (DART) antibody, (v) a F(ab’)2; (vi) a dual variable domain (DVD) antibody; (vii) a knob-into-hole (KiH) antibody; (viii) a dock and lock (DNL) antibody; (ix) a chemically cross-linked antibody; (x) a heteromultimeric antibody; or (xi) a heteroconjugate antibody. In some embodiments, the multispecific or bispecific anti-MUC16 construct comprises a first antibody moiety that immunospecifically recognizes MUC16, and a second antibody moiety that immunospecifically recognizes a second antigen. In certain embodiments, the second antigen is an antigen expressed on the surface of a T cell, optionally wherein the second antigen is a CD3 polypeptide selected from the group consisting of CD3γ, CD3δ, CD3ε, and CD3ζ. [0014] Additionally or alternatively, in some embodiments, the anti-MUC16 construct is a chimeric antigen receptor (CAR) or an antibody-T cell receptor (abTCR). [0015] In any and all embodiments of the anti-MUC16 construct disclosed herein, the anti- MUC16 construct is further conjugated to a peptide agent, a detection agent, an imaging agent, a therapeutic agent, or a cytotoxic agent. In certain embodiments, the anti-MUC16 construct is conjugated to an alpha emitter, an Auger-emitter, a beta-emitter, a gamma- emitter, a positron-emitters, or an x-ray emitter, optionally wherein the positron-emitter is 89Zr-desferrioxamine B (DFO). [0016] In one aspect, the present disclosure provides polynucleotides comprising nucleic acid sequences encoding any and all embodiments of the anti-MUC16 construct disclosed herein. Also disclosed herein are vectors comprising said polynucleotides operably linked to a promoter. [0017] In another aspect, the present disclosure provides a cell comprising any and all embodiments of the anti-MUC16 constructs, polynucleotides or vectors described herein. The cell may be a mammalian cell, an immune cell, a lymphocyte, a T cell or a B cell. [0018] In yet another aspect, the present disclosure provides a pharmaceutical composition comprising: a therapeutically effective amount of any and all embodiments of the anti- MUC16 constructs, polynucleotides, vectors, or cells described herein; and a pharmaceutically acceptable carrier. [0019] In one aspect, the present disclosure provides a method of treating a MUC16- associated disease or disorder in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of the anti-MUC16 constructs, or the pharmaceutical compositions of the present technology, optionally wherein said MUC16- associated disease or disorder is a cancer. In some embodiments, the cancer is a metastatic cancer and/or a cancer of the ovary, lung, pancreas, breast, uterine, fallopian tube, or primary peritoneum. Additionally or alternatively, in some embodiments, the pharmaceutical composition inhibits or reduces metastasis in the patient, optionally wherein said patient is a human patient. [0020] Also provided herein, in certain embodiments, are methods for producing an effector cell, comprising genetically modifying a cell with one or more nucleic acids encoding the anti-MUC16 construct provided herein. Also provided herein, in certain embodiments, are methods of treatment comprising introducing one or more nucleic acids encoding the anti-MUC16 construct provided herein into one or more primary cells isolated from a patient and administering cells comprising the one or more nucleic acids to the patient. In some embodiments, the method further comprises expanding the cells prior to administering the cells to the patient. In some embodiments, the primary cells are lymphocytes. In some embodiments, the primary cells are T cells. [0021] In some embodiments, the methods of treatment provided herein further comprises administering a therapeutically effective amount of an additional therapeutic agent to the patient. In some embodiments, the therapeutic agent is an anti-cancer agent. In some embodiments, the therapeutic agent is a chemotherapeutic agent. [0022] Also provided herein, in certain embodiments, are methods of detecting MUC16 in a sample, comprising: (a) contacting the sample with the anti- MUC16 construct provided herein; and (b) detecting the binding, directly or indirectly, between the anti-MUC16 construct and MUC16 that is present in the sample. In some embodiments, the anti-MUC16 construct is conjugated to a detectable label. In some embodiments, the detectable label is a chromogenic, enzymatic, radioisotopic, isotopic, fluorescent, toxic, chemiluminescent, nuclear magnetic resonance contrast agent. In some embodiments, the binding between the anti- MUC16 construct and any MUC16 in the sample is detected directly by detecting the detectable label. In some embodiments, the binding between the anti- MUC16 construct and any MUC16 in the sample is detected indirectly using a secondary antibody. [0023] Also provided herein, in certain embodiments, are methods of diagnosing an individual suspected of having a MUC16-associated disease or disorder, comprising a) administering an effective amount of the anti-MUC16 construct provided herein to the individual; and b) determining the level of the binding, directly or indirectly, between the anti- MUC16 construct and any MUC16 in the individual, wherein a level of the binding above a threshold level indicates that the individual has the MUC16-associated disease or disorder. In some embodiments, the anti-MUC16 construct is conjugated to a detectable label. In some embodiments, the detectable label is a chromogenic, enzymatic, radioisotopic, isotopic, fluorescent, toxic, chemiluminescent, nuclear magnetic resonance contrast agent. In some embodiments, the binding between the anti- MUC16 construct and any MUC16 in the sample is detected directly by detecting the detectable label. In some embodiments, the binding between the anti- MUC16 construct and any MUC16 in the sample is detected indirectly using a secondary antibody. [0024] Also provided herein, in certain embodiments, are methods of diagnosing an individual suspected of having a MUC16-associated disease or disorder, comprising a) contacting a sample comprising cells derived from the individual with the anti-MUC16 construct provided herein; and b) determining the number of cells in the sample bound to the anti-MUC16 construct, wherein a value for the number of cells bound to the anti-MUC16 construct above a threshold level indicates that the individual has the MUC16-associated disease or disorder. In some embodiments, the anti-MUC16 construct is conjugated to a detectable label. In some embodiments, the detectable label is a chromogenic, enzymatic, radioisotopic, isotopic, fluorescent, toxic, chemiluminescent, nuclear magnetic resonance contrast agent. In some embodiments, the binding between the anti- MUC16 construct and any MUC16 in the sample is detected directly by detecting the detectable label. In some embodiments, the binding between the anti- MUC16 construct and any MUC16 in the sample is detected indirectly using a secondary antibody. [0025] Also provided herein, in certain embodiments, are uses of anti-MUC16 constructs, polynucleotides encoding anti-MUC16 constructs, vectors comprising the polynucleotides, or cells comprising any of the anti-MUC16 constructs and polynucleotides thereof provided herein for the treatment of a disease or disorder associated with positive MUC16 expression. In some embodiments, the disease or disorder associated with positive MUC16 expression is a cancer. [0026] Also provided herein, in certain embodiments, are uses of the anti-MUC16 constructs, polynucleotides encoding anti-MUC16 constructs, vectors comprising the polynucleotides, or cells comprising any of the anti-MUC16 constructs and polynucleotides thereof provided herein in the manufacture of a medicament for the treatment of a disease or disorder associated with positive MUC16 expression. In some embodiments, the disease or disorder associated with positive MUC16 expression is a cancer. [0027] Also disclosed herein are methods for detecting cancer in a subject in vivo comprising (a) administering to the subject an effective amount of any of the anti-MUC16 constructs disclosed herein, wherein the anti-MUC16 constructs are configured to localize to a cancer cell expressing MUC16 and is labeled with a radioisotope; and (b) detecting the presence of a tumor in the subject by detecting radioactive levels emitted by the anti-MUC16 constructs that are higher than a reference value, optionally wherein the radioisotope is 89Zr- desferrioxamine B (DFO). The radioactive levels emitted by the anti-MUC16 constructs may be detected using positron emission tomography or single photon emission computed tomography. Additionally or alternatively, in some embodiments, the methods of the present technology further comprise administering to the subject an effective amount of an immunoconjugate comprising any of the anti-MUC16 constructs described herein conjugated to a radionuclide. In some embodiments, the radionuclide is an alpha particle-emitting isotope, a beta particle-emitting isotope, an Auger-emitter, or any combination thereof. BRIEF DESCRIPTION OF THE DRAWINGS [0028] FIGs.1A-1D show humanization of 4H11. FIG.1A shows structural overlay of 4H11 and human IgG frame template. The antibody structure modelling was performed by ABodyBuilder. 4H11 heavy (sky blue) and light (pink) chains. Human frame template (4dtg-3O2d) heavy (blue) and light (Magenta) chains. The numbers denote the positions of amino acid humanization. FIG.1B shows sequence alignment of: 4H11, human frame template and humanized h4H11 heavy and light chains, mVH and mVL, heavy chain and light chain of 4H11 mouse IgG1, hVHt, the framework template of human heavy chain(4dtg), hVLt, the framework template of human light chain (3O2d). HVH1 and 2, hVL1 and 2, and the humanized heavy chain and light chain of 4H11. Yellow highlighted sequences are CDRs. Humanized amino acids indicated in red (underlined) letters. FIG.1C shows structural overlay of 4H11 and humanized antibody structures. The structures of 4H11 and humanized antibody (4H11, hH1L1, hH1L2, hH2L1, hH2L2) were simulated by ABodyBuilder.4H11 heavy (sky blue) and light (pink) chains. HH1L1 heavy (TV blue) and light (dirty violet) chains. HH1L2 heavy (marine) and light (violet purple) chains. HH2L1 heavy (deep blue) and light (purple) chains. HH2L2 heavy (density) and light (deep purple) chains. FIG.1D shows binding kinetics of 4H11 and humanized h4H11 antibodies by ForteBio Octet analysis. [0029] FIGs.2A-2J show functional characterization of humanized Muc16^ecto antibody. FIG.2A shows matrigel invasion assays performed with or without the addition of anti- MUC16^ecto antibodies. The antibody 18C6 was used as the positive control and decreased inhibition of all three cell lines. Humanized anti-MUC16^ecto 4H11 antibodies H1L1, H1L2, H2L1, and H2L2 were tested. All antibodies showed statistically significant inhibition of Matrigel invasion except OVCAR3 cells treated with H2L2. FIG.2B shows 4-hour Cr release cytotoxicity assays conducted with MUC16^ecto – directed second-generation CAR T- cells derived from H1L2 and H2L1 scFv sequences at the indicated effector to target (E:T) ratios. Both CAR T-cells showed dose-dependent cytotoxicity against OVCAR3 and SKOV3- MUC16^ecto tumor cells. FIG.2C shows H1L24H11 CAR T-cells co-cultured with OVCR3 cells. FIG.2D shows SKOV3- MUC16^ecto tumor cells and evaluated for cytotoxicity after 72 hours of coculture. FIG.2E shows cytokine analysis of H1L24H11 CAR T-cells co-cultured with SKOV3- MUC16^ecto tumor cells for 72 hours. FIG.2F shows 8–12-week-old female NSG mice were inoculated with SKOV3- MUC16^ecto tumor cells i.p and treated with H1L24H11 CAR T-cells on day 14. Animals were subsequently monitored for development of ascites or signs of distress. ** p < 0.005. FIGs.2G-2H show SKOV3 (FIG.2G) and SKOV3- MUC16^ecto (FIG.2H) tumor cells were treated with increasing doses of m4H11 (gray) and mVK8 (black) ADCs for 72 hours and evaluated for cytotoxicity. OVCAR3k/o (FIG.2I) and OVCAR3 (FIG.2J). Statistically significant differences are marked (*p<0.05, **p<0.01, ***p<0.001). [0030] FIGs.3A-3H show structure of the scFv and MUC16 complex. FIGs.3A-3B show cartoon representations of 4H11-scFv in complex with MBP-fused MUC16-target. The MBP was used to facilitate crystallization by stabilizing the MUC`16 target peptide. MBP, maltose binding domain (grey); linker composed of NSSS (red dots); MUC16- target composed of 26 residues (orange); Heavy chain of 4H11-scFv (skyblue); linker composed of (GGGGS)5 repeats (black dots); Light chain of 4H11-scFv (pink). FIG.3C shows line representation for clarity. FIG.3D shows structure of MUC16-target (orange) bound to the VH (skyblue) and VL (pink) of 4H11-scFv. The view direction (left panel) is similar to that shown in FIG.2A and 90° rotation of the complex about a horizontal axis (right panel). FIG.3E shows the interaction between VH, VL and the MUC16ecto is enlarged for clarity. FIG.3F shows an open book view of the interface residues between 4H11-scFv and MUC16-target highlighted in the box in FIG.3E; The residues of MUC16 (S 15th, S 22nd, R 24th, D 25th, L 26th, and Q 30th ) in orange color form the hydrogen bonds or salt bridges with VH residues (S 52, S 53, A 54, N 103, D 106, and Y 108) in blue color, while the residues (Y 16th, G 17th, D 18th, and L 20th ) of MUC16 in cyan color form the hydrogen bonds with VL residues (S 180, Y 246, N 247 and L 248) in pink color. FIGs.3G-3H show that interacting residues are labeled in close-up views of the interfaces. See FIG.15, FIGs.9A-9E and FIGs.12A-12F for versions of the detailed interactions. [0031] FIGs.4A-4E show overall structure of 4H11-scFv and interaction between VH and VL. FIG.4A shows schematic diagram showing the domain structures of Heavy chain (Hc: 1-123) and Light chain (Lc: 149-261), as well as the positions of 3 CDRs (residue positions: 26-32, 53-56, 100-110) at V_H (cyan) and 3 CDRs (residue positions: 174-186, 204-206, 245- 248) at V_L (forest) interacting with MUC16^ecto. CDR: complementary determining region. The shortest distance from C-terminal of VH to N-terminal of VL, the flexible linker (GGGGS)₅ lengths (red dots) with no electron density map (residues 124-148), was 32 Å which corresponds to at least 13 amino acid-lengths. Each domain has one S-S bridge (red) (C22 – C96 at VH and C171 – C242 at VL) for stable folding. The solvent-accessible area of the interface between VH-VL was 926 Ų. FIGs.4B-4C show secondary structure topology diagram of V_H (left panel) or V_L (right panel) of 4H11-scFv, the eleven sheets and two short helices for VH and the thirteen sheets and one helix for VL are represented. C-terminal (red) of VH is connected to N-terminal (blue) of VL via (GGGGS)5 linker (red dots). FIG.4D shows interacting residues at interface regions between V_H and V_L are colored as blue (V_H residues) and pink (V_L residues). The cationic sidechain of R44 (V_H) form a favorable cation- π pair (black dot; 5.6 Å distance) with an aromatic sidechain of F251 (VL) to improve overall stability. FIG.4E shows an open-book view of the interface with interacting residues. See FIG.16 for detailed interacted residues. [0032] FIGs.5A-5H show that the target domain of 4H11-scFv is located at the juxta- membrane upward transmembrane (TM) of MUC16. FIG.5A shows schematic representation of MUC16 structure: MUC16 can be divided by three parts: N-terminal domain (~22,000 amino acid in length), tandem repeat domains interspersed with Sea urchin sperm protein Enterokinase and Agrin (SEA) domain including potential cleavage sites (DSVLV and PLARRVDR) and C-terminal domain that is further divided into an extracellular juxtamembrane portion, a single–span TM and a cytoplasmic tail of 32 amino acid length. The 4H11-scFv targets to the juxta-membrane as shown target sequence (red arrow). FIG.5B shows amino acid sequence alignment of the juxta-ectodomain among 8 different species. Secondary structure of human MUC16 is shown on the top as double β turns-linker-β-hairpin structures. Sequence alignments were made using Clustal Omega and ESPript 3.0. FIG.5C shows crystal structure and representative electron density maps of the MUC16^ecto residues (L31^st -N13^th) that are complexed with 4H11-scFv. The stick representation with a 2Fo-Fc electron density map for MUC16^ecto contoured at 1.0 σ shows two β- turns and one β-hairpin structures. Two β-turns (FIGs.5D-5E) and a β-hairpin (FIG. 5F) structures are highlighted in the box with distances of hydrogen bonds between F28^th (- N) – L31^st (-O), R24^th (-NH2) –T27^th (-OG1), V19^th (-N) – Y16^th (-O) and V19^th (-O) – Y16^th (-N). See FIG.17 for version of the detailed Phi (φ), Psi (ψ) and Omega (ω). FIG.5G shows the predicted glycosylation sites in 19 residues using web-server (crdd.osdd.net), N-or O-glycosylation sites; ”N” (red) or “T” (blue), respectively. FIG.5H shows the basic Local Alignment Search Tool (BLAST) for finding regions of local similarity between sequences. Only two proteins were found out in homo sapiens with 42% identities by the sequence of 19 residues that binds to the present 4H11-scFv. [0033] FIGs.6A-6C show structure alignment of the m4H11 and the h411 scFv. The structural alignment among (crystal structure at 2.36 Å) 4H11-scFv (unbound), (in silico predicted model) mouse 4H11-scFv and (crystal structure at 2.46 Å) 4H11-scFv (bound form with MUC16^ecto) on their shape and 3-Dimentional conformation with ribbon and stick representation. Human (h), Mouse (m), Water (w). FIG.6A shows structural superposition among (gray) human 4H11-scFv, (orange) mouse 4H11-scFv, and (blue) human 4H11-scFv, showing Root Mean Square Deviation (RMSD) 0.805 (by 1,277 atomic coordinate sets) between (h)4H11-scFv and (m)4H11-scFv, 0.915 (by 1,319 atomic coordinate sets) between (m)4H11-scFv and (h)4H11-scFv, respectively.7 amino acids (R19K, A40S, S78T, R166K, N170S, S217T, and V237L) showed different structural orientations or positions according to (h)4H11-scFv/(m)4H11-scFv sequences, these changes may specifically induce local movements at D106 and Y108 of VH-CDR3 and then, resulting in a weaker binding against (h)MUC16^ecto antigen. FIGs.6B-6C show in-depth views. D108 residue of (h)4H11-scFv interacts with S22^nd and R24^th residues of (h)MUC16^ecto by 3 hydrogen bonds including w2- medicated interaction, however (m)D106 showed a ∼180^o rotation shift. FIG.6C shows that the (h)Y108 residue of (h)4H11-scFv interacts with S15^th and S23^rd residues of (h) MUC16^ecto by 2 hydrogen bonds via w1-medicated interactions but, the side-chain of (m)Y108 residue located at a different place is shown as ∼11 Å apart from (h)4H11-scFv Y108, which also may induce a weaker interaction against human MUC16 antigen based on (m)4H11-scFv in silico model. [0034] FIGs.7A-7H show the binding modes of the 4H11-scFv rearrange the CDRs of the scFv. FIGs.7A-7B show the overall superpositions of the structures of the unbound and MUC16-target bound 4H11-scFv. The unbound V_H*-V_L* (grey), bound V_H (skyblue)-V_L (pink), MUC16-target (orange). The view directions in FIGs.5A-5B are similar to those shown in FIG.2A and 90° rotation of the complex about a horizontal axis (FIG.5B). FIGs. 7C-7D show the close-up views of the interfaces between V_H-V_H* (FIG.7C) or V_L-V_L* (FIG.7D) with the movement indicated by the red dotted arrow. The aromatic ring of Y108 with 2Fo-Fc map was moved to the left up to ~3.8 Å and The OG of S 180 with 2Fo-Fc map was also moved to the left up to ~ 2.5 Å. FIGs.7E-7G show the close-up views of the hydrogen bonds formed by water molecules (W1, W2, or W3) during the complex. Y16^th and G 17^th (cyan) of MUC16-target (FIG.7F) and S 15^th, S 23^rd and R 24^rd (orange) of MUC16-target (FIG.7G) formed the multi-hydrogen bonds with VH S180 and VL Y108/D106. See FIG.15 for detailed interactions. FIG.7H shows that pull-down assay was performed using 4H11-scFv and mutants as a prey and the MBP-tagged MUC16 (26 residues) as a bait. After binding, the MBP resins were washed three times and the bound proteins were released and subjected to SDS-PAGE. Lane 1-5: input proteins of MBP- tagged MUC16-target (lane 1), 4H11-scFv (lane 2), and the scFv mutants (lane 3-5); lane 6, pull- down as a control; lane 7-8, 4H11-scFv containing VH double mutations (S53A/D106A) or VL double mutations (Y246A/N247A); lane 9, the two double mutations (S53A/D106A, Y246A/N247A) of the scFv. [0035] FIGs.8A-8F show structure of the MBP-fused MUC16^ecto in complex with 4H11- scFv. FIG.8A shows a schematic diagram showing the domain organizations of MBP- tagged MUC16^ecto and the 4H11-scFv. MBP, maltose binding domain (grey); linker composed of NSSS (red dots); MUC16^ecto composed of 26 residues (orange); Heavy chain of 4H11-scFv (skyblue); linker composed of (GGGGS)₅ repeats (black dots); Light chain of 4H11-scFv (pink). 7 residues of MUC16^ecto sequences showed no electron density due to the flexibility (black line). FIG.8B shows that the MUC16 overexpressed in OVCAR3 and SKBR3 cancer cell lines can bind to 4H11-scFv that was conjugated to Alexa fluor^® 488 fluorescent dye (Alexa-4H11-scFv) while negative control cell lines, HEK293 and SKOV3, showed no binding. The fixed cell imaging; DIC images (upper panel) and immunofluorescence images of 4H11-scFv (lower panel). FIG.8C shows live cell imaging of OVCAR3 (10 nM, 12 hours). DIC image (left panel), Alexa-350-WGA that binds to sialic acid and N-acetylglucosaminyl residues of cell membranes and Alexa-4H11-scFv (right panel); the white arrows in the white dot boxes indicate the 4H11-scFv vesicles internalized into the cell. Scale bar: 30 μm. FIGs.8D-8E show thermodynamic studies of isothermal titration calorimetry (ITC). Representative titration profiles are shown for the binding of 4H11-scFv to the MBP-fused MUC16^ecto (K_d = 2 ± 1 nM; DH = -19.9 ± 0.6 kcal/mol; -TDS = 7.9 ± 0.8 kcal/mol; N = 1.16 ± 0.05) or the synthesized MUC16^ecto peptide (Kd = 1.4 ± 0.5 nM; DH = -21.2 ± 0.5 kcal/mol; -TDS = 9.1 ± 0.6 kcal/mol; N = 1.17 ± 0.08). The thermodynamic values reported are the average of three independent experiments (mean ± SD). FIG.8F shows MBP pull-down between MBP-tagged human MUC16^ecto and the antibody, 4H11-scFv; MBP-MUC16^ecto (lane 1), 4H11-scFv (lane 2) as input, washing steps (lane 3, lane 4), and output of pull-down (lane 5). Input molar ratio was 1:3 (MBP-MUC16: 4H11-scFv) and unbound proteins were eliminated at twice washing steps. [0036] FIGs.9A-9E show characterization of interactions between 4H11-scFv and MUC16^ecto by size-exclusion chromatography (SEC, Superdex 75 column). The separately expressed and purified the MBP-tagged MUC16^ecto (FIG.9A) and 4H11-scFv (FIG.9B) formed a stable complex (FIG.9C) when they are mixed, MBP-tagged MUC16^ecto (15 uM) and 4H11-scFv (30 uM) were mixed at 4 °C during 3 hours. The eluted peak positions shown in FIGs.9A-9C are 11.5 mL (brown), red (12.6 mL), and blue colors (10.2mL), respectively. FIG.9D shows a superposition of elution profiles, the extra 4H11-scFv (blue) peak shown at the same position with the 4H11-scFv eluted. FIG.9E shows the peak SEC fractions (# 1-10) were analyzed by SDS-PAGE and Coomassie staining. The fraction numbers are labeled on the top. “Bf” and “S” stand for the before injection and protein marker being analyzed, respectively. The lower band 4H11-scFv (28 kDa) can bind to the MBP-tagged MUC16^ecto (43 kDa) composed of 26-residues including a flexible loop with two β- turns and one β-hairpin motifs, that can bind to the CDR2 and 3 of the heavy chain (VH) and CDR1 and 3 of the light chain (VL) of 4H11-scFv. The complex fractions are shown around 10.2 mL peak (lane 3 – 5) and excess 4H11-scFv protein (black dot) was eluted around 12.6 mL position (lane 7 – 10). [0037] FIGs.10A-10D show thermal stability of 4H11-scFv or 4H11-scFv-MUC16 complex at acidic, neutral and basic pH. FIGs.10A-10B show that the thermal stability of wild type 4H11-scFv or 4H11-scFv-MUC16 was measured using a fluorescence-based thermal shift assay on a CFX96 real-time system (Bio-Rad, Hercules, CA). Protein melting was monitored using a hydrophobic dye, SYPRO Orange (Sigma-Aldrich, St. Louis, MO), as the temperature was increased in a linear ramp form 20 ^o C to 95 ^o C. The midpoint of the protein-melting curve (T_m) was determined using the software provided by the instrument manufacturer. The data are presented as mean ± S.D., n = 3. FIG.10A shows that the T_m of WT 4H11-scFv at pH 3.4 and 4.4 showed only one melting point while the Tm among pH 5.4 – 9.4 showed two melting points, implying either V_H or V_L may show a higher stability. However, the 4H11-scFv in complex with MUC16^ecto showed the higher T_m by 1 ^o C to 6 ^o C except for pH 9.4, where it showed 1 ^oC lower Tm than WT protein. The Tm of the complex at pH 3.4 could not be determined due to significant protein unfolding at the starting temperature. FIG.10C shows that the 2-D bar chart represents the T_m comparison of “a” and “b” according to pH values. 4H11-scFv is blue color and 4H11-scFv-MUC16^ecto complex is grey color, respectively. FIG.10D shows that the Tm measurement of MUC16^ecto peptide itself among multiple pH values had no peptide melting point, showing the peptide itself did not have any effect on the T_m of the complex. [0038] FIGs.11A-11F show that MBP-tagged MUC16^ecto variants adopt wild-type-like structures. FIGs.11A-11B show that the thermal stability of proteins was measured and monitored using SYPRO Orange dye as the temperature was increased in a linear ramp from 20 ^oC to 95 ^oC. All the MBP-tagged MUC16^ecto variants showed Tm values comparable to the wild-type protein, indicating correct protein folding. FIGs.11C-11E show close-up views of interfaces between V_H and D25^th residue (FIG.11C), V_H and R24^th (FIG.11D), and V_L and both (G18^th and G17^th) residues (FIG.11E), showing hydrogen bonds (black dots) between 4H11-scFv and MUC16^ecto. FIG.11F shows that pull-down assay was performed using MBP-tagged MUC16^ecto and variants as a bait and WT 4H11-scFv as a prey. After binding, the MBP resins were washed three times and the bound proteins were released and subject to SDS-PAGE. Lane 1-5: input proteins of WT 4H11-scFv (lane 1), MBP-tagged MUC16^ecto (lane 2), and the MBP-MUC16^ecto variants (lane 3-5); lane 6, pull-down as a control; lane 7-8, MUC16 double mutations (D25A/R24A) against V_H or double mutations (D18A/G17A) against VL; lane 9, two double mutations (D25A/R24A, D18A/G17A) of the MUC16^ecto. [0039] FIGs.12A-12F show the conformational dynamics of antibody V_H-V_L binding interface residues depending upon antigen binding. FIG.12A shows that 4H11-scFv itself can be extensively stabilized by VH (skyblue) and VL (pink) interaction. There are 11 hydrogen bonds based on the X-ray structure between VH and VL. FIG.12B shows that the interface residues showed a dramatic conformational change depending upon MUC16^ecto binding (orange), showing the reduced 6 hydrogen bonds with different atom-to-atom distances and new hydrogen bond was formed between Q196 (red) of V_H and S197 of V_L comparing to antibody itself, each CDRs for VH (blue) and VL (pink). FIG.12C shows the superimposed line model between bound and unbound status. Root-mean-square-deviation (R.M.S.D) between the backbone atoms of superimposed proteins was 0.454 (V_H*: V_H) or 0.355 (VL*: VL), respectively. FIGs.12D-12F show the representative residues with 2Fo-Fc electron density map (contoured at 1.0 σ) that showed the conformational dynamics. FIG. 12D shows that the hydrogen bond between Y104 (V_H) and K184 (V_L) was broken (red “x”) depending upon MUC16^ecto binding due to the movement of K184 by 2.2 Å (black bi-arrow) with the orientation change of Y104 aromatic ring. The measured distance between the moved K184 and Y104 was 4.4 Å with no contact. FIG.12E shows that Y108 (V_H) was moved toward MUC16 by 3.3 Å and the previous hydrogen bonds formed with V_L residues (T182, Q243, and S245) were broken (red ”x”) and it formed new hydrogen bonds with water-mediated interactions (FIG.15 for detailed version). FIG.12F shows that a new hydrogen bond was formed between Q115 (V_H) and S197 (V_L). The MUC16^ecto binding triggers a ~180^o rotation of the sidechain (red) to form a hydrogen bond with S197. [0040] FIGs.13A-13C show internalization mechanism of 4H11-scFv. FIG.13A shows that MUC16 (unshed form) can form the short-shed form by proteolytic cleavages at the specific sites (red dot arrows) and the 4H11-scFv binds to juxtamembrane regions (between N13^rd and L31^st) of both forms. However, only the complex of only shed form’s MUC16- scFv can be internalized into the cytosol from outside cancer microenvironment (pH ~ 6.4) by endocytosis, which form an endosome (pH 5.5 ~ 6.5) that might form endolysosome (pH 4.5 ~ 5.5) or move into the nucleus. FIG.13B shows the live cell imaging of SKBR3 using Alexa fluor^® 488 fluorescent dye (Alexa-4H11-scFv); DIC image (left panel), Alexa-350- WGA membrane staining (middle panel), and Alexa-4H11-scFv (right panel) after 12 hours that shows both the 4H11-scFv bound to MUC16 and endosome vesicle (white arrow in the white dot box) and Alexa-4H11-scFv accumulated in the cytosol after 48 hours (2 × enlarged image). Scale bar: 30 μm. FIG.13C shows that the 4H11-scFv enables various immunotherapeutic approaches: the antibody-radioactive isotopes for early cancer detections, the antibody-drug or –toxin conjugates for cell cytotoxicity, CAR-T (chimeric antigen receptor) therapy for use in immunotherapy using the engineered T-cells and bi-specific antibody for incorporating the immune cells and MUC16 for the treatments of MUC16- overexpressed cancers. [0041] FIG.14 shows data collection and refinement statistics for the x-ray crystallography. [0042] FIG.15 shows protein-protein interaction in the 4H11-scFv-MUC16^ecto complex. [0043] FIG.16 shows structural dynamics of V_H-V_L interface before/after binding to MUC16^ecto. [0044] FIG.17 shows analysis of torsional angles from L31^st to P14^th of MUC16^ecto. [0045] FIG.18 shows schematic description of yeast 2 hybrid strategy. [0046] FIG.19 shows line representation with stick residues at the specific positions for potentially artificial disulfide bridge based on h4H11-scFv structure. Up: Interesting residues for S-S bridge, A49 and I70 (blue) in VH and A39 and I53 (red) in VL with distances between. Low: Mutagenesis simulation for showing S-S pair obtained by calculating correct rotamer after mutations, A49-I70 (blue) in VH and A39-I53 (red) in VL are mutated to Cysteines (orange). [0047] FIG.20 shows specificity of killing efficiency by Anti-MUC16 antibody drug conjugate (ADC). DETAILED DESCRIPTION [0048] It is to be appreciated that certain aspects, modes, embodiments, variations and features of the present methods are described below in various levels of detail in order to provide a substantial understanding of the present technology. It is to be understood that the present disclosure is not limited to particular uses, methods, reagents, compounds, compositions or biological systems, which can, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting. [0049] In practicing the present methods, many conventional techniques in molecular biology, protein biochemistry, cell biology, immunology, microbiology and recombinant DNA are used. See, e.g., Sambrook and Russell eds. (2001) Molecular Cloning: A Laboratory Manual, 3rd edition; the series Ausubel et al. eds. (2007) Current Protocols in Molecular Biology; the series Methods in Enzymology (Academic Press, Inc., N.Y.); MacPherson et al. (1991) PCR 1: A Practical Approach (IRL Press at Oxford University Press); MacPherson et al. (1995) PCR 2: A Practical Approach; Harlow and Lane eds. (1999) Antibodies, A Laboratory Manual; Freshney (2005) Culture of Animal Cells: A Manual of Basic Technique, 5th edition; Gait ed. (1984) Oligonucleotide Synthesis; U.S. Patent No. 4,683,195; Hames and Higgins eds. (1984) Nucleic Acid Hybridization; Anderson (1999) Nucleic Acid Hybridization; Hames and Higgins eds. (1984) Transcription and Translation; Immobilized Cells and Enzymes (IRL Press (1986)); Perbal (1984) A Practical Guide to Molecular Cloning; Miller and Calos eds. (1987) Gene Transfer Vectors for Mammalian Cells (Cold Spring Harbor Laboratory); Makrides ed. (2003) Gene Transfer and Expression in Mammalian Cells; Mayer and Walker eds. (1987) Immunochemical Methods in Cell and Molecular Biology (Academic Press, London); and Herzenberg et al. eds (1996) Weir’s Handbook of Experimental Immunology. Methods to detect and measure levels of polypeptide gene expression products (i.e., gene translation level) are well-known in the art and include the use of polypeptide detection methods such as antibody detection and quantification techniques. (See also, Strachan & Read, Human Molecular Genetics, Second Edition. (John Wiley and Sons, Inc., NY, 1999)). [0050] Disclosed herein are structures, the molecular dynamics, internalization, and the binding mechanisms of the anti-MUC16 antibody fragment 4H11-scFv with respect to targeting MUC16-ectodomain. These studies reveal extensive conformational dynamics of 4H11-scFv depending upon MUC16 binding; these are determined as a unique flexible loop containing two continuative β-Turns and a β-hairpin. These results offer insight into how the 4H11-scFv interacts with the unshed form (MUC16^ecto) and permits the design of antibody agents with improved therapeutic properties. [0051] The present disclosure demonstrates that that targeting nonCA125 pure protein epitopes in the proximal MUC16 ectodomain may still block MUC16 related oncogenic functions. To mitigate the issues surrounding the use of murine antibodies as human drugs, disclosed herein are engineered humanized antibody variants against the MUC16^ecto recognized by murine 4H11 (m4H11). The present disclosure also demonstrates that the humanized 4H11 (h4H11) was substantially superior to the m4H11in Matrigel Invasion, antibody drug conjugate (ADC) killing, Chimeric Antigen Receptor (CAR)-T cell therapy and in vivo tumor binding Definitions [0052] Unless defined otherwise, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this technology belongs. As used in this specification and the appended claims, the singular forms “a”, “an” and “the” include plural referents unless the content clearly dictates otherwise. For example, reference to “a cell” includes a combination of two or more cells, and the like. Generally, the nomenclature used herein and the laboratory procedures in cell culture, molecular genetics, organic chemistry, analytical chemistry and nucleic acid chemistry and hybridization described below are those well-known and commonly employed in the art. [0053] As used herein, the term “about” in reference to a number is generally taken to include numbers that fall within a range of 1%, 5%, or 10% in either direction (greater than or less than) of the number unless otherwise stated or otherwise evident from the context (except where such number would be less than 0% or exceed 100% of a possible value). [0054] As used herein, the “administration” of an agent or drug to a subject includes any route of introducing or delivering to a subject a compound to perform its intended function. Administration can be carried out by any suitable route, including but not limited to, orally, intranasally, parenterally (intravenously, intramuscularly, intraperitoneally, or subcutaneously), rectally, intrathecally, intratumorally or topically. Administration includes self-administration and the administration by another. [0055] The term “amino acid” refers to naturally occurring and non-naturally occurring amino acids, as well as amino acid analogs and amino acid mimetics that function in a manner similar to the naturally occurring amino acids. Naturally encoded amino acids are the 20 common amino acids (alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine) and pyrolysine and selenocysteine. Amino acid analogs refer to agents that have the same basic chemical structure as a naturally occurring amino acid, i.e., an a carbon that is bound to a hydrogen, a carboxyl group, an amino group, and an R group, such as, homoserine, norleucine, methionine sulfoxide, methionine methyl sulfonium. Such analogs have modified R groups (such as norleucine) or modified peptide backbones, but retain the same basic chemical structure as a naturally occurring amino acid. In some embodiments, amino acids forming a polypeptide are in the D form. In some embodiments, the amino acids forming a polypeptide are in the L form. In some embodiments, a first plurality of amino acids forming a polypeptide are in the D form and a second plurality are in the L form. [0056] Amino acids are referred to herein by either their commonly known three letter symbols or by the one-letter symbols recommended by the IUPAC-IUB Biochemical Nomenclature Commission. Nucleotides, likewise, are referred to by their commonly accepted single-letter code. [0057] As used herein, the term “antibody” collectively refers to immunoglobulins or immunoglobulin-like molecules including by way of example and without limitation, IgA, IgD, IgE, IgG and IgM, combinations thereof, and similar molecules produced during an immune response in any vertebrate, for example, in mammals such as humans, goats, rabbits and mice, as well as non-mammalian species, such as shark immunoglobulins. As used herein, “antibodies” (includes intact immunoglobulins) and “antigen binding fragments” specifically bind to a molecule of interest (or a group of highly similar molecules of interest) to the substantial exclusion of binding to other molecules (for example, antibodies and antibody fragments that have a binding constant for the molecule of interest that is at least 10³ M^-1 greater, at least 10⁴ M^-1 greater or at least 10⁵ M^-1 greater than a binding constant for other molecules in a biological sample). The term “antibody” also includes native antibodies, monoclonal antibodies, human antibodies, humanized antibodies, camelised antibodies, multispecific antibodies, bispecific antibodies, chimeric antibodies, Fab, Fab', single chain V region fragments (scFv), single domain antibodies (e.g, nanobodies and single domain camelid antibodies), VNAR fragments, Bi-specific T-cell engager antibodies, minibodies, disulfide- linked Fvs (sdFv), and anti-idiotypic (anti-id) antibodies, intrabodies, fusion polypeptides, unconventional antibodies and antigen binding fragments of any of the above. See also, Pierce Catalog and Handbook, 1994-1995 (Pierce Chemical Co., Rockford, Ill.); Kuby, J., Immunology, 3^rd Ed., W.H. Freeman & Co., New York, 1997. [0058] More particularly, antibody refers to a polypeptide ligand comprising at least a light chain immunoglobulin variable region or heavy chain immunoglobulin variable region which specifically recognizes and binds an epitope of an antigen. Antibodies are composed of a heavy and a light chain, each of which has a variable region, termed the variable heavy (V_H) region and the variable light (V_L) region. Together, the V_H region and the V_L region are responsible for binding the antigen recognized by the antibody. Typically, an immunoglobulin has heavy (H) chains and light (L) chains interconnected by disulfide bonds. There are two types of light chain, lambda (λ) and kappa ( ^). There are five main heavy chain classes (or isotypes) which determine the functional activity of an antibody molecule: IgM, IgD, IgG, IgA and IgE. Each heavy and light chain contains a constant region and a variable region, (the regions are also known as “domains”). In combination, the heavy and the light chain variable regions specifically bind the antigen. Light and heavy chain variable regions contain a “framework” region interrupted by three hypervariable regions, also called “complementarity-determining regions” or “CDRs”. The extent of the framework region and CDRs have been defined (see, Kabat et al., Sequences of Proteins of Immunological Interest, U.S. Department of Health and Human Services, 1991, which is hereby incorporated by reference). The Kabat database is now maintained online. The sequences of the framework regions of different light or heavy chains are relatively conserved within a species. The framework region of an antibody, that is the combined framework regions of the constituent light and heavy chains, largely adopt a β-sheet conformation and the CDRs form loops which connect, and in some cases form part of, the β-sheet structure. Thus, framework regions act to form a scaffold that provides for positioning the CDRs in correct orientation by inter- chain, non-covalent interactions. [0059] The CDRs are primarily responsible for binding to an epitope of an antigen. The CDRs of each chain are typically referred to as CDR1, CDR2, and CDR3, numbered sequentially starting from the N-terminus, and are also typically identified by the chain in which the particular CDR is located. Thus, a VH CDR3 is located in the variable domain of the heavy chain of the antibody in which it is found, whereas a V_L CDR1 is the CDR1 from the variable domain of the light chain of the antibody in which it is found. An antibody that binds a target protein (e.g., MUC16) will have a specific VH region and the VL region sequence, and thus specific CDR sequences. Antibodies with different specificities (i.e. different combining sites for different antigens) have different CDRs. Although it is the CDRs that vary from antibody to antibody, only a limited number of amino acid positions within the CDRs are directly involved in antigen binding. These positions within the CDRs are called specificity determining residues (SDRs). “Immunoglobulin-related compositions” as used herein, refers to antibodies (including monoclonal antibodies, polyclonal antibodies, human antibodies, humanized antibodies, chimeric antibodies, recombinant antibodies, multi- specific antibodies, bispecific antibodies, etc.,) as well as antibody fragments. An antibody or antigen binding fragment thereof specifically binds to an antigen. [0060] As used herein, the term “antibody-related polypeptide” means antigen-binding antibody fragments, including single-chain antibodies, that can comprise the variable region(s) alone, or in combination, with all or part of the following polypeptide elements: hinge region, CH1, CH2, and CH3 domains of an antibody molecule. Also included in the technology are any combinations of variable region(s) and hinge region, CH1, CH2, and CH3 domains. Antibody-related molecules useful in the present methods, e.g., but are not limited to, Fab, Fab′ and F(ab′)₂, Fd, single-chain Fvs (scFv), single-chain antibodies, disulfide- linked Fvs (sdFv) and fragments comprising either a VL or VH domain. Examples include: (i) a Fab fragment, a monovalent fragment consisting of the V_L, V_H, C_L and CH₁ domains; (ii) a F(ab′)₂ fragment, a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region (A“F(ab')2” fragment can be split into two individual Fab' fragments.); (iii) a Fd fragment consisting of the VH and CH1 domains; (iv) a Fv fragment consisting of the V_L and V_H domains of a single arm of an antibody, (v) a dAb fragment (Ward et al., Nature 341: 544-546, 1989), which consists of a VH domain; and (vi) an isolated complementarity determining region (CDR). As such “antibody fragments” or “antigen binding fragments” can comprise a portion of a full length antibody, generally the antigen binding or variable region thereof. Examples of antibody fragments or antigen binding fragments include Fab, Fab', F(ab')2, and Fv fragments; diabodies (dscFvs); linear antibodies; single-chain antibody molecules; and multi-specific antibodies formed from antibody fragments. [0061] As used herein, an “antigen” refers to a molecule to which an antibody (or antigen binding fragment thereof) can selectively bind. The target antigen may be a protein, carbohydrate, nucleic acid, lipid, hapten, or other naturally occurring or synthetic compound. In some embodiments, the target antigen may be a polypeptide. An antigen may also be administered to an animal to generate an immune response in the animal. [0062] The term “antigen binding fragment” refers to a fragment of the whole immunoglobulin structure which possesses a part of a polypeptide responsible for binding to antigen. Examples of the antigen binding fragment useful in the present technology include scFv, (scFv)₂, scFvFc, Fab, Fab′ and F(ab′)₂, but are not limited thereto. Any of the above- noted antibody fragments are obtained using conventional techniques known to those of skill in the art, and the fragments are screened for binding specificity and neutralization activity in the same manner as are intact antibodies. [0063] As used herein, “binding affinity” means the strength of the total noncovalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen or antigenic peptide). The affinity of a molecule X for its partner Y can generally be represented by the dissociation constant (K_D). Affinity can be measured by standard methods known in the art, including those described herein. A low-affinity complex contains an antibody that generally tends to dissociate readily from the antigen, whereas a high-affinity complex contains an antibody that generally tends to remain bound to the antigen for a longer duration. [0064] Without being bound to theory, affinity depends on the closeness of stereochemical fit between antibody combining sites and antigen determinants, on the size of the area of contact between them, and on the distribution of charged and hydrophobic groups. Affinity also includes the term “avidity,” which refers to the strength of the antigen- antibody bond after formation of reversible complexes (e.g., either monovalent or multivalent). Methods for calculating the affinity of an antibody for an antigen are known in the art, comprising use of binding experiments to calculate affinity. Antibody activity in functional assays (e.g., flow cytometry assay) is also reflective of antibody affinity. Antibodies and affinities can be phenotypically characterized and compared using functional assays (e.g., flow cytometry assay). [0065] As used herein, the term “CDR grafting” means replacing at least one CDR of an “acceptor” antibody by a CDR “graft” from a “donor” antibody possessing a desirable antigen specificity. As used herein, the term “CDR-grafted antibody” means an antibody in which at least one CDR of an “acceptor” antibody is replaced by a CDR “graft” from a “donor” antibody possessing a desirable antigen specificity. [0066] As used herein, the term “conjugated” refers to the association of two molecules by any method known to those in the art. Suitable types of associations include chemical bonds and physical bonds. Chemical bonds include, for example, covalent bonds and coordinate bonds. Physical bonds include, for instance, hydrogen bonds, dipolar interactions, van der Waal forces, electrostatic interactions, hydrophobic interactions and aromatic stacking. [0067] As used herein, the term “consensus FR” means a framework (FR) antibody region in a consensus immunoglobulin sequence. The FR regions of an antibody do not contact the antigen. [0068] As used herein, the term "constant region" or "constant domain" is interchangeable and has its meaning common in the art. The constant region is an antibody portion, e.g, a carboxyl terminal portion of a light and/or heavy chain which is not directly involved in binding of an antibody to antigen but which can exhibit various effector functions, such as interaction with the Fc receptor. The constant region of an immunoglobulin molecule generally has a more conserved amino acid sequence relative to an immunoglobulin variable domain. [0069] As used herein, a "control" is an alternative sample used in an experiment for comparison purpose. A control can be "positive" or "negative." For example, where the purpose of the experiment is to determine a correlation of the efficacy of a therapeutic agent for the treatment for a particular type of disease, a positive control (a compound or composition known to exhibit the desired therapeutic effect) and a negative control (a subject or a sample that does not receive the therapy or receives a placebo) are typically employed. [0070] As used herein, the term “diabodies” refers to small antibody fragments with two antigen-binding sites, which fragments comprise a heavy-chain variable domain (VH) connected to a light-chain variable domain (V_L) in the same polypeptide chain (V_H V_L). By using a linker that is too short to allow pairing between the two domains on the same chain, the domains are forced to pair with the complementary domains of another chain and create two antigen binding sites. Diabodies are described more fully in, e.g., EP 404,097; WO 93/11161; and Hollinger et al., Proc Natl Acad Sci USA, 90: 6444-6448 (1993). [0071] As used herein, the term “effective amount” refers to a quantity sufficient to achieve a desired therapeutic and/or prophylactic effect, e.g., an amount which results in the prevention of, or a decrease in a disease or condition described herein or one or more signs or symptoms associated with a disease or condition described herein. In the context of therapeutic or prophylactic applications, the amount of a composition administered to the subject will vary depending on the composition, the degree, type, and severity of the disease and on the characteristics of the individual, such as general health, age, sex, body weight and tolerance to drugs. The skilled artisan will be able to determine appropriate dosages depending on these and other factors. The compositions can also be administered in combination with one or more additional therapeutic compounds. In the methods described herein, the therapeutic compositions may be administered to a subject having one or more signs or symptoms of a disease or condition described herein. As used herein, a "therapeutically effective amount" of a composition refers to composition levels in which the physiological effects of a disease or condition are ameliorated or eliminated. A therapeutically effective amount can be given in one or more administrations. [0072] As used herein, the term “epitope” means a protein determinant capable of specific binding to an antibody. Epitopes usually consist of chemically active surface groupings of molecules such as amino acids or sugar side chains and usually have specific three dimensional structural characteristics, as well as specific charge characteristics. Conformational and non-conformational epitopes are distinguished in that the binding to the former but not the latter is lost in the presence of denaturing solvents. In some embodiments, an “epitope” of the MUC16 protein is a region of the protein to which the anti-MUC16 antibodies of the present technology specifically bind (e.g., MUC16^ecto). In some embodiments, the epitope is a conformational epitope or a non-conformational epitope. To screen for anti-MUC16 antibodies which bind to an epitope, a routine cross-blocking assay such as that described in Antibodies, A Laboratory Manual, Cold Spring Harbor Laboratory, Ed Harlow and David Lane (1988), can be performed. This assay can be used to determine if an anti-MUC16 antibody binds the same site or epitope as an anti-MUC16 antibody of the present technology. Alternatively, or additionally, epitope mapping can be performed by methods known in the art. For example, the antibody sequence can be mutagenized such as by alanine scanning, to identify contact residues. In a different method, peptides corresponding to different regions of MUC16 protein can be used in competition assays with the test antibodies or with a test antibody and an antibody with a characterized or known epitope. An epitope can be, e.g., contiguous amino acids of a polypeptide (linear or contiguous epitope) or an epitope can, e.g., come together from two or more noncontiguous regions of a polypeptide or polypeptides (conformational, non-linear, discontinuous, or non- contiguous epitope). [0073] As used herein, the term “expression” refers to the process by which polynucleotides are transcribed into mRNA and/or the process by which the transcribed mRNA is subsequently being translated into peptides, polypeptides, or proteins. If the polynucleotide is derived from genomic DNA, expression can include splicing of the mRNA in a eukaryotic cell. The expression level of a gene can be determined by measuring the amount of mRNA or protein in a cell or tissue sample. In one aspect, the expression level of a gene from one sample can be directly compared to the expression level of that gene from a control or reference sample. In another aspect, the expression level of a gene from one sample can be directly compared to the expression level of that gene from the same sample following administration of the compositions disclosed herein. The term “expression” also refers to one or more of the following events: (1) production of an RNA template from a DNA sequence (e.g., by transcription) within a cell; (2) processing of an RNA transcript (e.g, by splicing, editing, 5’ cap formation, and/or 3’ end formation) within a cell; (3) translation of an RNA sequence into a polypeptide or protein within a cell; (4) post-translational modification of a polypeptide or protein within a cell; (5) presentation of a polypeptide or protein on the cell surface; and (6) secretion or presentation or release of a polypeptide or protein from a cell. [0074] As used herein, the term “gene” means a segment of DNA that contains all the information for the regulated biosynthesis of an RNA product, including promoters, exons, introns, and other untranslated regions that control expression. [0075] As used herein, “homology” or “identity” or “similarity” refers to sequence similarity between two peptides or between two nucleic acid molecules. Homology can be determined by comparing a position in each sequence which may be aligned for purposes of comparison. When a position in the compared sequence is occupied by the same base or amino acid, then the molecules are homologous at that position. A degree of homology between sequences is a function of the number of matching or homologous positions shared by the sequences. A polynucleotide or polynucleotide region (or a polypeptide or polypeptide region) has a certain percentage (for example, at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99%) of “sequence identity” to another sequence means that, when aligned, that percentage of bases (or amino acids) are the same in comparing the two sequences. This alignment and the percent homology or sequence identity can be determined using software programs known in the art. In some embodiments, default parameters are used for alignment. One alignment program is BLAST, using default parameters. In particular, programs are BLASTN and BLASTP, using the following default parameters: Genetic code=standard; filter=none; strand=both; cutoff=60; expect=10; Matrix=BLOSUM62; Descriptions=50 sequences; sort by ═HIGH SCORE; Databases=non-redundant, GenBank+EMBL+DDBJ+PDB+GenBank CDS translations+SwissProtein+SPupdate+PIR. Details of these programs can be found at the National Center for Biotechnology Information. Biologically equivalent polynucleotides are those having the specified percent homology and encoding a polypeptide having the same or similar biological activity. Two sequences are deemed “unrelated” or “non-homologous” if they share less than 40% identity, or less than 25% identity, with each other. [0076] As used herein, “humanized” forms of non-human (e.g., murine) antibodies are chimeric antibodies which contain minimal sequence derived from non-human immunoglobulin. For the most part, humanized antibodies are human immunoglobulins in which hypervariable region residues of the recipient are replaced by hypervariable region residues from a non-human species (donor antibody) such as mouse, rat, rabbit or nonhuman primate having the desired specificity, affinity, and capacity. In some embodiments, Fv framework region (FR) residues of the human immunoglobulin are replaced by corresponding non-human residues. Furthermore, humanized antibodies may comprise residues which are not found in the recipient antibody or in the donor antibody. These modifications are made to further refine antibody performance such as binding affinity. Generally, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains (e.g., Fab, Fab′, F(ab′)₂, or Fv), in which all or substantially all of the hypervariable loops correspond to those of a non-human immunoglobulin and all or substantially all of the FR regions are those of a human immunoglobulin consensus FR sequence although the FR regions may include one or more amino acid substitutions that improve binding affinity. The number of these amino acid substitutions in the FR are typically no more than 6 in the H chain, and in the L chain, no more than 3. The humanized antibody optionally may also comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin. For further details, see Jones et al., Nature 321:522-525 (1986); Reichmann et al., Nature 332:323-329 (1988); and Presta, Curr. Op. Struct. Biol.2:593-596 (1992). See e.g., Ahmed & Cheung, FEBS Letters 588(2):288- 297 (2014). By way of example, a humanized version of a murine antibody to a given antigen has on both of its heavy and light chains (1) constant regions of a human antibody; (2) framework regions from the variable domains of a human antibody; and (3) CDRs from the murine antibody. When necessary, one or more residues in the human framework regions can be changed to residues at the corresponding positions in the murine antibody so as to preserve the binding affinity of the humanized antibody to the antigen. This change is sometimes called “back mutation.” Similarly, forward mutations may be made to revert back to murine sequence for a desired reason, e.g., stability or affinity to antigen. [0077] As used herein, the term “hypervariable region” refers to the amino acid residues of an antibody which are responsible for antigen-binding. The hypervariable region generally comprises amino acid residues from a “complementarity determining region” or “CDR” (e.g., around about residues 24-34 (L1), 50-56 (L2) and 89-97 (L3) in the V_L, and around about 31- 35B (H1), 50-65 (H2) and 95-102 (H3) in the VH (Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD. (1991)) and/or those residues from a “hypervariable loop” (e.g., residues 26- 32 (L1), 50-52 (L2) and 91-96 (L3) in the VL, and 26-32 (H1), 52A-55 (H2) and 96-101 (H3) in the VH (Chothia and Lesk J. Mol. Biol.196:901-917 (1987)). [0078] As used herein, the terms “identical” or percent “identity”, when used in the context of two or more nucleic acids or polypeptide sequences, refer to two or more sequences or subsequences that are the same or have a specified percentage of amino acid residues or nucleotides that are the same (i.e., about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or higher identity over a specified region (e.g., nucleotide sequence encoding an antibody described herein or amino acid sequence of an antibody described herein)), when compared and aligned for maximum correspondence over a comparison window or designated region as measured using a BLAST or BLAST 2.0 sequence comparison algorithms with default parameters described below, or by manual alignment and visual inspection (e.g., NCBI web site). Such sequences are then said to be “substantially identical.” This term also refers to, or can be applied to, the complement of a test sequence. The term also includes sequences that have deletions and/or additions, as well as those that have substitutions. In some embodiments, identity exists over a region that is at least about 25 amino acids or nucleotides in length, or 50-100 amino acids or nucleotides in length. [0079] As used herein, the terms "immunospecifically binds," "immunospecifically recognizes," "specifically binds," and "specifically recognizes" are analogous terms in the context of antibodies and refer to antibodies and antigen binding fragments thereof that bind to an antigen (e.g., epitope or immune complex) via the antigen-binding sites as understood by one skilled in the art, and does not exclude cross-reactivity of the antibody or antigen binding fragment with other antigens. [0080] As used herein, the term “intact antibody” or “intact immunoglobulin” means an antibody that has at least two heavy (H) chain polypeptides and two light (L) chain polypeptides interconnected by disulfide bonds. Each heavy chain is comprised of a heavy chain variable region (abbreviated herein as HCVR or V_H) and a heavy chain constant region. The heavy chain constant region is comprised of three domains, CH₁, CH₂ and CH₃. Each light chain is comprised of a light chain variable region (abbreviated herein as LCVR or VL) and a light chain constant region. The light chain constant region is comprised of one domain, C_L. The V_H and V_L regions can be further subdivided into regions of hypervariability, termed complementarity determining regions (CDR), interspersed with regions that are more conserved, termed framework regions (FR). Each VH and VL is composed of three CDRs and four FRs, arranged from amino-terminus to carboxyl-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The variable regions of the heavy and light chains contain a binding domain that interacts with an antigen. The constant regions of the antibodies can mediate the binding of the immunoglobulin to host tissues or factors, including various cells of the immune system (e.g., effector cells) and the first component (Clq) of the classical complement system. [0081] As used herein, the term “ligand” refers to a molecule that binds to a receptor. In particular, the ligand binds a receptor on another cell, allowing for cell-to-cell recognition and/or interaction. [0082] As used herein, the term “linker” refers to a functional group (e.g., chemical or polypeptide) that covalently attaches two or more polypeptides or nucleic acids so that they are connected to one another. As used herein, a “peptide linker” refers to one or more amino acids used to couple two proteins together (e.g., to couple V_H and V_L domains). In certain embodiments, the linker comprises amino acids having the sequence (GGGGS)_n, wherein n is at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 12, 14, or 15. [0083] The term “monoclonal antibody” as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations that may be present in minor amounts. For example, a monoclonal antibody can be an antibody that is derived from a single clone, including any eukaryotic, prokaryotic, or phage clone, and not the method by which it is produced. A monoclonal antibody composition displays a single binding specificity and affinity for a particular epitope. Monoclonal antibodies are highly specific, being directed against a single antigenic site. Furthermore, in contrast to conventional (polyclonal) antibody preparations which typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a single determinant on the antigen. The modifier “monoclonal” indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies, and is not to be construed as requiring production of the antibody by any particular method. Monoclonal antibodies can be prepared using a wide variety of techniques known in the art including, e.g., but not limited to, hybridoma, recombinant, and phage display technologies. For example, the monoclonal antibodies to be used in accordance with the present methods may be made by the hybridoma method first described by Kohler et al., Nature 256:495 (1975), or may be made by recombinant DNA methods (See, e.g., U.S. Patent No.4,816,567). The “monoclonal antibodies” may also be isolated from phage antibody libraries using the techniques described in Clackson et al., Nature 352:624-628 (1991) and Marks et al., J. Mol. Biol.222:581-597 (1991), for example. [0084] As used herein, “anti-MUC16 antibody agents” refer to agents comprising anti- MUC16 antibodies or antigen binding fragments thereof, and include, but are not limited to, e.g., monoclonal antibodies, polyclonal antibodies, recombinantly produced antibodies, monospecific antibodies, multispecific antibodies (including bispecific antibodies (BsAb)), human antibodies, humanized antibodies, chimeric antibodies, immunoglobulins, synthetic antibodies, tetrameric antibodies comprising two heavy chain and two light chain molecules, an antibody light chain monomer, an antibody heavy chain monomer, an antibody light chain dimer, an antibody heavy chain dimer, an antibody light chain- antibody heavy chain pair, intrabodies, single domain antibodies, monovalent antibodies, single chain antibodies or single-chain variable fragments (scFv), camelized antibodies, affybodies, and disulfide-linked Fvs (dsFv), Fc fusion proteins, immunoconjugates, or fragments thereof. Such antibodies and antigen binding fragments can be made by methods known in the art. [0085] As used herein, the term "MUC16" or "MUC16 polypeptide" or "MUC16 peptide" refers to the MUC16 tethered mucin protein as described in Yin BW and Lloyd KO, 2001, J Biol Chem.276(29):27371-5. GenBank™ accession number NP 078966.2 (SEQ ID NO: 9) provides an exemplary human MUC16 amino acid sequence. Immature MUC16, NP 078966.2 (SEQ ID NO: 9)

[0086] Native MUC16 comprises an intracellular domain, a transmembrane domain, an ectodomain proximal to the putative cleavage site, and a large, heavily glycosylated region of 12-20 repeats, each 156 amino acids long. "Immature" MUC16 refers to SEQ ID NO: 9, which comprises the MUC16 signal sequence (amino acid residues 1-60 of SEQ ID NO: 9). "Mature MUC16" refers to native MUC16 as expressed on the cell surface, i.e., where the signal sequence has been removed by cellular processing, for example, SEQ ID NO: 10, where the first 60 amino acid residues of SEQ ID NO: 9 have been removed (i.e., SEQ ID NO: 9 is the "immature" form of MUC16). [0087] "Mature MUC16" (SEQ ID NO: 10)

ALDNDSLFVNGFTHRSSVSTTSTPGTPTVYLGASKTPASIFGPSAASHLLILFTLNFTIT NLRYEENMWPGSRKFNTTERVLQGLLRPLFKNTSVGPLYSGCRLTLLRPEKDGEATG VDAICTHRPDPTGPGLDREQLYLELSQLTHSITELGPYTLDRDSLYVNGFTHRSSVPT TSTGVVSEEPFTLNFTINNLRYMADMGQPGSLKFNITDNVMQHLLSPLFQRSSLGAR YTGCRVIALRSVKNGAETRVDLLCTYLQPLSGPGLPIKQVFHELSQQTHGITRLGPYS LDKDSLYLNGYNEPGPDEPPTTPKPATTFLPPLSEATTAMGYHLKTLTLNFTISNLQY SPDMGKGSATFNSTEGVLQHLLRPLFQKSSMGPFYLGCQLISLRPEKDGAATGVDTT CTYHPDPVGPGLDIQQLYWELSQLTHGVTQLGFYVLDRDSLFINGYAPQNLSIRGEY QINFHIVNWNLSNPDPTSSEYITLLRDIQDKVTTLYKGSQLHDTFRFCLVTNLTMDSV LVTVKALFSSNLDPSLVEQVFLDKTLNASFHWLGSTYQLVDIHVTEMESSVYQPTSS SSTQHFYLNFTITNLPYSQDKAQPGTTNYQRNKRNIEDALNQLFRNSSIKSYFSDCQV STFRSVPNRHHTGVDSLCNFSPLARRVDRVAIYEEFLRMTRNGTQLQNFTLDRSSVL VDGYSPNRNEPLTGNSDLPFWAVILIGLAGLLGVITCLICGVLVTTRRRKKEGEYNVQ

QQCPGYYQSHLDLEDLQ [0088] The polypeptide represented by the amino acid sequence of SEQ ID NO: 11 is referred to herein as MUC16^c114 and consists of the C-terminal 114 amino acid residues of mature MUC16 (SEQ ID NO: 10 being the sequence of mature MUC16). MUC16^c114 comprises a 58 amino acid ectodomain, a 25 amino acid transmembrane domain and a 31 amino acid cytoplasmic tail. MUC16^cl14 is capable of being N-glycosylated at the asparagine amino acid residues at positions 1, 24, and 30 of SEQ ID NO: 11 (also referred to as amino acid positions Asn1777, Asn1800, and Asn1806 according the original MUC16 publication Yin BW and Lloyd KO, 2001, J Biol Chem.276(29):27371-5). [0089] MUC16^cl14 (SEQ ID NO: 11) NFSPLARRVDRVAIYEEFLRMTRNGTQLQNFTLDRSSVLVDGYSPNRNEPLTGNSDL PFWAVILIGLAGLLGLITCLICGVLVTTRRRKKEGEYNVQQQCPGYYQSHLDLEDLQ

(SEQ ID NO: 11) [0090] The 58 amino acid ectodomain sequence present in MUC16 ^c114 is represented as SEQ ID NO: 12: [0091] NFSPLARRVDRVAIYEEFLRMTRNGTQLQNFTLDRSSVLVDGYSPNRNEPLTG NSDLP (SEQ ID NO: 12) [0092] As used herein, the terms “polypeptide,” “peptide” and “protein” are used interchangeably herein to mean a polymer comprising two or more amino acids joined to each other by peptide bonds or modified peptide bonds, i.e., peptide isosteres. Polypeptide refers to both short chains, commonly referred to as peptides, glycopeptides or oligomers, and to longer chains, generally referred to as proteins. Polypeptides may contain amino acids other than the 20 gene-encoded amino acids. Polypeptides include amino acid sequences modified either by natural processes, such as post-translational processing, or by chemical modification techniques that are well known in the art. Such modifications are well described in basic texts and in more detailed monographs, as well as in a voluminous research literature. [0093] As used herein, the term “recombinant” when used with reference, e.g., to a cell, or nucleic acid, protein, or vector, indicates that the cell, nucleic acid, protein or vector, has been modified by the introduction of a heterologous nucleic acid or protein or the alteration of a native nucleic acid or protein, or that the material is derived from a cell so modified. Thus, for example, recombinant cells express genes that are not found within the native (non- recombinant) form of the cell or express native genes that are otherwise abnormally expressed, under expressed or not expressed at all. [0094] As used herein, the term “separate” therapeutic use refers to an administration of at least two active ingredients at the same time or at substantially the same time by different routes. [0095] As used herein, the term “sequential” therapeutic use refers to administration of at least two active ingredients at different times, the administration route being identical or different. More particularly, sequential use refers to the whole administration of one of the active ingredients before administration of the other or others commences. It is thus possible to administer one of the active ingredients over several minutes, hours, or days before administering the other active ingredient or ingredients. There is no simultaneous treatment in this case. [0096] As used herein, the term “simultaneous” therapeutic use refers to the administration of at least two active ingredients by the same route and at the same time or at substantially the same time. [0097] As used herein, the terms “single-chain antibodies” or “single-chain Fv (scFv)” refer to an antibody fusion molecule of the two domains of the Fv fragment, V_L and V_H. Single- chain antibody molecules may comprise a polymer with a number of individual molecules, for example, dimer, trimer or other polymers. Furthermore, although the two domains of the F_v fragment, V_L and V_H, are coded for by separate genes, they can be joined, using recombinant methods, by a synthetic linker that enables them to be made as a single protein chain in which the VL and VH regions pair to form monovalent molecules (known as single- chain F_v (scF_v)). Bird et al. (1988) Science 242:423-426 and Huston et al. (1988) Proc Natl Acad Sci 85:5879-5883. Such single-chain antibodies can be prepared by recombinant techniques or enzymatic or chemical cleavage of intact antibodies. [0098] The VH and VL domains are either joined directly or joined by a peptide-encoding linker (e.g, about 10, 15, 20, 25 amino acids), which connects the N-terminus of the V_H with the C-terminus of the VL, or the C-terminus of the VH with the N-terminus of the VL. In some embodiments, the linker is usually rich in glycine for flexibility, as well as serine or threonine for solubility. The linker can link the heavy chain variable region and the light chain variable region of the extracellular antigen binding domain. [0099] Despite removal of the constant regions and the introduction of a linker, scFv proteins retain the specificity of the original immunoglobulin. Single chain Fv polypeptide antibodies can be expressed from a nucleic acid comprising V_H- and V_L-encoding sequences as described by Huston, et al, Proc. Nat. Acad. Sci. USA, 85:5879-5883 (1988)). See, also, U.S. Patent Nos.5,091,513, 5,132,405 and 4,956,778; and U.S. Patent Publication Nos. 20050196754 and 20050196754. Antagonistic scFvs having inhibitory activity have been described (see, e.g., Zhao et al, Hybridoma (Larchmt) 27(6):455-51 (2008); Peter et al, J Cachexia Sarcopenia Muscle (2012); Shieh et al, J Imunol 183(4):2277-85 (2009); Giomarelli et al, Thromb Haemost 97(6):955-63 (2007); Fife et al, J Clin Invst 116(8):2252- 61 (2006); Brocks et al, Immunotechnology 3(3): 173-84 (1997); Moosmayer et al, Ther Immunol 2(10):31- 40 (1995). Agonistic scFvs having stimulatory activity have been described (see, e.g ., Peter et al, J Biol Chem 25278(38):36740-7 (2003); Xie et al, Nat Biotech 15(8):768-71 (1997); Ledbetter et al, Crit Rev Immunol 17(5-6):427-55 (1997); Ho et al, Bio Chim Biophys Acta 1638(3):257-66 (2003)). [00100] As used herein, “specifically binds” refers to a molecule (e.g., an antibody or antigen binding fragment thereof) which recognizes and binds another molecule (e.g., an antigen), but that does not substantially recognize and bind other molecules. The terms “specific binding,” “specifically binds to,” or is “specific for” a particular molecule (e.g., a polypeptide, or an epitope on a polypeptide), as used herein, can be exhibited, for example, by a molecule having a K_D for the molecule to which it binds to of about 10⁻⁴ M, 10⁻⁵ M, 10⁻⁶ M, 10⁻⁷ M, 10⁻⁸ M, 10⁻⁹ M, 10⁻¹⁰ M, 10⁻¹¹ M, or 10⁻¹² M. The term “specifically binds” may also refer to binding where a molecule (e.g., an antibody or antigen binding fragment thereof) binds to a particular polypeptide (e.g., a MUC16 polypeptide), or an epitope on a particular polypeptide, without substantially binding to any other polypeptide, or polypeptide epitope. [00101] As used herein, the terms “subject”, “patient”, or “individual” can be an individual organism, a vertebrate, a mammal, or a human. In some embodiments, the subject, patient or individual is a human. As used herein, the terms “subject”, “patient”, or “individual” are used interchangeably. [00102] As used herein, the term “therapeutic agent” is intended to mean a compound that, when present in an effective amount, produces a desired therapeutic effect on a subject in need thereof. [00103] “Treating” or “treatment” as used herein covers the treatment of a disease or disorder described herein, in a subject, such as a human, and includes: (i) inhibiting a disease or disorder, i.e., arresting its development; (ii) relieving a disease or disorder, i.e., causing regression of the disorder; (iii) slowing progression of the disorder; and/or (iv) inhibiting, relieving, or slowing progression of one or more symptoms of the disease or disorder. In some embodiments, treatment means that the symptoms associated with the disease are, e.g., alleviated, reduced, cured, or placed in a state of remission. [00104] It is also to be appreciated that the various modes of treatment of disorders as described herein are intended to mean “substantial,” which includes total but also less than total treatment, and wherein some biologically or medically relevant result is achieved. The treatment may be a continuous prolonged treatment for a chronic disease or a single, or few time administrations for the treatment of an acute condition. Anti-MUC16 Antibody Agents of the Present Technology [00105] Provided herein are anti-MUC16 antibody agents that immunospecifically bind to MUC16. In some embodiments, the anti-MUC16 antibody agent immunospecifically binds to the retained extracellular domain of MUC16. In some embodiments, the anti-MUC16 antibody agent is an anti-MUC16 construct that comprises an antibody moiety that immunospecifically binds to MUC16. In some embodiments, the anti-MUC16 antibody agent is an anti-MUC16 antibody (e.g., a full-length anti-MUC16 antibody or an antigen binding fragment thereof). In some embodiments, the anti-MUC16 antibody agent binds to an MUC16-expressing cell (e.g., an MUC16-expressing cancer cell). [00106] Anti-MUC16 antibody agents, such as anti-MUC16 antibodies or antigen-binding fragments thereof, can include, e.g., monoclonal antibodies, polyclonal antibodies, recombinantly produced antibodies, monospecific antibodies, multispecific antibodies (including bispecific antibodies (BsAb)), human antibodies, humanized antibodies, chimeric antibodies, immunoglobulins, synthetic antibodies, tetrameric antibodies comprising two heavy chain and two light chain molecules, an antibody light chain monomer, an antibody heavy chain monomer, an antibody light chain dimer, an antibody heavy chain dimer, an antibody light chain- antibody heavy chain pair, intrabodies, single domain antibodies, monovalent antibodies, single chain antibodies or single-chain variable fragments (scFv), camelized antibodies, affybodies, and disulfide-linked Fvs (dsFv), Fc fusion proteins, immunoconjugates, or fragments thereof. Such antibodies and antigen-binding fragments can be made by methods known in the art. [00107] In some embodiments, the anti-MUC16 antibody agent is a full-length antibody (e.g., full-length IgG) or antigen-binding fragment thereof, which specifically binds to MUC16. [00108] In some embodiments, reference to an antibody agent that immunospecifically binds to MUC16 means that the antibody agent binds to MUC16 with an affinity that is at least about 10 times (including for example at least about any of 10, 10², 10³, 10⁴, 10⁵, 10⁶, or 10⁷ times) its binding affinity for non-target. In some embodiments, the non-target is an antigen that is not MUC16. Binding affinity can be determined by methods known in the art, such as ELISA, fluorescence activated cell sorting (FACS) analysis, or radioimmunoprecipitation assay (RIA). Kd can be determined by methods known in the art, such as surface plasmon resonance (SPR) assay utilizing, for example, Biacore instruments, or kinetic exclusion assay (KinExA) utilizing, for example, Sapidyne instruments. [00109] The complete amino acid sequence of an exemplary human MUC16 comprises or consists of the amino acid sequence of SEQ ID NO: 9. In some embodiments, the anti- MUC16 antibody agent described herein specifically recognizes an epitope within human MUC16. In some embodiments, the anti-MUC16 antibody agent described herein specifically recognizes an epitope within the retained extracellular domain of human MUC16. In some embodiments, the anti-MUC16 antibody agent described herein immunospecifically binds to that MUC16 ectodomain. In some embodiments, the anti-MUC16 antibody agent described herein immunospecifically binds to a cell expressing human MUC16. In some embodiments, the anti-MUC16 antibody agent described herein immunospecifically binds to a cell expressing a recombinant MUC16 polypeptide. In some embodiments, the MUC16 polypeptide is MUC16-c114 having the amino acid sequence set forth in SEQ ID NO: 11. [00110] In some embodiments, the anti-MUC16 antibody agent cross-reacts with MUC16 polypeptide from a species other than human. In some embodiments, the anti-MUC16 antibody agent is completely specific for human MUC16 and does not exhibit species or other types of non-human cross-reactivity. [00111] In some embodiments, the anti-MUC16 antibody agent specifically recognizes MUC16 expressed on the cell surface of a cancer cell (such as solid tumor). In some embodiments, the anti-MUC16 antibody agent specifically recognizes MUC16 expressed on the cell surface of one or more of ovarian cancer cells, breast cancer cells, prostate cancer cells, colon cancer cells, lung cancer cells, brain cancer cells, pancreatic cancer cells, kidney cancer cells, fallopian tube cancer cells, uterine (e.g., endometrial) cancer cells, primary peritoneum cancer cells or cancer cells of any other tissue that expresses MUC16. In some embodiments, the anti-MUC16 antibody agent specifically recognizes MUC16 expressed on the cell surface of a cancer cell line, e.g. ovarian cancer cell lines, such as OVCAR3, OVCA- 432, OVCA-433 and CAOV3. [00112] In some embodiments, the anti-MUC16 antibody agent cross-reacts with at least one allelic variant of the MUC16 protein, or fragments thereof. In some embodiments, the allelic variant has up to about 30, such as about any of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, or 30, amino acid substitutions, such as a conservative amino acid substitution, when compared to the naturally occurring MUC16, or fragments thereof. In some embodiments, the anti-MUC16 antibody agent does not cross-react with any allelic variant of the MUC16 protein, or fragments thereof. [00113] In some embodiments, the anti-MUC16 antibody agent cross-reacts with at least one interspecies variant of the MUC16 protein. In some embodiments, for example, the MUC16 protein, or fragments thereof is human MUC16 and the interspecies variant of the MUC16 protein, or fragments thereof, is a mouse or rat variant thereof. In some embodiments, the anti-MUC16 antibody agent does not cross-react with any interspecies variant of the MUC16 protein. [00114] In some embodiments, according to any of the anti-MUC16 antibody agents described herein, the anti-MUC16 antibody agent comprises an anti-MUC16 antibody moiety that specifically binds to MUC16. [00115] In some embodiments, the anti-MUC16 antibody moiety comprises an antibody heavy chain variable domain and an antibody light chain variable domain. In some embodiments, the anti-MUC16 antibody moiety comprises an antibody heavy chain variable domain and/or an antibody light chain variable domain of a humanized 4H11 anti-MUC16 antibody. [00116] The present disclosure provides variants of human anti-MUC16 immunoglobulin- related compositions that specifically bind to the C-terminal 114 amino acid residues of mature MUC16 (e.g., 4H11) and uses thereof. The antibody heavy chain variable domain and/or an antibody light chain variable domain of murine 4H11 anti-MUC16 antibody is described in WO2011/119979. [00117] Exemplary antibody sequences of the humanized 4H11 antibody agents provided herein are shown in the Tables below. The exemplary CDR sequences in Table 1 are predicted using the IgBLAST algorithm. See, for example, Ye J. et al., Nucleic Acids Research 41:W34-W40 (2013), the disclosure of which is incorporated herein by reference in its entirety. Those skilled in the art will recognize that many algorithms are known for prediction of CDR positions in antibody heavy chain and light chain variable regions, and antibody agents comprising CDRs from antibodies described herein, but based on prediction algorithms other than IgBLAST, are within the scope of the present technology. [00118] The exemplary antibody heavy chain and light chain variable region sequences are delimited according to the INTERNATIONAL IMMUNOGENETICS INFORMATION SYSTEM^® (IMGT). See, for example, Lefranc, M.-P. et al., Nucleic Acids Res., 43:D413- 422 (2015), the disclosure of which is incorporated herein by reference in its entirety. Those skilled in the art will recognize that antibody agents comprising V_H or V_L sequences from antibodies described herein, but based on algorithms other than IMGT, are within the scope of the present technology. [00119] Table 1. Exemplary anti-MUC16 antibody CDR sequences.

[00120] Table 2. Exemplary humanized 4H11 anti-MUC16 antibody V_H and V_L domain sequences.

The VH CDR1-3 and VL CDR1-3 sequences are underlined. [00121] In one aspect, the present disclosure provides anti-MUC16 antibody agents (e.g., anti-MUC16 antibody or antigen binding fragment) comprising a heavy chain immunoglobulin variable domain (VH) and a light chain immunoglobulin variable domain (VL), wherein: (a) the VH comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, and/or a V_L domain including an amino acid sequence of SEQ ID NO: 3 or SEQ ID NO: 4, wherein the V_H domain further comprises at least one amino acid substitution corresponding to at least one amino acid residue selected from among S30, A54, G55, G56, F101, and/or Y108 of SEQ ID NO: 1 or SEQ ID NO: 2 and/or wherein the VL domain further comprises at least one amino acid substitution corresponding to at least one amino acid residue selected from among N31, R33, Q38, and/or S97 of SEQ ID NO: 3 or SEQ ID NO: 4. [00122] Amino acid residues in the VH domain corresponding to S30, A54, G55, G56, F101, or Y108 of SEQ ID NO: 1 or SEQ ID NO: 2 and/or amino acid residues in the VL domain corresponding to N31, R33, Q38, and/or S97 of SEQ ID NO: 3 or SEQ ID NO: 4 may be substituted with alternate naturally occurring amino acids selected from among alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine. [00123] In some embodiments, the anti-MUC16 antibody moiety comprises a VH domain comprising an amino acid sequence that is at least about 95% (for example at least about any of 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 1 or SEQ ID NO: 2, and a V_L domain comprising an amino acid sequence that is at least about 95% (for example at least about any of 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 3 or SEQ ID NO: 4, wherein the VH domain further comprises at least one amino acid substitution corresponding to at least one amino acid residue selected from among S30, A54, G55, G56, F101, and/or Y108 of SEQ ID NO: 1 or SEQ ID NO: 2 and/or wherein the VL domain further comprises at least one amino acid substitution corresponding to at least one amino acid residue selected from among N31, R33, Q38, and/or S97 of SEQ ID NO: 3 or SEQ ID NO: 4. [00124] In any and all embodiments of the anti-MUC16 antibody moiety disclosed herein, the V_H domain further comprises 1, 2, 3, 4, 5 or 6 amino acid substitutions corresponding to any one or more amino acid residues selected from among S30, A54, G55, G56, F101, and/or Y108 of SEQ ID NO: 1 or SEQ ID NO: 2. Additionally or alternatively, in some embodiments of the anti-MUC16 antibody moiety disclosed herein, the V_L domain further comprises 1, 2, 3, or 4 amino acid substitutions corresponding to any one or more amino acid residues selected from among N31, R33, Q38, and/or S97 of SEQ ID NO: 3 or SEQ ID NO: 4. [00125] In any and all embodiments of the anti-MUC16 antibody moiety disclosed herein, the at least one amino acid substitution corresponding to S30, G55, G56, F101, and/or Y108 of SEQ ID NO: 1 or SEQ ID NO: 2 is one or more of S30Y, S30H, S30F, S30W, G55L, G55P, G55V, G55E, G56T, G56V, G56P, F101N, F101T, F101W, F101Q, or Y108R. Additionally or alternatively, in any and all embodiments of the anti-MUC16 antibody moiety disclosed herein, the at least one amino acid substitution corresponding to N31, R33, Q38, and/or S97 of SEQ ID NO: 3 or SEQ ID NO: 4 is one or more of N31Q, N31V, N31S, N31K, N31T, N31P, R33N, R33V, R33S, R33T, R33E, Q38T, Q38D, Q38L, Q38P, Q38H, Q38R, Q38V, S97R, S97Q, S97E, S97H, S97L, S97P, S97V, S97N, or S97D. [00126] In some embodiments, the anti-MUC16 antibody moiety comprises a sequence selected from among SEQ ID NOs: 5-8, wherein the anti-MUC16 antibody moiety further comprises at least one amino acid substitution corresponding to at least one amino acid residue selected from among S30, A54, G55, G56, F101, Y108, N179, R181, Q186, and/or S245 of any of SEQ ID NOs: 5-8. Additionally or alternatively, in some embodiments, the anti-MUC16 antibody moiety further comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions corresponding to any one or more amino acid residues selected from among S30, A54, G55, G56, F101, Y108, N179, R181, Q186, and/or S245 of any of SEQ ID NOs: 5-8. Additionally or alternatively, in some embodiments, the at least one amino acid substitution corresponding to S30, G55, G56, F101, Y108, N179, R181, Q186, and/or S245 of any of SEQ ID NOs: 5-8 is one or more of S30Y, S30H, S30F, S30W, G55L, G55P, G55V, G55E, G56T, G56V, G56P, F101N, F101T, F101W, F101Q, Y108R, N179Q, N179V, N179S, N179K, N179T, N179P, R181N, R181V, R181S, R181T, R181E, Q186T, Q186D, Q186L, Q186P, Q186H, Q186R, Q186V, S245R, S245Q, S245E, S245H, S245L, S245P, S245V, S245N, or S245D. [00127] In any of the above embodiments, the antibody further comprises a Fc domain of any isotype, e.g., but are not limited to, IgG (including IgG1, IgG2, IgG3, and IgG4), IgA (including IgA₁ and IgA₂), IgD, IgE, or IgM, and IgY. Non-limiting examples of constant region sequences include: [00128] Human IgD constant region, Uniprot: P01880 (SEQ ID NO: 19)

[00129] Human IgG1 constant region, Uniprot: P01857 (SEQ ID NO: 20)

[00130] Human IgG2 constant region, Uniprot: P01859 (SEQ ID NO: 21)

[00131] Human IgG3 constant region, Uniprot: P01860 (SEQ ID NO: 22)

[00132] Human IgM constant region, Uniprot: P01871 (SEQ ID NO: 23)

[00133] Human IgG4 constant region, Uniprot: P01861 (SEQ ID NO: 24)

[00134] Human IgA1 constant region, Uniprot: P01876 (SEQ ID NO: 25)

[00135] Human IgA2 constant region, Uniprot: P01877 (SEQ ID NO: 26)

[00136] Human Ig kappa constant region, Uniprot: P01834 (SEQ ID NO: 27)

[00137] Human Immunoglobulin lambda constant region, Uniprot: P0CG04 (SEQ ID NO: 28)

[00138] In some embodiments, the anti-MUC16 antibody moiety comprises an antibody heavy chain constant region and an antibody light chain constant region. [00139] In some embodiments, the anti-MUC16 antibody moiety of the present technology comprises a heavy chain constant region that is at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or is 100% identical to SEQ ID NOS: 19-26. Additionally or alternatively, in some embodiments, the anti-MUC16 antibody moiety of the present technology comprises a light chain constant region that is at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or is 100% identical to SEQ ID NO: 27 or SEQ ID NO: 28. [00140] The anti-MUC16 antibody agent in some embodiments is a full-length anti- MUC16 antibody. In some embodiments, the full-length anti-MUC16 antibody is an IgA, IgD, IgE, IgG, or IgM. In some embodiments, the full-length anti-MUC16 antibody comprises IgG constant domains, such as constant domains of any of IgG1, IgG2, IgG3, and IgG4 including variants thereof. In some embodiments, the full-length anti-MUC16 antibody comprises a lambda light chain constant region. In some embodiments, the full-length anti- MUC16 antibody comprises a kappa light chain constant region. In some embodiments, the full-length anti-MUC16 antibody is a full-length human anti-MUC16 antibody. In some embodiments, the full-length anti-MUC16 antibody comprises an Fc sequence of a mouse immunoglobulin. In some embodiments, the full-length anti-MUC16 antibody comprises an Fc sequence that has been altered or otherwise changed so that it has enhanced antibody dependent cellular cytotoxicity (ADCC) or complement dependent cytotoxicity (CDC) effector function. [00141] In some embodiments, there is provided a full-length anti-MUC16 antibody comprising IgG1 or IgG4 constant domains, wherein the anti-MUC16 antibody specifically binds to MUC16 on a tumor cell. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. [00142] In some embodiments, binding of the anti-MUC16 antibody to an MUC16- expressing cell (e.g., an MUC16-expressing cancer cell) inhibits tumor growth or metastasis of a tumor or induces regression of a tumor. In some embodiments, binding of the anti- MUC16 antibody to an MUC16-expressing cell (e.g., an MUC16-expressing cancer cell) inhibits Matrigel invasion in vitro of the MUC16-expressing cells. [00143] In some embodiments, the anti-MUC16 construct provided herein is monospecific. In some embodiments, the anti-MUC16 construct provided herein is multispecific. In some embodiments, the anti-MUC16 construct provided herein is bispecific. In some embodiments, the anti-MUC16 construct provided herein is a tandem scFv, a diabody (Db), a single chain diabody (scDb), a dual-affinity retargeting (DART) antibody, a F(abʹ)2, a dual variable domain (DVD) antibody, a knob-into-hole (KiH) antibody, a dock and lock (DNL) antibody, a chemically cross-linked antibody, a heteromultimeric antibody, or a heteroconjugate antibody. In some embodiments, the anti- MUC16 construct provided herein is a tandem scFv comprising two scFvs linked by a peptide linker. In some embodiments, the antibody moiety that immunospecifically recognizes MUC16 is a first antibody moiety, and wherein the anti-MUC16 construct further comprises a second antibody moiety that immunospecifically recognizes a second antigen. In some embodiments, the second antigen is an antigen on the surface of a T cell. In some embodiments, the second antigen is a CD3. In some embodiments, the second antigen is selected from the group consisting of CD3γ, CD3δ, CD3ε, and CD3ζ. In some embodiments, the second antigen is CD3ε. In some embodiments, a multispecific or bispecific anti-MUC16 construct comprises an anti-CD3 antibody moiety. [00144] Chimeric anti-MUC16 constructs [00145] In some embodiments, the anti-MUC16 antibody agent is an anti-MUC16 chimeric antigen receptor (CAR) or variant thereof that specifically binds to MUC16. In some embodiments, the anti-MUC16 antibody agent is an anti-MUC16 CAR. CARs are well known in the art, and the anti-MUC16 antibody agent can be a CAR according to any CAR known in the art, such as described in Sadelain et al., Nature 545: 423- 431 (2017), the disclosure of which is explicitly incorporated herein for use in the present technology. [00146] The term “chimeric antigen receptor (CAR)” as used herein refers to an artificially constructed hybrid single-chain protein or single-chain polypeptide containing a single-chain variable fragment (scFv) as a part of the extracellular antigen-binding domain, linked directly or indirectly to a transmembrane domain (e.g., an immune cell co-stimulatory signaling molecule transmembrane domain), which is in turn linked directly or indirectly to an intracellular immune cell (e.g., T cell or NK cell) signaling domain. The intracellular signaling domain (ISD) comprises a primary signaling sequence, or primary immune cell signaling sequence, from an antigen-dependent, TCR-associated T cell activation molecule, e.g., a portion of the intracellular domain of CD3ζ, TCRζ, FcRγ, FcRβ, CD3γ, CD3δ, CD3ε, CD5, CD22, CD79a, CD79b, or CD66d. The ISD can further comprise a co-stimulatory signaling sequence; e.g., a portion of the intracellular domain of an antigen-independent, co- stimulatory molecule such as CD27, CD28, 4-1BB (CD137), OX40, CD30, CD40, PD-1, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, B7- H3, a ligand that specifically binds with CD83, or the like. Characteristics of CARs include their ability to redirect immune cell (e.g., T cell or NK cell) specificity and reactivity toward a selected target in either MHC-restricted (in cases of TCR-mimic antibodies) or non-MHC- restricted (in cases of antibodies against cell surface proteins) manners, exploiting the antigen-binding properties of monoclonal antibodies. The non-MHC-restricted antigen recognition gives immune cells (e.g., T cells or NK cells) expressing CARs the ability to recognize antigen independent of antigen processing, thus bypassing a major mechanism of tumor escape. [00147] In some embodiments, the anti-MUC16 CAR comprises an anti-MUC16 antibody moiety according to any of the anti-MUC16 antibody moieties described herein. For example, in some embodiments, there is provided an anti-MUC16 CAR comprising an anti- MUC16 antibody moiety. [00148] In some embodiments, the anti-MUC16 antibody moiety of an anti-MUC16 CAR comprises a) a heavy chain variable domain (VH) comprising SEQ ID NO: 1 or SEQ ID NO: 2; and b) a light chain variable domain (VL) comprising SEQ ID NO: 3 or SEQ ID NO: 4, wherein the V_H domain of the anti-MUC16 CAR further comprises at least one amino acid substitution corresponding to at least one amino acid residue selected from among S30, A54, G55, G56, F101, and/or Y108 of SEQ ID NO: 1 or SEQ ID NO: 2 and/or wherein the VL domain of the anti-MUC16 CAR further comprises at least one amino acid substitution corresponding to at least one amino acid residue selected from among N31, R33, Q38, and/or S97 of SEQ ID NO: 3 or SEQ ID NO: 4. [00149] In some embodiments, the anti-MUC16 antibody moiety of an anti-MUC16 CAR comprises a V_H domain comprising an amino acid sequence that is at least about 95% (for example at least about any of 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 1 or SEQ ID NO: 2, and a VL domain comprising an amino acid sequence that is at least about 95% (for example at least about any of 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 3 or SEQ ID NO: 4, wherein the VH domain of the anti-MUC16 CAR further comprises at least one amino acid substitution corresponding to at least one amino acid residue selected from among S30, A54, G55, G56, F101, and/or Y108 of SEQ ID NO: 1 or SEQ ID NO: 2 and/or wherein the V_L domain of the anti-MUC16 CAR further comprises at least one amino acid substitution corresponding to at least one amino acid residue selected from among N31, R33, Q38, and/or S97 of SEQ ID NO: 3 or SEQ ID NO: 4. [00150] In some embodiments, the anti-MUC16 CAR comprises a sequence selected from among SEQ ID NOs: 5-8, wherein the anti-MUC16 CAR further comprises at least one amino acid substitution corresponding to at least one amino acid residue selected from among S30, A54, G55, G56, F101, Y108, N179, R181, Q186, and/or S245 of any of SEQ ID NOs: 5-8. [00151] In some embodiments, the anti-MUC16 antibody agent is an anti-MUC16 chimeric receptor comprising T cell receptor (TCR) transmembrane domains. For example, in some embodiments, the anti-MUC16 antibody agent is an antibody-T cell receptor (abTCR) as described in PCT Patent Application Publication No. WO2017070608, the disclosure of which is explicitly incorporated herein for use in the present technology and for possible inclusion in one or more claims herein. In some embodiments, the anti-MUC16 abTCR comprises an anti-MUC16 antibody moiety according to any of the anti-MUC16 antibody moieties described herein. For example, in some embodiments, there is provided an anti-MUC16 abTCR comprising an anti-MUC16 antibody moiety. [00152] In some embodiments, the anti-MUC16 antibody moiety of an anti-MUC16 abTCR comprises a) a heavy chain variable domain (VH) comprising SEQ ID NO: 1 or SEQ ID NO: 2; and b) a light chain variable domain (V_L) comprising SEQ ID NO: 3 or SEQ ID NO: 4, wherein the V_H domain of the anti-MUC16 abTCR further comprises at least one amino acid substitution corresponding to at least one amino acid residue selected from among S30, A54, G55, G56, F101, and/or Y108 of SEQ ID NO: 1 or SEQ ID NO: 2 and/or wherein the V_L domain of the anti-MUC16 abTCR further comprises at least one amino acid substitution corresponding to at least one amino acid residue selected from among N31, R33, Q38, and/or S97 of SEQ ID NO: 3 or SEQ ID NO: 4. [00153] In some embodiments, the anti-MUC16 antibody moiety of an anti-MUC16 abTCR comprises a VH domain comprising an amino acid sequence that is at least about 95% (for example at least about any of 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 1 or SEQ ID NO: 2, and a V_L domain comprising an amino acid sequence that is at least about 95% (for example at least about any of 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 3 or SEQ ID NO: 4, wherein the VH domain of the anti-MUC16 abTCR further comprises at least one amino acid substitution corresponding to at least one amino acid residue selected from among S30, A54, G55, G56, F101, and/or Y108 of SEQ ID NO: 1 or SEQ ID NO: 2 and/or wherein the VL domain of the anti-MUC16 abTCR further comprises at least one amino acid substitution corresponding to at least one amino acid residue selected from among N31, R33, Q38, and/or S97 of SEQ ID NO: 3 or SEQ ID NO: 4. [00154] In some embodiments, the anti-MUC16 antibody agent is a chimeric co- stimulatory receptor comprising an anti-MUC16 antibody moiety that specifically binds to MUC16 and a co-stimulatory signaling domain. In some embodiments, the anti-MUC16 chimeric co-stimulatory receptor is capable of stimulating an immune cell on the surface of which it is functionally expressed upon binding MUC16. In some embodiments, the anti- MUC16 chimeric co-stimulatory receptor lacks a functional primary immune cell signaling sequence. In some embodiments, the anti-MUC16 chimeric co-stimulatory receptor lacks any primary immune cell signaling sequence. In some embodiments, the anti-MUC16 chimeric co-stimulatory receptor comprises a single polypeptide chain comprising the anti- MUC16 antibody moiety, a transmembrane domain, and the co-stimulatory signaling domain. In some embodiments, the anti-MUC16 chimeric co-stimulatory receptor comprises a first polypeptide chain and a second polypeptide chain, wherein the first and second polypeptide chains together form the anti-MUC16 antibody moiety, a transmembrane module, and co- stimulatory signaling module comprising the co-stimulatory signaling domain. In some embodiments, the first and second polypeptide chains are separate polypeptide chains, and the anti-MUC16 chimeric co-stimulatory receptor is a multimer, such as a dimer. In some embodiments, the first and second polypeptide chains are covalently linked, such as by a peptide linkage, or by another chemical linkage, such as a disulfide linkage. In some embodiments, the first polypeptide chain and the second polypeptide chain are linked by at least one disulfide bond. In some embodiments, the anti-MUC16 antibody moiety is a Fab, a Fab’, a (Fab’)2, an Fv, or a single chain Fv (scFv). In some embodiments, the anti-MUC16 scFv comprise a sequence selected from any one of SEQ ID NOs: 5-8, wherein the anti- MUC16 scFv further comprises at least one amino acid substitution corresponding to at least one amino acid residue selected from among S30, A54, G55, G56, F101, Y108, N179, R181, Q186, and/or S245 of any of SEQ ID NOs: 5-8. [00155] Examples of co-stimulatory immune cell signaling domains for use in the anti- MUC16 chimeric co-stimulatory receptors of the present technology include the cytoplasmic sequences of co-receptors of the T cell receptor (TCR), which can act in concert with a chimeric receptor (e.g., a CAR or abTCR) to initiate signal transduction following chimeric receptor engagement, as well as any derivative or variant of these sequences and any synthetic sequence that has the same functional capability. [00156] It is known that signals generated through the TCR alone are insufficient for full activation of the T cell and that a secondary or co-stimulatory signal is also required. Thus, T cell activation can be said to be mediated by two distinct classes of intracellular signaling sequence: those that initiate antigen-dependent primary activation through the TCR (referred to herein as “primary immune cell signaling sequences”) and those that act in an antigen- independent manner to provide a secondary or co-stimulatory signal (referred to herein as “co-stimulatory immune cell signaling sequences”). [00157] Primary immune cell signaling sequences that act in a stimulatory manner may contain signaling motifs which are known as immunoreceptor tyrosine-based activation motifs or ITAMs. Examples of ITAM-containing primary immune cell signaling sequences include those derived from TCRζ, FcRγ, FcRβ, CD3γ, CD3δ, CD3ε, CD5, CD22, CD79a, CD79b, and CD66d. A “functional” primary immune cell signaling sequence is a sequence that is capable of transducing an immune cell activation signal when operably coupled to an appropriate receptor. “Non-functional” primary immune cell signaling sequences, which may comprise fragments or variants of primary immune cell signaling sequences, are unable to transduce an immune cell activation signal. The anti-MUC16 chimeric co-stimulatory receptors described herein lack a functional primary immune cell signaling sequence, such as a functional signaling sequence comprising an ITAM. In some embodiments, the anti- MUC16 chimeric co-stimulatory receptors lack any primary immune cell signaling sequence. [00158] The co-stimulatory immune cell signaling sequence can be a portion of the intracellular domain of a co-stimulatory molecule including, for example, CD27, CD28, 4- 1BB (CD137), OX40, CD30, CD40, PD-1, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, B7-H3, a ligand that specifically binds with CD83, and the like. [00159] In some embodiments, the anti-MUC16 antibody moiety of an anti-MUC16 chimeric co-stimulatory receptor comprises a) a heavy chain variable domain (VH) comprising SEQ ID NO: 1 or SEQ ID NO: 2; and b) a light chain variable domain (V_L) comprising SEQ ID NO: 3 or SEQ ID NO: 4, wherein the V_H domain of the anti-MUC16 chimeric co-stimulatory receptor further comprises at least one amino acid substitution corresponding to at least one amino acid residue selected from among S30, A54, G55, G56, F101, and/or Y108 of SEQ ID NO: 1 or SEQ ID NO: 2 and/or wherein the V_L domain of the anti-MUC16 chimeric co-stimulatory receptor further comprises at least one amino acid substitution corresponding to at least one amino acid residue selected from among N31, R33, Q38, and/or S97 of SEQ ID NO: 3 or SEQ ID NO: 4. [00160] In some embodiments, the anti-MUC16 antibody moiety of an anti-MUC16 chimeric co-stimulatory receptor comprises a V_H domain comprising an amino acid sequence that is at least about 95% (for example at least about any of 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 1 or SEQ ID NO: 2, and a VL domain comprising an amino acid sequence that is at least about 95% (for example at least about any of 96%, 97%, 98%, or 99%) identical to SEQ ID NO: 3 or SEQ ID NO: 4, wherein the VH domain of the anti- MUC16 chimeric co-stimulatory receptor further comprises at least one amino acid substitution corresponding to at least one amino acid residue selected from among S30, A54, G55, G56, F101, and/or Y108 of SEQ ID NO: 1 or SEQ ID NO: 2 and/or wherein the V_L domain of the anti-MUC16 chimeric co-stimulatory receptor further comprises at least one amino acid substitution corresponding to at least one amino acid residue selected from among N31, R33, Q38, and/or S97 of SEQ ID NO: 3 or SEQ ID NO: 4. [00161] In some embodiments, the anti-MUC16 chimeric co-stimulatory receptor is expressed in an immune cell. In some embodiments, the anti-MUC16 chimeric co- stimulatory receptor is expressed in an immune cell that expresses another chimeric receptor. In some embodiments, the other chimeric receptor is a CAR or an abTCR. In some embodiments, the other chimeric receptor binds to MUC16. In some embodiments, the other chimeric receptor does not bind to MUC16. In some embodiments, the other chimeric receptor binds to an antigen associated with a cancer characterized by high expression of MUC16 and/or high aerobic glycolysis. In some embodiments, the other chimeric receptor binds to an antigen associated with any of the cancers described herein (such as kidney cancer, cervical cancer, prostate cancer, breast cancer, colon cancer, brain cancer, or pancreatic cancer). In some embodiments, the other chimeric receptor binds to an antigen associated with kidney cancer. In some embodiments, the kidney cancer is renal cell carcinoma (RCC). In some embodiments, the RCC is metastatic RCC. In some embodiments, the immune cell is a T cell. In some embodiments, expression of the anti- MUC16 chimeric co-stimulatory receptor in the immune cell is inducible. In some embodiments, the expression of the anti-MUC16 chimeric co-stimulatory receptor in the immune cell is inducible upon signaling through the other chimeric receptor. [00162] Binding affinity [00163] Binding affinity can be indicated by K_d, K_off, K_on, or K_a. The term “K_off”, as used herein, is intended to refer to the off-rate constant for dissociation of an antibody agent from the antibody agent/antigen complex, as determined from a kinetic selection set up. The term “Kon”, as used herein, is intended to refer to the on- rate constant for association of an antibody agent to the antigen to form the antibody agent/antigen complex. The term equilibrium dissociation constant “Kd”, as used herein, refers to the dissociation constant of a particular antibody agent-antigen interaction, and describes the concentration of antigen required to occupy one half of all of the antibody- binding domains present in a solution of antibody agent molecules at equilibrium, and is equal to Koff/Kon. The measurement of Kd presupposes that all binding agents are in solution. In the case where the antibody agent is tethered to a cell wall, e.g., in a yeast expression system, the corresponding equilibrium rate constant is expressed as EC50, which gives a good approximation of Kd. The affinity constant, Ka, is the inverse of the dissociation constant, Kd. [00164] The dissociation constant (K_d) is used as an indicator showing affinity of antibody moieties to antigens. For example, easy analysis is possible by the Scatchard method using antibody agents marked with a variety of marker agents, as well as by using Biacore (made by Amersham Biosciences), analysis of biomolecular interactions by surface plasmon resonance, according to the user's manual and attached kit. The Kd value that can be derived using these methods is expressed in units of M (Mols). An antibody agent that specifically binds to a target may have a K_d of, for example, ≤ 10^-7 M, ≤ 10^-8 M, ≤ 10^-9 M, ≤ 10^-10 M, ≤ 10^-11 M, ≤ 10^-12 M, or ≤ 10^-13 M. [00165] Binding specificity of the antibody agent can be determined experimentally by methods known in the art. Such methods comprise, but are not limited to, Western blots, ELISA-, RIA-, ECL-, IRMA-, EIA-, BIAcore-tests and peptide scans. In some embodiments, the binding affinity of the anti-MUC16 antibody agent is measured by testing the binding affinity of the anti-MUC16 antibody agent to cells expressing MUC16 on the surface (e.g., HepG2 cells). [00166] In some embodiments, the anti-MUC16 antibody agent specifically binds to a target MUC16 (e.g., immature or native MUC16 (nMUC16)) with a K_d of about 10^-7 M to about 10^-13 M (such as about 10^-7 M to about 10^-13 M, about 10^-9 M to about 10^-13 M, or about 10^-10 M to about 10^-12 M). Thus in some embodiments, the Kd of the binding between the anti-nMUC16 antibody agent and nMUC16, the Kd of the binding between the anti-sMUC16 (cell-surface MUC16) antibody agent and sMUC16, or the K_d of the binding between the anti-MUC16 antibody agent and MUC16 (any format), is about 10⁻⁷ M to about 10⁻¹³ M, about 1×10⁻⁷ M to about 5×10⁻¹³ M, about 10⁻⁷ M to about 10⁻¹² M, about 10⁻⁷ M to about 10⁻¹¹ M, about 10⁻⁷ M to about 10⁻¹⁰ M, about 10⁻⁷ M to about 10⁻⁹ M, about 10⁻⁸ M to about 10⁻¹³ M, about 1×10⁻⁸ M to about 5×10⁻¹³ M, about 10⁻⁸ M to about 10⁻¹² M, about 10⁻⁸ M to about 10⁻¹¹ M, about 10⁻⁸ M to about 10⁻¹⁰ M, about 10⁻⁸ M to about 10⁻⁹ M, about 5×10⁻⁹ M to about 1×10⁻¹³ M, about 5×10⁻⁹ M to about 1×10⁻¹² M, about 5×10⁻⁹ M to about 1×10⁻¹¹ M, about 5×10⁻⁹ M to about 1×10⁻¹⁰ M, about 10⁻⁹ M to about 10⁻¹³ M, about 10⁻⁹ M to about 10⁻¹² M, about 10⁻⁹ M to about 10⁻¹¹ M, about 10⁻⁹ M to about 10⁻¹⁰ M, about 5×10⁻¹⁰ M to about 1×10⁻¹³ M, about 5×10⁻¹⁰ M to about 1×10⁻¹² M, about 5×10⁻¹⁰ M to about 1×10⁻¹¹ M, about 10⁻¹⁰ M to about10⁻¹³ M, about 1×10⁻¹⁰ M to about 5×10⁻¹³ M, about 1×10⁻¹⁰ M to about 1×10⁻¹² M, about 1×10⁻¹⁰ M to about 5×10⁻¹² M, about 1×10⁻¹⁰ M to about 1×10⁻¹¹ M, about 10⁻¹¹ M to about 10⁻¹³ M, about 1×10⁻¹¹ M to about 5×10⁻¹³ M, about 10⁻¹¹ M to about 10⁻¹² M, or about 10⁻¹² M to about 10⁻¹³ M. In some embodiments, the K_d of the binding between the anti-nMUC16 antibody agent and an nMUC16 is about 10^-7 M to about 10^-13 M. [00167] In some embodiments, the Kd of the binding between the anti-MUC16 antibody agent and a non-target is more than the K_d of the binding between the anti-MUC16 antibody agent and the target, and is herein referred to in some embodiments as the binding affinity of the anti-MUC16 antibody agent to the target (e.g., cell surface-bound MUC16) is higher than that to a non-target. In some embodiments, the non-target is an antigen that is not MUC16. In some embodiments, the K_d of the binding between the anti-MUC16 antibody agent (against nMUC16) and a non-MUC16 target can be at least about 10 times, such as about 10- 100 times, about 100-1000 times, about 10³-10⁴ times, about 10⁴-10⁵ times, about 10⁵-10⁶ times, about 10⁶-10⁷ times, about 10⁷-10⁸ times, about 10⁸-10⁹ times, about 10⁹-10¹⁰ times, about 10¹⁰-10¹¹ times, or about 10¹¹-10¹² times of the K_d of the binding between the anti- MUC16 antibody agent and a target MUC16. [00168] In some embodiments, the anti-MUC16 antibody agent binds to a non-target with a K_d of about 10^-1 M to about 10^-6 M (such as about 10^-1 M to about 10^-6 M, about 10^-1 M to about 10^-5 M, or about 10^-2 M to about 10^-4 M). In some embodiments, the non-target is an antigen that is not MUC16. Thus in some embodiments, the Kd of the binding between the anti-MUC16 antibody agent and a non-MUC16 target is about 10^-1 M to about 10^-6 M, about 1×10^-1 M to about 5×10^-6 M, about 10^-1 M to about 10^-5 M, about 1×10^-1 M to about 5×10^-5 M, about 10^-1 M to about 10^-4 M, about 1×10^-1 M to about 5×10^-4 M, about 10^-1 M to about 10^-3 M, about 1×10^-1 M to about 5×10^-3 M, about 10^-1 M to about 10^-2 M, about 10^-2 M to about 10^-6 M, about 1×10^-2 M to about 5×10^-6 M, about 10^-2 M to about 10^-5 M, about 1×10^-2 M to about 5×10^-5 M, about 10^-2 M to about 10^-4 M, about 1×10^-2 M to about 5×10^-4 M, about 10^-2 M to about 10^-3 M, about 10^-3 M to about 10^-6 M, about 1×10^-3 M to about 5×10^-6 M, about 10^-3 M to about 10^-5 M, about 1×10^-3 M to about 5×10^-5 M, about 10^-3 M to about 10^-4 M, about 10^-4 M to about 10^-6 M, about 1×10^-4 M to about 5×10^-6 M, about 10^-4 M to about 10^-5 M, or about 10^-5 M to about 10^-6 M. [00169] In some embodiments, when referring to that the anti-MUC16 antibody agent specifically recognizes a target MUC16 (e.g., cell surface-bound MUC16) at a high binding affinity, and binds to a non-target at a low binding affinity, the anti-MUC16 antibody agent will bind to the target MUC16 (e.g., cell surface-bound MUC16) with a Kd of about 10^-7 M to about 10^-13 M (such as about 10^-7 M to about 10^-13 M, about 10^-9 M to about 10^-13 M, or about 10^-10 M to about 10^-12 M), and will bind to the non-target with a Kd of about 10^-1 M to about 10^-6 M (such as about 10^-1 M to about 10^-6 M, about 10^-1 M to about 10^-5 M, or about 10^-2 M to about 10^-4 M). [00170] In some embodiments, when referring to that the anti-MUC16 antibody agent specifically recognizes a cell surface-bound MUC16, the binding affinity of the anti-MUC16 antibody agent is compared to a control anti-MUC16 antibody agent. In some embodiments, the K_d of the binding between the control anti-MUC16 antibody agent and a cell surface- bound MUC16 can be at least about 2 times, such as about 2 times, about 3 times, about 4 times, about 5 times, about 6 times, about 7 times, about 8 times, about 9 times, about 10 times, about 10-100 times, about 100-1000 times, about 10³-10⁴ times, about 10⁴-10⁵ times, about 10⁵-10⁶ times, about 10⁶-10⁷ times, about 10⁷-10⁸ times, about 10⁸-10⁹ times, about 10⁹-10¹⁰ times, about 10¹⁰-10¹¹ times, or about 10¹¹-10¹² times of the K_d of the binding between the anti-nMUC16 antibody agent described herein and a cell surface-bound MUC16. [00171] Functional Activities of anti-Muc16 antibody agents of the present disclosure [00172] In certain embodiments, an anti-MUC16 antibody agent or an antigen-binding fragment thereof described herein inhibits Matrigel invasion in vitro of cells recombinantly expressing a MUC16 polypeptide. In some embodiments the MUC16 comprises SEQ ID NO: 11 (MUC16 c114). In certain embodiments, the cells recombinantly expressing glycosylated MUC16 c114 are SKOV3 cells. In certain embodiments, the MUC16 polypeptide is glycosylated. In certain embodiments, the glycosylated form of MUC16 polypeptide is N-glycosylated at amino acid residue Asn30 (corresponding to Asn1806 of mature MUC16 (SEQ ID NO: 10)). In certain embodiments, MUC16 polypeptide is N- glycosylated at amino acid residues Asn24 and Asn30 (corresponding to Asn1800 and Asn1806, respectively, of mature MUC16 (SEQ ID NO: 10)). In certain embodiments, the MUC16 polypeptide is N-glycosylated at amino acid residues Asn1, Asn24, and Asn30 of SEQ ID NO: 11 (also referred to as Asn1777, Asn1800, and Asn1806, respectively, in Yin and Lloyd (2001) J Biol Chem 276: 27371–27375). In certain embodiments, the glycosylation comprises N- linked chitobiose. In certain embodiments, the glycosylation consists of an N-linked chitobiose. In certain embodiments, Matrigel invasion is inhibited by at least 1.25, 1.5, 1.75, 2, 3, 4, 5, 6, 7, 8, 9, or 10-fold as compared to Matrigel invasion in vitro of the cells wherein the cells are treated with a control antibody (e.g., an antibody that does not target MUC16). In certain embodiments, Matrigel invasion is inhibited by about 1.25, 1.5, 1.75, 2, 3, 4, 5, 6, 7, 8, 9, or 10-fold as compared to Matrigel invasion in vitro of the cells wherein the cells are treated with a control antibody (e.g., an antibody that does not target MUC16). [00173] Assays to determine the anti-MUC16 antibody agent or antigen-binding fragment- mediated inhibition of Matrigel invasion are known to a person skilled in the art. For example, BD BioCoat™ Matrigel™ Invasion Inserts or Chambers (catalog # 354480 in 24 well plate) and Control Inserts (catalog # 354578 in 24 well plate) can be purchased from BD Biosciences, MA. Matrigel Invasion assay can be performed as per manufacturer's protocol. Briefly, the Matrigel chambers in 24 well plates (stored at -20°C) and control inserts (stored at 4°C) are allowed to come to room temperature. Both inserts are rehydrated with 0.5 mL of serum free medium in the insert as well as in the outside well of the 24 well plate, for 2 hours at 37°C 5% CO2 humidified incubator. Cultured SKOV3 cells are trypsinized and washed with culture medium. A million cells are separated into another centrifuge tube and washed 3 times with serum free medium. These cells are later adjusted to give 5,000 cells in 0.5 mL serum free medium. The medium in the rehydrated inserts are removed and the insert was transferred into a new 24 well plate containing 0.75 mL of 10% Fetal Bovine Serum (FBS) containing culture medium in the well which serves as a chemo attractant. Immediately, 0.5 mL of the cells (5,000 cells) in serum free medium is added to the insert. Proper care is taken to see that there is no air bubble is trapped in the insert and the outside well. The 24 well plate is incubated at 37°C 5% CO₂ humidified incubator for 48 hrs. After incubation, the non-invading cells are removed from the upper surface of the membrane by "scrubbing" by inserting a cotton tipped swab into Matrigel or control insert and gently applied pressure while moving the tip of the swab over the membrane surface. The scrubbing is repeated with a second swab moistened with medium. Then the inserts are stained in a new 24 well plate containing 0.5 mL of 0.5% crystal violet stain in distilled water for 30 minutes. Following staining the inserts are rinsed in 3 beakers of distilled water to remove excess stain. The inserts are air dried for in a new 24 well plate. The invaded cells are hand counted under an inverted microscope at 200x magnification. Several fields of triplicate membranes were counted and recorded in the figure. [00174] In certain embodiments, an anti-MUC16 antibody agent or an antigen-binding fragment thereof described herein is capable of inhibiting or reducing metastasis, inhibiting tumor growth or inducing tumor regression in mouse model studies. For example, tumor cell lines can be introduced into athymic nude mice, and the athymic mice can be administered an anti-MUC16 antibody agent or an antigen-binding fragment thereof described herein one or more times, and tumor progression of the injected tumor cells can be monitored over a period of weeks and/or months. In some cases, administration of an anti-MUC16 antibody agent or an antigen-binding fragment thereof to the athymic nude mice can occur prior to introduction of the tumor cell lines. In a certain embodiment, SKOV3 cells expressing MUC16 c114 are utilized for the mouse xenograft models described herein. [00175] In some embodiments, an anti-MUC16 antibody agent or an antigen-binding fragment thereof described herein inhibits tumor growth or induce tumor regression in a mouse model by at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% as assessed by methods described herein or known to one of skill in the art, as compared to mock-treated mice. In some embodiments, an anti-MUC16 antibody agent or an antigen-binding fragment thereof described herein inhibits tumor growth or induce tumor regression in a mouse model by at least about 25% or 35%), optionally to about 75%, as assessed by methods described herein or known to one of skill in the art, as compared to mock-treated mice. In some embodiments, an anti-MUC16 antibody agent or an antigen-binding fragment thereof described herein inhibit tumor growth or induce tumor regression in a mouse model by at least about 1 fold, 1.2 fold, 1.3 fold, 1.4 fold, 1.5 fold, 2 fold, 2.5 fold, 3 fold, 3.5 fold, 4 fold, 4.5 fold, 5 fold, 6 fold, 7 fold, 8 fold, 9 fold, 10 fold, 15 fold, 20 fold, 30 fold, 40 fold, 50 fold, 60 fold, 70 fold, 80 fold, 90 fold, or 100 fold as assessed by methods described herein or known to one of skill in the art, as compared to mock-treated mice. Mock-treated mice can, for example, be treated with phosphate buffered saline or a control (e.g., anti-IgG antibody). [00176] Determining tumor growth inhibition or tumor regression can be assessed, for example, by monitoring tumor size over a period of time, such as by physical measurement of palpable tumors, or other visual detection methods. For example, tumor cell lines can be generated to recombinantly express a visualization agent, such as green fluorescent protein (GFP) or luciferase, then in vivo visualization of GFP can be carried out by microscopy, and in vivo visualization of luciferase can be carried out by administering luciferase substrate to the xenograft mice and detecting luminescent due to the luciferase enzyme processing the luciferase substrate. The degree or level of detection of GFP or luciferase correlates to the size of the tumor in the xenograft mice. [00177] In certain embodiments, an anti-MUC16 antibody agent or an antigen-binding fragment thereof described herein can increase survival of animals in tumor xenograft models as compared to mock-treated mice. In some embodiments, an anti-MUC16 antibody agent or an antigen-binding fragment thereof described herein increases survival of mice in tumor xenograft models by at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99% as assessed by methods described herein or known to one of skill in the art, as compared to mock-treated mice. In some embodiments, an anti-MUC16 antibody agent or an antigen-binding fragment thereof described herein increases survival of mice in tumor xenograft models by at least about 25% or 35%, optionally to about 75%), as assessed by methods described herein or known to one of skill in the art, as compared to mock-treated mice in tumor xenograft models. In some embodiments, an anti-MUC16 antibody agent or an antigen-binding fragment thereof described herein increases survival of mice in tumor xenograft models by at least about 1 fold, 1.2 fold, 1.3 fold, 1.4 fold, 1.5 fold, 2 fold, 2.5 fold, 3 fold, 3.5 fold, 4 fold, 4.5 fold, 5 fold, 6 fold, 7 fold, 8 fold, 9 fold, 10 fold, 15 fold, 20 fold, 30 fold, 40 fold, 50 fold, 60 fold, 70 fold, 80 fold, 90 fold, or 100 fold as assessed by methods described herein or known to one of skill in the art, as compared to mock- treated mice in tumor xenograft models. Survival can, for example, be determined by plotting a survival curve of number of surviving mice against time (e.g., days or weeks) after tumor cell line injection. Mock-treated mice can, for example, be treated with phosphate buffered saline or a control (e.g., anti-IgG antibody). [00178] In certain embodiments, an anti-MUC16 antibody agent or an antigen-binding fragment thereof described herein is internalized into a cell expressing a MUC16 polypeptide upon contacting the cell with the anti-MUC16 antibody agent or an antigen-binding fragment thereof. "Internalized" or "internalization," when in reference to a molecule that is internalized by a cell, refers to passage of the molecule that is in contact with the extracellular surface of a cell membrane across the cell membrane to the intracellular surface of the cell membrane and/or into the cell cytoplasm. In certain embodiments, the cells recombinantly expressing glycosylated MUC16 c114 are SKOV3 cells. In certain embodiments, the glycosylated form of MUC16 c114 is N-glycosylated, e.g., at Asn1, Asn24, and Asn30 of SEQ ID NO: 11 (also referred to as Asn1777, Asn1800, and Asn1806, respectively, in Yin and Lloyd (2001) J Biol Chem 276: 27371–27375). In certain embodiments, the glycosylation comprises N-linked chitobiose. In certain embodiments, the glycosylation consists of an N-linked chitobiose. [00179] Assays to determine internalization of an anti-MUC16 antibody agent or an antigen-binding fragment thereof described herein to a cell, such as, for example, using radiolabeled antibodies, are known to a person skilled in the art. For example, internalization of ⁸⁹Zr -labeled antibody can be investigated on SKOV3 cells expressing MUC16 c114. Briefly, approximately 1 × 10⁵ cells are seeded in a 12-well plate and incubated overnight at 37°C 5% CO2 incubator. A volume of radiolabeled protein is added to each well and the plates are incubated at 37°C and 4°C for 1, 5, 12, and 24 hours. Following each incubation period, the medium is collected and the cells are rinsed with 1 mL of phosphate buffered saline (PBS). Surface-bound activity is collected by washing the cells in 1 mL of 100 mM acetic acid with 100 mM glycine (1:1, pH 3.5) at 4°C. The adherent cells are then lysed with 1 mL of 1 M NaOH. Each wash is collected and counted for activity. The ratio of activity of the final wash to the total activity of all the washes is used to determine the % internalized. In certain embodiments, the assay is performed at 37°C. In certain embodiments, the anti- MUC16 antibody agent or an antigen-binding fragment thereof is internalized in at least 1, 2, 3, 5, 6, 7, 8, 9, or 10 percent of cells incubated with the anti-MUC16 antibody agent or an antigen-binding fragment thereof. In certain embodiments, the anti-MUC16 antibody agent or an antigen-binding fragment thereof is internalized in about 1, 2, 3, 5, 6, 7, 8, 9, or 10 percent of cells incubated with the anti-MUC16 antibody agent or an antigen-binding fragment thereof. In certain embodiments, the anti-MUC16 antibody agent or an antigen- binding fragment thereof is internalized within 1, 2, 3, 4, 8, 12, 16, 20, or 24 hours of contacting the cells with the anti-MUC16 antibody agent or an antigen-binding fragment thereof. [00180] Nucleic Acids [00181] Nucleic acid molecules encoding the anti-MUC16 antibody agents of the present technology (such as anti-MUC16 antibodies, e.g., full-length anti-MUC16 antibodies) are also contemplated. In some embodiments, there is provided a nucleic acid (or a set of nucleic acids) encoding a full-length anti-MUC16 antibody, including any of the full-length anti- MUC16 antibodies described herein, or an antigen-binding fragment thereof. In some embodiments, the nucleic acid (or a set of nucleic acids) encoding the anti-MUC16 antibody agent described herein may further comprise a nucleic acid sequence encoding a peptide tag (such as protein purification tag, e.g., His-tag, HA tag). [00182] Also contemplated here are isolated host cells comprising an anti-MUC16 antibody agent, an isolated nucleic acid encoding the polypeptide components of the anti- MUC16 antibody agent, or a vector comprising a nucleic acid encoding the polypeptide components of the anti-MUC16 antibody agent described herein. [00183] The present application also includes variants to these nucleic acid sequences. For example, the variants include nucleotide sequences that hybridize to the nucleic acid sequences encoding the anti-MUC16 antibody agents (such as anti-MUC16 antibodies, e.g., full-length anti-MUC16 antibodies), antigen-binding fragments thereof, or anti-MUC16 antibody moieties of the present application under at least moderately stringent hybridization conditions. [00184] The present technology also provides vectors in which a nucleic acid of the present technology is inserted. [00185] In brief summary, the expression of an anti-MUC16 antibody agent (e.g., full- length anti-MUC16 antibody or an antigen-binding fragment thereof) by a natural or synthetic nucleic acid encoding the anti-MUC16 antibody agent can be achieved by inserting the nucleic acid into an appropriate expression vector, such that the nucleic acid is operably linked to 5’ and 3’ regulatory elements, including for example a promoter (e.g., a lymphocyte-specific promoter) and a 3’ untranslated region (UTR). The vectors can be suitable for replication and integration in eukaryotic host cells. Typical cloning and expression vectors contain transcription and translation terminators, initiation sequences, and promoters useful for regulation of the expression of the desired nucleic acid sequence. [00186] The nucleic acids of the present technology may also be used for nucleic acid immunization and gene therapy, using standard gene delivery protocols. Methods for gene delivery are known in the art. See, e.g., U.S. Pat. Nos.5,399,346, 5,580,859, 5,589,466, incorporated by reference herein in their entireties. In some embodiments, the present technology provides a gene therapy vector. [00187] The nucleic acid can be cloned into a number of types of vectors. For example, the nucleic acid can be cloned into a vector including, but not limited to a plasmid, a phagemid, a phage derivative, an animal virus, and a cosmid. Vectors of particular interest include expression vectors, replication vectors, probe generation vectors, and sequencing vectors. [00188] Further, the expression vector may be provided to a cell in the form of a viral vector. Viral vector technology is well known in the art and is described, for example, in Green and Sambrook (2013, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, New York), and in other virology and molecular biology manuals. Viruses which are useful as vectors include, but are not limited to, retroviruses, adenoviruses, adeno- associated viruses, herpes viruses, and lentiviruses. In general, a suitable vector contains an origin of replication functional in at least one organism, a promoter sequence, convenient restriction endonuclease sites, and one or more selectable markers (see, e.g., WO 01/96584; WO 01/29058; and U.S. Pat. No.6,326,193). [00189] A number of viral based systems have been developed for gene transfer into mammalian cells. For example, retroviruses provide a convenient platform for gene delivery systems. A selected gene can be inserted into a vector and packaged in retroviral particles using techniques known in the art. The recombinant virus can then be isolated and delivered to cells of the subject either in vivo or ex vivo. A number of retroviral systems are known in the art. In some embodiments, adenovirus vectors are used. A number of adenovirus vectors are known in the art. In some embodiments, lentivirus vectors are used. Vectors derived from retroviruses such as the lentivirus are suitable tools to achieve long-term gene transfer since they allow long-term, stable integration of a transgene and its propagation in daughter cells. Lentiviral vectors have the added advantage over vectors derived from onco- retroviruses such as murine leukemia viruses in that they can transduce non-proliferating cells, such as hepatocytes. They also have the added advantage of low immunogenicity. [00190] Additional promoter elements, e.g., enhancers, regulate the frequency of transcriptional initiation. Typically, these are located in the region 30-110 bp upstream of the start site, although a number of promoters have recently been shown to contain functional elements downstream of the start site as well. The spacing between promoter elements frequently is flexible, so that promoter function is preserved when elements are inverted or moved relative to one another. In the thymidine kinase (tk) promoter, the spacing between promoter elements can be increased to 50 bp apart before activity begins to decline. [00191] One example of a suitable promoter is the immediate early cytomegalovirus (CMV) promoter sequence. This promoter sequence is a strong constitutive promoter sequence capable of driving high levels of expression of any polynucleotide sequence operatively linked thereto. Another example of a suitable promoter is Elongation Growth Factor-1α (EF-1α). However, other constitutive promoter sequences may also be used, including, but not limited to the simian virus 40 (SV40) early promoter, mouse mammary tumor virus (MMTV), human immunodeficiency virus (HIV) long terminal repeat (LTR) promoter, MoMuLV promoter, an avian leukemia virus promoter, an Epstein-Barr virus immediate early promoter, a Rous sarcoma virus promoter, as well as human gene promoters such as, but not limited to, the actin promoter, the myosin promoter, the hemoglobin promoter, and the creatine kinase promoter. Further, the present technology should not be limited to the use of constitutive promoters. Inducible promoters are also contemplated as part of the present technology. The use of an inducible promoter provides a molecular switch capable of turning on expression of the polynucleotide sequence which it is operatively linked when such expression is desired, or turning off the expression when expression is not desired. Examples of inducible promoters include, but are not limited to a metallothionine promoter, a glucocorticoid promoter, a progesterone promoter, and a tetracycline promoter. [00192] In some embodiments, the expression of the anti-MUC16 antibody agent is inducible. In some embodiments, a nucleic acid sequence encoding the anti-MUC16 antibody agent is operably linked to an inducible promoter, including any inducible promoter described herein. [00193] Inducible promoters [00194] The use of an inducible promoter provides a molecular switch capable of turning on expression of the polynucleotide sequence which it is operatively linked when such expression is desired, or turning off the expression when expression is not desired. Exemplary inducible promoter systems for use in eukaryotic cells include, but are not limited to, hormone-regulated elements (e.g., see Mader, S. and White, J. H. Proc. Natl. Acad. Sci. USA 90:5603-5607 (1993)), synthetic ligand-regulated elements (see, e.g., Spencer, D. M. et al 1993) Science 262: 1019-1024) and ionizing radiation-regulated elements (e.g., see Manome, Y. et al., Biochemistry 32: 10607-10613 (1993); Datta, R. et al., Proc. Natl. Acad. Sci. USA 89: 1014- 10153 (1992)). Further exemplary inducible promoter systems for use in in vitro or in vivo mammalian systems are reviewed in Gingrich et al., Annual Rev. Neurosci 21:377-405 (1998). In some embodiments, the inducible promoter system for use to express the anti-MUC16 antibody agent is the Tet system. In some embodiments, the inducible promoter system for use to express the anti-MUC16 antibody agent is the lac repressor system from E. coli. [00195] An exemplary inducible promoter system for use in the present technology is the Tet system. Such systems are based on the Tet system described by Gossen et al., (1993). In an exemplary embodiment, a polynucleotide of interest is under the control of a promoter that comprises one or more Tet operator (TetO) sites. In the inactive state, Tet repressor (TetR) will bind to the TetO sites and repress transcription from the promoter. In the active state, e.g., in the presence of an inducing agent such as tetracycline (Tc), anhydrotetracycline, doxycycline (Dox), or an active analog thereof, the inducing agent causes release of TetR from TetO, thereby allowing transcription to take place. Doxycycline is a member of the tetracycline family of antibiotics having the chemical name of 1-dimethylamino-2,4a,5,7,12- pentahydroxy-11-methyl-4,6-dioxo-1,4a,11,11a,12,12a-hexahydrotetracene-3-carboxamide. [00196] In one embodiment, a TetR is codon-optimized for expression in mammalian cells, e.g., murine or human cells. Most amino acids are encoded by more than one codon due to the degeneracy of the genetic code, allowing for substantial variations in the nucleotide sequence of a given nucleic acid without any alteration in the amino acid sequence encoded by the nucleic acid. However, many organisms display differences in codon usage, also known as “codon bias” (i.e., bias for use of a particular codon(s) for a given amino acid). Codon bias often correlates with the presence of a predominant species of tRNA for a particular codon, which in turn increases efficiency of mRNA translation. Accordingly, a coding sequence derived from a particular organism (e.g., a prokaryote) may be tailored for improved expression in a different organism (e.g., a eukaryote) through codon optimization. [00197] Other specific variations of the Tet system include the following “Tet-Off” and “Tet-On” systems. In the Tet-Off system, transcription is inactive in the presence of Tc or Dox. In that system, a tetracycline-controlled transactivator protein (tTA), which is composed of TetR fused to the strong transactivating domain of VP16 from Herpes simplex virus, regulates expression of a target nucleic acid that is under transcriptional control of a tetracycline-responsive promoter element (TRE). The TRE is made up of TetO sequence concatamers fused to a promoter (commonly the minimal promoter sequence derived from the human cytomegalovirus (hCMV) immediate-early promoter). In the absence of Tc or Dox, tTA binds to the TRE and activates transcription of the target gene. In the presence of Tc or Dox, tTA cannot bind to the TRE, and expression from the target gene remains inactive. [00198] Conversely, in the Tet-On system, transcription is active in the presence of Tc or Dox. The Tet-On system is based on a reverse tetracycline-controlled transactivator, rtTA. Like tTA, rtTA is a fusion protein comprised of the TetR repressor and the VP16 transactivation domain. However, a four amino acid change in the TetR DNA binding moiety alters rtTA's binding characteristics such that it can only recognize the tetO sequences in the TRE of the target transgene in the presence of Dox. Thus, in the Tet-On system, transcription of the TRE-regulated target gene is stimulated by rtTA only in the presence of Dox. [00199] Another inducible promoter system is the lac repressor system from E. coli (See Brown et al., Cell 49:603-612 (1987)). The lac repressor system functions by regulating transcription of a polynucleotide of interest operably linked to a promoter comprising the lac operator (lacO). The lac repressor (lacR) binds to LacO, thus preventing transcription of the polynucleotide of interest. Expression of the polynucleotide of interest is induced by a suitable inducing agent, e.g., isopropyl-β-D-thiogalactopyranoside (IPTG). [00200] In order to assess the expression of a polypeptide or portions thereof, the expression vector to be introduced into a cell can also contain either a selectable marker gene or a reporter gene or both to facilitate identification and selection of expressing cells from the population of cells sought to be transfected or infected through viral vectors. In other aspects, the selectable marker may be carried on a separate piece of DNA and used in a co- transfection procedure. Both selectable markers and reporter genes may be flanked with appropriate regulatory sequences to enable expression in the host cells. Useful selectable markers include, for example, antibiotic-resistance genes, such as neo and the like. [00201] Reporter genes are used for identifying potentially transfected cells and for evaluating the functionality of regulatory sequences. In general, a reporter gene is a gene that is not present in or expressed by the recipient organism or tissue and that encodes a polypeptide whose expression is manifested by some easily detectable property, e.g., enzymatic activity. Expression of the reporter gene is assayed at a suitable time after the DNA has been introduced into the recipient cells. Suitable reporter genes may include genes encoding luciferase, β-galactosidase, chloramphenicol acetyl transferase, secreted alkaline phosphatase, or the green fluorescent protein gene (e.g., Ui-Tel et al., 2000 FEBS Letters 479: 79-82). Suitable expression systems are well known and may be prepared using known techniques or obtained commercially. In general, the construct with the minimal 5’ flanking region showing the highest level of expression of reporter gene is identified as the promoter. Such promoter regions may be linked to a reporter gene and used to evaluate agents for the ability to modulate promoter-driven transcription. [00202] In some embodiments, there is provided nucleic acid encoding a full-length anti- MUC16 antibody according to any of the full-length anti-MUC16 antibodies described herein. In some embodiments, the nucleic acid comprises one or more nucleic acid sequences encoding the heavy and light chains of the full-length anti-MUC16 antibody. In some embodiments, each of the one or more nucleic acid sequences are contained in separate vectors. In some embodiments, at least some of the nucleic acid sequences are contained in the same vector. In some embodiments, all of the nucleic acid sequences are contained in the same vector. Vectors may be selected, for example, from the group consisting of mammalian expression vectors and viral vectors (such as those derived from retroviruses, adenoviruses, adeno-associated viruses, herpes viruses, and lentiviruses). [00203] Methods of introducing and expressing genes into a cell are known in the art. In the context of an expression vector, the vector can be readily introduced into a host cell, e.g., mammalian, bacterial, yeast, or insect cell by any method in the art. For example, the expression vector can be transferred into a host cell by physical, chemical, or biological means. [00204] Physical methods for introducing a polynucleotide into a host cell include calcium phosphate precipitation, lipofection, particle bombardment, microinjection, electroporation, and the like. Methods for producing cells comprising vectors and/or exogenous nucleic acids are well-known in the art. See, for example, Green and Sambrook (2013, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, New York). In some embodiments, the introduction of a polynucleotide into a host cell is carried out by calcium phosphate transfection. [00205] Biological methods for introducing a polynucleotide of interest into a host cell include the use of DNA and RNA vectors. Viral vectors, and especially retroviral vectors, have become the most widely used method of inserting genes into mammalian, e.g., human cells. Other viral vectors can be derived from lentivirus, poxviruses, herpes simplex virus 1, adenoviruses and adeno-associated viruses, and the like. See, for example, U.S. Pat. Nos. 5,350,674 and 5,585,362. [00206] Chemical means for introducing a polynucleotide into a host cell include colloidal dispersion systems, such as macromolecule complexes, nanocapsules, microspheres, beads, and lipid-based systems including oil-in-water emulsions, micelles, mixed micelles, and liposomes. An exemplary colloidal system for use as a delivery vehicle in vitro and in vivo is a liposome (e.g., an artificial membrane vesicle). [00207] In the case where a non-viral delivery system is utilized, an exemplary delivery vehicle is a liposome. The use of lipid formulations is contemplated for the introduction of the nucleic acids into a host cell (in vitro, ex vivo or in vivo). In another aspect, the nucleic acid may be associated with a lipid. The nucleic acid associated with a lipid may be encapsulated in the aqueous interior of a liposome, interspersed within the lipid bilayer of a liposome, attached to a liposome via a linking molecule that is associated with both the liposome and the oligonucleotide, entrapped in a liposome, complexed with a liposome, dispersed in a solution containing a lipid, mixed with a lipid, combined with a lipid, contained as a suspension in a lipid, contained or complexed with a micelle, or otherwise associated with a lipid. Lipid, lipid/DNA or lipid/expression vector associated compositions are not limited to any particular structure in solution. For example, they may be present in a bilayer structure, as micelles, or with a “collapsed” structure. They may also simply be interspersed in a solution, possibly forming aggregates that are not uniform in size or shape. Lipids are fatty substances which may be naturally occurring or synthetic lipids. For example, lipids include the fatty droplets that naturally occur in the cytoplasm as well as the class of compounds which contain long-chain aliphatic hydrocarbons and their derivatives, such as fatty acids, alcohols, amines, amino alcohols, and aldehydes. [00208] Regardless of the method used to introduce exogenous nucleic acids into a host cell or otherwise expose a cell to the inhibitor of the present technology, in order to confirm the presence of the recombinant DNA sequence in the host cell, a variety of assays may be performed. Such assays include, for example, “molecular biological” assays well known to those of skill in the art, such as Southern and Northern blotting, RT-PCR and PCR; “biochemical” assays, such as detecting the presence or absence of a particular peptide, e.g., by immunological means (ELISAs and Western blots) or by assays described herein to identify agents falling within the scope of the present technology. Preparation of the Anti-MUC16 Antibody Agents and Anti- MUC16 Antibody Moieties [00209] In some embodiments, the anti-MUC16 antibody agent of the present technology is a monoclonal antibody or derived from a monoclonal antibody. In some embodiments, the anti-MUC16 antibody agent of the present technology comprises VH and VL domains, or variants thereof, from the monoclonal antibody. In some embodiments, the anti-MUC16 antibody agent of the present technology further comprises C_H1 and C_L domains, or variants thereof, from the monoclonal antibody. Monoclonal antibodies can be prepared, e.g., using known methods in the art, including hybridoma methods, phage display methods, or using recombinant DNA methods. Additionally, exemplary phage display methods are described herein and in the Examples below. [00210] In a hybridoma method, a hamster, mouse, or other appropriate host animal is typically immunized with an immunizing agent to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the immunizing agent. Alternatively, the lymphocytes can be immunized in vitro. The immunizing agent can include a polypeptide or a fusion protein of the protein of interest. Generally, peripheral blood lymphocytes (“PBLs”) are used if cells of human origin are desired, or spleen cells or lymph node cells are used if non-human mammalian sources are desired. The lymphocytes are then fused with an immortalized cell line using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell. Immortalized cell lines are usually transformed mammalian cells, particularly myeloma cells of rodent, bovine, and human origin. Usually, rat or mouse myeloma cell lines are employed. The hybridoma cells can be cultured in a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, immortalized cells. For example, if the parental cells lack the enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT or HPRT), the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thymidine (“HAT medium”), which prevents the growth of HGPRT-deficient cells. [00211] In some embodiments, the immortalized cell lines fuse efficiently, support stable high-level expression of antibody by the selected antibody-producing cells, and are sensitive to a medium such as HAT medium. In some embodiments, the immortalized cell lines are murine myeloma lines, which can be obtained, for instance, from the Salk Institute Cell Distribution Center, San Diego, California and the American Type Culture Collection, Manassas, Virginia. Human myeloma and mouse-human heteromyeloma cell lines also have been described for the production of human monoclonal antibodies. [00212] The culture medium in which the hybridoma cells are cultured can then be assayed for the presence of monoclonal antibodies directed against the polypeptide. The binding specificity of monoclonal antibodies produced by the hybridoma cells can be determined by immunoprecipitation or by an in vitro binding assay, such as radioimmunoassay (RIA) or enzyme-linked immunosorbent assay (ELISA). Such techniques and assays are known in the art. The binding affinity of the monoclonal antibody can, for example, be determined by the Scatchard analysis of Munson and Pollard, Anal. Biochem., 107:220 (1980). [00213] After the desired hybridoma cells are identified, the clones can be sub cloned by limiting dilution procedures and grown by standard methods. Suitable culture media for this purpose include, for example, Dulbecco's Modified Eagle's Medium and RPMI-1640 medium. Alternatively, the hybridoma cells can be grown in vivo as ascites in a mammal. [00214] The monoclonal antibodies secreted by the sub clones can be isolated or purified from the culture medium or ascites fluid by conventional immunoglobulin purification procedures such as, for example, protein A-Sepharose, hydroxylapatite chromatography, gel electrophoresis, dialysis, or affinity chromatography. [00215] In some embodiments, according to any of the anti-MUC16 antibody agents described herein, the anti-MUC16 antibody agent comprises sequences from a clone selected from an antibody library (such as a phage library presenting scFv or Fab fragments). The clone may be identified by screening combinatorial libraries for antibody fragments with the desired activity or activities. For example, a variety of methods are known in the art for generating phage display libraries and screening such libraries for antibodies possessing the desired binding characteristics. Such methods are reviewed, e.g., in Hoogenboom et al., Methods in Molecular Biology 178:1-37 (O'Brien et al., ed., Human Press, Totowa, N.J., 2001) and further described, e.g., in McCafferty et al., Nature 348:552-554; Clackson et al., Nature 352: 624-628 (1991); Marks et al., J. Mol. Biol.222: 581-597 (1992); Marks and Bradbury, Methods in Molecular Biology 248:161-175 (Lo, ed., Human Press, Totowa, N.J., 2003); Sidhu et al., J. Mol. Biol.338(2): 299-310 (2004); Lee et al., J. Mol. Biol.340(5): 1073-1093 (2004); Fellouse, Proc. Natl. Acad. Sci. USA 101(34): 12467-12472 (2004); and Lee et al., J. Immunol. Methods 284(1-2): 119-132(2004). [00216] In certain phage display methods, repertoires of V_H and V_L genes are separately cloned by polymerase chain reaction (PCR) and recombined randomly in phage libraries, which can then be screened for antigen-binding phage as described in Winter et al., Ann. Rev. Immunol., 12: 433-455 (1994). Phage typically display antibody fragments, either as scFv fragments or as Fab fragments. Libraries from immunized sources provide high-affinity antibodies to the immunogen without the requirement of constructing hybridomas. Alternatively, the naive repertoire can be cloned (e.g., from human) to provide a single source of antibodies to a wide range of non-self and also self-antigens without any immunization as described by Griffiths et al., EMBO J, 12: 725-734 (1993). Finally, naive libraries can also be made synthetically by cloning unrearranged V-gene segments from stem cells, and using PCR primers containing random sequence to encode the highly variable CDR3 regions and to accomplish rearrangement in vitro, as described by Hoogenboom and Winter, J. Mol. Biol., 227: 381-388 (1992). Patent publications describing human antibody phage libraries include, for example: U.S. Pat. No.5,750,373, and US Patent Publication Nos.2005/0079574, 2005/0119455, 2005/0266000, 2007/0117126, 2007/0160598, 2007/0237764, 2007/0292936, and 2009/0002360. [00217] The anti-MUC16 antibody agents can be prepared using phage display to screen libraries for anti-MUC16 antibody moieties specific to the target MUC16 (e.g., nMUC16). The library can be a human scFv phage display library having a diversity of at least one x 10⁹ (such as at least about any of 1 × 10⁹, 2.5 × 10⁹, 5 × 10⁹, 7.5 × 10⁹, 1 × 10¹⁰, 2.5 × 10¹⁰, 5 × 10¹⁰, 7.5 × 10¹⁰, or 1 × 10¹¹) unique human antibody fragments. In some embodiments, the library is a naïve human library constructed from DNA extracted from human PMBCs and spleens from healthy donors, encompassing all human heavy and light chain subfamilies. In some embodiments, the library is a naïve human library constructed from DNA extracted from PBMCs isolated from patients with various diseases, such as patients with autoimmune diseases, cancer patients, and patients with infectious diseases. In some embodiments, the library is a semi-synthetic human library, wherein heavy chain CDR3 is completely randomized, with all amino acids (with the exception of cysteine) equally likely to be present at any given position (see, e.g., Hoet, R.M. et al., Nat. Biotechnol.23(3):344-348, 2005). In some embodiments, the heavy chain CDR3 of the semi-synthetic human library has a length from about 5 to about 24 (such as about any of 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24) amino acids. In some embodiments, the library is a fully-synthetic phage display library. In some embodiments, the library is a non-human phage display library. [00218] Phage clones that bind to the target MUC16 (e.g., nMUC16) with high affinity can be selected by iterative binding of phage to the target MUC16, which is bound to a solid support (such as, for example, beads for solution panning or mammalian cells for cell panning), followed by removal of non-bound phage and by elution of specifically bound phage. The bound phage clones are then eluted and used to infect an appropriate host cell, such as E. coli XL1-Blue, for expression and purification. In an example of cell panning, HEK293 cells over-expressing MUC16 on cell surface are mixed with the phage library, after which the cells are collected and the bound clones are eluted and used to infect an appropriate host cell for expression and purification (all see Examples). The panning can be performed for multiple (such as about any of 2, 3, 4, 5, 6 or more) rounds with solution panning, cell panning, or a combination of both, to enrich for phage clones binding specifically to the target MUC16. Enriched phage clones can be tested for specific binding to the target MUC16 by any methods known in the art, including for example ELISA and FACS. [00219] Monoclonal antibodies can also be made by recombinant DNA methods, such as those described in U.S. Patent No.4,816,567. DNA encoding the monoclonal antibodies of the present technology can be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of murine antibodies). Hybridoma cells as described above or MUC16-specific phage clones of the present technology can serve as a source of such DNA. Once isolated, the DNA can be placed into expression vectors, which are then transfected into host cells such as simian COS cells, Chinese hamster ovary (CHO) cells, or myeloma cells that do not otherwise produce immunoglobulin protein, to obtain the synthesis of monoclonal antibodies in the recombinant host cells. The DNA also can be modified, for example, by substituting the coding sequence for human heavy- and light-chain constant domains and/or framework regions in place of the homologous non-human sequences (U.S. Patent No.4,816,567; Morrison et al., supra) or by covalently joining to the immunoglobulin coding sequence all or part of the coding sequence for a non-immunoglobulin polypeptide. Such a non-immunoglobulin polypeptide can be substituted for the constant domains of an antibody agent of the present technology, or can be substituted for the variable domains of one antigen-combining site of an antibody agent of the present technology to create a chimeric bivalent antibody agent. [00220] The antibodies can be monovalent antibodies. Methods for preparing monovalent antibodies are known in the art. For example, one method involves recombinant expression of immunoglobulin light chain and modified heavy chain. The heavy chain is truncated generally at any point in the Fc region so as to prevent heavy-chain crosslinking. Alternatively, the relevant cysteine residues are substituted with another amino acid residue or are deleted so as to prevent crosslinking. [00221] In vitro methods are also suitable for preparing monovalent antibodies. Digestion of antibodies to produce fragments thereof, particularly Fab fragments, can be accomplished using any method known in the art. [00222] Antibody variable domains with the desired binding specificities (antibody- antigen combining sites) can be fused to immunoglobulin constant-domain sequences. The fusion preferably is with an immunoglobulin heavy-chain constant domain, comprising at least part of the hinge, CH2, and CH3 regions. In some embodiments, the first heavy-chain constant region (CH1) containing the site necessary for light-chain binding is present in at least one of the fusions. DNAs encoding the immunoglobulin heavy-chain fusions and, if desired, the immunoglobulin light chain, are inserted into separate expression vectors, and are co-transfected into a suitable host organism. [00223] Human and Humanized Antibodies [00224] The anti-MUC16 antibody agents of the present technology (e.g., full-length anti- MUC16 antibodies or an antigen binding fragment thereof) can be humanized antibody agents or human antibody agents. Humanized forms of non-human (e.g., murine) antibody moieties are chimeric immunoglobulins, immunoglobulin chains, or fragments thereof (such as Fv, Fab, Fab’, F(ab’)2, scFv, or other antigen-binding subsequences of antibodies) that typically contain minimal sequence derived from non-human immunoglobulin. Humanized antibody moieties include human immunoglobulins, immunoglobulin chains, or fragments thereof (recipient antibody) in which residues from a CDR of the recipient are replaced by residues from a CDR of a non-human species (donor antibody) such as mouse, rat, or rabbit having the desired specificity, affinity, and capacity. In some instances, Fv framework residues of the human immunoglobulin are replaced by corresponding non-human residues. Humanized antibody moieties can also comprise residues that are found neither in the recipient antibody nor in the imported CDR or framework sequences. In general, the humanized antibody can comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non- human immunoglobulin, and all or substantially all of the FR regions are those of a human immunoglobulin consensus sequence. [00225] Generally, a humanized antibody agent has one or more amino acid residues introduced into it from a source that is non-human. These non-human amino acid residues are often referred to as “import” residues, which are typically taken from an “import” variable domain. According to some embodiments, humanization can be essentially performed following the method of Winter and co-workers (Jones et al., Nature, 321: 522- 525 (1986); Riechmann et al., Nature, 332: 323-327 (1988); Verhoeyen et al., Science, 239: 1534-1536 (1988)), by substituting rodent CDRs or CDR sequences for the corresponding sequences of a human antibody. Accordingly, such “humanized” antibody moieties are antibody moieties (U.S. Patent No.4,816,567), wherein substantially less than an intact human variable domain has been substituted by the corresponding sequence from a non- human species. In practice, humanized antibody moieties are typically human antibody moieties in which some CDR residues and possibly some FR residues are substituted by residues from analogous sites in rodent antibodies. [00226] As an alternative to humanization, human antibody moieties can be generated. For example, it is now possible to produce transgenic animals (e.g., mice) that are capable, upon immunization, of producing a full repertoire of human antibodies in the absence of endogenous immunoglobulin production. For example, it has been described that the homozygous deletion of the antibody heavy-chain joining region (JH) gene in chimeric and germ-line mutant mice results in complete inhibition of endogenous antibody production. Transfer of the human germ-line immunoglobulin gene array into such germ-line mutant mice will result in the production of human antibodies upon antigen challenge. See, e.g., Jakobovits et al., PNAS USA, 90:2551 (1993); Jakobovits et al., Nature, 362:255-258 (1993); Bruggemann et al., Year in Immunol., 7:33 (1993); U.S. Patent Nos.5,545,806, 5,569,825, 5,591,669; 5,545,807; and WO 97/17852. Alternatively, human antibodies can be made by introducing human immunoglobulin loci into transgenic animals, e.g., mice in which the endogenous immunoglobulin genes have been partially or completely inactivated. Upon challenge, human antibody production is observed that closely resembles that seen in humans in all respects, including gene rearrangement, assembly, and antibody repertoire. This approach is described, for example, in U.S. Patent Nos.5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425; and 5,661,016, and Marks et al., Bio/Technology, 10: 779-783 (1992); Lonberg et al., Nature, 368: 856-859 (1994); Morrison, Nature, 368: 812-813 (1994); Fishwild et al., Nature Biotechnology, 14: 845-851 (1996); Neuberger, Nature Biotechnology, 14: 826 (1996); Lonberg and Huszar, Intern. Rev. Immunol., 13: 65-93 (1995). [00227] Human antibody agents may also be generated by in vitro activated B cells (see U.S. Patents 5,567,610 and 5,229,275) or by using various techniques known in the art, including phage display libraries. Hoogenboom and Winter, J. Mol. Biol., 227:381 (1991); Marks et al., J. Mol. Biol., 222:581 (1991). The techniques of Cole et al. and Boerner et al. are also available for the preparation of human monoclonal antibodies. Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p.77 (1985) and Boerner et al., J. Immunol., 147(1): 86-95 (1991). Modifications of the Anti-MUC16 Antibody Agents of the Present Technology [00228] In some embodiments, amino acid sequence modifications of the anti-MUC16 antibody agents (e.g., full-length anti-MUC16 antibody or an antigen binding fragment thereof) provided herein are contemplated. For example, it may be desirable to improve the binding affinity and/or other biological properties of the antibody agent. An antibody agent may be prepared by introducing appropriate modifications into the nucleotide sequence encoding the antibody agent, or by peptide synthesis. Such modifications include, for example, deletions from, and/or insertions into and/or substitutions of residues within the amino acid sequences of the antibody agent. Any combination of deletion, insertion, and substitution can be made to arrive at the final construct, provided that the final construct possesses the desired characteristics. [00229] In some embodiments, anti-MUC16 antibody agent variants having one or more amino acid substitutions are provided. Amino acid substitutions may be introduced into an antibody agent of interest and the products screened for a desired activity, e.g., retained/improved antigen binding, decreased immunogenicity, or improved ADCC or CDC. [00230] Conservative substitutions are shown below:

[00231] Amino acids may be grouped into different classes according to common side- chain properties: hydrophobic: Norleucine, Met, Ala, Val, Leu, Ile; neutral hydrophilic: Cys, Ser, Thr, Asn, Gln; acidic: Asp, Glu; basic: His, Lys, Arg; residues that influence chain orientation: Gly, Pro; and aromatic: Trp, Tyr, Phe. Non-conservative substitutions involve exchanging a member of one of these classes for another class. [00232] An exemplary substitutional variant is an affinity matured antibody agent, which may be conveniently generated, e.g., using phage display-based affinity maturation techniques. Briefly, one or more CDR residues are mutated and the variant antibody moieties displayed on phage and screened for a particular biological activity (e.g., binding affinity). Alterations (e.g., substitutions) may be made in HVRs, e.g., to improve antibody affinity. Such alterations may be made in HVR “hotspots,” i.e., residues encoded by codons that undergo mutation at high frequency during the somatic maturation process (see, e.g., Chowdhury, Methods Mol. Biol.207:179-196 (2008)), and/or specificity determining residues (SDRs), with the resulting variant V_H or V_L being tested for binding affinity. Affinity maturation by constructing and reselecting from secondary libraries has been described, e.g., in Hoogenboom et al., in Methods in Molecular Biology 178:1-37 (O'Brien et al., ed., Human Press, Totowa, NJ, (2001)). [00233] In some embodiments of affinity maturation, diversity is introduced into the variable genes chosen for maturation by any of a variety of methods (e.g., error-prone PCR, chain shuffling, or oligonucleotide-directed mutagenesis). A secondary library is then created. The library is then screened to identify any antibody agent variants with the desired affinity. Another method to introduce diversity involves HVR-directed approaches, in which several HVR residues (e.g., 4-6 residues at a time) are randomized. HVR residues involved in antigen binding may be specifically identified, e.g., using alanine scanning mutagenesis or modeling. CDR-H3 and CDR-L3 in particular are often targeted. [00234] In some embodiments, substitutions, insertions, or deletions may occur within one or more HVRs so long as such alterations do not substantially reduce the ability of the antibody agent to bind antigen. For example, conservative alterations (e.g., conservative substitutions as provided herein) that do not substantially reduce binding affinity may be made in HVRs. Such alterations may be outside of HVR “hotspots” or SDRs. In some embodiments of the variant VH and VL sequences provided above, each HVR either is unaltered, or contains no more than one, two or three amino acid substitutions. [00235] A useful method for identification of residues or regions of an antibody agent that may be targeted for mutagenesis is called “alanine scanning mutagenesis” as described by Cunningham and Wells (1989) Science, 244:1081-1085. In this method, a residue or group of target residues (e.g., charged residues such as Arg, Asp, His, Lys, and Glu) are identified and replaced by a neutral or negatively charged amino acid (e.g., alanine or polyalanine) to determine whether the interaction of the antibody agent with antigen is affected. Further substitutions may be introduced at the amino acid locations demonstrating functional sensitivity to the initial substitutions. Alternatively, or additionally, a crystal structure of an antigen-antibody agent complex can be determined to identify contact points between the antibody agent and antigen. Such contact residues and neighboring residues may be targeted or eliminated as candidates for substitution. Variants may be screened to determine whether they contain the desired properties. [00236] Amino acid sequence insertions include amino- and/or carboxyl-terminal fusions ranging in length from one residue to polypeptides containing a hundred or more residues, as well as intrasequence insertions of single or multiple amino acid residues. Examples of terminal insertions include an antibody agent with an N-terminal methionyl residue. Other insertional variants of the antibody agent molecule include the fusion to the N- or C-terminus of the antibody agent to an enzyme (e.g. for ADEPT) or a polypeptide which increases the serum half-life of the antibody agent. [00237] Fc Region Variants [00238] In some embodiments, one or more amino acid modifications may be introduced into the Fc region of an antibody agent (e.g., a full-length anti-MUC16 antibody or anti- MUC16 Fc fusion protein) provided herein, thereby generating an Fc region variant. In some embodiments, the Fc region variant has enhanced ADCC effector function, often related to binding to Fc receptors (FcRs). In some embodiments, the Fc region variant has decreased ADCC effector function. There are many examples of changes or mutations to Fc sequences that can alter effector function. For example, WO 00/42072 and Shields et al., J Biol. Chem. 9(2): 6591-6604 (2001) describe antibody variants with improved or diminished binding to FcRs. The contents of those publications are specifically incorporated herein by reference. [00239] Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) is a mechanism of action of therapeutic antibodies against tumor cells. ADCC is a cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell (e.g., a cancer cell), whose membrane-surface antigens have been bound by specific antibodies (e.g., an anti-MUC16 antibody). The typical ADCC involves activation of NK cells by antibodies. An NK cell expresses CD16 which is an Fc receptor. This receptor recognizes, and binds to, the Fc portion of an antibody bound to the surface of a target cell. The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII. Binding of the Fc receptor to the Fc region of an antibody results in NK cell activation, release of cytolytic granules and consequent target cell apoptosis. The contribution of ADCC to tumor cell killing can be measured with a specific test that uses NK-92 cells that have been transfected with a high- affinity FcR. Results are compared to wild-type NK-92 cells that do not express the FcR. [00240] In some embodiments, the present technology contemplates an anti-MUC16 antibody agent variant (such as a full-length anti-MUC16 antibody variant) comprising an Fc region that possesses some but not all effector functions, which makes it a desirable candidate for applications in which the half-life of the anti-MUC16 antibody agent in vivo is important yet certain effector functions (such as CDC and ADCC) are unnecessary or deleterious. In vitro and/or in vivo cytotoxicity assays can be conducted to confirm the reduction/depletion of CDC and/or ADCC activities. For example, Fc receptor (FcR) binding assays can be conducted to ensure that the antibody agent lacks FcγR binding (hence likely lacking ADCC activity), but retains FcRn binding ability. The primary cells for mediating ADCC, NK cells, express FcγRIII only, whereas monocytes express FcγRI, FcγRII and FcγRIII. FcR expression on hematopoietic cells is summarized in Table 3 on page 464 of Ravetch and Kinet, Annu. Rev. Immunol.9:457-492 (1991). Non-limiting examples of in vitro assays to assess ADCC activity of a molecule of interest is described in U.S. Pat. No.5,500,362 (see, e.g. Hellstrom, I. et al., Proc. Nat'l Acad. Sci. USA 83:7059-7063 (1986)) and Hellstrom, I et al., Proc. Nat'l Acad. Sci. USA 82:1499-1502 (1985); U.S. Pat. No.5,821,337 (see Bruggemann, M. et al., J. Exp. Med.166:1351-1361 (1987)). Alternatively, non-radioactive assay methods may be employed (see, for example, ACTI™ non-radioactive cytotoxicity assay for flow cytometry (CellTechnology, Inc. Mountain View, Calif.; and CytoTox 96™ non-radioactive cytotoxicity assay (Promega, Madison, Wis.). Useful effector cells for such assays include peripheral blood mononuclear cells (PBMC) and Natural Killer (NK) cells. Alternatively, or additionally, ADCC activity of the molecule of interest may be assessed in vivo, e.g., in an animal model such as that disclosed in Clynes et al., Proc. Nat'l Acad. Sci. USA 95:652-656 (1998). C1q binding assays may also be carried out to confirm that the antibody agent is unable to bind C1q and hence lacks CDC activity. See, e.g., C1q and C3c binding ELISA in WO 2006/029879 and WO 2005/100402. To assess complement activation, a CDC assay may be performed (see, for example, Gazzano-Santoro et al., J. Immunol. Methods 202:163 (1996); Cragg, M. S. et al., Blood 101:1045-1052 (2003); and Cragg, M. S. and M. J. Glennie, Blood 103:2738-2743 (2004)). FcRn binding and in vivo clearance/half-life determinations can also be performed using methods known in the art (see, e.g., Petkova, S. B. et al., Int'l. Immunol.18(12):1759-1769 (2006)). [00241] Antibodies with reduced effector function include those with substitution of one or more of Fc region residues 238, 265, 269, 270, 297, 327 and 329 (U.S. Pat. No. 6,737,056). Such Fc mutants include Fc mutants with substitutions at two or more of amino acid positions 265, 269, 270, 297 and 327, including the so-called “DANA” Fc mutant with substitution of residues 265 and 297 to alanine (U.S. Pat. No.7,332,581). [00242] Certain antibody agent variants with improved or diminished binding to FcRs are described. (See, e.g., U.S. Pat. No.6,737,056; WO 2004/056312, and Shields et al., J. Biol. Chem.9(2): 6591-6604 (2001)). [00243] In some embodiments, provided herein is an anti-MUC16 antibody agent of the present technology (such as a full-length anti-MUC16 antibody) comprising a variant Fc region comprising one or more amino acid substitutions which improve ADCC. In some embodiments, the variant Fc region comprises one or more amino acid substitutions which improve ADCC, wherein the substitutions are at positions 298, 333, and/or 334 of the variant Fc region (EU numbering of residues). In some embodiments, the anti-MUC16 antibody agent of the present technology (e.g., full-length anti-MUC16 antibody) comprises the following amino acid substitution in its variant Fc region: S298A, E333A, and K334A. [00244] In some embodiments, alterations are made in the Fc region that result in altered (i.e., either improved or diminished) C1q binding and/or Complement Dependent Cytotoxicity (CDC), e.g., as described in U.S. Pat. No.6,194,551, WO 99/51642, and Idusogie et al., J. Immunol.164: 4178-4184 (2000). [00245] In some embodiments, there is provided an anti-MUC16 antibody agent of the present technology (such as a full-length anti-MUC16 antibody) comprising a variant Fc region comprising one or more amino acid substitutions which increase half-life and/or improve binding to the neonatal Fc receptor (FcRn). Antibodies with increased half-lives and improved binding to FcRn are described in US2005/0014934A1 (Hinton et al.). Those antibodies comprise an Fc region with one or more substitutions therein which improve binding of the Fc region to FcRn. Such Fc variants include those with substitutions at one or more of Fc region residues: 238, 256, 265, 272, 286, 303, 305, 307, 311, 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, 413, 424 or 434, e.g., substitution of Fc region residue 434 (U.S. Pat. No.7,371,826). See also Duncan & Winter, Nature 322:738-40 (1988); U.S. Pat. No.5,648,260; U.S. Pat. No.5,624,821; and WO 94/29351 concerning other examples of Fc region variants. [00246] Anti-MUC16 antibody agents of the present technology (such as full-length anti- MUC16 antibodies) comprising any of the Fc variants described herein, or combinations thereof, are contemplated. [00247] Glycosylation Variants [00248] In some embodiments, an anti-MUC16 antibody agent of the present technology (such as a full-length anti-MUC16 antibody or an antigen binding fragment thereof) is altered to increase or decrease the extent to which the anti-MUC16 antibody agent is glycosylated. Addition or deletion of glycosylation sites to an anti-MUC16 antibody agent may be conveniently accomplished by altering the amino acid sequence of the anti-MUC16 antibody agent or polypeptide portion thereof such that one or more glycosylation sites is created or removed. [00249] Where the anti-MUC16 antibody agent or an antigen binding fragment thereof comprises an Fc region, the carbohydrate attached thereto may be altered. Native antibodies produced by mammalian cells typically comprise a branched, biantennary oligosaccharide that is generally attached by an N-linkage to Asn297 of the CH2 domain of the Fc region. See, e.g., Wright et al., TIBTECH 15:26-32 (1997). The oligosaccharide may include various carbohydrates, e.g., mannose, N-acetyl glucosamine (GlcNAc), galactose, and sialic acid, as well as a fucose attached to a GlcNAc in the “stem” of the biantennary oligosaccharide structure. In some embodiments, modifications of the oligosaccharide in an anti-MUC16 antibody agent of the present technology may be made in order to create anti-MUC16 antibody agent variants with certain improved properties. [00250] The N-glycans attached to the CH2 domain of Fc is heterogeneous. Antibodies or Fc fusion proteins generated in CHO cells are fucosylated by fucosyltransferase activity. See Shoji-Hosaka et al., J. Biochem.140:777- 83 (2006). Normally, a small percentage of naturally occurring afucosylated IgGs may be detected in human serum. N-glycosylation of the Fc is important for binding to FcγR; and afucosylation of the N-glycan increases Fc's binding capacity to FcγRIIIa. Increased FcγRIIIa binding can enhance ADCC, which can be advantageous in certain antibody agent therapeutic applications in which cytotoxicity is desirable. [00251] In some embodiments, an enhanced effector function can be detrimental when Fc- mediated cytotoxicity is undesirable. In some embodiments, the Fc fragment or CH2 domain is not glycosylated. In some embodiments, the N-glycosylation site in the CH2 domain is mutated to prevent from glycosylation. [00252] In some embodiments, anti-MUC16 antibody agent of the present technology (such as a full-length anti-MUC16 antibody) variants are provided comprising an Fc region wherein a carbohydrate structure attached to the Fc region has reduced fucose or lacks fucose, which may improve ADCC function. Specifically, anti-MUC16 antibody agents are contemplated herein that have reduced fucose relative to the amount of fucose on the same anti-MUC16 antibody agent produced in a wild-type CHO cell. That is, they are characterized by having a lower amount of fucose than they would otherwise have if produced by native CHO cells (e.g., a CHO cell that produce a native glycosylation pattern, such as, a CHO cell containing a native FUT8 gene). In some embodiments, the anti-MUC16 antibody agent is one wherein less than about 50%, 40%, 30%, 20%, 10%, or 5% of the N- linked glycans thereon comprise fucose. For example, the amount of fucose in such an anti- MUC16 antibody agent may be from 1% to 80%, from 1% to 65%, from 5% to 65% or from 20% to 40%. In some embodiments, the anti-MUC16 antibody agent is one wherein none of the N-linked glycans thereon comprise fucose, i.e., wherein the anti-MUC16 antibody agent is completely without fucose, or has no fucose or is afucosylated. The amount of fucose is determined by calculating the average amount of fucose within the sugar chain at Asn297, relative to the sum of all glycostructures attached to Asn 297 (e.g., complex, hybrid and high mannose structures) as measured by MALDI-TOF mass spectrometry, as described in WO 2008/077546, for example. Asn297 refers to the asparagine residue located at about position 297 in the Fc region (EU numbering of Fc region residues); however, Asn297 may also be located about ±3 amino acids upstream or downstream of position 297, i.e., between positions 294 and 300, due to minor sequence variations in antibodies. Such fucosylation variants may have improved ADCC function. See, e.g., US Patent Publication Nos. US 2003/0157108 (Presta, L.); US 2004/0093621 (Kyowa Hakko Kogyo Co., Ltd). Examples of publications related to “defucosylated” or “fucose-deficient” antibody agent variants include: US 2003/0157108; WO 2000/61739; WO 2001/29246; US 2003/0115614; US 2002/0164328; US 2004/0093621; US 2004/0132140; US 2004/0110704; US 2004/0110282; US 2004/0109865; WO 2003/085119; WO 2003/084570; WO 2005/035586; WO 2005/035778; WO2005/053742; WO2002/031140; Okazaki et al., J. Mol. Biol.336:1239-1249 (2004); Yamane-Ohnuki et al., Biotech. Bioeng.87: 614 (2004). Examples of cell lines capable of producing defucosylated antibodies include Lec13 CHO cells deficient in protein fucosylation (Ripka et al., Arch. Biochem. Biophys.249:533-545 (1986); US Pat Appl No US 2003/0157108 A1, Presta, L; and WO 2004/056312 A1, Adams et al., especially at Example 11), and knockout cell lines, such as α-1,6-fucosyltransferase gene, FUT8, knockout CHO cells (see, e.g., Yamane-Ohnuki et al., Biotech. Bioeng.87: 614 (2004); Kanda, Y. et al., Biotechnol. Bioeng., 94(4):680-688 (2006); and WO2003/085107). [00253] Anti-MUC16 antibody agent (such as a full-length anti-MUC16 antibody) variants are further provided with bisected oligosaccharides, e.g., in which a biantennary oligosaccharide attached to the Fc region of the anti-MUC16 antibody agent is bisected by GlcNAc. Such anti-MUC16 antibody agent (such as a full-length anti-MUC16 antibody) variants may have reduced fucosylation and/or improved ADCC function. Examples of such antibody agent variants are described, e.g., in WO 2003/011878 (Jean-Mairet et al.); U.S. Pat. No.6,602,684 (Umana et al.); US 2005/0123546 (Umana et al.), and Ferrara et al., Biotechnology and Bioengineering, 93(5): 851-861 (2006). Anti-MUC16 antibody agent (such as full-length anti-MUC16 antibody) variants with at least one galactose residue in the oligosaccharide attached to the Fc region are also provided. Such anti-MUC16 antibody agent variants may have improved CDC function. Such antibody agent variants are described, e.g., in WO 1997/30087 (Patel et al.); WO 1998/58964 (Raju, S.); and WO 1999/22764 (Raju, S.). [00254] In some embodiments, the anti-MUC16 antibody agent (such as a full-length anti- MUC16 antibody) variants comprising an Fc region are capable of binding to an FcγRIII. In some embodiments, the anti-MUC16 antibody agent (such as a full-length anti-MUC16 antibody) variants comprising an Fc region have ADCC activity in the presence of human effector cells (e.g., T cell) or have increased ADCC activity in the presence of human effector cells compared to the otherwise same anti-MUC16 antibody agent (such as a full-length anti- MUC16 antibody) comprising a human wild-type IgG1Fc region. [00255] Cysteine Engineered Variants [00256] In some embodiments, it may be desirable to create cysteine engineered anti- MUC16 antibody agents (such as a full-length anti-MUC16 antibody) or an antigen binding fragment thereof in which one or more amino acid residues are substituted with cysteine residues. In some embodiments, the substituted residues occur at accessible sites of the anti- MUC16 antibody agent or an antigen binding fragment thereof. By substituting those residues with cysteine, reactive thiol groups are thereby positioned at accessible sites of the anti-MUC16 antibody agent and may be used to conjugate the anti-MUC16 antibody agent to other moieties, such as drug moieties or linker-drug moieties, to create an anti-MUC16 immunoconjugate, as described further herein. Cysteine engineered anti-MUC16 antibody agents (such as anti-MUC16 antibodies, e.g., full-length anti-MUC16 antibodies) may be generated as described, e.g., in U.S. Pat. No.7,521,541. [00257] Derivatives [00258] In some embodiments, an anti-MUC16 antibody agent (such as a full-length anti- MUC16 antibody) or an antigen binding fragment thereof provided herein may be further modified to contain additional non-proteinaceous moieties that are known in the art and readily available. The moieties suitable for derivatization of the anti-MUC16 antibody agent include but are not limited to water soluble polymers. Non-limiting examples of water soluble polymers include, but are not limited to, polyethylene glycol (PEG), copolymers of ethylene glycol/propylene glycol, carboxymethylcellulose, dextran, polyvinyl alcohol, polyvinyl pyrrolidone, poly-1,3-dioxolane, poly-1,3,6-trioxane, ethylene/maleic anhydride copolymer, polyaminoacids (either homopolymers or random copolymers), and dextran or poly(n-vinyl pyrrolidone)polyethylene glycol, propropylene glycol homopolymers, prolypropylene oxide/ethylene oxide co-polymers, polyoxyethylated polyols (e.g., glycerol), polyvinyl alcohol, and mixtures thereof. Polyethylene glycol propionaldehyde may have advantages in manufacturing due to its stability in water. The polymer may be of any molecular weight, and may be branched or unbranched. The number of polymers attached to the anti-MUC16 antibody agent may vary, and if more than one polymer are attached, they can be the same or different molecules. In general, the number and/or type of polymers used for derivatization can be determined based on considerations including, but not limited to, the particular properties or functions of the anti-MUC16 antibody agent to be improved, whether the anti-MUC16 antibody agent derivative will be used in a therapy under defined conditions, etc. [00259] In some embodiments, conjugates of an anti-MUC16 antibody agent (such as a full-length anti-MUC16 antibody) or an antigen binding fragment thereof and nonproteinaceous moiety that may be selectively heated by exposure to radiation are provided. In some embodiments, the nonproteinaceous moiety is a carbon nanotube (Kam et al., Proc. Natl. Acad. Sci. USA 102: 11600-11605 (2005)). The radiation may be of any wavelength, and includes, but is not limited to, wavelengths that do not harm ordinary cells, but which heat the nonproteinaceous moiety to a temperature at which cells proximal to the anti-MUC16 antibody agent-nonproteinaceous moiety are killed. Antibody Conjugates [00260] In certain embodiments, provided herein are conjugates of the anti-MUC16 antibody agent or antigen binding fragments thereof as described herein, wherein said anti- MUC16 antibody agent or antigen binding fragments thereof is conjugated to one or more agents, e.g., an imaging agent or a cytotoxic agent. Also provided herein are bispecific antibody conjugates, wherein said bispecific antibody is conjugated to one or more agent, e.g., an imaging agent or a cytotoxic agent. Also provided herein are antibody heavy chain conjugates, wherein said antibody heavy chain is conjugated to one or more agent, e.g., an imaging agent or a cytotoxic agent. Also provided herein are antibody light chain conjugates, wherein said antibody light chain is conjugated to one or more agent, e.g., an imaging agent or a cytotoxic agent. Also provided herein are fusion protein conjugates, wherein said fusion protein is conjugated to an agent, e.g., an imaging agent or a cytotoxic agent. In certain embodiments, the agent is conjugated covalently or non-covalently. [00261] In certain embodiments, the imaging agent is a detectable label, such as, a chromogenic, enzymatic, radioisotopic, isotopic, fluorescent, toxic, chemiluminescent, nuclear magnetic resonance contrast agent or another label. [00262] The detectable group can be any material having a detectable physical or chemical property. Such detectable labels have been well-developed in the field of immunoassays and imaging. In general, almost any label useful in such methods can be applied to the present technology. Thus, a label is any composition detectable by spectroscopic, photochemical, biochemical, immunochemical, electrical, optical or chemical means. Labels useful in the practice of the present technology include magnetic beads (e.g., Dynabeads™), fluorescent dyes (e.g., fluorescein isothiocyanate, Texas red, rhodamine, and the like), radiolabels (e.g., ³H, ¹⁴C, ³⁵S, ¹²⁵I, ¹²¹I, ¹³¹I, ¹¹²In, ⁹⁹mTc), other imaging agents such as microbubbles (for ultrasound imaging), ¹⁸F, ¹¹C, ¹⁵O, ⁸⁹Zr, ⁸⁹Zr-DFO (for Positron emission tomography), ^99mTC, ¹¹¹In (for Single photon emission tomography), enzymes (e.g., horse radish peroxidase, alkaline phosphatase and others commonly used in an ELISA), and calorimetric labels such as colloidal gold or colored glass or plastic (e.g., polystyrene, polypropylene, latex, and the like) beads. Patents that describe the use of such labels include U.S. Pat. Nos. 3,817,837; 3,850,752; 3,939,350; 3,996,345; 4,277,437; 4,275,149; and 4,366,241, each incorporated herein by reference in their entirety and for all purposes. See also Handbook of Fluorescent Probes and Research Chemicals (6^th Ed., Molecular Probes, Inc., Eugene OR.). [00263] The label can be coupled directly or indirectly to the desired component of an assay according to methods well known in the art. As indicated above, a wide variety of labels can be used, with the choice of label depending on factors such as required sensitivity, ease of conjugation with the compound, stability requirements, available instrumentation, and disposal provisions. [00264] Non-limiting examples of suitable chromogenic labels include diaminobenzidine and 4-hydroxyazo-benzene-2-carboxylic acid. [00265] Non-limiting examples of suitable enzyme labels include malate dehydrogenase, staphylococcal nuclease, delta-5-steroid isomerase, yeast-alcohol dehydrogenase, alpha- glycerol phosphate dehydrogenase, triose phosphate isomerase, peroxidase, alkaline phosphatase, asparaginase, glucose oxidase, beta-galactosidase, ribonuclease, urease, catalase, glucose-6- phosphate dehydrogenase, glucoamylase, and acetylcholine esterase. [00266] Suitable radioisotopes are well known to those skilled in the art and include beta- emitters, gamma-emitters, positron-emitters, and x-ray emitters. Non-limiting examples of suitable radioisotopic labels include ³H, ¹⁸F, ¹¹¹In, ¹²⁵I, ¹³¹I, ³²P, ³³P, ³⁵S, ¹¹C, ¹⁴C, ⁵¹Cr, ⁵⁷To, ⁵⁸Co, ⁵⁹Fe, ⁷⁵Se, ¹⁵²Eu, ⁹⁰Y, ⁶⁷Cu, ²¹⁷Ci, ²¹¹At, ²¹²Pb, ⁴⁷Sc, ²²³Ra, ²²³Ra, ⁸⁹Zr, ¹⁷⁷Lu, and ¹⁰⁹Pd. In certain embodiments, ¹¹¹In is a preferred isotope for in vivo imaging as it avoids the problem of dehalogenation of ¹²⁵I or ¹³¹I-labeled anti-MUC16 antibody agents or antigen binding fragments thereof as described herein in the liver. In addition, ¹¹¹In has a more favorable gamma emission energy for imaging (Perkins et al, Eur. J. Nucl. Med.70:296-301 (1985); Carasquillo et al., J. Nucl. Med.25:281-287 (1987)). For example, ¹¹¹In coupled to monoclonal antibodies with 1-(P-isothiocyanatobenzyl)-DPTA has shown little uptake in non-tumorous tissues, particularly the liver, and therefore enhances specificity of tumor localization (Esteban et al., J. Nucl. Med.28:861-870 (1987)). [00267] Non-limiting examples of suitable non-radioactive isotopic labels include ¹⁵⁷Gd, ⁵⁵Mn, ¹⁶²Dy, ⁵²Tr, and ⁵⁶Fe. [00268] Non-limiting examples of suitable fluorescent labels include a ¹⁵²Eu label, a fluorescein label, an isothiocyanate label, a rhodamine label, a phycoerythrin label, a phycocyanin label, an allophycocyanin label, a Green Fluorescent Protein (GFP) label, an o- phthaldehyde label, and a fluorescamine label. [00269] Non-limiting examples of chemiluminescent labels include a luminol label, an isoluminol label, an aromatic acridinium ester label, an imidazole label, an acridinium salt label, an oxalate ester label, a luciferin label, a luciferase label, and an aequorin label. [00270] Non-limiting examples of nuclear magnetic resonance contrasting agents include heavy metal nuclei such as Gd, Mn, and iron. [00271] Techniques known to one of ordinary skill in the art for conjugating the above- described labels to said anti-MUC16 antibody agents or antigen binding fragments thereof of the present technology (e.g., bispecific antibodies, antibody heavy chains, antibody light chains, and fusion proteins) are described in, for example, Kennedy et at., Clin. CMm. Acta 70: 1-31 (1976), and Schurs et al, Clin. CMm. Acta 81: 1-40 (1977). Coupling techniques mentioned in the latter are the glutaraldehyde method, the periodate method, the dimaleimide method, the m-maleimidobenzyl- N-hydroxy-succinimide ester method, all of which methods are incorporated by reference herein. [00272] Nonlimiting examples of cytotoxic agents include a cytostatic or cytocidal agent, a radioactive metal ion, e.g., alpha-emitters, and toxins, e.g., pseudomonas exotoxin, abrin, cholera toxin, ricin A, and diphtheria toxin. [00273] In certain embodiments, the agent is a diagnostic agent. A diagnostic agent is an agent useful in diagnosing or detecting a disease by locating the cells containing the antigen. Useful diagnostic agents include, but are not limited to, radioisotopes, dyes (such as with the biotin-streptavidin complex), contrast agents, fluorescent compounds or molecules and enhancing agents (e.g., paramagnetic ions) for magnetic resonance imaging (MRI). U.S. Pat. No.6,331,175 describes MRI technique and the preparation of antibodies conjugated to a MRI enhancing agent and is incorporated in its entirety by reference. Preferably, the diagnostic agents are selected from the group consisting of radioisotopes, enhancing agents for use in magnetic resonance imaging, and fluorescent compounds. In order to load an anti- MUC16 antibody agent or antigen binding fragment thereof of the present technology with radioactive metals or paramagnetic ions, it may be necessary to react it with a reagent having a long tail to which are attached a multiplicity of chelating groups for binding the ions. Such a tail can be a polymer such as a polylysine, polysaccharide, or other derivatized or derivatizable chain having pendant groups to which can be bound chelating groups such as, for example, ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTP A), porphyrins, polyamines, crown ethers, bis- thiosemicarbazones, polyoximes, and like groups known to be useful for this purpose. Chelates are coupled to the antibodies using standard chemistries. The chelate is normally linked to the antibody by a group which enables formation of a bond to the molecule with minimal loss of immunoreactivity and minimal aggregation and/or internal cross-linking other, more unusual, methods and reagents for conjugating chelates to antibodies are disclosed in U.S. Pat. No.4,824,659 to Hawthorne, entitled "Antibody Conjugates," issued Apr.25, 1989, the disclosure of which is incorporated herein in its entirety by reference. Particularly useful metal-chelate combinations include 2- benzyl-DTPA and its monomethyl and cyclohexyl analogs, used with diagnostic isotopes for radio-imaging. The same chelates, when complexed with non-radioactive metals, such as manganese, iron and gadolinium are useful for MRI, when used along with an anti-MUC16 antibody agent or antigen binding fragment thereof provided herein. [00274] Macrocyclic chelates such as NOTA, DOTA, and TETA are of use with a variety of metals and radiometals, most particularly with radionuclides of gallium, yttrium and copper, respectively. Such metal-chelate complexes can be made very stable by tailoring the ring size to the metal of interest. Other ring-type chelates such as macrocyclic polyethers, which are of interest for stably binding nuclides, such as ²²³Ra for RAIT are encompassed herein. Pharmaceutical Compositions [00275] Also provided herein are compositions (such as pharmaceutical compositions, also referred to herein as formulations) comprising an anti-MUC16 antibody agent of the present technology (such as a full-length anti-MUC16 antibody or an antigen binding fragment thereof), nucleic acid encoding the antibody agent, vector comprising the nucleic acid encoding the antibody agent, or host cell comprising the nucleic acid or vector. In some embodiments, there is provided a pharmaceutical composition comprising an anti-MUC16 antibody agent disclosed herein and optionally a pharmaceutically acceptable carrier. [00276] Suitable formulations of the anti-MUC16 antibody agents of the present technology (such as anti-MUC16 antibodies, e.g., full-length anti-MUC16 antibodies or an antigen binding fragment thereof) are obtained by mixing an anti-MUC16 antibody agent having the desired degree of purity with optional pharmaceutically acceptable carriers, excipients or stabilizers (Remington's Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980)), in the form of lyophilized formulations or aqueous solutions. Acceptable carriers, excipients, or stabilizers are nontoxic to recipients at the dosages and concentrations employed, and include buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzyl ammonium chloride; hexamethonium chloride; benzalkonium chloride, benzethonium chloride; phenol, butyl or benzyl alcohol; alkyl parabens such as methyl or propylparaben; catechol; resorcinol; cyclohexanol; 3-pentanol; and m-cresol); low molecular weight (less than about 10 residues) polypeptides; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as olyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arginine, or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugars such as sucrose, mannitol, trehalose or sorbitol; salt-forming counter-ions such as sodium; metal complexes (e.g. Zn-protein complexes); and/or non-ionic surfactants such as TWEEN™, PLURONICS™ or polyethylene glycol (PEG). Exemplary formulations are described in WO98/56418, expressly incorporated herein by reference. Lyophilized formulations adapted for subcutaneous administration are described in WO97/04801. Such lyophilized formulations may be reconstituted with a suitable diluent to a high protein concentration and the reconstituted formulation may be administered subcutaneously to the individual to be treated herein. Lipofectins or liposomes can be used to deliver the anti-MUC16 antibody agents of this present technology into cells. [00277] The formulation herein may also contain one or more active compounds in addition to the anti-MUC16 antibody agent of the present technology (such as a full-length anti-MUC16 antibody or an antigen binding fragment thereof) as necessary for the particular indication being treated, preferably those with complementary activities that do not adversely affect each other. For example, it may be desirable to further provide an anti-neoplastic agent, a growth inhibitory agent, a cytotoxic agent, or a chemotherapeutic agent in addition to the anti-MUC16 antibody agent or an antigen binding fragment thereof as described herein. Such molecules are suitably present in combination in amounts that are effective for the purpose intended. The effective amount of such other agents depends on the amount of anti- MUC16 antibody agent present in the formulation, the type of disease or disorder or treatment, and other factors discussed above. These are generally used in the same dosages and with administration routes as described herein or about from 1 to 99% of the heretofore employed dosages. [00278] The anti-MUC16 antibody agents of the present technology (such as anti-MUC16 antibodies, e.g., full-length anti-MUC16 antibodies or an antigen binding fragment thereof) may also be entrapped in microcapsules prepared, for example, by coacervation techniques or by interfacial polymerization, for example, hydroxymethylcellulose or gelatin-microcapsules and poly-(methylmethacylate) microcapsules, respectively, in colloidal drug delivery systems (for example, liposomes, albumin microspheres, microemulsions, nanoparticles and nanocapsules) or in macroemulsions. Sustained-release preparations may be prepared. [00279] Sustained-release preparations of the anti-MUC16 antibody agents of the present technology (such as anti-MUC16 antibodies, e.g., full-length anti-MUC16 antibodies or an antigen binding fragment thereof) can be prepared. Suitable examples of sustained-release preparations include semipermeable matrices of solid hydrophobic polymers containing the antibody agent (or antigen binding fragment thereof), which matrices are in the form of shaped articles, e.g., films, or microcapsules. Examples of sustained-release matrices include polyesters, hydrogels (for example, poly(2-hydroxyethyl-methacrylate ), or poly(vinylalcohol)), polylactides (U.S. Pat. No.3,773,919), copolymers of L-glutamic acid and ethyl-L-glutamate, non-degradable ethylene-vinyl acetate, degradable lactic acid-glycolic acid copolymers such as the LUPRON DEPOT^TM (injectable microspheres composed of lactic acid-glycolic acid copolymer and leuprolide acetate), and poly-D (-)-3-hydroxybutyric acid. While polymers such as ethylene-vinyl acetate and lactic acid-glycolic acid enable release of molecules for over 100 days, certain hydro gels release proteins for shorter time periods. When encapsulated antibody agents remain in the body for a long time, they can denature or aggregate as a result of exposure to moisture at 37 °C, resulting in a loss of biological activity and possible changes in immunogenicity. Rational strategies can be devised for stabilization of anti-MUC16 antibody agents depending on the mechanism involved. For example, if the aggregation mechanism is discovered to be intermolecular S-S bond formation through thio-disulfide interchange, stabilization can be achieved by modifying sulfhydryl residues, lyophilizing from acidic solutions, controlling moisture content, using appropriate additives, and developing specific polymer matrix compositions. [00280] In some embodiments, the anti-MUC16 antibody agent of the present technology (such as a full-length anti-MUC16 antibody) or an antigen binding fragment thereof is formulated in a buffer comprising a citrate, NaCl, acetate, succinate, glycine, polysorbate 80 (Tween 80), or any combination of the foregoing. In some embodiments, the anti-MUC16 antibody agent or an antigen binding fragment thereof as described herein is formulated in a buffer comprising about 100 mM to about 150 mM glycine. In some embodiments, the anti- MUC16 antibody agent or an antigen binding fragment thereof as described herein is formulated in a buffer comprising about 50mM to about 100 mM NaCl. In some embodiments, the anti-MUC16 antibody agent or an antigen binding fragment thereof as described herein is formulated in a buffer comprising about 10mM to about 50 mM acetate. In some embodiments, the anti-MUC16 antibody agent or an antigen binding fragment thereof as described herein is formulated in a buffer comprising about 10mM to about 50 mM succinate. In some embodiments, the anti-MUC16 antibody agent or an antigen binding fragment thereof as described herein is formulated in a buffer comprising about 0.005% to about 0.02% polysorbate 80. In some embodiments, the anti-MUC16 antibody agent or an antigen binding fragment thereof as described herein is formulated in a buffer having a pH between about 5.1 and 5.6. In some embodiments, the anti-MUC16 antibody agent or an antigen binding fragment thereof as described herein is formulated in a buffer comprising 10 mM citrate, 100 mM NaCl, 100mM glycine, and 0.01% polysorbate 80, wherein the formulation is at pH 5.5. [00281] The formulations to be used for in vivo administration must be sterile. This is readily accomplished by, e.g., filtration through sterile filtration membranes. Methods of Treatment using Anti-MUC16 Antibody Agents of the Present Technology [00282] In certain embodiments, provided herein are methods for treating a cancer in a subject, in particular, a MUC16-positive cancer in a subject, comprising administering to the subject in need thereof a therapeutically effective amount of anti-MUC16 antibody agent or an antigen binding fragment thereof as described herein. In some embodiments, the anti- MUC16 antibody agent or antigen binding fragment thereof as described herein is administered at a therapeutically effective dose, such as a dose described herein. In some embodiments, the anti-MUC16 antibody agent or antigen binding fragment thereof as described herein is administered according to a method as described herein. In some embodiments, the anti-MUC16 antibody agent or antigen binding fragment thereof as described herein is administered in combination with one or more additional pharmaceutically active agents. [00283] For use of an anti-MUC16 antibody agent or antigen binding fragment thereof as described herein in a subject of a particular species, an anti-MUC16 antibody agent or antigen binding fragment thereof is used that binds to MUC16 of that particular species. For example, to treat a human, an anti-MUC16 antibody agent or antigen binding fragment thereof as described herein is used that binds to human MUC16. In some embodiments, the anti-MUC16 antibody agent or antigen binding fragment thereof as described herein is an immunoglobulin. [00284] In addition, for use of an anti-MUC16 antibody agent or antigen binding fragment thereof as described herein in a subject of a particular species, the anti-MUC16 antibody agent, preferably, the constant region of an anti-MUC16 antibody agent or antigen binding fragment thereof, is derived from that particular species. For example, to treat a human, an anti-MUC16 antibody agent or antigen binding fragment thereof as described herein can comprise an anti-MUC16 antibody agent or antigen binding fragment thereof that is an immunoglobulin, wherein the immunoglobulin comprises a human constant region. In some embodiments, the subject is a human. [00285] In some embodiments, the MUC16-positive cancer is ovarian cancer, lung cancer, pancreatic cancer, breast cancer, fallopian tube cancer, uterine (e.g., endometrial) cancer, primary peritoneum cancer or cancer of any other tissue that expresses the MUC16 receptor. [00286] In some embodiments, treatment can be to achieve beneficial or desired clinical results including, but not limited to, alleviation of a symptom, diminishment of extent of a disease, stabilizing (i.e., not worsening) of state of a disease, delay or slowing of disease progression, amelioration or palliation of the disease state, and remission (whether partial or total), whether detectable or undetectable. In a specific embodiment, "treatment" can also be to prolong survival as compared to expected survival if not receiving treatment. In some embodiments, the administration of an anti-MUC16 antibody agent or an antigen binding fragment thereof described herein, or a pharmaceutical composition described herein to a subject with cancer (e.g., ovarian cancer, lung cancer, pancreatic cancer, breast cancer, fallopian tube cancer, uterine (e.g., endometrial) cancer, or primary peritoneum cancer, or cancer of any other tissue that expresses the MUC16 receptor) achieves at least one, two, three, four or more of the following effects: (i) the reduction or amelioration of the severity of one or more symptoms of cancer; (ii) the reduction in the duration of one or more symptoms associated with cancer; (iii) the prevention in the recurrence of a symptom associated with cancer; (iv) the reduction in hospitalization of a subject; (v) a reduction in hospitalization length; (vi) the increase in the survival of a subject; (vii) the enhancement or improvement of the therapeutic effect of another therapy; (viii) the inhibition of the development or onset of one or more symptoms associated with cancer; (ix) the reduction in the number of symptoms associated with cancer; (x) improvement in quality of life as assessed by methods well known in the art; (x) inhibition of the recurrence of a tumor; (xi) the regression of tumors and/or one or more symptoms associated therewith; (xii) the inhibition of the progression of tumors and/or one or more symptoms associated therewith; (xiii) a reduction in the growth of a tumor; (xiv) a decrease in tumor size (e.g., volume or diameter); (xv) a reduction in the formation of a newly formed tumor; (xvi) prevention, eradication, removal, or control of primary, regional and/or metastatic tumors; (xvii) a decrease in the number or size of metastases; (xviii) a reduction in mortality; (xix) an increase in relapse free survival; (xx) the size of the tumor is maintained and does not increase or increases by less than the increase of a tumor after administration of a standard therapy as measured by conventional methods available to one of skill in the art, such as magnetic resonance imaging (MRI), dynamic contrast-enhanced MRI (DCE-MRI), X-ray, and computed tomography (CT) scan, or a positron emission tomography (PET) scan; and/or (xxi) an increase in the length of remission in patients. Treatment can be to achieve one or more of the foregoing. [00287] A subject treated in accordance with the methods provided herein can be any mammal, such as a rodent, a cat, a canine, a horse, a cow, a pig, a monkey, a primate, or a human, etc. In some embodiments, the subject is a human. In some embodiments, the subject is a canine. [00288] In certain embodiments, a subject treated in accordance with the methods provided herein has been diagnosed with a MUC16-positive cancer, including but not limited to, ovary, lung, pancreas, breast, uterine, fallopian tube, or primary peritoneum cancer, or cancer of any other tissue that expresses the MUC16. Diagnostic Uses [00289] In certain embodiments, anti-MUC16 antibody agents or antigen binding fragments thereof described herein can be used for diagnostic purposes to detect, diagnose, or monitor a condition described herein (e.g., a condition involving MUC16-positive cancer cells). In certain embodiments, anti-MUC16 antibody agents or antigen binding fragments thereof for use in diagnostic purposes are labeled. [00290] In certain embodiments, provided herein are methods for the detection of a condition described herein comprising (a) assaying the expression of MUC16 or a fragment thereof in cells or a tissue sample of a subject using one or more anti-MUC16 antibody agents or antigen binding fragments thereof described herein; and (b) comparing the expression level of MUC16 or the fragment thereof with a control level, for example, levels in normal tissue samples (e.g., from a subject not having a condition described herein, or from the same patient before onset of the condition), whereby an increase or decrease in the assayed level of MUC16 or the fragment thereof expression compared to the control level of MUC16 or the fragment thereof expression is indicative of a condition described herein. [00291] Antibodies described herein can be used to assay the levels of MUC16 or a fragment thereof in a biological sample using classical immunohistological methods as described herein or as known to those of skill in the art (e.g., see Jalkanen et al., J. Cell. Biol. 101: 976-985 (1985); and Jalkanen et al., J. Cell. Biol.105:3087-3096 (1987)). Other antibody-based methods useful for detecting protein gene expression include immunoassays, such as the enzyme linked immunosorbent assay (ELISA) and the radioimmunoassay (RIA). Suitable antibody assay labels are known in the art and include enzyme labels, such as, glucose oxidase; radioisotopes, such as iodine (¹²⁵I, 121I), carbon (¹⁴C), sulfur (³⁵S), tritium (³H), indium (¹²¹In), and technetium (⁹⁹Tc); luminescent labels, such as luminol; and fluorescent labels, such as fluorescein and rhodamine, and biotin. In some embodiments, the assay labels are conjugated to the anti-MUC16 antibody agents or antigen binding fragment thereof provided herein for direct detection. In some embodiments, the assay labels are conjugated to a secondary antibody that binds to an anti-MUC16 antibody agents or antigen binding fragment thereof provided herein. The secondary antibody type is selected according to the class of the primary antibody (e.g., IgG or IgM), the source host, and the kind of label which is preferred. In some embodiments, the secondary antibody is a class or isotype specific antibody (e.g., IgG, IgM, IgA, IgE or IgG). In some embodiments, the secondary antibody is a subclass specific antibody (e.g., IgG1, IgG2, IgG2, IgG4, IgA1, or IgA2). In some embodiments, the secondary antibody binds to one or more classes or subclasses of antibodies. In some embodiments, the secondary antibody binds to the heavy chain of the primary antibody. In some embodiments, the secondary antibody binds to the light chain of the primary antibody. In some embodiments, the secondary antibody binds to a kappa light chain of the primary antibody. In some embodiments, the secondary antibody binds to a lambda light chain of the primary antibody. In some embodiments, the secondary antibody is an anti-Fc or an anti-F(ab) or anti-(Fab')2 fragment antibody. In some embodiments, the secondary antibody is a rabbit, mouse, goat, donkey or chicken antibody. [00292] In certain embodiments, monitoring of a condition described herein (e.g., a MUC16- positive cancer), is carried out by repeating the method for diagnosing for a period of time after initial diagnosis. [00293] Presence of the labeled molecule can be detected in the subject (i.e., in vivo) using methods known in the art for in vivo scanning. Skilled artisans will be able to determine the appropriate method for detecting a particular label. Methods and devices that may be used in the diagnostic methods of the present technology include, but are not limited to, computed tomography (CT), whole body scan such as position emission tomography (PET), magnetic resonance imaging (MRI), and sonography. [00294] Also disclosed herein is a method for detecting cancer in a subject in vivo comprising (a) administering to the subject an effective amount of any of the anti-MUC16 constructs disclosed herein, wherein the anti-MUC16 construct is configured to localize to a cancer cell expressing MUC16 and is labeled with a radioisotope; and (b) detecting the presence of a tumor in the subject by detecting radioactive levels emitted by the anti-MUC16 construct that are higher than a reference value, optionally wherein the radioisotope is ⁸⁹Zr- desferrioxamine B (DFO). In some embodiments, the subject is diagnosed with or is suspected of having cancer. Additionally or alternatively, in some embodiments, the radioactive levels emitted by the anti-MUC16 construct are detected using positron emission tomography or single photon emission computed tomography. In any of the preceding embodiments, the method further comprises administering to the subject an effective amount of an immunoconjugate comprising an anti-MUC16 construct of the present technology conjugated to a radionuclide. The radionuclide may be an alpha particle-emitting isotope, a beta particle-emitting isotope, an Auger-emitter, or any combination thereof. Delivery of Anti-MUC16 Antibody Agents [00295] An anti-MUC16 antibody agent or antigen binding fragment thereof as described herein, or composition containing, or cells expressing the antibodies, or antigen binding fragments thereof, described herein may be delivered to a subject by a variety of routes. These include, but are not limited to, parenteral, intranasal, intratracheal, oral, intradermal, topical, intramuscular, intraperitoneal, transdermal, intravenous, intratumoral, conjunctival and subcutaneous routes. Pulmonary administration can also be employed, e.g., by use of an inhaler or nebulizer, and formulation with an aerosolizing agent for use as a spray. In one embodiment, an anti-MUC16 antibody agent or antigen binding fragment thereof, or a composition described herein is administered parenterally to a subject. In some embodiments, said parenteral administration is intravenous, intramuscular, or subcutaneous. [00296] The amount of an anti-MUC16 antibody agent or antigen binding fragment thereof as described herein, or composition which will be effective in the treatment and/or prevention of a condition will depend on the nature of the disease, and can be determined by standard clinical techniques. [00297] The precise dose to be employed in a composition will also depend on the route of administration, and the type of cancer, and should be decided according to the judgment of the practitioner and each subject's circumstances. For example, effective doses may also vary depending upon means of administration, target site, physiological state of the patient (including age, body weight and health), whether the patient is human or animal, other medications administered, or whether treatment is prophylactic or therapeutic. Treatment dosages are optimally titrated to optimize safety and efficacy. [00298] In certain embodiments, an in vitro assay is employed to help identify optimal dosage ranges. Effective doses may be extrapolated from dose response curves derived from in vitro or animal model test systems. [00299] For an anti-MUC16 antibody agent or an antigen binding fragment thereof as described herein, the dosage may range from about 0.0001 to 100 mg/kg, and more usually 0.01 to 15 mg/kg, of the patient body weight. For example, dosages can be 1 mg/kg body weight, 10 mg/kg body weight, or within the range of 1-10 mg/kg or in other words, 70 mg or 700 mg or within the range of 70- 700 mg, respectively, for a 70 kg patient. Generally, human antibodies have a longer half-life within the human body than antibodies from other species due to the immune response to the foreign polypeptides. Thus, lower dosages of human antibodies and less frequent administration is often possible. [00300] In certain embodiments, such as in the administration of engineered cells expressing the antibodies or antigen binding fragments thereof, or CARs, a subject is administered to the subject at a range of about one million to about 100 billion cells, such as, e.g., 1 million to about 50 billion cells (e.g., about 5 million cells, about 25 million cells, about 500 million cells, about 1 billion cells, about 5 billion cells, about 20 billion cells, about 30 billion cells, about 40 billion cells, or a range defined by any two of the foregoing values), such as about 10 million to about 100 billion cells (e.g., about 20 million cells, about 30 million cells, about 40 million cells, about 60 million cells, about 70 million cells, about 80 million cells, about 90 million cells, about 10 billion cells, about 25 billion cells, about 50 billion cells, about 75 billion cells, about 90 billion cells, or a range defined by any two of the foregoing values), and in some cases about 100 million cells to about 50 billion cells (e.g., about 120 million cells, about 250 million cells, about 350 million cells, about 450 million cells, about 650 million cells, about 800 million cells, about 900 million cells, about 3 billion cells, about 30 billion cells, about 45 billion cells) or any value in between these ranges. In some embodiments, the dose of total cells and/or dose of individual sub- populations of cells is within a range of between at or about 10⁴ and at or about 10⁹ cells/kilograms (kg) body weight, such as between 10⁵ and 10⁶ cells / kg body weight, for example, at or about 1 × 10⁵ cells/kg, 1.5 × 10⁵ cells/kg, 2 × 10⁵ cells/kg, or 1 × 10⁶ cells/kg, 2 × 10⁶ cells/kg, 5 × 10⁶ cells/kg, or 10 × 10⁶ cells/kg body weight. For example, in some embodiments, the cells are administered at, or within a certain range of error of, between at or about 10⁴ and at or about 10⁹ T cells/kilograms (kg) body weight, such as between 10⁵ and 10⁷ T cells / kg body weight. [00301] An anti-MUC16 antibody agent or antigen binding fragment thereof as described herein can be administered on multiple occasions. Intervals between single dosages can be 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 6 months, 1 year, or 2 years. Combination Therapies [00302] In some embodiments, the methods provided herein for treating cancer (e.g., ovarian cancer, pancreatic cancer, lung cancer, breast cancer, fallopian tube cancer, uterine (e.g., endometrial) cancer, or primary peritoneum cancer) in a subject, comprising administering to a subject in need thereof a pharmaceutical composition comprising an anti- MUC16 antibody agent or an antigen binding fragment thereof described herein, further comprise administering to the subject one or more additional therapeutic agents. In some embodiments, the additional therapeutic agent is for treating the cancer in the subject (e.g., ovarian cancer, pancreatic cancer, lung cancer, breast cancer, fallopian tube cancer, uterine (e.g., endometrial) cancer, and primary peritoneum cancer). In some embodiments, the additional therapeutic agent is for treating any side effects of treatment with an anti-MUC16 antibody agent or an antigen binding fragment thereof described herein. [00303] In some embodiments, the additional agent is an agent used to treat ovarian cancer. In some embodiments, the additional agent is an agent used to treat pancreatic cancer. In some embodiments, the additional agent is an agent used to treat lung cancer. In some embodiments, the additional agent is an agent used to treat breast cancer. In some embodiments, the additional agent is an agent used to treat fallopian tube cancer. In some embodiments, the additional agent is an agent used to treat uterine (e.g., endometrial) cancer. In some embodiments, the additional agent is an agent used to treat primary peritoneum cancer. [00304] An anti-MUC16 antibody agent or antigen binding fragment thereof described herein can be administered with an additional therapeutic agent concurrently or sequentially (before and/or after). The antibody or antigen binding fragment thereof and the additional therapeutic agent can be administered in the same or different compositions, and by the same or different routes of administration. A first therapy (which is an anti-MUC16 antibody agent or an antigen binding fragment thereof described herein, or the additional therapeutic agent) can be administered prior to (e.g., 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, or 12 weeks before), concomitantly with, or subsequent to (e.g., 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, or 12 weeks after) the administration of the second therapy (the anti-MUC16 antibody agent or an antigen binding fragment thereof described herein, or the additional therapeutic agent) to a subject with cancer (e.g., ovarian cancer, pancreatic cancer, lung cancer, breast cancer, fallopian tube cancer, uterine (e.g., endometrial) cancer, and primary peritoneum cancer). In certain embodiments, an additional therapeutic agent administered to a subject in combination with an anti-MUC16 antibody agent or an antigen binding fragment thereof described herein is administered in the same composition (pharmaceutical composition). In other embodiments, an additional therapeutic agent administered in combination with an anti-MUC16 antibody agent or an antigen binding fragment thereof described herein is administered to a subject in a different composition than the anti-MUC16 antibody agent or an antigen binding fragment thereof described herein (e.g., two or more pharmaceutical compositions are used). Articles of Manufacture and Kits [00305] Also disclosed herein is provided an article of manufacture containing materials useful for the treatment of a cancer characterized by high MUC16 expression and/or high aerobic glycolysis (e.g., kidney cancer, cervical cancer, or prostate cancer), or for delivering an anti-MUC16 antibody agent of the present technology (such as a full-length anti-MUC16 antibody or antigen binding fragment thereof) to a cell expressing MUC16 on its surface. The article of manufacture can comprise a container and a label or package insert on or associated with the container. Suitable containers include, for example, bottles, vials, syringes, etc. The containers may be formed from a variety of materials such as glass or plastic. Generally, the container holds a composition which is effective for treating a disease or disorder described herein, and may have a sterile access port (for example the container may be an intravenous solution bag or a vial having a stopper pierceable by a hypodermic injection needle). At least one active agent in the composition is an anti-MUC16 antibody agent of the present technology. The label or package insert indicates that the composition is used for treating the particular condition. The label or package insert will further comprise instructions for administering the anti-MUC16 antibody agent composition of the present technology to the patient. Articles of manufacture and kits comprising combinatorial therapies described herein are also contemplated. [00306] Package insert refers to instructions customarily included in commercial packages of therapeutic products that contain information about the indications, usage, dosage, administration, contraindications and/or warnings concerning the use of such therapeutic products. In some embodiments, the package insert indicates that the composition is used for treating cancer (such as HCC, melanoma, lung squamous cell carcinoma, ovarian carcinoma, yolk sac tumor, choriocarcinoma, neuroblastoma, hepatoblastoma, Wilms’ tumor, testicular nonseminomatous germ cell tumor, gastric carcinoma, or liposarcoma). [00307] Additionally, the article of manufacture may further comprise a second container comprising a pharmaceutically acceptable buffer, such as bacteriostatic water for injection (BWFI), phosphate-buffered saline, Ringer's solution and dextrose solution. It may further include other materials desirable from a commercial and user standpoint, including other buffers, diluents, filters, needles, and syringes. [00308] Kits are also provided that are useful for various purposes, e.g., for treatment of a cancer characterized by high MUC16 expression and/or high aerobic glycolysis (e.g., kidney cancer, cervical cancer, or prostate cancer), or for delivering an anti-MUC16 antibody agent of the present technology (such as a full-length anti-MUC16 antibody or antigen binding fragment thereof) to a cell expressing MUC16 on its surface, optionally in combination with the articles of manufacture. Kits of the present technology include one or more containers comprising an anti-MUC16 antibody agent composition disclosed herein (or unit dosage form and/or article of manufacture), and in some embodiments, further comprise another agent (such as the agents described herein) and/or instructions for use in accordance with any of the methods described herein. The kit may further comprise a description of selection of individuals suitable for treatment. Instructions supplied in the kits of the present technology are typically written instructions on a label or package insert (e.g., a paper sheet included in the kit), but machine-readable instructions (e.g., instructions carried on a magnetic or optical storage disk) are also acceptable. [00309] For example, in some embodiments, the kit comprises a composition comprising an anti-MUC16 antibody agent of the present technology (such as a full-length anti-MUC16 antibody or antigen binding fragment thereof). In some embodiments, the kit comprises a) a composition comprising an anti-MUC16 antibody agent disclosed herein, and b) an effective amount of at least one other agent, wherein the other agent enhances the effect (e.g., treatment effect, detecting effect) of the anti-MUC16 antibody agent. In some embodiments, the kit comprises a) a composition comprising an anti-MUC16 antibody agent of the present technology, and b) instructions for administering the anti-MUC16 antibody agent composition to an individual for treatment of a cancer characterized by high MUC16 expression and/or high aerobic glycolysis (e.g., kidney cancer, cervical cancer, or prostate cancer). In some embodiments, the kit comprises a) a composition comprising an anti- MUC16 antibody agent of the present technology, b) an effective amount of at least one other agent, wherein the other agent enhances the effect (e.g., treatment effect, detecting effect) of the anti-MUC16 antibody agent, and c) instructions for administering the anti-MUC16 antibody agent composition of the present technology and the other agent(s) to an individual for treatment of a cancer characterized by high MUC16 expression and/or high aerobic glycolysis (e.g., kidney cancer, cervical cancer, or prostate cancer). The anti-MUC16 antibody agent of the present technology and the other agent(s) can be present in separate containers or in a single container. For example, the kit may comprise one distinct composition or two or more compositions wherein one composition comprises an anti- MUC16 antibody agent disclosed herein and another composition comprises another agent. [00310] In some embodiments, the kit comprises a nucleic acid (or set of nucleic acids) encoding an anti-MUC16 antibody agent of the present technology (such as a full-length anti- MUC16 antibody or antigen binding fragment thereof). In some embodiments, the kit comprises a) a nucleic acid (or set of nucleic acids) encoding an anti-MUC16 antibody agent of the present technology, and b) a host cell for expressing the nucleic acid (or set of nucleic acids). In some embodiments, the kit comprises a) a nucleic acid (or set of nucleic acids) encoding an anti-MUC16 antibody agent of the present technology, and b) instructions for i) expressing the anti-MUC16 antibody agent in a host cell, ii) preparing a composition comprising the anti-MUC16 antibody agent, and iii) administering the composition comprising the anti-MUC16 antibody agent to an individual for the treatment of a cancer characterized by high MUC16 expression and/or high aerobic glycolysis (e.g., kidney cancer, cervical cancer, or prostate cancer). In some embodiments, the kit comprises a) a nucleic acid (or set of nucleic acids) encoding an anti-MUC16 antibody agent of the present technology, b) a host cell for expressing the nucleic acid (or set of nucleic acids), and c) instructions for i) expressing the anti-MUC16 antibody agent in the host cell, ii) preparing a composition comprising the anti-MUC16 antibody agent, and iii) administering the composition comprising the anti-MUC16 antibody agent to an individual for the treatment of a cancer characterized by high MUC16 expression and/or high aerobic glycolysis (e.g., kidney cancer, cervical cancer, or prostate cancer). [00311] The kits of the present technology are in suitable packaging. Suitable packaging includes, but is not limited to, vials, bottles, jars, flexible packaging (e.g., sealed Mylar or plastic bags), and the like. Kits may optionally provide additional components such as buffers and interpretative information. The present application thus also provides articles of manufacture, which include vials (such as sealed vials), bottles, jars, flexible packaging, and the like. [00312] The instructions relating to the use of the anti-MUC16 antibody agent compositions generally include information as to dosage, dosing schedule, and route of administration for the intended treatment. The containers may be unit doses, bulk packages (e.g., multi-dose packages) or sub-unit doses. For example, kits may be provided that contain sufficient dosages of an anti-MUC16 antibody agent of the present technology (such as a full- length anti-MUC16 antibody or antigen binding fragment thereof) as disclosed herein to provide effective treatment of an individual for an extended period, such as any of a week, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 3 months, 4 months, 5 months, 7 months, 8 months, 9 months, or more. Kits may also include multiple unit doses of the anti-MUC16 antibody agent of the present technology and pharmaceutical compositions and instructions for use and packaged in quantities sufficient for storage and use in pharmacies, for example, hospital pharmacies and compounding pharmacies. [00313] Those skilled in the art will recognize that several embodiments are possible within the scope and spirit of the present technology. The present technology will now be described in greater detail by reference to the following non-limiting examples. The following examples further illustrate the present technology but, of course, should not be construed as in any way limiting its scope. EXAMPLES [00314] The present technology is further illustrated by the following Examples, which should not be construed as limiting in any way. Example 1: Methods [00315] Cell lines [00316] HEK293T/17 and ExpiCHO-S (Thermo Fisher Scientific, Waltham, MA) cell lines were used for protein expression. Ovarian cancer cell lines SKOV3 (MUC16 negative control), SKOV3-MUC16^ecto (isogenic MUC16 positive cell line), OVCAR3 (MUC16 positive), OVCAR3^MUC16k/o (MUC16 negative), OVCA-433 (MUC16 positive), and CAOV3 (MUC16 positive) were used for in vitro and in vivo experiments, as described in Rao et al., ACS Chem Biol 12: 2085-2096 (2017); Rao et al., PloS one 10: e0126633 (2015); and Rao et al., Mol Cancer Ther 10: 1939-1948 (2011), which are herein incorporated by references in their entireties. SKBR3 (breast cancer) cell line was purchased from ATCC. All cell lines were maintained in their original culturing conditions according to supplier guidelines and tested negative for mycoplasma contamination. Stable HEK293T/17 cells were generated by lentiviral transduction with a construct expressing pLenti-C-Myc-DDK-IRES-Puro (Origene), followed by selection with puromycin. All cell lines have been verified and are routinely tested for mycoplasma. [00317] Antibody Modeling for Humanization [00318] Antibody structure modelling was performed by ABodyBuilder as described in Leem et al., MAbs 8, 1259-1268 (2016), which is herein incorporated by reference in its entirety. The best output models by ABodyBuilder were overlayed in PyMoL to confirm homology. [00319] Humanized antibody affinity analysis [00320] Epitope binding assay was performed on ForteBio Octet QK(ForteBio, Fremont, CA) in 8-channel 96-well plate mode at a shake speed of 1000 rpm. Biotinylated MUC16- peptide at 5 μg/mL was loaded onto the biosensor tips for saturating SA binding sites for 900s. The sensor tips were dipped into kinetics buffer for 300s to remove the non-specific binding. Then the sensor tips with were exposed to the antibodies at 10 μg/mL for association to saturate its binding epitope. Lastly, the sensor tips were moved into kinetics buffer for 1800s to check dissociation. [00321] Functional analysis of humanized antibodies [00322] Matrigel invasion assay. Antibody inhibition of basement membrane invasion was determined via Matrigel invasion assay, as previously described in Rao et al., ACS Chem Biol 12: 2085-2096 (2017); and Rao et al., PloS one 10: e0126633 (2015). Briefly, OVCAR3, OVCAR-433 and CAOV3 cells were pretreated with a 10 μg/ml of the indicated antibodies prior to exposure to the Matrigel invasion chambers. Control chambers were set up with cells that had not been exposed to antibody. Each insert contained 10,000 cells per chamber. Both experimental and control chambers were set up in three biologic replicates. The number of invading cells was counted after a 48-hour incubation period. [00323] Antibody Drug Conjugate Assay. SKOV3, SKOV3-MUC16^ecto OVCAR3 and OVCAR3^MUC16k/o tumor cells were incubated with murine VK8-VcMMAE ADC, 4H11- VcMMAE ADC and human 4H11-VcMMAE ADC using oYo -Link (AlphaThera, Philadelphia, PA) for 72hours in triplicate wells and quantitated viable cells using Cell Titer- Glo (Promega, Madison, WI) and with a SpectraMax iD3 multi-mode microplate reader (Molecular Devices, California CA). All studies included at least 3 replicates. [00324] Chimeric Antigen Receptor T-cell assay. Human T cells were derived from fresh blood-derived leukocyte concentrate (Leukopack) obtained from Research Blood Components LLC (Waltham, MA). Mononuclear cells were separated using density gradient centrifugation with Accuprep (axis-Shield PoC AS, Oslo, Norway). T cells were isolated, activated, and expanded with 2μl/mL PHA (Sigma Aldrich, St. Louis, MO). T cells were cultured in RPMI 1640 in the presence of 10 ng/mL recombinant human IL-2 (Proleukin). Viable cells were enumerated using flow cytometry and CAR T-cell transduction efficiency was determined using anti-F(ab)2 antibody (R&D Biosystem, Minneapolis, MN, F0101B) following manufacturer’s protocol. For 4-hour cytotoxicity experiments, 4H28ζ CAR T-cells or controls were cultured with indicated tumor cells and evaluated for cytotoxicity by standard ⁵¹Cr release assay as previously described in M. C. Gong et al., Neoplasia 1: 123- 127 (1999), which is herein incorporated by reference in its entirety. For 72-hour luciferase- based cytotoxicity assays, 4H28ζ CAR T-cells or controls were cultured with indicated T- cells, and subsequently mixed with luciferase assay reagent (Promega, Madison, WI). Luminescence of the lysates was analyzed using a plate spectrophotometer. Specific cytolysis was calculated using the formula; % specific lysis = 100 × (sample lysis – spontaneous lysis)/(maximal lysis –spontaneous lysis). To evaluate cytokine secretion from cocultured cells, indicated CAR T-cells cocultured with SKOV3-MUC16^ecto or OVCAR3 cells, untransduced T-cells, and tumor cells alone were cultured for 72 hours. Supernatant was collected and centrifuged at 1800 rpm for 10-15 mins to remove any contaminating cells or debris. The cell-free supernatant was then transferred to a fresh tube and frozen at -80°C until further analysis. Cytokine detection was performed using the High Sensitivity 9-Plex Human ProcartaPlex™ Panel. (Thermo Fisher Scientific, Waltham, MA, EPXS090-12199- 901), and the Luminex 200 system according to the manufacturers protocol. For in vivo studies, female NSG mice age 8-12 weeks were purchased the Massachusetts General Hospital COX7 animal facility.1x10⁷ SKOV3-MUC16^ecto tumor cells were injected intraperitoneally (i.p.) on D0, and animals were untreated, treated with 2 ×10⁶ CAR T-cells i.p on day 14. All mice were monitored for survival and were euthanized when showing signs of distress. All murine studies were done in the context of a Massachusetts General Hospital Institutional Animal Care and Use Committee approved protocol (2018N000207). [00325] Construct design, cloning, and preparation of lentiviral particles [00326] Protein sequence information for the 4H11-scFv were based on descriptions of murine 4H11 at Memorial Sloan Kettering Cancer Center (MSKCC) in New York, USA and Eureka Therapeutics (Emeryville, CA). The DNA sequences encoding the 4H11varible regions and a five repeated flexible glycine/serine linker (GGGGS)5 between Heavy chain (VH: E1-S123) and Light chain (VL: D1-R113), [VH-linker (GGGGS)5-VL] were optimized for a scFv mammalian cell expression, and then synthesized commercially (Genewiz, South Plainfield, NJ). This construct was subcloned into the lentiviral vector with an N-terminal signal peptide. The sequence corresponding to the targeted flexible loop domain (26 residues ^31stL-G^6th from TM) as a MUC16^ecto domain was cloned into expression vector pMal-C5X (New England Biolabs, Ipswich, MA) for bacterial expression as a Maltose Binding Protein fusion protein. All 4H11-scFv variants and MBP-MUC16 variants were generated by QuikChange site-directed mutagenesis (Stratagene, La Jolla, California). The 3^rd generation lentiviral packaging plasmids; pMDLg/pRRE, pMD2.G, and pRSV-Rev were purchased from Addgene. All lentiviral particles were produced according to the manufacturer’s manual. Briefly, the lentiviral transfer vector and packaging plasmids were co-transfected using LentiTran (Origene, Rockville, MD) transfection reagent. After 48 hours of transfection, the supernatant from the medium was harvested, filtered with 0.45 μM PES filter (Thermo Fisher Scientific, Waltham, MA), and the lentiviral particles was stored -80 ℃ after lentivirus titration, concentration, and stabilization. [00327] Protein expression and purification [00328] Liter-scale cultures of HEK293T/17 were infected with high-titer viral stocks expressing the 4H11-scFv. The secreted 4H11-scFv from the medium was collected 48-60 hours post-infection. The supernatant was dialyzed with Buffer A (50 mM Tris/pH 8.0, 400 mM NaCl) and applied to Ni-NTA agarose beads (nitrilotriacetic acid, Qiagen, Hilden, Germany). After washing with Buffer A supplemented with 20 mM imidazole, bound proteins were eluted with Buffer A supplemented with 500 mM imidazole. The eluted fractions including the scFv proteins were pooled, and the protein was further purified by a Superdex-75 SEC (GE Healthcare). The 4H11-scFv was concentrated up to ~8 mg/ml using Amicon Ultra centrifugal filters (Millipore) and stored at -80 ℃ until used for further characterization or crystallization. About 1mg of the purified scFv was labeled with Alexa Fluor 488 carboxylic acid (Life Technologies, Carlsbad, CA) according to the manufacturer’s instructions. The fluorescence-labeled 4H11-scFv was further purified by Superdex-75 in 20 mM Hepes buffer with 200 mM NaCl. For production of the variant scFv proteins cloned using the same lentivector, liter-scale suspension cultures of ExpiCHO-S were transfected using the ExpiCHO-S expression system according to the manufacturer’s protocol (Thermo Fisher Scientific, Waltham, MA). The recombinant MBP-MUC16^ecto was expressed in the E. coli BL21-RIL (DE3) (Novagen) and purified using Amylose resin (New England Biolabs, Ipswich, MA) and a Superdex-75 column with an FPLC NGC Quest System (Bio-Rad, Hercules, CA). The variants of recombinant MBP-MUC16^ecto were prepared using a similar protocol. [00329] Analytical Size-exclusion Chromatography (SEC) and Isothermal Titration Calorimetry (ITC) [00330] Purified 4H11-scFv and MBP-MUC16^ecto were mixed at a molar ratio of ~2.0:1 to assemble the scFv-MUC16^ecto complex and incubated at 4 °C for 3 hours in buffer containing 50 mM Tris-HCl, pH 8.0, 200 mM NaCl. Each protein of 4H11-scFv and MBP-MUC16^ecto was incubated in the same buffer as a control. Protein complex was resolved using Superdex- 7510/300 GL SEC. Excess 4H11-scFv was separated by SEC in the same buffer. ITC was performed at 23 °C on an ITC200 calorimeter from Microcal/GE Life Sciences (Northampton, MA). The scFv samples were used as the titrant in the cell and MUC16 was used as titrants in the syringe. To control for heat or dilution effects, protein samples were dialyzed extensively against the titration buffer (50 mM Tris, pH 8.0, and 400 mM NaCl) prior to each titration. The commercially synthesized MUC16^ecto (26 residues) and MBP- MUC16^ecto were dissolved in the same buffer. The following concentrations were used for pair-wise titrations: 4H11-scFv (12.8 μM ) vs. synthesized MUC16-target (144 μM ); 4H11- scFv (12.8 μM ) vs. MBP-MUC16^ecto (130 μM), respectively. Data were analyzed using the Origin software package provided by the ITC manufacturer. The thermodynamic values reported are the average of three independent experiments. [00331] Thermal denaturation assay [00332] The thermal stability of 4H11-scFv, 4H11-scFv-MUC16-target peptide were measured using a fluorescence-based thermal shift assay on a Stepone real-time machine (Life Technologies, Carlsbad, CA). Immediately before the experiment, the protein (3.2 ug) was mixed with the fluorescent dye SYPRO Orange (Sigma-Aldrich) at multi pH conditions (pH 3.4 through 9.4). The samples were heated from 20 °C to 95 °C in ~50 min. The midpoint of the protein-melting curve (Tm) was determined using the analysis software provided by the instrument manufacturer. The data obtained from three independent experiments were averaged to generate the bar graph. The T_m of 4H11-scFv-MUC16^ecto at pH 3.4 could not be determined due to high fluorescence signal at starting temperature. The Tm of MUC16^ecto and the mutants were measured using a similar protocol. [00333] Cell-based assay for internalization of 4H11-scFv into the MUC16- overexpressed cells [00334] The purified 4H11-scFv was conjugated to Alexa fluor^® 488 fluorescent dye (Alexa-4H11-scFv) using a labeling kit in accordance with the manufacturer’s protocol (Invitrogen, Carlsbad, CA). Two MUC16 negative control (HEK293T and SKOV3) and two MUC16-positive (OVCAR3 and SKBR3) cell lines were seeded in a 6-well plate and incubated with fresh culture medium for 24 hours. Each cell was fixed, permeabilized, and blocked for 1 hour using ImageiT Fixation kit (Life Technologies, Carlsbad, CA) as per manufacturer’s instruction and then, incubated with Alexa-4H11-scFv (10 nM) for 30 min at 25 °C and washed three times with PBS buffer. Images were collected using a confocal microscope (Nikon Eclipse TE2000-S microscope). To investigate the internalization of 4H11-scFv antibody, OVCAR3 and SKBR3 were plated on independent 6-well plate at a density of 2 × 10⁵ and left 24 hours. The medium was removed, washed twice PBS buffer and replaced with Live Cell Imaging Solution (Invitrogen, Carlsbad, CA). The Alexa-4H11- scFv was first added for 30 min to the each well and washed twice with the imaging solution. The Alexa-350-WGA (5 ug/mL), binding to sialic acid and N-acetylglucosaminyl residues of cell membranes, was then prepared by manufacturer’s protocol. The imaging solution with Alexa-350-WGA was removed after 20 min incubation and then, washed three times. Fluorescent images for scFv tracking were taken every 12-hour, from 2h - 48 h, using the same confocal microscope. [00335] Crystallization [00336] Initial crystallization screens were performed using a Phoenix crystallization robot (Art Robbins Instruments) and high-throughput crystallization screen kits (Hampton Research, Aliso Viejo; CA, Qiagen, Hilden, Germany; or Emerald BioSystems, Bainbridge Island, WA), followed by extensive manual optimization. The best single crystals were grown at 18 °C by the hanging-drop vapor-diffusion method in a 1:1 (v/v) ratio of protein and reservoir, as follows. (1) 4H11-scFv was crystallized with a reservoir solution composed of 0.1M sodium citrate tribasic dihydrate (pH 5.0) and 20% polyethylene glycol (PEG) 4K. Micro-seeding was necessary to obtain single crystals. (2) 4H11-scFv-MUC16-target complex was crystallized using a reservoir of 0.1 M sodium citrate tribasic dihydrate (pH 5.0), 10 mM barium chloride dihydrate, and 27% methoxypolyethylene glycol 5000 (PEG MME 5K). [00337] Diffraction data collection and structure determination [00338] The crystals were cryo-protected in the original mother liquor supplemented with 20% (v/v) glycerol and flash-frozen in liquid nitrogen. X-ray diffraction data were collected 100 K at NE-CAT beam line 24-ID-E, Advanced Photon Source (APS). The data were processed with HKL2000 or iMOSFLM. Data collection statistics are summarized in FIG. 14. The structure of the 4H11-scFv antibody was determined by molecular replacement (MR) software Phaser using VH (PDB: 6ATT) and VL (PDB: 3OKK) as the search models. Subsequent structure of the 4H11-scFv in complex with MBP-MUC16^ecto was determined by molecular replacement using the determined 4H11-scFv structure as a model, and an MBP (PDB: 3VD8) as the search model. An MBP-MUC16^ecto was modeled into the corresponding structure during the refinement based on the 2Fo-Fc electron density maps and a combination with a partial peptide structure of the SEA domain (PDB: 1IVZ). The manual model building and refinements were performed in COOT and PHENIX in an iterative manner until satisfactory model statistics was achieved. The refinement progress was monitored with the free R value using a 5% randomly selected test set. The structures were validated through MolProbity and showed excellent stereochemistry. Structural refinement statistics are listed in FIG.14. [00339] Pull-down assay [00340] A series of MBP pull-down assays in vitro to determine a physical interaction among MBP-tagged MUC16-target (wt), its alanine mutants (D25A/R24A, D18A/G17A, or D25A/R24A/D18A/G17A) as a bait, 4H11-scFv (wt) and the mutants (S53A/D106A, Y246A/N247A, or S53A/D106A/Y246A/N247A) as a prey were performed in parallel in a buffer containing 50 mM Tris-HCl, pH 8.0, 400 mM NaCl, 1 mM EDTA and 1 mM DTT using Amylose resin, which is an affinity matrix used for the isolation of proteins fused to MBP at 4 °C for 3 hours. The resins were washed three times before boiling with the addition of SDS sample buffer, and further analyzed by 4-20% gradient SDS-PAGE. Each pull-down was performed in triplicate and a representative SDS-PAGE gel is shown. MBP- tagged Protein baits were pre-incubated with Amylose resins at 4 °C for 2 hours, and unbound proteins was washed away. The resins were equally divided for repeated experiments into small aliquots where each has ~20 μg of bound protein bait, and 4H11-scFv (wt) or the mutated 4H11-scFv prey proteins used at 2-fold molar excess over MBP- MUC16^ecto were added. All pull-down were performed using the same protocol. [00341] Statistical Analysis [00342] Survival curves were analyzed using Mantel–Cox (log-rank) test and other analysis were performed using unpaired two-tailed T test (p value <0.05 considered as significant). All calculations were performed using Prism 7 (GraphPad) software. Data represent means ± SEM. Example 2: Humanization of 4H11 Antibody [00343] The sequence of the m4H11 antibody (see M. Koneru, et al. J Transl Med 13: 102 (2015); Rao, et al., Appl Immunohistochem Mol Morphol 18: 462-472 (2010), which are herein incorporated by reference in their entireties) was used to search international IMmunoGeneTics (IMGT) database for the closest human antibody framework, and antibody structure modelling was performed by ABodyBuilder. The best output models were overlayed in PyMoL and the simulated structures were overlapped to identify and design amino acid substitutions for humanization (FIG.1A). Two alternative humanized heavy chains (H1 and H2) and two light chains (L1 and L2) were designed in this manner (FIG. 1B). The designed amino acids changes was expected to not affect the binding affinity of the antibody. Using the same simulation model, the predicted structures of the humanized antibodies are very close to the structure of the original antibody m4H11 (FIG.1C). The affinities of the resulting antibodies were confirmed against MUC16 peptides from the MUC16^ecto to establish the avidity of the modified antibodies (FIG.1D). All 4 of the human heavy chain and light chain combinations were more avid for the MUC16 peptide target than m4H11. Example 3: Functional Analysis of the h4H11 antibody [00344] The m4H11 anti-MUC16^ecto antibodies were known to recognize cellular MUC16 expression in Fluorescence Activated Cell Sorting and CAR T-cell applications. The therapeutic potential of humanized 4H11 (h4H11) against MUC16 bearing tumor cells was evaluated using a variety of therapeutic modalities. First, ability of H1L1, H1L2, H2L1, and H2L2 h4H11 antibodies to inhibit Matrigel invasion of MUC16-positive tumor cell lines OVCAR3, OVCA-433, and CAOV3 was examined. The indicated cell lines were incubated with 10 µg/ml of murine 18C6 antibody, H1L1, H1L2, H2L1, or H2L2 for 48 hours. The number of invading cells in the absence (control) or presence of each of the antibodies are enumerated in FIG.2A. Using 18C6 as a positive control, and H1L1, H1L2, and H2L1 antibodies significantly inhibited migration of OVCAR3, OVCA-433 and CAOV3 cells compared to untreated control tumor cells (p = 0.001, p < 0.0001 and p = 0.001) (see Rao et al., ACS Chem Biol 12: 2085-2096 (2017)). The antibody h4H11 H2L2 consistently inhibited invasion of OVCA-433 and CAOV3 cell lines (p < 0.0001 and p = 0.001) but not invasion by OVCAR3 cells. Next, the variable heavy and light chain sequences (scFv) of h4H11 H1L2 and H2L1 were used to generate second-generation CD28-costimulated CAR T-cells; 4H28ζ- H1L2 and 4H28ζ-H2L1 respectively (FIG.2B). OVCAR3 and SKOV3-MUC16^ecto tumor cells were co-cultured with 4H28ζ-H1L2 or 4H28ζ-H2L1 for 4 hours and assessed for cytotoxicity using a chromium (⁵¹Cr) release assay. Both 4H28ζ-H1L2 and 4H28ζ-H2L1 showed dose-dependent cytotoxicity against OVCAR3 and SKOV3-MUC16^ecto tumor cells over a range of effector to target ratios (E:T). No significant cytotoxicity was detected using control CD19-directed CAR T-cells (FIG.2B). Due to the similarity in efficacy between 4H28ζ-H1L2 and 4H28ζ-H2L1, 4H28ζ-H1L2 was used for the reminder of the present experiments. Cytotoxicity of 4H28ζ-H1L2 over 72 hours were evaluated against OVCAR3 (FIG.2C) and SKOV3-MUC16^ecto cells (FIG.2D) and found significant dose-dependent cytotoxicity compared to untransduced T-cells (p < 0.05). Cytokine analysis of 4H28ζ-H1L2 cocultured with SKOV3-MUC16^ecto and OVCAR3 over 72 hours showed increased IL-2, IL- 6, IL-17, IFN-γ, and TNF-α secretion (FIG.2E). To evaluate the in vivo efficacy of 4H28ζ- H1L2, SKOV3-MUC16^ecto tumor-bearing female mice 14-days after they had been inoculated with tumor cells were treated (i.p/i.p). As shown in FIG.2F, 4H28ζ-H1L2 significantly prolonged survival in treated mice. Another common antibody therapeutic modality is antibody-drug complexes. The m4H11 antibody was first compared against the juxtamembrane portion of MUC16 to the more common CA125 epitope targeting class of anti- MUC16 antibodies. For this purpose, VK8, a well characterized, M11 class antibody, was used to compare to the m4H11 (see K. O. Lloyd, et al., International journal of cancer 71: 842-850 (1997); K. Nustad et al., Tumour Biol 23: 303-314 (2002), which are incorporated by reference herein in their entireties). The VK8 based ADC^MMAE, with multiple antigens in the MUC16 sequence, had much more off target effects than the m4H11based ADC against the wild type SKOV3 cells expressing no MUC16 (FIG.2G). In SKOV3-MUC16^ecto cells with expression of 114 amino acids of the MUC16 carboxyterminal region there was specific activity by the human m4H11_VcMMAE H11 lacking the CA125 epitope but the mVK8_VcMMAE ADC still showed similar off target effects (FIG 2H) (see Rao, et al., Appl Immunohistochem Mol Morphol 18: 462-472 (2010)). Finally, MMAE antibody-drug conjugates against OVCAR3 cells and an OVCAR3^MUC16k/o cell line without MUC16 was evaluated, using m4H11 and h4H11 (H2L1) antitbodies as carriers (FIGs.2I- 2J). In this setting, neither m4H11 or h4H11 had significant toxicity in the OVCAR3MUC16k/o line (FIG.2I) but the h4H11^MMAE ADC was substantially more effective that the parent m4H11^M

^E antibody ADC (FIG.2J). Taken together, there was strong function evidence that the h4H11 was superior to the parent murine antibody in CAR and ADC applications. To explain this observation and further optimize specific MUC16 ectodomain targeting, the structural determinants of antibody binding to the MUC16 juxtamembrane area was evaluated. Example 4: Construction and optimization of 4H11-scFv and MBP-MUC16^ecto [00345] For crystallization studies, an H2L14H11-scFv consisting of the variable heavy (V_H) and light chain (V_L) of its parent IgG connected by a repeated glycine-serine linker was designed (FIG.8A). _{[00346] Exemplary anti-MUC16 antibody VH and VL domain sequences of} ^{h4H11 are provided below:}

The VH CDR1-3 and VL CDR1-3 sequences are underlined. [00347] The linker length, optimized to 25 amino acids (Gly-Gly-Gly-Gly-Ser)_5, showed high stability and correct orientation as a monomeric form with excellent MUC16 binding. The scFv, [VH-linker (GGGGS)5-VL], was secreted into the culture media by the signal peptide located at the N-terminal and then, purified as pure homogeneous monomers using Ni-affinity and SEC. The MUC16^ecto domain, composed of 26 peptides, was fused with a MBP to facilitate its stability and crystallization (FIG.8A). The MBP fusion protein was recombinantly expressed in bacterial (E. coli) system and purified by a series of chromatographic procedures of MBP-affinity, Size Exclusion Chromatography (SEC) to high purity and prepared for the further experiments. _{[00348] Exemplary} ^{h4H11 scFv parent sequences are provided below:}

Boldface = residues for saturated mutagenesis to improve h4H11-MUC16 binding Example 5: The h4H11-scFv binds to MUC16^ecto and overexpressed-MUC16 on cancer cells [00349] Expression using two mammalian systems via lentiviral-based protein production by HEK293T/17 and transient protein production by ExpiCHO-S cells as a suspension culture were evaluated. Both showed similar expression levels of up to ~3 mg/Liter. Then, proteins were purified using Ni-affinity and SEC to examine the protein-protein interaction with MUC16^ecto in vitro. It was important to confirm that the single chain construction had similar interactive properties to the full length h4H11 antibody. To confirm the h4H11-scFv and MUC16^ecto interactions, four independent experiments were performed: (1) analytical SEC, (2) in vitro pull-down assay, (3) isothermal titration calorimetry (ITC), and (4) visualization of Alexa-labeled scFv’s on the cell surface. Analytical SEC was conducted to characterize the interactions between h4H11-scFv and MUC16 (MBP-MUC16^ecto) (FIGs. 8A-8F). As expected, the scFv monomers could be distinguished from the scFv-MUC16^ecto complex, which was eluted 2.4 mL earlier than the excess scFv and 1.3 mL earlier than unbound MBP-MUC16^ecto, respectively. Each eluted volume of the scFv, MBP- MUC16^ecto, and the scFv-MBP MUC16^ecto complex were 12.6 mL, 11.5 mL, and 10.2 mL based on Superdex 7510/300 GL, respectively (FIGs.9A-9E). [00350] Next, the scFv binding to MUC16-overexpressing cancer cells was investigated through fixed or live cell imaging analysis; and if internalization took place was also evaluated. Alexa-fluorescence conjugated scFv (Alexa-4H11-scFv) was prepared to verify cell-surface binding of the scFv, while Alexa-350-WGA fluorescent dye is used to identify the cell membrane. Control cell lines, HEK293T/17 and SKOV3, showed no immunofluorescence on the fixed cell imaging (FIG.8B). However, bright green fluorescent images were found on the cell membranes of both OVCAR3 and SKBR3 which express MUC16, indicating that the scFv can specifically bind to native MUC16 expressed on cancer cells (FIG.8B). Live cell imaging was performed to track the internalization during multi- point time course (2h - 48h). Confocal imaging revealed that the scFv could be localized into the cell membranes with gradual increase of enhanced fluorescence (FIG.8C). ITC experiments were performed as a label-free interaction analysis. Two types of MUC16^ecto, one was a commercially synthesized 26 amino acids of MUC16^ecto and the other was recombinantly expressed MBP-MUC16^ecto, were examined to investigate if the peptide itself functions as an antigen. The n4H11-scFv binds MBP-MUC16^ecto or the synthesized peptide with dissociation constant (K_d) of ~ 2 ± 1 nM or ~ 1.4 ± 0.5 nM at pH 7.4, respectively (FIGs.8D-8E). The complex form was further supported by an in vitro pull-down assay using h411-scFv as a prey and MBP-MUC16^ecto as a bait (FIG.8F). Taken together, these results indicate that h4H11-scFv binds to MUC16-expressing cells, and suggests that the complex can be internalized. Example 6: Synergistic action of V_H -V_L depending upon MUC16^ectoh [00351] To further understand the molecular basis of the antibody binding interaction, the crystal structures of a h4H11-scFv and a h4H11-scFv-MUC16^ecto complex (^31thLQNFTLDRSSVLVDGYSPNRNEPLTG^6th; numbering from TM) at 2.36 Å and 2.47 Å, respectively, were determined (FIGs.3A-3C, and FIG.14). The complex was crystallized at pH 5.0, which is a physiologically relevant pH, both inside an endosome and in a hypoxic tumor environment. A complete structure of the complex was built except for two regions; the linker domain composed of Gly-Ser repeats and the C-terminal 7 residues (RNEPLTG) of MUC16^ecto sequences, that have no visible electron density probably due to high structural flexibility. Regardless, the 7 residues placed outside of the interface of the complex did not affect the interaction based on the structural analysis. [00352] MUC16^ecto directly interacts with CDR2-CDR3 on V_H through a relatively large interface area (~617 Ų), covering residues in two β- turns (^31stLQNFTLDRSS^22nd) including the N29^th glycosylation site (FIGs.3D-3E). In contrast, the binding interface area for V_L was smaller (~301 Ų), mainly including residues in the C-terminal loop including a surface β- hairpin (FIG.3F). These structural findings at the interface region may explain the higher binding affinity of VH in comparison to VL and also suggest that VH may be superior at stabilizing the structure of the complex. These interactions are enlarged for clarity to better illustrate the interaction residues (FIGs.3G-3H) Example 7: Antigen-dependent structural dynamics of h4H11-scFv [00353] Each domain (V_H or V_L) contains three CDRs and four framework regions (FRs) that support each CDR by strengthening antigen surface recognition. Structural analysis demonstrated that all six CDR regions are composed of 5 flexible loop-like coiled coil and a short-helix (α₁) and canonical disulfide bonds at the C22-C96 of V_H and C23-C94 of V_L were formed to improve the correct folding and thermo-stability. The overall architecture of the scFv is ~37 Å tall and ~ 46 Å wide between the tips of neighboring loops (FIG.4A). The V_H-V_L complex is likely relatively independent of each other, and associate only through the interface. The V_H domain of the scFv is composed of 11 β strands (β1–β11) and 2 short helices (α1-α2), while 13 β strands (β1–β13) and one short helix (α1) for VL. C-terminal of VH is connected to the repeated Gly-Ser linker loop and following VL begins from D149 residue (FIGs.4B-4C). The crystal structure also revealed that the straight distance from the C- terminal of V_H to N-terminal of V_L was ~ 32.0 Å, corresponding to a distance of approximately 13 amino acid length (~2.7 Å per aa) (FIGs.4A-4C). It is worth noting that the number of amino acids constituting the linker region between V_H-V_L must be more than 13 residues to prevent an inactive or aggregated form due to the insecure space for interaction between VH-VL. A buried solvent-accessible area of 926 Ų (calculated by PDBePISA v1.52), forming hydrogen bonds and an energetically cation- π interaction (~ 5.6 Å distance) between cationic sidechain (R44 at V_H) and an aromatic sidechain (F251 at V_L) may improve overall stability between VH-VL (FIGs.4D-4E). [00354] A dramatic conformational change including reduced interactions and a new hydrogen bond between Q115 of V_H and S197 of V_L at the interface area between V_H-V_L during ligand MUC16^ecto binding was observed (FIG.11F). This clearly shows the structural dynamics of 4H11-scFv with an interface flexibility depending upon ligand MUC16^ecto binding. The observed changes of CDR residues participating in the interaction with MUC16 seems to happen almost simultaneously with the changes of the interface between V_H-V_L (FIGs.11A-11F). Then, how the antigen may affect the thermo-stability of antibody was investigated. Using a fluorescence-based thermal shift assay, it was found that the melting temperature (T_m) of h4H11-scFv was increased by 12.5% (acidic pH) and 4.2% (neutral pH) in the presence of MUC16^ecto peptide, whereas MUC16^ecto peptide itself had no effect (FIGs. 10A-10D). Independent melting points of each domain (VH or VL) between pH 5.4 and pH 9.4 implied that there is increased thermo-stability by ~13% at acidic and ~23% at neutral pH (FIG.10C). In contrast, the scFv in complex with ligand MUC16^ecto showed only one melting point at each pH value. These findings imply that the apo scFv (VH-VL) has a higher independence at even pH 4.4 and unfolding of the scFv can be inhibited depending on the MUC16^ecto ligand. The thermal stability of MBP-MUC16^ecto and its variants, double mutations of G17^thA/D18^thA, R24^thA/D25^thA, and two double mutations of (G17^thA/D18^thA/R24^thA/D25^thA) were also examined (FIGs.11A-11F). None of these variants interfere with protein folding as verified by a thermal shift assay. The interaction potential of the MUC16^ecto variants were explored as shown in FIG.11F; D25^thA/R24^thA and two double mutations did not show detectable binding to the scFv at the concentration tested (~470 nM), while the other variant (G17^thA/D18^thA) displayed very weak interactions compared to MBP-MUC16^ecto (wt) (FIG.11F). These results suggest that the V_H of V_H-V_L may be a key player to initially explore the binding pocket of MUC16^ecto. This position may also be occupied by each fragment at a different time, and these results support the present 4H11-scFv’s specificity and stability as a potential MUC16 ectodomain-based cancer immunotherapy agent. Example 8: The structure of MUC16^ecto is unique in humans, independent of glycosylation and conserved across phylogeny [00355] Following proteolytic cleavage of MUC16 in vivo, MUC16 fragments have two independent biological elements: the shed “tandem repeat element” and “proximal retained component”, including the ectodomain, transmembrane domain and cytosolic sequences. The juxtamembrane adjacent to TM is targeted by h4H11, a region more proximal to the membrane, with potential therapeutic advantages (FIG 5A). To evaluate phylogenetic stability of this region, the sequence alignment of the specific 31 amino acids (from L31^st to P1^st) among 8 different species to examine sequence conservation was performed (FIG.5B). The ectodomain was highly conserved with ~94% identity and, in particular, showed 100 % identities on the 16 residues (from L31^st to S15^th) except for Mus musculus. A structural view of MUC16^ecto revealed that it is composed of two consecutive β-turns of ^31stL~F^28th and ^27thT~R^24th residues and a β-hairpin of 9 residues (FIGs.5C-5F). As known, β-turns are one of the most common structural motifs in proteins and change the direction of the peptide backbone by nearly 180°, allowing the peptide chain to fold back into itself. The hydrophilic N29^th and D25^th might have a high propensity for the formation of β-turns due to their placement on solvent-exposed surfaces (FIGs.5D-5E). In addition to their role in protein folding, they can also serve as recognition motifs for protein-protein interactions (PPI), because the MUC16 C-terminal portion may function as a transcriptional motif in the nucleus. The torsional angles (ϕ_{i + 1}, ψ_{i + 1}, ϕ_{i + 2}, and ψ_{i + 2}) in residues i + 1 and i + 2 and additional omega (ω) from L31^st to P14^th except for phi (φ) and psi (ψ) of the L31^st owing to no calculation were analyzed (FIGs.12A-12F). The first β-turn seems to be type-I and the second β-turn as a mirror image of the backbone conformation of type-I based on the torsional angles. The β-hairpin is a simple motif that consists of two β-strands, oriented in an antiparallel direction (the N-terminus of one sheet is adjacent to the C-terminus of the next). It could be stabilized by two inter-hydrogen bonds between V19^th (-N) – Y16^th (-O) at 2.8 Å distance and V19^th (-O) – Y16^th (-N) at 3.1 Å distance, respectively (FIG.5F). Whether glycans in MUC16^ecto could be involved in antibody binding areas was also considered. As MUC16 is heavily glycosylated, N- or O-glycosylation sites based on the MUC16^ecto sequence were also predicted using webserver (crdd.osdd.net), confirming that N29^th and T27^th are likely to be glycosylated in vivo (FIG.5G). The N29^th amino acid was involved in N-glycosylation motif known sequence “N-X-S/T”. These potential glycosylation residues support interaction with the scFv in vivo. However, these two residues showed no direct interactions in the present structures. Taken together, the structural motifs of MUC16 ectodomain may play important roles for PPI in the cytosol or nucleus. Regions of local similarity with MUC16^ecto domain (19 residues) in homo sapiens was investigated using BLAST (www.uniprot.org/blast/) and only two non-related proteins, ATP-dependent RNA helicase TDRD9 and Hypoxia-induced HIG-1, showed 42% identities as highest similarities (FIG.5H). These results may explain the high specificity of the h4H11-scFv, owing to the unique nature of the CDR sequences. Example 9: Comparison of mouse and human 4H11 scFv interaction with MUC16 [00356] To better understand the improvement of the h4hH11 antibody-antigen binding mechanism over the murine parent, tertiary folding and potential interface region with MUC16^ecto were compared. Structural alignments was performed on a m4H11structure generated by sequence-based structure prediction method in silico. That (m)4H11-scFv model was structurally aligned with the crystallization derived models of (h)4H11-scFv or (h)4H11-scFv in complex with (h)MUC16^ecto. As a result of structural alignments presented as the root mean square deviation (RMSD), measuring of the average distance between the atoms of superimposed proteins, between (h)4H11-scFv (unbound)-(m)4H11-scFv(unbound) and (m)4H11(unbound)-scFv-(h)4H11-scFv(bound form with MUC16^ecto) were calculated as 0.805 (with 1,277 atoms) and 0.915 (with 1,319 atoms), respectively (FIG.6A). Seven (7) amino acids (R19, A40, S78, R166, N170, S217, and V237) in the (h)4H11-scFv are shown altered as K19, S40, T78, K166, S170, T217, and L237 in the (m)4H11-scFv. Interestingly, these residues are located at framework regions (FR) not CDRs. In particular, A40S is located at the interface of VH-VL. As reported, FR regions responsible for acting as a scaffold for the CDRs (also referred to as hypervariable regions). The mutation of FR regions may result in different antibody paratope states or conformational rearrangements of CDRs. From in silico modelling structure, only local changes at the D106 and Y108 residues of the heavy chain CDR3 without the overall distortion were found. The comparative activity assays (both CAR-T cell and ADC data) of ovarian cancer cells demonstrated that (h)4H11-scFv showed the much stronger killing activity than (m)4H11-scFv (FIGs.2A-2J). Then, why the binding affinity of (m)4H11-scFv can be weaker than (h)4H11-scFv against (h)MUC16^ecto antigen despite having the same CDR sequences of them was investigated. The predicted structural movements of D106 and Y108 at VH-CDR3 of mouse antibody may be induced by either some or all 7 different amino acids as expected allosteric movements, which may be specifically linked to a local change switch of VH-CDR3 from antigen binding interface to reduce the binding affinity. Many biological processes depend on allosteric communication between different parts of a protein, but the role of internal protein motion in propagating signals through the structure remains largely unknown. D106 of (h)4H11-scFv can interact with S22^nd and R24^th of (h)MUC16^ecto by forming 3 hydrogen bonds (including ‘water 2’- mediated hydrogen bond) however, (m)4H11-scFv D106 position showed a ~180^o rotation (FIG.6B). Y108 residue of (h)4H11-scFv can form ‘water-1’ mediated hydrogen bonds with S15^th and S23^rd of (h)MUC16^ecto, however the predicted side chain position of (m)Y108 was ~11 Å apart from side chain of the human scFv Y108 (FIG.6C). These findings help explain the murine scFv’s weaker binding affinity against human MUC16^ecto antigen. Taken together, the findings may provide a novel way for antibody allosteric changes to occur through the mutations of FR regions. The (mouse)antibody’s weaker binding against (human)MUC16 antigen may be explained by this allosteric network, valuable broad implications for understanding antibody engineering and folding mechanism. Example 10: Dynamic rearrangement of the 4H11 scFv CDR’s during binding with the MUC16 ectodomain [00357] Based on the structural model of the 4H11 scFv alone, specific sites in the 4H11 scFv underwent alteration when bound to MUC16^ecto. After careful structural analysis of the scFv apo and bound forms, antigen binding-induced changes were identified (FIGs.12A- 12F). Structural changes in the CDR loop regions of the V_H and V_L, corresponding with allosteric movements without overall distortion were found. Root-mean-square-deviation (R.M.S.D) between the backbone atoms of heavy chains (VH*: VH) or light chains (VL*: VL) with these changes were 0.454 or 0.355, respectively (FIG.12C, and FIG.16). FIGs.7A- 7B show superimposed ribbon structures which highlight the changes in the heavy chain and light chain when bound to the MUC16 target sequence in two views. These movements are illustrated in FIGs.7C-7D. In particular, the sidechain of VL S180 was moved ~2.5 Å, forming hydrogen bonds with Y16^th and G17^th of MUC16 (FIGs.7E-7F with the pink highlight. The aromatic ring of the V_H Y108 was also moved ~3.8 Å after MUC16 binding, toward S15^th and S23^rd residues of MUC16 (FIGs.7E-7G). These movements of Y108 and S180 are linked to water molecules (w1-w3) as illustrated in the (FIGs.7F-7G). Three water molecules (w1-w3) contribute 5 pairs of hydrogen bonds through bridging D106 and Y108, and S180 with the MUC16 ectodomain (FIGs.7F-7G). No water molecules at the specific positions were observed in the 4H11-scFv structure itself, probably because of the roles of water-binding residues at the V_H-V_L interface, implying the water molecules may contribute to gain increased interactions. [00358] Preliminary CDR mutagenesis studies demonstrate that the antibody’s binding affinity is dramatically improved when V_H and V_L together, the V_H-V_L complex, cooperated with each other against antigen MUC16^ecto (FIG.7H). As a synergistic effect, V_H-V_L heterodimer showed much stronger affinity than its variants designed for blocking each binding capacity, although each could independently occupy the specific positions of MUC16^ecto as shown in the pull down (FIG.7H). MUC16^ecto variants designed for blocking the interactions with VH or VL showed that VH binding affinity may be more critical for interaction than VL affinity to the antigen, based on the pull-down studies (FIG.11F). Example 11: Combination method of saturation mutagenesis & GAL4-based yeast two- hybrid [00359] Engineered 4H11-scFv will reduce ‘off-target’ side effect risk and be capable of binding with higher affinity, specificity with high thermostability to overexpressed-MUC16 (cell-associated unshed) that is classically seen in ovarian cancers. The first round of saturation mutagenesis is now well underway. Independent mutations of VH or VL to reduce the binding affinities at the positions, “S53 in CDR2 and D106 in CDR3 on V_H” and “Y246 and N247 in CDR3 on V_L” are designed for blue-colony-selection (by protein-protein interaction) later by yeast two hybrid, a part of the saturation mutagenesis. CDR library designs based on structure-based in silico selection by affinity and stability prediction are performed using molecular operating environment (MOE) and Rosetta software, particularly with map electrostatic hotspots and sidechain rotamer orientation. 9 independent mutational sites: S30, G55, G56, F101, Y108 for V_H and N179, R181, Q186, S245 for V_L were identified (FIG.18). Indeed, Error-prone PCR for saturation mutagenesis (initial independent QuikChanges with random -NNN- nucleotide for each of the proposed point mutation) on each mutational site of V_H and V_L is performed using the QuikChange^TM Site- directed mutagenesis protocol, generating a pool of constructs encoding all 20 possible amino acids at the selected site. Each construct library (scFv harboring mutated CDRs) produced by saturation mutagenesis can be cloned into the GAL4-based Yeast Two-Hybrid (Y2H) vector (pGADT7-scFv prey fused Gal4-Activation domain for Y187 strain, which provides the high- complexity library that expresses fusions with Gal4-AD) and the other vector pGBKT7- MUC16^ecto bait fused Gal4-DNA binding domain for Y2HGold (FIG.18). The transformed Y2HGold and Y187 are mixed together for creating diploids that contain four reporter gene HIS3, ADE2, MEL1, and AUR1-C that are activated in response to Y2H interaction. The transformed diploid yeast cells are cultured synthetically defined (SD) medium: SD/-Ade/- His/-Leu/-Trp dropout supplement is used to select for the bait and prey plasmids for the Y2H library screening with an X-α-Gal plate test, in which the transcription of a reporter gene (MEL1 from Y2HGold) leads to a change the color of yeast colonies to turn blue (usually various low to strong blue colors) if there is a complex between the engineered scFv and MUC16^ecto in the yeast, revealing binding strength of the specific mutations at each site (FIG.18). The plasmids from stronger blue colonies are extracted and deep-sequenced to check the identity of the mutated amino acid(s) at the selected site(s). These mutations are then validated by measuring α-galactosidase activity in yeast for the stronger activity search and up 5-10 plasmids showing the strongest activities is identified and this engineering will be continued until satisfactory results (low picomolar range K_d) are obtained. [00360] It is expected that new variant antibodies will improve the affinity of 4H11 MUC16 antibodies. Example 12: Effects of an artificial disulfide bond (S-S bridge) between each VH or VL in h4H11 [00361] The purpose of an additional disulfide bond within the each VH or VL domains is to improve thermostability, reduced aggregated forms, improve affinity and protection from proteases. The positions for the additional cysteine-pair are followed by three criteria: (i) the pairs have to contain Ala, Val, or Ile, (ii) requirement of around 10 Å solvent-exposed surface area, and (iii) the 3.5 Å ~ 4.5 Å distance between the two b-carbon of cysteines. The corresponding potential intra-molecular cys-cys positions of the VH or VL in h4H11 are either A49 and I70 for VH or A40 and I54 for VL in the scFv sequence, respectively (FIG. 19). Based on these models, site specific mutagenesis will be used to create both h4H11scFv^(A49C/I70C) and h4H11scFv^A40C/I54C to compare with the parent scFv. [00362] Comparisons will be made for i) production efficacy in ExpiCHO (loss of >50% efficacy=rejection); ii) melting temperature at physiological conditions, iii) binding affinity to the MUC16 peptide of interest by ITC (improvement by >50% = success). Stability of scFV protein at 4°C, 25°C, and 37°C will be examined by binding over times of up to 1 week through ITC (stability is a desired criterion but will be used only select among otherwise equivalent sequences. Additional analogous studies are planned for other anti-MUC16 antibodies which may have better direct inhibitory properties than h4H11 but suffers from poor stability in its current form. Example 13: Optimization of current MUC16 directed antibody therapeutics for use in Antibody Drug Conjugates [00363] Development of Antibody Drug Conjugate of MUC16^ecto. The variables will be explored to identify the optimal MUC16 targeting ADC. In parallel with the mutagenesis work, the best payload for MUC16 will be evaluated for ovarian cancer targeting. Some of the preliminary results are shown in FIG.20. MUC16 transfected SKOV3 cells had an IC50 of about 18nM while SKOV3 cells lacking MUC16 were 1000 fold less sensitive. The ID8 cells with native murine Muc16 expression had an IC50 of 8nM. The experimental plan will be performed in 2 parallel paths. The first is a full characterization of the h4H11-Maytansine (h4H11-May) product across multiple characterized ovarian cell lines as single agent, followed by combination studies with cisplatin (CDDP) at the cell line IC50 for CDDP and similar h4H11-May combination studies of paclitaxel. At the end, the relative sensitivity of the target lines in vitro to h4H11-May and known characteristics of the cell lines will be examined. [00364] h4H11-MMAE Killing assays. A variety of MUC16 + and negative cell lines will undergo analysis, first in simple 96 well plate assays over 1-3 and 5 days as shown above as well as clonogenic survival assays. The goal will be to establish appropriate effective levels in vitro. After 15-20 cell lines have been examined and collated according to MUC16 expression, selected cell lines will be tested in vivo using both single dose- growth delay assays and multiple dosing strategies. Plasma and tumor pharmacology for the antibody will be done with anti-h4H11^ecto ELISA. Improved versions of the 4H11scFv from saturation mutagenesis will be conjugated and compared to the parent scFv for killing and internalization. [00365] In vivo confirmation of ADC. Initial dose exploration of single dose, BIW and weekly x 3 dosing is planned with the h4H11-May with small pilot 8 mouse groups (76 mice). Following the in vitro work above, the three compounds (Maytansine, cisplatin, paclitaxel) will be tested in three animal MUC16 + models (ID8 murine tumor, OV429 xenograft (MUC16+) and MUC16^ecto + patient derived organoid (with Path core, 6-Mice). As above, it is estimated that 6 animals/group with parallel mouse controls for each of three ADC payload candidates (60 mice). These will be tested in vivo as well (54 mice). The most promising ADC will be extended across 3-5 patient derived xenografts for wider validation (60 mice). Persistent tumors will be collected for bulk RNAseq analysis and rechecked for MUC16^ecto positivity. [00366] Integration of the best antibody scFv carrier. The choice of antibody carrier will be revisited as the epitope optimization studies outlined above are completed. The best payload, schedule and linker to be integrated into the most selective, highest affinity antibody will be selected for development. The optimized payload can be used to create a final MUC16^ecto ADC for clinical development, optimized for binding from the structural studies. EQUIVALENTS [00367] The present technology is not to be limited in terms of the particular embodiments described in this application, which are intended as single illustrations of individual aspects of the present technology. Many modifications and variations of this present technology can be made without departing from its spirit and scope, as will be apparent to those skilled in the art. Functionally equivalent methods and apparatuses within the scope of the present technology, in addition to those enumerated herein, will be apparent to those skilled in the art from the foregoing descriptions. Such modifications and variations are intended to fall within the scope of the present technology. It is to be understood that this present technology is not limited to particular methods, reagents, compounds compositions or biological systems, which can, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting. [00368] In addition, where features or aspects of the disclosure are described in terms of Markush groups, those skilled in the art will recognize that the disclosure is also thereby described in terms of any individual member or subgroup of members of the Markush group. [00369] As will be understood by one skilled in the art, for any and all purposes, particularly in terms of providing a written description, all ranges disclosed herein also encompass any and all possible subranges and combinations of subranges thereof. Any listed range can be easily recognized as sufficiently describing and enabling the same range being broken down into at least equal halves, thirds, quarters, fifths, tenths, etc. As a non-limiting example, each range discussed herein can be readily broken down into a lower third, middle third and upper third, etc. As will also be understood by one skilled in the art all language such as “up to,” “at least,” “greater than,” “less than,” and the like, include the number recited and refer to ranges which can be subsequently broken down into subranges as discussed above. Finally, as will be understood by one skilled in the art, a range includes each individual member. Thus, for example, a group having 1-3 cells refers to groups having 1, 2, or 3 cells. Similarly, a group having 1-5 cells refers to groups having 1, 2, 3, 4, or 5 cells, and so forth. [00370] All patents, patent applications, provisional applications, and publications referred to or cited herein are incorporated by reference in their entirety, including all figures and tables, to the extent they are not inconsistent with the explicit teachings of this specification.

Claims

Claims 1. An anti-mucin 16 (MUC16) construct comprising an antibody moiety that immunospecifically recognizes a mucin 16 (MUC16) polypeptide, wherein the antibody moiety comprises a heavy chain immunoglobulin variable domain (V_H) and a light chain immunoglobulin variable domain (V_L), wherein: (a) the VH comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, and (b) a V_L domain including an amino acid sequence of SEQ ID NO: 3 or SEQ ID NO: 4, wherein the VH domain further comprises at least one amino acid substitution corresponding to at least one amino acid residue selected from among S30, A54, G55, G56, F101, and/or Y108 of SEQ ID NO: 1 or SEQ ID NO: 2, and/or wherein the V_L domain further comprises at least one amino acid substitution corresponding to at least one amino acid residue selected from among N31, R33, Q38, and/or S97 of SEQ ID NO: 3 or SEQ ID NO: 4, optionally wherein the at least one amino acid substitution corresponding to S30, G55, G56, F101, and/or Y108 of SEQ ID NO: 1 or SEQ ID NO: 2 is one or more of S30Y, S30H, S30F, S30W, G55L, G55P, G55V, G55E, G56T, G56V, G56P, F101N, F101T, F101W, F101Q, or Y108R and/or the at least one amino acid substitution corresponding to N31, R33, Q38, and/or S97 of SEQ ID NO: 3 or SEQ ID NO: 4 is one or more of N31Q, N31V, N31S, N31K, N31T, N31P, R33N, R33V, R33S, R33T, R33E, Q38T, Q38D, Q38L, Q38P, Q38H, Q38R, Q38V, S97R, S97Q, S97E, S97H, S97L, S97P, S97V, S97N, or S97D.

2. An anti-mucin 16 (MUC16) construct comprising an antibody moiety that immunospecifically recognizes a mucin 16 (MUC16) polypeptide, wherein the antibody moiety comprises a sequence selected from among SEQ ID NOs: 5-8, wherein the anti- MUC16 antibody moiety further comprises at least one amino acid substitution corresponding to at least one amino acid residue selected from among S30, A54, G55, G56, F101, Y108, N179, R181, Q186, and/or S245 of any of SEQ ID NOs: 5-8, optionally wherein the at least one amino acid substitution corresponding to S30, G55, G56, F101, Y108, N179, R181, Q186, and/or S245 of any of SEQ ID NOs: 5-8 is one or more of S30Y, S30H, S30F, S30W, G55L, G55P, G55V, G55E, G56T, G56V, G56P, F101N, F101T, F101W, F101Q, Y108R, N179Q, N179V, N179S, N179K, N179T, N179P, R181N, R181V, R181S, R181T, R181E, Q186T, Q186D, Q186L, Q186P, Q186H, Q186R, Q186V, S245R, S245Q, S245E, S245H, S245L, S245P, S245V, S245N, or S245D.

3. The anti-MUC16 construct of claim 1 or 2, wherein the antibody moiety immunospecifically binds to the ectodomain of MUC16, or to a MUC16 c114 polypeptide comprising the amino acid sequence of SEQ ID NO: 11.

4. The anti-MUC16 construct of any one of claims 1-3, wherein the antibody moiety is a full-length antibody, a monoclonal antibody, a Fab, a Fabʹ, a F(abʹ)2, an Fv, or a single chain Fv (scFv).

5. The anti-MUC16 construct of any one of claims 1-4, wherein the anti-MUC16 construct inhibits in vitro invasion of a MUC16-expressing tumor cell in a Matrigel invasion assay, optionally wherein the MUC16-expressing tumor cell is an ovarian tumor cell.

6. The anti-MUC16 construct of claim 5, wherein MUC16 is glycosylated, preferably at N24 or N30 relative to SEQ ID NO: 11.

7. The anti-MUC16 construct of any one of claims 1-6, wherein the antibody moiety comprises human-derived heavy and light chain constant regions, optionally wherein the heavy chain constant region has an isotype selected from the group consisting of gamma l, gamma 2, gamma 3, and gamma 4, and optionally wherein the light chain constant region has an isotype selected from the group consisting of kappa and lambda.

8. The anti-MUC16 construct of any one of claims 1-7, wherein the antibody moiety is an immunoglobulin comprising two identical heavy chains and two identical light chains, optionally wherein the immunoglobulin is an IgG.

9. The anti-MUC16 construct of any one of claims 1-8, wherein the anti-MUC16 construct is monospecific, multispecific, or bispecific, optionally wherein the multispecific or bispecific anti-MUC16 construct comprises an anti-CD3 antibody moiety.

10. The anti-MUC16 construct of any one of claims 1-9, wherein the anti-MUC16 construct is (i) a tandem scFv, optionally wherein the tandem scFv comprises two scFvs linked by a peptide linker; (ii) a diabody (Db); (iii) a single chain diabody (scDb); (iv) a dual- affinity retargeting (DART) antibody, (v) a F(ab’)2; (vi) a dual variable domain (DVD) antibody; (vii) a knob-into-hole (KiH) antibody; (viii) a dock and lock (DNL) antibody; (ix) a chemically cross-linked antibody; (x) a heteromultimeric antibody; or (xi) a heteroconjugate antibody.

11. The anti-MUC16 construct of any one of claims 9-10, wherein the multispecific or bispecific anti-MUC16 construct comprises a first antibody moiety that immunospecifically recognizes MUC16, and a second antibody moiety that immunospecifically recognizes a second antigen.

12. The anti-MUC16 construct of claim 11, wherein the second antigen is an antigen expressed on the surface of a T cell, optionally wherein the second antigen is a CD3 polypeptide selected from the group consisting of CD3γ, CD3δ, CD3ε, and CD3ζ.

13. The anti-MUC16 construct of any one of claims 1-6, wherein the anti-MUC16 construct is a chimeric antigen receptor (CAR) or an antibody-T cell receptor (abTCR).

14. The anti-MUC16 construct of any one of claims 1-13, further conjugated to a peptide agent, a detection agent, an imaging agent, a therapeutic agent, or a cytotoxic agent.

15. The anti-MUC16 construct of claim 14, wherein the anti-MUC16 construct is conjugated to an alpha emitter, an Auger-emitter, a beta-emitter, a gamma-emitter, a positron- emitters, or an x-ray emitter, optionally wherein the positron-emitter is 89Zr-desferrioxamine B (DFO).

16. A polynucleotide comprising a nucleic acid sequence encoding the anti-MUC16 construct of any one of claims 1-15.

17. A vector comprising the polynucleotide of claim 16 operably linked to a promoter.

18. A cell comprising the anti-MUC16 construct of any one of claims 1-15, the polynucleotide of claim 16, or the vector of claim 17, optionally wherein the cell is a mammalian cell, an immune cell, a lymphocyte, a T cell or a B cell.

19. A pharmaceutical composition comprising: a therapeutically effective amount of the anti-MUC16 construct of any one of claims 1-15, the polynucleotide of claim 16, or the vector of claim 17, or the cell of claim 18; and a pharmaceutically acceptable carrier.

20. A method of treating a MUC16-associated disease or disorder in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of the anti-MUC16 construct of any one of claims 1-15, or the pharmaceutical composition of claim 19, optionally wherein said MUC16-associated disease or disorder is a cancer.

21. The method of claim 20, wherein said cancer is a metastatic cancer and/or a cancer of the ovary, lung, pancreas, breast, uterine, fallopian tube, or primary peritoneum.

22. The method of any one of claims 20-21, wherein the pharmaceutical composition inhibits or reduces metastasis in the patient, optionally wherein said patient is a human patient.

23. A method of producing an effector cell, comprising genetically modifying a cell with one or more nucleic acids encoding the anti-MUC16 construct of any one of claims 1-15.

24. A method of treatment comprising introducing one or more nucleic acids encoding the anti-MUC16 construct of any one of claims 1-15 into one or more primary cells isolated from a patient and administering cells comprising the one or more nucleic acids to the patient, optionally wherein the primary cells are lymphocytes or T cells.

25. The method of claim 24, further comprising expanding the cells prior to administering the cells to the patient.

26. The method of any one of claims 24-25, further comprising administering a therapeutically effective amount of an additional therapeutic agent to the patient.

27. A method of detecting MUC16 in a sample, comprising: (a) contacting the sample with the anti-MUC16 construct of any one of claims 1-15; and (b) detecting direct or indirect binding between the anti- MUC16 construct and a MUC16 polypeptide in the sample, optionally wherein the anti-MUC16 construct is conjugated to a detectable label selected from among a chromogenic label, an enzymatic label, a radioisotopic label, an isotopic label, a fluorescent label, a toxic label, a chemiluminescent label, and a nuclear magnetic resonance contrast agent.

28. A method of diagnosing an individual suspected of having a MUC16-associated disease or disorder, comprising: a) administering an effective amount of the anti-MUC16 construct of any one of claims 1-10 to the individual; and b) determining the level of direct or indirect binding between the anti- MUC16 construct and a MUC16 polypeptide in the individual, wherein a level of direct or indirect binding above a threshold level indicates that the individual has the MUC16-associated disease or disorder.

29. A method for detecting cancer in a subject in vivo comprising (a) administering to the subject an effective amount of the anti-MUC16 construct of any one of claims 1-14, wherein the anti-MUC16 construct is configured to localize to a cancer cell expressing MUC16 and is labeled with a radioisotope; and (b) detecting the presence of a tumor in the subject by detecting radioactive levels emitted by the anti-MUC16 construct that are higher than a reference value, optionally wherein the radioisotope is 89Zr-desferrioxamine B (DFO).

30. The method of claim 29, wherein the radioactive levels emitted by the anti-MUC16 construct are detected using positron emission tomography or single photon emission computed tomography.

31. The method of any one of claims 29-30, further comprising administering to the subject an effective amount of an immunoconjugate comprising the anti-MUC16 construct of any one of claims 1-14 conjugated to a radionuclide.

32. The method of claim 31, wherein the radionuclide is an alpha particle-emitting isotope, a beta particle-emitting isotope, an Auger-emitter, or any combination thereof.